Sample records for access channel md

  1. 77 FR 42464 - Special Local Regulations for Marine Events; Potomac River, National Harbor Access Channel, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-19

    ...--AA08 Special Local Regulations for Marine Events; Potomac River, National Harbor Access Channel, MD... Harbor'' triathlon, a marine event to be held on the waters of the Potomac River in Prince George's...; Potomac River, National Harbor Access Channel, MD'' in the Federal Register (77 FR 20750). The rulemaking...

  2. 77 FR 20750 - Special Local Regulations for Marine Events; Potomac River, National Harbor Access Channel, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-06

    ...-AA08 Special Local Regulations for Marine Events; Potomac River, National Harbor Access Channel, MD...'' triathlon, a marine event to be held on the waters of the Potomac River in Prince George's County, Maryland... portion of the Potomac River and National Harbor Access Channel during the event. DATES: Comments and...

  3. 78 FR 20849 - Special Local Regulations; Marine Events, Potomac River; National Harbor Access Channel, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-08

    ...-AA08 Special Local Regulations; Marine Events, Potomac River; National Harbor Access Channel, MD AGENCY... special local regulations during the ``Swim Across the Potomac'' swimming competition, to be held on the waters of the Potomac River on June 2, 2013. These special local regulations are necessary to provide for...

  4. 33 CFR 100.35T05-0276 - Special Local Regulations for Marine Events; Potomac River, National Harbor Access Channel, MD.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Marine Events; Potomac River, National Harbor Access Channel, MD. 100.35T05-0276 Section 100.35T05-0276... SAFETY OF LIFE ON NAVIGABLE WATERS § 100.35T05-0276 Special Local Regulations for Marine Events; Potomac... area: All waters of the Potomac River, within lines connecting the following positions: From 38°47′35...

  5. 33 CFR 100.35T05-0276 - Special Local Regulations for Marine Events; Potomac River, National Harbor Access Channel, MD.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Marine Events; Potomac River, National Harbor Access Channel, MD. 100.35T05-0276 Section 100.35T05-0276... SAFETY OF LIFE ON NAVIGABLE WATERS § 100.35T05-0276 Special Local Regulations for Marine Events; Potomac... area: All waters of the Potomac River, within lines connecting the following positions: From 38°47′35...

  6. 77 FR 39630 - Special Local Regulations for Marine Events; Potomac River, National Harbor Access Channel, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-05

    ... 1625-AA08 Special Local Regulations for Marine Events; Potomac River, National Harbor Access Channel... special local regulations during the swim segment of the ``Swim Across the Potomac River'' swimming competition, to be held on the waters of the Potomac River on July 8, 2012. These special local regulations...

  7. Channel Access in Erlang

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

    Nicklaus, Dennis J.

    2013-10-13

    We have developed an Erlang language implementation of the Channel Access protocol. Included are low-level functions for encoding and decoding Channel Access protocol network packets as well as higher level functions for monitoring or setting EPICS process variables. This provides access to EPICS process variables for the Fermilab Acnet control system via our Erlang-based front-end architecture without having to interface to C/C++ programs and libraries. Erlang is a functional programming language originally developed for real-time telecommunications applications. Its network programming features and list management functions make it particularly well-suited for the task of managing multiple Channel Access circuits and PVmore » monitors.« less

  8. 77 FR 36394 - Safety Zone for Fireworks Display, Potomac River, National Harbor Access Channel; Oxon Hill, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-19

    ... 1625-AA00 Safety Zone for Fireworks Display, Potomac River, National Harbor Access Channel; Oxon Hill... safety zone upon specified waters of the Potomac River. This action is necessary to provide for the... zone is intended to protect the maritime public in a portion of the Potomac River. DATES: This rule is...

  9. 47 CFR 76.701 - Leased access channels.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Leased access channels. 76.701 Section 76.701 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Television Access § 76.701 Leased access channels. (a) Notwithstanding 47...

  10. 47 CFR 76.701 - Leased access channels.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 4 2013-10-01 2013-10-01 false Leased access channels. 76.701 Section 76.701... CABLE TELEVISION SERVICE Cable Television Access § 76.701 Leased access channels. (a) Notwithstanding 47 U.S.C. 532(b)(2) (Communications Act of 1934, as amended, section 612), a cable operator, in...

  11. 47 CFR 76.701 - Leased access channels.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Television Access § 76.701 Leased access channels. (a) Notwithstanding 47... reasonably believes, describes or depicts sexual or excretory activities or organs in a patently offensive...

  12. 47 CFR 76.701 - Leased access channels.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Television Access § 76.701 Leased access channels. (a) Notwithstanding 47... reasonably believes, describes or depicts sexual or excretory activities or organs in a patently offensive...

  13. 47 CFR 76.701 - Leased access channels.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) BROADCAST RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Television Access § 76.701 Leased access channels. (a) Notwithstanding 47... reasonably believes, describes or depicts sexual or excretory activities or organs in a patently offensive...

  14. 77 FR 56115 - Safety Zone for Fireworks Display, Potomac River, National Harbor Access Channel; Oxon Hill, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-12

    ..., MD AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a... safety of life on navigable waters during a fireworks display launched from a floating platform located... zone is intended to protect the maritime public in a portion of the Potomac River. DATES: This rule is...

  15. Distributed reservation control protocols for random access broadcasting channels

    NASA Technical Reports Server (NTRS)

    Greene, E. P.; Ephremides, A.

    1981-01-01

    Attention is given to a communication network consisting of an arbitrary number of nodes which can communicate with each other via a time-division multiple access (TDMA) broadcast channel. The reported investigation is concerned with the development of efficient distributed multiple access protocols for traffic consisting primarily of single packet messages in a datagram mode of operation. The motivation for the design of the protocols came from the consideration of efficient multiple access utilization of moderate to high bandwidth (4-40 Mbit/s capacity) communication satellite channels used for the transmission of short (1000-10,000 bits) fixed length packets. Under these circumstances, the ratio of roundtrip propagation time to packet transmission time is between 100 to 10,000. It is shown how a TDMA channel can be adaptively shared by datagram traffic and constant bandwidth users such as in digital voice applications. The distributed reservation control protocols described are a hybrid between contention and reservation protocols.

  16. An Adaptive Channel Access Method for Dynamic Super Dense Wireless Sensor Networks.

    PubMed

    Lei, Chunyang; Bie, Hongxia; Fang, Gengfa; Zhang, Xuekun

    2015-12-03

    Super dense and distributed wireless sensor networks have become very popular with the development of small cell technology, Internet of Things (IoT), Machine-to-Machine (M2M) communications, Vehicular-to-Vehicular (V2V) communications and public safety networks. While densely deployed wireless networks provide one of the most important and sustainable solutions to improve the accuracy of sensing and spectral efficiency, a new channel access scheme needs to be designed to solve the channel congestion problem introduced by the high dynamics of competing nodes accessing the channel simultaneously. In this paper, we firstly analyzed the channel contention problem using a novel normalized channel contention analysis model which provides information on how to tune the contention window according to the state of channel contention. We then proposed an adaptive channel contention window tuning algorithm in which the contention window tuning rate is set dynamically based on the estimated channel contention level. Simulation results show that our proposed adaptive channel access algorithm based on fast contention window tuning can achieve more than 95 % of the theoretical optimal throughput and 0 . 97 of fairness index especially in dynamic and dense networks.

  17. Reproductive health information for young women in Kazakhstan: disparities in access by channel.

    PubMed

    Buckley, Cynthia; Barrett, Jennifer; Adkins, Kristen

    2008-01-01

    This study explores young women's reliance on reproductive and sexual health information channels, examining the relationship between information sources and reproductive health knowledge. Utilizing 1995 and 1999 Kazakhstan Demographic and Health Surveys, we investigate access to reproductive health knowledge among young women (ages 15-24) during a key period in the development of wide-scale reproductive health programs in Kazakhstan. Despite reproductive health campaigns throughout the 1990s, we find consistently high proportions of young women without family planning information access. Among young women with access to information, few received information from channels most strongly linked to knowledge and behavioral changes (family and medical professionals). Mass media sources and peer information networks remained the most often utilized channels. Urban residence, non-Kazakh ethnicity, older age (20-24), and higher education significantly increased the odds of accessing family planning information among young Kazakhstani women, and these same factors were especially important in terms of the relative odds of accessing medical and parental channels. While overall contraceptive knowledge and prevalence rose in Kazakhstan during the 1990s, we find knowledge varied by the information channel accessed. Findings also indicate that young women, regardless of marital status, possessed consistently low levels of reproductive health knowledge at the decade's end.

  18. Zinc chelation with hydroxamate in histone deacetylases modulated by water access to the linker binding channel.

    PubMed

    Wu, Ruibo; Lu, Zhenyu; Cao, Zexing; Zhang, Yingkai

    2011-04-27

    It is of significant biological interest and medical importance to develop class- and isoform-selective histone deacetylase (HDAC) modulators. The impact of the linker component on HDAC inhibition specificity has been revealed but is not understood. Using Born-Oppenheimer ab initio QM/MM MD simulations, a state-of-the-art approach to simulating metallo-enzymes, we have found that the hydroxamic acid remains to be protonated upon its binding to HDAC8, and thus disproved the mechanistic hypothesis that the distinct zinc-hydroxamate chelation modes between two HDAC subclasses come from different protonation states of the hydroxamic acid. Instead, our simulations suggest a novel mechanism in which the chelation mode of hydroxamate with the zinc ion in HDACs is modulated by water access to the linker binding channel. This new insight into the interplay between the linker binding and the zinc chelation emphasizes its importance and gives guidance regarding linker design for the development of new class-IIa-specific HDAC inhibitors.

  19. Small Ion Channel Linking Molecular Simulations and Electrophysiology

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrzej

    2017-01-01

    Ion channels are pore-forming protein assemblies that mediate the transport of small ions across cell membranes. Otherwise, membrane bilayers would be almost impermeable to ions incapable to traverse the low dielectric constant, hydrophobic membrane core. Ion channels are ubiquitous to all life forms. In humans and other higher organisms they play the central role in conducting nerve impulses, cardiac functions, muscle contraction and apoptosis. On the other extreme of biological complexity, viral ion channels (viroporins) influence many stages of the virus infection cycle either through regulating virus replication, such as entry, assembly and release or modulating the electrochemical balance in the subcellular compartments of host cells. Ion channels were crucial components of protocells. Their emergence facilitated adaptation of nascent life to different environmental conditions. The earliest ion channels must have been much simpler than most of their modern ancestors. Viral channels are among only a few naturally occurring models to study the structure, function and evolution of primordial channels. Experimental studies of these properties are difficult and often unreliable. In principle, computational methods, and molecular dynamics (MD) simulations in particular, can aid in providing information about both the structure and the function of ion channels. However, MD suffers from its own problems, such as inability to access sufficiently long time scales or limited accuracy of force fields. It is, therefore, essential to determine the reliability of MD simulations. We propose to do so on the basis of two criteria. One is channel stability on time scales that extend for several microseconds or longer. The other is the ability to reproduce the measured ionic conductance as a function of applied voltage. If both the stability and the calculated ionic conductance are satisfactory it will greatly increase our confidence that the structure and the function of a

  20. Sidedness of Carbamazepine Accessibility to Voltage-Gated Sodium Channels

    PubMed Central

    Jo, Sooyeon

    2014-01-01

    Voltage-gated sodium channels are inhibited by many local anesthetics, antiarrhythmics, and antiepileptic drugs. The local anesthetic lidocaine appears to be able to access its binding site in the sodium channel only from the membrane phase or from the internal face of the channel. In contrast, the antiepileptic drug carbamazepine was found to inhibit voltage-gated sodium channels only with external, but not internal, application, implying a major difference. We investigated this point using both whole-cell and inside-out patch recordings from human Nav1.7 channels in a stable cell line. In the whole-cell configuration, carbamazepine inhibited sodium current within seconds when applied externally, but had little or no effect when applied internally for up to 15 minutes, confirming previous results. However, carbamazepine inhibited sodium channels effectively and rapidly when applied to the internal face of the membrane using inside-out patch recording. We found that lidocaine also has little or no effect when applied intracellularly in whole-cell recording, but blocks effectively and rapidly when applied to the internal surface using inside-out patches. In contrast, the cationic lidocaine derivative QX-314 (N-ethyl-lidocaine) blocks effectively when applied internally with whole-cell dialysis, as well as when applied to inside-out patches. We conclude that carbamazepine and lidocaine access the sodium channel in similar ways and hypothesize that their lack of effect with internal dialysis in whole-cell recording reflects rapid exit through membrane near the pipette recording site. This effect likely limits the ability of any compound with significant membrane permeability to be applied intracellularly by whole-cell dialysis. PMID:24319110

  1. 78 FR 33219 - Special Local Regulations; Swim Across the Potomac, Potomac River; National Harbor Access Channel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-04

    ... Channel, MD AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is... provide for the safety of life on navigable waters during the event. This action is intended to temporarily restrict vessel traffic in a portion of the Potomac River during the event. DATES: This rule is...

  2. Hybrid MD-Nernst Planck Model of Alpha-hemolysin Conductance Properties

    NASA Technical Reports Server (NTRS)

    Cozmuta, Ioana; O'Keefer, James T.; Bose, Deepak; Stolc, Viktor

    2006-01-01

    Motivated by experiments in which an applied electric field translocates polynucleotides through an alpha-hemolysin protein channel causing ionic current transient blockade, a hybrid simulation model is proposed to predict the conductance properties of the open channel. Time scales corresponding to ion permeation processes are reached using the Poisson-Nemst-Planck (PNP) electro-diffusion model in which both solvent and local ion concentrations are represented as a continuum. The diffusion coefficients of the ions (K(+) and Cl(-)) input in the PNP model are, however, calculated from all-atom molecular dynamics (MD). In the MD simulations, a reduced representation of the channel is used. The channel is solvated in a 1 M KCI solution, and an external electric field is applied. The pore specific diffusion coefficients for both ionic species are reduced 5-7 times in comparison to bulk values. Significant statistical variations (17-45%) of the pore-ions diffusivities are observed. Within the statistics, the ionic diffusivities remain invariable for a range of external applied voltages between 30 and 240mV. In the 2D-PNP calculations, the pore stem is approximated by a smooth cylinder of radius approx. 9A with two constriction blocks where the radius is reduced to approx. 6A. The electrostatic potential includes the contribution from the atomistic charges. The MD-PNP model shows that the atomic charges are responsible for the rectifying behaviour and for the slight anion selectivity of the a-hemolysin pore. Independent of the hierarchy between the anion and cation diffusivities, the anionic contribution to the total ionic current will dominate. The predictions of the MD-PNP model are in good agreement with experimental data and give confidence in the present approach of bridging time scales by combining a microscopic and macroscopic model.

  3. Method for Evaluation of Outage Probability on Random Access Channel in Mobile Communication Systems

    NASA Astrophysics Data System (ADS)

    Kollár, Martin

    2012-05-01

    In order to access the cell in all mobile communication technologies a so called random-access procedure is used. For example in GSM this is represented by sending the CHANNEL REQUEST message from Mobile Station (MS) to Base Transceiver Station (BTS) which is consequently forwarded as an CHANNEL REQUIRED message to the Base Station Controller (BSC). If the BTS decodes some noise on the Random Access Channel (RACH) as random access by mistake (so- called ‘phantom RACH') then it is a question of pure coincidence which èstablishment cause’ the BTS thinks to have recognized. A typical invalid channel access request or phantom RACH is characterized by an IMMEDIATE ASSIGNMENT procedure (assignment of an SDCCH or TCH) which is not followed by sending an ESTABLISH INDICATION from MS to BTS. In this paper a mathematical model for evaluation of the Power RACH Busy Threshold (RACHBT) in order to guaranty in advance determined outage probability on RACH is described and discussed as well. It focuses on Global System for Mobile Communications (GSM) however the obtained results can be generalized on remaining mobile technologies (ie WCDMA and LTE).

  4. Influence of the membrane lipophilic environment on the structure and on the substrate access/egress routes of the human aromatase enzyme. A computational study.

    PubMed

    Sgrignani, Jacopo; Magistrato, Alessandra

    2012-06-25

    Human aromatase (HA), an enzyme located on the membrane of the endoplasmatic reticulum, is of crucial biological importance in the biosynthesis of estrogens. High levels of estrogens are related with important pathologies, conferring to HA a key role as a pharmacological target. In this study we provide, for the first time, an atomistic model of HA embedded on a membrane model to understand the influence of the membrane lipophilic environment on the structural and dynamical properties of HA and on the access/egress pathways of the substrate (androstenedione, ASD) and of the oxygen molecule (involved in the enzymatic process) into/from the HA active site. To this end we used several computational techniques such as force field-based molecular dynamics (MD) simulations, Random Expulsion MD, Steered MD, and Implicit Ligand Sampling. Our results show that the membrane anchoring does not markedly affect the structural properties and the flexibility of the protein, but they clearly point out that the membrane has a marked effect on the access/egress routes of the reactants, stabilizing the formation of different channels for both ASD and O(2) with respect to those observed in pure water solution. Due to the importance of HA in medicine and since access/egress channels may influence its substrate selectivity, a detailed understanding of the role of the membrane in shaping these channels may be of valuable help in drug design.

  5. Molecular Dynamics Simulations of KirBac1.1 Mutants Reveal Global Gating Changes of Kir Channels.

    PubMed

    Linder, Tobias; Wang, Shizhen; Zangerl-Plessl, Eva-Maria; Nichols, Colin G; Stary-Weinzinger, Anna

    2015-04-27

    Prokaryotic inwardly rectifying (KirBac) potassium channels are homologous to mammalian Kir channels. Their activity is controlled by dynamical conformational changes that regulate ion flow through a central pore. Understanding the dynamical rearrangements of Kir channels during gating requires high-resolution structure information from channels crystallized in different conformations and insight into the transition steps, which are difficult to access experimentally. In this study, we use MD simulations on wild type KirBac1.1 and an activatory mutant to investigate activation gating of KirBac channels. Full atomistic MD simulations revealed that introducing glutamate in position 143 causes significant widening at the helix bundle crossing gate, enabling water flux into the cavity. Further, global rearrangements including a twisting motion as well as local rearrangements at the subunit interface in the cytoplasmic domain were observed. These structural rearrangements are similar to recently reported KirBac3.1 crystal structures in closed and open conformation, suggesting that our simulations capture major conformational changes during KirBac1.1 opening. In addition, an important role of protein-lipid interactions during gating was observed. Slide-helix and C-linker interactions with lipids were strengthened during activation gating.

  6. Experience with ActiveX control for simple channel access

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

    Timossi, C.; Nishimura, H.; McDonald, J.

    2003-05-15

    Accelerator control system applications at Berkeley Lab's Advanced Light Source (ALS) are typically deployed on operator consoles running Microsoft Windows 2000 and utilize EPICS[2]channel access for data access. In an effort to accommodate the wide variety of Windows based development tools and developers with little experience in network programming, ActiveX controls have been deployed on the operator stations. Use of ActiveX controls for use in the accelerator control environment has been presented previously[1]. Here we report on some of our experiences with the use and development of these controls.

  7. Assessing the allelotypic effect of two aminocyclopropane carboxylic acid synthase-encoding genes MdACS1 and MdACS3a on fruit ethylene production and softening in Malus

    PubMed Central

    Dougherty, Laura; Zhu, Yuandi; Xu, Kenong

    2016-01-01

    Phytohormone ethylene largely determines apple fruit shelf life and storability. Previous studies demonstrated that MdACS1 and MdACS3a, which encode 1-aminocyclopropane-1-carboxylic acid synthases (ACS), are crucial in apple fruit ethylene production. MdACS1 is well-known to be intimately involved in the climacteric ethylene burst in fruit ripening, while MdACS3a has been regarded a main regulator for ethylene production transition from system 1 (during fruit development) to system 2 (during fruit ripening). However, MdACS3a was also shown to have limited roles in initiating the ripening process lately. To better assess their roles, fruit ethylene production and softening were evaluated at five time points during a 20-day post-harvest period in 97 Malus accessions and in 34 progeny from 2 controlled crosses. Allelotyping was accomplished using an existing marker (ACS1) for MdACS1 and two markers (CAPS866 and CAPS870) developed here to specifically detect the two null alleles (ACS3a-G289V and Mdacs3a) of MdACS3a. In total, 952 Malus accessions were allelotyped with the three markers. The major findings included: The effect of MdACS1 was significant on fruit ethylene production and softening while that of MdACS3a was less detectable; allele MdACS1–2 was significantly associated with low ethylene and slow softening; under the same background of the MdACS1 allelotypes, null allele Mdacs3a (not ACS3a-G289V) could confer a significant delay of ethylene peak; alleles MdACS1–2 and Mdacs3a (excluding ACS3a-G289V) were highly enriched in M. domestica and M. hybrid when compared with those in M. sieversii. These findings are of practical implications in developing apples of low and delayed ethylene profiles by utilizing the beneficial alleles MdACS1-2 and Mdacs3a. PMID:27231553

  8. Molecular Dynamics Simulations of Voltage-Gated Cation Channels: Insights on Voltage-Sensor Domain Function and Modulation

    PubMed Central

    Delemotte, Lucie; Klein, Michael L.; Tarek, Mounir

    2012-01-01

    Since their discovery in the 1950s, the structure and function of voltage-gated cation channels (VGCC) has been largely understood thanks to results stemming from electrophysiology, pharmacology, spectroscopy, and structural biology. Over the past decade, computational methods such as molecular dynamics (MD) simulations have also contributed, providing molecular level information that can be tested against experimental results, thereby allowing the validation of the models and protocols. Importantly, MD can shed light on elements of VGCC function that cannot be easily accessed through “classical” experiments. Here, we review the results of recent MD simulations addressing key questions that pertain to the function and modulation of the VGCC’s voltage-sensor domain (VSD) highlighting: (1) the movement of the S4-helix basic residues during channel activation, articulating how the electrical driving force acts upon them; (2) the nature of the VSD intermediate states on transitioning between open and closed states of the VGCC; and (3) the molecular level effects on the VSD arising from mutations of specific S4 positively charged residues involved in certain genetic diseases. PMID:22654756

  9. Modes of Access: The Influence of Dissemination Channels on the Use of Open Access Monographs

    ERIC Educational Resources Information Center

    Snijder, Ronald

    2014-01-01

    Introduction: This paper studies the effects of several dissemination channels in an open access environment by analysing the download data of the OAPEN Library. Method: Download data were obtained containing the number of downloads and the name of the Internet provider. Based on public information, each Internet provider was categorised. The…

  10. EPICS Channel Access Server for LabVIEW

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

    Zhukov, Alexander P.

    It can be challenging to interface National Instruments LabVIEW (http://www.ni.com/labview/) with EPICS (http://www.aps.anl.gov/epics/). Such interface is required when an instrument control program was developed in LabVIEW but it also has to be part of global control system. This is frequently useful in big accelerator facilities. The Channel Access Server is written in LabVIEW, so it works on any hardware/software platform where LabVIEW is available. It provides full server functionality, so any EPICS client can communicate with it.

  11. 47 CFR 69.709 - Dedicated transport and special access services other than channel terminations between LEC end...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... transport and special access services other than channel terminations between LEC end offices and customer... services other than channel terminations between LEC end offices and customer premises, determined as... 47 Telecommunication 3 2010-10-01 2010-10-01 false Dedicated transport and special access services...

  12. The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels.

    PubMed

    Ozoe, Yoshihisa; Asahi, Miho; Ozoe, Fumiyo; Nakahira, Kunimitsu; Mita, Takeshi

    2010-01-01

    A structurally unique isoxazoline class compound, A1443, exhibits antiparasitic activity against cat fleas and dog ticks comparable to that of the commercial ectoparasiticide fipronil. This isoxazoline compound inhibits specific binding of the gamma-aminobutyric acid (GABA) receptor channel blocker [(3)H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) to housefly-head membranes, with an IC(50) value of 455pM. In contrast, the IC(50) value in rat-brain membranes is>10muM. To study the mode of action of this isoxazoline, we utilized MdGBCl and MdGluCl cDNAs, which encode the subunits of housefly GABA- and glutamate-gated chloride channels, respectively. Two-electrode voltage clamp electrophysiology was used to confirm that A1443 blocks GABA- and glutamate-induced chloride currents in Xenopus oocytes expressing MdGBCl or MdGluCl channels, with IC(50) values of 5.32 and 79.9 nM, respectively. Blockade by A1443 was observed in A2'S-MdGBCl and S2'A-MdGluCl mutant channels at levels similar to those of the respective wild-types, and houseflies expressing A2'S-MdGBCl channels were as susceptible to A1443 as standard houseflies. These findings indicate that A1443 is a novel and specific blocker of insect ligand-gated chloride channels. Copyright 2009 Elsevier Inc. All rights reserved.

  13. 3MdB: the Mexican Million Models database

    NASA Astrophysics Data System (ADS)

    Morisset, C.; Delgado-Inglada, G.

    2014-10-01

    The 3MdB is an original effort to construct a large multipurpose database of photoionization models. This is a more modern version of a previous attempt based on Cloudy3D and IDL tools. It is accessed by MySQL requests. The models are obtained using the well known and widely used Cloudy photoionization code (Ferland et al, 2013). The database is aimed to host grids of models with different references to identify each project and to facilitate the extraction of the desired data. We present here a description of the way the database is managed and some of the projects that use 3MdB. Anybody can ask for a grid to be run and stored in 3MdB, to increase the visibility of the grid and the potential side applications of it.

  14. A Continuum Poisson-Boltzmann Model for Membrane Channel Proteins

    PubMed Central

    Xiao, Li; Diao, Jianxiong; Greene, D'Artagnan; Wang, Junmei; Luo, Ray

    2017-01-01

    Membrane proteins constitute a large portion of the human proteome and perform a variety of important functions as membrane receptors, transport proteins, enzymes, signaling proteins, and more. Computational studies of membrane proteins are usually much more complicated than those of globular proteins. Here we propose a new continuum model for Poisson-Boltzmann calculations of membrane channel proteins. Major improvements over the existing continuum slab model are as follows:1) The location and thickness of the slab model are fine-tuned based on explicit-solvent MD simulations. 2) The highly different accessibility in the membrane and water regions are addressed with a two-step, two-probe grid labeling procedure, and 3) The water pores/channels are automatically identified. The new continuum membrane model is optimized (by adjusting the membrane probe, as well as the slab thickness and center) to best reproduce the distributions of buried water molecules in the membrane region as sampled in explicit water simulations. Our optimization also shows that the widely adopted water probe of 1.4 Å for globular proteins is a very reasonable default value for membrane protein simulations. It gives the best compromise in reproducing the explicit water distributions in membrane channel proteins, at least in the water accessible pore/channel regions that we focus on. Finally, we validate the new membrane model by carrying out binding affinity calculations for a potassium channel, and we observe a good agreement with experiment results. PMID:28564540

  15. Structural Determinants of the Closed KCa3.1 Channel Pore in Relation to Channel Gating: Results from a Substituted Cysteine Accessibility Analysis

    PubMed Central

    Klein, Hélène; Garneau, Line; Banderali, Umberto; Simoes, Manuel; Parent, Lucie; Sauvé, Rémy

    2007-01-01

    In this work we address the question of the KCa3.1 channel pore structure in the closed configuration in relation to the contribution of the C-terminal end of the S6 segments to the Ca2+-dependent gating process. Our results based on SCAM (substituted cysteine accessibility method) experiments first demonstrate that the S6 transmembrane segment of the open KCa3.1 channel contains two distinct functional domains delimited by V282 with MTSEA and MTSET binding leading to a total channel inhibition at positions V275, T278, and V282 and to a steep channel activation at positions A283 and A286. The rates of modification by MTSEA (diameter 4.6 Å) of the 275C (central cavity) and 286C residues (S6 C-terminal end) for the closed channel configuration were found to differ by less than sevenfold, whereas experiments performed with the larger MTSET reagent (diameter 5.8 Å) resulted in modification rates 103–104 faster for cysteines at 286 compared with 275. Consistent with these results, the modification rates of the cavity lining 275C residue by MTSEA, Et-Hg+, and Ag+ appeared poorly state dependent, whereas modification rates by MTSET were 103 faster for the open than the closed configuration. A SCAM analysis of the channel inner vestibule in the closed state revealed in addition that cysteine residues at 286 were accessible to MTS reagents as large as MTS-PtrEA, a result supported by the observation that binding of MTSET to cysteines at positions 283 or 286 could neither sterically nor electrostatically block the access of MTSEA to the closed channel cavity (275C). It follows that the closed KCa3.1 structure can hardly be accountable by an inverted teepee-like structure as described for KcsA, but is better represented by a narrow passage centered at V282 (equivalent to V474 in Shaker) connecting the channel central cavity to the cytosolic medium. This passage would not be however restrictive to the diffusion of small reagents such as MTSEA, Et-Hg+, and Ag+, arguing

  16. Simple Ion Channels: From Structure to Electrophysiology and Back

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrzej

    2018-01-01

    A reliable way to establish whether our understanding of a channel is satisfactory is to reproduce its measured ionic conductance over a broad range of applied voltages in computer simulations. In molecular dynamics (MD), this can be done by way of applying an external electric field to the system and counting the number of ions that traverse the channel per unit time. Since this approach is computationally very expensive, we have developed a markedly more efficient alternative in which MD is combined with the electrodiffusion (ED) equation. In this approach, the assumptions of the ED equation can be rigorously tested, and the precision and consistency of the calculated conductance can be determined. We have demonstrated that the full current/voltage dependence and the underlying free energy profile for a simple channel can be reliably calculated from equilibrium or non-equilibrium MD simulations at a single voltage. To carry out MD simulations, a structural model of a channel has to be assumed, which is an important constraint, considering that high-resolution structures are available for only very few simple channels. If the comparison of calculated ionic conductance with electrophysiological data is satisfactory, it greatly increases our confidence that the structure and the function are described sufficiently accurately. We examined the validity of the ED for several channels embedded in phospholipid membranes - four naturally occurring channels: trichotoxin, alamethicin, p7 from hepatitis C virus (HCV) and Vpu from the HIV-1 virus, and a synthetic, hexameric channel, formed by a 21-residue peptide that contains only leucine and serine. All these channels mediate transport of potassium and chloride ions. It was found that the ED equation is satisfactory for these systems. In some of them experimental and calculated electrophysiological properties are in good agreement, whereas in others there are strong indications that the structural models are incorrect.

  17. PHYSICAL PROPERTIES OF NEAR-EARTH ASTEROID 2011 MD

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

    Mommert, M.; Trilling, D. E.; Farnocchia, D.

    We report on observations of near-Earth asteroid 2011 MD with the Spitzer Space Telescope. We have spent 19.9 hr of observing time with channel 2 (4.5 μm) of the Infrared Array Camera and detected the target within the 2σ positional uncertainty ellipse. Using an asteroid thermophysical model and a model of nongravitational forces acting upon the object, we constrain the physical properties of 2011 MD, based on the measured flux density and available astrometry data. We estimate 2011 MD to be (6{sub −2}{sup +4}) m in diameter with a geometric albedo of 0.3{sub −0.2}{sup +0.4} (uncertainties are 1σ). We find the asteroid's most probablemore » bulk density to be (1.1{sub −0.5}{sup +0.7}) g cm{sup –3}, which implies a total mass of (50-350) t and a macroporosity of ≥65%, assuming a material bulk density typical of non-primitive meteorite materials. A high degree of macroporosity suggests that 2011 MD is a rubble-pile asteroid, the rotation of which is more likely to be retrograde than prograde.« less

  18. MD-CTS: An integrated terminology reference of clinical and translational medicine.

    PubMed

    Ray, Will; Finamore, Joe; Rastegar-Mojarad, Majid; Kadolph, Chris; Ye, Zhan; Bohne, Jacquie; Xu, Yin; Burish, Dan; Sondelski, Joshua; Easker, Melissa; Finnegan, Brian; Bartkowiak, Barbara; Smith, Catherine Arnott; Tachinardi, Umberto; Mendonca, Eneida A; Weichelt, Bryan; Lin, Simon M

    2016-01-01

    New vocabularies are rapidly evolving in the literature relative to the practice of clinical medicine and translational research. To provide integrated access to new terms, we developed a mobile and desktop online reference-Marshfield Dictionary of Clinical and Translational Science (MD-CTS). It is the first public resource that comprehensively integrates Wiktionary (word definition), BioPortal (ontology), Wiki (image reference), and Medline abstract (word usage) information. MD-CTS is accessible at http://spellchecker.mfldclin.edu/. The website provides a broadened capacity for the wider clinical and translational science community to keep pace with newly emerging scientific vocabulary. An initial evaluation using 63 randomly selected biomedical words suggests that online references generally provided better coverage (73%-95%) than paper-based dictionaries (57-71%).

  19. On Channel Sharing in Discrete-Time, Multi-Access Broadcast Communications,

    DTIC Science & Technology

    1980-09-01

    towards a physical intepretation . of the solutions. 1.4.3 THE PROBLEM OF CAPACITY Our discussion of capacity has two objectives. First, to explore...8021 (DARPA). Yemnii, Y., "On Channel Sharing in Discrete-Time, Multi-Access Broadcast Communication," Sep- tember 1980, UCLA-ENG-8061. (DARPA). 280 FILMED 9-83 DTIC 𔃾’W 9111 ’K4VFClMlP-- Om mFoca 1,00,

  20. A phenomenological continuum model for force-driven nano-channel liquid flows

    NASA Astrophysics Data System (ADS)

    Ghorbanian, Jafar; Celebi, Alper T.; Beskok, Ali

    2016-11-01

    A phenomenological continuum model is developed using systematic molecular dynamics (MD) simulations of force-driven liquid argon flows confined in gold nano-channels at a fixed thermodynamic state. Well known density layering near the walls leads to the definition of an effective channel height and a density deficit parameter. While the former defines the slip-plane, the latter parameter relates channel averaged density with the desired thermodynamic state value. Definitions of these new parameters require a single MD simulation performed for a specific liquid-solid pair at the desired thermodynamic state and used for calibration of model parameters. Combined with our observations of constant slip-length and kinematic viscosity, the model accurately predicts the velocity distribution and volumetric and mass flow rates for force-driven liquid flows in different height nano-channels. Model is verified for liquid argon flow at distinct thermodynamic states and using various argon-gold interaction strengths. Further verification is performed for water flow in silica and gold nano-channels, exhibiting slip lengths of 1.2 nm and 15.5 nm, respectively. Excellent agreements between the model and the MD simulations are reported for channel heights as small as 3 nm for various liquid-solid pairs.

  1. IQ imbalance tolerable parallel-channel DMT transmission for coherent optical OFDMA access network

    NASA Astrophysics Data System (ADS)

    Jung, Sang-Min; Mun, Kyoung-Hak; Jung, Sun-Young; Han, Sang-Kook

    2016-12-01

    Phase diversity of coherent optical communication provides spectrally efficient higher-order modulation for optical communications. However, in-phase/quadrature (IQ) imbalance in coherent optical communication degrades transmission performance by introducing unwanted signal distortions. In a coherent optical orthogonal frequency division multiple access (OFDMA) passive optical network (PON), IQ imbalance-induced signal distortions degrade transmission performance by interferences of mirror subcarriers, inter-symbol interference (ISI), and inter-channel interference (ICI). We propose parallel-channel discrete multitone (DMT) transmission to mitigate transceiver IQ imbalance-induced signal distortions in coherent orthogonal frequency division multiplexing (OFDM) transmissions. We experimentally demonstrate the effectiveness of parallel-channel DMT transmission compared with that of OFDM transmission in the presence of IQ imbalance.

  2. 78 FR 14547 - Praxedes E. Alverez Santiago, M.D., Daniel Perez Brisebois, M.D., Jorge Grillasca Palou, M.D...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-06

    ...., Angel B. Rivera Santos, M.D., Cosme D. Santos Torres, M.D., and Juan L. Vilaro Chardon, M.D.; Analysis... attached Analysis to Aid Public Comment describes both the allegations in the draft complaint and the terms... record for a period of thirty (30) days. The following Analysis to Aid Public Comment describes the terms...

  3. Investigation of polarization effects in the gramicidin A channel from ab initio molecular dynamics simulations.

    PubMed

    Timko, Jeff; Kuyucak, Serdar

    2012-11-28

    Polarization is an important component of molecular interactions and is expected to play a particularly significant role in inhomogeneous environments such as pores and interfaces. Here we investigate the effects of polarization in the gramicidin A ion channel by performing quantum mechanics/molecular mechanics molecular dynamics (MD) simulations and comparing the results with those obtained from classical MD simulations with non-polarizable force fields. We consider the dipole moments of backbone carbonyl groups and channel water molecules as well as a number of structural quantities of interest. The ab initio results show that the dipole moments of the carbonyl groups and water molecules are highly sensitive to the hydrogen bonds (H-bonds) they participate in. In the absence of a K(+) ion, water molecules in the channel are quite mobile, making the H-bond network highly dynamic. A central K(+) ion acts as an anchor for the channel waters, stabilizing the H-bond network and thereby increasing their average dipole moments. In contrast, the K(+) ion has little effect on the dipole moments of the neighboring carbonyl groups. The weakness of the ion-peptide interactions helps to explain the near diffusion-rate conductance of K(+) ions through the channel. We also address the sampling issue in relatively short ab initio MD simulations. Results obtained from a continuous 20 ps ab initio MD simulation are compared with those generated by sampling ten windows from a much longer classical MD simulation and running each window for 2 ps with ab initio MD. Both methods yield similar results for a number of quantities of interest, indicating that fluctuations are fast enough to justify the short ab initio MD simulations.

  4. Perspectives on continuum flow models for force-driven nano-channel liquid flows

    NASA Astrophysics Data System (ADS)

    Beskok, Ali; Ghorbanian, Jafar; Celebi, Alper

    2017-11-01

    A phenomenological continuum model is developed using systematic molecular dynamics (MD) simulations of force-driven liquid argon flows confined in gold nano-channels at a fixed thermodynamic state. Well known density layering near the walls leads to the definition of an effective channel height and a density deficit parameter. While the former defines the slip-plane, the latter parameter relates channel averaged density with the desired thermodynamic state value. Definitions of these new parameters require a single MD simulation performed for a specific liquid-solid pair at the desired thermodynamic state and used for calibration of model parameters. Combined with our observations of constant slip-length and kinematic viscosity, the model accurately predicts the velocity distribution and volumetric and mass flow rates for force-driven liquid flows in different height nano-channels. Model is verified for liquid argon flow at distinct thermodynamic states and using various argon-gold interaction strengths. Further verification is performed for water flow in silica and gold nano-channels, exhibiting slip lengths of 1.2 nm and 15.5 nm, respectively. Excellent agreements between the model and the MD simulations are reported for channel heights as small as 3 nm for various liquid-solid pairs.

  5. Apple fruit acidity is genetically diversified by natural variations in three hierarchical epistatic genes MdSAUR37, MdPP2CH and MdALMTII.

    PubMed

    Jia, Dongjie; Shen, Fei; Wang, Yi; Wu, Ting; Xu, Xuefeng; Zhang, Xinzhong; Han, Zhenhai

    2018-05-11

    Many efforts have been made to map quantitative trait loci (QTLs) to facilitate practical marker-assisted selection (MAS) in plants. In the present study, we identified four genome-wide major QTLs responsible for apple fruit acidity by MapQTL and BSA-seq analyses using two independent pedigree-based populations. Candidate genes were screened in major QTL regions, and three functional gene markers, including a non-synonymous A/G single nucleotide polymorphism (SNP) in the coding region of MdPP2CH, a 36-bp insertion in the promoter of MdSAUR37, and a previously reported SNP in MdALMTII, were validated to influence the malate content of apple fruits. In addition, MdPP2CH inactivated three vacuolar H + -ATPases (MdVHA-A3, MdVHA-B2 and MdVHA-D2) and one aluminium-activated malate transporter (MdALMTII) via dephosphorylation and negatively influenced fruit malate accumulation. The dephosphotase activity of MdPP2CH was suppressed by MdSAUR37, which implied a higher hierarchy of genetic interaction. Therefore, the MdSAUR37/MdPP2CH/MdALMTII chain cascaded hierarchical epistatic genetic effects to precisely determine apple fruit malate content. An A/G SNP (-1010) on MdMYB44 promoter region from a major QTL (qtl08.1) was closely associated with fruit malate content. The predicted phenotype values (PPVs) were estimated using the tentative genotype values of the gene markers, and the PPVs were significantly correlated with the observed phenotype values. Our findings provide an insight into plant genome-based selection in apples and will aid in conducting research to understand the physiological fundamentals of quantitative genetics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Metadata (MD)

    Treesearch

    Robert E. Keane

    2006-01-01

    The Metadata (MD) table in the FIREMON database is used to record any information about the sampling strategy or data collected using the FIREMON sampling procedures. The MD method records metadata pertaining to a group of FIREMON plots, such as all plots in a specific FIREMON project. FIREMON plots are linked to metadata using a unique metadata identifier that is...

  7. Exploring intentions of physician-scientist trainees: factors influencing MD and MD/PhD interest in research careers.

    PubMed

    Kwan, Jennifer M; Daye, Dania; Schmidt, Mary Lou; Conlon, Claudia Morrissey; Kim, Hajwa; Gaonkar, Bilwaj; Payne, Aimee S; Riddle, Megan; Madera, Sharline; Adami, Alexander J; Winter, Kate Quinn

    2017-07-11

    Prior studies have described the career paths of physician-scientist candidates after graduation, but the factors that influence career choices at the candidate stage remain unclear. Additionally, previous work has focused on MD/PhDs, despite many physician-scientists being MDs. This study sought to identify career sector intentions, important factors in career selection, and experienced and predicted obstacles to career success that influence the career choices of MD candidates, MD candidates with research-intense career intentions (MD-RI), and MD/PhD candidates. A 70-question survey was administered to students at 5 academic medical centers with Medical Scientist Training Programs (MSTPs) and Clinical and Translational Science Awards (CTSA) from the NIH. Data were analyzed using bivariate or multivariate analyses. More MD/PhD and MD-RI candidates anticipated or had experienced obstacles related to balancing academic and family responsibilities and to balancing clinical, research, and education responsibilities, whereas more MD candidates indicated experienced and predicted obstacles related to loan repayment. MD/PhD candidates expressed higher interest in basic and translational research compared to MD-RI candidates, who indicated more interest in clinical research. Overall, MD-RI candidates displayed a profile distinct from both MD/PhD and MD candidates. MD/PhD and MD-RI candidates experience obstacles that influence their intentions to pursue academic medical careers from the earliest training stage, obstacles which differ from those of their MD peers. The differences between the aspirations of and challenges facing MD, MD-RI and MD/PhD candidates present opportunities for training programs to target curricula and support services to ensure the career development of successful physician-scientists.

  8. Multiple-access relaying with network coding: iterative network/channel decoding with imperfect CSI

    NASA Astrophysics Data System (ADS)

    Vu, Xuan-Thang; Renzo, Marco Di; Duhamel, Pierre

    2013-12-01

    In this paper, we study the performance of the four-node multiple-access relay channel with binary Network Coding (NC) in various Rayleigh fading scenarios. In particular, two relay protocols, decode-and-forward (DF) and demodulate-and-forward (DMF) are considered. In the first case, channel decoding is performed at the relay before NC and forwarding. In the second case, only demodulation is performed at the relay. The contributions of the paper are as follows: (1) two joint network/channel decoding (JNCD) algorithms, which take into account possible decoding error at the relay, are developed in both DF and DMF relay protocols; (2) both perfect channel state information (CSI) and imperfect CSI at receivers are studied. In addition, we propose a practical method to forward the relays error characterization to the destination (quantization of the BER). This results in a fully practical scheme. (3) We show by simulation that the number of pilot symbols only affects the coding gain but not the diversity order, and that quantization accuracy affects both coding gain and diversity order. Moreover, when compared with the recent results using DMF protocol, our proposed DF protocol algorithm shows an improvement of 4 dB in fully interleaved Rayleigh fading channels and 0.7 dB in block Rayleigh fading channels.

  9. VIEW IN OPPOSITE DIRECTION AS MD1351 AND MD1352. RAW MATERIAL ...

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

    VIEW IN OPPOSITE DIRECTION AS MD-135-1 AND MD-135-2. RAW MATERIAL CONVEYOR AT LEFT DEPOSITS SHELL INTO MILLING MACHINE AT LOWER LEFT. ENGINE IS AT LOWER RIGHT AND RADIATOR AT LOWER CENTER. ROLLER SORTER IS AT TOP OF CONVEYOR. - F. & H. Benning Company Oyster Mill, 14430 Solomons Island Road (moved from 1014 Benning Road, Galesville, Anne Arundel County, Maryland), Solomons, Calvert County, MD

  10. Effect of modifying the screw access channels of zirconia implant abutment on the cement flow pattern and retention of zirconia restorations.

    PubMed

    Wadhwani, Chandur; Chung, Kwok-Hung

    2014-07-01

    The effect of managing the screw access channels of zirconia implant abutments in the esthetic zone has not been extensively evaluated. The purpose of this study was to determine the effect of an insert placed within the screw access channel of an anterior zirconia implant abutment on the amount of cement retained within the restoration-abutment system and on the dislodging force. Thirty-six paired zirconia abutments and restorations were fabricated by computer-aided design and computer-aided manufacturing and were divided into 3 groups: open abutment, with the screw access channel unfilled; closed abutment, with the screw access channel sealed; and insert abutment, with a thin, tubular metal insert projection continuous with the screw head and placed into the abutment screw access channel. The restorations were cemented to the abutments with preweighed eugenol-free zinc oxide cement (TempBond NE). Excess cement was removed, and the weight of the cement that remained in the restoration-abutment system was measured. Vertical tensile dislodging forces were recorded at a crosshead speed of 5 mm/min after incubation in a 37°C water bath for 24 hours. The specimens were examined for the cement flow pattern into the screw access channel after dislodgement. Data were analyzed with ANOVA, followed by multiple comparisons by using the Tukey honestly significant difference test (α = .05). The mean (standard deviation) of retentive force values ranged from 108.1 ± 29.9 N to 148.3 ± 21.0 N. The retentive force values differed significantly between the insert abutment and both the open abutment (P < .05) and closed abutment groups (P < .01). Distinct patterns of cement failure were noted. The weight of the cement that remained in the system differed significantly, with both open abutment and insert abutment being greater than closed abutment (P < .05). Modifying the internal configuration of the screw access channel of an esthetic zirconia implant abutment with a metal

  11. Channel access schemes and fiber optic configurations for integrated-services local area networks

    NASA Astrophysics Data System (ADS)

    Nassehi, M. Mehdi

    1987-03-01

    Local Area Networks are in common use for data communications and have enjoyed great success. Recently, there is a growing interest in using a single network to support many applications in addition to traditional data traffic. These additional applications introduce new requirements in terms of volume of traffic and real-time delivery of data which are not met by existing networks. To satisfy these requirements, a high-bandwidth tranmission medium, such as fiber optics, and a distributed channel access scheme for the efficient sharing of the bandwidth among the various applications are needed. As far as the throughput-delay requirements of the various application are concerned, a network structure along with a distributed channel access are proposed which incorporate appropriate scheduling policies for the transmission of outstanding messages on the network. A dynamic scheduling policy was devised which outperforms all existing policies in terms of minimizing the expected cost per message. A broadcast mechanism was devised for the efficient dissemination of all relevant information. Fiber optic technology is considered for the high-bandwidth transmisison medium.

  12. 75 FR 6162 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-81 (MD-81), DC-9-82 (MD-82...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-08

    ... Corporation Model DC- 9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes... Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 airplanes. This...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service...

  13. Online distribution channel increases article usage on Mendeley: a randomized controlled trial.

    PubMed

    Kudlow, Paul; Cockerill, Matthew; Toccalino, Danielle; Dziadyk, Devin Bissky; Rutledge, Alan; Shachak, Aviv; McIntyre, Roger S; Ravindran, Arun; Eysenbach, Gunther

    2017-01-01

    Prior research shows that article reader counts (i.e. saves) on the online reference manager, Mendeley, correlate to future citations. There are currently no evidenced-based distribution strategies that have been shown to increase article saves on Mendeley. We conducted a 4-week randomized controlled trial to examine how promotion of article links in a novel online cross-publisher distribution channel (TrendMD) affect article saves on Mendeley. Four hundred articles published in the Journal of Medical Internet Research were randomized to either the TrendMD arm ( n  = 200) or the control arm ( n  = 200) of the study. Our primary outcome compares the 4-week mean Mendeley saves of articles randomized to TrendMD versus control. Articles randomized to TrendMD showed a 77% increase in article saves on Mendeley relative to control. The difference in mean Mendeley saves for TrendMD articles versus control was 2.7, 95% CI (2.63, 2.77), and statistically significant ( p  < 0.01). There was a positive correlation between pageviews driven by TrendMD and article saves on Mendeley (Spearman's rho r  = 0.60). This is the first randomized controlled trial to show how an online cross-publisher distribution channel (TrendMD) enhances article saves on Mendeley. While replication and further study are needed, these data suggest that cross-publisher article recommendations via TrendMD may enhance citations of scholarly articles.

  14. Apple (Malus domestica) MdERF2 negatively affects ethylene biosynthesis during fruit ripening by suppressing MdACS1 transcription.

    PubMed

    Li, Tong; Jiang, Zhongyu; Zhang, Lichao; Tan, Dongmei; Wei, Yun; Yuan, Hui; Li, Tianlai; Wang, Aide

    2016-12-01

    Ripening in climacteric fruit requires the gaseous phytohormone ethylene. Although ethylene signaling has been well studied, knowledge of the transcriptional regulation of ethylene biosynthesis is still limited. Here we show that an apple (Malus domestica) ethylene response factor, MdERF2, negatively affects ethylene biosynthesis and fruit ripening by suppressing the transcription of MdACS1, a gene that is critical for biosynthesis of ripening-related ethylene. Expression of MdERF2 was suppressed by ethylene during ripening of apple fruit, and we observed that MdERF2 bound to the promoter of MdACS1 and directly suppressed its transcription. Moreover, MdERF2 suppressed the activity of the promoter of MdERF3, a transcription factor that we found to bind to the MdACS1 promoter, thereby increasing MdACS1 transcription. We determined that the MdERF2 and MdERF3 proteins directly interact, and this interaction suppresses the binding of MdERF3 to the MdACS1 promoter. Moreover, apple fruit with transiently downregulated MdERF2 expression showed higher ethylene production and faster ripening. Our results indicate that MdERF2 negatively affects ethylene biosynthesis and fruit ripening in apple by suppressing the transcription of MdACS1 via multiple mechanisms, thereby acting as an antagonist of positive ripening regulators. Our findings offer a deep understanding of the transcriptional regulation of ethylene biosynthesis during climacteric fruit ripening. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  15. Local anesthetic and antiepileptic drug access and binding to a bacterial voltage-gated sodium channel

    PubMed Central

    Boiteux, Céline; Vorobyov, Igor; French, Robert J.; French, Christopher; Yarov-Yarovoy, Vladimir; Allen, Toby W.

    2014-01-01

    Voltage-gated sodium (Nav) channels are important targets in the treatment of a range of pathologies. Bacterial channels, for which crystal structures have been solved, exhibit modulation by local anesthetic and anti-epileptic agents, allowing molecular-level investigations into sodium channel-drug interactions. These structures reveal no basis for the “hinged lid”-based fast inactivation, seen in eukaryotic Nav channels. Thus, they enable examination of potential mechanisms of use- or state-dependent drug action based on activation gating, or slower pore-based inactivation processes. Multimicrosecond simulations of NavAb reveal high-affinity binding of benzocaine to F203 that is a surrogate for FS6, conserved in helix S6 of Domain IV of mammalian sodium channels, as well as low-affinity sites suggested to stabilize different states of the channel. Phenytoin exhibits a different binding distribution owing to preferential interactions at the membrane and water–protein interfaces. Two drug-access pathways into the pore are observed: via lateral fenestrations connecting to the membrane lipid phase, as well as via an aqueous pathway through the intracellular activation gate, despite being closed. These observations provide insight into drug modulation that will guide further developments of Nav inhibitors. PMID:25136136

  16. Medical-Grade Channel Access and Admission Control in 802.11e EDCA for Healthcare Applications

    PubMed Central

    Son, Sunghwa; Park, Kyung-Joon; Park, Eun-Chan

    2016-01-01

    In this paper, we deal with the problem of assuring medical-grade quality of service (QoS) for real-time medical applications in wireless healthcare systems based on IEEE 802.11e. Firstly, we show that the differentiated channel access of IEEE 802.11e cannot effectively assure medical-grade QoS because of priority inversion. To resolve this problem, we propose an efficient channel access algorithm. The proposed algorithm adjusts arbitrary inter-frame space (AIFS) in the IEEE 802.11e protocol depending on the QoS measurement of medical traffic, to provide differentiated near-absolute priority for medical traffic. In addition, based on rigorous capacity analysis, we propose an admission control scheme that can avoid performance degradation due to network overload. Via extensive simulations, we show that the proposed mechanism strictly assures the medical-grade QoS and improves the throughput of low-priority traffic by more than several times compared to the conventional IEEE 802.11e. PMID:27490666

  17. Exploring the Structure of the Voltage-gated Na+ Channel by an Engineered Drug Access Pathway to the Receptor Site for Local Anesthetics*

    PubMed Central

    Lukacs, Peter; Gawali, Vaibhavkumar S.; Cervenka, Rene; Ke, Song; Koenig, Xaver; Rubi, Lena; Zarrabi, Touran; Hilber, Karlheinz; Stary-Weinzinger, Anna; Todt, Hannes

    2014-01-01

    Despite the availability of several crystal structures of bacterial voltage-gated Na+ channels, the structure of eukaryotic Na+ channels is still undefined. We used predictions from available homology models and crystal structures to modulate an external access pathway for the membrane-impermeant local anesthetic derivative QX-222 into the internal vestibule of the mammalian rNaV1.4 channel. Potassium channel-based homology models predict amino acid Ile-1575 in domain IV segment 6 to be in close proximity to Lys-1237 of the domain III pore-loop selectivity filter. The mutation K1237E has been shown previously to increase the diameter of the selectivity filter. We found that an access pathway for external QX-222 created by mutations of Ile-1575 was abolished by the additional mutation K1237E, supporting the notion of a close spatial relationship between sites 1237 and 1575. Crystal structures of bacterial voltage-gated Na+ channels predict that the side chain of rNaV1.4 Trp-1531 of the domain IV pore-loop projects into the space between domain IV segment 6 and domain III pore-loop and, therefore, should obstruct the putative external access pathway. Indeed, mutations W1531A and W1531G allowed for exceptionally rapid access of QX-222. In addition, W1531G created a second non-selective ion-conducting pore, bypassing the outer vestibule but probably merging into the internal vestibule, allowing for control by the activation gate. These data suggest a strong structural similarity between bacterial and eukaryotic voltage-gated Na+ channels. PMID:24947510

  18. An Apple Protein Kinase MdSnRK1.1 Interacts with MdCAIP1 to Regulate ABA Sensitivity.

    PubMed

    Liu, Xiao-Juan; Liu, Xin; An, Xiu-Hong; Han, Peng-Liang; You, Chun-Xiang; Hao, Yu-Jin

    2017-10-01

    ABA is a crucial phytohormone for development and stress responses in plants. Snf1-related protein kinase 1.1 (SnRK1.1) is involved in the ABA response. However, the molecular mechanism underlying the SnRK1.1 response to ABA is largely unknown. Here, it was found that overexpression of the apple MdSnRK1.1 gene enhanced ABA sensitivity in both transgenic apple calli and Arabidopsis seedlings. Subsequently, a yeast two-hybrid screen demonstrated that MdCAIP1 (C2-domain ABA Insensitive Protein1) interacted with MdSnRK1.1. Their interaction was further confirmed by pull-down and co-immunoprecipitation assays. Expression of the MdCAIP1 gene was positively induced by ABA. Its overexpression enhanced ABA sensitivity in transgenic apple calli. Furthermore, it was found that MdSnRK1.1 phosphorylated the MdCAIP1 protein in vivo and promoted its degradation in vitro and in vivo. As a result, MdSnRK1.1 inhibited MdCAIP1-mediated ABA sensitivity, and MdCAIP1 partially reduced MdSnRK1.1-mediated ABA sensitivity. Our findings indicate that MdSnRK1.1 plays an important role in the ABA response, partially by controlling the stability of the MdCAIP1 protein. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  19. Apple RING E3 ligase MdMIEL1 inhibits anthocyanin accumulation by ubiquitinating and degrading MdMYB1 protein.

    PubMed

    An, Jian-Ping; Liu, Xin; Li, Hao-Hao; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

    2017-11-01

    MdMYB1 is an important regulator for anthocyanin accumulation in apple (Malus × domestica). Here, an apple RING E3 ligase, MdMIEL1, was screened out as a partner of MdMYB1 with a yeast two-hybrid approach. Pull-down, bimolecular fluorescence complementation and coimmunoprecipitation assays further verified the interaction between MdMIEL1 and MdMYB1 proteins. Subsequently, in vitro and in vivo experiments indicated that MdMIEL1 functioned as a ubiquitin E3 ligase to ubiquitinate MdMYB1 protein, followed by degradation through a 26S proteasome pathway. Furthermore, transgenic studies in apple calli and Arabidopsis demonstrated that MdMIEL1 negatively regulated anthocyanin accumulation by modulating the degradation of MdMYB1 protein. Taken together, our findings provide a new insight into the molecular mechanism by which MdMIEL1 negatively regulates anthocyanin biosynthesis by ubiquitinating and degrading MdMYB1 protein. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  20. The Users of Cable TV Access Channels: A Study of the Diffusion and Adoption of a Communications Innovation.

    ERIC Educational Resources Information Center

    Sparkes, Vernone M.

    A mail survey of 91 past and present users of the community programing (public access) channels in the Toronto, Canada, area revealed that personal contact is most important in the diffusion of knowledge about access opportunities. Friends and colleagues were the most often cited initial source of information; but contact by the cable company…

  1. MdSOS2L1 phosphorylates MdVHA-B1 to modulate malate accumulation in response to salinity in apple.

    PubMed

    Hu, Da-Gang; Sun, Cui-Hui; Sun, Mei-Hong; Hao, Yu-Jin

    2016-03-01

    Salt-induced phosphorylation of MdVHA-B1 protein was mediated by MdSOS2L1 protein kinase, and thereby increasing malate content in apple. Salinity is an important environmental factor that influences malate accumulation in apple. However, the molecular mechanism by which salinity regulates this process is poorly understood. In this work, we found that MdSOS2L1, a novel AtSOS2-LIKE protein kinase, interacts with V-ATPase subunit MdVHA-B1. Furthermore, MdSOS2L1 directly phosphorylates MdVHA-B1 at Ser(396) site to modulate malate accumulation in response to salt stress. Meanwhile, a series of transgenic analyses in apple calli showed that the MdSOS2L1-MdVHAB1 pathway was involved in the regulation of malate accumulation. Finally, a viral vector-based transformation approach demonstrated that the MdSOS2L1-MdVHAB1 pathway also modulated malate accumulation in apple fruits with or without salt stress. Collectively, our findings provide a new insight into the mechanism by which MdSOS2L1 phosphorylates MdVHA-B1 to modulate malate accumulation in response to salinity in apple.

  2. Atomic Force Microscopy and MD Simulations Reveal Pore-Like Structures of All-D-Enantiomer of Alzheimer’s β-Amyloid Peptide: Relevance to the Ion Channel Mechanism of AD Pathology

    PubMed Central

    Connelly, Laura; Arce, Fernando Teran; Jang, Hyunbum; Capone, Ricardo; Kotler, Samuel A.; Ramachandran, Srinivasan; Kagan, Bruce L.; Nussinov, Ruth; Lal, Ratnesh

    2012-01-01

    Alzheimer’s disease (AD) is a protein misfolding disease characterized by a build-up of β-amyloid (Aβ) peptide as senile plaques, uncontrolled neurodegeneration, and memory loss. AD pathology is linked to the destabilization of cellular ionic homeostasis and involves Aβ peptide-plasma membrane interactions. In principle, there are two possible ways through which disturbance of the ionic homeostasis can take place: directly, where the Aβ peptide either inserts into the membrane and creates ion-conductive pores or destabilizes the membrane organization; or, indirectly, where the Aβ peptide interacts with existing cell membrane receptors. To distinguish between these two possible types of Aβ-membrane interactions, we took advantage of the biochemical tenet that ligand-receptor interactions are stereospecific; L-amino acid peptides, but not their D-counterparts, bind to cell membrane receptors. However, with respect to the ion channel-mediated mechanism, like L-amino acids, D-amino acid peptides will also form ion channel-like structures. Using atomic force microscopy (AFM) we imaged the structures of both D- and L-enantiomers of the full length Aβ1-42 when reconstituted in lipid bilayers. AFM imaging shows that both L- and D-Aβ isomers form similar channel-like structures. Molecular dynamics (MD) simulations support the AFM imaged 3D structures. Earlier we have shown that D-Aβ1-42 channels conduct ions similarly to their L-counter parts. Taken together, our results support the direct mechanism of Aβ ion channel-mediated destabilization of ionic homeostasis rather than the indirect mechanism through Aβ interaction with membrane receptors. PMID:22217000

  3. Md-miR156ab and Md-miR395 Target WRKY Transcription Factors to Influence Apple Resistance to Leaf Spot Disease.

    PubMed

    Zhang, Qiulei; Li, Yang; Zhang, Yi; Wu, Chuanbao; Wang, Shengnan; Hao, Li; Wang, Shengyuan; Li, Tianzhong

    2017-01-01

    MicroRNAs (miRNAs) are key regulators of gene expression that post-transcriptionally regulate transcription factors involved in plant physiological activities. Little is known about the effects of miRNAs in disease resistance in apple ( Malus × domestica ). We globally profiled miRNAs in the apple cultivar Golden Delicious (GD) infected or not with the apple leaf spot fungus Alternaria alternaria f. sp. mali (ALT1), and identified 58 miRNAs that exhibited more than a 2-fold upregulation upon ALT1 infection. We identified a pair of miRNAs that target protein-coding genes involved in the defense response against fungal pathogens; Md-miR156ab targets a novel WRKY transcription factor, MdWRKYN1, which harbors a TIR and a WRKY domain. Md-miR395 targets another transcription factor, MdWRKY26, which contains two WRKY domains. Real-time PCR analysis showed that Md-miR156ab and Md-miR395 levels increased, while MdWRKYN1 and MdWRKY26 expression decreased in ALT1-inoculated GD leaves; furthermore, the overexpression of Md-miR156ab and Md-miR395 resulted in a significant reduction in MdWRKYN1 and MdWRKY26 expression. To investigate whether these miRNAs and their targets play a crucial role in plant defense, we overexpressed MdWRKYN1 or knocked down Md-miR156ab activity, which in both cases enhanced the disease resistance of the plants by upregulating the expression of the WRKY-regulated pathogenesis-related (PR) protein-encoding genes MdPR3-1, MdPR3-2, MdPR4, MdPR5, MdPR10-1 , and MdPR10-2 . In a similar analysis, we overexpressed MdWRKY26 or suppressed Md-miR395 activity, and found that many PR protein-encoding genes were also regulated by MdWRKY26 . In GD, ALT-induced Md-miR156ab and Md-miR395 suppress MdWRKYN1 and MdWRKY26 expression, thereby decreasing the expression of some PR genes, and resulting in susceptibility to ALT1.

  4. Partially Glycosylated Dendrimers Block MD-2 and Prevent TLR4-MD-2-LPS Complex Mediated Cytokine Responses

    PubMed Central

    Barata, Teresa S.; Teo, Ian; Brocchini, Steve; Zloh, Mire; Shaunak, Sunil

    2011-01-01

    The crystal structure of the TLR4-MD-2-LPS complex responsible for triggering powerful pro-inflammatory cytokine responses has recently become available. Central to cell surface complex formation is binding of lipopolysaccharide (LPS) to soluble MD-2. We have previously shown, in biologically based experiments, that a generation 3.5 PAMAM dendrimer with 64 peripheral carboxylic acid groups acts as an antagonist of pro-inflammatory cytokine production after surface modification with 8 glucosamine molecules. We have also shown using molecular modelling approaches that this partially glycosylated dendrimer has the flexibility, cluster density, surface electrostatic charge, and hydrophilicity to make it a therapeutically useful antagonist of complex formation. These studies enabled the computational study of the interactions of the unmodified dendrimer, glucosamine, and of the partially glycosylated dendrimer with TLR4 and MD-2 using molecular docking and molecular dynamics techniques. They demonstrate that dendrimer glucosamine forms co-operative electrostatic interactions with residues lining the entrance to MD-2's hydrophobic pocket. Crucially, dendrimer glucosamine interferes with the electrostatic binding of: (i) the 4′phosphate on the di-glucosamine of LPS to Ser118 on MD-2; (ii) LPS to Lys91 on MD-2; (iii) the subsequent binding of TLR4 to Tyr102 on MD-2. This is followed by additional co-operative interactions between several of the dendrimer glucosamine's carboxylic acid branches and MD-2. Collectively, these interactions block the entry of the lipid chains of LPS into MD-2's hydrophobic pocket, and also prevent TLR4-MD-2-LPS complex formation. Our studies have therefore defined the first nonlipid-based synthetic MD-2 antagonist using both animal model-based studies of pro-inflammatory cytokine responses and molecular modelling studies of a whole dendrimer with its target protein. Using this approach, it should now be possible to computationally design

  5. mdFoam+: Advanced molecular dynamics in OpenFOAM

    NASA Astrophysics Data System (ADS)

    Longshaw, S. M.; Borg, M. K.; Ramisetti, S. B.; Zhang, J.; Lockerby, D. A.; Emerson, D. R.; Reese, J. M.

    2018-03-01

    This paper introduces mdFoam+, which is an MPI parallelised molecular dynamics (MD) solver implemented entirely within the OpenFOAM software framework. It is open-source and released under the same GNU General Public License (GPL) as OpenFOAM. The source code is released as a publicly open software repository that includes detailed documentation and tutorial cases. Since mdFoam+ is designed entirely within the OpenFOAM C++ object-oriented framework, it inherits a number of key features. The code is designed for extensibility and flexibility, so it is aimed first and foremost as an MD research tool, in which new models and test cases can be developed and tested rapidly. Implementing mdFoam+ in OpenFOAM also enables easier development of hybrid methods that couple MD with continuum-based solvers. Setting up MD cases follows the standard OpenFOAM format, as mdFoam+ also relies upon the OpenFOAM dictionary-based directory structure. This ensures that useful pre- and post-processing capabilities provided by OpenFOAM remain available even though the fully Lagrangian nature of an MD simulation is not typical of most OpenFOAM applications. Results show that mdFoam+ compares well to another well-known MD code (e.g. LAMMPS) in terms of benchmark problems, although it also has additional functionality that does not exist in other open-source MD codes.

  6. A Chronostratigraphic and Environment Magnetic Study of Drill Cores Collected in the Mozambique Channel on Cruise MD13

    NASA Astrophysics Data System (ADS)

    Ray, D. J.; DeBone, K. N.; Smesny, J.; Chadinha, C.; Mitchell, B.; Acton, G. D.; Kulhanek, D. K.

    2017-12-01

    The South Atlantic Petroleum Company donated drill cores from 18 sites cored in October 2013 in the Mozambique Channel off Madagascar by the RV Marion Dufresne. Up to 30.11 m of sediment was recovered from cores collected at two localities, referred to as Juan de Nova ( 16.5°S, 42.9°E) and Belo Profound ( 19.5°S, 42.2°E), in water depths of 2,157-2,795 m. The cores are composed mostly of mixtures of fairly homogenous biogenic ooze and clay that is highly bioturbated, with turbidites occurring relatively commonly (about every meter or two) in most of the cores, although rarely in others (e.g., Core MD13-3506). The core color varies between light tan, olive gray, light brown, and light reddish brown. The darker colors probably reflect higher proportion of terrigenous input and the lighter intervals more biogenic input. We collected rock magnetic and paleomagnetic data along the cores and conducted initial calcareous nannofossil biostratigraphic analyses in order to provide stratigraphic and chronologic constraints and to investigate paleoenvironment changes. Records of magnetic susceptibility are used to correlate stratigraphy between sites and then are correlated to well-dated global records of climate change, such as the marine oxygen isotope record. The correlation to oxygen isotope records, which is constrained by biostratigraphic and paleomagnetic observations, helps refine the chronostratigraphy and allows us to interpret the variations in lithology and magnetic properties in the context of global climate change.

  7. Hydrodynamic Modeling for Channel and Shoreline Stabilization at Rhodes Point, Smith Island, MD

    DTIC Science & Technology

    2016-11-01

    shorelines. Both Alternatives included the same revetment structure for protecting the south shoreline. The Coastal Modeling System (CMS, including CMS...ER D C/ CH L TR -1 6- 17 Coastal Inlets Research Program Hydrodynamic Modeling for Channel and Shoreline Stabilization at Rhodes Point...acwc.sdp.sirsi.net/client/default. Coastal Inlets Research Program ERDC/CHL TR-16-17 November 2016 Hydrodynamic Modeling for Channel and Shoreline

  8. Water transport in human aquaporin-4: molecular dynamics (MD) simulations.

    PubMed

    Cui, Yubao; Bastien, David A

    2011-09-09

    Aquaporin-4 (AQP4) is the predominant water channel in the central nervous system, where it has been reported to be involved in many pathophysiological roles including water transport. In this paper, the AQP4 tetramer was modeled from its PDB structure file, embedded in a palmitoyl-oleoyl-phosphatidyl-choline (POPC) lipid bilayer, solvated in water, then minimized and equilibrated by means of molecular dynamics simulations. Analysis of the equilibrated structure showed that the central pore along the fourfold axis of the tetramers is formed with hydrophobic amino acid residues. In particular, Phe-195, Leu-191 and Leu-75, form the narrowest part of the pore. Therefore water molecules are not expected to transport through the central pore, which was confirmed by MD simulations. Each monomer of the AQP4 tetramers forms a channel whose walls consist mostly of hydrophilic residues. There are eight water molecules in single file observed in each of the four channels, transporting through the selectivity filter containing Arg-216, His-201, Phe-77, Ala-210, and the two conserved Asn-Pro-Ala (NPA) motifs containing Asn-213 and Asn-97. By using Brownian dynamics fluctuation-dissipation-theorem (BD-FDT), the overall free-energy profile was obtained for water transporting through AQP4 for the first time, which gives a complete map of the entire channel of water permeation. Copyright © 2011. Published by Elsevier Inc.

  9. MdHIR proteins repress anthocyanin accumulation by interacting with the MdJAZ2 protein to inhibit its degradation in apples

    PubMed Central

    Chen, Ke-Qin; Zhao, Xian-Yan; An, Xiu-Hong; Tian, Yi; Liu, Dan-Dan; You, Chun-Xiang; Hao, Yu-Jin

    2017-01-01

    In higher plants, jasmonate ZIM-domain (JAZ) proteins negatively regulate the biosynthesis of anthocyanins by interacting with bHLH transcription factors. However, it is largely unknown if and how other regulators are involved in this process. In this study, the apple MdJAZ2 protein was characterized in regards to its function in the negative regulation of anthocyanin accumulation and peel coloration. MdJAZ2 was used as a bait to screen a cDNA library using the yeast two-hybrid method. The hypersensitive induced reaction (HIR) proteins, MdHIR2 and MdHIR4, were obtained from this yeast two-hybrid. The ZIM domain of MdJAZ2 and the PHB domain of the MdHIR proteins are necessary for their interactions. The interactions were further verified using an in vitro pull-down assay. Subsequently, immunoblotting assays demonstrated that MdHIR4 enhanced the stability of the MdJAZ2-GUS protein. Finally, a viral vector-based transformation method showed that MdHIR4 inhibited anthocyanin accumulation and fruit coloration in apple by modulating the expression of genes associated with anthocyanin biosynthesis. PMID:28317851

  10. Preparing MD-PhD students for clinical rotations: navigating the interface between PhD and MD training.

    PubMed

    Goldberg, Charles; Insel, Paul A

    2013-06-01

    Many aspects of MD-PhD training are not optimally designed to prepare students for their future roles as translational clinician-scientists. The transition between PhD research efforts and clinical rotations is one hurdle that must be overcome. MD-PhD students have deficits in clinical skills compared with those of their MD-only colleagues at the time of this transition. Reimmersion programs (RPs) targeted to MD-PhD students have the potential to help them navigate this transition.The authors draw on their experience creating and implementing an RP that incorporates multiple types of activities (clinical exam review, objective structured clinical examination, and supervised practice in patient care settings) designed to enhance the participants' skills and readiness for clinical efforts. On the basis of this experience, they note that MD-PhD students' time away from the clinical environment negatively affects their clinical skills, causing them to feel underprepared for clinical rotations. The authors argue that participation in an RP can help students feel more comfortable speaking with and examining patients and decrease their anxiety regarding clinical encounters. The authors propose that RPs can have positive outcomes for improving the transition from PhD to clinical MD training in dual-degree programs. Identifying and addressing this and other transitions need to be considered to improve the educational experience of MD-PhD students.

  11. Channel access schemes and fiber optic configurations for integrated-services local area networks. Ph.D. Thesis

    NASA Technical Reports Server (NTRS)

    Nassehi, M. Mehdi

    1987-01-01

    Local Area Networks are in common use for data communications and have enjoyed great success. Recently, there is a growing interest in using a single network to support many applications in addition to traditional data traffic. These additional applications introduce new requirements in terms of volume of traffic and real-time delivery of data which are not met by existing networks. To satisfy these requirements, a high-bandwidth tranmission medium, such as fiber optics, and a distributed channel access scheme for the efficient sharing of the bandwidth among the various applications are needed. As far as the throughput-delay requirements of the various application are concerned, a network structure along with a distributed channel access are proposed which incorporate appropriate scheduling policies for the transmission of outstanding messages on the network. A dynamic scheduling policy was devised which outperforms all existing policies in terms of minimizing the expected cost per message. A broadcast mechanism was devised for the efficient dissemination of all relevant information. Fiber optic technology is considered for the high-bandwidth transmisison medium.

  12. Registration of cotton germplasm USDA MD 16-1 and USDA MD 16-2 with enhanced lint yield and fiber quality.

    USDA-ARS?s Scientific Manuscript database

    Upland cotton germplasm USDA MD 16-1 (Reg. No. __ and PI ___ ), and USDA MD 16-2 (Reg. No. ___ and PI___) (Gossypium hirsutum L.), have enhanced yield and good fiber quality. These germplasm lines were developed by the USDA-ARS, Stoneville, MS and released in 2017. Two crosses, MD 25-51 X MD 10-9-1 ...

  13. 33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

  14. 33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

  15. 33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

  16. 33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

  17. 33 CFR 334.180 - Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Naval Mine Warfare Test Station, or of U.S. Naval Air Station property. A person in the water or a... areas, U.S. Naval Air Test Center, Patuxent River, Md. 334.180 Section 334.180 Navigation and Navigable... REGULATIONS § 334.180 Patuxent River, Md.; restricted areas, U.S. Naval Air Test Center, Patuxent River, Md...

  18. Acrylic resin guide for locating the abutment screw access channel of cement-retained implant prostheses.

    PubMed

    Ahmed, Ayman; Maroulakos, Georgios; Garaicoa, Jorge

    2016-05-01

    Abutment screw loosening represents a common and challenging technical complication of cement-retained implant prostheses. This article describes the fabrication of a simple and accurate poly(methyl methacrylate) guide for identifying the location and angulation of the abutment screw access channel of a cement-retained implant prosthesis with a loosened abutment screw. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  19. Registration of cotton germplasm line md 10-5

    USDA-ARS?s Scientific Manuscript database

    MD 10-5 (Reg. No. ______, PI 675077) is a noncommercial breeding line of cotton (Gossypium hirsutum L.) released by the USDA-ARS at Stoneville, MS in 2015. MD 10-5 was selected in F4 progenies from a cross between MD 15 (PI 642769) and JJ 1145ne. MD 10-5 has a desirable combination between lint yi...

  20. Ion Transport in Confined Geometries below the Nanoscale: Access Resistance Dominates Protein Channel Conductance in Diluted Solutions.

    PubMed

    Alcaraz, Antonio; López, M Lidón; Queralt-Martín, María; Aguilella, Vicente M

    2017-10-24

    Synthetic nanopores and mesoscopic protein channels have common traits like the importance of electrostatic interactions between the permeating ions and the nanochannel. Ion transport at the nanoscale occurs under confinement conditions so that the usual assumptions made in microfluidics are challenged, among others, by interfacial effects such as access resistance (AR). Here, we show that a sound interpretation of electrophysiological measurements in terms of channel ion selective properties requires the consideration of interfacial effects, up to the point that they dominate protein channel conductance in diluted solutions. We measure AR in a large ion channel, the bacterial porin OmpF, by means of single-channel conductance measurements in electrolyte solutions containing varying concentrations of high molecular weight PEG, sterically excluded from the pore. Comparison of experiments performed in charged and neutral planar membranes shows that lipid surface charges modify the ion distribution and determine the value of AR, indicating that lipid molecules are more than passive scaffolds even in the case of large transmembrane proteins. We also found that AR may reach up to 80% of the total channel conductance in diluted solutions, where electrophysiological recordings register essentially the AR of the system and depend marginally on the pore characteristics. These findings may have implications for several low aspect ratio biological channels that perform their physiological function in a low ionic strength and macromolecule crowded environment, just the two conditions enhancing the AR contribution.

  1. Human-induced stream channel abandonment/capture and filling of floodplain channels within the Atchafalaya River Basin, Louisiana

    USGS Publications Warehouse

    Kroes, Daniel E.; Kraemer, Thomas F.

    2013-01-01

    The Atchafalaya River Basin is a distributary system of the Mississippi River containing the largest riparian area in the lower Mississippi River Valley and the largest remaining forested bottomland in North America. Reductions in the area of open water in the Atchafalaya have been occurring over the last 100 years, and many historical waterways are increasingly filled by sediment. This study examines two cases of swamp channels (3/s) that are filling and becoming unnavigable as a result of high sediment loads and slow water velocities. The water velocities in natural bayous are further reduced because of flow capture by channels constructed for access. Bathymetry, flow, suspended sediment, deposited bottom-material, isotopes, and photointerpretation were used to characterize the channel fill. On average, water flowing through these two channels lost 23% of the suspended sediment load in the studied reaches. Along one of the studied reaches, two constructed access channels diverted significant flow out of the primary channel and into the adjacent swamp. Immediately downstream of each of the two access channels, the cross-sectional area of the studied channel was reduced. Isotopic analyses of bottom-material cores indicate that bed filling has been rapid and occurred after detectable levels of Cesium-137 were no longer being deposited. Interpretation of aerial photography indicates that water is bypassing the primary channels in favor of the more hydraulically efficient access channels, resulting in low or no-velocity flow conditions in the primary channel. These swamp channel conditions are typical in the Atchafalaya River Basin where relict large channel dimensions result in flow velocities that are normally too low to carry fine-grained sediment. Constructed channels increase the rate of natural channel avulsion and abandonment as a result of flow capture.

  2. Apple fruit copper amine oxidase isoforms: peroxisomal MdAO1 prefers diamines as substrates, whereas extracellular MdAO2 exclusively utilizes monoamines.

    PubMed

    Zarei, Adel; Trobacher, Christopher P; Cooke, Alison R; Meyers, Ashley J; Hall, J Christopher; Shelp, Barry J

    2015-01-01

    4-Aminobutyrate (GABA) accumulates in apple fruit during controlled atmosphere storage. A potential source of GABA is the polyamine putrescine, which can be oxidized via copper-containing amine oxidase (CuAO), resulting in the production 4-aminobutanal/Δ(1)-pyrroline, with the consumption of O2 and release of H2O2 and ammonia. Five putative CuAO genes (MdAO genes) were cloned from apple (Malus domestica Borkh. cv. Empire) fruit, and the deduced amino acid sequences found to contain the active sites typically conserved in CuAOs. Genes encoding two of these enzymes, MdAO1 and MdAO2, were highly expressed in apple fruit and selected for further analysis. Amino acid sequence analysis predicted the presence of a C-terminal peroxisomal targeting signal 1 tripeptide in MdAO1 and an N-terminal signal peptide and N-glycosylation site in MdAO2. Transient expression of green fluorescent fusion proteins in Arabidopsis protoplasts or onion epidermal cells revealed a peroxisomal localization for MdAO1 and an extracellular localization for MdAO2. The enzymatic activities of purified recombinant MdAO1 and MdAO2 were measured continuously as H2O2 production using a coupled reaction. MdAO1 did not use monoamines or polyamines and displayed high catalytic efficiency for 1,3-diaminopropane, putrescine and cadaverine, whereas MdAO2 exclusively utilized aliphatic and aromatic monoamines, including 2-phenylethylamine and tyramine. Together, these results indicate that MdAO1 may contribute to GABA production via putrescine oxidation in the peroxisome of apple fruit under controlled atmosphere conditions. MdAO2 seems to be involved in deamination of 2-phenylethylamine, which is a step in the biosynthesis of 2-phenylethanol, a contributor to fruit flavor and flower fragrance. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Binding site in eag voltage sensor accommodates a variety of ions and is accessible in closed channel.

    PubMed

    Silverman, William R; Bannister, John P A; Papazian, Diane M

    2004-11-01

    In ether-a-go-go K+ channels, voltage-dependent activation is modulated by ion binding to a site located in an extracellular-facing crevice between transmembrane segments S2 and S3 in the voltage sensor. We find that acidic residues D278 in S2 and D327 in S3 are able to coordinate a variety of divalent cations, including Mg2+, Mn2+, and Ni2+, which have qualitatively similar functional effects, but different half-maximal effective concentrations. Our data indicate that ions binding to individual voltage sensors in the tetrameric channel act without cooperativity to modulate activation gating. We have taken advantage of the unique phenotype of Ni2+ in the D274A channel, which contains a mutation of a nonbinding site residue, to demonstrate that ions can access the binding site from the extracellular solution when the voltage sensor is in the resting conformation. Our results are difficult to reconcile with the x-ray structure of the KvAP K+ channel, in which the binding site residues are widely separated, and with the hydrophobic paddle model for voltage-dependent activation, in which the voltage sensor domain, including the S3-S4 loop, is near the cytoplasmic side of the membrane in the closed channel.

  4. ProtoMD: A prototyping toolkit for multiscale molecular dynamics

    NASA Astrophysics Data System (ADS)

    Somogyi, Endre; Mansour, Andrew Abi; Ortoleva, Peter J.

    2016-05-01

    ProtoMD is a toolkit that facilitates the development of algorithms for multiscale molecular dynamics (MD) simulations. It is designed for multiscale methods which capture the dynamic transfer of information across multiple spatial scales, such as the atomic to the mesoscopic scale, via coevolving microscopic and coarse-grained (CG) variables. ProtoMD can be also be used to calibrate parameters needed in traditional CG-MD methods. The toolkit integrates 'GROMACS wrapper' to initiate MD simulations, and 'MDAnalysis' to analyze and manipulate trajectory files. It facilitates experimentation with a spectrum of coarse-grained variables, prototyping rare events (such as chemical reactions), or simulating nanocharacterization experiments such as terahertz spectroscopy, AFM, nanopore, and time-of-flight mass spectroscopy. ProtoMD is written in python and is freely available under the GNU General Public License from github.com/CTCNano/proto_md.

  5. A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels

    PubMed Central

    Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, Matteo; Marchesi, Arin; Arcangeletti, Manuel; Demitri, Nicola; Mazzolini, Monica; Rodriguez, Alex; Magistrato, Alessandra; Onesti, Silvia; Laio, Alessandro; Torre, Vincent

    2015-01-01

    Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K+ channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na+, Cs+, and dimethylammonium (DMA+), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels. PMID:26100907

  6. A structural, functional, and computational analysis suggests pore flexibility as the base for the poor selectivity of CNG channels.

    PubMed

    Napolitano, Luisa Maria Rosaria; Bisha, Ina; De March, Matteo; Marchesi, Arin; Arcangeletti, Manuel; Demitri, Nicola; Mazzolini, Monica; Rodriguez, Alex; Magistrato, Alessandra; Onesti, Silvia; Laio, Alessandro; Torre, Vincent

    2015-07-07

    Cyclic nucleotide-gated (CNG) ion channels, despite a significant homology with the highly selective K(+) channels, do not discriminate among monovalent alkali cations and are permeable also to several organic cations. We combined electrophysiology, molecular dynamics (MD) simulations, and X-ray crystallography to demonstrate that the pore of CNG channels is highly flexible. When a CNG mimic is crystallized in the presence of a variety of monovalent cations, including Na(+), Cs(+), and dimethylammonium (DMA(+)), the side chain of Glu66 in the selectivity filter shows multiple conformations and the diameter of the pore changes significantly. MD simulations indicate that Glu66 and the prolines in the outer vestibule undergo large fluctuations, which are modulated by the ionic species and the voltage. This flexibility underlies the coupling between gating and permeation and the poor ionic selectivity of CNG channels.

  7. Access channels to the buried active site control substrate specificity in CYP1A P450 enzymes.

    PubMed

    Urban, Philippe; Truan, Gilles; Pompon, Denis

    2015-04-01

    A cytochrome P450 active site is buried within the protein molecule and several channels connect the catalytic cavity to the protein surface. Their role in P450 catalysis is still matter of debate. The aim of this study was to understand the possible relations existing between channels and substrate specificity. Time course studies were carried out with a collection of polycyclic substrates of increasing sizes assayed with a library of wild-type and chimeric CYP1A enzymes. This resulted in a matrix of activities sufficiently large to allow statistical analysis. Multivariate statistical tools were used to decipher the correlation between observed activity shifts and sequence segment swaps. The global kinetic behavior of CYP1A enzymes toward polycyclic substrates is significantly different depending on the size of the substrate. Mutations which are close or lining the P450 channels significantly affect this discrimination, whereas mutations distant from the P450 channels do not. Size discrimination is taking place for polycyclic substrates at the entrance of the different P450 access channels. It is thus hypothesized that channels differentiate small from large substrates in CYP1A enzymes, implying that residues located at the surface of the protein may be implied in this differential recognition. Catalysis thus occurs after a two-step recognition process, one at the surface of the protein and the second within the catalytic cavity in enzymes with a buried active site. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Combining Rosetta with molecular dynamics (MD): A benchmark of the MD-based ensemble protein design.

    PubMed

    Ludwiczak, Jan; Jarmula, Adam; Dunin-Horkawicz, Stanislaw

    2018-07-01

    Computational protein design is a set of procedures for computing amino acid sequences that will fold into a specified structure. Rosetta Design, a commonly used software for protein design, allows for the effective identification of sequences compatible with a given backbone structure, while molecular dynamics (MD) simulations can thoroughly sample near-native conformations. We benchmarked a procedure in which Rosetta design is started on MD-derived structural ensembles and showed that such a combined approach generates 20-30% more diverse sequences than currently available methods with only a slight increase in computation time. Importantly, the increase in diversity is achieved without a loss in the quality of the designed sequences assessed by their resemblance to natural sequences. We demonstrate that the MD-based procedure is also applicable to de novo design tasks started from backbone structures without any sequence information. In addition, we implemented a protocol that can be used to assess the stability of designed models and to select the best candidates for experimental validation. In sum our results demonstrate that the MD ensemble-based flexible backbone design can be a viable method for protein design, especially for tasks that require a large pool of diverse sequences. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Nonadditivity of quantum and classical capacities for entanglement breaking multiple-access channels and the butterfly network

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

    Grudka, Andrzej; National Quantum Information Centre of Gdansk, PL-81-824 Sopot; Horodecki, Pawel

    2010-06-15

    We analyze quantum network primitives which are entanglement breaking. We show superadditivity of quantum and classical capacity regions for quantum multiple-access channels and the quantum butterfly network. Since the effects are especially visible at high noise they suggest that quantum information effects may be particularly helpful in the case of the networks with occasional high noise rates. The present effects provide a qualitative borderline between superadditivities of bipartite and multipartite systems.

  10. Joint channel estimation and multi-user detection for multipath fading channels in DS-CDMA systems

    NASA Astrophysics Data System (ADS)

    Wu, Sau-Hsuan; Kuo, C.-C. Jay

    2002-11-01

    The technique of joint blind channel estimation and multiple access interference (MAI) suppression for an asynchronous code-division multiple-access (CDMA) system is investigated in this research. To identify and track dispersive time-varying fading channels and to avoid the phase ambiguity that come with the second-order statistic approaches, a sliding-window scheme using the expectation maximization (EM) algorithm is proposed. The complexity of joint channel equalization and symbol detection for all users increases exponentially with system loading and the channel memory. The situation is exacerbated if strong inter-symbol interference (ISI) exists. To reduce the complexity and the number of samples required for channel estimation, a blind multiuser detector is developed. Together with multi-stage interference cancellation using soft outputs provided by this detector, our algorithm can track fading channels with no phase ambiguity even when channel gains attenuate close to zero.

  11. All-d-Enantiomer of β-Amyloid Peptide Forms Ion Channels in Lipid Bilayers

    PubMed Central

    2012-01-01

    Alzheimer’s disease (AD) is the most common type of senile dementia in aging populations. Amyloid β (Aβ)-mediated dysregulation of ionic homeostasis is the prevailing underlying mechanism leading to synaptic degeneration and neuronal death. Aβ-dependent ionic dysregulation most likely occurs either directly via unregulated ionic transport through the membrane or indirectly via Aβ binding to cell membrane receptors and subsequent opening of existing ion channels or transporters. Receptor binding is expected to involve a high degree of stereospecificity. Here, we investigated whether an Aβ peptide enantiomer, whose entire sequence consists of d-amino acids, can form ion-conducting channels; these channels can directly mediate Aβ effects even in the absence of receptor–peptide interactions. Using complementary approaches of planar lipid bilayer (PLB) electrophysiological recordings and molecular dynamics (MD) simulations, we show that the d-Aβ isomer exhibits ion conductance behavior in the bilayer indistinguishable from that described earlier for the l-Aβ isomer. The d isomer forms channel-like pores with heterogeneous ionic conductance similar to the l-Aβ isomer channels, and the d-isomer channel conductance is blocked by Zn2+, a known blocker of l-Aβ isomer channels. MD simulations further verify formation of β-barrel-like Aβ channels with d- and l-isomers, illustrating that both d- and l-Aβ barrels can conduct cations. The calculated values of the single-channel conductance are approximately in the range of the experimental values. These findings are in agreement with amyloids forming Ca2+ leaking, unregulated channels in AD, and suggest that Aβ toxicity is mediated through a receptor-independent, nonstereoselective mechanism. PMID:22423218

  12. UV - GAITHERSBURG MD

    EPA Science Inventory

    Brewer 105 is located in Gaithersburg MD, measuring ultraviolet solar radiation. Irradiance and column ozone are derived from this data. Ultraviolet solar radiation is measured with a Brewer Mark IV, single-monochrometer, spectrophotometer manufactured by SCI-TEC Instruments, Inc...

  13. Celastrol reverses palmitic acid (PA)-caused TLR4-MD2 activation-dependent insulin resistance via disrupting MD2-related cellular binding to PA.

    PubMed

    Zhang, Xue; Wang, Ying; Ge, Hui-Ya; Gu, Yi-Jun; Cao, Fan-Fan; Yang, Chun-Xin; Uzan, Georges; Peng, Bin; Zhang, Deng-Hai

    2018-04-18

    Elevated plasma statured fatty acids (FFAs) cause TLR4/MD2 activation-dependent inflammation and insulin tolerance, which account for the occurrence and development of obesity. It has been confirmed that statured palmitic acid (PA) (the most abundant FFA) could bind MD2 to cause cellular inflammation. The natural compound celastrol could improve obesity, which is suggested via inhibiting inflammation, yet the detailed mechanism for celastrol is still unclear. As celastrol is reported to directly target MD2, we thought disrupting the binding between FFAs and MD2 might be one of the ways for celastrol to inhibit FFAs-caused inflammation and insulin resistance. In this study, we found evidence to support our hypothesis: celastrol could reverse PA-caused TLR4/MD2 activation-dependent insulin resistance, as determined by glucose-lowering ability, cellular glucose uptake, insulin action-related proteins and TLR4/MD2/NF-κB activation. Bioinformatics and cellular experiments showed that both celastrol and PA could bind MD2, and that celastrol could expel PA from cells. Finally, celastrol could reverse high fat diet caused hyperglycemia and obesity, and liver NF-kB activations. Taking together, we proved that celastrol could reverses PA-caused TLR4-MD2 activation-dependent insulin resistance via disrupting PA binding to MD2. © 2018 Wiley Periodicals, Inc.

  14. Wired and wireless convergent extended-reach optical access network using direct-detection of all-optical OFDM super-channel signal.

    PubMed

    Chow, C W; Yeh, C H; Sung, J Y; Hsu, C W

    2014-12-15

    We propose and demonstrate the feasibility of using all-optical orthogonal frequency division multiplexing (AO-OFDM) for the convergent optical wired and wireless access networks. AO-OFDM relies on all-optically generated orthogonal subcarriers; hence, high data rate (> 100 Gb/s) can be easily achieved without hitting the speed limit of electronic digital-to-analog and analog-to-digital converters (DAC/ADC). A proof-of-concept convergent access network using AO-OFDM super-channel (SC) is demonstrated supporting 40 - 100 Gb/s wired and gigabit/s 100 GHz millimeter-wave (MMW) ROF transmissions.

  15. MdCOP1 Ubiquitin E3 Ligases Interact with MdMYB1 to Regulate Light-Induced Anthocyanin Biosynthesis and Red Fruit Coloration in Apple1[W][OA

    PubMed Central

    Li, Yuan-Yuan; Mao, Ke; Zhao, Cheng; Zhao, Xian-Yan; Zhang, Hua-Lei; Shu, Huai-Rui; Hao, Yu-Jin

    2012-01-01

    MdMYB1 is a crucial regulator of light-induced anthocyanin biosynthesis and fruit coloration in apple (Malus domestica). In this study, it was found that MdMYB1 protein accumulated in the light but degraded via a ubiquitin-dependent pathway in the dark. Subsequently, the MdCOP1-1 and MdCOP1-2 genes were isolated from apple fruit peel and were functionally characterized in the Arabidopsis (Arabidopsis thaliana) cop1-4 mutant. Yeast (Saccharomyces cerevisiae) two-hybrid, bimolecular fluorescence complementation, and coimmunoprecipitation assays showed that MdMYB1 interacts with the MdCOP1 proteins. Furthermore, in vitro and in vivo experiments indicated that MdCOP1s are necessary for the ubiquitination and degradation of MdMYB1 protein in the dark and are therefore involved in the light-controlled stability of the MdMYB1 protein. Finally, a viral vector-based transformation approach demonstrated that MdCOP1s negatively regulate the peel coloration of apple fruits by modulating the degradation of the MdMYB1 protein. Our findings provide new insight into the mechanism by which light controls anthocyanin accumulation and red fruit coloration in apple and even other plant species. PMID:22855936

  16. A virtual observatory for photoionized nebulae: the Mexican Million Models database (3MdB).

    NASA Astrophysics Data System (ADS)

    Morisset, C.; Delgado-Inglada, G.; Flores-Fajardo, N.

    2015-04-01

    Photoionization models obtained with numerical codes are widely used to study the physics of the interstellar medium (planetary nebulae, HII regions, etc). Grids of models are performed to understand the effects of the different parameters used to describe the regions on the observables (mainly emission line intensities). Most of the time, only a small part of the computed results of such grids are published, and they are sometimes hard to obtain in a user-friendly format. We present here the Mexican Million Models dataBase (3MdB), an effort to resolve both of these issues in the form of a database of photoionization models, easily accessible through the MySQL protocol, and containing a lot of useful outputs from the models, such as the intensities of 178 emission lines, the ionic fractions of all the ions, etc. Some examples of the use of the 3MdB are also presented.

  17. Sulforaphane inhibits the engagement of LPS with TLR4/MD2 complex by preferential binding to Cys133 in MD2.

    PubMed

    Koo, Jung Eun; Park, Zee-Yong; Kim, Nam Doo; Lee, Joo Young

    2013-05-10

    Toll-like receptors (TLRs) are key pattern-recognition receptors that recognize invading pathogens and non-microbial endogenous molecules to induce innate and adaptive immune responses. Since activation of TLRs is deeply implicated in the pathological progress of autoimmune diseases, sepsis, metabolic diseases, and cancer, modulation of TLR activity is considered one of the most important therapeutic approaches. Lipopolysaccharide (LPS), an endotoxin of gram-negative bacteria, is a well-known agonist for TLR4 triggering inflammation and septic shock. LPS interacts with TLR4 through binding to a hydrophobic pocket in myeloid differentiation 2 (MD2), a co-receptor of TLR4. In this study, we showed that sulforaphane (SFN) interfered with the binding of LPS to MD2 as determined by in vitro binding assay and co-immunoprecipitation of MD2 and LPS in a cell system. The inhibitory effect of SFN on the interaction of LPS and MD2 was reversed by thiol supplementation with N-acetyl-L-cysteine or dithiothreitol showing that the inhibitory effect of SFN is dependent on its thiol-modifying activity. Indeed, micro LC-MS/MS analysis showed that SFN preferentially formed adducts with Cys133 in the hydrophobic pocket of MD2, but not with Cys95 and Cys105. Molecular modeling showed that SFN bound to Cys133 blocks the engagement of LPS and lipid IVa to hydrophobic pocket of MD2. Our results demonstrate that SFN interrupts LPS engagement to TLR4/MD2 complex by direct binding to Cys133 in MD2. Our data suggest a novel mechanism for the anti-inflammatory activity of SFN, and provide a novel target for the regulation of TLR4-mediated inflammatory and immune responses by phytochemicals. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. LifeBridge new publication: Md.MD. Listing of 1,200 physicians a major part of consumer-type magazine.

    PubMed

    Botvin, Judith D

    2004-01-01

    LifeBridge Health, Baltimore, created a directory of its physicians, which developed into a 100-page consumer magazine titled Md.MD A Directory of the Region's Finest Physicians. Written and designed in-house, the premier edition paid for itself, thanks to publishing partner, Alter Communications. The premier edition was mailed to 50,000 Baltimore area homes last September.

  19. 33 CFR 110.72 - Blackhole Creek, Md.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Blackhole Creek, Md. 110.72 Section 110.72 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.72 Blackhole Creek, Md. The waters on the west side of...

  20. 33 CFR 110.72 - Blackhole Creek, Md.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Blackhole Creek, Md. 110.72 Section 110.72 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.72 Blackhole Creek, Md. The waters on the west side of...

  1. Expression of MdCAS1 and MdCAS2, encoding apple beta-cyanoalanine synthase homologs, is concomitantly induced during ripening and implicates MdCASs in the possible role of the cyanide detoxification in Fuji apple (Malus domestica Borkh.) fruits.

    PubMed

    Han, Sang Eun; Seo, Young Sam; Kim, Daeil; Sung, Soon-Kee; Kim, Woo Taek

    2007-08-01

    Fruit ripening involves complex biochemical and physiological changes. Ethylene is an essential hormone for the ripening of climacteric fruits. In the process of ethylene biosynthesis, cyanide (HCN), an extremely toxic compound, is produced as a co-product. Thus, most cyanide produced during fruit ripening should be detoxified rapidly by fruit cells. In higher plants, the key enzyme involved in the detoxification of HCN is beta-cyanoalanine synthase (beta-CAS). As little is known about the molecular function of beta-CAS genes in climacteric fruits, we identified two homologous genes, MdCAS1 and MdCAS2, encoding Fuji apple beta-CAS homologs. The structural features of the predicted polypeptides as well as an in vitro enzyme activity assay with bacterially expressed recombinant proteins indicated that MdCAS1 and MdCAS2 may indeed function as beta-CAS isozymes in apple fruits. RNA gel-blot studies revealed that both MdCAS1 and MdCAS2 mRNAs were coordinately induced during the ripening process of apple fruits in an expression pattern comparable with that of ACC oxidase and ethylene production. The MdCAS genes were also activated effectively by exogenous ethylene treatment and mechanical wounding. Thus, it seems like that, in ripening apple fruits, expression of MdCAS1 and MdCAS2 genes is intimately correlated with a climacteric ethylene production and ACC oxidase activity. In addition, beta-CAS enzyme activity was also enhanced as the fruit ripened, although this increase was not as dramatic as the mRNA induction pattern. Overall, these results suggest that MdCAS may play a role in cyanide detoxification in ripening apple fruits.

  2. Channel MAC Protocol for Opportunistic Communication in Ad Hoc Wireless Networks

    NASA Astrophysics Data System (ADS)

    Ashraf, Manzur; Jayasuriya, Aruna; Perreau, Sylvie

    2008-12-01

    Despite significant research effort, the performance of distributed medium access control methods has failed to meet theoretical expectations. This paper proposes a protocol named "Channel MAC" performing a fully distributed medium access control based on opportunistic communication principles. In this protocol, nodes access the channel when the channel quality increases beyond a threshold, while neighbouring nodes are deemed to be silent. Once a node starts transmitting, it will keep transmitting until the channel becomes "bad." We derive an analytical throughput limit for Channel MAC in a shared multiple access environment. Furthermore, three performance metrics of Channel MAC—throughput, fairness, and delay—are analysed in single hop and multihop scenarios using NS2 simulations. The simulation results show throughput performance improvement of up to 130% with Channel MAC over IEEE 802.11. We also show that the severe resource starvation problem (unfairness) of IEEE 802.11 in some network scenarios is reduced by the Channel MAC mechanism.

  3. Retrospective review of adverse incidents involving passengers seated in wheeled mobility devices while traveling in large accessible transit vehicles.

    PubMed

    Frost, Karen L; Bertocci, Gina

    2010-04-01

    Characterize wheeled mobility device (WhMD) adverse incidents on large accessible transit vehicles (LATVs) based on vehicle motion, WhMD activity during incident, incident scenario and injury. Retrospective records review. WhMD passengers traveling on LATVs while remaining seated in their. Adverse incidents characterized based on vehicle motion, WhMD activity during incident, and incident scenario. Injury characterized based on outcome, medical attention sought, vehicle activity, WhMD activity and incident scenario. 115 WhMD-related incident reports for years 2000-2005 were analyzed. Most incidents occurred when the LATV was stopped (73.9%), during ingress/egress (42.6%), and at the securement station (33.9%) when the LATV was moving. The combination of WhMD tipping and passenger falling (43.4%) occurred most frequently, and was 1.8 times more likely to occur during ingress/egress than at the securement station. One-third (33.6%) of all incidents resulted in injury, and injuries were equally distributed between ingress/egress (43.6%) and at the securement station (43.6%). WhMD users have a greater chance of incurring injury during ingress/egress than during transit. Research is needed to objectively assess real world transportation experiences of WhMD passengers, and to assess the adequacy of existing federal legislation/guidelines for accessible ramps used in public transportation. Copyright 2009 IPEM. Published by Elsevier Ltd. All rights reserved.

  4. The AINTEGUMENTA genes, MdANT1 and MdANT2, are associated with the regulation of cell production during fruit growth in apple (Malus × domestica Borkh.).

    PubMed

    Dash, Madhumita; Malladi, Anish

    2012-06-25

    Fruit growth in apple (Malus × domestica Borkh.) is mediated by cell production and expansion. Genes involved in regulating these processes and thereby fruit growth, are not well characterized. We hypothesized that the apple homolog(s) of AINTEGUMENTA (ANT), an APETALA2-repeat containing transcription factor, regulates cell production during fruit growth in apple. Two ANT genes, MdANT1 and MdANT2, were isolated from apple and their expression was studied during multiple stages of fruit development. MdANT1 and MdANT2 expression was high during early fruit growth coincident with the period of cell production, rapidly declined during exit from cell production, and remained low during the rest of fruit development. The effects of increase in carbohydrate availability during fruit growth were characterized. Increase in carbohydrate availability enhanced fruit growth largely through an increase in cell production. Expression of MdANT1 and MdANT2 increased sharply by up to around 5-fold in response to an increase in carbohydrate availability. Expression of the ANT genes was compared across two apple genotypes, 'Gala' and 'Golden Delicious Smoothee' (GS), which differ in the extent of fruit growth, largely due to differences in cell production. In comparison to 'Gala', the larger fruit-size genotype, GS, displayed higher levels and a longer duration of MdANT1 and MdANT2 expression. Expression of the ANTs and cell cycle genes in the fruit core and cortex tissues isolated using laser capture microdissection was studied. During early fruit growth, expression of the MdANTs was higher within the cortex, the tissue that constitutes the majority of the fruit. Additionally, MdANT1 and MdANT2 expression was positively correlated with that of A- and B-type CYCLINS, B-type CYCLIN-DEPENDENT-KINASES (CDKBs) and MdDEL1. Multiple lines of evidence from this study suggest that MdANT1 and MdANT2 regulate cell production during fruit growth in apple. ANTs may coordinate the expression of

  5. Theoretical analysis of the performance of code division multiple access communications over multimode optical fiber channels. Part 1: Transmission and detection

    NASA Astrophysics Data System (ADS)

    Walker, Ernest L.

    1994-05-01

    This paper presents results of a theoretical investigation to evaluate the performance of code division multiple access communications over multimode optical fiber channels in an asynchronous, multiuser communication network environment. The system is evaluated using Gold sequences for spectral spreading of the baseband signal from each user employing direct-sequence biphase shift keying and intensity modulation techniques. The transmission channel model employed is a lossless linear system approximation of the field transfer function for the alpha -profile multimode optical fiber. Due to channel model complexity, a correlation receiver model employing a suboptimal receive filter was used in calculating the peak output signal at the ith receiver. In Part 1, the performance measures for the system, i.e., signal-to-noise ratio and bit error probability for the ith receiver, are derived as functions of channel characteristics, spectral spreading, number of active users, and the bit energy to noise (white) spectral density ratio. In Part 2, the overall system performance is evaluated.

  6. Theory and simulation of ion conduction in the pentameric GLIC channel.

    PubMed

    Zhu, Fangqiang; Hummer, Gerhard

    2012-10-09

    GLIC is a bacterial member of the large family of pentameric ligand-gated ion channels. To study ion conduction through GLIC and other membrane channels, we combine the one-dimensional potential of mean force for ion passage with a Smoluchowski diffusion model, making it possible to calculate single-channel conductance in the regime of low ion concentrations from all-atom molecular dynamics (MD) simulations. We then perform MD simulations to examine sodium ion conduction through the GLIC transmembrane pore in two systems with different bulk ion concentrations. The ion potentials of mean force, calculated from umbrella sampling simulations with Hamiltonian replica exchange, reveal a major barrier at the hydrophobic constriction of the pore. The relevance of this barrier for ion transport is confirmed by a committor function that rises sharply in the barrier region. From the free evolution of Na(+) ions starting at the barrier top, we estimate the effective diffusion coefficient in the barrier region, and subsequently calculate the conductance of the pore. The resulting diffusivity compares well with the position-dependent ion diffusion coefficient obtained from restrained simulations. The ion conductance obtained from the diffusion model agrees with the value determined via a reactive-flux rate calculation. Our results show that the conformation in the GLIC crystal structure, with an estimated conductance of ~1 picosiemens at 140 mM ion concentration, is consistent with a physiologically open state of the channel.

  7. The AINTEGUMENTA genes, MdANT1 and MdANT2, are associated with the regulation of cell production during fruit growth in apple (Malus × domestica Borkh.)

    PubMed Central

    2012-01-01

    Background Fruit growth in apple (Malus × domestica Borkh.) is mediated by cell production and expansion. Genes involved in regulating these processes and thereby fruit growth, are not well characterized. We hypothesized that the apple homolog(s) of AINTEGUMENTA (ANT), an APETALA2–repeat containing transcription factor, regulates cell production during fruit growth in apple. Results Two ANT genes, MdANT1 and MdANT2, were isolated from apple and their expression was studied during multiple stages of fruit development. MdANT1 and MdANT2 expression was high during early fruit growth coincident with the period of cell production, rapidly declined during exit from cell production, and remained low during the rest of fruit development. The effects of increase in carbohydrate availability during fruit growth were characterized. Increase in carbohydrate availability enhanced fruit growth largely through an increase in cell production. Expression of MdANT1 and MdANT2 increased sharply by up to around 5-fold in response to an increase in carbohydrate availability. Expression of the ANT genes was compared across two apple genotypes, ‘Gala’ and ‘Golden Delicious Smoothee’ (GS), which differ in the extent of fruit growth, largely due to differences in cell production. In comparison to ‘Gala’, the larger fruit-size genotype, GS, displayed higher levels and a longer duration of MdANT1 and MdANT2 expression. Expression of the ANTs and cell cycle genes in the fruit core and cortex tissues isolated using laser capture microdissection was studied. During early fruit growth, expression of the MdANTs was higher within the cortex, the tissue that constitutes the majority of the fruit. Additionally, MdANT1 and MdANT2 expression was positively correlated with that of A- and B-type CYCLINS, B-type CYCLIN-DEPENDENT-KINASES (CDKBs) and MdDEL1. Conclusions Multiple lines of evidence from this study suggest that MdANT1 and MdANT2 regulate cell production during fruit growth in

  8. Remains of abutments for Bridge No. 1575 at MD Rt. ...

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

    Remains of abutments for Bridge No. 1575 at MD Rt. 51 in Spring Gap, Maryland, looking northeast. (Compare with HAER MD-115 photos taken 1988). - Western Maryland Railway, Cumberland Extension, Pearre to North Branch, from WM milepost 125 to 160, Pearre, Washington County, MD

  9. Apple MdACS6 Regulates Ethylene Biosynthesis During Fruit Development Involving Ethylene-Responsive Factor.

    PubMed

    Li, Tong; Tan, Dongmei; Liu, Zhi; Jiang, Zhongyu; Wei, Yun; Zhang, Lichao; Li, Xinyue; Yuan, Hui; Wang, Aide

    2015-10-01

    Ethylene biosynthesis in plants involves different 1-aminocyclopropane-1-carboxylic acid synthase (ACS) genes. The regulation of each ACS gene during fruit development is unclear. Here, we characterized another apple (Malus×domestica) ACS gene, MdACS6. The transcript of MdACS6 was observed not only in fruits but also in other tissues. During fruit development, MdACS6 was initiated at a much earlier stage, whereas MdACS3a and MdACS1 began to be expressed at 35 d before harvest and immediateley after harvest, respectively. Moreover, the enzyme activity of MdACS6 was significantly lower than that of MdACS3a and MdACS1, accounting for the low ethylene biosynthesis in young fruits. Overexpression of MdACS6 (MdACS6-OE) by transient assay in apple showed enhanced ethylene production, and MdACS3a was induced in MdACS6-OE fruits but not in control fruits. In MdACS6 apple fruits silenced by the virus-induced gene silencing (VIGS) system (MdACS6-AN), neither ethylene production nor MdACS3a transcript was detectable. In order to explore the mechanism through which MdACS3a was induced in MdACS6-OE fruits, we investigated the expression of apple ethylene-responsive factor (ERF) genes. The results showed that the expression of MdERF2 was induced in MdACS6-OE fruits and inhibited in MdACS6-AN fruits. Yeast one-hybrid assay showed that MdERF2 protein could bind to the promoter of MdACS3a. Moreover, down-regulation of MdERF2 in apple flesh callus led to a decrease of MdACS3a expression, demonstrating the regulation of MdERF2 on MdACS3a. The mechanism through which MdACS6 regulates the action of MdACS3a was discussed. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. 76 FR 51424 - Satinder Dang, M.D.; Revocation of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-4] Satinder Dang, M.D... Control, Drug Enforcement Administration, issued an Order to Show Cause to Satinder K. Dang, M.D....'' Id. (citing Harrell E. Robinson, M.D., 74 FR 61370, 61376-77 (2010)). The ALJ also found that...

  11. 77 FR 67673 - Fernando Valle, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 12-56] Fernando Valle, M.D... Certificate of Registration Numbers FV1935595, FV2000711, and FV2000735, issued to Fernando Valle, M.D., be, and they hereby are, revoked. I further order that any pending applications of Fernando Valle, M.D...

  12. A permeation theory for single-file ion channels: one- and two-step models.

    PubMed

    Nelson, Peter Hugo

    2011-04-28

    How many steps are required to model permeation through ion channels? This question is investigated by comparing one- and two-step models of permeation with experiment and MD simulation for the first time. In recent MD simulations, the observed permeation mechanism was identified as resembling a Hodgkin and Keynes knock-on mechanism with one voltage-dependent rate-determining step [Jensen et al., PNAS 107, 5833 (2010)]. These previously published simulation data are fitted to a one-step knock-on model that successfully explains the highly non-Ohmic current-voltage curve observed in the simulation. However, these predictions (and the simulations upon which they are based) are not representative of real channel behavior, which is typically Ohmic at low voltages. A two-step association/dissociation (A/D) model is then compared with experiment for the first time. This two-parameter model is shown to be remarkably consistent with previously published permeation experiments through the MaxiK potassium channel over a wide range of concentrations and positive voltages. The A/D model also provides a first-order explanation of permeation through the Shaker potassium channel, but it does not explain the asymmetry observed experimentally. To address this, a new asymmetric variant of the A/D model is developed using the present theoretical framework. It includes a third parameter that represents the value of the "permeation coordinate" (fractional electric potential energy) corresponding to the triply occupied state n of the channel. This asymmetric A/D model is fitted to published permeation data through the Shaker potassium channel at physiological concentrations, and it successfully predicts qualitative changes in the negative current-voltage data (including a transition to super-Ohmic behavior) based solely on a fit to positive-voltage data (that appear linear). The A/D model appears to be qualitatively consistent with a large group of published MD simulations, but no

  13. 78 FR 7813 - Sanjay Trivedi, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 12-57] Sanjay Trivedi, M.D....100(b), I order that DEA Certificate of Registration FT0896754, issued to Sanjay Trivedi, M.D., be, and it hereby is, revoked. I further order that any pending application of Sanjay Trivedi, M.D., to...

  14. Binding mode prediction and MD/MMPBSA-based free energy ranking for agonists of REV-ERBα/NCoR.

    PubMed

    Westermaier, Yvonne; Ruiz-Carmona, Sergio; Theret, Isabelle; Perron-Sierra, Françoise; Poissonnet, Guillaume; Dacquet, Catherine; Boutin, Jean A; Ducrot, Pierre; Barril, Xavier

    2017-08-01

    The knowledge of the free energy of binding of small molecules to a macromolecular target is crucial in drug design as is the ability to predict the functional consequences of binding. We highlight how a molecular dynamics (MD)-based approach can be used to predict the free energy of small molecules, and to provide priorities for the synthesis and the validation via in vitro tests. Here, we study the dynamics and energetics of the nuclear receptor REV-ERBα with its co-repressor NCoR and 35 novel agonists. Our in silico approach combines molecular docking, molecular dynamics (MD), solvent-accessible surface area (SASA) and molecular mechanics poisson boltzmann surface area (MMPBSA) calculations. While docking yielded initial hints on the binding modes, their stability was assessed by MD. The SASA calculations revealed that the presence of the ligand led to a higher exposure of hydrophobic REV-ERB residues for NCoR recruitment. MMPBSA was very successful in ranking ligands by potency in a retrospective and prospective manner. Particularly, the prospective MMPBSA ranking-based validations for four compounds, three predicted to be active and one weakly active, were confirmed experimentally.

  15. Molecular dynamics and brownian dynamics investigation of ion permeation and anesthetic halothane effects on a proton-gated ion channel.

    PubMed

    Cheng, Mary Hongying; Coalson, Rob D; Tang, Pei

    2010-11-24

    Bacterial Gloeobacter violaceus pentameric ligand-gated ion channel (GLIC) is activated to cation permeation upon lowering the solution pH. Its function can be modulated by anesthetic halothane. In the present work, we integrate molecular dynamics (MD) and Brownian dynamics (BD) simulations to elucidate the ion conduction, charge selectivity, and halothane modulation mechanisms in GLIC, based on recently resolved X-ray crystal structures of the open-channel GLIC. MD calculations of the potential of mean force (PMF) for a Na(+) revealed two energy barriers in the extracellular domain (R109 and K38) and at the hydrophobic gate of transmembrane domain (I233), respectively. An energy well for Na(+) was near the intracellular entrance: the depth of this energy well was modulated strongly by the protonation state of E222. The energy barrier for Cl(-) was found to be 3-4 times higher than that for Na(+). Ion permeation characteristics were determined through BD simulations using a hybrid MD/continuum electrostatics approach to evaluate the energy profiles governing the ion movement. The resultant channel conductance and a near-zero permeability ratio (P(Cl)/P(Na)) were comparable to experimental data. On the basis of these calculations, we suggest that a ring of five E222 residues may act as an electrostatic gate. In addition, the hydrophobic gate region may play a role in charge selectivity due to a higher dehydration energy barrier for Cl(-) ions. The effect of halothane on the Na(+) PMF was also evaluated. Halothane was found to perturb salt bridges in GLIC that may be crucial for channel gating and open-channel stability, but had no significant impact on the single ion PMF profiles.

  16. IBiSA_Tools: A Computational Toolkit for Ion-Binding State Analysis in Molecular Dynamics Trajectories of Ion Channels.

    PubMed

    Kasahara, Kota; Kinoshita, Kengo

    2016-01-01

    Ion conduction mechanisms of ion channels are a long-standing conundrum. Although the molecular dynamics (MD) method has been extensively used to simulate ion conduction dynamics at the atomic level, analysis and interpretation of MD results are not straightforward due to complexity of the dynamics. In our previous reports, we proposed an analytical method called ion-binding state analysis to scrutinize and summarize ion conduction mechanisms by taking advantage of a variety of analytical protocols, e.g., the complex network analysis, sequence alignment, and hierarchical clustering. This approach effectively revealed the ion conduction mechanisms and their dependence on the conditions, i.e., ion concentration and membrane voltage. Here, we present an easy-to-use computational toolkit for ion-binding state analysis, called IBiSA_tools. This toolkit consists of a C++ program and a series of Python and R scripts. From the trajectory file of MD simulations and a structure file, users can generate several images and statistics of ion conduction processes. A complex network named ion-binding state graph is generated in a standard graph format (graph modeling language; GML), which can be visualized by standard network analyzers such as Cytoscape. As a tutorial, a trajectory of a 50 ns MD simulation of the Kv1.2 channel is also distributed with the toolkit. Users can trace the entire process of ion-binding state analysis step by step. The novel method for analysis of ion conduction mechanisms of ion channels can be easily used by means of IBiSA_tools. This software is distributed under an open source license at the following URL: http://www.ritsumei.ac.jp/~ktkshr/ibisa_tools/.

  17. Quasi-specific access of the potassium channel inactivation gate

    PubMed Central

    Venkataraman, Gaurav; Srikumar, Deepa; Holmgren, Miguel

    2014-01-01

    Many voltage-gated potassium channels open in response to membrane depolarization and then inactivate within milliseconds. Neurons use these channels to tune their excitability. In Shaker K+ channels, inactivation is caused by the cytoplasmic amino terminus, termed the inactivation gate. Despite having four such gates, inactivation is caused by the movement of a single gate into a position that occludes ion permeation. The pathway that this single inactivation gate takes into its inactivating position remains unknown. Here we show that a single gate threads through the intracellular entryway of its own subunit, but the tip of the gate has sufficient freedom to interact with all four subunits deep in the pore, and does so with equal probability. This pathway demonstrates that flexibility afforded by the inactivation peptide segment at the tip of the N-terminus is used to mediate function. PMID:24909510

  18. 75 FR 80744 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-81 (MD-81), DC-9-82 (MD-82...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-23

    ...: We propose to adopt a new airworthiness directive (AD) for all Model DC-9-81 (MD-81), DC-9-82 (MD-82... inspections for cracking of the left and right upper center skin panels of the horizontal stabilizer, and..., West Building Ground Floor, Room W12-140, 1200 New Jersey Avenue, SE., Washington, DC 20590. Hand...

  19. Swiss national MD-PhD-program: an outcome analysis.

    PubMed

    Kuehnle, Katrin; Winkler, David T; Meier-Abt, Peter J

    2009-09-19

    This study aims at a first evaluation of the outcome of the Swiss national MD-PhD program during the last 16 years. One hundred and twenty six former and current students in the Swiss national MD-PhD program were surveyed via a Web-based questionnaire in September 2007. Twenty-four questions assessed information regarding participant demographics, information on the PhD thesis and publication activity, current positions and research activity, as well as participant's opinions, attitudes and career goals. Eighty questionnaires were received from 126 MD-PhD students and graduates (63.5% response rate). The responders consisted of present students (36%), former graduates (56%), and dropouts (8%). The percentage of women in the program was 23%, and the average duration of the program was 4.2 +/- 1.4 years. Research interests were predominantly in the fields of neuroscience, immunology, molecular biology and cancer research. A considerable portion of the MD-PhD graduates had an excellent publication record stemming from their PhD research work, and 89% were planning to continue a research-orientated career. Over 50% of those MD-PhD graduates completing their thesis before 2002 had already reached an assistant or full professor position at the time of the survey. Nearly all participants considered the MD-PhD training helpful to their career and high quality standards were assigned to the acquired practical and intellectual skills. However, criticism was expressed concerning the general mentoring and the career related mentoring. Moreover, general mentoring and career related mentoring were significantly less well perceived in research groups employing more than seven PhD students at the same time. The MD-PhD students and graduates surveyed were satisfied with their education and most of them continued a research-orientated career. Regarding the overall positive evaluation, this study supports the view that MD-PhD graduates are well qualified for a successful career in

  20. Should MD-PhD programs encourage graduate training in disciplines beyond conventional biomedical or clinical sciences?

    PubMed

    O'Mara, Ryan J; Hsu, Stephen I; Wilson, Daniel R

    2015-02-01

    The goal of MD-PhD training programs is to produce physician-scientists with unique capacities to lead the future biomedical research workforce. The current dearth of physician-scientists with expertise outside conventional biomedical or clinical sciences raises the question of whether MD-PhD training programs should allow or even encourage scholars to pursue doctoral studies in disciplines that are deemed nontraditional, yet are intrinsically germane to major influences on health. This question is especially relevant because the central value and ultimate goal of the academic medicine community is to help attain the highest level of health and health equity for all people. Advances in medical science and practice, along with improvements in health care access and delivery, are steps toward health equity, but alone they will not come close to eliminating health inequalities. Addressing the complex health issues in our communities and society as a whole requires a biomedical research workforce with knowledge, practice, and research skills well beyond conventional biomedical or clinical sciences. To make real progress in advancing health equity, educational pathways must prepare physician-scientists to treat both micro and macro determinants of health. The authors argue that MD-PhD programs should allow and encourage their scholars to cross boundaries into less traditional disciplines such as epidemiology, statistics, anthropology, sociology, ethics, public policy, management, economics, education, social work, informatics, communications, and marketing. To fulfill current and coming health care needs, nontraditional MD-PhD students should be welcomed and supported as valuable members of our biomedical research workforce.

  1. MD-11 PCA - Research flight team photo

    NASA Technical Reports Server (NTRS)

    1995-01-01

    On Aug. 30, 1995, a the McDonnell Douglas MD-11 transport aircraft landed equipped with a computer-assisted engine control system that has the potential to increase flight safety. In landings at NASA Dryden Flight Research Center, Edwards, California, on August 29 and 30, the aircraft demonstrated software used in the aircraft's flight control computer that essentially landed the MD-11 without a need for the pilot to manipulate the flight controls significantly. In partnership with McDonnell Douglas Aerospace (MDA), with Pratt & Whitney and Honeywell helping to design the software, NASA developed this propulsion-controlled aircraft (PCA) system following a series of incidents in which hydraulic failures resulted in the loss of flight controls. This new system enables a pilot to operate and land the aircraft safely when its normal, hydraulically-activated control surfaces are disabled. This August 29, 1995, photo shows the MD-11 team. Back row, left to right: Tim Dingen, MDA pilot; John Miller, MD-11 Chief pilot (MDA); Wayne Anselmo, MD-11 Flight Test Engineer (MDA); Gordon Fullerton, PCA Project pilot; Bill Burcham, PCA Chief Engineer; Rudey Duran, PCA Controls Engineer (MDA); John Feather, PCA Controls Engineer (MDA); Daryl Townsend, Crew Chief; Henry Hernandez, aircraft mechanic; Bob Baron, PCA Project Manager; Don Hermann, aircraft mechanic; Jerry Cousins, aircraft mechanic; Eric Petersen, PCA Manager (Honeywell); Trindel Maine, PCA Data Engineer; Jeff Kahler, PCA Software Engineer (Honeywell); Steve Goldthorpe, PCA Controls Engineer (MDA). Front row, left to right: Teresa Hass, Senior Project Management Analyst; Hollie Allingham (Aguilera), Senior Project Management Analyst; Taher Zeglum, PCA Data Engineer (MDA); Drew Pappas, PCA Project Manager (MDA); John Burken, PCA Control Engineer.

  2. Monitoring Urban Stream Restoration Efforts in Relation to Flood Behavior Along Minebank Run, Towson, MD

    NASA Astrophysics Data System (ADS)

    Lee, G.; Miller, A. J.

    2017-12-01

    Urban stream restoration efforts are commonly undertaken to combat channel degradation and restore natural stream hydrology. We examine changes in flood patterns along an approximately 1.5-mile reach of Minebank Run, located in Towson, MD, by comparing pre-restoration morphology from surveys conducted in 2001, post-restoration morphology in 2007, and current conditions in 2017 following damage to the restoration project from persistent flooding. Hydraulic modeling was conducted in HEC-RAS 2D using three alternative scenarios: 1) topographic contours from a 2001 survey of pre-restoration topography combined with 2005 LiDAR, 2) 2007 survey combined with 2005 LiDAR data representing the post-restoration channel morphology, and 3) a March 2017 DEM of current channel conditions. The 2017 DEM was created using Structure from Motion (SfM) from high resolution 4K video collected via Unmanned Aerial Vehicle (UAV) flights at a resolution of 0.05 meters. Flood hydrographs from a USGS stream gage located within the study reach as well as a simulated hydrograph of the 100-year storm event were routed through the pre-restoration, post-restoration, and current modeled terrain and analyzed for changes in water-surface elevation and depth, inundation extent, 2-d velocity fields, and translation vs. attenuation of the flood wave to assess the net impact on potential flood hazards. In addition, our study demonstrates that SfM is a quick and inexpensive method for collecting topographic data for hydrologic modeling, assessing stream characteristics including channel bed roughness, and for examining short term changes of channel morphology at a very fine scale.

  3. 75 FR 31835 - Environmental Impact Statement: Calvert and St. Mary's Counties, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-04

    ...: Calvert and St. Mary's Counties, MD AGENCY: Federal Highway Administration (FHWA), DOT. ACTION: Notice of... project in Calvert and St. Mary's Counties, Maryland (Federal Register Vol. 72, No. 203; FR Doc. 07-5190... replacement of MD 4 from MD 2 to MD 235 in Calvert and St. Mary's Counties, a distance of approximately 4.1...

  4. A novel gene, MdSSK1, as a component of the SCF complex rather than MdSBP1 can mediate the ubiquitination of S-RNase in apple.

    PubMed

    Yuan, Hui; Meng, Dong; Gu, Zhaoyu; Li, Wei; Wang, Aide; Yang, Qing; Zhu, Yuandi; Li, Tianzhong

    2014-07-01

    As a core factor in S-RNase-based gametophytic self-incompatibility (GSI), the SCF (SKP1-Cullin1-F-box-Rbx1) complex (including pollen determinant SLF, S-locus-F-box) functions as an E3 ubiquitin ligase on non-self S-RNase. The SCF complex is formed by SKP1 bridging between SLF, CUL1, and Rbx1; however, it is not known whether an SCF complex lacking SKP1 can mediate the ubiquitination of S-RNase. Three SKP1-like genes from pollen were cloned based on the structural features of the SLF-interacting-SKP1-like (SSK) gene and the 'Golden Delicious' apple genome. These genes have a motif of five amino acids following the standard 'WAFE' at the C terminal and, in addition, contain eight sheets and two helices. All three genes were expressed exclusively in pollen. In the yeast two-hybrid and pull-down assays only one was found to interact with MdSFBB and MdCUL1, suggesting it is the SLF-interacting SKP1-like gene in apple which was named MdSSK1. In vitro experiments using MdSSK1, S2-MdSFBB1 (S2-Malus domestica S-locus-F-box brother) and MdCUL1 proteins incubated with S 2-RNase and ubiquitin revealed that the SCF complex ubiquitinylates S-RNase in vitro, while MdSBP1 (Malus domestica S-RNase binding protein 1) could not functionally replace MdSSK1 in the SCF complex in ubiquitinylating S-RNase. According to the above experiments, MdSBP1 is probably the only factor responsible for recognition with S-RNase, while not a component of the SCF complex, and an SCF complex containing MdSSK1 is required for mediating the ubiquitination of S-RNase. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  5. Medium Access Control for Opportunistic Concurrent Transmissions under Shadowing Channels

    PubMed Central

    Son, In Keun; Mao, Shiwen; Hur, Seung Min

    2009-01-01

    We study the problem of how to alleviate the exposed terminal effect in multi-hop wireless networks in the presence of log-normal shadowing channels. Assuming node location information, we propose an extension of the IEEE 802.11 MAC protocol that sched-ules concurrent transmissions in the presence of log-normal shadowing, thus mitigating the exposed terminal problem and improving network throughput and delay performance. We observe considerable improvements in throughput and delay achieved over the IEEE 802.11 MAC under various network topologies and channel conditions in ns-2 simulations, which justify the importance of considering channel randomness in MAC protocol design for multi-hop wireless networks. PMID:22408556

  6. Evolutionarily conserved intracellular gate of voltage-dependent sodium channels

    NASA Astrophysics Data System (ADS)

    Oelstrom, Kevin; Goldschen-Ohm, Marcel P.; Holmgren, Miguel; Chanda, Baron

    2014-03-01

    Members of the voltage-gated ion channel superfamily (VGIC) regulate ion flux and generate electrical signals in excitable cells by opening and closing pore gates. The location of the gate in voltage-gated sodium channels, a founding member of this superfamily, remains unresolved. Here we explore the chemical modification rates of introduced cysteines along the S6 helix of domain IV in an inactivation-removed background. We find that state-dependent accessibility is demarcated by an S6 hydrophobic residue; substituted cysteines above this site are not modified by charged thiol reagents when the channel is closed. These accessibilities are consistent with those inferred from open- and closed-state structures of prokaryotic sodium channels. Our findings suggest that an intracellular gate composed of a ring of hydrophobic residues is not only responsible for regulating access to the pore of sodium channels, but is also a conserved feature within canonical members of the VGIC superfamily.

  7. 75 FR 11563 - Jovencio L. Raneses, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-11

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Jovencio L. Raneses, M.D.; Denial of... Enforcement Administration, issued an Order to Show Cause to Jovencio L. Raneses, M.D. (Respondent), of San... issued by the Medical Board of California. See In re Jovencio L. Raneses, M.D., Default Decision and...

  8. 76 FR 48898 - Robert Leigh Kale, M.D., Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-09

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Robert Leigh Kale, M.D., Decision and Order... Enforcement Administration, issued an Order to Show Cause to Robert Leigh Kale, M.D. (Registrant), of Fort... Certificate of Registration, BK9514375, issued to Robert Leigh Kale, M.D., be, and it hereby is, revoked. I...

  9. 78 FR 52802 - Tin T. Win, M.D., Dismissal of Proceeding

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Tin T. Win, M.D., Dismissal of Proceeding On... Cause and Immediate Suspension of Registration to Tin T. Win, M.D. (hereinafter, Registrant), of Lake... order that the Order to Show Cause and Immediate Suspension of Registration issued to Tin T. Win, M.D...

  10. 76 FR 5686 - Drawbridge Operation Regulation; Pocomoke River, Pocomoke City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-02

    ... Operation Regulation; Pocomoke River, Pocomoke City, MD AGENCY: Coast Guard, DHS. ACTION: Notice of... River, mile 15.6, at Pocomoke City, MD. The deviation restricts the operation of the draw span to.... The Route 675 Bridge across Pocomoke River, mile 15.6 at Pocomoke City MD, has a vertical clearance in...

  11. 76 FR 81826 - Drawbridge Operation Regulation; Pocomoke River, Pocomoke City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... Operation Regulation; Pocomoke River, Pocomoke City, MD AGENCY: Coast Guard, DHS. ACTION: Notice of... River, mile 15.6, at Pocomoke City, MD. The deviation restricts the operation of the draw span to... City, MD, has a vertical clearance in the closed position of three feet above mean high water. Under...

  12. On Searching Available Channels with Asynchronous MAC-Layer Spectrum Sensing

    NASA Astrophysics Data System (ADS)

    Jiang, Chunxiao; Ma, Xin; Chen, Canfeng; Ma, Jian; Ren, Yong

    Dynamic spectrum access has become a focal issue recently, in which identifying the available spectrum plays a rather important role. Lots of work has been done concerning secondary user (SU) synchronously accessing primary user's (PU's) network. However, on one hand, SU may have no idea about PU's communication protocols; on the other, it is possible that communications among PU are not based on synchronous scheme at all. In order to address such problems, this paper advances a strategy for SU to search available spectrums with asynchronous MAC-layer sensing. With this method, SUs need not know the communication mechanisms in PU's network when dynamically accessing. We will focus on four aspects: 1) strategy for searching available channels; 2) vacating strategy when PUs come back; 3) estimation of channel parameters; 4) impact of SUs' interference on PU's data rate. The simulations show that our search strategy not only can achieve nearly 50% less interference probability than equal allocation of total search time, but also well adapts to time-varying channels. Moreover, access by our strategies can attain 150% more access time than random access. The moment matching estimator shows good performance in estimating and tracing time-varying channels.

  13. ISYS-MD: A Surgeon's Influence on System Design

    PubMed Central

    Cavaye, Graham

    1982-01-01

    ISYS-MD, the Integrated SYStem in MUMPS for MD's, is a new design and a completely re-written system for a computerized medical record. It possesses the functionality of COSTAR combined with a comprehensive accountancy system. In addition, various ideas have been incorporated from the author's extensive experience in medical practice, making the system very practical in a clinical environment.

  14. Bearer channel control protocol for the dynamic VB5.2 interface in ATM access networks

    NASA Astrophysics Data System (ADS)

    Fragoulopoulos, Stratos K.; Mavrommatis, K. I.; Venieris, Iakovos S.

    1996-12-01

    In the multi-vendor systems, a customer connected to an Access network (AN) must be capable of selecting a specific Service Node (SN) according to the services the SN provides. The multiplicity of technologically varying AN calls for the definition of a standard reference point between the AN and the SN widely known as the VB interface. Two versions are currently offered. The VB5.1 is simpler to implement but is not as flexible as the VB5.2, which supports switched connections. The VB5.2 functionality is closely coupled to the Broadband Bearer Channel Connection Protocol (B-BCCP). The B-BCCP is used for conveying the necessary information for dynamic resource allocation, traffic policing and routing in the AN as well as for information exchange concerning the status of the AN before a new call is established by the SN. By relying on such a protocol for the exchange of information instead of intercepting and interpreting signalling messages in the AN, the architecture of the AN is simplified because the functionality related to processing is not duplicated. In this paper a prominent B- BCCP candidate is defined, called the Service node Access network Interaction Protocol.

  15. 76 FR 71369 - Robert G. Crummie, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-60] Robert G. Crummie, M.D... Registration, BC2964965, issued to Robert G. Crummie, M.D., be, and it hereby is, revoked. I further order that any pending application of Robert G. Crummie, M.D., to renew or modify his registration, be, and it...

  16. 78 FR 19012 - Pawan Kumar Jain, M.D.; Decision And Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-28

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 13-13] Pawan Kumar Jain, M.D...), I order that DEA Certificate of Registration BJ5128067, issued to Pawan Kumar Jain, M.D., be, and it hereby is, revoked. I further order that any pending application of Pawan Kumar Jain, M.D., to renew or...

  17. 75 FR 49955 - Hung Thien Ly, M.D.; Revocation of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Hung Thien Ly, M.D.; Revocation of... Enforcement Administration, issued an Order to Show Cause to Hung Thien Ly, M.D. (Respondent), of McRae..., BL8586147, issued to Hung Thien Ly, M.D., be, and it hereby is, revoked. I further order that any pending...

  18. Public Access Report.

    ERIC Educational Resources Information Center

    Anshien, Carol M.; And Others

    A short review of the development of cable television in New York City, a brief description of wiring patterns, a history of public access, and some statistical data on public channel usage are provided in the first portion of this report. The second major part describes the Public Access Celebration, a three-day informational event held in July…

  19. Digging into Lipid Membrane Permeation for Cardiac Ion Channel Blocker d-Sotalol with All-Atom Simulations

    PubMed Central

    DeMarco, Kevin R.; Bekker, Slava; Clancy, Colleen E.; Noskov, Sergei Y.; Vorobyov, Igor

    2018-01-01

    Interactions of drug molecules with lipid membranes play crucial role in their accessibility of cellular targets and can be an important predictor of their therapeutic and safety profiles. Very little is known about spatial localization of various drugs in the lipid bilayers, their active form (ionization state) or translocation rates and therefore potency to bind to different sites in membrane proteins. All-atom molecular simulations may help to map drug partitioning kinetics and thermodynamics, thus providing in-depth assessment of drug lipophilicity. As a proof of principle, we evaluated extensively lipid membrane partitioning of d-sotalol, well-known blocker of a cardiac potassium channel Kv11.1 encoded by the hERG gene, with reported substantial proclivity for arrhythmogenesis. We developed the positively charged (cationic) and neutral d-sotalol models, compatible with the biomolecular CHARMM force field, and subjected them to all-atom molecular dynamics (MD) simulations of drug partitioning through hydrated lipid membranes, aiming to elucidate thermodynamics and kinetics of their translocation and thus putative propensities for hydrophobic and aqueous hERG access. We found that only a neutral form of d-sotalol accumulates in the membrane interior and can move across the bilayer within millisecond time scale, and can be relevant to a lipophilic channel access. The computed water-membrane partitioning coefficient for this form is in good agreement with experiment. There is a large energetic barrier for a cationic form of the drug, dominant in water, to cross the membrane, resulting in slow membrane translocation kinetics. However, this form of the drug can be important for an aqueous access pathway through the intracellular gate of hERG. This route will likely occur after a neutral form of a drug crosses the membrane and subsequently re-protonates. Our study serves to demonstrate a first step toward a framework for multi-scale in silico safety pharmacology, and

  20. Public Television Channels in New York City: The First Six Months.

    ERIC Educational Resources Information Center

    Calhoun, Richard

    The end results of the first six months of public access cable television (CATV) channels in New York City were in some ways disappointing. Franchise agreements for each of New York's two CATV systems called for two public-access channels to be in operation by July 1, 1971, one year after the date of the franchise awards. The channels were to be…

  1. Trends in MD/PhD Graduates Entering Psychiatry: Assessing the Physician-Scientist Pipeline.

    PubMed

    Arbuckle, Melissa R; Luo, Sean X; Pincus, Harold Alan; Gordon, Joshua A; Chung, Joyce Y; Chavez, Mark; Oquendo, Maria A

    2018-06-01

    The goal of this study was to identify trends in MD/PhD graduates entering psychiatry, to compare these trends with other specialties, and to review strategies for enhancing the physician-scientist pipeline. Data on 226,588 medical students graduating from Liaison Committee on Medical Education accredited programs between 1999 and 2012 (6626 MD/PhDs) were used to evaluate the number, percentage, and proportion of MD/PhDs entering psychiatry in comparison with other specialties (neurology, neurosurgery, internal medicine, family medicine, and radiation oncology). Linear regression and multiple linear regression determined whether these values increased over time and varied by sex. Over 14 years, an average of 18 MD/PhDs (range 13-29) enrolled in psychiatry each year. The number of MD/PhDs going into psychiatry significantly increased, although these gains were modest (less than one additional MD/PhD per year). The proportion of students entering psychiatry who were MD/PhDs varied between 2.9 and 5.9 per 100 residents, with no significant change over time. There was also no change in the percentage of MD/PhDs entering psychiatry from among all MD/PhD graduates. The rate of increase in the number of MD/PhDs going into psychiatry did not differ significantly from other specialties except for family medicine, which is decreasing. The rate of MD/PhDs going into psychiatry was higher for women, suggesting closure of the sex gap in 17 years. Despite the increase in the number of MD/PhDs entering psychiatry, these numbers remain low. Expanding the cohort of physician-scientists dedicated to translational research in psychiatry will require a multipronged approach.

  2. [MD PhD programs: Providing basic science education for ophthalmologists].

    PubMed

    Spaniol, K; Geerling, G

    2015-06-01

    Enrollment in MD PhD programs offers the opportunity of a basic science education for medical students and doctors. These programs originated in the USA where structured programs have been offered for many years, but now German universities also run MD PhD programs. The MD PhD programs provided by German universities were investigated regarding entrance requirements, structure and financing modalities. An internet and telephone-based search was carried out. Out of 34 German universities 22 offered MD PhD programs. At 15 of the 22 universities a successfully completed course of studies in medicine was required for enrollment, 7 programs admitted medical students in training and 7 programs required a medical doctoral thesis, which had to be completed with at least a grade of magna cum laude in 3 cases. Financing required scholarships in many cases. Several German universities currently offer MD PhD programs; however, these differ considerably regarding entrance requirements, structure and financing. A detailed analysis investigating the success rates of these programs (e.g. successful completion and career paths of graduates) would be of benefit.

  3. Groundwater controls on river channel pattern

    NASA Astrophysics Data System (ADS)

    Bätz, Nico; Colombini, Pauline; Cherubini, Paolo; Lane, Stuart N.

    2017-04-01

    Braided rivers are characterized by high rates of morphological change. However, despite the potential for frequent disturbance, vegetated patches may develop within this system and influence long-term channel dynamics and channel patterns through the "engineering effects" of vegetation. The stabilizing effect of developing vegetation on morphological change has been widely shown by flume experiments and (historic) aerial pictures analysis. Thus, there is a balance between disturbance and stabilization, mediated through vegetation, that may determine the long-term geomorphic and biogeomorphic evolution of the river. It follows that with a change in disturbance frequency relative to the rate of vegetation establishment, a systematic geomorphological shift could occur. Research has addressed how changes in disturbance frequency affect river channel pattern, but has rarely addressed the way in which the stabilizing effects of biogeomorphic succession interact with disturbance frequency to maintain a river in a more dynamic or a less dynamic state. Here, we quantify how the interplay between groundwater access, disturbance frequency and vegetation succession, drive changes in channel pattern. We studied this complex interplay on a transitional gravel-bed river system (braided, wandering, meandering) close to Geneva (Switzerland) - the Allondon River. Dendroecological analysis demonstrate that vegetation growth is driven by groundwater access. Groundwater access conditions the rate of vegetation stabilization at the sub-reach scale and, due to a reduction in flood-related disturbance frequency over the last 50 years, drives a change in channel pattern. Where groundwater is shallower, vegetation encroachment rates were high and as flood-related disturbance decreased, the river has shifted towards a meandering state. Where groundwater was deeper, vegetation growth was limited by water-access and thus vegetation encroachment rates were low. Even though there was a

  4. BGK-MD, Version 1.0

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

    Haack, Jeffrey; Shohet, Gil

    2016-12-02

    The software implements a heterogeneous multiscale method (HMM), which involves solving a classical molecular dynamics (MD) problem and then computes the entropy production in order to compute the relaxation times towards equilibrium for use in a Bhatnagar-Gross-Krook (BGK) solver.

  5. 33 CFR 110.71a - Cabin Creek, Grasonville, Md.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

  6. 33 CFR 110.71a - Cabin Creek, Grasonville, Md.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

  7. 33 CFR 110.71a - Cabin Creek, Grasonville, Md.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

  8. 33 CFR 110.71a - Cabin Creek, Grasonville, Md.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

  9. 33 CFR 110.71a - Cabin Creek, Grasonville, Md.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Cabin Creek, Grasonville, Md. 110.71a Section 110.71a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71a Cabin Creek, Grasonville, Md. The waters...

  10. 76 FR 70647 - Safety Zone; Fireworks Display, Potomac River, National Harbor Access Channel, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-15

    ... Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a safety zone upon specified waters of the Potomac River. This action is necessary to provide for the safety of life on... maritime public in a portion of the Potomac River. DATES: This rule is effective from 6 p.m. on November 19...

  11. Spitzer observations of two mission-accessible, tiny asteroids

    NASA Astrophysics Data System (ADS)

    Mommert, M.; Hora, J.; Farnocchia, D.; Chesley, S.; Vokrouhlicky, D.; Trilling, D.; Mueller, M.; Harris, A.; Smith, H.; Fazio, G.

    2014-07-01

    Small asteroids are most likely collisional fragments of larger objects and make up a large fraction of the near-Earth-object (NEO) population. Despite their abundance, little is known about the physical properties of these objects, which is mainly due to their faintness, which also impedes their discovery. We report on Spitzer Space Telescope observations of two small NEOs, both of which are of interest as potential spacecraft targets. We observed NEOs 2009 BD using 25 hrs and 2011 MD using ˜20 hrs of Spitzer Infrared Array Camera Channel 2 time. For each target, we have combined the data into maps in the moving frame of the target, minimizing the background confusion. We did not detect 2009 BD and place an upper limit on its flux density, but we detected 2011 MD as a 2.2σ detection. We have analyzed the data on both objects in a combined model approach, using an asteroid thermophysical model and a model of non-gravitational forces acting on the object. As a result, we are able to constrain the physical properties of both objects. In the case of 2009 BD (Mommert et al. 2014), a wealth of existing astrometry data significantly constrains the physical properties of the object. We find two physically possible solutions. The first solution shows 2009 BD as a 2.9±0.3 m-sized massive rock body (bulk density ρ=2.9±0.5 g cm^{-3}) with an extremely high albedo of 0.85_{-0.10}^{+0.20} that is covered with regolith-like material, causing it to exhibit a low thermal inertia (thermal inertia Γ=30_{-10}^{+20} SI units). The second solution suggests 2009 BD to be a 4±1 m-sized asteroid with p_{V}=0.45_{-0.15}^{+0.35} that consists of a collection of individual bare rock slabs (Γ = 2000±1000 SI units, ρ = 1.7_{-0.4}^{+0.7} g cm^{-3}). We are unable to rule out either solution based on physical reasoning. The preliminary analysis of 2011 MD shows this object as a ˜6 m-sized asteroid with an albedo of ˜0.3. Additional constraints on the physical properties of these

  12. CoMD Implementation Suite in Emerging Programming Models

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

    Haque, Riyaz; Reeve, Sam; Juallmes, Luc

    CoMD-Em is a software implementation suite of the CoMD [4] proxy app using different emerging programming models. It is intended to analyze the features and capabilities of novel programming models that could help ensure code and performance portability and scalability across heterogeneous platforms while improving programmer productivity. Another goal is to provide the authors and venders with some meaningful feedback regarding the capabilities and limitations of their models. The actual application is a classical molecular dynamics (MD) simulation using either the Lennard-Jones method (LJ) or the embedded atom method (EAM) for primary particle interaction. The code can be extended tomore » support alternate interaction models. The code is expected ro run on a wide class of heterogeneous hardware configurations like shard/distributed/hybrid memory, GPU's and any other platform supported by the underlying programming model.« less

  13. Random access with adaptive packet aggregation in LTE/LTE-A.

    PubMed

    Zhou, Kaijie; Nikaein, Navid

    While random access presents a promising solution for efficient uplink channel access, the preamble collision rate can significantly increase when massive number of devices simultaneously access the channel. To address this issue and improve the reliability of the random access, an adaptive packet aggregation method is proposed. With the proposed method, a device does not trigger a random access for every single packet. Instead, it starts a random access when the number of aggregated packets reaches a given threshold. This method reduces the packet collision rate at the expense of an extra latency, which is used to accumulate multiple packets into a single transmission unit. Therefore, the tradeoff between packet loss rate and channel access latency has to be carefully selected. We use semi-Markov model to derive the packet loss rate and channel access latency as functions of packet aggregation number. Hence, the optimal amount of aggregated packets can be found, which keeps the loss rate below the desired value while minimizing the access latency. We also apply for the idea of packet aggregation for power saving, where a device aggregates as many packets as possible until the latency constraint is reached. Simulations are carried out to evaluate our methods. We find that the packet loss rate and/or power consumption are significantly reduced with the proposed method.

  14. 33 CFR 110.71b - Wye River, Wye, Md.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Wye River, Wye, Md. 110.71b Section 110.71b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71b Wye River, Wye, Md. The waters of a cove on the...

  15. 33 CFR 110.71b - Wye River, Wye, Md.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Wye River, Wye, Md. 110.71b Section 110.71b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71b Wye River, Wye, Md. The waters of a cove on the...

  16. 33 CFR 110.71b - Wye River, Wye, Md.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Wye River, Wye, Md. 110.71b Section 110.71b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71b Wye River, Wye, Md. The waters of a cove on the...

  17. 33 CFR 110.71b - Wye River, Wye, Md.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Wye River, Wye, Md. 110.71b Section 110.71b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71b Wye River, Wye, Md. The waters of a cove on the...

  18. 33 CFR 110.71b - Wye River, Wye, Md.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Wye River, Wye, Md. 110.71b Section 110.71b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71b Wye River, Wye, Md. The waters of a cove on the...

  19. Apple F-Box Protein MdMAX2 Regulates Plant Photomorphogenesis and Stress Response.

    PubMed

    An, Jian-Ping; Li, Rui; Qu, Feng-Jia; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

    2016-01-01

    MAX2 (MORE AXILLARY GROWTH2) is involved in diverse physiological processes, including photomorphogenesis, the abiotic stress response, as well as karrikin and strigolactone signaling-mediated shoot branching. In this study, MdMAX2, an F-box protein that is a homolog of Arabidopsis MAX2, was identified and characterized. Overexpression of MdMAX2 in apple calli enhanced the accumulation of anthocyanin. Ectopic expression of MdMAX2 in Arabidopsis exhibited photomorphogenesis phenotypes, including increased anthocyanin content and decreased hypocotyl length. Further study indicated that MdMAX2 might promote plant photomorphogenesis by affecting the auxin signaling as well as other plant hormones. Transcripts of MdMAX2 were noticeably up-regulated in response to NaCl and Mannitol treatments. Moreover, compared with the wild-type, the MdMAX2 -overexpressing apple calli and Arabidopsis exhibited increased tolerance to salt and drought stresses. Taken together, these results suggest that MdMAX2 plays a positive regulatory role in plant photomorphogenesis and stress response.

  20. Coarse-Grained MD Simulations and Protein-Protein Interactions: The Cohesin-Dockerin System.

    PubMed

    Hall, Benjamin A; Sansom, Mark S P

    2009-09-08

    Coarse-grained molecular dynamics (CG-MD) may be applied as part of a multiscale modeling approach to protein-protein interactions. The cohesin-dockerin interaction provides a valuable test system for evaluation of the use of CG-MD, as structural (X-ray) data indicate a dual binding mode for the cohesin-dockerin pair. CG-MD simulations (of 5 μs duration) of the association of cohesin and dockerin identify two distinct binding modes, which resemble those observed in X-ray structures. For each binding mode, ca. 80% of interfacial residues are predicted correctly. Furthermore, each of the binding modes identified by CG-MD is conformationally stable when converted to an atomistic model and used as the basis of a conventional atomistic MD simulation of duration 20 ns.

  1. MD Simulations of P-Type ATPases in a Lipid Bilayer System.

    PubMed

    Autzen, Henriette Elisabeth; Musgaard, Maria

    2016-01-01

    Molecular dynamics (MD) simulation is a computational method which provides insight on protein dynamics with high resolution in both space and time, in contrast to many experimental techniques. MD simulations can be used as a stand-alone method to study P-type ATPases as well as a complementary method aiding experimental studies. In particular, MD simulations have proved valuable in generating and confirming hypotheses relating to the structure and function of P-type ATPases. In the following, we describe a detailed practical procedure on how to set up and run a MD simulation of a P-type ATPase embedded in a lipid bilayer using software free of use for academics. We emphasize general considerations and problems typically encountered when setting up simulations. While full coverage of all possible procedures is beyond the scope of this chapter, we have chosen to illustrate the MD procedure with the Nanoscale Molecular Dynamics (NAMD) and the Visual Molecular Dynamics (VMD) software suites.

  2. 75 FR 8749 - Dwayne LaFrantz Wilson, M.D.; Revocation of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-25

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Dwayne LaFrantz Wilson, M.D.; Revocation of... Enforcement Administration, issued an Order to Show Cause to Dwayne LaFrantz Wilson, M.D. (Respondent), of... Registration, BW6030857, issued to Dwayne LaFrantz Wilson, M.D., be, and it hereby is, revoked. I further order...

  3. Computational membrane biophysics: From ion channel interactions with drugs to cellular function.

    PubMed

    Miranda, Williams E; Ngo, Van A; Perissinotti, Laura L; Noskov, Sergei Yu

    2017-11-01

    The rapid development of experimental and computational techniques has changed fundamentally our understanding of cellular-membrane transport. The advent of powerful computers and refined force-fields for proteins, ions, and lipids has expanded the applicability of Molecular Dynamics (MD) simulations. A myriad of cellular responses is modulated through the binding of endogenous and exogenous ligands (e.g. neurotransmitters and drugs, respectively) to ion channels. Deciphering the thermodynamics and kinetics of the ligand binding processes to these membrane proteins is at the heart of modern drug development. The ever-increasing computational power has already provided insightful data on the thermodynamics and kinetics of drug-target interactions, free energies of solvation, and partitioning into lipid bilayers for drugs. This review aims to provide a brief summary about modeling approaches to map out crucial binding pathways with intermediate conformations and free-energy surfaces for drug-ion channel binding mechanisms that are responsible for multiple effects on cellular functions. We will discuss post-processing analysis of simulation-generated data, which are then transformed to kinetic models to better understand the molecular underpinning of the experimental observables under the influence of drugs or mutations in ion channels. This review highlights crucial mathematical frameworks and perspectives on bridging different well-established computational techniques to connect the dynamics and timescales from all-atom MD and free energy simulations of ion channels to the physiology of action potentials in cellular models. This article is part of a Special Issue entitled: Biophysics in Canada, edited by Lewis Kay, John Baenziger, Albert Berghuis and Peter Tieleman. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. 78 FR 20255 - Leased Commercial Access

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

    ... follows: Sec. 76.970 Commercial leased access rates. (a) Cable operators shall designate channel capacity... U.S.C. 532. For purposes of 47 U.S.C. 532(b)(1)(A) and (B), only those channels that must be carried pursuant to 47 U.S.C. 534 and 535 qualify as channels that are required for use by Federal law or...

  5. Chondrocyte channel transcriptomics

    PubMed Central

    Lewis, Rebecca; May, Hannah; Mobasheri, Ali; Barrett-Jolley, Richard

    2013-01-01

    To date, a range of ion channels have been identified in chondrocytes using a number of different techniques, predominantly electrophysiological and/or biomolecular; each of these has its advantages and disadvantages. Here we aim to compare and contrast the data available from biophysical and microarray experiments. This letter analyses recent transcriptomics datasets from chondrocytes, accessible from the European Bioinformatics Institute (EBI). We discuss whether such bioinformatic analysis of microarray datasets can potentially accelerate identification and discovery of ion channels in chondrocytes. The ion channels which appear most frequently across these microarray datasets are discussed, along with their possible functions. We discuss whether functional or protein data exist which support the microarray data. A microarray experiment comparing gene expression in osteoarthritis and healthy cartilage is also discussed and we verify the differential expression of 2 of these genes, namely the genes encoding large calcium-activated potassium (BK) and aquaporin channels. PMID:23995703

  6. Possibilities of production of transfermium nuclei in charged-particle evaporation channels

    NASA Astrophysics Data System (ADS)

    Hong, Juhee; Adamian, G. G.; Antonenko, N. V.

    2016-10-01

    The possibilities of direct production of the isotopes of transfermium nuclei Md,260259, No,261260, Lr-264261, Rf,265264, Db-268264, Sg-269266, Bh-271266, Hs-274267, and Mt-274270 in various asymmetric hot fusion-evaporation reactions are studied. The excitation functions of the formation of these isotopes in the α x n and p x n evaporation channels are predicted for the first time. The optimal reaction partners and conditions for the synthesis of new isotopes are suggested. The products of the suggested reactions can fill a gap of unknown isotopes between the isotopes of heaviest nuclei obtained in the x n evaporation channels of the cold and hot complete fusion reactions.

  7. Single or Multiple Access Channels to the CYP450s Active Site? An Answer from Free Energy Simulations of the Human Aromatase Enzyme.

    PubMed

    Magistrato, Alessandra; Sgrignani, Jacopo; Krause, Rolf; Cavalli, Andrea

    2017-05-04

    Cytochromes P450 (CYP450s), in particular, CYP19A1 and CYP17A1, are key clinical targets of breast and prostate anticancer therapies, critical players in drug metabolism, and their overexpression in tumors is associated with drug resistance. In these enzymes, ligand (substrates, drugs) metabolism occurs in deeply buried active sites accessible only via several grueling channels, whose exact biological role remains unclear. Gaining direct insights on the mechanism by which ligands travel in and out is becoming increasingly important given that channels are involved in the modulation of binding/dissociation kinetics and the specificity of ligands toward a CYP450. This has profound implications for enzymatic efficiency and drug efficacy/toxicity. Here, by applying free energy methods, for a cumulative simulation time of 20 μs, we provide detailed atomistic characterization and free energy profiles of the entry/exit routes preferentially followed by a substrate (androstenedione) and a last-generation inhibitor (letrozole) to/from the catalytic site of CYP19A1 (the human aromatase (HA) enzyme), a key clinical target against breast cancer, studied here as prototypical CYP450. Despite the remarkably different size/shape/hydrophobicity of the ligands, two channels appear accessible to their entrance, while only one exit route appears to be preferential. Our study shows that the preferential paths may be conserved among different CYP450s. Moreover, our results highlight that, at least in the case of HA, ligand channeling is associated with large enzyme structural rearrangements. A wise choice of the computational method and very long simulations are, thus, required to obtain fully converged quantitative free energy profiles, which might be used to design novel biocatalysts or next-generation cytochrome inhibitors with an in silico tuned K m .

  8. 76 FR 20034 - Calvin Ramsey, M.D.; Revocation of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-25] Calvin Ramsey, M.D... Control, Drug Enforcement Administration, issued an Order to Show Cause to Calvin Ramsey, M.D. (Respondent.... Respondent's Resp., at 1. Therein, Respondent asserted that ``[d]ue process dictates that this Court must...

  9. 77 FR 37068 - Muzaffer Aslan, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-20

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Muzaffer Aslan, M.D.; Decision and Order On... Cause and Immediate Suspension of Registration to Muzaffer Aslan, M.D. (hereinafter, Respondent), of Los....C. 824, of the CSA. Calvin Ramsey, 76 FR 20034, 20036 (2011) (other citations omitted); Brenton D...

  10. Developing the MD Explorer

    NASA Astrophysics Data System (ADS)

    Howie, Philip V.

    1993-04-01

    The MD Explorer is an eight-seat twin-turbine engine helicopter which is being developed using integrated product definition (IPD) team methodology. New techniques include NOTAR antitorque system for directional control, a composite fuselage, an all-composite bearingless main rotor, and digital cockpit displays. Three-dimensional CAD models are the basis of the entire Explorer design. Solid models provide vendor with design clarification, removing much of the normal drawing interpretation errors.

  11. Modeling of dislocation channel width evolution in irradiated metals

    NASA Astrophysics Data System (ADS)

    Doyle, Peter J.; Benensky, Kelsa M.; Zinkle, Steven J.

    2018-02-01

    Defect-free dislocation channel formation has been reported to promote plastic instability during tensile testing via localized plastic flow, leading to a distinct loss of ductility and strain hardening in many low-temperature irradiated materials. In order to study the underlying mechanisms governing dislocation channel width and formation, the channel formation process is modeled via a simple stochastic dislocation-jog process dependent upon grain size, defect cluster density, and defect size. Dislocations traverse a field of defect clusters and jog stochastically upon defect interaction, forming channels of low defect-density. Based upon prior molecular dynamics (MD) simulations and in-situ experimental transmission electron microscopy (TEM) observations, each dislocation encounter with a dislocation loop or stacking fault tetrahedron (SFT) is assumed to cause complete absorption of the defect cluster, prompting the dislocation to jog up or down by a distance equal to half the defect cluster diameter. Channels are predicted to form rapidly and are comparable to reported TEM measurements for many materials. Predicted channel widths are found to be most strongly dependent on mean defect size and correlated well with a power law dependence on defect diameter and density, and distance from the dislocation source. Due to the dependence of modeled channel width on defect diameter and density, maximum channel width is predicted to slowly increase as accumulated dose increases. The relatively weak predicted dependence of channel formation width with distance, in accordance with a diffusion analogy, implies that after only a few microns from the source, most channels observed via TEM analyses may not appear to vary with distance because of limitations in the field-of-view to a few microns. Further, examinations of the effect of the so-called "source-broadening" mechanism of channel formation showed that its effect is simply to add a minimum thickness to the channel

  12. 76 FR 71370 - Silviu Ziscovici, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 11-3] Silviu Ziscovici, M.D.; Decision and Order On December 10, 2010, Administrative Law Judge (ALJ) Timothy D. Wing, issued the... Certificate of Registration, BZ4692756, issued to Silviu Ziscovici, M.D., be, and it hereby is, revoked. I...

  13. ATP transport through VDAC and the VDAC-tubulin complex probed by equilibrium and nonequilibrium MD simulations.

    PubMed

    Noskov, Sergei Yu; Rostovtseva, Tatiana K; Bezrukov, Sergey M

    2013-12-23

    Voltage-dependent anion channel (VDAC), the major channel of the mitochondrial outer membrane, serves as a principal pathway for ATP, ADP, and other respiratory substrates across this membrane. Using umbrella-sampling simulations, we established the thermodynamic and kinetic components governing ATP transport across the VDAC1 channel. We found that there are several low-affinity binding sites for ATP along the translocation pathway and that the main barrier for ATP transport is located around the center of the channel and is formed predominantly by residues in the N-terminus. The binding affinity of ATP to an open channel was found to be in the millimolar to micromolar range. However, we show that this weak binding increases the ATP translocation probability by about 10-fold compared with the VDAC pore in which attractive interactions were artificially removed. Recently, it was found that free dimeric tubulin induces a highly efficient, reversible blockage of VDAC reconstituted into planar lipid membranes. It was proposed that by blocking VDAC permeability for ATP/ADP and other mitochondrial respiratory substrates tubulin controls mitochondrial respiration. Using the Rosetta protein-protein docking algorithm, we established a tentative structure of the VDAC-tubulin complex. An extensive set of equilibrium and nonequilibrium (under applied electric field) molecular dynamics (MD) simulations was used to establish the conductance of the open and blocked channel. It was found that the presence of the unstructured C-terminal tail of tubulin in the VDAC pore decreases its conductance by more than 40% and switches its selectivity from anionic to cationic. The subsequent 1D potential of mean force (PMF) computations for the VDAC-tubulin complex show that the state renders ATP transport virtually impossible. A number of residues pivotal for tubulin binding to the channel were identified that help to clarify the molecular details of VDAC-tubulin interaction and to provide

  14. 33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

  15. 33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

  16. 33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

  17. 33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

  18. 33 CFR 110.71 - Jacobs Nose Cove, Elk River, Md.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Jacobs Nose Cove, Elk River, Md. 110.71 Section 110.71 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water...

  19. 77 FR 24838 - Safety Zone; Magothy River, Sillery Bay, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-26

    ...-AA00 Safety Zone; Magothy River, Sillery Bay, MD AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: The Coast Guard is establishing a safety zone in certain waters of the Magothy River, in Sillery Bay... a notice of proposed rulemaking (NPRM) entitled ``Safety Zone; Magothy River, Sillery Bay, MD'' in...

  20. 75 FR 30860 - Shepard Ginandes, M.D.; Revocation of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-02

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-14] Shepard Ginandes, M.D... Administration, issued an Order to Show Cause and Immediate Suspension of Registration to Shepard Ginandes, M.D... right to a hearing.'' Id. (citing 21 CFR 1301.43(d) & (e)). On September 30, 2009, the Order was served...

  1. Analysis of MD5 authentication in various routing protocols using simulation tools

    NASA Astrophysics Data System (ADS)

    Dinakaran, M.; Darshan, K. N.; Patel, Harsh

    2017-11-01

    Authentication being an important paradigm of security and Computer Networks require secure paths to make the flow of the data even more secure through some security protocols. So MD-5(Message Digest 5) helps in providing data integrity to the data being sent through it and authentication to the network devices. This paper gives a brief introduction to the MD-5, simulation of the networks by including MD-5 authentication using various routing protocols like OSPF, EIGRP and RIPv2. GNS3 is being used to simulate the scenarios. Analysis of the MD-5 authentication is done in the later sections of the paper.

  2. Cummins MD & HD Accessory Hybridization CRADA -Annual Report FY15

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

    Deter, Dean D.

    2015-10-01

    There are many areas of MD and HD vehicles that can be improved by new technologies and optimized control strategies. Component optimization and idle reduction need to be addressed, this is best done by a two part approach that includes selecting the best component technology, and/or architecture, and optimized controls that are vehicle focused. While this is a common focus in the light duty industry it has been gaining momentum in the MD and HD market as the market gets more competitive and the regulations become more stringent. When looking into systems optimization and idle reduction technologies, affected vehicle systemsmore » must first be considered, and if possible included in the new architecture to get the most benefit out of these new capabilities. Typically, when looking into idle reduction or component optimization for MD/HD, the vehicle s accessories become a prime candidate for electrification or hybridization. While this has already been studied on light duty vehicles (especially on hybrids and electric vehicles) it has not made any head way or market penetration in most MD and HD applications. If hybrids and electric MD and HD vehicles begin to break into the market this would be a necessary step into the ability to make those vehicles successful by allowing for independent, optimized operation separate from the engine.« less

  3. Drosophila Nociceptors Mediate Larval Aversion to Dry Surface Environments Utilizing Both the Painless TRP Channel and the DEG/ENaC Subunit, PPK1

    PubMed Central

    Johnson, Wayne A.; Carder, Justin W.

    2012-01-01

    A subset of sensory neurons embedded within the Drosophila larval body wall have been characterized as high-threshold polymodal nociceptors capable of responding to noxious heat and noxious mechanical stimulation. They are also sensitized by UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very similar to that observed in vertebrate nociceptors. We show that the class IV multiple-dendritic(mdIV) nociceptors are also required for a normal larval aversion to locomotion on to a dry surface environment. Drosophila melanogaster larvae are acutely susceptible to desiccation displaying a strong aversion to locomotion on dry surfaces severely limiting the distance of movement away from a moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in larvae moving inappropriately into regions of low humidity at the top of the vial reflected as an increased overall pupation height and larval desiccation. This larval lethal desiccation phenotype was not observed in wild-type controls and was completely suppressed by growth in conditions of high humidity. Transgenic hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry surfaces resulting in drastically decreased pupation height but did not induce the writhing nocifensive response previously associated with mdIV nociceptor activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed the same inappropriate increased pupation height and lethal desiccation observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces appears to utilize the same or overlapping sensory transduction pathways activated by noxious heat and harsh mechanical stimulation but with strikingly different sensitivities and disparate physiological responses. PMID:22403719

  4. 33 CFR 110.70a - Northeast River, North East, Md.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

  5. 33 CFR 110.70a - Northeast River, North East, Md.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

  6. 33 CFR 110.70a - Northeast River, North East, Md.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

  7. 33 CFR 110.70a - Northeast River, North East, Md.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

  8. 33 CFR 110.70a - Northeast River, North East, Md.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Northeast River, North East, Md. 110.70a Section 110.70a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.70a Northeast River, North East, Md. The water...

  9. 76 FR 71374 - Joseph Giacchino, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-54] Joseph Giacchino, M.D.; Decision and Order On July 9, 2010, Administrative Law Judge (ALJ) Timothy D. Wing, issued the attached... prevail. See, e.g., Bourne Pharmacy, 72 FR 18,273, 18,274 (2007); Agostino Carlucci, M.D., 49 FR 33,184...

  10. Trypsin-sensitive modulation of intestinal epithelial MD-2 as mechanism of lipopolysaccharide tolerance.

    PubMed

    Cario, Elke; Golenbock, Douglas T; Visintin, Alberto; Rünzi, Michael; Gerken, Guido; Podolsky, Daniel K

    2006-04-01

    Intestinal epithelial cells (IEC) are constantly exposed to both high concentrations of the bacterial ligand LPS and the serine protease trypsin. MD-2, which contains multiple trypsin cleavage sites, is an essential accessory glycoprotein required for LPS recognition and signaling through TLR4. The aim of this study was to characterize the expression and subcellular distribution of intestinal epithelial MD-2 and to delineate potential functional interactions with trypsin and then alteration in inflammatory bowel disease (IBD). Although MD-2 protein expression was minimal in primary IEC of normal colonic or ileal mucosa, expression was significantly increased in IEC from patients with active IBD colitis, but not in ileal areas from patients with severe Crohn's disease. Endogenous MD-2 was predominantly retained in the calnexin-calreticulin cycle of the endoplasmic reticulum; only a small fraction was exported to the Golgi. MD-2 expression correlated inversely with trypsin activity. Biochemical evidence and in vitro experiments demonstrated that trypsin exposure resulted in extensive proteolysis of endogenous and soluble MD-2 protein, but not of TLR4 in IEC, and was associated with desensitization of IEC to LPS. In conclusion, the present study suggests that endoplasmic reticulum-associated MD-2 expression in IBD may be altered by ileal protease in inflammation, leading to impaired LPS recognition and hyporesponsiveness through MD-2 proteolysis in IEC, thus implying a physiologic mechanism that helps maintain LPS tolerance in the intestine.

  11. A pilot study of MD (psychiatry) theses-based research.

    PubMed

    Srivastava, Shrikant; Agarwal, Vivek; Subramanyam, Alka; Srivastava, Mona; Sathyanarayana Rao, T S; Rao, G Prasad; Khurana, Hitesh; Singh, Archana

    2018-01-01

    Undertaking a research project is mandatory for MD Psychiatry trainees. The present study was undertaken to assess the type of research activity being undertaken as part of MD Psychiatry dissertation, and its contribution to national and international literature. Three medical colleges supplied the data about the topic, names of the supervisor and the candidate, collaboration, funding accrued, and publication details of MD-based research carried out between years 2000 and 2010 inclusive; 95 records were collected for the final analysis. The details of the publications provided were cross-checked on the internet, which would have taken care of missed publications as well. Most studies were single-point assessment clinical studies. Only 2 studies had been funded, 11 had collaboration with other departments within the same institute, and 5 had inter-institute collaborations. Majority of the studies were not published. Only 30 were published as full paper and 9 as abstracts. Of these 30 full publications, only 3 were published in journals having JCI impact factor values (1.4, 1.3, and 1.4, respectively). The main finding of this pilot study was that MD-based research has low contribution to the national and international literature, and those articles which are published are in low impact journals. Suggestions for modifying this state of affairs are discussed.

  12. Rhodotorula taiwanensis MD1149 produces hypoacetylated PEFA compounds with increased surface activity compared to Rhodotorula babjevae MD1169

    PubMed Central

    Rubinfeld, Bonnee; Leif, Roald; Mulcahy, Heather; Dugan, Lawrence; Souza, Brian

    2018-01-01

    Biosurfactants have several desirable characteristics in the industrial sector: detergency, antimicrobial effects, skin hydration, and emulsibility. Several yeast glycolipids are currently being utilized in these capacities: sophorolipids, ustilagic acid, and mannosylerythritol lipids (MELs). An emerging class of glycolipids, termed polyol esters of fatty acids (PEFA), have recently been reported for Rhodotorula babjevae, a basidiomycetous yeast species that secretes hyperacetylated congeners of PEFA (typically with 3–6 acetylation modifications). While screening Rhodotorula species for surfactant production, we identified a new environmental isolate identified as Rhodotorula taiwanensis MD1149 that dropped the surface tension of the liquid medium, indicating that it produced a potent biosurfactant. Acid depolymerization of the purified biosurfactants, followed by gas chromatography-mass spectrometry (GC-MS) analysis revealed that the biosurfactants were composed of PEFA compounds composed mainly of mannitol and arabitol esters of 3-hydroxy fatty acid, 3-methoxy fatty acid, and fatty acids with a single double bond; chain lengths were mainly C16 and C18. Liquid chromatography-mass spectrometry (LC-MS) confirmed the predicted accurate mass of these compounds. Interestingly, PEFA compounds produced by Rhodotorula taiwanensis MD1149 were more surface active due to their hypoacetylation profile (0–4 acetylation modifications) compared to Rhodotorula babjevae MD1169. These disparate surface active properties, based on acetylation, change the hydrophilic-lipophilic balance (HLB) of these compounds, and their potential utility within industrial applications. PMID:29293588

  13. Rhodotorula taiwanensis MD1149 produces hypoacetylated PEFA compounds with increased surface activity compared to Rhodotorula babjevae MD1169.

    PubMed

    Lyman, Mathew; Rubinfeld, Bonnee; Leif, Roald; Mulcahy, Heather; Dugan, Lawrence; Souza, Brian

    2018-01-01

    Biosurfactants have several desirable characteristics in the industrial sector: detergency, antimicrobial effects, skin hydration, and emulsibility. Several yeast glycolipids are currently being utilized in these capacities: sophorolipids, ustilagic acid, and mannosylerythritol lipids (MELs). An emerging class of glycolipids, termed polyol esters of fatty acids (PEFA), have recently been reported for Rhodotorula babjevae, a basidiomycetous yeast species that secretes hyperacetylated congeners of PEFA (typically with 3-6 acetylation modifications). While screening Rhodotorula species for surfactant production, we identified a new environmental isolate identified as Rhodotorula taiwanensis MD1149 that dropped the surface tension of the liquid medium, indicating that it produced a potent biosurfactant. Acid depolymerization of the purified biosurfactants, followed by gas chromatography-mass spectrometry (GC-MS) analysis revealed that the biosurfactants were composed of PEFA compounds composed mainly of mannitol and arabitol esters of 3-hydroxy fatty acid, 3-methoxy fatty acid, and fatty acids with a single double bond; chain lengths were mainly C16 and C18. Liquid chromatography-mass spectrometry (LC-MS) confirmed the predicted accurate mass of these compounds. Interestingly, PEFA compounds produced by Rhodotorula taiwanensis MD1149 were more surface active due to their hypoacetylation profile (0-4 acetylation modifications) compared to Rhodotorula babjevae MD1169. These disparate surface active properties, based on acetylation, change the hydrophilic-lipophilic balance (HLB) of these compounds, and their potential utility within industrial applications.

  14. CNG channel subunit glycosylation regulates MMP-dependent changes in channel gating

    PubMed Central

    Meighan, Starla E.; Meighan, Peter C.; Rich, Elizabeth D.; Brown, R. Lane; Varnum, Michael D.

    2013-01-01

    Cyclic-nucleotide gated (CNG) channels are essential for phototransduction within retinal photoreceptors. We have demonstrated previously that enzymatic activity of matrix metalloproteinase-2 and -9, members of the MMP family of extracellular, Ca+2- and Zn+2-dependent proteases, enhances the ligand sensitivity of both rod (CNGA1 + CNGB1) and cone CNGA3 + CNGB3) CNG channels. Additionally, we have observed a decrease in maximal CNG channel current (IMAX) that begins late during MMP-directed gating changes. Here we demonstrate that CNG channels become non-conductive after prolonged MMP exposure. Concurrent with the loss of conductive channels is the increased relative contribution of channels exhibiting non-modified gating properties, suggesting the presence of a subpopulation of channels that are protected from MMP-induced gating effects. CNGA subunits are known to possess one extracellular core glycosylation site, located at one of two possible positions within the turret loop near the pore-forming region. Our results indicate that CNGA glycosylation can impede MMP-dependent modification of CNG channels. Furthermore, the relative position of the glycosylation site within the pore turret influences the extent of MMP-dependent proteolysis. Glycosylation at the site found in CNGA3 subunits was found to be protective, while glycosylation at the bovine CNGA1 site was not. Relocating the glycosylation site in CNGA1 to the position found in CNGA3 recapitulated CNGA3-like protection from MMP-dependent processing. Taken together, these data indicate that CNGA glycosylation may protect CNG channels from MMP-dependent proteolysis, consistent with MMP modification of channel function having a requirement for physical access to the extracellular face of the channel. PMID:24164424

  15. Parallel cascade selection molecular dynamics (PaCS-MD) to generate conformational transition pathway

    NASA Astrophysics Data System (ADS)

    Harada, Ryuhei; Kitao, Akio

    2013-07-01

    Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

  16. Advanced Tools for River Science: EAARL and MD_SWMS: Chapter 3

    USGS Publications Warehouse

    Kinzel, Paul J.

    2009-01-01

    Disruption of flow regimes and sediment supplies, induced by anthropogenic or climatic factors, can produce dramatic alterations in river form, vegetation patterns, and associated habitat conditions. To improve habitat in these fluvial systems, resource managers may choose from a variety of treatments including flow and/or sediment prescriptions, vegetation management, or engineered approaches. Monitoring protocols developed to assess the morphologic response of these treatments require techniques that can measure topographic changes above and below the water surface efficiently, accurately, and in a standardized, cost-effective manner. Similarly, modeling of flow, sediment transport, habitat, and channel evolution requires characterization of river morphology for model input and verification. Recent developments by the U.S. Geological Survey with regard to both remotely sensed methods (the Experimental Advanced Airborne Research LiDAR; EAARL) and computational modeling software (the Multi-Dimensional Surface-Water Modeling System; MD_SWMS) have produced advanced tools for spatially explicit monitoring and modeling in aquatic environments. In this paper, we present a pilot study conducted along the Platte River, Nebraska, that demonstrates the combined use of these river science tools.

  17. Optimal Policy of Cross-Layer Design for Channel Access and Transmission Rate Adaptation in Cognitive Radio Networks

    NASA Astrophysics Data System (ADS)

    He, Hao; Wang, Jun; Zhu, Jiang; Li, Shaoqian

    2010-12-01

    In this paper, we investigate the cross-layer design of joint channel access and transmission rate adaptation in CR networks with multiple channels for both centralized and decentralized cases. Our target is to maximize the throughput of CR network under transmission power constraint by taking spectrum sensing errors into account. In centralized case, this problem is formulated as a special constrained Markov decision process (CMDP), which can be solved by standard linear programming (LP) method. As the complexity of finding the optimal policy by LP increases exponentially with the size of action space and state space, we further apply action set reduction and state aggregation to reduce the complexity without loss of optimality. Meanwhile, for the convenience of implementation, we also consider the pure policy design and analyze the corresponding characteristics. In decentralized case, where only local information is available and there is no coordination among the CR users, we prove the existence of the constrained Nash equilibrium and obtain the optimal decentralized policy. Finally, in the case that the traffic load parameters of the licensed users are unknown for the CR users, we propose two methods to estimate the parameters for two different cases. Numerical results validate the theoretic analysis.

  18. Cell lines, Md108 and Md66, from the hemocytes of Malacosoma disstria (Lepidoptera) display aspects of plasma-free innate non-self activities.

    PubMed

    Lapointe, Jason F; Dunphy, Gary B; Giannoulis, Paschalis; Mandato, Craig A; Nardi, James B; Gharib, Osama H; Niven, Donald F

    2011-11-01

    The innate non-self response systems of the deciduous tree pest, the forest tent caterpillar, Malacosoma disstria has been documented by us in terms of in vitro and in vivo reactions towards the Gram-positive nonpathogenic bacterium, Bacillus subtilis and Gram-negative pathogenic microbe, Xenorhabdus nematophila and their respective surface antigens, lipopoteichoic acids (LTA) and lipopolysaccharides (LPS). These studies, often conducted in whole and diluted hemolymph, preclude examination of plasma-free cellular (hemocyte) responses. Plasma-free hemocytes as primary cultures are difficult to obtain. The floating cell line Md66 and attached cell line Md108 from M. disstria hemocytes were examined as a model for plasma-free M. disstria hemocyte non-self responses. Herein, it was established that although both lines differed from each other and from the primary hemocyte cultures of M. disstria in growth parameters, cell composition and sizes both cell lines displayed granular cell-like (GL) cells and plasmatocyte-like (PL) cells according to morphological criteria and to some extent antigenic similarities based on labeling with anti-Chrysodeixis includens hemocyte monoclonal antibodies. Hemocyte-specific neuroglian-like protein was detected on cells of both cell lines and in the primary hemocyte cultures albeit with staining patterns differing according to culture and cell types, confluency levels and cell-cell adhesion. Both cell lines bound B. subtilis and X. nematophila, the reaction extent varying with the cell line and its cell types. LPS damaged both cell types in the two cell lines whereas LTA enhanced the adhesion of Md66 GL cells to flask surfaces followed by PL cell adhesion. PL cells of both lines, like the primary cultures, phagocytosed FITC-labeled B. subtilis; only Md108 GL cells phagocytosed B. subtilis. In either case phagocytosis was always less in frequency and intensity than the primary cultures. Proteins released from the cell lines differed in

  19. Center of excellence for mobile sensor data-to-knowledge (MD2K).

    PubMed

    Kumar, Santosh; Abowd, Gregory D; Abraham, William T; al'Absi, Mustafa; Beck, J Gayle; Chau, Duen Horng; Condie, Tyson; Conroy, David E; Ertin, Emre; Estrin, Deborah; Ganesan, Deepak; Lam, Cho; Marlin, Benjamin; Marsh, Clay B; Murphy, Susan A; Nahum-Shani, Inbal; Patrick, Kevin; Rehg, James M; Sharmin, Moushumi; Shetty, Vivek; Sim, Ida; Spring, Bonnie; Srivastava, Mani; Wetter, David W

    2015-11-01

    Mobile sensor data-to-knowledge (MD2K) was chosen as one of 11 Big Data Centers of Excellence by the National Institutes of Health, as part of its Big Data-to-Knowledge initiative. MD2K is developing innovative tools to streamline the collection, integration, management, visualization, analysis, and interpretation of health data generated by mobile and wearable sensors. The goal of the big data solutions being developed by MD2K is to reliably quantify physical, biological, behavioral, social, and environmental factors that contribute to health and disease risk. The research conducted by MD2K is targeted at improving health through early detection of adverse health events and by facilitating prevention. MD2K will make its tools, software, and training materials widely available and will also organize workshops and seminars to encourage their use by researchers and clinicians. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Molecular Dynamics Simulations and XAFS (MD-XAFS)

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

    Schenter, Gregory K.; Fulton, John L.

    2017-01-20

    MD-XAFS (Molecular Dynamics X-ray Adsorption Fine Structure) makes the connection between simulation techniques that generate an ensemble of molecular configurations and the direct signal observed from X-ray measurement.

  1. MdHB1 down-regulation activates anthocyanin biosynthesis in the white-fleshed apple cultivar 'Granny Smith'.

    PubMed

    Jiang, Yonghua; Liu, Cuihua; Yan, Dan; Wen, Xiaohong; Liu, Yanli; Wang, Haojie; Dai, Jieyu; Zhang, Yujie; Liu, Yanfei; Zhou, Bin; Ren, Xiaolin

    2017-02-01

    Coloration in apple (Malus×domestica) flesh is mainly caused by the accumulation of anthocyanin. Anthocyanin is biosynthesized through the flavonoid pathway and regulated by MYB, bHLH, and WD40 transcription factors (TFs). Here, we report that the HD-Zip I TF MdHB1 was also involved in the regulation of anthocyanin accumulation. MdHB1 silencing caused the accumulation of anthocyanin in 'Granny Smith' flesh, whereas its overexpression reduced the flesh content of anthocyanin in 'Ballerina' (red-fleshed apple). Moreover, flowers of transgenic tobacco (Nicotiana tabacum 'NC89') overexpressing MdHB1 showed a remarkable reduction in pigmentation. Transient promoter activation assays and yeast one-hybrid results indicated that MdHB1 indirectly inhibited expression of the anthocyanin biosynthetic genes encoding dihydroflavonol-4-reductase (DFR) and UDP-glucose:flavonoid 3-O-glycosyltransferase (UFGT). Yeast two-hybrid and bimolecular fluorescence complementation determined that MdHB1 acted as a homodimer and could interact with MYB, bHLH, and WD40 in the cytoplasm, consistent with its cytoplasmic localization by green fluorescent protein fluorescence observations. Together, these results suggest that MdHB1 constrains MdMYB10, MdbHLH3, and MdTTG1 to the cytoplasm, and then represses the transcription of MdDFR and MdUFGT indirectly. When MdHB1 is silenced, these TFs are released to activate the expression of MdDFR and MdUFGT and also anthocyanin biosynthesis, resulting in red flesh in 'Granny Smith'. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  2. Exploration of the pore structure of a peptide-gated Na+channel

    PubMed Central

    Poët, Mallorie; Tauc, Michel; Lingueglia, Eric; Cance, Peggy; Poujeol, Philippe; Lazdunski, Michel; Counillon, Laurent

    2001-01-01

    The FMRF-amide-activated sodium channel (FaNaC), a member of the ENaC/Degenerin family, is a homotetramer, each subunit containing two transmembrane segments. We changed independently every residue of the first transmembrane segment (TM1) into a cysteine and tested each position’s accessibility to the cysteine covalent reagents MTSET and MTSES. Eleven mutants were accessible to the cationic MTSET, showing that TM1 faces the ion translocation pathway. This was confirmed by the accessibility of cysteines present in the acid-sensing ion channels and other mutations introduced in FaNaC TM1. Modification of accessibilities for positions 69, 71 and 72 in the open state shows that the gating mechanism consists of the opening of a constriction close to the intracellular side. The anionic MTSES did not penetrate into the channel, indicating the presence of a charge selectivity filter in the outer vestibule. Furthermore, amiloride inhibition resulted in the channel occlusion in the middle of the pore. Summarizing, the ionic pore of FaNaC includes a large aqueous cavity, with a charge selectivity filter in the outer vestibule and the gate close to the interior. PMID:11598003

  3. Antinociceptive synergism of MD-354 and clonidine. Part II. The alpha-adrenoceptor component.

    PubMed

    Young, Shawquia; Vainio, Minna; Scheinin, Mika; Dukat, Małgorzata

    2010-08-01

    Previously, we reported that antinociceptive synergism of a 5-HT(3)/alpha(2)-adrenoceptor ligand MD-354 (m-chlorophenylguanidine) and clonidine combination occurs, in part, through a 5-HT(3) receptor antagonist mechanism. In the present investigation, a possible role for alpha(2)-adrenoceptors was examined. Mechanistic studies using yohimbine (a subtype non-selective alpha(2)-adrenoceptor antagonist), BRL 44408 (a preferential alpha(2A)-adrenoceptor antagonist) and imiloxan (a preferential alpha(2B/C)-adrenoceptor antagonist) on the antinociceptive actions of a MD-354/clonidine combination were conducted. Subcutaneous pre-treatment with all three antagonists inhibited the antinociceptive synergism of MD-354 and clonidine in the mouse tail-flick assay in a dose-dependent manner (AD(50) = 0.33, 2.1, and 0.17 mg/kg, respectively). Enhancement of clonidine antinociception by MD-354 did not potentiate clonidine's locomotor suppressant activity in a mouse locomotor assay. When [ethyl-3H]RS-79948-197 was used as radioligand, MD-354 displayed almost equal affinity to alpha(2A)- and alpha(2B)-adrenoceptors (K(i) = 110 and 220 nM) and showed lower affinity at alpha(2C)-adrenoceptors (K(i) = 4,700 nM). MD-354 had no subtype-selectivity for the alpha(2)-adrenoceptor subtypes as an antagonist in functional [35S]GTPgammaS binding assays. MD-354 was a weak partial agonist at alpha(2A)-adrenoceptors. Overall, in addition to the 5-HT(3) receptor component, the present investigation found MD-354 to be a weak partial alpha(2A)-adrenoceptor agonist that enhances clonidine's thermal antinociceptive actions through an alpha(2)-adrenoceptor-mediated mechanism without augmenting sedation.

  4. Interior view, general view in covered causeway (MD1109W) near ward ...

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

    Interior view, general view in covered causeway (MD-1109-W) near ward 114, looking from the northwest - National Park Seminary, Music Hall, Linden Lane at western edge of campus, Silver Spring, Montgomery County, MD

  5. Local anesthetic inhibition of a bacterial sodium channel

    PubMed Central

    Lee, Sora; Goodchild, Samuel J.

    2012-01-01

    Recent structural breakthroughs with the voltage-gated sodium channel from Arcobacter butzleri suggest that such bacterial channels may provide a structural platform to advance the understanding of eukaryotic sodium channel gating and pharmacology. We therefore set out to determine whether compounds known to interact with eukaryotic NaVs could also inhibit the bacterial channel from Bacillus halodurans and NaChBac and whether they did so through similar mechanisms as in their eukaryotic homologues. The data show that the archetypal local anesthetic (LA) lidocaine inhibits resting NaChBac channels with a dissociation constant (Kd) of 260 µM, and channels displayed a left-shifted steady-state inactivation gating relationship in the presence of the drug. Extracellular application of QX-314 to expressed NaChBac channels had no effect on sodium current, whereas internal exposure via injection of a bolus of the quaternary derivative rapidly reduced sodium conductance, consistent with a hydrophilic cytoplasmic access pathway to an internal binding site. However, the neutral derivative benzocaine applied externally inhibited NaChBac channels, suggesting that hydrophobic pathways can also provide drug access to inhibit channels. Alternatively, ranolazine, a putative preopen state blocker of eukaryotic NaVs, displayed a Kd of 60 µM and left-shifted the NaChBac activation-voltage relationship. In each case, block enhanced entry into the inactivated state of the channel, an effect that is well described by a simple kinetic scheme. The data suggest that although significant differences exist, LA block of eukaryotic NaVs also occurs in bacterial sodium channels and that NaChBac shares pharmacological homology to the resting state of vertebrate NaV homologues. PMID:22641643

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

    PubMed

    Omotuyi, Olaposi; Matsunaga, Hayato; Ueda, Hiroshi

    2015-01-01

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

  7. Modeling of dislocation channel width evolution in irradiated metals

    DOE PAGES

    Doyle, Peter J.; Benensky, Kelsa M.; Zinkle, Steven J.

    2017-11-08

    Defect-free dislocation channel formation has been reported to promote plastic instability during tensile testing via localized plastic flow, leading to a distinct loss of ductility and strain hardening in many low-temperature irradiated materials. In order to study the underlying mechanisms governing dislocation channel width and formation, the channel formation process is modeled via a simple stochastic dislocation-jog process dependent upon grain size, defect cluster density, and defect size. Dislocations traverse a field of defect clusters and jog stochastically upon defect interaction, forming channels of low defect-density. And based upon prior molecular dynamics (MD) simulations and in-situ experimental transmission electron microscopymore » (TEM) observations, each dislocation encounter with a dislocation loop or stacking fault tetrahedron (SFT) is assumed to cause complete absorption of the defect cluster, prompting the dislocation to jog up or down by a distance equal to half the defect cluster diameter. Channels are predicted to form rapidly and are comparable to reported TEM measurements for many materials. Predicted channel widths are found to be most strongly dependent on mean defect size and correlated well with a power law dependence on defect diameter and density, and distance from the dislocation source. Due to the dependence of modeled channel width on defect diameter and density, maximum channel width is predicted to slowly increase as accumulated dose increases. The relatively weak predicted dependence of channel formation width with distance, in accordance with a diffusion analogy, implies that after only a few microns from the source, most channels observed via TEM analyses may not appear to vary with distance because of limitations in the field-of-view to a few microns. Furthermore, examinations of the effect of the so-called “source-broadening” mechanism of channel formation showed that its effect is simply to add a minimum thickness

  8. Modeling of dislocation channel width evolution in irradiated metals

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

    Doyle, Peter J.; Benensky, Kelsa M.; Zinkle, Steven J.

    Defect-free dislocation channel formation has been reported to promote plastic instability during tensile testing via localized plastic flow, leading to a distinct loss of ductility and strain hardening in many low-temperature irradiated materials. In order to study the underlying mechanisms governing dislocation channel width and formation, the channel formation process is modeled via a simple stochastic dislocation-jog process dependent upon grain size, defect cluster density, and defect size. Dislocations traverse a field of defect clusters and jog stochastically upon defect interaction, forming channels of low defect-density. And based upon prior molecular dynamics (MD) simulations and in-situ experimental transmission electron microscopymore » (TEM) observations, each dislocation encounter with a dislocation loop or stacking fault tetrahedron (SFT) is assumed to cause complete absorption of the defect cluster, prompting the dislocation to jog up or down by a distance equal to half the defect cluster diameter. Channels are predicted to form rapidly and are comparable to reported TEM measurements for many materials. Predicted channel widths are found to be most strongly dependent on mean defect size and correlated well with a power law dependence on defect diameter and density, and distance from the dislocation source. Due to the dependence of modeled channel width on defect diameter and density, maximum channel width is predicted to slowly increase as accumulated dose increases. The relatively weak predicted dependence of channel formation width with distance, in accordance with a diffusion analogy, implies that after only a few microns from the source, most channels observed via TEM analyses may not appear to vary with distance because of limitations in the field-of-view to a few microns. Furthermore, examinations of the effect of the so-called “source-broadening” mechanism of channel formation showed that its effect is simply to add a minimum thickness

  9. Studies of the TLR4-associated protein MD-2 using yeast-display and mutational analyses

    PubMed Central

    Mattis, Daiva M.; Chervin, Adam; Ranoa, Diana; Kelley, Stacy; Tapping, Richard; Kranz, David M.

    2015-01-01

    Bacterial lipopolysaccharide (LPS) activates the innate immune system by forming a complex with myeloid differentiation factor 2 (MD-2) and Toll-like receptor 4 (TLR4), which is present on antigen presenting cells. MD-2 plays an essential role in this activation of the innate immune system as a member of the ternary complex, TLR4:MD-2:LPS. With the goal of further understanding the molecular details of the interaction of MD-2 with LPS and TLR4, and possibly toward engineering dominant negative regulators of the MD-2 protein, here we subjected MD-2 to a mutational analysis using yeast display. The approach included generation of site-directed alanine mutants, and ligand-driven selections of MD-2 mutant libraries. Our findings showed that: 1) proline mutations in the F119-K132 loop that binds LPS were strongly selected for enhanced yeast surface stability, 2) there was a preference for positive-charged side chains (R/K) at residue 120 for LPS binding, and negative-charged side chains (D/E) for TLR4 binding, 3) aromatic residues were strongly preferred at F119 and F121 for LPS binding, and 4) an MD-2 mutant (T84N/D101A/S118A/S120D/K122P) exhibited increased binding to TLR4 but decreased binding to LPS. These studies revealed the impact of specific residues and regions of MD-2 on the binding of LPS and TLR4, and they provide a framework for further directed evolution of the MD-2 protein. PMID:26320630

  10. Distributed Joint Source-Channel Coding in Wireless Sensor Networks

    PubMed Central

    Zhu, Xuqi; Liu, Yu; Zhang, Lin

    2009-01-01

    Considering the fact that sensors are energy-limited and the wireless channel conditions in wireless sensor networks, there is an urgent need for a low-complexity coding method with high compression ratio and noise-resisted features. This paper reviews the progress made in distributed joint source-channel coding which can address this issue. The main existing deployments, from the theory to practice, of distributed joint source-channel coding over the independent channels, the multiple access channels and the broadcast channels are introduced, respectively. To this end, we also present a practical scheme for compressing multiple correlated sources over the independent channels. The simulation results demonstrate the desired efficiency. PMID:22408560

  11. Purification of oily wastewater by hybrid UF/MD.

    PubMed

    Gryta, M; Karakulski, K; Morawski, A W

    2001-10-01

    Investigations on the treatment of oily wastewater by a combination of ultrafiltration (UF) and membrane distillation (MD) as a final purification method have been performed. A tubular UF module equipped with polyvinylidene fluoride (PVDF) membranes and a capillary MD module with polypropylene membranes were tested using a typical bilge water collected from a harbour without pretreatment. The permeate obtained from the UF process generally contains less than 5 ppm of oil. A further purification of the UF permeate by membrane distillation results in a complete removal of oil from wastewater and a very high reduction of the total organic carbon (99.5%) and total dissolved solids (99.9%).

  12. Direct NOE simulation from long MD trajectories.

    PubMed

    Chalmers, G; Glushka, J N; Foley, B L; Woods, R J; Prestegard, J H

    2016-04-01

    A software package, MD2NOE, is presented which calculates Nuclear Overhauser Effect (NOE) build-up curves directly from molecular dynamics (MD) trajectories. It differs from traditional approaches in that it calculates correlation functions directly from the trajectory instead of extracting inverse sixth power distance terms as an intermediate step in calculating NOEs. This is particularly important for molecules that sample conformational states on a timescale similar to molecular reorientation. The package is tested on sucrose and results are shown to differ in small but significant ways from those calculated using an inverse sixth power assumption. Results are also compared to experiment and found to be in reasonable agreement despite an expected underestimation of water viscosity by the water model selected. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Mathematic Model of Digital Control System with PID Regulator and Regular Step of Quantization with Information Transfer via the Channel of Plural Access

    NASA Astrophysics Data System (ADS)

    Abramov, G. V.; Emeljanov, A. E.; Ivashin, A. L.

    Theoretical bases for modeling a digital control system with information transfer via the channel of plural access and a regular quantization cycle are submitted. The theory of dynamic systems with random changes of the structure including elements of the Markov random processes theory is used for a mathematical description of a network control system. The characteristics of similar control systems are received. Experimental research of the given control systems is carried out.

  14. Spread-Spectrum Random-Access Communications for HF Channels.

    DTIC Science & Technology

    1981-08-21

    variables Zsm which are defined by (8) with cos[.] replaced by sin[-], have the same properties as Z . cm I. 9 IIII. PERFORMANCE OF FH/SSMA SYSTEM...patterns). An approximation which is valid under the same conditions is 18 P e,1 A PL + k (k+P 0 )(K-I)(1’_)K-2 ( 35 ) This approximation is very accurate...and approximation given in (32)-( 35 ) can be applied to any particular nonselective fading channel by substituting the appropriate expression for P0

  15. 77 FR 29692 - Segun M. Rasaki, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 12-28] Segun M. Rasaki, M.D...'s action at which he may ultimately prevail.'' Kamal Tiwari, M.D., 76 FR 71604, 71606 (2011); see....100(b), I order that DEA Certificate of Registration BR9738595, issued to Segun M. Rasaki, M.D., be...

  16. 76 FR 51412 - Joe C. Fermo, M.D.; Revocation of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Joe C. Fermo, M.D.; Revocation of... Enforcement Administration, issued an Order to Show Cause to Joe C. Fermo, M.D. (Registrant), of Tulsa... Order at 1 (citing 21 U.S.C. 823(f) and 824(a)(4)). The Show Cause Order specifically alleged that on...

  17. The Multidimensional Curriculum Model (MdCM)

    ERIC Educational Resources Information Center

    Vidergor, Hava E.

    2010-01-01

    The multidimensional Curriculum Model (MdCM) helps teachers to better prepare gifted and able students for our changing world, acquiring much needed skills. It is influenced by general learning theory of constructivism, notions of preparing students for 21st century, Teaching the Future Model, and current comprehensive curriculum models for…

  18. Twenty-Channel Voice Response System

    DOT National Transportation Integrated Search

    1981-06-01

    This report documents the design and implementation of a Voice Response System, which provides Direct-User Access to the FAA's aviation-weather data base. This system supports 20 independent audio channels, and as of this report, speaks three weather...

  19. RadNet Air Data From Baltimore, MD

    EPA Pesticide Factsheets

    This page presents radiation air monitoring and air filter analysis data for Baltimore, MD from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

  20. Scalable Video Transmission Over Multi-Rate Multiple Access Channels

    DTIC Science & Technology

    2007-06-01

    Rate - compatible punctured convolutional codes (RCPC codes ) and their ap- plications,” IEEE...source encoded using the MPEG-4 video codec. The source encoded bitstream is then channel encoded with Rate Compatible Punctured Convolutional (RCPC...Clark, and J. M. Geist, “ Punctured convolutional codes or rate (n-1)/n and simplified maximum likelihood decoding,” IEEE Transactions on

  1. Ubiquitination-Related MdBT Scaffold Proteins Target a bHLH Transcription Factor for Iron Homeostasis1[OPEN

    PubMed Central

    Zhao, Qiang; Wang, Qing-Jie; Wang, Xiao-Fei; You, Chun-Xiang

    2016-01-01

    Iron (Fe) homeostasis is crucial for plant growth and development. A network of basic helix-loop-helix (bHLH) transcription factors positively regulates Fe uptake during iron deficiency. However, their up-regulation or overexpression leads to Fe overload and reactive oxygen species generation, thereby damaging the plants. Here, we found that two BTB/TAZ proteins, MdBT1 and MdBT2, interact with the MbHLH104 protein in apple. In addition, the function of MdBT2 was characterized as a regulator of MdbHLH104 degradation via ubiquitination and the 26S proteasome pathway, thereby controlling the activity of plasma membrane H+-ATPases and the acquisition of iron. Furthermore, MdBT2 interacted with MdCUL3 proteins, which were required for the MdBT2-mediated ubiquitination modification of MdbHLH104 and its degradation. In sum, our findings demonstrate that MdBT proteins interact with MdCUL3 to bridge the formation of the MdBTsMdCUL3 complex, which negatively modulates the degradation of the MdbHLH104 protein in response to changes in Fe status to maintain iron homeostasis in plants. PMID:27660166

  2. Validity of the Medical College Admission Test for Predicting MD-PhD Student Outcomes

    ERIC Educational Resources Information Center

    Bills, James L.; VanHouten, Jacob; Grundy, Michelle M.; Chalkley, Roger; Dermody, Terence S.

    2016-01-01

    The Medical College Admission Test (MCAT) is a quantitative metric used by MD and MD-PhD programs to evaluate applicants for admission. This study assessed the validity of the MCAT in predicting training performance measures and career outcomes for MD-PhD students at a single institution. The study population consisted of 153 graduates of the…

  3. The bZIP transcription factor MdHY5 regulates anthocyanin accumulation and nitrate assimilation in apple.

    PubMed

    An, Jian-Ping; Qu, Feng-Jia; Yao, Ji-Fang; Wang, Xiao-Na; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

    2017-01-01

    The basic leucine zipper (bZIP) transcription factor HY5 plays a multifaceted role in plant growth and development. Here the apple MdHY5 gene was cloned based on its homology with Arabidopsis HY5 . Expression analysis demonstrated that MdHY5 transcription was induced by light and abscisic acid treatments. Electrophoretic mobility shift assays and transient expression assays subsequently showed that MdHY5 positively regulated both its own transcription and that of MdMYB10 by binding to E-box and G-box motifs, respectively. Furthermore, we obtained transgenic apple calli that overexpressed the MdHY5 gene, and apple calli coloration assays showed that MdHY5 promoted anthocyanin accumulation by regulating expression of the MdMYB10 gene and downstream anthocyanin biosynthesis genes. In addition, the transcript levels of a series of nitrate reductase genes and nitrate uptake genes in both wild-type and transgenic apple calli were detected. In association with increased nitrate reductase activities and nitrate contents, the results indicated that MdHY5 might be an important regulator in nutrient assimilation. Taken together, these results indicate that MdHY5 plays a vital role in anthocyanin accumulation and nitrate assimilation in apple.

  4. Quantum internet using code division multiple access

    PubMed Central

    Zhang, Jing; Liu, Yu-xi; Özdemir, Şahin Kaya; Wu, Re-Bing; Gao, Feifei; Wang, Xiang-Bin; Yang, Lan; Nori, Franco

    2013-01-01

    A crucial open problem inS large-scale quantum networks is how to efficiently transmit quantum data among many pairs of users via a common data-transmission medium. We propose a solution by developing a quantum code division multiple access (q-CDMA) approach in which quantum information is chaotically encoded to spread its spectral content, and then decoded via chaos synchronization to separate different sender-receiver pairs. In comparison to other existing approaches, such as frequency division multiple access (FDMA), the proposed q-CDMA can greatly increase the information rates per channel used, especially for very noisy quantum channels. PMID:23860488

  5. Divalent ions are potential permeating blockers of the non-selective NaK ion channel: combined QM and MD based investigations.

    PubMed

    Sadhu, Biswajit; Sundararajan, Mahesh; Bandyopadhyay, Tusar

    2017-10-18

    The bacterial NaK ion channel is distinctly different from other known ion channels due to its inherent non-selective feature. One of the unexplored and rather interesting features is its ability to permeate divalent metal ions (such as Ca 2+ and Ba 2+ ) and not monovalent alkali metal ions. Several intriguing questions about the energetics and structural aspects still remain unanswered. For instance, what causes Ca 2+ to permeate as well as block the selectivity filter (SF) of the NaK ion channel and act as a "permeating blocker"? How and at what energetic cost does another chemical congener, Sr 2+ , as well as Ba 2+ , a potent blocker of the K + ion channel, permeate through the SF of the NaK ion channel? Finally, how do their translocation energetics differ from those of monovalent ions such as K + ? Here, in an attempt to address these outstanding issues, we elucidate the structure, binding and selectivity of divalent ions (Ca 2+ , Sr 2+ and Ba 2+ ) as they permeate through the SF of the NaK ion channel using all-atom molecular dynamics simulations and density functional theory based calculations. We unveil mechanistic insight into this translocation event using well-tempered metadynamics simulations in a polarizable environment using the mean-field model of water and incorporating electronic continuum corrections for ions via charge rescaling. The results show that, akin to K + coordination, Sr 2+ and Ba 2+ bind at the SF in a very similar fashion and remain octa-coordinated at all sites. Interestingly, differing from its local hydration structure, Ca 2+ interacts with eight carbonyls to remain at the middle of the S3 site. Furthermore, the binding of divalent metals at SF binding sites is more favorable than the binding of K + . However, their permeation through the extracellular entrance faces a considerably higher energetic barrier compared to that for K + , which eventually manifests their inherent blocking feature.

  6. PuReMD-GPU: A reactive molecular dynamics simulation package for GPUs

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

    Kylasa, S.B., E-mail: skylasa@purdue.edu; Aktulga, H.M., E-mail: hmaktulga@lbl.gov; Grama, A.Y., E-mail: ayg@cs.purdue.edu

    2014-09-01

    We present an efficient and highly accurate GP-GPU implementation of our community code, PuReMD, for reactive molecular dynamics simulations using the ReaxFF force field. PuReMD and its incorporation into LAMMPS (Reax/C) is used by a large number of research groups worldwide for simulating diverse systems ranging from biomembranes to explosives (RDX) at atomistic level of detail. The sub-femtosecond time-steps associated with ReaxFF strongly motivate significant improvements to per-timestep simulation time through effective use of GPUs. This paper presents, in detail, the design and implementation of PuReMD-GPU, which enables ReaxFF simulations on GPUs, as well as various performance optimization techniques wemore » developed to obtain high performance on state-of-the-art hardware. Comprehensive experiments on model systems (bulk water and amorphous silica) are presented to quantify the performance improvements achieved by PuReMD-GPU and to verify its accuracy. In particular, our experiments show up to 16× improvement in runtime compared to our highly optimized CPU-only single-core ReaxFF implementation. PuReMD-GPU is a unique production code, and is currently available on request from the authors.« less

  7. 39. SAME VIEW AS MD6A38, ONLY WITH A HORIZONTAL ORIENTATION. ...

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

    39. SAME VIEW AS MD-6A-38, ONLY WITH A HORIZONTAL ORIENTATION. - Baltimore & Ohio Railroad, Mount Clare Shops, South side of Pratt Street between Carey & Poppleton Streets, Baltimore, Independent City, MD

  8. RysannMD: A biomedical semantic annotator balancing speed and accuracy.

    PubMed

    Cuzzola, John; Jovanović, Jelena; Bagheri, Ebrahim

    2017-07-01

    Recently, both researchers and practitioners have explored the possibility of semantically annotating large and continuously evolving collections of biomedical texts such as research papers, medical reports, and physician notes in order to enable their efficient and effective management and use in clinical practice or research laboratories. Such annotations can be automatically generated by biomedical semantic annotators - tools that are specifically designed for detecting and disambiguating biomedical concepts mentioned in text. The biomedical community has already presented several solid automated semantic annotators. However, the existing tools are either strong in their disambiguation capacity, i.e., the ability to identify the correct biomedical concept for a given piece of text among several candidate concepts, or they excel in their processing time, i.e., work very efficiently, but none of the semantic annotation tools reported in the literature has both of these qualities. In this paper, we present RysannMD (Ryerson Semantic Annotator for Medical Domain), a biomedical semantic annotation tool that strikes a balance between processing time and performance while disambiguating biomedical terms. In other words, RysannMD provides reasonable disambiguation performance when choosing the right sense for a biomedical term in a given context, and does that in a reasonable time. To examine how RysannMD stands with respect to the state of the art biomedical semantic annotators, we have conducted a series of experiments using standard benchmarking corpora, including both gold and silver standards, and four modern biomedical semantic annotators, namely cTAKES, MetaMap, NOBLE Coder, and Neji. The annotators were compared with respect to the quality of the produced annotations measured against gold and silver standards using precision, recall, and F 1 measure and speed, i.e., processing time. In the experiments, RysannMD achieved the best median F 1 measure across the

  9. MdHY5 positively regulates cold tolerance via CBF-dependent and CBF-independent pathways in apple.

    PubMed

    An, Jian-Ping; Yao, Ji-Fang; Wang, Xiao-Na; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

    2017-11-01

    Cold stress is a major external stimulator that affects crop quality and productivity. The CBF cold regulatory pathway has been regarded as a master regulator in the response to cold stress. In this study, we found that the apple bZIP transcription factor, MdHY5, was responsive to cold treatment both at the transcriptional and at the post-translational levels. Moreover, overexpression of MdHY5 enhanced cold tolerance in apple calli and Arabidopsis. Subsequently, EMSA assay and transient expression assay demonstrated that MdHY5 positively regulated the transcript of MdCBF1 by binding to G-Box motif of its promoter. Furthermore, MdHY5 also regulated the expression of CBF-independent cold-regulated genes. Taken together, our data suggest that MdHY5 positively modulates plant cold tolerance through CBF-dependent and CBF-independent pathways, providing a deeper understanding of MdHY5-regulated cold tolerance in apple. Copyright © 2017 Elsevier GmbH. All rights reserved.

  10. Channel erosion in a rapidly urbanizing region of Tijuana, Mexico: Enlargement downstream of channel hardpoints

    NASA Astrophysics Data System (ADS)

    Taniguchi, Kristine; Biggs, Trent; Langendoen, Eddy; Castillo, Carlos; Gudiño, Napoleon; Yuan, Yongping; Liden, Douglas

    2016-04-01

    Urban-induced erosion in Tijuana, Mexico, has led to excessive sediment deposition in the Tijuana Estuary in the United States. Urban areas in developing countries, in contrast to developed countries, are characterized by much lower proportions of vegetation and impervious surfaces due to limited access to urban services such as road paving and landscaping, and larger proportions of exposed soils. In developing countries, traditional watershed scale variables such as impervious surfaces may not be good predictors of channel enlargement. In this research, we surveyed the stream channel network of an erodible tributary of the Tijuana River Watershed, Los Laureles Canyon, at 125 locations, including repeat surveys from 2008. Structure from Motion (SfM) and 3D photo-reconstruction techniques were used to create digital terrain models of stream reaches upstream and downstream of channel hardpoints. Channels are unstable downstream of hardpoints, with incision up to 2 meters and widening up to 12 meters. Coordinated channelization is essential to avoid piece-meal approaches that lead to channel degradation. Watershed impervious area is not a good predictor of channel erosion due to the overriding importance of hardpoints and likely to the high sediment supply from the unpaved roads which prevents channel erosion throughout the stream network.

  11. MD-2 is required for disulfide HMGB1–dependent TLR4 signaling

    PubMed Central

    Wang, Haichao; Ju, Zhongliang; Ragab, Ahmed A.; Lundbäck, Peter; Long, Wei; Valdes-Ferrer, Sergio I.; He, Mingzhu; Pribis, John P.; Li, Jianhua; Lu, Ben; Gero, Domokos; Szabo, Csaba; Antoine, Daniel J.; Harris, Helena E.; Golenbock, Doug T.; Meng, Jianmin; Roth, Jesse; Chavan, Sangeeta S.; Andersson, Ulf; Billiar, Timothy R.; Al-Abed, Yousef

    2015-01-01

    Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2–deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist preventing MD-2–HMGB1 interaction and TLR4 signaling. P5779 does not interfere with lipopolysaccharide-induced cytokine/chemokine production, thus preserving PAMP-mediated TLR4–MD-2 responses. Furthermore, P5779 can protect mice against hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms. The results may direct toward strategies aimed at attenuating DAMP-mediated inflammation while preserving antimicrobial immune responsiveness. PMID:25559892

  12. Optimum Adaptive Modulation and Channel Coding Scheme for Frequency Domain Channel-Dependent Scheduling in OFDM Based Evolved UTRA Downlink

    NASA Astrophysics Data System (ADS)

    Miki, Nobuhiko; Kishiyama, Yoshihisa; Higuchi, Kenichi; Sawahashi, Mamoru; Nakagawa, Masao

    In the Evolved UTRA (UMTS Terrestrial Radio Access) downlink, Orthogonal Frequency Division Multiplexing (OFDM) based radio access was adopted because of its inherent immunity to multipath interference and flexible accommodation of different spectrum arrangements. This paper presents the optimum adaptive modulation and channel coding (AMC) scheme when resource blocks (RBs) is simultaneously assigned to the same user when frequency and time domain channel-dependent scheduling is assumed in the downlink OFDMA radio access with single-antenna transmission. We start by presenting selection methods for the modulation and coding scheme (MCS) employing mutual information both for RB-common and RB-dependent modulation schemes. Simulation results show that, irrespective of the application of power adaptation to RB-dependent modulation, the improvement in the achievable throughput of the RB-dependent modulation scheme compared to that for the RB-common modulation scheme is slight, i.e., 4 to 5%. In addition, the number of required control signaling bits in the RB-dependent modulation scheme becomes greater than that for the RB-common modulation scheme. Therefore, we conclude that the RB-common modulation and channel coding rate scheme is preferred, when multiple RBs of the same coded stream are assigned to one user in the case of single-antenna transmission.

  13. A novel triazine ring compound (MD568) exerts in vivo and in vitro effects on lipid metabolism.

    PubMed

    Jia, Dan; Li, Ziwen; Gao, Ying; Feng, Yifan; Li, Weimin

    2018-07-01

    In this study, we investigated the toxicity and biological activity of a novel triazine ring compound named magnolol derivative 568 (MD568). The LD 50 of MD568 was determined in Sprague-Dawley (SD) rats by intraperitoneal injection. Treatment of high fat diet-induced obese rats with MD568 demonstrated that MD568 displayed significant anti-obesity effects. MD568 markedly reduced body weight, blood lipid contents, white adipose tissue (WAT) and liver mass in obese rats. In addition, MD568 modulated lesions in WAT through regulating PPAR-Ɣ, C/EBP-a, SREBP-1c and FABP-4 proteins in the liver through regulating PPAR-α, SREBP-1c and FABP-4. We also evaluated the effects of MD568 on the proliferation and differentiation of 3T3-L1 pre-adipocytes and investigated the underlying mechanism by microarray analysis. Results showed that MD568 has good inhibitory activity on lipogenesis and lipid accumulation in 3T3-L1 pre-adipocytes. The protein expression levels of the adipogenic transcription factors PPAR-Ɣ, C/EBP-a, SREBP-1c and FABP-4 were reduced by MD568. In addition, the gene expression of FAS and LDL was also significantly down-regulated by MD568. Microarray data enrichment analysis demonstrated that the underlying mechanism of action of MD568 may be related to its regulatory effects on genes associated with the biological processes or pathways in lipid metabolism. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  14. Is channel segmentation necessary to reach a multiethnic population with weight-related health promotion? An analysis of use and perception of communication channels.

    PubMed

    Hartman, Marieke A; Nierkens, Vera; Cremer, Stephan W; Verhoeff, Arnoud; Stronks, Karien

    2015-01-01

    To explore similarities and differences in the use and perception of communication channels to access weight-related health promotion among women in three ethnic minority groups. The ultimate aim was to determine whether similar channels might reach ethnic minority women in general or whether segmentation to ethnic groups would be required. Eight ethnically homogeneous focus groups were conducted among 48 women of Ghanaian, Antillean/Aruban, or Afro-Surinamese background living in Amsterdam. Our questions concerned which communication channels they usually used to access weight-related health advice or information about programs and whose information they most valued. The content analysis of data was performed. The participants mentioned four channels - regular and traditional health care, general or ethnically specific media, multiethnic and ethnic gatherings, and interpersonal communication with peers in the Netherlands and with people in the home country. Ghanaian women emphasized ethnically specific channels (e.g., traditional health care, Ghanaian churches). They were comfortable with these channels and trusted them. They mentioned fewer general channels - mainly limited to health care - and if discussed, negative perceptions were expressed. Antillean women mentioned the use of ethnically specific channels (e.g., communication with Antilleans in the home country) on balance with general audience-oriented channels (e.g., regular health care). Perceptions were mixed. Surinamese participants discussed, in a positive manner, the use of general audience-oriented channels, while they said they did not use traditional health care or advice from Surinam. Local language proficiency, time resided in the Netherlands, and approaches and messages received seemed to explain channel use and perception. The predominant differences in channel use and perception among the ethnic groups indicate a need for channel segmentation to reach a multiethnic target group with weight

  15. Monomerization alters the dynamics of the lid region in Campylobacter jejuni CstII: an MD simulation study.

    PubMed

    Prabhakar, Pradeep Kumar; Srivastava, Alka; Rao, K Krishnamurthy; Balaji, Petety V

    2016-01-01

    CstII, a bifunctional (α2,3/8) sialyltransferase from Campylobacter jejuni, is a homotetramer. It has been reported that mutation of the interface residues Phe121 (F121D) or Tyr125 (Y125Q) leads to monomerization and partial loss of enzyme activity, without any change in the secondary or tertiary structures. MD simulations of both tetramer and monomer, with and without bound donor substrate, were performed for the two mutants and WT to understand the reasons for partial loss of activity due to monomerization since the active site is located within each monomer. RMSF values were found to correlate with the crystallographic B-factor values indicating that the simulations are able to capture the flexibility of the molecule effectively. There were no gross changes in either the secondary or tertiary structure of the proteins during MD simulations. However, interface is destabilized by the mutations, and more importantly the flexibility of the lid region (Gly152-Lys190) is affected. The lid region accesses three major conformations named as open, intermediate, and closed conformations. In both Y121Q and F121D mutants, the closed conformation is accessed predominantly. In this conformation, the catalytic base His188 is also displaced. Normal mode analysis also revealed differences in the lid movement in tetramer and monomer. This provides a possible explanation for the partial loss of enzyme activity in both interface mutants. The lid region controls the traffic of substrates and products in and out of the active site, and the dynamics of this region is regulated by tetramerization. Thus, this study provides valuable insights into the role of loop dynamics in enzyme activity of CstII.

  16. Sustainable water recovery from oily wastewater via forward osmosis-membrane distillation (FO-MD).

    PubMed

    Zhang, Sui; Wang, Peng; Fu, Xiuzhu; Chung, Tai-Shung

    2014-04-01

    This study proposed and investigated a hybrid forward osmosis - membrane distillation (FO-MD) system for sustainable water recovery from oily wastewater by employing lab-fabricated FO and MD hollow fiber membranes. Stable oil-in-water emulsions of different concentrations with small droplet sizes (<1 μm) were firstly prepared and applied as the feed solution in the FO process. Fouling was immediately observed in the FO mode and was low on the cellulose triacetate (CTA) - based thin film composite (TFC) membranes. Moreover, slight increment of fouling was observed in the first few hours and the water flux was then stabilized over 24 h. The characterizations of water flux and solute rejection in separate FO and MD processes revealed that a high water flux, good NaCl rejection, impressively high retention of oil droplets and partial permeation of acetic acid could be achieved. Finally, an integrated FO-MD system was developed to treat the oily wastewater containing petroleum, surfactant, NaCl and acetic acid at 60 °C in the batch mode. The water flux in FO undergoes three-stage decline due to fouling and reduction in osmotic driving force, but is quite stable in MD regardless of salt concentration. Oily wastewater with relatively high salinity could be effectively recovered by the FO-MD hybrid system while maintaining large water flux, at least 90% feed water recovery could be readily attained with only trace amounts of oil and salts, and the draw solution was re-generated for the next rounds of FO-MD run. Interestingly, significant amount of acetic acid was also retained in the permeate for further reuse as a chemical additive during the production of crude oil. The work has demonstrated that not only water but also organic additives in the wastewater could be effectively recovered by FO-MD systems for reuse or other utilizations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. InforMD: a new initiative to raise public awareness about breast density

    PubMed Central

    Hugo, Honor J; Zysk, Aneta; Dasari, Pallave; Britt, Kara; Hopper, John L; Stone, Jennifer; Thompson, Erik W; Ingman, Wendy V

    2018-01-01

    On a mammogram, breast density (also known as mammographic density) is shown as white and bright regions and is associated with reduced sensitivity in cancer detection and increased breast cancer risk. However, many Australian women are unaware of the significance of breast density as it is not routinely reported or discussed. In order to address this lack of knowledge, Australian breast cancer researchers with expertise in mammographic density formed the InforMD alliance (INformation FORum on Mammographic Density) in 2016. The alliance is working to raise awareness of breast density with the goal of improving breast cancer diagnosis and health outcomes for women. The InforMD website (www.InforMD.org.au) was launched in October 2016, coinciding with a major nationwide public awareness campaign by the alliance during breast cancer awareness month. The website contains unbiased, accurate, updated information on breast density. The website also provides summaries of major research articles in layperson language, recent news items related to breast density, links to relevant information for health professionals, events, and feature articles. Members of the public and health professionals can also subscribe for news updates. The interactive online Forum section facilitates discussion between health professionals, scientists and members of the public. To increase online traffic to the website, Facebook (www.facebook.com/BeInforMD) and Twitter (https://twitter.com/BeInforMD_) pages were launched in December 2016. Since its launch, InforMD has generated considerable interest. The public awareness campaign reached over 7 million Australians through a combination of newspaper, TV, radio, and online news. The website has attracted 13,058 unique visitors and 30,353 page views (data as of 19/12/2017). Breast cancer researchers have a significant role to play in disseminating information to the public on breast density. A combination of mainstream and social media, together with

  18. InforMD: a new initiative to raise public awareness about breast density.

    PubMed

    Hugo, Honor J; Zysk, Aneta; Dasari, Pallave; Britt, Kara; Hopper, John L; Stone, Jennifer; Thompson, Erik W; Ingman, Wendy V

    2018-01-01

    On a mammogram, breast density (also known as mammographic density) is shown as white and bright regions and is associated with reduced sensitivity in cancer detection and increased breast cancer risk. However, many Australian women are unaware of the significance of breast density as it is not routinely reported or discussed. In order to address this lack of knowledge, Australian breast cancer researchers with expertise in mammographic density formed the InforMD alliance (INformation FORum on Mammographic Density) in 2016. The alliance is working to raise awareness of breast density with the goal of improving breast cancer diagnosis and health outcomes for women. The InforMD website (www.InforMD.org.au) was launched in October 2016, coinciding with a major nationwide public awareness campaign by the alliance during breast cancer awareness month. The website contains unbiased, accurate, updated information on breast density. The website also provides summaries of major research articles in layperson language, recent news items related to breast density, links to relevant information for health professionals, events, and feature articles. Members of the public and health professionals can also subscribe for news updates. The interactive online Forum section facilitates discussion between health professionals, scientists and members of the public. To increase online traffic to the website, Facebook (www.facebook.com/BeInforMD) and Twitter (https://twitter.com/BeInforMD_) pages were launched in December 2016. Since its launch, InforMD has generated considerable interest. The public awareness campaign reached over 7 million Australians through a combination of newspaper, TV, radio, and online news. The website has attracted 13,058 unique visitors and 30,353 page views (data as of 19/12/2017). Breast cancer researchers have a significant role to play in disseminating information to the public on breast density. A combination of mainstream and social media, together with

  19. An apple B-box protein, MdCOL11, is involved in UV-B- and temperature-induced anthocyanin biosynthesis.

    PubMed

    Bai, Songling; Saito, Takanori; Honda, Chikako; Hatsuyama, Yoshimichi; Ito, Akiko; Moriguchi, Takaya

    2014-11-01

    Our studies showed that an apple B-box protein, MdCOL11, the homolog of AtBBX22, is involved in UV-B- and temperature-induced anthocyanin biosynthesis in apple peel. Anthocyanin is responsible for the red pigmentation in apple peel and a R2R3 MYB gene, MdMYBA/1/10, a homolog of MdMYBA, controls its accumulation. Arabidopsis PAP1 is under the control of a series of upstream factors involved in light signal transduction and photomorphogenesis, such as ELONGATED HYPOCOTYL 5 (HY5) and B-box family (BBX) proteins. In this study, we identified and characterized the homolog of Arabidopsis BBX22 in apple, designated as MdCOL11. Overexpression of MdCOL11 in Arabidopsis enhanced the accumulation of anthocyanin. In apples, MdCOL11 was differentially expressed in all tissues, with the highest expression in petals and the lowest expression in the xylem. Transcripts of MdCOL11 noticeably accumulated at the ripening stage, concomitant with increases in the expressions of anthocyanin biosynthesis-related genes. In an in vitro treatment experiment, MdCOL11 was upregulated in an ultra-violet (UV)-B- and temperature-dependent manner, together with the inductions of anthocyanin biosynthesis-related genes and anthocyanin accumulation in apple peel. Furthermore, a dual-luciferase assay indicated that (1) MdCOL11 regulated the expression of MdMYBA and (2) MdCOL11 was a target of MdHY5. Taken together, our results suggest that MdCOL11 is involved in MdHY5-mediated signal transduction and regulates anthocyanin accumulation in apple peel, which sheds new light on anthocyanin accumulation in apples.

  20. Ion channel regulation by phosphoinositides analyzed with VSPs—PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility

    PubMed Central

    Rjasanow, Alexandra; Leitner, Michael G.; Thallmair, Veronika; Halaszovich, Christian R.; Oliver, Dominik

    2015-01-01

    The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids. Voltage-sensitive phosphatases (VSPs) turn over PI(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5)P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs. PMID

  1. Performance analysis of replication ALOHA for fading mobile communications channels

    NASA Technical Reports Server (NTRS)

    Yan, Tsun-Yee; Clare, Loren P.

    1986-01-01

    This paper describes an ALOHA random access protocol for fading communications channels. A two-state Markov model is used for the channel error process to account for the channel fading memory. The ALOHA protocol is modified to send multiple contiguous copies of a message at each transmission attempt. Both pure and slotted ALOHA channels are considered. The analysis is applicable to fading environments where the channel memory is short compared to the propagation delay. It is shown that smaller delay may be achieved using replications and, in noisy conditions, can also improve throughput.

  2. A comparison between elastic network interpolation and MD simulation of 16S ribosomal RNA.

    PubMed

    Kim, Moon K; Li, Wen; Shapiro, Bruce A; Chirikjian, Gregory S

    2003-12-01

    In this paper a coarse-grained method called elastic network interpolation (ENI) is used to generate feasible transition pathways between two given conformations of the core central domain of 16S Ribosomal RNA (16S rRNA). The two given conformations are the extremes generated by a molecular dynamics (MD) simulation, which differ from each other by 10A in root-mean-square deviation (RMSD). It takes only several hours to build an ENI pathway on a 1.5GHz Pentium with 512 MB memory, while the MD takes several weeks on high-performance multi-processor servers such as the SGI ORIGIN 2000/2100. It is shown that multiple ENI pathways capture the essential anharmonic motions of millions of timesteps in a particular MD simulation. A coarse-grained normal mode analysis (NMA) is performed on each intermediate ENI conformation, and the lowest 1% of the normal modes (representing about 40 degrees of freedom (DOF)) are used to parameterize fluctuations. This combined ENI/NMA method captures all intermediate conformations in the MD run with 1.5A RMSD on average. In addition, if we restrict attention to the time interval of the MD run between the two extreme conformations, the RMSD between the closest ENI/NMA pathway and the MD results is about 1A. These results may serve as a paradigm for reduced-DOF dynamic simulations of large biological macromolecules as well as a method for the reduced-parameter interpretation of massive amounts of MD data.

  3. A Novel Dynamic Spectrum Access Framework Based on Reinforcement Learning for Cognitive Radio Sensor Networks.

    PubMed

    Lin, Yun; Wang, Chao; Wang, Jiaxing; Dou, Zheng

    2016-10-12

    Cognitive radio sensor networks are one of the kinds of application where cognitive techniques can be adopted and have many potential applications, challenges and future research trends. According to the research surveys, dynamic spectrum access is an important and necessary technology for future cognitive sensor networks. Traditional methods of dynamic spectrum access are based on spectrum holes and they have some drawbacks, such as low accessibility and high interruptibility, which negatively affect the transmission performance of the sensor networks. To address this problem, in this paper a new initialization mechanism is proposed to establish a communication link and set up a sensor network without adopting spectrum holes to convey control information. Specifically, firstly a transmission channel model for analyzing the maximum accessible capacity for three different polices in a fading environment is discussed. Secondly, a hybrid spectrum access algorithm based on a reinforcement learning model is proposed for the power allocation problem of both the transmission channel and the control channel. Finally, extensive simulations have been conducted and simulation results show that this new algorithm provides a significant improvement in terms of the tradeoff between the control channel reliability and the efficiency of the transmission channel.

  4. A Novel Dynamic Spectrum Access Framework Based on Reinforcement Learning for Cognitive Radio Sensor Networks

    PubMed Central

    Lin, Yun; Wang, Chao; Wang, Jiaxing; Dou, Zheng

    2016-01-01

    Cognitive radio sensor networks are one of the kinds of application where cognitive techniques can be adopted and have many potential applications, challenges and future research trends. According to the research surveys, dynamic spectrum access is an important and necessary technology for future cognitive sensor networks. Traditional methods of dynamic spectrum access are based on spectrum holes and they have some drawbacks, such as low accessibility and high interruptibility, which negatively affect the transmission performance of the sensor networks. To address this problem, in this paper a new initialization mechanism is proposed to establish a communication link and set up a sensor network without adopting spectrum holes to convey control information. Specifically, firstly a transmission channel model for analyzing the maximum accessible capacity for three different polices in a fading environment is discussed. Secondly, a hybrid spectrum access algorithm based on a reinforcement learning model is proposed for the power allocation problem of both the transmission channel and the control channel. Finally, extensive simulations have been conducted and simulation results show that this new algorithm provides a significant improvement in terms of the tradeoff between the control channel reliability and the efficiency of the transmission channel. PMID:27754316

  5. 75 FR 79063 - Maryland Disaster #MD-00014

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-17

    ... SMALL BUSINESS ADMINISTRATION [Disaster Declaration 12411 and 12412] Maryland Disaster MD-00014 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Administrative declaration of a disaster for the State of Maryland dated 12/09/2010. Incident: Severe Storms and...

  6. Effect of Endodontic Access on the Failure Load of Lithium Disilicate and Resin Nano-ceramic CADCAM Crowns

    DTIC Science & Technology

    2017-06-09

    3 August 2016 Douglas D. Lancaster, COL, DC Army Post Graduate Dental School Effect of Endodontic Access on the Failure Load of Lithium...University of the Health Sciences, Bethesda, MD; Schofield Barracks Dental Clinic, Schofield Barracks, HI; Tripler Army Medical Center, Honolulu...underlying die was reached. (Neo Diamond, Microcopy Dental ). The access outline was then completed with a medium (100-110µm) grit round-ended

  7. In silico Analysis of Conformational Changes Induced by Mutation of Aromatic Binding Residues: Consequences for Drug Binding in the hERG K+ Channel

    PubMed Central

    Knape, Kirsten; Linder, Tobias; Wolschann, Peter; Beyer, Anton; Stary-Weinzinger, Anna

    2011-01-01

    Pharmacological inhibition of cardiac hERG K+ channels is associated with increased risk of lethal arrhythmias. Many drugs reduce hERG current by directly binding to the channel, thereby blocking ion conduction. Mutation of two aromatic residues (F656 and Y652) substantially decreases the potency of numerous structurally diverse compounds. Nevertheless, some drugs are only weakly affected by mutation Y652A. In this study we utilize molecular dynamics simulations and docking studies to analyze the different effects of mutation Y652A on a selected number of hERG blockers. MD simulations reveal conformational changes in the binding site induced by mutation Y652A. Loss of π-π-stacking between the two aromatic residues induces a conformational change of the F656 side chain from a cavity facing to cavity lining orientation. Docking studies and MD simulations qualitatively reproduce the diverse experimentally observed modulatory effects of mutation Y652A and provide a new structural interpretation for the sensitivity differences. PMID:22194911

  8. Lactobacillus farciminis MD, a newer strain with potential for bacteriocin and antibiotic assay.

    PubMed

    Halami, P M; Chandrashekar, A; Nand, K

    2000-03-01

    A native isolate Lactobacillus farciminis MD isolated from fermenting mushroom exhibited a high degree of sensitivity to the majority of the bacteriocins produced by strains of lactobacilli, leuconostoc and pediococci. Also, the efficacy of Lact. farciminis MD as a sensitive strain for antibiotic assay was established against different antibiotics including ampicillin, cefazoline, chloramphenicol and nitrofurantoin at concentrations of 30 microg each, showing an inhibition zone of 30 mm diameter. The high degree of sensitivity towards bacteriocins and antibiotics provide potential for the exploitation of Lact. farciminis MD in establishing very well-defined bacteriocin producers.

  9. Channel One in the Public Schools: Widening the Gaps.

    ERIC Educational Resources Information Center

    Morgan, Michael

    Channel One, an in-school television program, provides a centrally prepared, 10-minute daily newscast accompanied by 2 minutes of commercials. Several states ban Channel One because of concerns about providing advertisers such direct access to students within the walls of tax-supported public school buildings. This paper examines what kinds of…

  10. Cross-scale MD simulations of dynamic strength of tantalum

    NASA Astrophysics Data System (ADS)

    Bulatov, Vasily

    2017-06-01

    Dislocations are ubiquitous in metals where their motion presents the dominant and often the only mode of plastic response to straining. Over the last 25 years computational prediction of plastic response in metals has relied on Discrete Dislocation Dynamics (DDD) as the most fundamental method to account for collective dynamics of moving dislocations. Here we present first direct atomistic MD simulations of dislocation-mediated plasticity that are sufficiently large and long to compute plasticity response of single crystal tantalum while tracing the underlying dynamics of dislocations in all atomistic details. Where feasible, direct MD simulations sidestep DDD altogether thus reducing uncertainties of strength predictions to those of the interatomic potential. In the specific context of shock-induced material dynamics, the same MD models predict when, under what conditions and how dislocations interact and compete with other fundamental mechanisms of dynamic response, e.g. twinning, phase-transformations, fracture. In collaboration with: Luis Zepeda-Ruiz, Lawrence Livermore National Laboratory; Alexander Stukowski, Technische Universitat Darmstadt; Tomas Oppelstrup, Lawrence Livermore National Laboratory. This work was performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

  11. Angiotensin II induces kidney inflammatory injury and fibrosis through binding to myeloid differentiation protein-2 (MD2).

    PubMed

    Xu, Zheng; Li, Weixin; Han, Jibo; Zou, Chunpeng; Huang, Weijian; Yu, Weihui; Shan, Xiaoou; Lum, Hazel; Li, Xiaokun; Liang, Guang

    2017-03-21

    Growing evidence indicates that angiotensin II (Ang II), a potent biologically active product of RAS, is a key regulator of renal inflammation and fibrosis. In this study, we tested the hypothesis that Ang II induces renal inflammatory injury and fibrosis through interaction with myeloid differentiation protein-2 (MD2), the accessory protein of toll-like receptor 4 (TLR4) of the immune system. Results indicated that in MD2 -/- mice, the Ang II-induced renal fibrosis, inflammation and kidney dysfunction were significantly reduced compared to control Ang II-infused wild-type mice. Similarly, in the presence of small molecule MD2 specific inhibitor L6H21 or siRNA-MD2, the Ang II-induced increases of pro-fibrotic and pro-inflammatory molecules were prevented in tubular NRK-52E cells. MD2 blockade also inhibited activation of NF-κB and ERK. Moreover, MD2 blockade prevented the Ang II-stimulated formation of the MD2/TLR4/MyD88 signaling complex, as well as the increased surface binding of Ang II in NRK-52E cells. In addition, Ang II directly bound recombinant MD2 protein, rather than TLR4 protein. We conclude that MD2 is a significant contributor in the Ang II-induced kidney inflammatory injury in chronic renal diseases. Furthermore, MD2 inhibition could be a new and important therapeutic strategy for preventing progression of chronic renal diseases.

  12. MdMYB1 Regulates Anthocyanin and Malate Accumulation by Directly Facilitating Their Transport into Vacuoles in Apples.

    PubMed

    Hu, Da-Gang; Sun, Cui-Hui; Ma, Qi-Jun; You, Chun-Xiang; Cheng, Lailiang; Hao, Yu-Jin

    2016-03-01

    Tonoplast transporters, including proton pumps and secondary transporters, are essential for plant cell function and for quality formation of fleshy fruits and ornamentals. Vacuolar transport of anthocyanins, malate, and other metabolites is directly or indirectly dependent on the H(+)-pumping activities of vacuolar H(+)-ATPase (VHA) and/or vacuolar H(+)-pyrophosphatase, but how these proton pumps are regulated in modulating vacuolar transport is largely unknown. Here, we report a transcription factor, MdMYB1, in apples that binds to the promoters of two genes encoding the B subunits of VHA, MdVHA-B1 and MdVHA-B2, to transcriptionally activate its expression, thereby enhancing VHA activity. A series of transgenic analyses in apples demonstrates that MdMYB1/10 controls cell pH and anthocyanin accumulation partially by regulating MdVHA-B1 and MdVHA-B2. Furthermore, several other direct target genes of MdMYB10 are identified, including MdVHA-E2, MdVHP1, MdMATE-LIKE1, and MdtDT, which are involved in H(+)-pumping or in the transport of anthocyanins and malates into vacuoles. Finally, we show that the mechanism by which MYB controls malate and anthocyanin accumulation in apples also operates in Arabidopsis (Arabidopsis thaliana). These findings provide novel insights into how MYB transcription factors directly modulate the vacuolar transport system in addition to anthocyanin biosynthesis, consequently controlling organ coloration and cell pH in plants. © 2016 American Society of Plant Biologists. All Rights Reserved.

  13. 78 FR 32556 - Safety Zone; 2013 Ocean City Air Show, Atlantic Ocean; Ocean City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-31

    ...-AA00 Safety Zone; 2013 Ocean City Air Show, Atlantic Ocean; Ocean City, MD AGENCY: Coast Guard, DHS... navigable waters of the Atlantic Ocean in the vicinity of Ocean City, MD to support the Ocean City Air Show... June 9, 2013, Ocean City, MD will host an air show event between Talbot Street and 33rd Street over the...

  14. Image fusion in craniofacial virtual reality modeling based on CT and 3dMD photogrammetry.

    PubMed

    Xin, Pengfei; Yu, Hongbo; Cheng, Huanchong; Shen, Shunyao; Shen, Steve G F

    2013-09-01

    The aim of this study was to demonstrate the feasibility of building a craniofacial virtual reality model by image fusion of 3-dimensional (3D) CT models and 3 dMD stereophotogrammetric facial surface. A CT scan and stereophotography were performed. The 3D CT models were reconstructed by Materialise Mimics software, and the stereophotogrammetric facial surface was reconstructed by 3 dMD patient software. All 3D CT models were exported as Stereo Lithography file format, and the 3 dMD model was exported as Virtual Reality Modeling Language file format. Image registration and fusion were performed in Mimics software. Genetic algorithm was used for precise image fusion alignment with minimum error. The 3D CT models and the 3 dMD stereophotogrammetric facial surface were finally merged into a single file and displayed using Deep Exploration software. Errors between the CT soft tissue model and 3 dMD facial surface were also analyzed. Virtual model based on CT-3 dMD image fusion clearly showed the photorealistic face and bone structures. Image registration errors in virtual face are mainly located in bilateral cheeks and eyeballs, and the errors are more than 1.5 mm. However, the image fusion of whole point cloud sets of CT and 3 dMD is acceptable with a minimum error that is less than 1 mm. The ease of use and high reliability of CT-3 dMD image fusion allows the 3D virtual head to be an accurate, realistic, and widespread tool, and has a great benefit to virtual face model.

  15. Improved Iterative Decoding of Network-Channel Codes for Multiple-Access Relay Channel.

    PubMed

    Majumder, Saikat; Verma, Shrish

    2015-01-01

    Cooperative communication using relay nodes is one of the most effective means of exploiting space diversity for low cost nodes in wireless network. In cooperative communication, users, besides communicating their own information, also relay the information of other users. In this paper we investigate a scheme where cooperation is achieved using a common relay node which performs network coding to provide space diversity for two information nodes transmitting to a base station. We propose a scheme which uses Reed-Solomon error correcting code for encoding the information bit at the user nodes and convolutional code as network code, instead of XOR based network coding. Based on this encoder, we propose iterative soft decoding of joint network-channel code by treating it as a concatenated Reed-Solomon convolutional code. Simulation results show significant improvement in performance compared to existing scheme based on compound codes.

  16. Epigenetic regulation of MdMYB1 is associated with paper bagging-induced red pigmentation of apples.

    PubMed

    Bai, Songling; Tuan, Pham Anh; Saito, Takanori; Honda, Chikako; Hatsuyama, Yoshimichi; Ito, Akiko; Moriguchi, Takaya

    2016-09-01

    Paper-bagging treatment can transform non-transcribed MdMYB1 - 2 and MdMYB1 - 3 alleles into transcribed alleles through epigenetic regulations, resulting in the red pigmentation of a normally non-red apple cultivar 'Mutsu.' Anthocyanin biosynthesis in apples is regulated by MdMYB1/A/10, an R2R3-Type MYB gene. 'Mutsu,' a triploid apple cultivar harboring non-transcribed MdMYB1-2 and MdMYB1-3 alleles, retains green skin color under field conditions. However, it can show red/pink pigmentation under natural or artificial ultraviolet-B (UV-B) light exposure after paper-bagging and bag removal treatment. In the present study, we found that in 'Mutsu,' paper bagging-induced red pigmentation was due to the activation of non-transcribed MdMYB1-2/-3 alleles, which triggered the expression of downstream anthocyanin biosynthesis genes in a UV-B-dependent manner. By monitoring the epigenetic changes during UV-B-induced pigmentation, no significant differences in DNA methylation and histone modifications in the 5' upstream region of MdMYB1-2/-3 were recorded between the UV-B-treated fruit skin (red) and the fruit skin treated only by white light (green). In contrast, bag treatment lowered the DNA methylation in this region of MdMYB1-2/-3 alleles. Similarly, higher levels of histone H3 acetylation and trimethylation of H3 tail at lysine 4, and lower level of trimethylation of H3 tail at lysine 27 were observed in the 5' upstream region of MdMYB1-2/-3 in the skin of the fruit immediately after bag removal. These results suggest that bagging treatment can induce epigenetic changes, facilitating the binding of trans factor(s) to MdMYB1-2/-3 alleles, resulting in the activation of these MYBs after bag removal.

  17. Arbitrarily small amounts of correlation for arbitrarily varying quantum channels

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

    Boche, H., E-mail: boche@tum.de, E-mail: janis.noetzel@tum.de; Nötzel, J., E-mail: boche@tum.de, E-mail: janis.noetzel@tum.de

    2013-11-15

    As our main result show that in order to achieve the randomness assisted message and entanglement transmission capacities of a finite arbitrarily varying quantum channel it is not necessary that sender and receiver share (asymptotically perfect) common randomness. Rather, it is sufficient that they each have access to an unlimited amount of uses of one part of a correlated bipartite source. This access might be restricted to an arbitrary small (nonzero) fraction per channel use, without changing the main result. We investigate the notion of common randomness. It turns out that this is a very costly resource – generically, itmore » cannot be obtained just by local processing of a bipartite source. This result underlines the importance of our main result. Also, the asymptotic equivalence of the maximal- and average error criterion for classical message transmission over finite arbitrarily varying quantum channels is proven. At last, we prove a simplified symmetrizability condition for finite arbitrarily varying quantum channels.« less

  18. The MdTFL1 gene of apple (Malus x domestica Borkh.) reduces vegetative growth and generation time.

    PubMed

    Flachowsky, Henryk; Szankowski, Iris; Waidmann, Sascha; Peil, Andreas; Tränkner, Conny; Hanke, Magda-Viola

    2012-10-01

    TFL1 is known as a floral repressor in Arabidopsis thaliana (L.) Heynh. In apple there are two TFL1 homologs, MdTFL1-1 and MdTFL1-2. The MdTFL1-1 gene was silenced in transgenic clones expressing a hairpin gene construct of a 323 bp fragment of MdTFL1-1. The hairpin gene construct was transferred to three different apple genotypes. Of 22 transgenic clones, 21 showed a significant reduction in MdTFL1-1 mRNA expression. Precocious flowering was obtained for 20 clones, which flowered already during in vitro cultivation. Nineteen clones could successfully be transferred to the greenhouse where 18 of them flowered within a few weeks followed by the death or at least a strongly inhibited vegetative growth of the plant. Most of the transgenic flowers developed abnormally. Results obtained on greenhouse-grown plants of the transgenic clones and transgenic seedlings clearly demonstrated the major role of MdTFL1 genes in maintaining the vegetative growth as prerequisite for a perennial lifecycle. It was shown that MdTFL1 dsRNAi promotes a life history similar to annual plants. Preliminary results obtained from grafting experiments with non-transgenic scions grafted onto MdTFL1 dsRNAi transgenic rootstocks indicated that the flower-inducing signal obtained after silencing of MdTFL1 genes seems not to be graft-transmissible.

  19. Spontaneous and training-induced cortical plasticity in MD patients: Hints from lateral masking.

    PubMed

    Maniglia, Marcello; Soler, Vincent; Cottereau, Benoit; Trotter, Yves

    2018-01-08

    Macular degeneration (MD) affects central vision and represents the leading cause of visual diseases in elderly population worldwide. As a consequence of central vision loss, MD patients develop a preferred retinal locus (PRL), an eccentric fixation point that replaces the fovea. Here, our aim was to determine whether and to what extent spontaneous plasticity takes place in the cortical regions formerly responding to central vision and whether a visual training based on perceptual learning (PL) can boost this plasticity within the PRL area. Spontaneous and PL-induced cortical plasticity were characterized by using lateral masking, a contrast sensitivity modulation induced by collinear flankers. This configuration is known to be sensitive to neural plasticity and underlies several rehabilitation trainings. Results in a group of 4 MD patients showed that collinear facilitation was similar to what observed in age- and eccentricity-matched controls. However, MD patients exhibited significantly reduced collinear inhibition, a sign of neural plasticity, consistent with the hypothesis of partial cortical reorganization. Three AMD patients from the same group showed a further reduction of inhibition after training, but not controls. This result suggests that PL might further boost neural plasticity, opening promising perspectives for the development of rehabilitation protocols for MD patients.

  20. PAD-MAC: Primary User Activity-Aware Distributed MAC for Multi-Channel Cognitive Radio Networks

    PubMed Central

    Ali, Amjad; Piran, Md. Jalil; Kim, Hansoo; Yun, Jihyeok; Suh, Doug Young

    2015-01-01

    Cognitive radio (CR) has emerged as a promising technology to solve problems related to spectrum scarcity and provides a ubiquitous wireless access environment. CR-enabled secondary users (SUs) exploit spectrum white spaces opportunistically and immediately vacate the acquired licensed channels as primary users (PUs) arrive. Accessing the licensed channels without the prior knowledge of PU traffic patterns causes severe throughput degradation due to excessive channel switching and PU-to-SU collisions. Therefore, it is significantly important to design a PU activity-aware medium access control (MAC) protocol for cognitive radio networks (CRNs). In this paper, we first propose a licensed channel usage pattern identification scheme, based on a two-state Markov model, and then estimate the future idle slots using previous observations of the channels. Furthermore, based on these past observations, we compute the rank of each available licensed channel that gives SU transmission success assessment during the estimated idle slot. Secondly, we propose a PU activity-aware distributed MAC (PAD-MAC) protocol for heterogeneous multi-channel CRNs that selects the best channel for each SU to enhance its throughput. PAD-MAC controls SU activities by allowing them to exploit the licensed channels only for the duration of estimated idle slots and enables predictive and fast channel switching. To evaluate the performance of the proposed PAD-MAC, we compare it with the distributed QoS-aware MAC (QC-MAC) and listen-before-talk MAC schemes. Extensive numerical results show the significant improvements of the PAD-MAC in terms of the SU throughput, SU channel switching rate and PU-to-SU collision rate. PMID:25831084

  1. Free-Energy Calculations. A Mathematical Perspective

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrzej

    2015-01-01

    Ion channels are pore-forming assemblies of transmembrane proteins that mediate and regulate ion transport through cell walls. They are ubiquitous to all life forms. In humans and other higher organisms they play the central role in conducting nerve impulses. They are also essential to cardiac processes, muscle contraction and epithelial transport. Ion channels from lower organisms can act as toxins or antimicrobial agents, and in a number of cases are involved in infectious diseases. Because of their important and diverse biological functions they are frequent targets of drug action. Also, simple natural or synthetic channels find numerous applications in biotechnology. For these reasons, studies of ion channels are at the forefront of biophysics, structural biology and cellular biology. In the last decade, the increased availability of X-ray structures has greatly advanced our understanding of ion channels. However, their mechanism of action remains elusive. This is because, in order to assist controlled ion transport, ion channels are dynamic by nature, but X-ray crystallography captures the channel in a single, sometimes non-native state. To explain how ion channels work, X-ray structures have to be supplemented with dynamic information. In principle, molecular dynamics (MD) simulations can aid in providing this information, as this is precisely what MD has been designed to do. However, MD simulations suffer from their own problems, such as inability to access sufficiently long time scales or limited accuracy of force fields. To assess the reliability of MD simulations it is only natural to turn to the main function of channels - conducting ions - and compare calculated ionic conductance with electrophysiological data, mainly single channel recordings, obtained under similar conditions. If this comparison is satisfactory it would greatly increase our confidence that both the structures and our computational methodologies are sufficiently accurate. Channel

  2. Web Based Data Access to the World Data Center for Climate

    NASA Astrophysics Data System (ADS)

    Toussaint, F.; Lautenschlager, M.

    2006-12-01

    The World Data Center for Climate (WDC-Climate, www.wdc-climate.de) is hosted by the Model &Data Group (M&D) of the Max Planck Institute for Meteorology. The M&D department is financed by the German government and uses the computers and mass storage facilities of the German Climate Computing Centre (Deutsches Klimarechenzentrum, DKRZ). The WDC-Climate provides web access to 200 Terabytes of climate data; the total mass storage archive contains nearly 4 Petabytes. Although the majority of the datasets concern model output data, some satellite and observational data are accessible as well. The underlying relational database is distributed on five servers. The CERA relational data model is used to integrate catalogue data and mass data. The flexibility of the model allows to store and access very different types of data and metadata. The CERA metadata catalogue provides easy access to the content of the CERA database as well as to other data in the web. Visit ceramodel.wdc-climate.de for additional information on the CERA data model. The majority of the users access data via the CERA metadata catalogue, which is open without registration. However, prior to retrieving data user are required to check in and apply for a userid and password. The CERA metadata catalogue is servlet based. So it is accessible worldwide through any web browser at cera.wdc-climate.de. In addition to data and metadata access by the web catalogue, WDC-Climate offers a number of other forms of web based data access. All metadata are available via http request as xml files in various metadata formats (ISO, DC, etc., see wini.wdc-climate.de) which allows for easy data interchange with other catalogues. Model data can be retrieved in GRIB, ASCII, NetCDF, and binary (IEEE) format. WDC-Climate serves as data centre for various projects. Since xml files are accessible by http, the integration of data into applications of different projects is very easy. Projects supported by WDC-Climate are e.g. CEOP

  3. Is channel segmentation necessary to reach a multiethnic population with weight-related health promotion? An analysis of use and perception of communication channels

    PubMed Central

    Nierkens, Vera; Cremer, Stephan W.; Verhoeff, Arnoud; Stronks, Karien

    2014-01-01

    Objective To explore similarities and differences in the use and perception of communication channels to access weight-related health promotion among women in three ethnic minority groups. The ultimate aim was to determine whether similar channels might reach ethnic minority women in general or whether segmentation to ethnic groups would be required. Design Eight ethnically homogeneous focus groups were conducted among 48 women of Ghanaian, Antillean/Aruban, or Afro-Surinamese background living in Amsterdam. Our questions concerned which communication channels they usually used to access weight-related health advice or information about programs and whose information they most valued. The content analysis of data was performed. Results The participants mentioned four channels – regular and traditional healthcare, general or ethnically specific media, multiethnic and ethnic gatherings, and interpersonal communication with peers in the Netherlands and with people in the home country. Ghanaian women emphasized ethnically specific channels (e.g., traditional healthcare, Ghanaian churches). They were comfortable with these channels and trusted them. They mentioned fewer general channels – mainly limited to healthcare – and if discussed, negative perceptions were expressed. Antillean women mentioned the use of ethnically specific channels (e.g., communication with Antilleans in the home country) on balance with general audience–oriented channels (e.g., regular healthcare). Perceptions were mixed. Surinamese participants discussed, in a positive manner, the use of general audience–oriented channels, while they said they did not use traditional healthcare or advice from Surinam. Local language proficiency, time resided in the Netherlands, and approaches and messages received seemed to explain channel use and perception. Conclusion The predominant differences in channel use and perception among the ethnic groups indicate a need for channel segmentation to reach a

  4. PoopMD, a Mobile Health Application, Accurately Identifies Infant Acholic Stools.

    PubMed

    Franciscovich, Amy; Vaidya, Dhananjay; Doyle, Joe; Bolinger, Josh; Capdevila, Montserrat; Rice, Marcus; Hancock, Leslie; Mahr, Tanya; Mogul, Douglas B

    2015-01-01

    Biliary atresia (BA) is the leading cause of pediatric end-stage liver disease in the United States. Education of parents in the perinatal period with stool cards depicting acholic and normal stools has been associated with improved time-to-diagnosis and survival in BA. PoopMD is a mobile application that utilizes a smartphone's camera and color recognition software to analyze an infant's stool and determine if additional follow-up is indicated. PoopMD was developed using custom HTML5/CSS3 and wrapped to work on iOS and Android platforms. In order to define the gold standard regarding stool color, seven pediatricians were asked to review 45 photographs of infant stool and rate them as acholic, normal, or indeterminate. Samples for which 6+ pediatricians demonstrated agreement defined the gold standard, and only these samples were included in the analysis. Accuracy of PoopMD was assessed using an iPhone 5s with incandescent lighting. Variability in analysis of stool photographs as acholic versus normal with intermediate rating weighted as 50% agreement (kappa) was compared between three laypeople and one expert user. Variability in output was also assessed between an iPhone 5s and a Samsung Galaxy S4, as well as between incandescent lighting and compact fluorescent lighting. Six-plus pediatricians agreed on 27 normal and 7 acholic photographs; no photographs were defined as indeterminate. The sensitivity was 7/7 (100%). The specificity was 24/27 (89%) with 3/27 labeled as indeterminate; no photos of normal stool were labeled as acholic. The Laplace-smoothed positive likelihood ratio was 6.44 (95% CI 2.52 to 16.48) and the negative likelihood ratio was 0.13 (95% CI 0.02 to 0.83). kappauser was 0.68, kappaphone was 0.88, and kappalight was 0.81. Therefore, in this pilot study, PoopMD accurately differentiates acholic from normal color with substantial agreement across users, and almost perfect agreement across two popular smartphones and ambient light settings. PoopMD

  5. 77 FR 25106 - Special Local Regulations for Marine Events; Potomac River, National Harbor Access Channel, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-27

    ..., an email address, or a telephone number in the body of your document so that we can contact you if we... period, we will issue maritime advisories so mariners can adjust their plans accordingly. If you think...) explaining why you think it qualifies and how and to what degree this rule would economically affect it...

  6. Find an Orthopaedic Foot and Ankle MD/DO

    MedlinePlus

    ... All Site Content AOFAS / FootCareMD / Find a Surgeon Find a Foot & Ankle Orthopaedic Surgeon Page Content Who ... your prescribed treatment (surgical and/or non-surgical) ​ Find a Surgeon ​ Click here to find a foot ...

  7. An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development.

    PubMed

    Yamashita, Shinji; Kataoka, Makoto; Suzaki, Yuki; Imai, Hiromitsu; Morimoto, Takuya; Ohashi, Kyoichi; Inano, Akihiro; Togashi, Kazutaka; Mutaguchi, Kuninori; Sugiyama, Yuichi

    2015-09-01

    A cassette-microdose (MD) clinical study was performed to demonstrate its usefulness for identifying the most promising compound for oral use. Three Ca-channel blockers (nifedipine, nicardipine, and diltiazem) were chosen as model drugs. In the MD clinical study, a cassette-dose method was employed in which three model drugs were administered simultaneously. Both intravenous (i.v.) and oral (p.o.) administration studies were conducted to calculate the oral bioavailability (BA). For comparison, p.o. studies with therapeutic dose (ThD) levels were also performed. In all studies, blood concentrations of each drug were successfully determined using liquid chromatography-mass spectrometry with the lower limit of quantification of 0.2-2.0 pg/mL. Oral BA of nifedipine in the MD study was approximately 50% and in the same range with that obtained in the ThD study, whereas other two drugs showed significantly lower BA in the MD study, indicating a dose-dependent absorption. In addition, compared with the ThD study, absorption of nicardipine was delayed in the MD study. As a result, nifedipine was considered to be most promising for oral use. In conclusion, a cassette-MD clinical study is of advantage for oral drug development that enables to identify the candidate having desired properties for oral use. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  8. Exploring transmembrane transport through alpha-hemolysin with grid-steered molecular dynamics.

    PubMed

    Wells, David B; Abramkina, Volha; Aksimentiev, Aleksei

    2007-09-28

    The transport of biomolecules across cell boundaries is central to cellular function. While structures of many membrane channels are known, the permeation mechanism is known only for a select few. Molecular dynamics (MD) is a computational method that can provide an accurate description of permeation events at the atomic level, which is required for understanding the transport mechanism. However, due to the relatively short time scales accessible to this method, it is of limited utility. Here, we present a method for all-atom simulation of electric field-driven transport of large solutes through membrane channels, which in tens of nanoseconds can provide a realistic account of a permeation event that would require a millisecond simulation using conventional MD. In this method, the average distribution of the electrostatic potential in a membrane channel under a transmembrane bias of interest is determined first from an all-atom MD simulation. This electrostatic potential, defined on a grid, is subsequently applied to a charged solute to steer its permeation through the membrane channel. We apply this method to investigate permeation of DNA strands, DNA hairpins, and alpha-helical peptides through alpha-hemolysin. To test the accuracy of the method, we computed the relative permeation rates of DNA strands having different sequences and global orientations. The results of the G-SMD simulations were found to be in good agreement in experiment.

  9. A combined coarse-grained and all-atom simulation of TRPV1 channel gating and heat activation

    PubMed Central

    Qin, Feng

    2015-01-01

    The transient receptor potential (TRP) channels act as key sensors of various chemical and physical stimuli in eukaryotic cells. Despite years of study, the molecular mechanisms of TRP channel activation remain unclear. To elucidate the structural, dynamic, and energetic basis of gating in TRPV1 (a founding member of the TRPV subfamily), we performed coarse-grained modeling and all-atom molecular dynamics (MD) simulation based on the recently solved high resolution structures of the open and closed form of TRPV1. Our coarse-grained normal mode analysis captures two key modes of collective motions involved in the TRPV1 gating transition, featuring a quaternary twist motion of the transmembrane domains (TMDs) relative to the intracellular domains (ICDs). Our transition pathway modeling predicts a sequence of structural movements that propagate from the ICDs to the TMDs via key interface domains (including the membrane proximal domain and the C-terminal domain), leading to sequential opening of the selectivity filter followed by the lower gate in the channel pore (confirmed by modeling conformational changes induced by the activation of ICDs). The above findings of coarse-grained modeling are robust to perturbation by lipids. Finally, our MD simulation of the ICD identifies key residues that contribute differently to the nonpolar energy of the open and closed state, and these residues are predicted to control the temperature sensitivity of TRPV1 gating. These computational predictions offer new insights to the mechanism for heat activation of TRPV1 gating, and will guide our future electrophysiology and mutagenesis studies. PMID:25918362

  10. Molecular cloning and functional analysis of a blue light receptor gene MdCRY2 from apple (Malus domestica).

    PubMed

    Li, Yuan-Yuan; Mao, Ke; Zhao, Cheng; Zhao, Xian-Yan; Zhang, Rui-Fen; Zhang, Hua-Lei; Shu, Huai-Rui; Hao, Yu-Jin

    2013-04-01

    MdCRY2 was isolated from apple fruit skin, and its function was analyzed in MdCRY2 transgenic Arabidopsis. The interaction between MdCRY2 and AtCOP1 was found by yeast two-hybrid and BiFC assays. Cryptochromes are blue/ultraviolet-A (UV-A) light receptors involved in regulating various aspects of plant growth and development. Investigations of the structure and functions of cryptochromes in plants have largely focused on Arabidopsis (Arabidopsis thaliana), tomato (Solanum lycopersicum), pea (Pisum sativum), and rice (Oryza sativa). However, no data on the function of CRY2 are available in woody plants. In this study, we isolated a cryptochrome gene, MdCRY2, from apple (Malus domestica). The deduced amino acid sequences of MdCRY2 contain the conserved N-terminal photolyase-related domain and the flavin adenine dinucleotide (FAD) binding domain, as well as the C-terminal DQXVP-acidic-STAES (DAS) domain. Relationship analysis indicates that MdCRY2 shows the highest similarity to the strawberry FvCRY protein. The expression of MdCRY2 is induced by blue/UV-A light, which represents a 48-h circadian rhythm. To investigate the function of MdCRY2, we overexpressed the MdCRY2 gene in a cry2 mutant and wild type (WT) Arabidopsis, assessed the phenotypes of the resulting transgenic plants, and found that MdCRY2 functions to regulate hypocotyl elongation, root growth, flower initiation, and anthocyanin accumulation. Furthermore, we examined the interaction between MdCRY2 and AtCOP1 using a yeast two-hybrid assay and a bimolecular fluorescence complementation assay. These data provide functional evidence for a role of blue/UV-A light-induced MdCRY2 in controlling photomorphogenesis in apple.

  11. Threading the biophysics of mammalian Slo1 channels onto structures of an invertebrate Slo1 channel

    PubMed Central

    2017-01-01

    For those interested in the machinery of ion channel gating, the Ca2+ and voltage-activated BK K+ channel provides a compelling topic for investigation, by virtue of its dual allosteric regulation by both voltage and intracellular Ca2+ and because its large-single channel conductance facilitates detailed kinetic analysis. Over the years, biophysical analyses have illuminated details of the allosteric regulation of BK channels and revealed insights into the mechanism of BK gating, e.g., inner cavity size and accessibility and voltage sensor-pore coupling. Now the publication of two structures of an Aplysia californica BK channel—one liganded and one metal free—promises to reinvigorate functional studies and interpretation of biophysical results. The new structures confirm some of the previous functional inferences but also suggest new perspectives regarding cooperativity between Ca2+-binding sites and the relationship between voltage- and Ca2+-dependent gating. Here we consider the extent to which the two structures explain previous functional data on pore-domain properties, voltage-sensor motions, and divalent cation binding and activation of the channel. PMID:29025867

  12. Cytoplasmic Domains and Voltage-Dependent Potassium Channel Gating

    PubMed Central

    Barros, Francisco; Domínguez, Pedro; de la Peña, Pilar

    2012-01-01

    The basic architecture of the voltage-dependent K+ channels (Kv channels) corresponds to a transmembrane protein core in which the permeation pore, the voltage-sensing components and the gating machinery (cytoplasmic facing gate and sensor–gate coupler) reside. Usually, large protein tails are attached to this core, hanging toward the inside of the cell. These cytoplasmic regions are essential for normal channel function and, due to their accessibility to the cytoplasmic environment, constitute obvious targets for cell-physiological control of channel behavior. Here we review the present knowledge about the molecular organization of these intracellular channel regions and their role in both setting and controlling Kv voltage-dependent gating properties. This includes the influence that they exert on Kv rapid/N-type inactivation and on activation/deactivation gating of Shaker-like and eag-type Kv channels. Some illustrative examples about the relevance of these cytoplasmic domains determining the possibilities for modulation of Kv channel gating by cellular components are also considered. PMID:22470342

  13. 33 CFR 165.509 - Security Zone; Severn River and College Creek, Annapolis, MD.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... College Creek, Annapolis, MD. 165.509 Section 165.509 Navigation and Navigable Waters COAST GUARD... § 165.509 Security Zone; Severn River and College Creek, Annapolis, MD. (a) Definitions. For purposes of... the Naval Academy waterfront. This security zone includes the waters of College Creek eastward of the...

  14. Asynchronous, Decentralized DS-CDMA Using Feedback-Controlled Spreading Sequences for Time-Dispersive Channels

    NASA Astrophysics Data System (ADS)

    Miyatake, Teruhiko; Chiba, Kazuki; Hamamura, Masanori; Tachikawa, Shin'ichi

    We propose a novel asynchronous direct-sequence codedivision multiple access (DS-CDMA) using feedback-controlled spreading sequences (FCSSs) (FCSS/DS-CDMA). At the receiver of FCSS/DS-CDMA, the code-orthogonalizing filter (COF) produces a spreading sequence, and the receiver returns the spreading sequence to the transmitter. Then the transmitter uses the spreading sequence as its updated version. The performance of FCSS/DS-CDMA is evaluated over time-dispersive channels. The results indicate that FCSS/DS-CDMA greatly suppresses both the intersymbol interference (ISI) and multiple access interference (MAI) over time-invariant channels. FCSS/DS-CDMA is applicable to the decentralized multiple access.

  15. Water at silica/liquid water interfaces investigated by DFT-MD simulations

    NASA Astrophysics Data System (ADS)

    Gaigeot, Marie-Pierre

    This talk is dedicated to probing the microscopic structural organization of water at silica/liquid water interfaces including electrolytes by first principles DFT-based molecular dynamics simulations (DFT-MD). We will present our very recent DFT-MD simulations of electrolytic (KCl, NaCl, NaI) silica/liquid water interfaces in order to unravel the intertwined structural properties of water and electrolytes at the crystalline quartz/liquid water and amorphous silica/liquid water interfaces. DFT-MD simulations provide direct knowledge of the structural organization of water and the H-Bond network formed between the water molecules within the different water layers above the silica surface. One can furthermore extract vibrational signatures of the water molecules within the interfacial layers from the DFT-MD simulations, especially non-linear SFG (Sum Frequency generation) signatures that are active at solid/liquid interfaces. The strength of the simulated spectra is that a detailed analysis of the signatures in terms of the water/water H-Bond networks formed within the interfacial water layers and in terms of the water/silica or water/electrolytes H-Bond networks can be given. Comparisons of SFG spectra between quartz/water/electrolytes and amorphous silica/water/electrolytes interfaces allow us to definitely conclude on how the structural arrangements of liquid water at these electrolytic interfaces modulate the final spectroscopic signatures. Invited speaker.

  16. Computation of shear viscosity of colloidal suspensions by SRD-MD

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

    Laganapan, A. M. K.; Videcoq, A., E-mail: arnaud.videcoq@unilim.fr; Bienia, M.

    2015-04-14

    The behaviour of sheared colloidal suspensions with full hydrodynamic interactions (HIs) is numerically studied. To this end, we use the hybrid stochastic rotation dynamics-molecular dynamics (SRD-MD) method. The shear viscosity of colloidal suspensions is computed for different volume fractions, both for dilute and concentrated cases. We verify that HIs help in the collisions and the streaming of colloidal particles, thereby increasing the overall shear viscosity of the suspension. Our results show a good agreement with known experimental, theoretical, and numerical studies. This work demonstrates the ability of SRD-MD to successfully simulate transport coefficients that require correct modelling of HIs.

  17. 78 FR 11725 - Maryland Disaster Number MD-00024

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-19

    ... SMALL BUSINESS ADMINISTRATION [Disaster Declaration 13425 and 13426] Maryland Disaster Number MD-00024 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1. SUMMARY: This is an amendment of... information in the original declaration remains unchanged. (Catalog of Federal Domestic Assistance Numbers...

  18. 76 FR 70527 - Maryland Disaster Number MD-00018

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... SMALL BUSINESS ADMINISTRATION [Disaster Declaration 12874 and 12875] Maryland Disaster Number MD-00018 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1. SUMMARY: This is an amendment of... the original declaration remains unchanged .(Catalog of Federal Domestic Assistance Numbers 59002 and...

  19. Molecular cloning and functional characterization of the apple sucrose transporter gene MdSUT2.

    PubMed

    Ma, Qi-Jun; Sun, Mei-Hong; Liu, Ya-Jing; Lu, Jing; Hu, Da-Gang; Hao, Yu-Jin

    2016-12-01

    Sucrose is not only the primary photosynthetic product but also the major component translocated in the phloem of economically important plant species. Sucrose transporters or carriers (SUTs or SUCs), function as sucrose/H + symporters and play a crucial role in determining the cell-to-cell distribution of sucrose throughout the entire plant. However, whether such genes are involved in responses to abiotic stress and other biological processes is largely unknown. Here, we report that MdSUT2 in apple is a homolog of the Arabidopsis vacuolar sucrose transporter AtSUT2. Ectopic expression of MdSUT2 in Arabidopsis decreased sucrose sensitivity in germination and seeding stage and increased sucrose transport activity. In addition, our results showed that MdSUT2 impacted on plant growth by accelerating vegetative growth and promoting early flowering in Arabidopsis. Overexpression of MdSUT2 significantly improved abiotic stress tolerance including NaCl, ABA, and mannitol in apple calli and Arabidopsis. Together, these findings provide evidence that the apple sucrose transporter MdSUT2 is involved in abiotic stress resistance and the regulation of plant growth and development. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. A Mathematic Model That Describes Modes of MdSGHV Transmission within House Fly Populations.

    PubMed

    Vallejo, Celeste R; Lee, Jo Ann; Keesling, James E; Geden, Christopher J; Lietze, Verena-Ulrike; Boucias, Drion G

    2013-11-20

    In this paper it is proposed that one potential component by which the Musca domestica salivary gland hypertrophy virus (MdSGHV) infects individual flies is through cuticular damage. Breaks in the cuticle allow entry of the virus into the hemocoel causing the infection. Male flies typically have a higher rate of infection and a higher rate of cuticular damage than females. A model for the transmission of MdSGHV was formulated assuming several potential and recognized means of transmission. The model yields results that are in agreement with field data that measured the infection rate in house flies on dairy farms in Florida. The results from this model indicate that MdSGHV will be maintained at a stable rate within house fly populations and support the future use of MdSGHV as a birth control agent in house fly management.

  1. Cross-sectional-derived determinants of satisfaction with physician-scientist training among Canadian MD/PhD graduates.

    PubMed

    Twa, David D W; Skinnider, Michael A; Squair, Jordan W; Lukac, Christine D

    2017-01-01

    Although MD/PhD programs require considerable commitment on behalf of students and learning institutions, they serve as an integral means of training future physician-scientists; individuals who engage in translational medicine. As attrition from these programs has longstanding effects on the community of translational medicine and comes at substantial cost to MD/PhD programs, we aimed to identify determinants that were associated with satisfaction among MD/PhD graduates, a feature that might inform on limiting program attrition. Anonymized data from a national survey of 139 Canadian MD/PhD alumni was analyzed. Factor analysis was conducted to evaluate the reliability of three questions that measured satisfaction and logistic regression was used to assess the association of outcomes with 17 independent determinants. Eighty-one percent of graduates were satisfied with MD/PhD training. Factor analysis confirmed the reliability of the questions measuring satisfaction. Determinants of self-reported satisfaction with physician-scientist training included co-authorship of more than six manuscripts during MD/PhD training. Additionally, protected research time at the place of current appointment was strongly associated with agreement that MD/PhD training had helped career progression. Demographic variables were not associated with any satisfaction indicator. Taken together, the majority of Canadian MD/PhD graduates are satisfied with their physician-scientist training. Project collaboration leading to co-authorships and protected research time were strongly associated with training satisfaction among graduates. If the value of collaboration can be realized among current and future physician-scientist trainees who are dissatisfied with their training, this might ultimately reduce program attrition.

  2. Frequency of a natural truncated allele of MdMLO19 in the germplasm of Malus domestica.

    PubMed

    Pessina, Stefano; Palmieri, Luisa; Bianco, Luca; Gassmann, Jennifer; van de Weg, Eric; Visser, Richard G F; Magnago, Pierluigi; Schouten, Henk J; Bai, Yuling; Riccardo Velasco, R; Malnoy, Mickael

    2017-01-01

    Podosphaera leucotricha is the causal agent of powdery mildew (PM) in apple. To reduce the amount of fungicides required to control this pathogen, the development of resistant apple cultivars should become a priority. Resistance to PM was achieved in various crops by knocking out specific members of the MLO gene family that are responsible for PM susceptibility (S-genes). In apple, the knockdown of MdMLO19 resulted in PM resistance. However, since gene silencing technologies such as RNAi are perceived unfavorably in Europe, a different approach that exploits this type of resistance is needed. This work evaluates the presence of non-functional naturally occurring alleles of MdMLO19 in apple germplasm. The screening of the re-sequencing data of 63 apple individuals led to the identification of 627 single nucleotide polymorphisms (SNPs) in five MLO genes ( MdMLO5, MdMLO7, MdMLO11, MdMLO18 , and MdMLO19 ), 127 of which were located in exons. The T-1201 insertion of a single nucleotide in MdMLO19 caused the formation of an early stop codon, resulting in a truncated protein lacking 185 amino acids, including the calmodulin-binding domain. The presence of the insertion was evaluated in 115 individuals. It was heterozygous in 64 and homozygous in 25. Twelve of the 25 individuals carrying the insertion in homozygosity were susceptible to PM. After barley, pea, cucumber, and tomato, apple would be the fifth species for which a natural non-functional mlo allele has been found.

  3. Movement of NH3 through the human urea transporter B: a new gas channel

    PubMed Central

    Musa-Aziz, Raif; Enkavi, Giray; Mahinthichaichan, P.; Tajkhorshid, Emad; Boron, Walter F.

    2013-01-01

    Aquaporins and Rh proteins can function as gas (CO2 and NH3) channels. The present study explores the urea, H2O, CO2, and NH3 permeability of the human urea transporter B (UT-B) (SLC14A1), expressed in Xenopus oocytes. We monitored urea uptake using [14C]urea and measured osmotic water permeability (Pf) using video microscopy. To obtain a semiquantitative measure of gas permeability, we used microelectrodes to record the maximum transient change in surface pH (ΔpHS) caused by exposing oocytes to 5% CO2/33 mM HCO3− (pHS increase) or 0.5 mM NH3/NH4+ (pHS decrease). UT-B expression increased oocyte permeability to urea by >20-fold, and Pf by 8-fold vs. H2O-injected control oocytes. UT-B expression had no effect on the CO2-induced ΔpHS but doubled the NH3-induced ΔpHS. Phloretin reduced UT-B-dependent urea uptake (Jurea*) by 45%, Pf* by 50%, and (−ΔpHS*)NH3 by 70%. p-Chloromercuribenzene sulfonate reduced Jurea* by 25%, Pf* by 30%, and (ΔpHS*)NH3 by 100%. Molecular dynamics (MD) simulations of membrane-embedded models of UT-B identified the monomeric UT-B pores as the main conduction pathway for both H2O and NH3 and characterized the energetics associated with permeation of these species through the channel. Mutating each of two conserved threonines lining the monomeric urea pores reduced H2O and NH3 permeability. Our data confirm that UT-B has significant H2O permeability and for the first time demonstrate significant NH3 permeability. Thus the UTs become the third family of gas channels. Inhibitor and mutagenesis studies and results of MD simulations suggest that NH3 and H2O pass through the three monomeric urea channels in UT-B. PMID:23552862

  4. The R2R3-MYB transcription factor MdMYB73 is involved in malate accumulation and vacuolar acidification in apple.

    PubMed

    Hu, Da-Gang; Li, Yuan-Yuan; Zhang, Quan-Yan; Li, Ming; Sun, Cui-Hui; Yu, Jian-Qiang; Hao, Yu-Jin

    2017-08-01

    Malate, the predominant organic acid in many fruits, is a crucial component of the organoleptic quality of fruit, including taste and flavor. The genetic and environmental mechanisms affecting malate metabolism in fruit cells have been studied extensively. However, the transcriptional regulation of malate-metabolizing enzymes and vacuolar transporters remains poorly understood. Our previous studies demonstrated that MdMYB1 modulates anthocyanin accumulation and vacuolar acidification by directly activating vacuolar transporters, including MdVHA-B1, MdVHA-E, MdVHP1 and MdtDT. Interestingly, we isolated and identified a MYB transcription factor, MdMYB73, a distant relative of MdMYB1 in this study. It was subsequently found that MdMYB73 protein bound directly to the promoters of MdALMT9 (aluminum-activated malate transporter 9), MdVHA-A (vacuolar ATPase subunit A) and MdVHP1 (vacuolar pyrophosphatase 1), transcriptionally activating their expression and thereby enhancing their activities. Analyses of transgenic apple calli demonstrated that MdMYB73 influenced malate accumulation and vacuolar pH. Furthermore, MdCIbHLH1 interacted with MdMYB73 and enhanced its activity upon downstream target genes. These findings help to elucidate how MdMYB73 directly modulates the vacuolar transport system to affect malate accumulation and vacuolar pH in apple. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  5. 78 FR 3496 - Maryland Disaster Number MD-00025

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-16

    ... SMALL BUSINESS ADMINISTRATION [Disaster Declaration 13394 and 13395] Maryland Disaster Number MD-00025 AGENCY: U.S. Small Business Administration. ACTION: Amendment 3. SUMMARY: This is an amendment of.... (Catalog of Federal Domestic Assistance Numbers 59002 and 59008) James E. Rivera, Associate Administrator...

  6. 76 FR 70528 - Maryland Disaster Number MD-00018

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... SMALL BUSINESS ADMINISTRATION [Disaster Declaration 12874 and 12875] Maryland Disaster Number MD-00018 AGENCY: U.S. Small Business Administration. ACTION: Amendment 2. SUMMARY: This is an amendment of... declaration remains unchanged. (Catalog of Federal Domestic Assistance Numbers 59002 and 59008) James E...

  7. 77 FR 74908 - Maryland Disaster Number MD-00025

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-18

    ... SMALL BUSINESS ADMINISTRATION [Disaster Declaration 13394 and 13395] Maryland Disaster Number MD-00025 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1. SUMMARY: This is an amendment of... declaration remains unchanged. (Catalog of Federal Domestic Assistance Numbers 59002 and 59008) James E...

  8. Two-Channel Kondo Effect in a Modified Single Electron Transistor

    NASA Astrophysics Data System (ADS)

    Oreg, Yuval; Goldhaber-Gordon, David

    2003-04-01

    We suggest a simple system of two electron droplets which should display two-channel Kondo behavior at experimentally accessible temperatures. Stabilization of the two-channel Kondo fixed point requires fine control of the electrochemical potential in each droplet, which can be achieved by adjusting voltages on nearby gate electrodes. We study the conditions for obtaining this type of two-channel Kondo behavior, discuss the experimentally observable consequences, and explore the gener­alization to the multichannel Kondo case.

  9. Eva Szabo, MD | Division of Cancer Prevention

    Cancer.gov

    Dr. Eva Szabo is Chief of the Lung and Upper Aerodigestive Cancer Research Group at the NCI Division of Cancer Prevention. She graduated from Yale University with a BS in Molecular Biophysics and Biochemistry, received her MD from Duke University, and completed her internal medicine residency at Bellevue-NYU Medical Center. After completing her medical oncology fellowship at

  10. Species-Specific Activation of TLR4 by Hypoacylated Endotoxins Governed by Residues 82 and 122 of MD-2

    PubMed Central

    Oblak, Alja; Jerala, Roman

    2014-01-01

    The Toll-like receptor 4/MD-2 receptor complex recognizes endotoxin, a Gram-negative bacterial cell envelope component. Recognition of the most potent hexaacylated form of endotoxin is mediated by the sixth acyl chain that protrudes from the MD-2 hydrophobic pocket and bridges TLR4/MD-2 to the neighboring TLR4 ectodomain, driving receptor dimerization via hydrophobic interactions. In hypoacylated endotoxins all acyl chains could be accommodated within the binding pocket of the human hMD-2. Nevertheless, tetra- and pentaacylated endotoxins activate the TLR4/MD-2 receptor of several species. We observed that amino acid residues 82 and 122, located at the entrance to the endotoxin binding site of MD-2, have major influence on the species-specific endotoxin recognition. We show that substitution of hMD-2 residue V82 with an amino acid residue with a bulkier hydrophobic side chain enables activation of TLR4/MD-2 by pentaacylated and tetraacylated endotoxins. Interaction of the lipid A phosphate group with the amino acid residue 122 of MD-2 facilitates the appropriate positioning of the hypoacylated endotoxin. Moreover, mouse TLR4 contributes to the agonistic effect of pentaacylated msbB endotoxin. We propose a molecular model that explains how the molecular differences between the murine or equine MD-2, which both have sufficiently large hydrophobic pockets to accommodate all five or four acyl chains, influence the positioning of endotoxin so that one of the acyl chains remains outside the pocket and enables hydrophobic interactions with TLR4, leading to receptor activation. PMID:25203747

  11. Species-specific activation of TLR4 by hypoacylated endotoxins governed by residues 82 and 122 of MD-2.

    PubMed

    Oblak, Alja; Jerala, Roman

    2014-01-01

    The Toll-like receptor 4/MD-2 receptor complex recognizes endotoxin, a Gram-negative bacterial cell envelope component. Recognition of the most potent hexaacylated form of endotoxin is mediated by the sixth acyl chain that protrudes from the MD-2 hydrophobic pocket and bridges TLR4/MD-2 to the neighboring TLR4 ectodomain, driving receptor dimerization via hydrophobic interactions. In hypoacylated endotoxins all acyl chains could be accommodated within the binding pocket of the human hMD-2. Nevertheless, tetra- and pentaacylated endotoxins activate the TLR4/MD-2 receptor of several species. We observed that amino acid residues 82 and 122, located at the entrance to the endotoxin binding site of MD-2, have major influence on the species-specific endotoxin recognition. We show that substitution of hMD-2 residue V82 with an amino acid residue with a bulkier hydrophobic side chain enables activation of TLR4/MD-2 by pentaacylated and tetraacylated endotoxins. Interaction of the lipid A phosphate group with the amino acid residue 122 of MD-2 facilitates the appropriate positioning of the hypoacylated endotoxin. Moreover, mouse TLR4 contributes to the agonistic effect of pentaacylated msbB endotoxin. We propose a molecular model that explains how the molecular differences between the murine or equine MD-2, which both have sufficiently large hydrophobic pockets to accommodate all five or four acyl chains, influence the positioning of endotoxin so that one of the acyl chains remains outside the pocket and enables hydrophobic interactions with TLR4, leading to receptor activation.

  12. Ensemble MD simulations restrained via crystallographic data: Accurate structure leads to accurate dynamics

    PubMed Central

    Xue, Yi; Skrynnikov, Nikolai R

    2014-01-01

    Currently, the best existing molecular dynamics (MD) force fields cannot accurately reproduce the global free-energy minimum which realizes the experimental protein structure. As a result, long MD trajectories tend to drift away from the starting coordinates (e.g., crystallographic structures). To address this problem, we have devised a new simulation strategy aimed at protein crystals. An MD simulation of protein crystal is essentially an ensemble simulation involving multiple protein molecules in a crystal unit cell (or a block of unit cells). To ensure that average protein coordinates remain correct during the simulation, we introduced crystallography-based restraints into the MD protocol. Because these restraints are aimed at the ensemble-average structure, they have only minimal impact on conformational dynamics of the individual protein molecules. So long as the average structure remains reasonable, the proteins move in a native-like fashion as dictated by the original force field. To validate this approach, we have used the data from solid-state NMR spectroscopy, which is the orthogonal experimental technique uniquely sensitive to protein local dynamics. The new method has been tested on the well-established model protein, ubiquitin. The ensemble-restrained MD simulations produced lower crystallographic R factors than conventional simulations; they also led to more accurate predictions for crystallographic temperature factors, solid-state chemical shifts, and backbone order parameters. The predictions for 15N R1 relaxation rates are at least as accurate as those obtained from conventional simulations. Taken together, these results suggest that the presented trajectories may be among the most realistic protein MD simulations ever reported. In this context, the ensemble restraints based on high-resolution crystallographic data can be viewed as protein-specific empirical corrections to the standard force fields. PMID:24452989

  13. Molecular mechanism of voltage sensing in voltage-gated proton channels

    PubMed Central

    Rebolledo, Santiago; Perez, Marta E.

    2013-01-01

    Voltage-gated proton (Hv) channels play an essential role in phagocytic cells by generating a hyperpolarizing proton current that electrically compensates for the depolarizing current generated by the NADPH oxidase during the respiratory burst, thereby ensuring a sustained production of reactive oxygen species by the NADPH oxidase in phagocytes to neutralize engulfed bacteria. Despite the importance of the voltage-dependent Hv current, it is at present unclear which residues in Hv channels are responsible for the voltage activation. Here we show that individual neutralizations of three charged residues in the fourth transmembrane domain, S4, all reduce the voltage dependence of activation. In addition, we show that the middle S4 charged residue moves from a position accessible from the cytosolic solution to a position accessible from the extracellular solution, suggesting that this residue moves across most of the membrane electric field during voltage activation of Hv channels. Our results show for the first time that the charge movement of these three S4 charges accounts for almost all of the measured gating charge in Hv channels. PMID:23401575

  14. Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) for Conformational Space Search of Peptide and Miniprotein

    PubMed Central

    Hao, Ge-Fei; Xu, Wei-Fang; Yang, Sheng-Gang; Yang, Guang-Fu

    2015-01-01

    Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation. PMID:26492886

  15. Genome-wide histone modification profile induced by MDV in MD-resistant and -susceptible chickens

    USDA-ARS?s Scientific Manuscript database

    Marek’s disease (MD) is a lymphoproliferative disease in chicken caused by oncogenic Marek’s disease virus (MDV). MD is characterized by infiltration of proliferating lymphoid cells in organs, such as peripheral nerve, skin, muscle, liver, spleen, heart, kidney, gonads and proventriculus. Epigenetic...

  16. Ultrasteep Voltage Dependence in a Membrane Channel

    NASA Astrophysics Data System (ADS)

    Mangan, Patrick S.; Colombini, Marco

    1987-07-01

    A mechanism for regulating voltage-gated channels is presented. The treatment amplifies the effect of the applied membrane potential resulting in a dramatic increase in the channel's voltage dependence. Addition of a large polyvalent anion to the medium bathing a phospholipid bilayer containing the voltage-dependent channel from the mitochondrial outer membrane, VDAC, induced up to a 12-fold increase in the channel's voltage sensitivity. The highest polyvalent anion concentration tested resulted in an e-fold conductance change for a 0.36-mV change in membrane potential. On the low end, a concentration of 2 μ M resulted in a 50% increase in VDAC voltage dependence. A mechanism based on polyvalent anion accumulation in the access resistance region at the mouth of the pore is consistent with all findings. Perhaps the voltage dependence of voltage-gated channels is amplified in vivo by polyvalent ions. If so, the control of excitable phenomena may be under much finer regulation than that provided by membrane potential alone.

  17. Thomas Secker M.D.: Archbishop and man-midwife.

    PubMed

    Morgan-Guy, John

    2018-05-01

    This paper provides a biographical outline of the career of Thomas Secker, MD, who from 1758-68 was Archbishop of Canterbury. Although much has been written on Secker, this study seeks to highlight his training in medicine, which has been largely overlooked hitherto by historians.

  18. NBodyLab Simulation Experiments with GRAPE-6a AND MD-GRAPE2 Acceleration

    NASA Astrophysics Data System (ADS)

    Johnson, V.; Ates, A.

    2005-12-01

    NbodyLab is an astrophysical N-body simulation testbed for student research. It is accessible via a web interface and runs as a backend framework under Linux. NbodyLab can generate data models or perform star catalog lookups, transform input data sets, perform direct summation gravitational force calculations using a variety of integration schemes, and produce analysis and visualization output products. NEMO (Teuben 1994), a popular stellar dynamics toolbox, is used for some functions. NbodyLab integrators can optionally utilize two types of low-cost desktop supercomputer accelerators, the newly available GRAPE-6a (125 Gflops peak) and the MD-GRAPE2 (64-128 Gflops peak). The initial version of NBodyLab was presented at ADASS 2002. This paper summarizes software enhancements developed subsequently, focusing on GRAPE-6a related enhancements, and gives examples of computational experiments and astrophysical research, including star cluster and solar system studies, that can be conducted with the new testbed functionality.

  19. David Kasner, MD, and the Road to Pars Plana Vitrectomy

    PubMed Central

    Blodi, Christopher F.

    2016-01-01

    David Kasner, MD (1927–2001), used his extensive dissections of eye bank eyes and experiences in teaching cataract surgery to resident physicians to realize that excision of vitreous when present in the anterior chamber of eyes undergoing cataract surgery was preferable to prior intraoperative procedures. Noting that eyes tolerated his maneuvers, he then performed planned subtotal open-sky vitrectomies; first on a traumatized eye in 1961, then on two eyes of patients with amyloidosis (1966–1967). The success of these operations was noted by others, most particularly Robert Machemer, MD. Kasner’s work directly led to further surgical developments, including closed pars plana vitrectomy. PMID:27660504

  20. Message passing with queues and channels

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

    Dozsa, Gabor J; Heidelberger, Philip; Kumar, Sameer

    In an embodiment, a send thread receives an identifier that identifies a destination node and a pointer to data. The send thread creates a first send request in response to the receipt of the identifier and the data pointer. The send thread selects a selected channel from among a plurality of channels. The selected channel comprises a selected hand-off queue and an identification of a selected message unit. Each of the channels identifies a different message unit. The selected hand-off queue is randomly accessible. If the selected hand-off queue contains an available entry, the send thread adds the first sendmore » request to the selected hand-off queue. If the selected hand-off queue does not contain an available entry, the send thread removes a second send request from the selected hand-off queue and sends the second send request to the selected message unit.« less

  1. Humanized TLR4/MD-2 mice reveal LPS recognition differentially impacts susceptibility to Yersinia pestis and Salmonella enterica.

    PubMed

    Hajjar, Adeline M; Ernst, Robert K; Fortuno, Edgardo S; Brasfield, Alicia S; Yam, Cathy S; Newlon, Lindsay A; Kollmann, Tobias R; Miller, Samuel I; Wilson, Christopher B

    2012-01-01

    Although lipopolysaccharide (LPS) stimulation through the Toll-like receptor (TLR)-4/MD-2 receptor complex activates host defense against Gram-negative bacterial pathogens, how species-specific differences in LPS recognition impact host defense remains undefined. Herein, we establish how temperature dependent shifts in the lipid A of Yersinia pestis LPS that differentially impact recognition by mouse versus human TLR4/MD-2 dictate infection susceptibility. When grown at 37°C, Y. pestis LPS is hypo-acylated and less stimulatory to human compared with murine TLR4/MD-2. By contrast, when grown at reduced temperatures, Y. pestis LPS is more acylated, and stimulates cells equally via human and mouse TLR4/MD-2. To investigate how these temperature dependent shifts in LPS impact infection susceptibility, transgenic mice expressing human rather than mouse TLR4/MD-2 were generated. We found the increased susceptibility to Y. pestis for "humanized" TLR4/MD-2 mice directly paralleled blunted inflammatory cytokine production in response to stimulation with purified LPS. By contrast, for other Gram-negative pathogens with highly acylated lipid A including Salmonella enterica or Escherichia coli, infection susceptibility and the response after stimulation with LPS were indistinguishable between mice expressing human or mouse TLR4/MD-2. Thus, Y. pestis exploits temperature-dependent shifts in LPS acylation to selectively evade recognition by human TLR4/MD-2 uncovered with "humanized" TLR4/MD-2 transgenic mice.

  2. Howard Parnes, MD | Division of Cancer Prevention

    Cancer.gov

    Dr. Howard Parnes received a BA from Cornell University in 1977 and an MD from the University of Medicine and Dentistry of New Jersey in 1981. He trained in internal medicine at the Johns Hopkins Bayview Medical Center from 1981 to 1984 followed by a medical oncology fellowship at the University of Maryland Cancer Center (UMCC) from 1984 to 1987. |

  3. A CIPK protein kinase targets sucrose transporter MdSUT2.2 at Ser254 for phosphorylation to enhance salt tolerance.

    PubMed

    Ma, Qi-Jun; Sun, Mei-Hong; Kang, Hui; Lu, Jing; You, Chun-Xiang; Hao, Yu-Jin

    2018-05-23

    Soil salinity is one of the major abiotic stressors that negatively affect crop growth and yield. Salt stress can regulate antioxidants and the accumulation of osmoprotectants. In the study, a sucrose transporter MdSUT2.2 was identified in apple. Overexpression of MdSUT2.2 gene increased salt tolerance in the transgenic apple, compared with the WT control 'Gala'. In addition, it was found that protein MdSUT2.2 was phosphorylated at Ser 254 site in response to salt. A DUAL membrane yeast hybridization system through an apple cDNA library demonstrated that a protein kinase MdCIPK13 interacted with MdSUT2.2. A series of transgenic analysis in apple calli showed that MdCIPK13 was required for the salt-induced phosphorylation of MdSUT2.2 protein and enhanced its stability and transport activity. Finally, it was found that MdCIPK13 improved salt resistance in an MdSUT2.2-dependent manner. These findings had enriched our understanding of the molecular mechanisms underlying abiotic stress. This article is protected by copyright. All rights reserved.

  4. Molecular Basis of the Membrane Interaction of the β2e Subunit of Voltage-Gated Ca2+ Channels

    PubMed Central

    Kim, Dong-Il; Kang, Mooseok; Kim, Sangyeol; Lee, Juhwan; Park, Yongsoo; Chang, Iksoo; Suh, Byung-Chang

    2015-01-01

    The auxiliary β subunit plays an important role in the regulation of voltage-gated calcium (CaV) channels. Recently, it was revealed that β2e associates with the plasma membrane through an electrostatic interaction between N-terminal basic residues and anionic phospholipids. However, a molecular-level understanding of β-subunit membrane recruitment in structural detail has remained elusive. In this study, using a combination of site-directed mutagenesis, liposome-binding assays, and multiscale molecular-dynamics (MD) simulation, we developed a physical model of how the β2e subunit is recruited electrostatically to the plasma membrane. In a fluorescence resonance energy transfer assay with liposomes, binding of the N-terminal peptide (23 residues) to liposome was significantly increased in the presence of phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2). A mutagenesis analysis suggested that two basic residues proximal to Met-1, Lys-2 (K2) and Trp-5 (W5), are more important for membrane binding of the β2e subunit than distal residues from the N-terminus. Our MD simulations revealed that a stretched binding mode of the N-terminus to PS is required for stable membrane attachment through polar and nonpolar interactions. This mode obtained from MD simulations is consistent with experimental results showing that K2A, W5A, and K2A/W5A mutants failed to be targeted to the plasma membrane. We also investigated the effects of a mutated β2e subunit on inactivation kinetics and regulation of CaV channels by PIP2. In experiments with voltage-sensing phosphatase (VSP), a double mutation in the N-terminus of β2e (K2A/W5A) increased the PIP2 sensitivity of CaV2.2 and CaV1.3 channels by ∼3-fold compared with wild-type β2e subunit. Together, our results suggest that membrane targeting of the β2e subunit is initiated from the nonspecific electrostatic insertion of N-terminal K2 and W5 residues into the membrane. The PS-β2e interaction observed here

  5. MdMYB1 Regulates Anthocyanin and Malate Accumulation by Directly Facilitating Their Transport into Vacuoles in Apples1[OPEN

    PubMed Central

    Hu, Da-Gang; Sun, Cui-Hui; Ma, Qi-Jun; You, Chun-Xiang; Hao, Yu-Jin

    2016-01-01

    Tonoplast transporters, including proton pumps and secondary transporters, are essential for plant cell function and for quality formation of fleshy fruits and ornamentals. Vacuolar transport of anthocyanins, malate, and other metabolites is directly or indirectly dependent on the H+-pumping activities of vacuolar H+-ATPase (VHA) and/or vacuolar H+-pyrophosphatase, but how these proton pumps are regulated in modulating vacuolar transport is largely unknown. Here, we report a transcription factor, MdMYB1, in apples that binds to the promoters of two genes encoding the B subunits of VHA, MdVHA-B1 and MdVHA-B2, to transcriptionally activate its expression, thereby enhancing VHA activity. A series of transgenic analyses in apples demonstrates that MdMYB1/10 controls cell pH and anthocyanin accumulation partially by regulating MdVHA-B1 and MdVHA-B2. Furthermore, several other direct target genes of MdMYB10 are identified, including MdVHA-E2, MdVHP1, MdMATE-LIKE1, and MdtDT, which are involved in H+-pumping or in the transport of anthocyanins and malates into vacuoles. Finally, we show that the mechanism by which MYB controls malate and anthocyanin accumulation in apples also operates in Arabidopsis (Arabidopsis thaliana). These findings provide novel insights into how MYB transcription factors directly modulate the vacuolar transport system in addition to anthocyanin biosynthesis, consequently controlling organ coloration and cell pH in plants. PMID:26637549

  6. Characteristics and outcomes of Canadian MD/PhD program graduates: a cross-sectional survey

    PubMed Central

    Skinnider, Michael A.; Squair, Jordan W.; Twa, David D.W.; Ji, Jennifer X.; Kuzyk, Alexandra; Wang, Xin; Steadman, Patrick E.; Zaslavsky, Kirill; Dey, Ayan K.; Eisenberg, Mark J.; Gagné, Ève-Reine; HayGlass, Kent T.; Lewis, James F.; Margetts, Peter J.; Underhill, D. Alan; Rosenblum, Norman D.; Raymond, Lynn A.

    2017-01-01

    Background: Combined MD/PhD programs provide a structured path for physician-scientist training, but assessment of their success within Canada is limited by a lack of quantitative data. We collected outcomes data for graduates of Canadian MD/PhD programs. Methods: We developed and implemented a Web-based survey consisting of 41 questions designed to collect outcomes data for Canadian MD/PhD program alumni from 8 Canadian universities who had graduated before September 2015. Respondents were categorized into 2 groups according to whether they had or had not completed all training. Results: Of the 186 eligible alumni of MD/PhD programs, 139 (74.7%) completed the survey. A total of 136/138 respondents (98.6%) had completed or were currently completing residency training, and 66/80 (82%) had completed at least 1 postgraduate fellowship. Most (58 [83%]) of the 70 respondents who had completed all training were appointed as faculty at academic institutions, and 37 (53%) had been principal investigators on at least 1 recent funded project. Among the 58 respondents appointed at academic institutions, 44/57 (77%) dedicated at least 20% of their time to research, and 25/57 (44%) dedicated at least 50% to research. During their combined degree, 102/136 respondents (75.0%) published 3 or more first-author papers, and 133/136 (97.8%) matched with their first choice of specialty. The median length of physician-scientist training was 13.5 years. Most respondents graduated with debt despite having been supported by Canadian Institutes of Health Research MD/PhD studentships. Interpretation: Most Canadian MD/PhD program alumni pursued careers consistent with their physician-scientist training, which indicates that these programs are meeting their primary objective. Nevertheless, our findings highlight that a minority of these positions are research intensive; this finding warrants further study. Our data provide a baseline for future monitoring of the output of Canadian MD

  7. Voltage-dependent conformational changes in connexin channels.

    PubMed

    Bargiello, Thaddeus A; Tang, Qingxiu; Oh, Seunghoon; Kwon, Taekyung

    2012-08-01

    Channels formed by connexins display two distinct types of voltage-dependent gating, termed V(j)- or fast-gating and loop- or slow-gating. Recent studies, using metal bridge formation and chemical cross-linking have identified a region within the channel pore that contributes to the formation of the loop-gate permeability barrier. The conformational changes are remarkably large, reducing the channel pore diameter from 15 to 20Å to less than 4Å. Surprisingly, the largest conformational change occurs in the most stable region of the channel pore, the 3(10) or parahelix formed by amino acids in the 42-51 segment. The data provide a set of positional constraints that can be used to model the structure of the loop-gate closed state. Less is known about the conformation of the V(j)-gate closed state. There appear to be two different mechanisms; one in which conformational changes in channel structure are linked to a voltage sensor contained in the N-terminus of Cx26 and Cx32 and a second in which the C-terminus of Cx43 and Cx40 may act either as a gating particle to block the channel pore or alternatively to stabilize the closed state. The later mechanism utilizes the same domains as implicated in effecting pH gating of Cx43 channels. It is unclear if the two V(j)-gating mechanisms are related or if they represent different gating mechanisms that operate separately in different subsets of connexin channels. A model of the V(j)-closed state of Cx26 hemichannel that is based on the X-ray structure of Cx26 and electron crystallographic structures of a Cx26 mutation suggests that the permeability barrier for V(j)-gating is formed exclusively by the N-terminus, but recent information suggests that this conformation may not represent a voltage-closed state. Closed state models are considered from a thermodynamic perspective based on information from the 3.5Å Cx26 crystal structure and molecular dynamics (MD) simulations. The applications of computational and experimental

  8. Preliminary comparison of the Essie and PubMed search engines for answering clinical questions using MD on Tap, a PDA-based program for accessing biomedical literature

    PubMed Central

    Sutton, Victoria R.; Hauser, Susan E.

    2005-01-01

    MD on Tap, a PDA application that searches and retrieves biomedical literature, is specifically designed for use by mobile healthcare professionals. With the goal of improving the usability of the application, a preliminary comparison was made of two search engines (PubMed and Essie) to determine which provided most efficient path to the desired clinically-relevant information. PMID:16779415

  9. Preliminary comparison of the Essie and PubMed search engines for answering clinical questions using MD on Tap, a PDA-based program for accessing biomedical literature.

    PubMed

    Sutton, Victoria R; Hauser, Susan E

    2005-01-01

    MD on Tap, a PDA application that searches and retrieves biomedical literature, is specifically designed for use by mobile healthcare professionals. With the goal of improving the usability of the application, a preliminary comparison was made of two search engines (PubMed and Essie) to determine which provided most efficient path to the desired clinically-relevant information.

  10. Effect of salinity and temperature on treatment of concentrated wastewater from RO by FO-MD

    NASA Astrophysics Data System (ADS)

    Zhou, Yingru; Huang, Manhong; Deng, Qian

    2018-02-01

    In this study the appropriate temperature of the membrane distillation (MD) hot side (the permeation flux of MD was controlled by adjusting the hot side temperature) was selected according to the water flux of FO process so that the water transfer rate on both sides of FO and MD was consistent and the FO-MD process could be stable operation. When the salt concentration of feed solution was 30, 55, 80 and 100 g/L, the desalination rates changed little, which were 99.1%, 98.4%, 98.9% and 98.7%, respectively. The removal rate of COD was 93.8%, 94.2%, 91.6% and 92.7% which also changed little like the desalination rates. The removal rate of chromaticity increased with the increase of salinity, which attained 96.6%, 97.0%, 97.2% and 97.9%, respectively. This study proved that salinity of the feed solution affected little on the removal rate of contaminants but great on the water flux, with the increase of salinity from 30 to 100 g/L, the water flux was 6.05, 4.81, 4.33 and 3.87 LMH with the appropriate temperature (67.5±0.5, 64.5±0.5, 62.5±0.5 and 60.5±0.5 °C) of MD hot side. In a word, FO-MD was first used to treat the high salinity RO water with over 30 g/L total dissolved solids (TDS), FO-MD was a promising new process for high salinity wastewater treatment, and the hybrid system can solve the problem of lower draw solution concentration, and the high-quality production water will be obtained directly by this hybrid system with low membrane fouling tendency.

  11. An adaptive bias - hybrid MD/kMC algorithm for protein folding and aggregation.

    PubMed

    Peter, Emanuel K; Shea, Joan-Emma

    2017-07-05

    In this paper, we present a novel hybrid Molecular Dynamics/kinetic Monte Carlo (MD/kMC) algorithm and apply it to protein folding and aggregation in explicit solvent. The new algorithm uses a dynamical definition of biases throughout the MD component of the simulation, normalized in relation to the unbiased forces. The algorithm guarantees sampling of the underlying ensemble in dependency of one average linear coupling factor 〈α〉 τ . We test the validity of the kinetics in simulations of dialanine and compare dihedral transition kinetics with long-time MD-simulations. We find that for low 〈α〉 τ values, kinetics are in good quantitative agreement. In folding simulations of TrpCage and TrpZip4 in explicit solvent, we also find good quantitative agreement with experimental results and prior MD/kMC simulations. Finally, we apply our algorithm to study growth of the Alzheimer Amyloid Aβ 16-22 fibril by monomer addition. We observe two possible binding modes, one at the extremity of the fibril (elongation) and one on the surface of the fibril (lateral growth), on timescales ranging from ns to 8 μs.

  12. 77 FR 23599 - Special Local Regulations for Marine Events; Potomac River, Charles County, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-20

    ...-AA08 Special Local Regulations for Marine Events; Potomac River, Charles County, MD AGENCY: Coast Guard...; telephone 410-576-2674, email Ronald.L[email protected] . If you have questions on viewing the docket, call... ``Special Local Regulations for Marine Events; Potomac River, Charles County, MD'' in the Federal Register...

  13. Mechanisms Responsible for ω-Pore Currents in Cav Calcium Channel Voltage-Sensing Domains.

    PubMed

    Monteleone, Stefania; Lieb, Andreas; Pinggera, Alexandra; Negro, Giulia; Fuchs, Julian E; Hofer, Florian; Striessnig, Jörg; Tuluc, Petronel; Liedl, Klaus R

    2017-10-03

    Mutations of positively charged amino acids in the S4 transmembrane segment of a voltage-gated ion channel form ion-conducting pathways through the voltage-sensing domain, named ω-current. Here, we used structure modeling and MD simulations to predict pathogenic ω-currents in Ca V 1.1 and Ca V 1.3 Ca 2+ channels bearing several S4 charge mutations. Our modeling predicts that mutations of Ca V 1.1-R1 (R528H/G, R897S) or Ca V 1.1-R2 (R900S, R1239H) linked to hypokalemic periodic paralysis type 1 and of Ca V 1.3-R3 (R990H) identified in aldosterone-producing adenomas conducts ω-currents in resting state, but not during voltage-sensing domain activation. The mechanism responsible for the ω-current and its amplitude depend on the number of charges in S4, the position of the mutated S4 charge and countercharges, and the nature of the replacing amino acid. Functional characterization validates the modeling prediction showing that Ca V 1.3-R990H channels conduct ω-currents at hyperpolarizing potentials, but not upon membrane depolarization compared with wild-type channels. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. In-service communication channel sensing based on reflectometry for TWDM-PON systems

    NASA Astrophysics Data System (ADS)

    Iida, Daisuke; Kuwano, Shigeru; Terada, Jun

    2014-05-01

    Many base stations are accommodated in TWDM-PON based mobile backhaul and fronthaul networks for future radio access, and failed connections in an optical network unit (ONU) wavelength channel severely degrade system performance. A cost effective in-service ONU wavelength channel monitor is essential to ensure proper system operation without failed connections. To address this issue we propose a reflectometry-based remote sensing method that provides wavelength channel information with the optical line terminal (OLT)-ONU distance. The method realizes real-time monitoring of ONU wavelength channels without signal quality degradation. Experimental results show it achieves wavelength channel distinction with high distance resolution.

  15. Opinion of stakeholders on existing curriculum for postgraduate (MD) course in Pharmacology: A survey.

    PubMed

    Badyal, Dinesh K; Daniel, Sujit R

    2016-10-01

    To survey the opinion about various curricular components of Doctor of Medicine (MD) pharmacology curriculum in India by stakeholders, including faculty and students. An online survey was done to evaluate the various curricular components of MD pharmacology curriculum being used in India. A total of 393 respondents including faculty, MD students, and other stakeholders completed the survey. The survey was developed using SurveyMonkey platform and link to survey was E-mailed to stakeholders. The results were expressed as percentages. There was a balanced representation of respondents from various designations, teaching experience, regions, and age groups. Most of the respondents (83%) were aware of the MD pharmacology curriculum. However, they reported that it is more inclined to knowledge domain. About half of respondents (53%) said that animal experiments are being used. The most common teaching methods mentioned are seminars (98.5%), journal clubs (95%), and practical exercises by postgraduates (73%), but there is less use of newer methods (25%) in theory and less of clinical pharmacology exercise (39%) in practical classes. The log books are maintained but not assessed regularly. Internal assessment is sparingly used. The MD pharmacology curriculum needs to be made uniform at the national level and updated to include the newer methods in teaching-learning and assessment. There should be sharing of newer methods at a common platform implemented at the national level.

  16. MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA.

    PubMed

    Meng, Jianmin; Drolet, Joshua R; Monks, Brian G; Golenbock, Douglas T

    2010-09-03

    Lipopolysaccharide (LPS) activates the innate immune response through the Toll-like receptor 4 (TLR4).MD-2 complex. A synthetic lipid A precursor, lipid IV(A), induces an innate immune response in mice but not in humans. Both TLR4 and MD-2 are required for the agonist activity of lipid IV(A) in mice, with TLR4 interacting through specific surface charges at the dimerization interface. In this study, we used site-directed mutagenesis to identify the MD-2 residues that determine lipid IV(A) species specificity. A single mutation of murine MD-2 at the hydrophobic pocket entrance, E122K, substantially reduced the response to lipid IV(A). Combining the murine MD-2 E122K with the murine TLR4 K367E/S386K/R434Q mutations completely abolished the response to lipid IV(A), effectively converting the murine cellular response to a human-like response. In human cells, however, simultaneous mutations of K122E, K125L, Y41F, and R69G on human MD-2 were required to promote a response to lipid IV(A). Combining the human MD-2 quadruple mutations with the human TLR4 E369K/Q436R mutations completely converted the human MD-2/human TLR4 receptor to a murine-like receptor. Because MD-2 residues 122 and 125 reside at the dimerization interface near the pocket entrance, surface charge differences here directly affect receptor dimerization. In comparison, residues 42 and 69 reside at the MD-2/TLR4 interaction surface opposite the dimerization interface. Surface charge differences there likely affect the binding angle and/or rigidity between MD-2 and TLR4, exerting an indirect influence on receptor dimerization and activation. Thus, surface charge differences at the two MD-2/TLR4 interfaces determine the species-specific activation of lipid IV(A).

  17. The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening.

    PubMed

    Li, Tong; Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui; Wang, Aide

    2017-06-01

    The plant hormone ethylene is critical for ripening in climacteric fruits, including apple ( Malus domestica ). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1 , an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2 , encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3 , encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1 This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1 Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. © 2017 American Society of Plant Biologists. All rights reserved.

  18. Gordon Fullerton in PCA (MD-11) Simulator

    NASA Technical Reports Server (NTRS)

    1998-01-01

    NASA research pilot Gordon Fullerton 'flying' in the MD-11 simulator during the Propulsion Controlled Aircraft (PCA) project. This investigation grew out of the crash of a DC-10 airliner on July 19, 1989, following an explosion in the rear engine which caused the loss of all manual flight controls. The flight crew attempted to control the airliner using only the thrust from the two remaining engines. Although the DC-10 crashed during the landing attempt, 184 of the 296 passengers and crew aboard survived. The PCA effort at the Dryden Flight Research Center grew out of the crash, and attempted to develop a means to successfully land an aircraft using only engine thrust. After more than five years of work, on August 29, 1995, Gordon Fullerton made the first PCA touchdown aboard an MD-11 airliner (a later version of the DC-10). The concept was further refined over the years that followed this first landing. Simulators were essential ingredients of the PCA development process. The feasibility of the concept was first tested with an F-15 simulator, then the results of actual flight tests in an F-15 were incorporated back into the simulator. Additional simulations were run on the Boeing 720 airliner simulator used in the Controlled Impact Demonstration project. After the MD-11 test landings, Boeing 747 and 757 simulators tested a wide range of possible situations. Simulations even helped develop a method of landing an airliner if it lost its complete hydraulic system as well as a wing engine, by transferring fuel to shift the center of gravity toward the working engine. The most extreme procedure was undertaken in a 747 simulator. The aircraft simulated the loss of the hydraulic system at 35,000 feet and rolled upside down. Then, the PCA mode was engaged, the airliner righted itself, leveled its wings, and made an approach nearly identical to that of a normal auto landing.

  19. Data Processing for NASA's TDRSS DAMA Channel

    NASA Technical Reports Server (NTRS)

    Long, Christopher C.; Horan, Stephen

    1996-01-01

    A concept for the addition of a Demand Assignment Multiple Access (DAMA) service to NASA's current Space Network (SN) is developed. Specifically, the design of a receiver for the DAMA channel is outlined. Also, an outline of the procedures taken to process the received service request is presented. The modifications to the (SN) system are minimal. The post reception processing is accomplished using standard commercial off the shelf (COTS) packages. The result is a random access system capable of receiving requests for service.

  20. 18 CFR 1304.207 - Channel excavation on TVA-owned residential access shoreland.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Resources TENNESSEE VALLEY AUTHORITY APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER SYSTEM AND REGULATION... the reservoir bottom is exposed and dry. (h) Spoil material from channel excavations must be placed in...

  1. On a quantum particle in laser channels

    NASA Astrophysics Data System (ADS)

    Dik, A. V.; Frolov, E. N.; Dabagov, S. B.

    2018-02-01

    In this paper the effective potential describing interaction of a scalar quantum particle with arbitrary nonuniform laser field is derived for a wide spectrum of the particle energies. The presented method allows to take into account all the features of the effective potential for a scalar particle. The derived expression for effective potential for quantum particle has the same form as the one presented earlier for a classical particle. A special case for channeling of a quantum particle as well as accompanying channeling radiation in a field formed by two crossed plane laser waves is considered. It is shown that relativistic particles moving near the laser channel bottom should be examined as quantum ones at both arbitrarily large longitudinal energies and laser fields of accessible intensities.

  2. Massively parallel processor networks with optical express channels

    DOEpatents

    Deri, R.J.; Brooks, E.D. III; Haigh, R.E.; DeGroot, A.J.

    1999-08-24

    An optical method for separating and routing local and express channel data comprises interconnecting the nodes in a network with fiber optic cables. A single fiber optic cable carries both express channel traffic and local channel traffic, e.g., in a massively parallel processor (MPP) network. Express channel traffic is placed on, or filtered from, the fiber optic cable at a light frequency or a color different from that of the local channel traffic. The express channel traffic is thus placed on a light carrier that skips over the local intermediate nodes one-by-one by reflecting off of selective mirrors placed at each local node. The local-channel-traffic light carriers pass through the selective mirrors and are not reflected. A single fiber optic cable can thus be threaded throughout a three-dimensional matrix of nodes with the x,y,z directions of propagation encoded by the color of the respective light carriers for both local and express channel traffic. Thus frequency division multiple access is used to hierarchically separate the local and express channels to eliminate the bucket brigade latencies that would otherwise result if the express traffic had to hop between every local node to reach its ultimate destination. 3 figs.

  3. Massively parallel processor networks with optical express channels

    DOEpatents

    Deri, Robert J.; Brooks, III, Eugene D.; Haigh, Ronald E.; DeGroot, Anthony J.

    1999-01-01

    An optical method for separating and routing local and express channel data comprises interconnecting the nodes in a network with fiber optic cables. A single fiber optic cable carries both express channel traffic and local channel traffic, e.g., in a massively parallel processor (MPP) network. Express channel traffic is placed on, or filtered from, the fiber optic cable at a light frequency or a color different from that of the local channel traffic. The express channel traffic is thus placed on a light carrier that skips over the local intermediate nodes one-by-one by reflecting off of selective mirrors placed at each local node. The local-channel-traffic light carriers pass through the selective mirrors and are not reflected. A single fiber optic cable can thus be threaded throughout a three-dimensional matrix of nodes with the x,y,z directions of propagation encoded by the color of the respective light carriers for both local and express channel traffic. Thus frequency division multiple access is used to hierarchically separate the local and express channels to eliminate the bucket brigade latencies that would otherwise result if the express traffic had to hop between every local node to reach its ultimate destination.

  4. Ectopically expressing MdPIP1;3, an aquaporin gene, increased fruit size and enhanced drought tolerance of transgenic tomatoes.

    PubMed

    Wang, Lin; Li, Qing-Tian; Lei, Qiong; Feng, Chao; Zheng, Xiaodong; Zhou, Fangfang; Li, Lingzi; Liu, Xuan; Wang, Zhi; Kong, Jin

    2017-12-19

    Water deficit severely reduces apple growth and production, is detrimental to fruit quality and size. This problem is exacerbated as global warming is implicated in producing more severe drought stress. Thus water-efficiency has becomes the major target for apple breeding. A desired apple tree can absorb and transport water efficiently, which not only confers improved drought tolerance, but also guarantees fruit size for higher income returns. Aquaporins, as water channels, control water transportation across membranes and can regulate water flow by changing their amount and activity. The exploration of molecular mechanism of water efficiency and the gene wealth will pave a way for molecular breeding of drought tolerant apple tree. In the current study, we screened out a drought inducible aquaporin gene MdPIP1;3, which specifically enhanced its expression during fruit expansion in 'Fuji' apple (Malus domestica Borkh. cv. Red Fuji). It localized on plasma membranes and belonged to PIP1 subfamily. The tolerance to drought stress enhanced in transgenic tomato plants ectopically expressing MdPIP1;3, showing that the rate of losing water in isolated transgenic leaves was slower than wild type, and stomata of transgenic plants closed sensitively to respond to drought compared with wild type. Besides, length and diameter of transgenic tomato fruits increased faster than wild type, and in final, fruit sizes and fresh weights of transgenic tomatoes were bigger than wild type. Specially, in cell levels, fruit cell size from transgenic tomatoes was larger than wild type, showing that cell number per mm 2 in transgenic fruits was less than wild type. Altogether, ectopically expressing MdPIP1;3 enhanced drought tolerance of transgenic tomatoes partially via reduced water loss controlled by stomata closure in leaves. In addition, the transgenic tomato fruits are larger and heavier with larger cells via more efficient water transportation across membranes. Our research will

  5. A Highly Parallelized Special-Purpose Computer for Many-Body Simulations with an Arbitrary Central Force: MD-GRAPE

    NASA Astrophysics Data System (ADS)

    Fukushige, Toshiyuki; Taiji, Makoto; Makino, Junichiro; Ebisuzaki, Toshikazu; Sugimoto, Daiichiro

    1996-09-01

    We have developed a parallel, pipelined special-purpose computer for N-body simulations, MD-GRAPE (for "GRAvity PipE"). In gravitational N- body simulations, almost all computing time is spent on the calculation of interactions between particles. GRAPE is specialized hardware to calculate these interactions. It is used with a general-purpose front-end computer that performs all calculations other than the force calculation. MD-GRAPE is the first parallel GRAPE that can calculate an arbitrary central force. A force different from a pure 1/r potential is necessary for N-body simulations with periodic boundary conditions using the Ewald or particle-particle/particle-mesh (P^3^M) method. MD-GRAPE accelerates the calculation of particle-particle force for these algorithms. An MD- GRAPE board has four MD chips and its peak performance is 4.2 GFLOPS. On an MD-GRAPE board, a cosmological N-body simulation takes 6O0(N/10^6^)^3/2^ s per step for the Ewald method, where N is the number of particles, and would take 24O(N/10^6^) s per step for the P^3^M method, in a uniform distribution of particles.

  6. 75 FR 81125 - Drawbridge Operation Regulation; Sassafras River, Georgetown, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-27

    ..., in Georgetown, MD. The deviation is necessary to facilitate mechanical repairs and gate replacement... facilitate mechanical repairs and barrier gate replacement. The Sassafras River Bridge (Route 213), at mile...

  7. Functional identification of MdSIZ1 as a SUMO E3 ligase in apple.

    PubMed

    Zhang, Rui-Fen; Guo, Ying; Li, Yuan-Yuan; Zhou, Li-Jie; Hao, Yu-Jin; You, Chun-Xiang

    2016-07-01

    SUMOylation, the conjugation of target proteins with SUMO (small ubiquitin-related modifier), is a type of post-translational modification in eukaryotes and involves the sequential action of activation (E1), conjugation (E2) and ligation (E3) enzymes. In Arabidopsis, the AtSIZ1 protein is a SUMO E3 ligase that promotes the conjugation of SUMO proteins to target substrates. Here, we isolated and identified a SUMO E3 ligase, MdSIZ1, in apple, which was similar to AtSIZ1. SUMOylation analysis showed that MdSIZ1 had SUMO E3 ligase activity in vitro and in vivo. SUMO conjugation was increased by high temperatures, low temperatures, and abscisic acid (ABA). The ectopic expression of MdSIZ1 in Arabidopsis siz1-2 mutant plants partially complemented the morphological mutant phenotype and enhanced the levels of SUMO conjugation. Taken together, these results suggest that MdSIZ1-mediated SUMO conjugation of target proteins is an important process that regulates the adaptation of apple plants to various environmental stresses. Copyright © 2016 Elsevier GmbH. All rights reserved.

  8. Random-access algorithms for multiuser computer communication networks. Doctoral thesis, 1 September 1986-31 August 1988

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

    Papantoni-Kazakos, P.; Paterakis, M.

    1988-07-01

    For many communication applications with time constraints (e.g., transmission of packetized voice messages), a critical performance measure is the percentage of messages transmitted within a given amount of time after their generation at the transmitting station. This report presents a random-access algorithm (RAA) suitable for time-constrained applications. Performance analysis demonstrates that significant message-delay improvement is attained at the expense of minimal traffic loss. Also considered is the case of noisy channels. The noise effect appears at erroneously observed channel feedback. Error sensitivity analysis shows that the proposed random-access algorithm is insensitive to feedback channel errors. Window Random-Access Algorithms (RAAs) aremore » considered next. These algorithms constitute an important subclass of Multiple-Access Algorithms (MAAs); they are distributive, and they attain high throughput and low delays by controlling the number of simultaneously transmitting users.« less

  9. Stephen Baylin, M.D., Explains Genetics and Epigenetics - TCGA

    Cancer.gov

    Stephen Baylin, M.D., at the Johns Hopkins Kimmel Cancer Center discusses the how alterations in the DNA code are deciphered in a combined effort with The Cancer Genome Atlas at the National Cancer Institute to decode the brain cancer genome.

  10. MOLEonline 2.0: interactive web-based analysis of biomacromolecular channels.

    PubMed

    Berka, Karel; Hanák, Ondrej; Sehnal, David; Banás, Pavel; Navrátilová, Veronika; Jaiswal, Deepti; Ionescu, Crina-Maria; Svobodová Vareková, Radka; Koca, Jaroslav; Otyepka, Michal

    2012-07-01

    Biomolecular channels play important roles in many biological systems, e.g. enzymes, ribosomes and ion channels. This article introduces a web-based interactive MOLEonline 2.0 application for the analysis of access/egress paths to interior molecular voids. MOLEonline 2.0 enables platform-independent, easy-to-use and interactive analyses of (bio)macromolecular channels, tunnels and pores. Results are presented in a clear manner, making their interpretation easy. For each channel, MOLEonline displays a 3D graphical representation of the channel, its profile accompanied by a list of lining residues and also its basic physicochemical properties. The users can tune advanced parameters when performing a channel search to direct the search according to their needs. The MOLEonline 2.0 application is freely available via the Internet at http://ncbr.muni.cz/mole or http://mole.upol.cz.

  11. Estimation of Hydrogen-Exchange Protection Factors from MD Simulation Based on Amide Hydrogen Bonding Analysis.

    PubMed

    Park, In-Hee; Venable, John D; Steckler, Caitlin; Cellitti, Susan E; Lesley, Scott A; Spraggon, Glen; Brock, Ansgar

    2015-09-28

    Hydrogen exchange (HX) studies have provided critical insight into our understanding of protein folding, structure, and dynamics. More recently, hydrogen exchange mass spectrometry (HX-MS) has become a widely applicable tool for HX studies. The interpretation of the wealth of data generated by HX-MS experiments as well as other HX methods would greatly benefit from the availability of exchange predictions derived from structures or models for comparison with experiment. Most reported computational HX modeling studies have employed solvent-accessible-surface-area based metrics in attempts to interpret HX data on the basis of structures or models. In this study, a computational HX-MS prediction method based on classification of the amide hydrogen bonding modes mimicking the local unfolding model is demonstrated. Analysis of the NH bonding configurations from molecular dynamics (MD) simulation snapshots is used to determine partitioning over bonded and nonbonded NH states and is directly mapped into a protection factor (PF) using a logistics growth function. Predicted PFs are then used for calculating deuteration values of peptides and compared with experimental data. Hydrogen exchange MS data for fatty acid synthase thioesterase (FAS-TE) collected for a range of pHs and temperatures was used for detailed evaluation of the approach. High correlation between prediction and experiment for observable fragment peptides is observed in the FAS-TE and additional benchmarking systems that included various apo/holo proteins for which literature data were available. In addition, it is shown that HX modeling can improve experimental resolution through decomposition of in-exchange curves into rate classes, which correlate with prediction from MD. Successful rate class decompositions provide further evidence that the presented approach captures the underlying physical processes correctly at the single residue level. This assessment is further strengthened in a comparison of

  12. Estimation of Hydrogen-Exchange Protection Factors from MD Simulation Based on Amide Hydrogen Bonding Analysis

    PubMed Central

    Park, In-Hee; Venable, John D.; Steckler, Caitlin; Cellitti, Susan E.; Lesley, Scott A.; Spraggon, Glen; Brock, Ansgar

    2015-01-01

    Hydrogen exchange (HX) studies have provided critical insight into our understanding of protein folding, structure and dynamics. More recently, Hydrogen Exchange Mass Spectrometry (HX-MS) has become a widely applicable tool for HX studies. The interpretation of the wealth of data generated by HX-MS experiments as well as other HX methods would greatly benefit from the availability of exchange predictions derived from structures or models for comparison with experiment. Most reported computational HX modeling studies have employed solvent-accessible-surface-area based metrics in attempts to interpret HX data on the basis of structures or models. In this study, a computational HX-MS prediction method based on classification of the amide hydrogen bonding modes mimicking the local unfolding model is demonstrated. Analysis of the NH bonding configurations from Molecular Dynamics (MD) simulation snapshots is used to determine partitioning over bonded and non-bonded NH states and is directly mapped into a protection factor (PF) using a logistics growth function. Predicted PFs are then used for calculating deuteration values of peptides and compared with experimental data. Hydrogen exchange MS data for Fatty acid synthase thioesterase (FAS-TE) collected for a range of pHs and temperatures was used for detailed evaluation of the approach. High correlation between prediction and experiment for observable fragment peptides is observed in the FAS-TE and additional benchmarking systems that included various apo/holo proteins for which literature data were available. In addition, it is shown that HX modeling can improve experimental resolution through decomposition of in-exchange curves into rate classes, which correlate with prediction from MD. Successful rate class decompositions provide further evidence that the presented approach captures the underlying physical processes correctly at the single residue level. This assessment is further strengthened in a comparison of

  13. Modeling Nanocomposites for Molecular Dynamics (MD) Simulations

    DTIC Science & Technology

    2015-01-01

    Parallel Simulator ( LAMMPS ) is used as the MD simulator [9], the coordinates must be formatted for use in LAMMPSs. VMD has a set of tools (TopoTools...that can be used to generate a LAMMPS -readable format [6]. 3 Figure 4. Ethylene Monomer Produced From Coordinates in PDB and Rendered Using...where, i and j are the atom subscripts. Simulations are performed using LAMMPS simulation software. Periodic boundary conditions are

  14. 78 FR 17996 - MCM Rail Services LLC-Petition for Retroactive Exemption-In Sparrows Point, Md.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-25

    ... LLC--Petition for Retroactive Exemption--In Sparrows Point, Md. AGENCY: Surface Transportation Board... of rail line in Sparrows Point, Md. (the Line). DATES: MCM's supplemental information is due by April... Railroad, and currently named the Baltimore Industrial Railway, is located at 1430 Sparrows Point Boulevard...

  15. 76 FR 31235 - Safety Zone; Ocean City Air Show, Atlantic Ocean, Ocean City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ...-AA00 Safety Zone; Ocean City Air Show, Atlantic Ocean, Ocean City, MD AGENCY: Coast Guard, DHS. ACTION... in the vicinity of Ocean City, MD to support the Ocean City Air Show. This action is necessary to provide for the safety of life on navigable waters during the Ocean City Air Show. This action is intended...

  16. The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening[OPEN

    PubMed Central

    Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui

    2017-01-01

    The plant hormone ethylene is critical for ripening in climacteric fruits, including apple (Malus domestica). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1, an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2, encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3, encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1. This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1. Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. PMID:28550149

  17. 77 FR 18963 - Airworthiness Directives; MD Helicopters, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-29

    ...) Model MD900 helicopters. The existing AD requires a visual inspection, and if necessary, an eddy current... with an airworthy lower hub. If there is no crack as a result of the visual inspection, eddy current... nondestructive eddy current inspection of the lower hub. That AD was prompted by cracks found on four lower hubs...

  18. Crystal MD: The massively parallel molecular dynamics software for metal with BCC structure

    NASA Astrophysics Data System (ADS)

    Hu, Changjun; Bai, He; He, Xinfu; Zhang, Boyao; Nie, Ningming; Wang, Xianmeng; Ren, Yingwen

    2017-02-01

    Material irradiation effect is one of the most important keys to use nuclear power. However, the lack of high-throughput irradiation facility and knowledge of evolution process, lead to little understanding of the addressed issues. With the help of high-performance computing, we could make a further understanding of micro-level-material. In this paper, a new data structure is proposed for the massively parallel simulation of the evolution of metal materials under irradiation environment. Based on the proposed data structure, we developed the new molecular dynamics software named Crystal MD. The simulation with Crystal MD achieved over 90% parallel efficiency in test cases, and it takes more than 25% less memory on multi-core clusters than LAMMPS and IMD, which are two popular molecular dynamics simulation software. Using Crystal MD, a two trillion particles simulation has been performed on Tianhe-2 cluster.

  19. Mendel,MD: A user-friendly open-source web tool for analyzing WES and WGS in the diagnosis of patients with Mendelian disorders

    PubMed Central

    D. Linhares, Natália; Pena, Sérgio D. J.

    2017-01-01

    Whole exome and whole genome sequencing have both become widely adopted methods for investigating and diagnosing human Mendelian disorders. As pangenomic agnostic tests, they are capable of more accurate and agile diagnosis compared to traditional sequencing methods. This article describes new software called Mendel,MD, which combines multiple types of filter options and makes use of regularly updated databases to facilitate exome and genome annotation, the filtering process and the selection of candidate genes and variants for experimental validation and possible diagnosis. This tool offers a user-friendly interface, and leads clinicians through simple steps by limiting the number of candidates to achieve a final diagnosis of a medical genetics case. A useful innovation is the “1-click” method, which enables listing all the relevant variants in genes present at OMIM for perusal by clinicians. Mendel,MD was experimentally validated using clinical cases from the literature and was tested by students at the Universidade Federal de Minas Gerais, at GENE–Núcleo de Genética Médica in Brazil and at the Children’s University Hospital in Dublin, Ireland. We show in this article how it can simplify and increase the speed of identifying the culprit mutation in each of the clinical cases that were received for further investigation. Mendel,MD proved to be a reliable web-based tool, being open-source and time efficient for identifying the culprit mutation in different clinical cases of patients with Mendelian Disorders. It is also freely accessible for academic users on the following URL: https://mendelmd.org. PMID:28594829

  20. Esthetic abutment design for angulated screw channels: A technical report.

    PubMed

    Sakamoto, Satoshi; Ro, Munehiko; Al Ardah, Aladdin; Goodacre, Charles

    2017-11-15

    Angulated screw channel system abutments (ASCs) have recently been introduced to address the problem with visible screw access that may compromise esthetics. ASCs allow the screw access to be modified up to 25 degrees relative to the implant axis. However, a widened channel, which may cause thinning of the facial ceramic, is needed at the implant screw head to allow for proper engagement of the screwdriver. This technical report introduces a custom titanium insert design, the Satoshi Sakamoto (SS) abutment. The SS abutment consists of a custom titanium metal insert and zirconia coping in which the access hole is located in an esthetic position with an ASC system. The SS abutment results in a crown with more normal crown dimensions that also provides more space for the soft tissues. This SS abutment design allows clinicians to obtain screw-retained restorations with optimal esthetics and mechanical strength. Copyright © 2017 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  1. Review of 40-year MD theses in medical oncology.

    PubMed

    Zeeneldin, Ahmed; Diyaa, Amira; Moneer, Manar; Elgammal, Mosaad; Buhoush, Wafa

    2014-09-01

    It is almost 40 years since the foundation of the Medical Oncology (MO) Department. We aimed to appraise the clinical research to fulfill the Medical Doctorate (MD) degree in MO at the National Cancer Institute, Cairo University (NCI, CU). This review included 62 MD theses containing 66 studies. They were reviewed regarding aims, type of study, clinical trial phase, design and methodology, statistical tests, results, limitations, consent and IRB approval. Theses were grouped into 3 periods: 1970-1989, 1990-1999 and 2000-2008. Almost 76% of the studies were interventional and 24% were observational. Informed consent and Institutional Review Board approval were mentioned in 18 and 2 studies, respectively. While all studies mentioned the aims, none, clearly mentioned the research question. Outcomes were mainly efficacy followed by safety. Study design was inadequately considered, especially in 70's-80's period (p=0.038). Median sample size and study duration were almost stable through the three periods (p=0.441, 0.354, respectively). Most of the studies used both descriptive and analytical statistical methods. In a descending order, researched cancers were lymphoma, breast, leukemia, liver, urinary bladder, lung and colorectal. The commonest stages researched were IV and III. The number of studies focused on assessing biomarkers, biomarkers plus drugs/procedures, drugs and procedures are 20, 20, 16 and 6, respectively. With time, research within MD theses in MO increased quantitatively and qualitatively. Improvements were noticeable in documentation of study design. Copyright © 2014. Production and hosting by Elsevier B.V.

  2. Multiuser TOA Estimation Algorithm in DS-CDMA Sparse Channel for Radiolocation

    NASA Astrophysics Data System (ADS)

    Kim, Sunwoo

    This letter considers multiuser time delay estimation in a sparse channel environment for radiolocation. The generalized successive interference cancellation (GSIC) algorithm is used to eliminate the multiple access interference (MAI). To adapt GSIC to sparse channels the alternating maximization (AM) algorithm is considered, and the continuous time delay of each path is estimated without requiring a priori known data sequences.

  3. Biochemical characterisation of MdCXE1, a carboxylesterase from apple that is expressed during fruit ripening.

    PubMed

    Souleyre, Edwige J F; Marshall, Sean D G; Oakeshott, John G; Russell, Robyn J; Plummer, Kim M; Newcomb, Richard D

    2011-05-01

    Esters are an important component of apple (Malus×domestica) flavour. Their biosynthesis increases in response to the ripening hormone ethylene, but their metabolism by carboxylesterases (CXEs) is poorly understood. We have identified 16 members of the CXE multigene family from the commercial apple cultivar, 'Royal Gala', that contain all the conserved features associated with CXE members of the α/β hydrolase fold superfamily. The expression of two genes, MdCXE1 and MdCXE16 was characterised in an apple fruit development series and in a transgenic line of 'Royal Gala' (AO3) that is unable to synthesise ethylene in fruit. In wild-type MdCXE1 is expressed at low levels during early stages of fruit development, rising to a peak of expression in apple fruit at harvest maturity. It is not significantly up-regulated by ethylene in the skin of AO3 fruit. MdCXE16 is expressed constitutively in wild-type throughout fruit development, and is up-regulated by ethylene in skin of AO3 fruit. Semi-purified recombinant MdCXE1 was able to hydrolyse a range of 4-methyl umbelliferyl ester substrates that included those containing acyl moieties that are found in esters produced by apple fruit. Kinetic characterisation of MdCXE1 revealed that the enzyme could be inhibited by organophosphates and that its ability to hydrolyse esters showed increasing affinity (K(m)) but decreasing turnover (k(cat)) as substrate acyl carbon length increases from C2 to C16. Our results suggest that MdCXE1 may have an impact on apple flavour through its ability to hydrolyse relevant flavour esters in ripe apple fruit. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. From in silico to in vitro: a trip to reveal flavonoid binding on the Rattus norvegicus Kir6.1 ATP-sensitive inward rectifier potassium channel.

    PubMed

    Trezza, Alfonso; Cicaloni, Vittoria; Porciatti, Piera; Langella, Andrea; Fusi, Fabio; Saponara, Simona; Spiga, Ottavia

    2018-01-01

    ATP-sensitive inward rectifier potassium channels (Kir), are a potassium channel family involved in many physiological processes. K ATP dysfunctions are observed in several diseases such as hypoglycaemia, hyperinsulinemia, Prinzmetal angina-like symptoms, cardiovascular diseases. A broader view of the K ATP mechanism is needed in order to operate on their regulation, and in this work we clarify the structure of the Rattus norvegicus ATP-sensitive inward rectifier potassium channel 8 (Kir6.1), which has been obtained through a homology modelling procedure. Due to the medical use of flavonoids, a considerable increase in studies on their influence on human health has recently been observed, therefore our aim is to study, through computational methods, the three-dimensional (3D) conformation together with mechanism of action of Kir6.1 with three flavonoids. Computational analysis by performing molecular dynamics (MD) and docking simulation on rat 3D modelled structure have been completed, in its closed and open conformation state and in complex with Quercetin, 5-Hydroxyflavone and Rutin flavonoids. Our study showed that only Quercetin and 5-Hydroxyflavone were responsible for a significant down-regulation of the Kir6.1 activity, stabilising it in a closed conformation. This hypothesis was supported by in vitro experiments demonstrating that Quercetin and 5-Hydroxyflavone were capable to inhibit K ATP currents of rat tail main artery myocytes recorded by the patch-clamp technique. Combined methodological approaches, such as molecular modelling, docking and MD simulations of Kir6.1 channel, used to elucidate flavonoids intrinsic mechanism of action, are introduced, revealing a new potential druggable protein site.

  5. 75 FR 1705 - Drawbridge Operation Regulations; Curtis Creek, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ..., mile 0.9, at Baltimore, MD. The deviation is necessary to facilitate mechanical repairs to the bridge... facilitate mechanical repairs. The I695 Bridge, a double-leaf bascule drawbridge, has a vertical clearance in...

  6. 78 FR 38001 - Special Local Regulations; Marine Events, Breton Bay; St. Mary's County, Leonardtown, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-25

    ...-AA08 Special Local Regulations; Marine Events, Breton Bay; St. Mary's County, Leonardtown, MD AGENCY... marine event to be held on the waters of Breton Bay in St. Mary's County, Maryland on July 13, 2013, and... ``Special Local Regulations; Marine Events, Breton Bay; St. Mary's County, Leonardtown, MD'' in the Federal...

  7. The Structural Basis for Lipid and Endotoxin Binding in RP105-MD-1, and Consequences for Regulation of Host Lipopolysaccharide Sensitivity.

    PubMed

    Ortiz-Suarez, Maite L; Bond, Peter J

    2016-01-05

    MD-1 is a member of the MD-2-related lipid-recognition (ML) family, and associates with RP105, a cell-surface protein that resembles Toll-like receptor 4 (TLR4). The RP105⋅MD-1 complex has been proposed to play a role in fine-tuning the innate immune response to endotoxin such as bacterial lipopolysaccharide (LPS) via TLR4⋅MD-2, but controversy surrounds its mechanism. We have used atomically detailed simulations to reveal the structural basis for ligand binding and consequent functional dynamics of MD-1 and the RP105 complex. We rationalize reports of endogenous phospholipid binding, by showing that they prevent collapse of the malleable MD-1 fold, before refining crystallographic models and uncovering likely binding modes for LPS analogs. Subsequent binding affinity calculations reveal that endotoxin specificity arises from the entropic cost of expanding the MD-1 cavity to accommodate bulky lipid tails, and support the role of MD-1 as a "sink" that sequesters endotoxin from TLR4 and stabilizes RP105/TLR4 interactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Semaphorin 3F Is a Bifunctional Guidance Cue for Dopaminergic Axons and Controls Their Fasciculation, Channeling, Rostral Growth, and Intracortical Targeting

    PubMed Central

    Kolk, Sharon M.; Gunput, Rou-Afza F.; Tran, Tracy S.; van den Heuvel, Dianne M. A.; Prasad, Asheeta A.; Hellemons, Anita J. C. G. M.; Adolfs, Youri; Ginty, David D.; Kolodkin, Alex L.; Burbach, J. Peter H.; Smidt, Marten P.; Pasterkamp, R. Jeroen

    2010-01-01

    Dopaminergic neurons in the mesodiencephalon (mdDA neurons) make precise synaptic connections with targets in the forebrain via the mesostriatal, mesolimbic, and mesoprefrontal pathways. Because of the functional importance of these remarkably complex ascending axon pathways and their implication in human disease, the mechanisms underlying the development of these connections are of considerable interest. Despite extensive in vitro studies, the molecular determinants that ensure the perfect formation of these pathways in vivo remain mostly unknown. Here, we determine the embryonic origin and ontogeny of the mouse mesoprefrontal pathway and use these data to reveal an unexpected requirement for semaphorin 3F (Sema3F) and its receptor neuropilin-2 (Npn-2) during mdDA pathway development using tissue culture approaches and analysis of sema3F−/−, npn-2−/−, and npn-2−/−;TH-Cre mice. We show that Sema3F is a bifunctional guidance cue for mdDA axons, some of which have the remarkable ability to regulate their responsiveness to Sema3F as they develop. During early developmental stages, Sema3F chemorepulsion controls previously uncharacterized aspects of mdDA pathway development through both Npn-2-dependent (axon fasciculation and channeling) and Npn-2-independent (rostral growth) mechanisms. Later on, chemoattraction mediated by Sema3F and Npn-2 is required to orient mdDA axon projections in the cortical plate of the medial prefrontal cortex. This latter finding demonstrates that regulation of axon orientation in the target field occurs by chemoattractive mechanisms, and this is likely to also apply to other neural systems. In all, this study provides a framework for additional dissection of the molecular basis of mdDA pathway development and disease. PMID:19812329

  9. Population patch clamp electrophysiology: a breakthrough technology for ion channel screening.

    PubMed

    Dale, Tim J; Townsend, Claire; Hollands, Emma C; Trezise, Derek J

    2007-10-01

    Population patch clamp (PPC) is a novel high throughput planar array electrophysiology technique that allows ionic currents to be recorded from populations of cells under voltage clamp. For the drug discovery pharmacologist, PPC promises greater speed and precision than existing methods for screening compounds at voltage-gated ion channel targets. Moreover, certain constitutively active or slow-ligand gated channels that have hitherto proved challenging to screen with planar array electrophysiology (e.g. SK/IK channels) are now more accessible. In this article we review early findings using PPC and provide a perspective on its likely impact on ion channel drug discovery. To support this, we include some new data on ion channel assay duplexing and on modulator assays, approaches that have thus far not been described.

  10. Validity of the Medical College Admission Test for predicting MD-PhD student outcomes.

    PubMed

    Bills, James L; VanHouten, Jacob; Grundy, Michelle M; Chalkley, Roger; Dermody, Terence S

    2016-03-01

    The Medical College Admission Test (MCAT) is a quantitative metric used by MD and MD-PhD programs to evaluate applicants for admission. This study assessed the validity of the MCAT in predicting training performance measures and career outcomes for MD-PhD students at a single institution. The study population consisted of 153 graduates of the Vanderbilt Medical Scientist Training Program (combined MD-PhD program) who matriculated between 1963 and 2003 and completed dual-degree training. This population was divided into three cohorts corresponding to the version of the MCAT taken at the time of application. Multivariable regression (logistic for binary outcomes and linear for continuous outcomes) was used to analyze factors associated with outcome measures. The MCAT score and undergraduate GPA (uGPA) were treated as independent variables; medical and graduate school grades, time-to-PhD defense, USMLE scores, publication number, and career outcome were dependent variables. For cohort 1 (1963-1977), MCAT score was not associated with any assessed outcome, although uGPA was associated with medical school preclinical GPA and graduate school GPA (gsGPA). For cohort 2 (1978-1991), MCAT score was associated with USMLE Step II score and inversely correlated with publication number, and uGPA was associated with preclinical GPA (mspGPA) and clinical GPA (mscGPA). For cohort 3 (1992-2003), the MCAT score was associated with mscGPA, and uGPA was associated with gsGPA. Overall, MCAT score and uGPA were inconsistent or weak predictors of training metrics and career outcomes for this population of MD-PhD students.

  11. MD and BCA simulations of He and H bombardment of fuzz in bcc elements

    NASA Astrophysics Data System (ADS)

    Klaver, T. P. C.; Zhang, S.; Nordlund, K.

    2017-08-01

    We present results of MD simulations of low energy He ion bombardment of low density fuzz in bcc elements. He ions can penetrate several micrometers into sparse fuzz, which allows for a sufficient He flux through it to grow the fuzz further. He kinetic energy falls off exponentially with penetration depth. A BCA code was used to carry out the same ion bombardment on the same fuzz structures as in MD simulations, but with simpler, 10 million times faster calculations. Despite the poor theoretical basis of the BCA at low ion energies, and the use of somewhat different potentials in MD and BCA calculations, the ion penetration depths predicted by BCA are only ∼12% less than those predicted by MD. The MD-BCA differences are highly systematic and trends in the results of the two methods are very similar. We have carried out more than 200 BCA calculation runs of ion bombardment of fuzz, in which parameters in the ion bombardment process were varied. For most parameters, the results show that the ion bombardment process is quite generic. The ion species (He or H), ion mass, fuzz element (W, Ta, Mo, Fe) and fuzz element lattice parameter turned out to have a modest influence on ion penetration depths at most. An off-normal angle of incidence strongly reduces the ion penetration depth. Increasing the ion energy increases the ion penetration, but the rate by which ion energy drops off at high ion energies follows the same exponential pattern as at lower energies.

  12. CCSDS Advanced Orbiting Systems Virtual Channel Access Service for QoS MACHETE Model

    NASA Technical Reports Server (NTRS)

    Jennings, Esther H.; Segui, John S.

    2011-01-01

    To support various communications requirements imposed by different missions, interplanetary communication protocols need to be designed, validated, and evaluated carefully. Multimission Advanced Communications Hybrid Environment for Test and Evaluation (MACHETE), described in "Simulator of Space Communication Networks" (NPO-41373), NASA Tech Briefs, Vol. 29, No. 8 (August 2005), p. 44, combines various tools for simulation and performance analysis of space networks. The MACHETE environment supports orbital analysis, link budget analysis, communications network simulations, and hardware-in-the-loop testing. By building abstract behavioral models of network protocols, one can validate performance after identifying the appropriate metrics of interest. The innovators have extended the MACHETE model library to include a generic link-layer Virtual Channel (VC) model supporting quality-of-service (QoS) controls based on IP streams. The main purpose of this generic Virtual Channel model addition was to interface fine-grain flow-based QoS (quality of service) between the network and MAC layers of the QualNet simulator, a commercial component of MACHETE. This software model adds the capability of mapping IP streams, based on header fields, to virtual channel numbers, allowing extended QoS handling at link layer. This feature further refines the QoS v existing at the network layer. QoS at the network layer (e.g. diffserv) supports few QoS classes, so data from one class will be aggregated together; differentiating between flows internal to a class/priority is not supported. By adding QoS classification capability between network and MAC layers through VC, one maps multiple VCs onto the same physical link. Users then specify different VC weights, and different queuing and scheduling policies at the link layer. This VC model supports system performance analysis of various virtual channel link-layer QoS queuing schemes independent of the network-layer QoS systems.

  13. MD1003 (high-dose biotin) for the treatment of progressive multiple sclerosis: A randomised, double-blind, placebo-controlled study.

    PubMed

    Tourbah, Ayman; Lebrun-Frenay, Christine; Edan, Gilles; Clanet, Michel; Papeix, Caroline; Vukusic, Sandra; De Sèze, Jerome; Debouverie, Marc; Gout, Olivier; Clavelou, Pierre; Defer, Gilles; Laplaud, David-Axel; Moreau, Thibault; Labauge, Pierre; Brochet, Bruno; Sedel, Frédéric; Pelletier, Jean

    2016-11-01

    Treatment with MD1003 (high-dose biotin) showed promising results in progressive multiple sclerosis (MS) in a pilot open-label study. To confirm the efficacy and safety of MD1003 in progressive MS in a double-blind, placebo-controlled study. Patients (n = 154) with a baseline Expanded Disability Status Scale (EDSS) score of 4.5-7 and evidence of disease worsening within the previous 2 years were randomised to 12-month MD1003 (100 mg biotin) or placebo thrice daily, followed by 12-month MD1003 for all patients. The primary endpoint was the proportion of patients with disability reversal at month 9, confirmed at month 12, defined as an EDSS decrease of ⩾1 point (⩾0.5 for EDSS 6-7) or a ⩾20% decrease in timed 25-foot walk time compared with the best baseline among screening or randomisation visits. A total of 13 (12.6%) MD1003-treated patients achieved the primary endpoint versus none of the placebo-treated patients (p = 0.005). MD1003 treatment also reduced EDSS progression and improved clinical impression of change compared with placebo. Efficacy was maintained over follow-up, and the safety profile of MD1003 was similar to that of placebo. MD1003 achieves sustained reversal of MS-related disability in a subset of patients with progressive MS and is well tolerated. © The Author(s), 2016.

  14. Theory of Transport of Long Polymer Molecules through Carbon Nanotube Channels

    NASA Technical Reports Server (NTRS)

    Wei, Chenyu; Srivastava, Deepak

    2003-01-01

    A theory of transport of long chain polymer molecules through carbon nanotube (CNT) channels is developed using Fokker-Planck equation and direct molecular dynamics (MD) simulations. The mean transport or translocation time tau is found to depend on the chemical potential energy, entropy and diffusion coefficient. A power law dependence tau approx. N(sup 2)is found where N is number of monomers in a molecule. For 10(exp 5)-unit long polyethylene molecules, tau is estimated to be approx. 1micro-s. The diffusion coefficient of long polymer molecules inside CNTs, like that of short ones, are found to be few orders of magnitude larger than in ordinary silicate based zeolite systems.

  15. The cold-induced basic helix-loop-helix transcription factor gene MdCIbHLH1 encodes an ICE-like protein in apple

    PubMed Central

    2012-01-01

    Background Plant growth is greatly affected by low temperatures, and the expression of a number of genes is induced by cold stress. Although many genes in the cold signaling pathway have been identified in Arabidopsis, little is known about the transcription factors involved in the cold stress response in apple. Results Here, we show that the apple bHLH (basic helix-loop-helix) gene MdCIbHLH1 (Cold-Induced bHLH1), which encodes an ICE-like protein, was noticeably induced in response to cold stress. The MdCIbHLH1 protein specifically bound to the MYC recognition sequences in the AtCBF3 promoter, and MdCIbHLH1 overexpression enhanced cold tolerance in transgenic Arabidopsis. In addition, the MdCIbHLH1 protein bound to the promoters of MdCBF2 and favorably contributed to cold tolerance in transgenic apple plants by upregulating the expression of MdCBF2 through the CBF (C-repeat-binding factor) pathway. Our findings indicate that MdCIbHLH1 functions in stress tolerance in different species. For example, ectopic MdCIbHLH1 expression conferred enhanced chilling tolerance in transgenic tobacco. Finally, we observed that cold induces the degradation of the MdCIbHLH1 protein in apple and that this degradation was potentially mediated by ubiquitination and sumoylation. Conclusions Based on these findings, MdCIbHLH1 encodes a transcription factor that is important for the cold tolerance response in apple. PMID:22336381

  16. Locating the Anion-selectivity Filter of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Chloride Channel

    PubMed Central

    Cheung, Min; Akabas, Myles H.

    1997-01-01

    The cystic fibrosis transmembrane conductance regulator forms an anion-selective channel; the site and mechanism of charge selectivity is unknown. We previously reported that cysteines substituted, one at a time, for Ile331, Leu333, Arg334, Lys335, Phe337, Ser341, Ile344, Arg347, Thr351, Arg352, and Gln353, in and flanking the sixth membrane-spanning segment (M6), reacted with charged, sulfhydryl-specific, methanethiosulfonate (MTS) reagents. We inferred that these residues are on the water-accessible surface of the protein and may line the ion channel. We have now measured the voltage-dependence of the reaction rates of the MTS reagents with the accessible, engineered cysteines. By comparing the reaction rates of negatively and positively charged MTS reagents with these cysteines, we measured the extent of anion selectivity from the extracellular end of the channel to eight of the accessible residues. We show that the major site determining anion vs. cation selectivity is near the cytoplasmic end of the channel; it favors anions by ∼25-fold and may involve the residues Arg347 and Arg352. From the voltage dependence of the reaction rates, we calculated the electrical distance to the accessible residues. For the residues from Leu333 to Ser341 the electrical distance is not significantly different than zero; it is significantly different than zero for the residues Thr351 to Gln353. The maximum electrical distance measured was 0.6 suggesting that the channel extends more cytoplasmically and may include residues flanking the cytoplasmic end of the M6 segment. Furthermore, the electrical distance calculations indicate that R352C is closer to the extracellular end of the channel than either of the adjacent residues. We speculate that the cytoplasmic end of the M6 segment may loop back into the channel narrowing the lumen and thereby forming both the major resistance to current flow and the anion-selectivity filter. PMID:9089437

  17. Improved estimation of ligand macromolecule binding affinities by linear response approach using a combination of multi-mode MD simulation and QM/MM methods

    NASA Astrophysics Data System (ADS)

    Khandelwal, Akash; Balaz, Stefan

    2007-01-01

    Structure-based predictions of binding affinities of ligands binding to proteins by coordination bonds with transition metals, covalent bonds, and bonds involving charge re-distributions are hindered by the absence of proper force fields. This shortcoming affects all methods which use force-field-based molecular simulation data on complex formation for affinity predictions. One of the most frequently used methods in this category is the Linear Response (LR) approach of Åquist, correlating binding affinities with van der Waals and electrostatic energies, as extended by Jorgensen's inclusion of solvent-accessible surface areas. All these terms represent the differences, upon binding, in the ensemble averages of pertinent quantities, obtained from molecular dynamics (MD) or Monte Carlo simulations of the complex and of single components. Here we report a modification of the LR approach by: (1) the replacement of the two energy terms through the single-point QM/MM energy of the time-averaged complex structure from an MD simulation; and (2) a rigorous consideration of multiple modes (mm) of binding. The first extension alleviates the force-field related problems, while the second extension deals with the ligands exhibiting large-scale motions in the course of an MD simulation. The second modification results in the correlation equation that is nonlinear in optimized coefficients, but does not lead to an increase in the number of optimized coefficients. The application of the resulting mm QM/MM LR approach to the inhibition of zinc-dependent gelatinase B (matrix metalloproteinase 9) by 28 hydroxamate ligands indicates a significant improvement of descriptive and predictive abilities.

  18. Neurology Falls. Patient Falls Risk Assessment, Neurology Clinic, Johns Hopkins Hospital, Baltimore, MD

    DTIC Science & Technology

    2009-07-06

    currently valid ()MB control number. PLEASE DO NOT RETURN YOf IR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 21 JUL 2008 2. REPORT TYPE Final...Hospital, Baltimore, MD 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) LT John M Gardner, MSC, USN 5d. PROJECT...NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) Johns Hopkins Hospital, Baltimore, MD Residency Site

  19. 77 FR 22523 - Safety Zone; 2012 Ocean City Air Show; Atlantic Ocean, Ocean City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-16

    ...-AA00 Safety Zone; 2012 Ocean City Air Show; Atlantic Ocean, Ocean City, MD AGENCY: Coast Guard, DHS... the navigable waters of the Atlantic Ocean in Ocean City, MD. This action is necessary to provide for the safety of life on navigable waters during the 2012 Ocean City Air Show. This action is intended to...

  20. MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery

    PubMed Central

    Li, Rongzhong; Macnamara, Lindsay M.; Leuchter, Jessica D.; Alexander, Rebecca W.; Cho, Samuel S.

    2015-01-01

    While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. Throughout the review, we briefly discuss important historical events to provide a context for how far the field has progressed over the past few decades. We then review the background of tRNA molecules, aminoacyl-tRNA synthetases, and current state of the art MD simulation techniques for those who may be unfamiliar with any of those fields. Recent MD simulations of tRNA dynamics and folding and of aminoacyl-tRNA synthetase dynamics and mechanistic characterizations are discussed. We highlight the recent successes and discuss how important questions can be addressed using current MD simulations techniques. We also outline several natural next steps for computational studies of AARS:tRNA complexes. PMID:26184179

  1. Structure and functional dynamics characterization of the ion channel of the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH) transmembrane domain by combining molecular dynamics with excited normal modes.

    PubMed

    Araujo, Gabriela C; Silva, Ricardo H T; Scott, Luis P B; Araujo, Alexandre S; Souza, Fatima P; de Oliveira, Ronaldo Junio

    2016-12-01

    The human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infection in children and elderly people worldwide. Its genome encodes 11 proteins including SH protein, whose functions are not well known. Studies show that SH protein increases RSV virulence degree and permeability to small compounds, suggesting it is involved in the formation of ion channels. The knowledge of SH structure and function is fundamental for a better understanding of its infection mechanism. The aim of this study was to model, characterize, and analyze the structural behavior of SH protein in the phospholipids bilayer environment. Molecular modeling of SH pentameric structure was performed, followed by traditional molecular dynamics (MD) simulations of the protein immersed in the lipid bilayer. Molecular dynamics with excited normal modes (MDeNM) was applied in the resulting system in order to investigate long time scale pore dynamics. MD simulations support that SH protein is stable in its pentameric form. Simulations also showed the presence of water molecules within the bilayer by density distribution, thus confirming that SH protein is a viroporin. This water transport was also observed in MDeNM studies with histidine residues of five chains (His22 and His51), playing a key role in pore permeability. The combination of traditional MD and MDeNM was a very efficient protocol to investigate functional conformational changes of transmembrane proteins that act as molecular channels. This protocol can support future investigations of drug candidates by acting on SH protein to inhibit viral infection. Graphical Abstract The ion channel of the human respiratory syncytial virus (hRSV) small hydrophobic protein (SH) transmembrane domainᅟ.

  2. Going beyond Clustering in MD Trajectory Analysis: An Application to Villin Headpiece Folding

    PubMed Central

    Rajan, Aruna; Freddolino, Peter L.; Schulten, Klaus

    2010-01-01

    Recent advances in computing technology have enabled microsecond long all-atom molecular dynamics (MD) simulations of biological systems. Methods that can distill the salient features of such large trajectories are now urgently needed. Conventional clustering methods used to analyze MD trajectories suffer from various setbacks, namely (i) they are not data driven, (ii) they are unstable to noise and changes in cut-off parameters such as cluster radius and cluster number, and (iii) they do not reduce the dimensionality of the trajectories, and hence are unsuitable for finding collective coordinates. We advocate the application of principal component analysis (PCA) and a non-metric multidimensional scaling (nMDS) method to reduce MD trajectories and overcome the drawbacks of clustering. To illustrate the superiority of nMDS over other methods in reducing data and reproducing salient features, we analyze three complete villin headpiece folding trajectories. Our analysis suggests that the folding process of the villin headpiece is structurally heterogeneous. PMID:20419160

  3. Going beyond clustering in MD trajectory analysis: an application to villin headpiece folding.

    PubMed

    Rajan, Aruna; Freddolino, Peter L; Schulten, Klaus

    2010-04-15

    Recent advances in computing technology have enabled microsecond long all-atom molecular dynamics (MD) simulations of biological systems. Methods that can distill the salient features of such large trajectories are now urgently needed. Conventional clustering methods used to analyze MD trajectories suffer from various setbacks, namely (i) they are not data driven, (ii) they are unstable to noise and changes in cut-off parameters such as cluster radius and cluster number, and (iii) they do not reduce the dimensionality of the trajectories, and hence are unsuitable for finding collective coordinates. We advocate the application of principal component analysis (PCA) and a non-metric multidimensional scaling (nMDS) method to reduce MD trajectories and overcome the drawbacks of clustering. To illustrate the superiority of nMDS over other methods in reducing data and reproducing salient features, we analyze three complete villin headpiece folding trajectories. Our analysis suggests that the folding process of the villin headpiece is structurally heterogeneous.

  4. Cross-point-type spin-transfer-torque magnetoresistive random access memory cell with multi-pillar vertical body channel MOSFET

    NASA Astrophysics Data System (ADS)

    Sasaki, Taro; Endoh, Tetsuo

    2018-04-01

    In this paper, from the viewpoint of cell size and sensing margin, the impact of a novel cross-point-type one transistor and one magnetic tunnel junction (1T–1MTJ) spin-transfer-torque magnetoresistive random access memory (STT-MRAM) cell with a multi-pillar vertical body channel (BC) MOSFET is shown for high density and wide sensing margin STT-MRAM, with a 10 ns writing period and 1.2 V V DD. For that purpose, all combinations of n/p-type MOSFETs and bottom/top-pin MTJs are compared, where the diameter of MTJ (D MTJ) is scaled down from 55 to 15 nm and the tunnel magnetoresistance (TMR) ratio is increased from 100 to 200%. The results show that, benefiting from the proposed STT-MRAM cell with no back bias effect, the MTJ with a high TMR ratio (200%) can be used in the design of smaller STT-MRAM cells (over 72.6% cell size reduction), which is a difficult task for conventional planar MOSFET based design.

  5. [Professor Frantisek Por MD and Professor Robert Klopstock MD, students at Budapest and Prague Faculties of Medicine].

    PubMed

    Mydlík, M; Derzsiová, K

    2010-11-01

    Professor Frantisek Por MD and Professor Robert Klopstock MD were contemporaries, both born in 1899, one in Zvolen, the other in Dombovar, at the time of Austro-Hungarian Monarchy. Prof. Por attended the Faculty of Medicine in Budapest from 1918 to 1920, and Prof. Klopstock studied at the same place between 1917 and 1919. From 1920 until graduation on 6th February 1926, Prof. Por continued his studies at the German Faculty of Medicine, Charles University in Prague. Prof. Klopstock had to interrupt his studies in Budapest due to pulmonary tuberculosis; he received treatment at Tatranske Matliare where he befriended Franz Kafka. Later, upon Kafka's encouragement, he changed institutions and continued his studies at the German Faculty of Medicine, Charles University in Prague, where he graduated the first great go. It is very likely that, during their studies in Budapest and Prague, both professors met repeatedly, even though their life paths later separated. Following his graduation, Prof. Por practiced as an internist in Prague, later in Slovakia, and from 1945 in Kosice. In 1961, he was awarded the title of university professor of internal medicine at the Faculty of Medicine, Pavol Jozef Safarik University in Kosice, where he practiced until his death in 1980. Prof. Klopstock continued his studies in Kiel and Berlin. After his graduation in 1933, he practiced in Berlin as a surgeon and in 1938 left for USA. In 1962, he was awarded the title of university professor of pulmonary surgery in NewYork, where he died in 1972.

  6. Applicability of effective fragment potential version 2 - Molecular dynamics (EFP2-MD) simulations for predicting excess properties of mixed solvents

    NASA Astrophysics Data System (ADS)

    Kuroki, Nahoko; Mori, Hirotoshi

    2018-02-01

    Effective fragment potential version 2 - molecular dynamics (EFP2-MD) simulations, where the EFP2 is a polarizable force field based on ab initio electronic structure calculations were applied to water-methanol binary mixture. Comparing EFP2s defined with (aug-)cc-pVXZ (X = D,T) basis sets, it was found that large sets are necessary to generate sufficiently accurate EFP2 for predicting mixture properties. It was shown that EFP2-MD could predict the excess molar volume. Since the computational cost of EFP2-MD are far less than ab initio MD, the results presented herein demonstrate that EFP2-MD is promising for predicting physicochemical properties of novel mixed solvents.

  7. The knock-down of the expression of MdMLO19 reduces susceptibility to powdery mildew (Podosphaera leucotricha) in apple (Malus domestica).

    PubMed

    Pessina, Stefano; Angeli, Dario; Martens, Stefan; Visser, Richard G F; Bai, Yuling; Salamini, Francesco; Velasco, Riccardo; Schouten, Henk J; Malnoy, Mickael

    2016-10-01

    Varieties resistant to powdery mildew (PM; caused by Podosphaera leucotricha) are a major component of sustainable apple production. Resistance can be achieved by knocking-out susceptibility S-genes to be singled out among members of the MLO (Mildew Locus O) gene family. Candidates are MLO S-genes of phylogenetic clade V up-regulated upon PM inoculation, such as MdMLO11 and 19 (clade V) and MdMLO18 (clade VII). We report the knock-down through RNA interference of MdMLO11 and 19, as well as the complementation of resistance with MdMLO18 in the Arabidopsis thaliana triple mlo mutant Atmlo2/6/12. The knock-down of MdMLO19 reduced PM disease severity by 75%, whereas the knock-down of MdMLO11, alone or in combination with MdMLO19, did not result in any reduction or additional reduction of susceptibility compared with MdMLO19 alone. The test in A. thaliana excluded a role for MdMLO18 in PM susceptibility. Cell wall appositions (papillae) were present in both PM-resistant and PM-susceptible plants, but were larger in resistant lines. No obvious negative phenotype was observed in plants with mlo genes knocked down. Apparently, MdMLO19 plays the pivotal role in apple PM susceptibility and its knock-down induces a very significant level of resistance. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  8. The draft genome of MD-2 pineapple using hybrid error correction of long reads

    PubMed Central

    Redwan, Raimi M.; Saidin, Akzam; Kumar, S. Vijay

    2016-01-01

    The introduction of the elite pineapple variety, MD-2, has caused a significant market shift in the pineapple industry. Better productivity, overall increased in fruit quality and taste, resilience to chilled storage and resistance to internal browning are among the key advantages of the MD-2 as compared with its previous predecessor, the Smooth Cayenne. Here, we present the genome sequence of the MD-2 pineapple (Ananas comosus (L.) Merr.) by using the hybrid sequencing technology from two highly reputable platforms, i.e. the PacBio long sequencing reads and the accurate Illumina short reads. Our draft genome achieved 99.6% genome coverage with 27,017 predicted protein-coding genes while 45.21% of the genome was identified as repetitive elements. Furthermore, differential expression of ripening RNASeq library of pineapple fruits revealed ethylene-related transcripts, believed to be involved in regulating the process of non-climacteric pineapple fruit ripening. The MD-2 pineapple draft genome serves as an example of how a complex heterozygous genome is amenable to whole genome sequencing by using a hybrid technology that is both economical and accurate. The genome will make genomic applications more feasible as a medium to understand complex biological processes specific to pineapple. PMID:27374615

  9. Ab Initio ONIOM-Molecular Dynamics (MD) Study on the Deamination Reaction by Cytidine Deaminase

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

    Matsubara, Toshiaki; Dupuis, Michel; Aida, Misako

    2007-08-23

    We applied the ONIOM-molecular dynamics (MD) method to the hydrolytic deamination of cytidine by cytidine deaminase, which is an essential step of the activation process of the anticancer drug inside the human body. The direct MD simulations were performed for the realistic model of cytidine deaminase calculating the energy and its gradient by the ab initio ONIOM method on the fly. The ONIOM-MD calculations including the thermal motion show that the neighboring amino acid residue is an important factor of the environmental effects and significantly affects not only the geometry and energy of the substrate trapped in the pocket ofmore » the active site but also the elementary step of the catalytic reaction. We successfully simulate the second half of the catalytic cycle, which has been considered to involve the rate-determining step, and reveal that the rate-determing step is the release of the NH3 molecule. TM and MA were supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan. MD was supported by the Division of Chemical Sciences, Office of Basic Energy Sciences, and by the Office of Biological and Environmental Research of the U.S. Department of Energy DOE. Battelle operates Pacific Northwest National Laboratory for DOE.« less

  10. Cherry-picking functionally relevant substates from long md trajectories using a stratified sampling approach.

    PubMed

    Chandramouli, Balasubramanian; Mancini, Giordano

    2016-01-01

    Classical Molecular Dynamics (MD) simulations can provide insights at the nanoscopic scale into protein dynamics. Currently, simulations of large proteins and complexes can be routinely carried out in the ns-μs time regime. Clustering of MD trajectories is often performed to identify selective conformations and to compare simulation and experimental data coming from different sources on closely related systems. However, clustering techniques are usually applied without a careful validation of results and benchmark studies involving the application of different algorithms to MD data often deal with relatively small peptides instead of average or large proteins; finally clustering is often applied as a means to analyze refined data and also as a way to simplify further analysis of trajectories. Herein, we propose a strategy to classify MD data while carefully benchmarking the performance of clustering algorithms and internal validation criteria for such methods. We demonstrate the method on two showcase systems with different features, and compare the classification of trajectories in real and PCA space. We posit that the prototype procedure adopted here could be highly fruitful in clustering large trajectories of multiple systems or that resulting especially from enhanced sampling techniques like replica exchange simulations. Copyright: © 2016 by Fabrizio Serra editore, Pisa · Roma.

  11. In Memoriam: Claude Klee, M.D. | Center for Cancer Research

    Cancer.gov

    Claude Klee, M.D., a true giant among the many great biochemists at the National Institutes of Health (NIH), died on Monday, April 3, after suffering a heart attack. She was 85 years old.  Learn more...     

  12. Science in the clinic: a qualitative study of the positioning of MD-PhDs in the everyday clinical setting.

    PubMed

    Andreassen, Pernille; Christensen, Mette Krogh

    2018-05-25

    MD-PhDs have been hailed as significant to the advancement of medicine and health care. Yet when it comes to which positions MD-PhDs should be holding in the clinic and the academic world, there seems to be no real consensus. This article examines the ways in which a PhD-degree may contribute to medical doctors' professional practice in the clinic and discusses the positioning of MD-PhDs in the clinic. The study is explorative and qualitative, based on interviews with MD-PhDs, their physician colleagues without a PhD-degree, and their leaders. Positioning theory was applied as the analytical framework for data analysis. We found two opposing positions cutting across the groups of informants with one side critiquing the MD-PhDs for not doing enough research and for using the PhD-degree to climb the career ladder, while the other side emphasized the ways in which MD-PhDs increase the clinical focus on evidence-based medicine and integrate it with clinical decision making, thereby enhancing patient care. A debate is needed to establish more clearly how we wish to position MD-PhDs in the clinic, which in turn will give us a better idea of how many to educate and how to make better use of their competencies.

  13. 33 CFR 165.556 - Regulated Navigation Area; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD. 165.556 Section 165.556 Navigation and..., Chesapeake City Anchorage Basin, MD. (a) Location. The following area is a regulated navigation area: All waters of the Chesapeake and Delaware (C & D) Canal within the anchorage basin at Chesapeake City...

  14. 33 CFR 165.556 - Regulated Navigation Area; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD. 165.556 Section 165.556 Navigation and..., Chesapeake City Anchorage Basin, MD. (a) Location. The following area is a regulated navigation area: All waters of the Chesapeake and Delaware (C & D) Canal within the anchorage basin at Chesapeake City...

  15. 33 CFR 165.556 - Regulated Navigation Area; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD. 165.556 Section 165.556 Navigation and..., Chesapeake City Anchorage Basin, MD. (a) Location. The following area is a regulated navigation area: All waters of the Chesapeake and Delaware (C & D) Canal within the anchorage basin at Chesapeake City...

  16. 33 CFR 165.556 - Regulated Navigation Area; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD. 165.556 Section 165.556 Navigation and..., Chesapeake City Anchorage Basin, MD. (a) Location. The following area is a regulated navigation area: All waters of the Chesapeake and Delaware (C & D) Canal within the anchorage basin at Chesapeake City...

  17. 33 CFR 165.556 - Regulated Navigation Area; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...; Chesapeake and Delaware Canal, Chesapeake City Anchorage Basin, MD. 165.556 Section 165.556 Navigation and..., Chesapeake City Anchorage Basin, MD. (a) Location. The following area is a regulated navigation area: All waters of the Chesapeake and Delaware (C & D) Canal within the anchorage basin at Chesapeake City...

  18. Reversal of Ion Charge Selectivity Renders the Pentameric Ligand-Gated Ion Channel GLIC Insensitive to Anesthetics

    PubMed Central

    Tillman, Tommy; Cheng, Mary H.; Chen, Qiang; Tang, Pei; Xu, Yan

    2014-01-01

    Pentameric ligand gated ion channels (pLGICs) are a family of structurally homologous cationic and anionic channels involved in neurotransmission. Cationic members of the pLGIC family are typically inhibited by general anesthetics, while anionic members are potentiated. GLIC is a prokaryotic cationic pLGIC and can be inhibited by clinical concentrations of general anesthetics. The introduction of three mutations, Y221A (Y–3′A), E222P (E–2′P) and N224R (N0′R), at the selectivity filter and one, A237T (A13′T), at the hydrophobic gate, converted GLIC to an anion channel. The mutated GLIC (GLIC4) became insensitive to the anesthetics propofol and etomidate as well as the channel blocker picrotoxin. Molecular dynamics (MD) simulations revealed changes in the structure and dynamics of GLIC4 in comparison to GLIC, particularly in the tilting angles of the pore-lining helix (TM2) that consequently resulted in different pore radius and hydration profiles. Propofol binding to an intra-subunit site of GLIC shifted the tilting angles of TM2 towards closure at the hydrophobic gate region, consistent with propofol inhibition of GLIC. In contrast, the pore of GLIC4 was much more resilient to perturbation from propofol binding. This study underscores the importance of pore dynamics and conformation to anesthetic effects on channel functions. PMID:22978431

  19. Inhibition of Large-Conductance Ca2+-Activated K+ Channels by Nanomolar Concentrations of Ag+S⃞

    PubMed Central

    Xia, Xiaoming; Lingle, Christopher J.

    2010-01-01

    Silver has been widely used in various medical products because of its antibacterial properties. However, there is only limited information concerning silver-related cytotoxicity. In this study we show that Ag+ at low nanomolar concentrations (<10 nM) strongly inhibits the activity of large-conductance Ca2+-activated K+ channels (BK) (Slo1), a widely expressed and physiologically important potassium channel. The Ag+ inhibition is caused by irreversible modification on cytosolically accessible parts of the BK channel. At least four intracellular cysteines are involved in this process. In addition, at least one of these key cysteines is not accessible to the bulkier thiolate-active reagent [2-(trimethylammonium)ethyl] methanethiosulfonate bromide. One of the cysteine-less constructs generated in this study shows gating properties similar to wild-type BK channel but with much lower Ag+ sensitivity, in which the Ag+ modification rate was decreased by approximately 20-fold. The results from the present study suggest a possible contribution of BK channel inhibition to the cytotoxicity of Ag+ in humans and other species. PMID:20729303

  20. Analysis of the MdMYB1 gene sequence and development of new molecular markers related to apple skin color and fruit-bearing traits.

    PubMed

    Yuan, Kejun; Wang, Changjun; Wang, Jianghui; Xin, Li; Zhou, Guangfang; Li, Linguang; Shen, Guangning

    2014-12-01

    MdMYB1, a key transcription factor determining apple skin color, coordinately regulates genes in the anthocyanin pathway. In this study, we analyzed the MdMYB1 gene and its relationship to apple skin color and fruit-bearing traits to better understand this gene and its application to apple breeding. A previously reported MdMYB1 dCAPS marker failed to identify alleles of the MdMYB1 gene in 'Fuji', a very important apple cultivar. In this study, we revealed that the polymorphic site related to the MdMYB1 dCAPS marker is heterozygous in 'Fuji'. In addition, two new polymorphic sites related to apple skin color were identified in the MdMYB1 gene, with two new molecular markers accordingly developed. Testing of these markers in 'Fuji' and its progeny revealed that they could predict apple skin color and identify alleles of the MdMYB1 gene in this cultivar. Most interestingly, the allele MdMYB1-2 in 'Gala' apple and its hybrid plants was found to be related to the fruit-bearing trait, and the molecular marker Mb2 was able to identify the MdMYB1-2 allele. Our study is apparently the first to report a relationship between the MdMYB1 allele and the fruit-bearing trait in apple. More work is needed to determine whether and how the MdMYB1 gene or a gene linked to the MdMYB1-2 allele influences the flowering trait in perennial apple trees, and whether flowering in other plants is influenced by related genes.

  1. MD-2-mediated Ionic Interactions between Lipid A and TLR4 Are Essential for Receptor Activation*

    PubMed Central

    Meng, Jianmin; Lien, Egil; Golenbock, Douglas T.

    2010-01-01

    Lipopolysaccharide (LPS) activates innate immune responses through TLR4·MD-2. LPS binds to the MD-2 hydrophobic pocket and bridges the dimerization of two TLR4·MD-2 complexes to activate intracellular signaling. However, exactly how lipid A, the endotoxic moiety of LPS, activates myeloid lineage cells remains unknown. Lipid IVA, a tetra-acylated lipid A precursor, has been used widely as a model for lipid A activation. For unknown reasons, lipid IVA activates proinflammatory responses in rodent cells but inhibits the activity of LPS in human cells. Using stable TLR4-expressing cell lines and purified monomeric MD-2, as well as MD-2-deficient bone marrow-derived macrophages, we found that both mouse TLR4 and mouse MD-2 are required for lipid IVA activation. Computational studies suggested that unique ionic interactions exist between lipid IVA and TLR4 at the dimerization interface in the mouse complex only. The negatively charged 4′-phosphate on lipid IVA interacts with two positively charged residues on the opposing mouse, but not human, TLR4 (Lys367 and Arg434) at the dimerization interface. When replaced with their negatively charged human counterparts Glu369 and Gln436, mouse TLR4 was no longer responsive to lipid IVA. In contrast, human TLR4 gained lipid IVA responsiveness when ionic interactions were enabled by charge reversal at the dimerization interface, defining the basis of lipid IVA species specificity. Thus, using lipid IVA as a selective lipid A agonist, we successfully decoupled and coupled two sequential events required for intracellular signaling: receptor engagement and dimerization, underscoring the functional role of ionic interactions in receptor activation. PMID:20018893

  2. Safety and efficacy of a backpassaged rMd5-delta-Meq vaccine virus in chickens

    USDA-ARS?s Scientific Manuscript database

    Marek’s disease virus EcoR1-Q fragment of the viral genome encodes meq (MDV EcoQ) gene. Meq is an unique oncogene, present only in serotype 1 MDV and is consistently expressed in all latent or tumor cells. The meq gene was deleted from the very virulent rMd5 genome and was designated as rMd5-delta-M...

  3. Dynamics of the GB3 loop regions from MD simulation: how much of it is real?

    PubMed

    Li, Tong; Jing, Qingqing; Yao, Lishan

    2011-04-07

    A total of 1.1 μs of molecular dynamics (MD) simulations were performed to study the structure and dynamics of protein GB3. The simulation motional amplitude of the loop regions is generally overestimated in comparison with the experimental backbone N-H order parameters S(2). Two-state behavior is observed for several residues in these regions, with the minor state population in the range of 3-13%. Further inspection suggests that the (φ, ψ) dihedral angles of the minor states deviate from the GB3 experimental values, implying the existence of nonnative states. After fitting the MD trajectories of these residues to the NMR RDCs, the minor state populations are significantly reduced by at least 80%, suggesting that MD simulations are strongly biased toward the minor states, thus overestimating the dynamics of the loop regions. The optimized trajectories produce intra, sequential H(N)-H(α) RDCs and intra (3)J(HNHα) that are not included in the trajectories fitting for these residues that are closer to the experimental data. Unlike GB3, 0.55 μs MD simulations of protein ubiquitin do not show distinctive minor states, and the derived NMR order parameters are better converged. Our findings indicate that the artifacts of the simulations depend on the specific system studied and that one should be cautious interpreting the enhanced dihedral dynamics from long MD simulations.

  4. Real-time Data Access From Remote Observatories

    NASA Astrophysics Data System (ADS)

    Detrick, D. L.; Lutz, L. F.; Etter, J. E.; Rosenberg, T. J.; Weatherwax, A. T.

    2006-12-01

    Real-time access to solar-terrestrial data is becoming increasingly important, not only because it is now possible to acquire and access data rapidly via the internet, but also because of the need for timely publication of real-time data for analysis and modeling efforts. Currently, engineering-scaled summary data are available routinely on a daily basis from many observatories, but only when the observatories have continuous, or at least daily network access. Increasingly, the upgrading of remote data acquisition hardware makes it possible to provide data in real-time, and it is becoming normal to expect timely access to data products. The NSF- supported PENGUIn/AGO constellation of autonomous Antarctic research observatories has provided real-time data since December, 2002, when Iridium satellite modems were installed at three sites. The Iridium telecommunications links are maintained continuously, transferring data between the remote observatories and a U.S.-based data acquisition site. The time-limiting factor with this scenario is now the delay in completing a data record before transmission, which can be as short as minutes depending on the sampling rate. The single-channel data throughput of the current systems is 20-MB/day (megabytes per day), but planned installations will be capable of operating with multiple modem channels. The data records are currently posted immediately to a web site accessible by anonymous FTP client software, for use by the instruments' principal investigators, and survey plots of selected signals are published daily. The web publication facilities are being upgraded, in order to allow other interested researchers rapid access to engineering-scaled data products, in several common formats, as well as providing interactive plotting capabilities. The web site will provide access to data from other collaborating observatories (including South Pole and McMurdo Stations), as well as ancillary data accessible from public sites (e.g., Kp

  5. Mechanism of allosteric activation of TMEM16A/ANO1 channels by a commonly used chloride channel blocker

    PubMed Central

    Ta, Chau M; Adomaviciene, Aiste; Rorsman, Nils J G; Garnett, Hannah

    2016-01-01

    Background and Purpose Calcium‐activated chloride channels (CaCCs) play varied physiological roles and constitute potential therapeutic targets for conditions such as asthma and hypertension. TMEM16A encodes a CaCC. CaCC pharmacology is restricted to compounds with relatively low potency and poorly defined selectivity. Anthracene‐9‐carboxylic acid (A9C), an inhibitor of various chloride channel types, exhibits complex effects on native CaCCs and cloned TMEM16A channels providing both activation and inhibition. The mechanisms underlying these effects are not fully defined. Experimental Approach Patch‐clamp electrophysiology in conjunction with concentration jump experiments was employed to define the mode of interaction of A9C with TMEM16A channels. Key Results In the presence of high intracellular Ca2+, A9C inhibited TMEM16A currents in a voltage‐dependent manner by entering the channel from the outside. A9C activation, revealed in the presence of submaximal intracellular Ca2+ concentrations, was also voltage‐dependent. The electric distance of A9C inhibiting and activating binding site was ~0.6 in each case. Inhibition occurred according to an open‐channel block mechanism. Activation was due to a dramatic leftward shift in the steady‐state activation curve and slowed deactivation kinetics. Extracellular A9C competed with extracellular Cl−, suggesting that A9C binds deep in the channel's pore to exert both inhibiting and activating effects. Conclusions and Implications A9C is an open TMEM16A channel blocker and gating modifier. These effects require A9C to bind to a region within the pore that is accessible from the extracellular side of the membrane. These data will aid the future drug design of compounds that selectively activate or inhibit TMEM16A channels. PMID:26562072

  6. Flexible and Comprehensive Implementation of MD-PMM Approach in a General and Robust Code.

    PubMed

    Carrillo-Parramon, Oliver; Del Galdo, Sara; Aschi, Massimiliano; Mancini, Giordano; Amadei, Andrea; Barone, Vincenzo

    2017-11-14

    The Perturbed Matrix Method (PMM) approach to be used in combination with Molecular Dynamics (MD) trajectories (MD-PMM) has been recoded from scratch, improved in several aspects, and implemented in the Gaussian suite of programs for allowing a user-friendly and yet flexible tool to estimate quantum chemistry observables in complex systems in condensed phases. Particular attention has been devoted to a description of rigid and flexible quantum centers together with powerful essential dynamics and clustering approaches. The default implementation is fully black-box and does not require any external action concerning both MD and PMM sections. At the same time, fine-tuning of different parameters and use of external data are allowed in all the steps of the procedure. Two specific systems (Tyrosine and Uridine) have been reinvestigated with the new version of the code in order to validate the implementation, check the performances, and illustrate some new features.

  7. Ab initio ONIOM-molecular dynamics (MD) study on the deamination reaction by cytidine deaminase.

    PubMed

    Matsubara, Toshiaki; Dupuis, Michel; Aida, Misako

    2007-08-23

    We applied the ONIOM-molecular dynamics (MD) method to the hydrolytic deamination of cytidine by cytidine deaminase, which is an essential step of the activation process of the anticancer drug inside the human body. The direct MD simulations were performed for the realistic model of cytidine deaminase by calculating the energy and its gradient by the ab initio ONIOM method on the fly. The ONIOM-MD calculations including the thermal motion show that the neighboring amino acid residue is an important factor of the environmental effects and significantly affects not only the geometry and energy of the substrate trapped in the pocket of the active site but also the elementary step of the catalytic reaction. We successfully simulate the second half of the catalytic cycle, which has been considered to involve the rate-determining step, and reveal that the rate-determining step is the release of the NH3 molecule.

  8. Access to a scale and self-weighing habits among public housing residents.

    PubMed

    Bramante, C T; Clark, J M; Gudzune, K A

    2018-05-31

    Having access to a scale is essential for individuals to engage in self-weighing; however, few studies examine scale access, particularly among low-income individuals. Our objectives were to (i) determine how many public housing residents have access to a scale and (ii) describe their self-weighing habits. We conducted a cross-sectional survey of public housing residents in Baltimore, MD, from August 2014 to August 2015. Participants answered questions about their access to a scale ('yes'/'no') and daily self-weighing habits ('no scale/never or hardly ever' vs. 'some/about half/much of the time/always'). We used t-tests or chi-square tests to examine the association of scale access with respondent characteristics. Overall, 266 adults participated (48% response rate). Mean age was 45 years with 86% women, 95% black and 54% with obesity. Only 32% had access to a scale; however, 78% of those with this access reported engaging in some self-weighing. Residents who lacked access to a scale were younger (P = 0.03), and more likely to be unemployed/disabled (P = 0.01) or food insecure (P < 0.01). While few public housing residents have access to a scale, those who do report daily self-weighing with some regularity. Financial hardship may influence scale access in this population, as potential proxies of this status were associated with no scale access. © 2018 World Obesity Federation.

  9. A workshop on leadership for senior MD-PhD students.

    PubMed

    Meador, Catherine B; Parang, Bobak; Musser, Melissa A; Haliyur, Rachana; Owens, David A; Dermody, Terence S

    2016-01-01

    Leadership skills are essential for a successful career as a physician-scientist, yet many MD-PhD training programs do not offer formal training in leadership. The Vanderbilt Medical Scientist Training Program (MSTP) previously established a 2-day leadership workshop that has been held biennially since 2006 for students in the first and second years of the graduate school portion of combined MD and PhD training (G1/G2 students). Workshop attendees have consistently rated this workshop as a highly effective experience. However, opportunities for structured training in leadership competencies during the subsequent 3-5 years of MD-PhD training are limited. Given the success of the G1/G2 leadership workshop and the need for continuity in this model of leadership training, we developed a half-day workshop for MSTP students in the clinical years of medical school (M3/M4 students) to foster continued training in leadership. Our workshop curriculum, based in part on original cases drafted by Vanderbilt MSTP students, provides concrete strategies to manage conflict and navigate leadership transitions in the physician-scientist career path. The curriculum emphasizes both short-term competencies, such as effective participation as a member of a clinical team, and long-term competencies, such as leadership of a research team, division, or department. Our inaugural senior leadership workshop, held in August, 2015, was judged by student participants to be well organized and highly relevant to leadership concepts and skills. It will be offered biennially in our training curriculum for M3 and M4 MSTP students.

  10. 75 FR 26993 - Alvin Darby, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-13

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 09-6] Alvin Darby, M.D.; Denial... Gretna, Louisiana. The Show Cause Order proposed the denial of Respondent's pending application for a DEA... attempts to serve Respondent were constitutionally adequate, the date when service was initially attempted...

  11. Sub-1-V-60 nm vertical body channel MOSFET-based six-transistor static random access memory array with wide noise margin and excellent power delay product and its optimization with the cell ratio on static random access memory cell

    NASA Astrophysics Data System (ADS)

    Ogasawara, Ryosuke; Endoh, Tetsuo

    2018-04-01

    In this study, with the aim to achieve a wide noise margin and an excellent power delay product (PDP), a vertical body channel (BC)-MOSFET-based six-transistor (6T) static random access memory (SRAM) array is evaluated by changing the number of pillars in each part of a SRAM cell, that is, by changing the cell ratio in the SRAM cell. This 60 nm vertical BC-MOSFET-based 6T SRAM array realizes 0.84 V operation under the best PDP and up to 31% improvement of PDP compared with the 6T SRAM array based on a 90 nm planar MOSFET whose gate length and channel width are the same as those of the 60 nm vertical BC-MOSFET. Additionally, the vertical BC-MOSFET-based 6T SRAM array achieves an 8.8% wider read static noise margin (RSNM), a 16% wider write margin (WM), and an 89% smaller leakage. Moreover, it is shown that changing the cell ratio brings larger improvements of RSNM, WM, and write time in the vertical BC-MOSFET-based 6T SRAM array.

  12. IDMA-Based MAC Protocol for Satellite Networks with Consideration on Channel Quality

    PubMed Central

    2014-01-01

    In order to overcome the shortcomings of existing medium access control (MAC) protocols based on TDMA or CDMA in satellite networks, interleave division multiple access (IDMA) technique is introduced into satellite communication networks. Therefore, a novel wide-band IDMA MAC protocol based on channel quality is proposed in this paper, consisting of a dynamic power allocation algorithm, a rate adaptation algorithm, and a call admission control (CAC) scheme. Firstly, the power allocation algorithm combining the technique of IDMA SINR-evolution and channel quality prediction is developed to guarantee high power efficiency even in terrible channel conditions. Secondly, the effective rate adaptation algorithm, based on accurate channel information per timeslot and by the means of rate degradation, can be realized. What is more, based on channel quality prediction, the CAC scheme, combining the new power allocation algorithm, rate scheduling, and buffering strategies together, is proposed for the emerging IDMA systems, which can support a variety of traffic types, and offering quality of service (QoS) requirements corresponding to different priority levels. Simulation results show that the new wide-band IDMA MAC protocol can make accurate estimation of available resource considering the effect of multiuser detection (MUD) and QoS requirements of multimedia traffic, leading to low outage probability as well as high overall system throughput. PMID:25126592

  13. MdPIN1b encodes a putative auxin efflux carrier and has different expression patterns in BC and M9 apple rootstocks.

    PubMed

    Gan, Zengyu; Wang, Yi; Wu, Ting; Xu, Xuefeng; Zhang, Xinzhong; Han, Zhenhai

    2018-03-01

    Lower promoter activity is closely associated with lower MdPIN1b expression in the M9 interstem, which might contribute to the dwarfing effect in apple trees. Apple trees grafted onto dwarfing rootstock Malling 9 (M9) produce dwarfing tree architecture with high yield and widely applying in production. Previously, we have reported that in Malus 'Red Fuji' (RF) trees growing on M9 interstem and Baleng Crab (BC) rootstock, IAA content was relatively higher in bark tissue of M9 interstem than that in scion or rootstock. As IAA polar transportation largely depends on the PIN-FORMED (PIN) auxin efflux carrier. Herein, we identify two putative auxin efflux carrier genes in Malus genus, MdPIN1a and MdPIN1b, which were closely related to the AtPIN1. We found that MdPIN1b was expressed preferentially in BC and M9, and the expression of MdPIN1b was significantly lower in the phloem of M9 interstem than that in the scion and rootstock. The distinct expression of MdPIN1b and IAA content were concentrated in the cambium and adjacent xylem or phloem, and MdPIN1b protein was localized on cell plasma membrane in onion epidermal cells transiently expressing 35S:MdPIN1b-GFP fusion protein. Interestingly, an MdPIN1b mutant allele in the promoter region upstream of M9 exhibited decreased MdPIN1b expression compared to BC. MdPIN1b over-expressing interstem in tobacco exhibited increased polar auxin transport. It is proposed that natural allelic differences decreased promoter activity is closely associated with lower MdPIN1b expression in the M9 interstem, which might limit the basipetal transport of auxin, and in turn might contribute to the dwarfing effect. Taken together, these results reveal allelic variation underlying an important apple rootstock trait, and specifically a novel molecular genetic mechanism underlying dwarfing mechanism.

  14. Combination of advanced encryption standard 256 bits with md5 to secure documents on android smartphone

    NASA Astrophysics Data System (ADS)

    Pasaribu, Hendra; Sitanggang, Delima; Rizki Damanik, Rudolfo; Rudianto Sitompul, Alex Chandra

    2018-04-01

    File transfer by using a smartphone has some security issues like data theft by irresponsible parties. To improve the quality of data security systems on smartphones, in this research the integration of AES 256 bit algorithm by using MD5 hashing is proposed. The use of MD5 aims to increase the key strength of the encryption and decryption process of document files. The test results show that the proposed method can increase the key strength of the encryption and decryption process in the document file. Encryption and decryption time by using AES and MD5 combination is faster than using AES only on *.txt file type and reverse results for *.docx, *.xlsx, *.pptx and *.pdf file files.

  15. Construction, MD simulation, and hydrodynamic validation of an all-atom model of a monoclonal IgG antibody.

    PubMed

    Brandt, J Paul; Patapoff, Thomas W; Aragon, Sergio R

    2010-08-04

    At 150 kDa, antibodies of the IgG class are too large for their structure to be determined with current NMR methodologies. Because of hinge-region flexibility, it is difficult to obtain atomic-level structural information from the crystal, and questions regarding antibody structure and dynamics in solution remain unaddressed. Here we describe the construction of a model of a human IgG1 monoclonal antibody (trastuzumab) from the crystal structures of fragments. We use a combination of molecular-dynamics (MD) simulation, continuum hydrodynamics modeling, and experimental diffusion measurements to explore antibody behavior in aqueous solution. Hydrodynamic modeling provides a link between the atomic-level details of MD simulation and the size- and shape-dependent data provided by hydrodynamic measurements. Eight independent 40 ns MD trajectories were obtained with the AMBER program suite. The ensemble average of the computed transport properties over all of the MD trajectories agrees remarkably well with the value of the translational diffusion coefficient obtained with dynamic light scattering at 20 degrees C and 27 degrees C, and the intrinsic viscosity measured at 20 degrees C. Therefore, our MD results likely represent a realistic sampling of the conformational space that an antibody explores in aqueous solution. 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  16. Addressing data access challenges in seismology

    NASA Astrophysics Data System (ADS)

    Trabant, C. M.; Ahern, T.; Weertman, B.; Benson, R. B.; Van Fossen, M.; Weekly, R. T.; Casey, R. E.; Suleiman, Y. Y.; Stults, M.

    2016-12-01

    The development of web services at the IRIS Data Management Center (DMC) over the last 6 years represents the most significant enhancement of data access ever introduced at the DMC. These web services have allowed the us to focus our internal operations around a single, consistent data access layer while facilitating development of a new generation of tools and methods for researchers to conduct their work. This effort led the DMC to propose standardized web service interfaces within the International Federation of Digital Seismograph Networks (FDSN), enabling other seismological data centers to offer data using compatible interfaces. With this new foundation, we now turn our attention to more advanced data access challenges. In particular, we will present the status of two developments intending to address 1) access to data of consistent quality for science and 2) discovery and access of data from multiple data centers. To address the challenge of requesting high or consistent quality data we will introduce our Research-Ready Data Sets (RRDS) initiative. The purpose of the RRDS project is to reduce the time a researcher spends culling and otherwise identifying data appropriate for given study. RRDS will provide users with additional criteria related to data quality that can be specified when requesting data. Leveraging the data quality measurements provided by our MUSTANG system, these criteria will include ambient noise, completeness, dead channel identification and more. To address the challenge of seismological data discovery and access, we have built and continue to improve the IRIS Federator. The Federator takes advantage of the FDSN-standard web services at various data centers to help a user locate specific channels, wherever they may be offered globally. The search interface provides results that are pre-formatted requests, ready for submission to each data center that serves that data. These two developments are aimed squarely at reducing the time

  17. Substrate channel in nitrogenase revealed by a molecular dynamics approach.

    PubMed

    Smith, Dayle; Danyal, Karamatullah; Raugei, Simone; Seefeldt, Lance C

    2014-04-15

    Mo-dependent nitrogenase catalyzes the biological reduction of N2 to two NH3 molecules at FeMo-cofactor buried deep inside the MoFe protein. Access of substrates, such as N2, to the active site is likely restricted by the surrounding protein, requiring substrate channels that lead from the surface to the active site. Earlier studies on crystallographic structures of the MoFe protein have suggested three putative substrate channels. Here, we have utilized submicrosecond atomistic molecular dynamics simulations to allow the nitrogenase MoFe protein to explore its conformational space in an aqueous solution at physiological ionic strength, revealing a putative substrate channel. The viability of this observed channel was tested by examining the free energy of passage of N2 from the surface through the channel to FeMo-cofactor, resulting in the discovery of a very low energy barrier. These studies point to a viable substrate channel in nitrogenase that appears during thermal motions of the protein in an aqueous environment and that approaches a face of FeMo-cofactor earlier implicated in substrate binding.

  18. The Convergence of Business and Medicine: A Study of MD/MBA Programs in the United States

    ERIC Educational Resources Information Center

    Keogh, Timothy J.; Martin, William Marty

    2011-01-01

    The purpose of this paper is to identify the convergence of business and medical education and describe the curricula of MD/MBA (Medical Doctor/Master of Business Administration) programs in the US. The focus of this study is to provide a guide to dual MD/MBA programs for physicians, aspiring physicians, policy makers and healthcare organizations.…

  19. 77 FR 18862 - Zhiwei Lin, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-54] Zhiwei Lin, M.D.; Decision and Order On September 19, 2011, Administrative Law Judge (ALJ) Timothy D. Wing issued the....C. 824, of the CSA. Calvin Ramsey, 76 FR 20034, 20036 (2011) (other citations omitted); Brenton D...

  20. 76 FR 21406 - Roni Dreszer, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-37] Roni Dreszer, M.D.; Decision and Order ACTION: Correction. On Thursday, April 7, 2011, the Drug Enforcement Administration published the above-titled Decision and Order, as well as the Decision of the Administrative Law Judge (76...

  1. 76 FR 21406 - Beau Boshers, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-35] Beau Boshers, M.D.; Decision and Order ACTION: Correction. On Thursday, April 7, 2011, the Drug Enforcement Administration published the above-titled Decision and Order, as well as the Decision of the Administrative Law Judge (76...

  2. 76 FR 21406 - Jacobo Dreszer, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-36] Jacobo Dreszer, M.D.; Decision and Order ACTION: Correction. On Thursday, April 7, 2011, the Drug Enforcement Administration published the above-titled Decision and Order, as well as the Decision of the Administrative Law Judge (76...

  3. Multi terabits/s optical access transport technologies

    NASA Astrophysics Data System (ADS)

    Binh, Le Nguyen; Wang Tao, Thomas; Livshits, Daniil; Gubenko, Alexey; Karinou, Fotini; Liu Ning, Gordon; Shkolnik, Alexey

    2016-02-01

    Tremendous efforts have been developed for multi-Tbps over ultra-long distance and metro and access optical networks. With the exponential increase demand on data transmission, storage and serving, especially the 5G wireless access scenarios, the optical Internet networking has evolved to data-center based optical networks pressuring on novel and economical access transmission systems. This paper reports (1) Experimental platforms and transmission techniques employing band-limited optical components operating at 10G for 100G based at 28G baud. Advanced modulation formats such as PAM-4, DMT, duo-binary etc are reported and their advantages and disadvantages are analyzed so as to achieve multi-Tbps optical transmission systems for access inter- and intra- data-centered-based networks; (2) Integrated multi-Tbps combining comb laser sources and micro-ring modulators meeting the required performance for access systems are reported. Ten-sub-carrier quantum dot com lasers are employed in association with wideband optical intensity modulators to demonstrate the feasibility of such sources and integrated micro-ring modulators acting as a combined function of demultiplexing/multiplexing and modulation, hence compactness and economy scale. Under the use of multi-level modulation and direct detection at 56 GBd an aggregate of higher than 2Tbps and even 3Tbps can be achieved by interleaved two comb lasers of 16 sub-carrier lines; (3) Finally the fundamental designs of ultra-compacts flexible filters and switching integrated components based on Si photonics for multi Tera-bps active interconnection are presented. Experimental results on multi-channels transmissions and performances of optical switching matrices and effects on that of data channels are proposed.

  4. Laser-Driven Ion Acceleration from Plasma Micro-Channel Targets

    PubMed Central

    Zou, D. B.; Pukhov, A.; Yi, L. Q.; Zhou, H. B.; Yu, T. P.; Yin, Y.; Shao, F. Q.

    2017-01-01

    Efficient energy boost of the laser-accelerated ions is critical for their applications in biomedical and hadron research. Achiev-able energies continue to rise, with currently highest energies, allowing access to medical therapy energy windows. Here, a new regime of simultaneous acceleration of ~100 MeV protons and multi-100 MeV carbon-ions from plasma micro-channel targets is proposed by using a ~1020 W/cm2 modest intensity laser pulse. It is found that two trains of overdense electron bunches are dragged out from the micro-channel and effectively accelerated by the longitudinal electric-field excited in the plasma channel. With the optimized channel size, these “superponderomotive” energetic electrons can be focused on the front surface of the attached plastic substrate. The much intense sheath electric-field is formed on the rear side, leading to up to ~10-fold ionic energy increase compared to the simple planar geometry. The analytical prediction of the optimal channel size and ion maximum energies is derived, which shows good agreement with the particle-in-cell simulations. PMID:28218247

  5. Laser-Driven Ion Acceleration from Plasma Micro-Channel Targets

    NASA Astrophysics Data System (ADS)

    Zou, D. B.; Pukhov, A.; Yi, L. Q.; Zhou, H. B.; Yu, T. P.; Yin, Y.; Shao, F. Q.

    2017-02-01

    Efficient energy boost of the laser-accelerated ions is critical for their applications in biomedical and hadron research. Achiev-able energies continue to rise, with currently highest energies, allowing access to medical therapy energy windows. Here, a new regime of simultaneous acceleration of ~100 MeV protons and multi-100 MeV carbon-ions from plasma micro-channel targets is proposed by using a ~1020 W/cm2 modest intensity laser pulse. It is found that two trains of overdense electron bunches are dragged out from the micro-channel and effectively accelerated by the longitudinal electric-field excited in the plasma channel. With the optimized channel size, these “superponderomotive” energetic electrons can be focused on the front surface of the attached plastic substrate. The much intense sheath electric-field is formed on the rear side, leading to up to ~10-fold ionic energy increase compared to the simple planar geometry. The analytical prediction of the optimal channel size and ion maximum energies is derived, which shows good agreement with the particle-in-cell simulations.

  6. Characterizing a point mutation within the UL5 gene that reduces in vivo replication and MD incidence

    USDA-ARS?s Scientific Manuscript database

    Marek’s disease virus (MDV) is an oncogenic alphaherpesvirus of chickens and the causative agent for Marek’s disease (MD). Vaccination is the primary method to control MD. Despite the success of vaccination, more virulent field strains are evolving, requiring the development of new vaccines. Attenua...

  7. 77 FR 63290 - Foreign-Trade Zone 74-Baltimore, MD, Authorization of Production Activity, J.D. Neuhaus LP...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board [B-47-2012] Foreign-Trade Zone 74--Baltimore, MD, Authorization of Production Activity, J.D. Neuhaus LP, (Overhead Lifting Equipment Production), Sparks, MD On June 13, 2012, the Baltimore Development Corporation, grantee of FTZ 74, submitted a notification of...

  8. Universal filtered multi-carrier system for asynchronous uplink transmission in optical access network

    NASA Astrophysics Data System (ADS)

    Kang, Soo-Min; Kim, Chang-Hun; Han, Sang-Kook

    2016-02-01

    In passive optical network (PON), orthogonal frequency division multiplexing (OFDM) has been studied actively due to its advantages such as high spectra efficiency (SE), dynamic resource allocation in time or frequency domain, and dispersion robustness. However, orthogonal frequency division multiple access (OFDMA)-PON requires tight synchronization among multiple access signals. If not, frequency orthogonality could not be maintained. Also its sidelobe causes inter-channel interference (ICI) to adjacent channel. To prevent ICI caused by high sidelobes, guard band (GB) is usually used which degrades SE. Thus, OFDMA-PON is not suitable for asynchronous uplink transmission in optical access network. In this paper, we propose intensity modulation/direct detection (IM/DD) based universal filtered multi-carrier (UFMC) PON for asynchronous multiple access. The UFMC uses subband filtering to subsets of subcarriers. Since it reduces sidelobe of each subband by applying subband filtering, it could achieve better performance compared to OFDM. For the experimental demonstration, different sample delay was applied to subbands to implement asynchronous transmission condition. As a result, time synchronization robustness of UFMC was verified in asynchronous multiple access system.

  9. Coupling proton movements to c-ring rotation in F(1)F(o) ATP synthase: aqueous access channels and helix rotations at the a-c interface.

    PubMed

    Fillingame, Robert H; Angevine, Christine M; Dmitriev, Oleg Y

    2002-09-10

    F(1)F(o) ATP synthases generate ATP by a rotary catalytic mechanism in which H(+) transport is coupled to rotation of a ring of c subunits within the transmembrane sector of the enzyme. Protons bind to and then are released from the aspartyl-61 residue of subunit c at the center of the membrane. Proton access channels to and from aspartyl-61 are thought to form in subunit a of the F(o) sector. Here, we summarize new information on the structural organization of subunit a and the mapping of aqueous accessible residues in the fourth and fifth transmembrane helices (TMHs). Cysteine substituted residues, lying on opposite faces of aTMH-4, preferentially react with either N-ethyl-maleimide (NEM) or Ag(+). We propose that aTMH-4 rotates to alternately expose each helical face to aspartyl-61 of subunit c during the proton transport cycle. The concerted helical rotation of aTMH-4 and cTMH-2 are proposed to be coupled to the stepwise mechanical movement of the c-rotor.

  10. 47 CFR 76.977 - Minority and educational programming used in lieu of designated commercial leased access capacity.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... commercial leased access capacity. (a) A cable operator required by this section to designate channel capacity for commercial use pursuant to 47 U.S.C. 532, may use any such channel capacity for the provision... programming sources, whether or not such source is affiliated with cable operator. The channel capacity used...

  11. An apple MYB transcription factor, MdMYB3, is involved in regulation of anthocyanin biosynthesis and flower development.

    PubMed

    Vimolmangkang, Sornkanok; Han, Yuepeng; Wei, Guochao; Korban, Schuyler S

    2013-11-07

    Red coloration of fruit is an important trait in apple, and it is mainly attributed to the accumulation of anthocyanins, a class of plant flavonoid metabolites. Anthocyanin biosynthesis is genetically determined by structural and regulatory genes. Plant tissue pigmentation patterns are mainly controlled by expression profiles of regulatory genes. Among these regulatory genes are MYB transcription factors (TFs), wherein the class of two-repeats (R2R3) is deemed the largest, and these are associated with the anthocyanin biosynthesis pathway. Although three MdMYB genes, almost identical in nucleotide sequences, have been identified in apple, it is likely that there are other R2R3 MYB TFs that are present in the apple genome that are also involved in the regulation of coloration of red color pigmentation of the skin of apple fruits. In this study, a novel R2R3 MYB gene has been isolated and characterized in apple. This MYB gene is closely related to the Arabidopsis thaliana AtMYB3, and has been designated as MdMYB3. This TF belongs to the subgroup 4 R2R3 family of plant MYB transcription factors. This apple MdMYB3 gene is mapped onto linkage group 15 of the integrated apple genetic map. Transcripts of MdMYB3 are detected in all analyzed tissues including leaves, flowers, and fruits. However, transcripts of MdMYB3 are higher in excocarp of red-skinned apple cultivars than that in yellowish-green skinned apple cultivars. When this gene is ectopically expressed in Nicotiana tabacum cv. Petite Havana SR1, flowers of transgenic tobacco lines carrying MdMYB3 have exhibited increased pigmentation and accumulate higher levels of anthocyanins and flavonols than wild-type flowers. Overexpression of MdMYB3 has resulted in transcriptional activation of several flavonoid pathway genes, including CHS, CHI, UFGT, and FLS. Moreover, peduncles of flowers and styles of pistils of transgenic plants overexpressing MdMYB3 are longer than those of wild-type plants, thus suggesting that this

  12. Integrated multi-channel vehicle-vehicle and vehicle-roadside communications for ITS

    DOT National Transportation Integrated Search

    2008-12-01

    This research describes a medium access control (MAC) protocol to Enable multi-channel operation for dedicated short-range communication (DSRC). In particular, we focus on the challenge of supporting potentially high-bandwidth commercial or infotainm...

  13. Program Spotlight: UPR and MD Anderson Partnership Welcomes Its First Graduates

    Cancer.gov

    CRCHD joins the PIs and Diversity Training co-leaders of the Univ. of Puerto Rico and the Univ. of Texas MD Anderson Cancer Center U54 Partnership for Excellence in Cancer Research in congratulating its first graduates.

  14. 33 CFR 334.155 - Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area. 334.155 Section 334.155 Navigation and... RESTRICTED AREA REGULATIONS § 334.155 Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD...

  15. 33 CFR 334.155 - Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area. 334.155 Section 334.155 Navigation and... RESTRICTED AREA REGULATIONS § 334.155 Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD...

  16. 33 CFR 334.155 - Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area. 334.155 Section 334.155 Navigation and... RESTRICTED AREA REGULATIONS § 334.155 Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area. (a) The area. The waters within the Naval Station Annapolis small boat basin and...

  17. 33 CFR 334.155 - Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area. 334.155 Section 334.155 Navigation and... RESTRICTED AREA REGULATIONS § 334.155 Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area. (a) The area. The waters within the Naval Station Annapolis small boat basin and...

  18. 33 CFR 334.155 - Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area. 334.155 Section 334.155 Navigation and... RESTRICTED AREA REGULATIONS § 334.155 Severn River, Naval Station Annapolis, Small Boat Basin, Annapolis, MD; naval restricted area. (a) The area. The waters within the Naval Station Annapolis small boat basin and...

  19. Segmentized Clear Channel Assessment for IEEE 802.15.4 Networks.

    PubMed

    Son, Kyou Jung; Hong, Sung Hyeuck; Moon, Seong-Pil; Chang, Tae Gyu; Cho, Hanjin

    2016-06-03

    This paper proposed segmentized clear channel assessment (CCA) which increases the performance of IEEE 802.15.4 networks by improving carrier sense multiple access with collision avoidance (CSMA/CA). Improving CSMA/CA is important because the low-power consumption feature and throughput performance of IEEE 802.15.4 are greatly affected by CSMA/CA behavior. To improve the performance of CSMA/CA, this paper focused on increasing the chance to transmit a packet by assessing precise channel status. The previous method used in CCA, which is employed by CSMA/CA, assesses the channel by measuring the energy level of the channel. However, this method shows limited channel assessing behavior, which comes from simple threshold dependent channel busy evaluation. The proposed method solves this limited channel decision problem by dividing CCA into two groups. Two groups of CCA compare their energy levels to get precise channel status. To evaluate the performance of the segmentized CCA method, a Markov chain model has been developed. The validation of analytic results is confirmed by comparing them with simulation results. Additionally, simulation results show the proposed method is improving a maximum 8.76% of throughput and decreasing a maximum 3.9% of the average number of CCAs per packet transmission than the IEEE 802.15.4 CCA method.

  20. Segmentized Clear Channel Assessment for IEEE 802.15.4 Networks

    PubMed Central

    Son, Kyou Jung; Hong, Sung Hyeuck; Moon, Seong-Pil; Chang, Tae Gyu; Cho, Hanjin

    2016-01-01

    This paper proposed segmentized clear channel assessment (CCA) which increases the performance of IEEE 802.15.4 networks by improving carrier sense multiple access with collision avoidance (CSMA/CA). Improving CSMA/CA is important because the low-power consumption feature and throughput performance of IEEE 802.15.4 are greatly affected by CSMA/CA behavior. To improve the performance of CSMA/CA, this paper focused on increasing the chance to transmit a packet by assessing precise channel status. The previous method used in CCA, which is employed by CSMA/CA, assesses the channel by measuring the energy level of the channel. However, this method shows limited channel assessing behavior, which comes from simple threshold dependent channel busy evaluation. The proposed method solves this limited channel decision problem by dividing CCA into two groups. Two groups of CCA compare their energy levels to get precise channel status. To evaluate the performance of the segmentized CCA method, a Markov chain model has been developed. The validation of analytic results is confirmed by comparing them with simulation results. Additionally, simulation results show the proposed method is improving a maximum 8.76% of throughput and decreasing a maximum 3.9% of the average number of CCAs per packet transmission than the IEEE 802.15.4 CCA method. PMID:27271626

  1. Effect of Pore Topology and Accessibility on Gas Adsorption Capacity in Zeolitic-Imidazolate Frameworks: Bringing Molecular Simulation Close to Experiment

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

    Babarao, Ravichandar; Dai, Sheng; Jiang, Deen

    2011-01-01

    When all cages are assumed to be accessible, popular force fields such as universal force field (UFF) and DREIDING dramatically overpredicted gas adsorption capacity in two widely studied zeolitic-imidazolate frameworks (ZIFs), ZIF-68 and -69. Instead of adjusting the force-field parameters to match the experiments, herein we show that when the pore topology and accessibility are correctly taken into account, simulations with the standard force fields agree very well with the experiments. Careful inspection shows that ZIF-68 and -69 have two one-dimensional channels, which are not interaccessible to gases. The small channel consists of alternating small (HPR) and medium (GME) cages,more » while the large channel comprises the large (KNO) cages. Our analysis indicates that the small channel is not accessible to gases such as CO{sub 2}. So when the cages in the small channel are intentionally blocked in our simulation, the predicted adsorption capacities of CO{sub 2}, CH{sub 4} and N{sub 2} at room temperature from standard force-field parameters for the framework show excellent agreement with the experimental results. In the case of H{sub 2}, all cages are accessible, so simulation results without cage-blocking show excellent agreement with experiment. Due to the promising potential of ZIFs in gas storage and separation, our work here shows that pore topology and accessibility should be carefully examined to understand how gases adsorb in ZIFs.« less

  2. Exploration of the Ca2+ interaction modes of the nifedipine calcium channel antagonist.

    PubMed

    Liu, Huichun; Zhang, Liang; Li, Ping; Cukier, Robert I; Bu, Yuxiang

    2007-02-02

    A comprehensive study is carried out using quantum chemical computation and molecular dynamics (MD) simulations to gain insight into the interaction between Ca(2+) ions and the most important class of calcium channel antagonists--nifedipine. First, the chelating structures and energetic characters of nifedipine-Ca(2+) in the gas phase are explored, and 25 isomers are found. The most favorable chelating mode is a tridentate one, that is, Ca(2+) binds to two carbonyl O atoms and one nitryl O atom, where Ca(2+) is above the plane of the three O atoms to form a pyramidal structure. Accurate geometric structures, relative stabilities, vertical and adiabatic binding energies, and charge distributions are discussed. The differences in the geometries and energies among these isomers are analyzed from the contributions of chelating sites, electrostatics and polarizations, steric repulsions, and charge distributions. The interconversions among isomers with similar geometries and energies are also investigated because of the importance of the geometric transformation in the biological system. Furthermore, certain numbers of water molecules are added to the nifedipine-Ca(2+) system to probe the effect of water. A detailed study is performed on the hydrated geometries on the basis of the most stable isomer 1. Stepwise hydration can weaken the nifedipine-Ca(2+) interaction, and the chelating sites of nifedipine are gradually replaced by the added water molecules. Hexacoordination is found to be the most favorable geometry no matter how many water molecules were added, which can be verified by the MD simulations. The transfer of water molecules from the inner shell to the outer shell is also supported by MD simulations of the hexahydrated complexes.

  3. Verina Morton Jones, MD.

    PubMed

    Rishworth, Susan K

    2012-01-01

    The purpose of this historical article is to demonstrate, as the biography of Verina Morton Jones, MD, is uncovered, the difficulties inherent in researching original source material on the lives of 19th- and early 20th-century African American physicians as well as the great benefits derived from doing this research. The procedures used include basic archival research and close examination of published materials about her in the past, in conjunction with oral history. Original correspondence from Dr Morton Jones to her niece and nephew is used to illustrate events in her life and the thoughts and attitudes she expressed. Some of these thoughts and attitudes reflect those current situations in which African Americans found themselves, and others are quite unique, no doubt owing to her privileged position in the African American community. The principle conclusions reached include the great benefits derived from doing this kind of research, as difficult and time-consuming as that may be, with the enhanced knowledge and appreciation of the heritage of African American physicians, and insights into American social history during this period.

  4. 47 CFR 76.971 - Commercial leased access terms and conditions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Rate Regulation § 76.971 Commercial leased... channel designated for part-time leased access use that is programmed with less than 18 hours of part-time...

  5. 47 CFR 76.971 - Commercial leased access terms and conditions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Rate Regulation § 76.971 Commercial leased... channel designated for part-time leased access use that is programmed with less than 18 hours of part-time...

  6. 47 CFR 76.971 - Commercial leased access terms and conditions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Rate Regulation § 76.971 Commercial leased... channel designated for part-time leased access use that is programmed with less than 18 hours of part-time...

  7. 47 CFR 76.971 - Commercial leased access terms and conditions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Rate Regulation § 76.971 Commercial leased... channel designated for part-time leased access use that is programmed with less than 18 hours of part-time...

  8. 47 CFR 76.971 - Commercial leased access terms and conditions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Cable Rate Regulation § 76.971 Commercial leased... channel designated for part-time leased access use that is programmed with less than 18 hours of part-time...

  9. Calcium channel blockers for inhibiting preterm labour and birth.

    PubMed

    Flenady, Vicki; Wojcieszek, Aleena M; Papatsonis, Dimitri N M; Stock, Owen M; Murray, Linda; Jardine, Luke A; Carbonne, Bruno

    2014-06-05

    Preterm birth is a major contributor to perinatal mortality and morbidity, affecting around 9% of births in high-income countries and an estimated 13% of births in low- and middle-income countries. Tocolytics are drugs used to suppress uterine contractions for women in preterm labour. The most widely used tocolytic are the betamimetics, however, these are associated with a high frequency of unpleasant and sometimes severe maternal side effects. Calcium channel blockers (CCBs) (such as nifedipine) may have similar tocolytic efficacy with less side effects than betamimetics. Oxytocin receptor antagonists (ORAs) (e.g. atosiban) also have a low side-effect profile. To assess the effects on maternal, fetal and neonatal outcomes of CCBs, administered as a tocolytic agent, to women in preterm labour. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (12 November 2013). All published and unpublished randomised trials in which CCBs were used for tocolysis for women in labour between 20 and 36 completed weeks' gestation. Two review authors independently assessed trial eligibility, undertook quality assessment and data extraction. Results are presented using risk ratio (RR) for categorical data and mean difference (MD) for data measured on a continuous scale with the 95% confidence interval (CI). The number needed to treat to benefit (NNTB) and the number needed to treat to harm (NNTH) were calculated for categorical outcomes that were statistically significantly different. This update includes 26 additional trials involving 2511 women, giving a total of 38 included trials (3550 women). Thirty-five trials used nifedipine as the CCB and three trials used nicardipine. Blinding of intervention and outcome assessment was undertaken in only one of the trials (a placebo controlled trial). However, objective outcomes defined according to timing of birth and perinatal mortality were considered to have low risk of detection bias.Two small trials comparing CCBs

  10. Molecular cloning and functional analysis of a UV-B photoreceptor gene, MdUVR8 (UV Resistance Locus 8), from apple.

    PubMed

    Zhao, Cheng; Mao, Ke; You, Chun-Xiang; Zhao, Xian-Yan; Wang, Shu-Hui; Li, Yuan-Yuan; Hao, Yu-Jin

    2016-06-01

    UVR8 (UV Resistance Locus 8) is an ultraviolet-B (UV-B; 280-315nm) light receptor that is involved in regulating many aspects of plant growth and development. UV-B irradiation can increase the development of flower and fruit coloration in many fruit trees, such as grape, pear and apple. Previous investigations of the structure and functions of UVR8 in plants have largely focused on Arabidopsis. Here, we isolated the UVR8 gene from apple (Malus domestica) and analyzed its function in transgenic Arabidopsis. Genomic and protein sequence analysis showed that MdUVR8 shares high similarity with the AtUVR8 protein from Arabidopsis, including the conserved seven-bladed β-propeller, the C27 region, the 3 "GWRHT" motifs and crucial amino-acid residues (14 Trps, 2 Args). A point mutation prediction and three-dimensional structural analysis of MdUVR8 indicated that it has a similar structure to AtUVR8 and that the crucial residues are also important in MdUVR8. In terms of transcript levels, MdUVR8 expression was up-regulated by UV-B light, which suggests that its expression follows a 24-h circadian rhythm. Using heterologous expression of MdUVR8 in both uvr8-1 mutant and wild-type (WT) Arabidopsis, we found that MdUVR8 regulates hypocotyl elongation and gene expression under UV-B light. These data provide functional evidence for a role of MdUVR8 in controlling photomorphogenesis under UV-B light and indicate that the function of UVR8 is conserved between Arabidopsis and apple. Furthermore, we examined the interaction between MdUVR8 and MdCOP1 (constitutive photomorphogenic1) using a yeast two-hybrid assay and a co-immunoprecipitation assay. This interaction provides a direction for investigating the regulatory mechanisms of the UV-B-light pathway in apple. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Full-Scale Crash Test of an MD-500 Helicopter

    NASA Technical Reports Server (NTRS)

    Littell, Justin

    2011-01-01

    A full-scale crash test was successfully conducted in March 2010 of an MD-500 helicopter at NASA Langley Research Center s Landing and Impact Research Facility. The reasons for conducting this test were threefold: 1 To generate data to be used with finite element computer modeling efforts, 2 To study the crashworthiness features typically associated with a small representative helicopter, and 3 To compare aircraft response to data collected from a previously conducted MD-500 crash test, which included an externally deployable energy absorbing (DEA) concept. Instrumentation on the airframe included accelerometers on various structural components of the airframe; and strain gages on keel beams, skid gear and portions of the skin. Three Anthropomorphic Test Devices and a specialized Human Surrogate Torso Model were also onboard to collect occupant loads for evaluation with common injury risk criteria. This paper presents background and results from this crash test conducted without the DEA concept. These results showed accelerations of approximately 30 to 50 g on the airframe at various locations, little energy attenuation through the airframe, and moderate to high probability of occupant injury for a variety of injury criteria.

  12. 77 FR 11423 - Safety Zone; Magothy River, Sillery Bay, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-27

    ...-AA00 Safety Zone; Magothy River, Sillery Bay, MD AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast Guard proposes to establish a safety zone in certain waters of the Magothy... in the Magothy River, in Sillery Bay, Maryland. The proposed rule is needed to control movement...

  13. Toward elucidating the heat activation mechanism of the TRPV1 channel gating by molecular dynamics simulation.

    PubMed

    Wen, Han; Qin, Feng; Zheng, Wenjun

    2016-12-01

    As a key cellular sensor, the TRPV1 cation channel undergoes a gating transition from a closed state to an open state in response to various physical and chemical stimuli including noxious heat. Despite years of study, the heat activation mechanism of TRPV1 gating remains enigmatic at the molecular level. Toward elucidating the structural and energetic basis of TRPV1 gating, we have performed molecular dynamics (MD) simulations (with cumulative simulation time of 3 μs), starting from the high-resolution closed and open structures of TRPV1 solved by cryo-electron microscopy. In the closed-state simulations at 30°C, we observed a stably closed channel constricted at the lower gate (near residue I679), while the upper gate (near residues G643 and M644) is dynamic and undergoes flickery opening/closing. In the open-state simulations at 60°C, we found higher conformational variation consistent with a large entropy increase required for the heat activation, and both the lower and upper gates are dynamic with transient opening/closing. Through ensemble-based structural analyses of the closed state versus the open state, we revealed pronounced closed-to-open conformational changes involving the membrane proximal domain (MPD) linker, the outer pore, and the TRP helix, which are accompanied by breaking/forming of a network of closed/open-state specific hydrogen bonds. By comparing the closed-state simulations at 30°C and 60°C, we observed heat-activated conformational changes in the MPD linker, the outer pore, and the TRP helix that resemble the closed-to-open conformational changes, along with partial formation of the open-state specific hydrogen bonds. Some of the residues involved in the above key hydrogen bonds were validated by previous mutational studies. Taken together, our MD simulations have offered rich structural and dynamic details beyond the static structures of TRPV1, and promising targets for future mutagenesis and functional studies of the TRPV1 channel

  14. Toward elucidating the heat activation mechanism of the TRPV1 channel gating by molecular dynamics simulation

    PubMed Central

    Wen, Han; Qin, Feng; Zheng, Wenjun

    2016-01-01

    As a key cellular sensor, the TRPV1 cation channel undergoes a gating transition from a closed state to an open state in response to various physical and chemical stimuli including noxious heat. Despite years of study, the heat activation mechanism of TRPV1 gating remains enigmatic at the molecular level. Toward elucidating the structural and energetic basis of TRPV1 gating, we have performed molecular dynamics (MD) simulations (with cumulative simulation time of 3 μs), starting from the high-resolution closed and open structures of TRPV1 solved by cryo-electron microscopy. In the closed-state simulations at 30°C, we observed a stably closed channel constricted at the lower gate (near residue I679), while the upper gate (near residues G643 and M644) is dynamic and undergoes flickery opening/closing. In the open-state simulations at 60°C, we found higher conformational variation consistent with a large entropy increase required for the heat activation, and both the lower and upper gates are dynamic with transient opening/closing. Through ensemble-based structural analyses of the closed state vs. the open state, we revealed pronounced closed-to-open conformational changes involving the membrane proximal domain (MPD) linker, the outer pore, and the TRP helix, which are accompanied by breaking/forming of a network of closed/open-state specific hydrogen bonds. By comparing the closed-state simulations at 30°C and 60°C, we observed heat-activated conformational changes in the MPD linker, the outer pore, and the TRP helix that resemble the closed-to-open conformational changes, along with partial formation of the open-state specific hydrogen bonds. Some of the residues involved in the above key hydrogen bonds were validated by previous mutational studies. Taken together, our MD simulations have offered rich structural and dynamic details beyond the static structures of TRPV1, and promising targets for future mutagenesis and functional studies of the TRPV1 channel

  15. Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury

    PubMed Central

    Zhang, Yali; Wu, Jianzhang; Ying, Shilong; Chen, Gaozhi; Wu, Beibei; Xu, Tingting; Liu, Zhiguo; Liu, Xing; Huang, Lehao; Shan, Xiaoou; Dai, Yuanrong; Liang, Guang

    2016-01-01

    Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases. In this study, we designed and synthesized 31 chalcone derivatives that contain the moiety of (E)-4-phenylbut-3-en-2-one, which we consider the core structure of current MD2 inhibitors. We first evaluated the anti-inflammatory activities of these compounds in MPMs. For the most active compound 20, we confirmed that it is a specific MD2 inhibitor through a series of biochemical experiments and elucidated that it binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg90 and Tyr102 residues. Compound 20 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with compound 20 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives we identified is a potential candidate for treating acute inflammatory diseases. PMID:27118147

  16. Distributed reservation-based code division multiple access

    NASA Astrophysics Data System (ADS)

    Wieselthier, J. E.; Ephremides, A.

    1984-11-01

    The use of spread spectrum signaling, motivated primarily by its antijamming capabilities in military applications, leads naturally to the use of Code Division Multiple Access (CDMA) techniques that permit the successful simultaneous transmission by a number of users over a wideband channel. In this paper we address some of the major issues that are associated with the design of multiple access protocols for spread spectrum networks. We then propose, analyze, and evaluate a distributed reservation-based multiple access protocol that does in fact exploit CDMA properties. Especially significant is the fact that no acknowledgment or feedback information from the destination is required (thus facilitating communication with a radio-silent mode), nor is any form of coordination among the users necessary.

  17. Toxic β-Amyloid (Aβ) Alzheimer's Ion Channels: From Structure to Function and Design

    NASA Astrophysics Data System (ADS)

    Nussinov, Ruth

    2012-02-01

    Full-length amyloid beta peptides (Aβ1-40/42) form neuritic amyloid plaques in Alzheimer's disease (AD) patients and are implicated in AD pathology. Recent biophysical and cell biological studies suggest a direct mechanism of amyloid beta toxicity -- ion channel mediated loss of calcium homeostasis. Truncated amyloid beta fragments (Aβ11-42 and Aβ17-42), commonly termed as non-amyloidogenic are also found in amyloid plaques of Alzheimer's disease (AD) and in the preamyloid lesions of Down's syndrome (DS), a model system for early onset AD study. Very little is known about the structure and activity of these smaller peptides although they could be key AD and DS pathological agents. Using complementary techniques of explicit solvent molecular dynamics (MD) simulations, atomic force microscopy (AFM), channel conductance measurements, cell calcium uptake assays, neurite degeneration and cell death assays, we have shown that non-amyloidogenic Aβ9-42 and Aβ17-42 peptides form ion channels with loosely attached subunits and elicit single channel conductances. The subunits appear mobile suggesting insertion of small oligomers, followed by dynamic channel assembly and dissociation. These channels allow calcium uptake in APP-deficient cells and cause neurite degeneration in human cortical neurons. Channel conductance, calcium uptake and neurite degeneration are selectively inhibited by zinc, a blocker of amyloid ion channel activity. Thus truncated Aβ fragments could account for undefined roles played by full length Aβs and provide a novel mechanism of AD and DS pathology. The emerging picture from our large-scale simulations is that toxic ion channels formed by β-sheets are highly polymorphic, and spontaneously break into loosely interacting dynamic units (though still maintaining ion channel structures as imaged with AFM), that associate and dissociate leading to toxic ion flux. This sharply contrasts intact conventional gated ion channels that consist of tightly

  18. Open-access microfluidic patch-clamp array with raised lateral cell trapping sites.

    PubMed

    Lau, Adrian Y; Hung, Paul J; Wu, Angela R; Lee, Luke P

    2006-12-01

    A novel open-access microfluidic patch-clamp array chip with lateral cell trapping sites raised above the bottom plane of the chip was developed by combining both a microscale soft-lithography and a macroscale polymer fabrication method. This paper demonstrates the capability of using such an open-access fluidic system for patch-clamp measurements. The surface of the open-access patch-clamp sites prepared by the macroscale hole patterning method of soft-state elastic polydimethylsiloxane (PDMS) is examined; the seal resistances are characterized and correlated with the aperture dimensions. Whole cell patch-clamp measurements are carried out with CHO cells expressing Kv2.1 ion channels. Kv2.1 ion channel blocker (TEA) dosage response is characterized and the binding activity is examined. The results demonstrate that the system is capable of performing whole cell measurements and drug profiling in a more efficient manner than the traditional patch-clamp set-up.

  19. Structural basis for binding of aurora-AG198N- INCENP complex: MD simulations and free energy calculations.

    PubMed

    Tanneeru, Karunakar; Guruprasad, Lalitha

    2013-11-01

    Aurora-A, B and C are non-receptor serine/threonine kinases in Homo sapiens. In spite of high similarity in their sequences, they possess distinct binding partners. These kinases play an important role in cell division and overexpressed in certain cancers. It has been demonstrated that Gly198 in Aurora-A kinase is responsible for its basal kinase activity, the mutation G198N transforms Aurora-A to Aurora-B like function and localization by binding to Inner centromere protein (INCENP). The molecular mechanisms, structural determinants and the binding energetics of the Aurora-A - INCENP complex owing to a single amino acid G198N mutation are not studied. Therefore, we have docked INCENP into human Aurora-A kinase, mutated Gly198 to Asn, Leu and Ala. The wild type and mutant Aurora-A - INCENP complexes were subjected to 40 ns molecular dynamics (MD) simulations. The Asn198 is located in the amphipathic cavity comprising Leu869(IN), Glu868(IN), Thr872(IN), Tyr197(AurA) and Tyr199(AurA) and the interactions mediated via hydrogen bonds are important to stabilize the Aurora-A(G198N) - INCENP complex. The fluctuations in the secondary structural elements and the solvent accessible surface area of all the four complexes during the MD simulations were studied. We calculated the binding free energy upon mutation in the three mutant complexes. The Aurora-A(G198N) - INCENP complex with hydrophilic amino acid mutation has the negative free energy of solvation indicating favorable interactions with INCENP. Our results provide the structural basis and energetics of the human Aurora-A(G198N) - INCENP complex.

  20. 76 FR 9225 - Drawbridge Operation Regulation; Curtis Creek, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ...; Department of Homeland Security Delegation No. 0170.1. 0 2. From February 17, 2011 to November 30, 2011... of the Pennington Avenue Bridge, across Curtis Creek, mile 0.9, at Baltimore, MD. This temporary... replacement of the grid deck, floor beams and stringers. DATES: This temporary final rule is effective from 6...

  1. 75 FR 30296 - Special Local Regulation for Marine Event; Maryland Swim for Life, Chester River, Chestertown, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-01

    ...-AA08 Special Local Regulation for Marine Event; Maryland Swim for Life, Chester River, Chestertown, MD... Chestertown, MD during the Maryland Swim for Life. Special local regulations are necessary to provide for the safety of life on navigable waters during the event. DATES: This rule is effective from 5:30 a.m. to 2:30...

  2. Analysis of physical layer performance of hybrid optical-wireless access network

    NASA Astrophysics Data System (ADS)

    Shaddad, R. Q.; Mohammad, A. B.; Al-hetar, A. M.

    2011-09-01

    The hybrid optical-wireless access network (HOWAN) is a favorable architecture for next generation access network. It is an optimal combination of an optical backhaul and a wireless front-end for an efficient access network. In this paper, the HOWAN architecture is designed based on a wavelengths division multiplexing/time division multiplexing passive optical network (WDM/TDM PON) at the optical backhaul and a wireless fidelity (WiFi) technology at the wireless front-end. The HOWAN is proposed that can provide blanket coverage of broadband and flexible connection for end-users. Most of the existing works, based on performance evaluation are concerned on network layer aspects. This paper reports physical layer performance in terms of the bit error rate (BER), eye diagram, and signal-to-noise ratio (SNR) of the communication system. It accommodates 8 wavelength channels with 32 optical network unit/wireless access points (ONU/APs). It is demonstrated that downstream and upstream of 2 Gb/s can be achieved by optical backhaul for each wavelength channel along optical fiber length of 20 km and a data rate of 54 Mb/s per ONU/AP along a 50 m outdoor wireless link.

  3. Scalable Lunar Surface Networks and Adaptive Orbit Access

    NASA Technical Reports Server (NTRS)

    Wang, Xudong

    2015-01-01

    Teranovi Technologies, Inc., has developed innovative network architecture, protocols, and algorithms for both lunar surface and orbit access networks. A key component of the overall architecture is a medium access control (MAC) protocol that includes a novel mechanism of overlaying time division multiple access (TDMA) and carrier sense multiple access with collision avoidance (CSMA/CA), ensuring scalable throughput and quality of service. The new MAC protocol is compatible with legacy Institute of Electrical and Electronics Engineers (IEEE) 802.11 networks. Advanced features include efficiency power management, adaptive channel width adjustment, and error control capability. A hybrid routing protocol combines the advantages of ad hoc on-demand distance vector (AODV) routing and disruption/delay-tolerant network (DTN) routing. Performance is significantly better than AODV or DTN and will be particularly effective for wireless networks with intermittent links, such as lunar and planetary surface networks and orbit access networks.

  4. An apple MYB transcription factor, MdMYB3, is involved in regulation of anthocyanin biosynthesis and flower development

    PubMed Central

    2013-01-01

    Background Red coloration of fruit is an important trait in apple, and it is mainly attributed to the accumulation of anthocyanins, a class of plant flavonoid metabolites. Anthocyanin biosynthesis is genetically determined by structural and regulatory genes. Plant tissue pigmentation patterns are mainly controlled by expression profiles of regulatory genes. Among these regulatory genes are MYB transcription factors (TFs), wherein the class of two-repeats (R2R3) is deemed the largest, and these are associated with the anthocyanin biosynthesis pathway. Although three MdMYB genes, almost identical in nucleotide sequences, have been identified in apple, it is likely that there are other R2R3 MYB TFs that are present in the apple genome that are also involved in the regulation of coloration of red color pigmentation of the skin of apple fruits. Results In this study, a novel R2R3 MYB gene has been isolated and characterized in apple. This MYB gene is closely related to the Arabidopsis thaliana AtMYB3, and has been designated as MdMYB3. This TF belongs to the subgroup 4 R2R3 family of plant MYB transcription factors. This apple MdMYB3 gene is mapped onto linkage group 15 of the integrated apple genetic map. Transcripts of MdMYB3 are detected in all analyzed tissues including leaves, flowers, and fruits. However, transcripts of MdMYB3 are higher in excocarp of red-skinned apple cultivars than that in yellowish-green skinned apple cultivars. When this gene is ectopically expressed in Nicotiana tabacum cv. Petite Havana SR1, flowers of transgenic tobacco lines carrying MdMYB3 have exhibited increased pigmentation and accumulate higher levels of anthocyanins and flavonols than wild-type flowers. Overexpression of MdMYB3 has resulted in transcriptional activation of several flavonoid pathway genes, including CHS, CHI, UFGT, and FLS. Moreover, peduncles of flowers and styles of pistils of transgenic plants overexpressing MdMYB3 are longer than those of wild-type plants, thus

  5. 76 FR 20032 - Thomas E. Mitchell, M.D.; Dismissal of Proceeding

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-7] Thomas E. Mitchell, M.D.; Dismissal of Proceeding On September 11, 2009, the Deputy Assistant Administrator, Office of Diversion... procedural misconduct, misrepresentations and the subsequent illegitimate denial of due process.'' Id. On...

  6. 77 FR 36003 - Patrick K. Chau, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration Patrick K. Chau, M.D.; Decision and Order On August 8, 2011, the Deputy Assistant Administrator, Office of Diversion Control, Drug Enforcement... drug-seeking and diversion behaviors, and not requesting medical records from other providers or...

  7. Dynamics and intramolecular ligand binding of DtxR studied by MD simulations and NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Yi, Myunggi; Bhattacharya, Nilakshee; Zhou, Huan-Xiang

    2005-11-01

    Diphtheria toxin repressor (DtxR) regulates the expression of the diphtheria toxin gene through intramolecular ligand binding (Wylie et al., Biochemistry 2005, 44:40-51). Protein dynamics is essential to the binding process of the Pro-rich (Pr) ligand to the C-terminal SH3 domain. We present MD and NMR results on the dynamics and ligand interactions of a Pr-SH3 construct of DtxR. NMR relaxation data (T1, T2, and NOE) showed that the Pr ligand is very flexible, suggesting that it undergoes binding/unbinding transitions. A 50-ns MD trajectory of the protein was used to calculate T1, T2, and NOE, reproducing the NMR results for the SH3 domain but not for the Pr segment. During the MD simulation, the ligand stayed bound to the SH3 domain; thus the simulation represented the bound state. The NMR data for the Pr-segment could be explained by assuming that they represented the average behavior of a fast binding/unbinding exchange. Though unbinding was not observed in the MD simulation, the simulation did show large fluctuations of a loop which forms part of the wall of the binding pocket. The fluctuations led to opening up of the binding pocket, thus weakening the interaction with the Pr segment and perhaps ultimately leading to ligand unbinding.

  8. Characterization of dual-polarization LTE radio over a free-space optical turbulence channel.

    PubMed

    Bohata, J; Zvanovec, S; Korinek, T; Mansour Abadi, M; Ghassemlooy, Z

    2015-08-10

    A dual polarization (DP) radio over a free-space optical (FSO) communication link using a long-term evolution (LTE) radio signal is proposed and analyzed under different turbulence channel conditions. Radio signal transmission over the DP FSO channel is experimentally verified by means of error vector magnitude (EVM) statistics. We demonstrate that such a system, employing a 64 quadrature amplitude modulation at the frequency bands of 800 MHz and 2.6 GHz, evinces reliability with <8% of EVM in a turbulent channel. Based on the results, we show that transmitting the LTE signal over the FSO channel is a potential solution for last-mile access or backbone networks, when using multiple-input multiple-output based DP signals.

  9. Wettability of graphitic-carbon and silicon surfaces: MD modeling and theoretical analysis

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

    Ramos-Alvarado, Bladimir; Kumar, Satish; Peterson, G. P.

    2015-07-28

    The wettability of graphitic carbon and silicon surfaces was numerically and theoretically investigated. A multi-response method has been developed for the analysis of conventional molecular dynamics (MD) simulations of droplets wettability. The contact angle and indicators of the quality of the computations are tracked as a function of the data sets analyzed over time. This method of analysis allows accurate calculations of the contact angle obtained from the MD simulations. Analytical models were also developed for the calculation of the work of adhesion using the mean-field theory, accounting for the interfacial entropy changes. A calibration method is proposed to providemore » better predictions of the respective contact angles under different solid-liquid interaction potentials. Estimations of the binding energy between a water monomer and graphite match those previously reported. In addition, a breakdown in the relationship between the binding energy and the contact angle was observed. The macroscopic contact angles obtained from the MD simulations were found to match those predicted by the mean-field model for graphite under different wettability conditions, as well as the contact angles of Si(100) and Si(111) surfaces. Finally, an assessment of the effect of the Lennard-Jones cutoff radius was conducted to provide guidelines for future comparisons between numerical simulations and analytical models of wettability.« less

  10. Modeling surface-water flow and sediment mobility with the Multi-Dimensional Surface-Water Modeling System (MD_SWMS)

    USGS Publications Warehouse

    McDonald, Richard; Nelson, Jonathan; Kinzel, Paul; Conaway, Jeffrey S.

    2006-01-01

    The Multi-Dimensional Surface-Water Modeling System (MD_SWMS) is a Graphical User Interface for surface-water flow and sediment-transport models. The capabilities of MD_SWMS for developing models include: importing raw topography and other ancillary data; building the numerical grid and defining initial and boundary conditions; running simulations; visualizing results; and comparing results with measured data.

  11. A cAMP-Regulated Chloride Channel in Lymphocytes that is Affected in Cystic Fibrosis

    NASA Astrophysics Data System (ADS)

    Chen, Jennifer H.; Schulman, Howard; Gardner, Phyllis

    1989-02-01

    A defect in regulation of a chloride channel appears to be the molecular basis for cystic fibrosis (CF), a common lethal genetic disease. It is shown here that a chloride channel with kinetic and regulatory properties similar to those described for secretory epithelial cells is present in both T and B lymphocyte cell lines. The regulation of the channels by adenosine 3',5'-monophosphate (cAMP)--dependent protein kinase in transformed B cells from CF patients is defective. Thus, lymphocytes may be an accessible source of CF tissue for study of this defect, for cloning of the chloride channel complex, and for diagnosis of the disease.

  12. 75 FR 54069 - Drawbridge Operation Regulations; Curtis Creek, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... Baltimore, MD. The requested change would have allowed the bridge to operate from a remote location at the...) 398-6629, e-mail [email protected] . If you have questions on viewing material in the... eliminating the need for a bridge tender by allowing the bridge to be operated from a remote location at the...

  13. Reduced-rank technique for joint channel estimation in TD-SCDMA systems

    NASA Astrophysics Data System (ADS)

    Kamil Marzook, Ali; Ismail, Alyani; Mohd Ali, Borhanuddin; Sali, Adawati; Khatun, Sabira

    2013-02-01

    In time division-synchronous code division multiple access systems, increasing the system capacity by exploiting the inserting of the largest number of users in one time slot (TS) requires adding more estimation processes to estimate the joint channel matrix for the whole system. The increase in the number of channel parameters due the increase in the number of users in one TS directly affects the precision of the estimator's performance. This article presents a novel channel estimation with low complexity, which relies on reducing the rank order of the total channel matrix H. The proposed method exploits the rank deficiency of H to reduce the number of parameters that characterise this matrix. The adopted reduced-rank technique is based on truncated singular value decomposition algorithm. The algorithms for reduced-rank joint channel estimation (JCE) are derived and compared against traditional full-rank JCEs: least squares (LS) or Steiner and enhanced (LS or MMSE) algorithms. Simulation results of the normalised mean square error showed the superiority of reduced-rank estimators. In addition, the channel impulse responses founded by reduced-rank estimator for all active users offers considerable performance improvement over the conventional estimator along the channel window length.

  14. A mobile communication system providing integrated voice/data services over power limited satellite channels

    NASA Astrophysics Data System (ADS)

    Bose, Sanjay K.; Gordon, J. J.

    The modeling and analysis of a system providing integrated voice/data services to mobile terminals over a power-limited satellite channel are discussed. The mobiles use slotted Aloha random access to send requests for channel assignments to a central station. For successful requests, the actual transmission of voice/data within a call is done using the channel assigned for this purpose by the central station. The satellite channel is assumed to be power limited. Taking into account the known burstiness of voice sources (which use a voice-activated switch), the central station overassigns channels so that the average total power is below the power limit of the satellite transponder. The performance of this model is analyzed. Certain simple, static control strategies for improving performance are also proposed.

  15. Low-cost high performance distributed data storage for multi-channel observations

    NASA Astrophysics Data System (ADS)

    Liu, Ying-bo; Wang, Feng; Deng, Hui; Ji, Kai-fan; Dai, Wei; Wei, Shou-lin; Liang, Bo; Zhang, Xiao-li

    2015-10-01

    The New Vacuum Solar Telescope (NVST) is a 1-m solar telescope that aims to observe the fine structures in both the photosphere and the chromosphere of the Sun. The observational data acquired simultaneously from one channel for the chromosphere and two channels for the photosphere bring great challenges to the data storage of NVST. The multi-channel instruments of NVST, including scientific cameras and multi-band spectrometers, generate at least 3 terabytes data per day and require high access performance while storing massive short-exposure images. It is worth studying and implementing a storage system for NVST which would balance the data availability, access performance and the cost of development. In this paper, we build a distributed data storage system (DDSS) for NVST and then deeply evaluate the availability of real-time data storage on a distributed computing environment. The experimental results show that two factors, i.e., the number of concurrent read/write and the file size, are critically important for improving the performance of data access on a distributed environment. Referring to these two factors, three strategies for storing FITS files are presented and implemented to ensure the access performance of the DDSS under conditions of multi-host write and read simultaneously. The real applications of the DDSS proves that the system is capable of meeting the requirements of NVST real-time high performance observational data storage. Our study on the DDSS is the first attempt for modern astronomical telescope systems to store real-time observational data on a low-cost distributed system. The research results and corresponding techniques of the DDSS provide a new option for designing real-time massive astronomical data storage system and will be a reference for future astronomical data storage.

  16. Ectopic expression of an apple cytochrome P450 gene MdCYPM1 negatively regulates plant photomorphogenesis and stress response in Arabidopsis.

    PubMed

    An, Jian-Ping; Li, Rui; Qu, Feng-Jia; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

    2017-01-29

    Cytochrome P450s play an important role in plant growth and are involved in multiple stresses response. However, little is known about the functions of cytochrome P450s in apple. Here, a Malus × domestica cytochrome P450 monooxygenase 1 gene, MdCYPM1, was identified and subsequently cloned from apple 'Gala' (Malus × domestica). To verify the functions of MdCYPM1, we generated transgenic Arabidopsis plants expressing the apple MdCYPM1 gene under the control of the Cauliflower mosaic virus 35S promoter. Four transgenic lines (#3, #5, #7 and #8) were selected for further study. The transgenic plants exhibited a series of skotomorphogenesis phenotypes relative to wild-type controls, such as reduction of the chlorophyll, anthocyanins content and hypocotyls elongation. In addition, overexpression of MdCYPM1 influenced auxin transport and flowering time in transgenic Arabidopsis. Furthermore, MdCYPM1 expression was induced by salt and mannitol treatments, and the transgenic plants were negatively regulated by salinity and osmotic stresses during germination. These results suggest that MdCYPM1 plays a vital role in plant growth and development. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. PyContact: Rapid, Customizable, and Visual Analysis of Noncovalent Interactions in MD Simulations.

    PubMed

    Scheurer, Maximilian; Rodenkirch, Peter; Siggel, Marc; Bernardi, Rafael C; Schulten, Klaus; Tajkhorshid, Emad; Rudack, Till

    2018-02-06

    Molecular dynamics (MD) simulations have become ubiquitous in all areas of life sciences. The size and model complexity of MD simulations are rapidly growing along with increasing computing power and improved algorithms. This growth has led to the production of a large amount of simulation data that need to be filtered for relevant information to address specific biomedical and biochemical questions. One of the most relevant molecular properties that can be investigated by all-atom MD simulations is the time-dependent evolution of the complex noncovalent interaction networks governing such fundamental aspects as molecular recognition, binding strength, and mechanical and structural stability. Extracting, evaluating, and visualizing noncovalent interactions is a key task in the daily work of structural biologists. We have developed PyContact, an easy-to-use, highly flexible, and intuitive graphical user interface-based application, designed to provide a toolkit to investigate biomolecular interactions in MD trajectories. PyContact is designed to facilitate this task by enabling identification of relevant noncovalent interactions in a comprehensible manner. The implementation of PyContact as a standalone application enables rapid analysis and data visualization without any additional programming requirements, and also preserves full in-program customization and extension capabilities for advanced users. The statistical analysis representation is interactively combined with full mapping of the results on the molecular system through the synergistic connection between PyContact and VMD. We showcase the capabilities and scientific significance of PyContact by analyzing and visualizing in great detail the noncovalent interactions underlying the ion permeation pathway of the human P2X 3 receptor. As a second application, we examine the protein-protein interaction network of the mechanically ultrastable cohesin-dockering complex. Copyright © 2017 Biophysical Society

  18. THE NATIONAL COASTAL ASSESSMENT SETAC ANNUAL MEETING, BALTIMORE, MD NOV 2001

    EPA Science Inventory

    To be presented at the 22nd Annual Meeting of the Society of Environmental Toxicology and Chemistry: Changing Environmental Awareness: Societal Concerns and Scientific Responses, 11-15 November 2001, Baltimore, MD. 1 p. (ERL,GB R859).

    The primary purpose of the Environmen...

  19. 75 FR 47736 - Amendment of Class D and E Airspace, Establishment of Class E Airspace; Patuxent River, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-09

    ... Air Station (NAS), Patuxent River, MD, to reflect the part-time operating status of the control tower... extension to Class D surface area at Patuxent River NAS, Patuxent River, MD, to reflect the part-time... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 71 [Docket No. FAA-2010...

  20. Coded DS-CDMA Systems with Iterative Channel Estimation and no Pilot Symbols

    DTIC Science & Technology

    2010-08-01

    ar X iv :1 00 8. 31 96 v1 [ cs .I T ] 1 9 A ug 2 01 0 1 Coded DS - CDMA Systems with Iterative Channel Estimation and no Pilot Symbols Don...sequence code-division multiple-access ( DS - CDMA ) systems with quadriphase-shift keying in which channel estimation, coherent demodulation, and decoding...amplitude, phase, and the interference power spectral density (PSD) due to the combined interference and thermal noise is proposed for DS - CDMA systems

  1. 77 FR 42459 - Airworthiness Directives; MD Helicopters, Inc. (MDHI) Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-19

    ... the retirement life of certain T-T straps, marking each T-T strap with the expiration date, creating a... strap with an expiration date; creating a component record card for each affected T-T strap; replacing T...-101, P/N 900R3442009-103, or P/N 900R6442009-103 (installed on MDHI Model MD900 helicopters); Creating...

  2. Allocation and Routing of CRAF MD80 Aircraft

    DTIC Science & Technology

    1990-03-01

    8217I0P N2 COF Allocation and Routing of CRAF MD80 Aircraft William B. Carter Captain, USAF AFIT/GST/ENS/90M-4 DISTRIBUTION STATEMENT A D0TE4 I C...posture. My experience as an airlift pilot drew me to this topic dealing with a very special part of our airlift forces, aeromedical evacuation. This...thesis attempts to make a "first cut" in the analysis of how the new Civil Reserve Air Fleet (CRAF) aeromedical evacuation mission should operate. My

  3. Null mutation of the MdACS3 gene, coding for a ripening-specific 1-aminocyclopropane-1-carboxylate synthase, leads to long shelf life in apple fruit.

    PubMed

    Wang, Aide; Yamakake, Junko; Kudo, Hisayuki; Wakasa, Yuhya; Hatsuyama, Yoshimichi; Igarashi, Megumi; Kasai, Atsushi; Li, Tianzhong; Harada, Takeo

    2009-09-01

    Expression of MdACS1, coding for 1-aminocyclopropane-1-carboxylate synthase (ACS), parallels the level of ethylene production in ripening apple (Malus domestica) fruit. Here we show that expression of another ripening-specific ACS gene (MdACS3) precedes the initiation of MdACS1 expression by approximately 3 weeks; MdACS3 expression then gradually decreases as MdACS1 expression increases. Because MdACS3 expression continues in ripening fruit treated with 1-methylcyclopropene, its transcription appears to be regulated by a negative feedback mechanism. Three genes in the MdACS3 family (a, b, and c) were isolated from a genomic library, but two of them (MdACS3b and MdACS3c) possess a 333-bp transposon-like insertion in their 5' flanking region that may prevent transcription of these genes during ripening. A single nucleotide polymorphism in the coding region of MdACS3a results in an amino acid substitution (glycine-289 --> valine) in the active site that inactivates the enzyme. Furthermore, another null allele of MdACS3a, Mdacs3a, showing no ability to be transcribed, was found by DNA sequencing. Apple cultivars homozygous or heterozygous for both null allelotypes showed no or very low expression of ripening-related genes and maintained fruit firmness. These results suggest that MdACS3a plays a crucial role in regulation of fruit ripening in apple, and is a possible determinant of ethylene production and shelf life in apple fruit.

  4. A dsRNA-binding protein MdDRB1 associated with miRNA biogenesis modifies adventitious rooting and tree architecture in apple.

    PubMed

    You, Chun-Xiang; Zhao, Qiang; Wang, Xiao-Fei; Xie, Xing-Bin; Feng, Xiao-Ming; Zhao, Ling-Ling; Shu, Huai-Rui; Hao, Yu-Jin

    2014-02-01

    Although numerous miRNAs have been already isolated from fruit trees, knowledge about miRNA biogenesis is largely unknown in fruit trees. Double-strand RNA-binding (DRB) protein plays an important role in miRNA processing and maturation; however, its role in the regulation of economically important traits is not clear yet in fruit trees. EST blast and RACE amplification were performed to isolate apple MdDRB1 gene. Following expression analysis, RNA binding and protein interaction assays, MdDRB1 was transformed into apple callus and in vitro tissue cultures to characterize the functions of MdDRB1 in miRNA biogenesis, adventitious rooting, leaf development and tree growth habit. MdDRB1 contained two highly conserved DRB domains. Its transcripts existed in all tissues tested and are induced by hormones. It bound to double-strand RNAs and interacted with AtDCL1 (Dicer-Like 1) and MdDCL1. Chip assay indicated its role in miRNA biogenesis. Transgenic analysis showed that MdDRB1 controls adventitious rooting, leaf curvature and tree architecture by modulating the accumulation of miRNAs and the transcript levels of miRNA target genes. Our results demonstrated that MdDRB1 functions in the miRNA biogenesis in a conserved way and that it is a master regulator in the formation of economically important traits in fruit trees. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  5. Multiple channel programmable coincidence counter

    DOEpatents

    Arnone, Gaetano J.

    1990-01-01

    A programmable digital coincidence counter having multiple channels and featuring minimal dead time. Neutron detectors supply electrical pulses to a synchronizing circuit which in turn inputs derandomized pulses to an adding circuit. A random access memory circuit connected as a programmable length shift register receives and shifts the sum of the pulses, and outputs to a serializer. A counter is input by the adding circuit and downcounted by the seralizer, one pulse at a time. The decoded contents of the counter after each decrement is output to scalers.

  6. A comparative study of Message Digest 5(MD5) and SHA256 algorithm

    NASA Astrophysics Data System (ADS)

    Rachmawati, D.; Tarigan, J. T.; Ginting, A. B. C.

    2018-03-01

    The document is a collection of written or printed data containing information. The more rapid advancement of technology, the integrity of a document should be kept. Because of the nature of an open document means the document contents can be read and modified by many parties so that the integrity of the information as a content of the document is not preserved. To maintain the integrity of the data, it needs to create a mechanism which is called a digital signature. A digital signature is a specific code which is generated from the function of producing a digital signature. One of the algorithms that used to create the digital signature is a hash function. There are many hash functions. Two of them are message digest 5 (MD5) and SHA256. Those both algorithms certainly have its advantages and disadvantages of each. The purpose of this research is to determine the algorithm which is better. The parameters which used to compare that two algorithms are the running time and complexity. The research results obtained from the complexity of the Algorithms MD5 and SHA256 is the same, i.e., ⊖ (N), but regarding the speed is obtained that MD5 is better compared to SHA256.

  7. Multicale modeling of the detonation of aluminized explosives using SPH-MD-QM method

    NASA Astrophysics Data System (ADS)

    Peng, Qing; Wang, Guangyu; Liu, Gui-Rong; de, Suvranu

    Aluminized explosives have been applied in military industry since decades ago. Compared with ideal explosives, aluminized explosives feature both fast detonation and slow metal combustion chemistry, generating a complex multi-phase reactive flow. Here, we introduce a sequential multiscale model of SPH-MD-QM to simulate the detonation behavior of aluminized explosives. At the bottom level, first-principles quantum mechanics (QM) calculations are employed to obtain the training sets for fitting the ReaxFF potentials, which are used in turn in the reactive molecular dynamics (MD) simulations in the middle level to obtain the chemical reaction rates and equations of states. At the up lever, a smooth particle hydrodynamics (SPH) method incorporated ignition and growth model and afterburning model has been used for the simulation of the detonation and combustion of the aluminized explosive. Simulation is compared with experiment and good agreement is observed. The proposed multiscale method of SPH-MD-QM could be used to optimize the performance of aluminized explosives. The authors would like to acknowledge the generous financial support from the Defense Threat Reduction Agency (DTRA) Grant No. HDTRA1-13-1-0025 and the Office of Naval Research Grants ONR Award No. N00014-08-1-0462 and No. N00014-12-1-0527.

  8. A Systematic Scheme for Multiple Access in Ethernet Passive Optical Access Networks

    NASA Astrophysics Data System (ADS)

    Ma, Maode; Zhu, Yongqing; Hiang Cheng, Tee

    2005-11-01

    While backbone networks have experienced substantial changes in the last decade, access networks have not changed much. Recently, passive optical networks (PONs) seem to be ready for commercial deployment as access networks, due to the maturity of a number of enabling technologies. Among the PON technologies, Ethernet PON (EPON) standardized by the IEEE 802.3ah Ethernet in the First Mile (EFM) Task Force is the most attractive one because of its high speed, low cost, familiarity, interoperability, and low overhead. In this paper, we consider the issue of upstream channel sharing in the EPONs. We propose a novel multiple-access control scheme to provide bandwidth-guaranteed service for high-demand customers, while providing best effort service to low-demand customers according to the service level agreement (SLA). The analytical and simulation results prove that the proposed scheme performs best in what it is designed to do compared to another well-known scheme that has not considered providing differentiated services. With business customers preferring premium services with guaranteed bandwidth and residential users preferring low-cost best effort services, our scheme could benefit both groups of subscribers, as well as the operators.

  9. 75 FR 24774 - Fairmount Bank, Baltimore, MD; Approval of Conversion Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... DEPARTMENT OF THE TREASURY Office of Thrift Supervision [AC-36 OTS Nos. 08193 and H4677] Fairmount Bank, Baltimore, MD; Approval of Conversion Application Notice is hereby given that on April 15, 2010, the Office of Thrift Supervision approved the application of Fairmount Bank, Baltimore, Maryland, to...

  10. 76 FR 21406 - Michael J. Aruta, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-40] Michael J. Aruta, M.D.; Decision and Order ACTION: Correction. On Thursday, April 7, 2011, the Drug Enforcement Administration published the above-titled Decision and Order, as well as the Decision of the Administrative Law Judge (76...

  11. Concretions in Exhumed Channels Near Hanksville Utah: Implications for Mars

    NASA Technical Reports Server (NTRS)

    Clarke, Jonathan; Stoker, Carol R.

    2011-01-01

    The landscape near Hanksville, Utah, contains a diversity of Mars analogue features. These included segmented and inverted anatasomosing palaeochannels exhumed from the Late Jurassic Brushy Basin Member of the Morrison Formation that hosts abundant small carbonate concretions. The exhumed and inverted channels closely resemble many seen on the surface of Mars in satellite imagery and which may be visited by surface missions in the near future. The channels contain a wealth of palaeo-environmental information, but intrinsically difficult terrain would make their study challenging on Mars. We show that an unexhumed channel feature can be detected geophysically, this may allow their study in more easily accessed terrain. The concretions morphologically and in their surface expression parallel the haematite blue berries that are strewn across the surface of Meridiani Planum on Mars. They are best developed in poorly cemented medium to coarse channel sandstones and appear to have formed early in the diagenetic history.

  12. Initial steps of inactivation at the K+ channel selectivity filter

    PubMed Central

    Thomson, Andrew S.; Heer, Florian T.; Smith, Frank J.; Hendron, Eunan; Bernèche, Simon; Rothberg, Brad S.

    2014-01-01

    K+ efflux through K+ channels can be controlled by C-type inactivation, which is thought to arise from a conformational change near the channel’s selectivity filter. Inactivation is modulated by ion binding near the selectivity filter; however, the molecular forces that initiate inactivation remain unclear. We probe these driving forces by electrophysiology and molecular simulation of MthK, a prototypical K+ channel. Either Mg2+ or Ca2+ can reduce K+ efflux through MthK channels. However, Ca2+, but not Mg2+, can enhance entry to the inactivated state. Molecular simulations illustrate that, in the MthK pore, Ca2+ ions can partially dehydrate, enabling selective accessibility of Ca2+ to a site at the entry to the selectivity filter. Ca2+ binding at the site interacts with K+ ions in the selectivity filter, facilitating a conformational change within the filter and subsequent inactivation. These results support an ionic mechanism that precedes changes in channel conformation to initiate inactivation. PMID:24733889

  13. Low expression of nicotinic acetylcholine receptor subunit Mdα2 in neonicotinoid-resistant strains of Musca domestica L.

    PubMed

    Markussen, Mette D K; Kristensen, Michael

    2010-11-01

    Neonicotinoid action as well as resistance involves interaction with nicotinic acetylcholine receptors (nAChRs). In the housefly, neonicotinoid resistance also involves cytochrome P450, as indicated by bioassay with synergist as well as altered expression. In bioassay, synergism was only partial and indicated possible target-site resistance. The nAChR α2 subunit is important in neonicotinoid toxicity to insects, and gene expression of the Mdα2 subunit was investigated in field populations and laboratory strains of neonicotinoid-resistant and insecticide-susceptible houseflies, Musca domestica L. The genomic sequence covering exon III-VII of Mdα2 was analysed for mutations. Gene expression profiling of Mdα2 revealed notable differences between neonicotinoid-resistant and insecticide-susceptible houseflies. On average, the neonicotinoid-resistant field population 766b and the imidacloprid selected strain 791imi had 60% lower copy numbers of Mdα2 compared with the susceptible reference strain. Sequencing of exon III-VII of the Mdα2, encoding acetylcholine binding-site regions and three out of four transmembrane domains, did not reveal any mutations explaining the increased neonicotinoid tolerance in the strains examined. Previous discoveries and the results of this study suggest that the neonicotinoid resistance mechanism in Danish houseflies involves both cytochrome P450 monooxygenase-mediated detoxification and reduced expression of the nAChR subunit α2. Copyright © 2010 Society of Chemical Industry.

  14. 33 CFR 334.160 - Severn River, at U.S. Naval Academy Santee Basin, Annapolis, Md.; naval restricted area.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Severn River, at U.S. Naval Academy Santee Basin, Annapolis, Md.; naval restricted area. 334.160 Section 334.160 Navigation and... RESTRICTED AREA REGULATIONS § 334.160 Severn River, at U.S. Naval Academy Santee Basin, Annapolis, Md.; naval...

  15. 33 CFR 334.160 - Severn River, at U.S. Naval Academy Santee Basin, Annapolis, Md.; naval restricted area.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Severn River, at U.S. Naval Academy Santee Basin, Annapolis, Md.; naval restricted area. 334.160 Section 334.160 Navigation and... RESTRICTED AREA REGULATIONS § 334.160 Severn River, at U.S. Naval Academy Santee Basin, Annapolis, Md.; naval...

  16. Glucose Sensor MdHXK1 Phosphorylates and Stabilizes MdbHLH3 to Promote Anthocyanin Biosynthesis in Apple

    PubMed Central

    Hu, Da-Gang; Zhang, Quan-Yan; An, Jian-Ping; You, Chun-Xiang; Hao, Yu-Jin

    2016-01-01

    Glucose induces anthocyanin accumulation in many plant species; however, the molecular mechanism involved in this process remains largely unknown. Here, we found that apple hexokinase MdHXK1, a glucose sensor, was involved in sensing exogenous glucose and regulating anthocyanin biosynthesis. In vitro and in vivo assays suggested that MdHXK1 interacted directly with and phosphorylated an anthocyanin-associated bHLH transcription factor (TF) MdbHLH3 at its Ser361 site in response to glucose. Furthermore, both the hexokinase_2 domain and signal peptide are crucial for the MdHXK1-mediated phosphorylation of MdbHLH3. Moreover, phosphorylation modification stabilized MdbHLH3 protein and enhanced its transcription of the anthocyanin biosynthesis genes, thereby increasing anthocyanin biosynthesis. Finally, a series of transgenic analyses in apple calli and fruits demonstrated that MdHXK1 controlled glucose-induced anthocyanin accumulation at least partially, if not completely, via regulating MdbHLH3. Overall, our findings provide new insights into the mechanism of the glucose sensor HXK1 modulation of anthocyanin accumulation, which occur by directly regulating the anthocyanin-related bHLH TFs in response to a glucose signal in plants. PMID:27560976

  17. Heterogeneous wireless/wireline optical access networks with the R-EAT as backend component

    NASA Astrophysics Data System (ADS)

    Hagedorn, Klaus; Gindera, Ralf; Stohr, Andreas; Jager, Dieter

    2004-09-01

    A heterogeneous wireless/wireline optical transmission link using a reflection type electroabsorption transceiver (R-EAT) is presented. Simultaneous transmission of full-duplex broadband wireless LAN (WLAN) channels and 1Gb/s base band data is experimentally demonstrated. The system link employs sub-carrier multiplexing (SCM) and two optical channels for full duplex transmission of various analog WLAN channels and downlink digital base band data. The developed link architecture is suitable for simultaneous transmission of broadband wireline and wireless signals, it enables the coexistence and interoperability between wireline and wireless access technologies. The developed R-EAT component employed in this wireline/wireless access system, features "single-chip-component" base stations in access networks with star type topology where only a single optical fiber is used for bidirectional optical transmission. The R-EAT can be used within the optical C-band (1530- 1560nm) and is suitable for (D)WDM networks. Bit error rate measurements demonstrate the capabilities of the R-EAT for 1Gb/s base band transmission. The analog performance for WLAN transmission is characterised by a spurious free dynamic range (SFDR) of more than 75dB and 90dB for uplink and downlink transmission, respectively. The link gain for uplink and downlink transmission is -42dB and -37dB, respectively. The demonstrates the analog performances of the R-EAT for being used in wireless access networks such as W-LAN.

  18. Structural and dynamical properties of the porins OmpF and OmpC: insights from molecular simulations

    NASA Astrophysics Data System (ADS)

    Kumar, Amit; Hajjar, Eric; Ruggerone, Paolo; Ceccarelli, Matteo

    2010-11-01

    In this paper we investigate the structural and dynamical properties of the two major porins (OmpF and OmpC) in Escherichia coli, using molecular dynamics (MD) simulations. In particular we characterized the atomic fluctuations, correlated motions, temperature dependence, solvent-accessible cross-sectional area and water dynamics in the key regions of the two channels. Our in-depth analysis allows us to highlight the importance of both the key conserved and substituted residues between OmpF and OmpC. The latter is characterized by a narrower and longer constriction region with respect to OmpF. OmpC also showed a higher stability upon increasing temperature. We then present the results of transport properties by using accelerated MD simulations to probe the diffusion of norfloxacin (a fluoroquinolone antibiotic) through the two porins OmpF/OmpC. Our study constitutes a step forward towards understanding the structure-function relationship of the two porins' channels. This will benefit the research of antibacterials with improved permeation properties and nanopores that aim to use these porins as sensing systems.

  19. Open- and closed-state fast inactivation in sodium channels

    PubMed Central

    Lehmann-Horn, Frank; Holzherr, Boris D

    2011-01-01

    The role of sodium channel closed-state fast inactivation in membrane excitability is not well understood. We compared open- and closed-state fast inactivation, and the gating charge immobilized during these transitions, in skeletal muscle channel hNaV1.4. A significant fraction of total charge movement and its immobilization occurred in the absence of channel opening. Simulated action potentials in skeletal muscle fibers were attenuated when pre-conditioned by subthreshold depolarization. Anthopleurin A, a site-3 toxin that inhibits gating charge associated with the movement of DIVS4, was used to assess the role of this voltage sensor in closed-state fast inactivation. Anthopleurin elicited opposing effects on the gating mode, kinetics and charge immobilized during open- versus closed-state fast inactivation. This same toxin produced identical effects on recovery of channel availability and remobilization of gating charge, irrespective of route of entry into fast inactivation. Our findings suggest that depolarization promoting entry into fast inactivation from open versus closed states provides access to the IFMT receptor via different rate-limiting conformational translocations of DIVS4. PMID:21099342

  20. Promoting new practices to increase access to and retention in addiction treatment: an analysis of five communication channels.

    PubMed

    Johnson, Kimberly A; Ford, James H; McCluskey, Matthew

    2012-11-01

    Addiction treatment programs adopt evidence-based practices slowly, in part because adopting a new practice is a process, not an event. Using different communication channels may have a different effect at different points in the process. This paper reports the effectiveness of five communication channels in getting substance abuse treatment programs to adopt new business practices. In this study, national trade media coverage produced the greatest interest among programs and the greatest number of decisions to adopt. Conference presentations produced fewer decisions to adopt than national media, but were the most effective channel when compared to the number of programs they reached. Peers were the greatest influence in moving clinic staff from the decision to adopt to implementation. These findings give preliminary evidence for using different communication channels at different times during an effort to promote the adoption of best practices. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Novel 3D/VR interactive environment for MD simulations, visualization and analysis.

    PubMed

    Doblack, Benjamin N; Allis, Tim; Dávila, Lilian P

    2014-12-18

    The increasing development of computing (hardware and software) in the last decades has impacted scientific research in many fields including materials science, biology, chemistry and physics among many others. A new computational system for the accurate and fast simulation and 3D/VR visualization of nanostructures is presented here, using the open-source molecular dynamics (MD) computer program LAMMPS. This alternative computational method uses modern graphics processors, NVIDIA CUDA technology and specialized scientific codes to overcome processing speed barriers common to traditional computing methods. In conjunction with a virtual reality system used to model materials, this enhancement allows the addition of accelerated MD simulation capability. The motivation is to provide a novel research environment which simultaneously allows visualization, simulation, modeling and analysis. The research goal is to investigate the structure and properties of inorganic nanostructures (e.g., silica glass nanosprings) under different conditions using this innovative computational system. The work presented outlines a description of the 3D/VR Visualization System and basic components, an overview of important considerations such as the physical environment, details on the setup and use of the novel system, a general procedure for the accelerated MD enhancement, technical information, and relevant remarks. The impact of this work is the creation of a unique computational system combining nanoscale materials simulation, visualization and interactivity in a virtual environment, which is both a research and teaching instrument at UC Merced.

  2. Novel 3D/VR Interactive Environment for MD Simulations, Visualization and Analysis

    PubMed Central

    Doblack, Benjamin N.; Allis, Tim; Dávila, Lilian P.

    2014-01-01

    The increasing development of computing (hardware and software) in the last decades has impacted scientific research in many fields including materials science, biology, chemistry and physics among many others. A new computational system for the accurate and fast simulation and 3D/VR visualization of nanostructures is presented here, using the open-source molecular dynamics (MD) computer program LAMMPS. This alternative computational method uses modern graphics processors, NVIDIA CUDA technology and specialized scientific codes to overcome processing speed barriers common to traditional computing methods. In conjunction with a virtual reality system used to model materials, this enhancement allows the addition of accelerated MD simulation capability. The motivation is to provide a novel research environment which simultaneously allows visualization, simulation, modeling and analysis. The research goal is to investigate the structure and properties of inorganic nanostructures (e.g., silica glass nanosprings) under different conditions using this innovative computational system. The work presented outlines a description of the 3D/VR Visualization System and basic components, an overview of important considerations such as the physical environment, details on the setup and use of the novel system, a general procedure for the accelerated MD enhancement, technical information, and relevant remarks. The impact of this work is the creation of a unique computational system combining nanoscale materials simulation, visualization and interactivity in a virtual environment, which is both a research and teaching instrument at UC Merced. PMID:25549300

  3. 78 FR 47412 - Tyson D. Quy, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-05

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 11-69] Tyson D. Quy, M.D... the state law offense of driving while under the influence of drugs (DUI), see Okla. Stat. tit. 47... manufacture, distribution, or dispensing of controlled substances); Super Rite Drugs, 56 FR 46014, 46015 (1991...

  4. 76 FR 21406 - Cynthia M. Cadet, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 10-34] Cynthia M. Cadet, M.D.; Decision and Order ACTION: Correction. On Thursday, April 7, 2011, the Drug Enforcement Administration... column. Dated: April 8, 2011. Michele M. Leonhart, Administrator. [FR Doc. 2011-9170 Filed 4-14-11; 8:45...

  5. 76 FR 53942 - Richard A. Herbert, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 09-33] Richard A. Herbert, M.D.; Decision and Order On June 15, 2010, Administrative Law Judge (ALJ) Mary Ellen Bittner issued the attached recommended decision. Thereafter, Respondent filed Exceptions to the ALJ's decision. Having reviewed the entire record including Respondent's...

  6. Red colouration in apple fruit is due to the activity of the MYB transcription factor, MdMYB10

    PubMed Central

    Espley, Richard V; Hellens, Roger P; Putterill, Jo; Stevenson, David E; Kutty-Amma, Sumathi; Allan, Andrew C

    2007-01-01

    Anthocyanin concentration is an important determinant of the colour of many fruits. In apple (Malus × domestica), centuries of breeding have produced numerous varieties in which levels of anthocyanin pigment vary widely and change in response to environmental and developmental stimuli. The apple fruit cortex is usually colourless, although germplasm does exist where the cortex is highly pigmented due to the accumulation of either anthocyanins or carotenoids. From studies in a diverse array of plant species, it is apparent that anthocyanin biosynthesis is controlled at the level of transcription. Here we report the transcript levels of the anthocyanin biosynthetic genes in a red-fleshed apple compared with a white-fleshed cultivar. We also describe an apple MYB transcription factor, MdMYB10, that is similar in sequence to known anthocyanin regulators in other species. We further show that this transcription factor can induce anthocyanin accumulation in both heterologous and homologous systems, generating pigmented patches in transient assays in tobacco leaves and highly pigmented apple plants following stable transformation with constitutively expressed MdMYB10. Efficient induction of anthocyanin biosynthesis in transient assays by MdMYB10 was dependent on the co-expression of two distinct bHLH proteins from apple, MdbHLH3 and MdbHLH33. The strong correlation between the expression of MdMYB10 and apple anthocyanin levels during fruit development suggests that this transcription factor is responsible for controlling anthocyanin biosynthesis in apple fruit; in the red-fleshed cultivar and in the skin of other varieties, there is an induction of MdMYB10 expression concurrent with colour formation during development. Characterization of MdMYB10 has implications for the development of new varieties through classical breeding or a biotechnological approach. PMID:17181777

  7. Microsecond MD Simulations of Nano-patterned Polymer Brushes on Self-Assembled Monolayers

    NASA Astrophysics Data System (ADS)

    Buie, Creighton; Qiu, Liming; Cheng, Kwan; Park, Soyeun

    2010-03-01

    Nano-patterned polymer brushes end-grafted onto self-assembled monolayers have gained increasing research interests due to their unique thermodynamic properties and their chemical and biomedical applications in colloids, biosensing and tissue engineering. So far, the interactions between the polymer brushes with the surrounding environments such as the floor and solvent at the nanometer length scale and microsecond time scale are still difficult to obtained experimentally and computationally. Using a Coarse-Grained MD approach, polymer brushes of different monomeric lengths, grafting density and hydrophobicity of the monomers grafted on self-assembled monolayers and in explicit solvent were studied. Molecular level information, such as lateral diffusion, transverse height and volume contour of the brushes, were calculated from our microsecond-MD simulations. Our results demonstrated the significance of the hydration of the polymer in controlling the conformational arrangement of the polymer brushes.

  8. Pilot-Assisted Channel Estimation for Orthogonal Multi-Carrier DS-CDMA with Frequency-Domain Equalization

    NASA Astrophysics Data System (ADS)

    Shima, Tomoyuki; Tomeba, Hiromichi; Adachi, Fumiyuki

    Orthogonal multi-carrier direct sequence code division multiple access (orthogonal MC DS-CDMA) is a combination of time-domain spreading and orthogonal frequency division multiplexing (OFDM). In orthogonal MC DS-CDMA, the frequency diversity gain can be obtained by applying frequency-domain equalization (FDE) based on minimum mean square error (MMSE) criterion to a block of OFDM symbols and can improve the bit error rate (BER) performance in a severe frequency-selective fading channel. FDE requires an accurate estimate of the channel gain. The channel gain can be estimated by removing the pilot modulation in the frequency domain. In this paper, we propose a pilot-assisted channel estimation suitable for orthogonal MC DS-CDMA with FDE and evaluate, by computer simulation, the BER performance in a frequency-selective Rayleigh fading channel.

  9. Exploring Beta-Amyloid Protein Transmembrane Insertion Behavior and Residue-Specific Lipid Interactions in Lipid Bilayers Using Multiscale MD Simulations

    NASA Astrophysics Data System (ADS)

    Qiu, Liming; Vaughn, Mark; Cheng, Kelvin

    2013-03-01

    Beta-amyloid (Abeta) interactions with neurons are linked to Alzheimer's. Using a multiscale MD simulation strategy that combines the high efficiency of phase space sampling of coarse-grained MD (CGD) and the high spatial resolution of Atomistic MD (AMD) simulations, we studied the Abeta insertion dynamics in cholesterol-enriched and -depleted lipid bilayers that mimic the neuronal membranes domains. Forward (AMD-CGD) and reverse (CGD-AMD) mappings were used. At the atomistic level, cholesterol promoted insertion of Abeta with high (folded) or low (unfolded) helical contents of the lipid insertion domain (Lys28-Ala42), and the insertions were stabilized by the Lys28 snorkeling and Ala42-anchoring to the polar lipid groups of the bilayer up to 200ns. After the forward mapping, the folded inserted state switched to a new extended inserted state with the Lys28 descended to the middle of the bilayer while the unfolded inserted state migrated to the membrane surface up to 4000ns. The two new states remained stable for 200ns at the atomistic scale after the reverse mapping. Our results suggested that different Abeta membrane-orientation states separated by free energy barriers can be explored by the multiscale MD more effectively than by Atomistic MD simulations alone. NIH RC1-GM090897-02

  10. Multi-wavelength access gate for WDM-formatted words in optical RAM row architectures

    NASA Astrophysics Data System (ADS)

    Fitsios, D.; Alexoudi, T.; Vagionas, C.; Miliou, A.; Kanellos, G. T.; Pleros, N.

    2013-03-01

    Optical RAM has emerged as a promising solution for overcoming the "Memory Wall" of electronics, indicating the use of light in RAM architectures as the approach towards enabling ps-regime memory access times. Taking a step further towards exploiting the unique wavelength properties of optical signals, we reveal new architectural perspectives in optical RAM structures by introducing WDM principles in the storage area. To this end, we demonstrate a novel SOAbased multi-wavelength Access Gate for utilization in a 4x4 WDM optical RAM bank architecture. The proposed multiwavelength Access Gate can simultaneously control random access to a 4-bit optical word, exploiting Cross-Gain-Modulation (XGM) to process 8 Bit and Bit channels encoded in 8 different wavelengths. It also suggests simpler optical RAM row architectures, allowing for the effective sharing of one multi-wavelength Access Gate for each row, substituting the eight AGs in the case of conventional optical RAM architectures. The scheme is shown to support 10Gbit/s operation for the incoming 4-bit data streams, with a power consumption of 15mW/Gbit/s. All 8 wavelength channels demonstrate error-free operation with a power penalty lower than 3 dB for all channels, compared to Back-to-Back measurements. The proposed optical RAM architecture reveals that exploiting the WDM capabilities of optical components can lead to RAM bank implementations with smarter column/row encoders/decoders, increased circuit simplicity, reduced number of active elements and associated power consumption. Moreover, exploitation of the wavelength entity can release significant potential towards reconfigurable optical cache mapping schemes when using the wavelength dimension for memory addressing.

  11. Interaction of the BKCa channel gating ring with dendrotoxins

    PubMed Central

    Takacs, Zoltan; Imredy, John P; Bingham, Jon-Paul; Zhorov, Boris S; Moczydlowski, Edward G

    2014-01-01

    Two classes of small homologous basic proteins, mamba snake dendrotoxins (DTX) and bovine pancreatic trypsin inhibitor (BPTI), block the large conductance Ca2+-activated K+ channel (BKCa, KCa1.1) by production of discrete subconductance events when added to the intracellular side of the membrane. This toxin-channel interaction is unlikely to be pharmacologically relevant to the action of mamba venom, but as a fortuitous ligand-protein interaction, it has certain biophysical implications for the mechanism of BKCa channel gating. In this work we examined the subconductance behavior of 9 natural dendrotoxin homologs and 6 charge neutralization mutants of δ-dendrotoxin in the context of current structural information on the intracellular gating ring domain of the BKCa channel. Calculation of an electrostatic surface map of the BKCa gating ring based on the Poisson-Boltzmann equation reveals a predominantly electronegative surface due to an abundance of solvent-accessible side chains of negatively charged amino acids. Available structure-activity information suggests that cationic DTX/BPTI molecules bind by electrostatic attraction to site(s) on the gating ring located in or near the cytoplasmic side portals where the inactivation ball peptide of the β2 subunit enters to block the channel. Such an interaction may decrease the apparent unitary conductance by altering the dynamic balance of open versus closed states of BKCa channel activation gating. PMID:25483585

  12. Orthogonal Pilot Channel Using Combination of FDMA and CDMA in Single-Carrier FDMA-Based Evolved UTRA Uplink

    NASA Astrophysics Data System (ADS)

    Kawamura, Teruo; Kishiyama, Yoshihisa; Higuchi, Kenichi; Sawahashi, Mamoru

    In the Evolved UTRA (UMTS Terrestrial Radio Access) uplink, single-carrier frequency division multiple access (SC-FDMA) radio access was adopted owing to its advantageous low peak-to-average power ratio (PAPR) feature, which leads to wide coverage area provisioning with limited peak transmission power of user equipments. This paper proposes orthogonal pilot channel generation using the combination of FDMA and CDMA in the SC-FDMA-based Evolved UTRA uplink. In the proposed method, we employ distributed FDMA transmission for simultaneous accessing users with different transmission bandwidths, and employ CDMA transmission for simultaneous accessing users with identical transmission bandwidth. Moreover, we apply a code sequence with a good auto-correlation property such as a Constant Amplitude Zero Auto-Correlation (CAZAC) sequence employing a cyclic shift to increase the number of sequences. Simulation results show that the average packet error rate performance using an orthogonal pilot channel with the combination of FDMA and CDMA in a six-user environment, i. e., four users each with a 1.25-MHz transmission bandwidth and two users each with a 5-MHz transmission bandwidth, employing turbo coding with the coding r of R=1/2 and QPSK and 16QAM data modulation coincides well with that in a single-user environment with the same transmission bandwidth. We show that the proposed orthogonal pilot channel structure using the combination of distributed FDMA and CDMA transmissions and the application of the CAZAC sequence is effective in the SC-FDMA-based Evolved UTRA uplink.

  13. Random access to mobile networks with advanced error correction

    NASA Technical Reports Server (NTRS)

    Dippold, Michael

    1990-01-01

    A random access scheme for unreliable data channels is investigated in conjunction with an adaptive Hybrid-II Automatic Repeat Request (ARQ) scheme using Rate Compatible Punctured Codes (RCPC) Forward Error Correction (FEC). A simple scheme with fixed frame length and equal slot sizes is chosen and reservation is implicit by the first packet transmitted randomly in a free slot, similar to Reservation Aloha. This allows the further transmission of redundancy if the last decoding attempt failed. Results show that a high channel utilization and superior throughput can be achieved with this scheme that shows a quite low implementation complexity. For the example of an interleaved Rayleigh channel and soft decision utilization and mean delay are calculated. A utilization of 40 percent may be achieved for a frame with the number of slots being equal to half the station number under high traffic load. The effects of feedback channel errors and some countermeasures are discussed.

  14. Folding of guanine quadruplex molecules-funnel-like mechanism or kinetic partitioning? An overview from MD simulation studies.

    PubMed

    Šponer, Jiří; Bussi, Giovanni; Stadlbauer, Petr; Kührová, Petra; Banáš, Pavel; Islam, Barira; Haider, Shozeb; Neidle, Stephen; Otyepka, Michal

    2017-05-01

    Guanine quadruplexes (GQs) play vital roles in many cellular processes and are of much interest as drug targets. In contrast to the availability of many structural studies, there is still limited knowledge on GQ folding. We review recent molecular dynamics (MD) simulation studies of the folding of GQs, with an emphasis paid to the human telomeric DNA GQ. We explain the basic principles and limitations of all types of MD methods used to study unfolding and folding in a way accessible to non-specialists. We discuss the potential role of G-hairpin, G-triplex and alternative GQ intermediates in the folding process. We argue that, in general, folding of GQs is fundamentally different from funneled folding of small fast-folding proteins, and can be best described by a kinetic partitioning (KP) mechanism. KP is a competition between at least two (but often many) well-separated and structurally different conformational ensembles. The KP mechanism is the only plausible way to explain experiments reporting long time-scales of GQ folding and the existence of long-lived sub-states. A significant part of the natural partitioning of the free energy landscape of GQs comes from the ability of the GQ-forming sequences to populate a large number of syn-anti patterns in their G-tracts. The extreme complexity of the KP of GQs typically prevents an appropriate description of the folding landscape using just a few order parameters or collective variables. We reconcile available computational and experimental studies of GQ folding and formulate basic principles characterizing GQ folding landscapes. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. 33 CFR 110.72a - Chester River, southeast of Chestertown, Md.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 1 2012-07-01 2012-07-01 false Chester River, southeast of Chestertown, Md. 110.72a Section 110.72a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.72a Chester River, southeast of...

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    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Chester River, southeast of Chestertown, Md. 110.72a Section 110.72a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.72a Chester River, southeast of...

  17. 33 CFR 110.72a - Chester River, southeast of Chestertown, Md.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 1 2014-07-01 2014-07-01 false Chester River, southeast of Chestertown, Md. 110.72a Section 110.72a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.72a Chester River, southeast of...

  18. 33 CFR 110.72a - Chester River, southeast of Chestertown, Md.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Chester River, southeast of Chestertown, Md. 110.72a Section 110.72a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.72a Chester River, southeast of...

  19. 33 CFR 110.72a - Chester River, southeast of Chestertown, Md.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Chester River, southeast of Chestertown, Md. 110.72a Section 110.72a Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.72a Chester River, southeast of...

  20. 33 CFR 165.513 - Safety Zone; Magothy River, Sillery Bay, MD.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Safety Zone; Magothy River... Safety Zone; Magothy River, Sillery Bay, MD. (a) Regulated area. The following area is a safety zone: All waters of the Magothy River, in Sillery Bay, contained within lines connecting the following positions...