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Sample records for access channel md

  1. 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

    ... notice regarding our public dockets in the January 17, 2008, issue of the Federal Register (73 FR 3316... River, National Harbor Access Channel, MD AGENCY: Coast Guard, DHS. ACTION: Notice of proposed... click ``SEARCH.'' Click on Open Docket Folder on the line associated with this rulemaking. You may...

  2. 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

    ... Department of Homeland Security FR Federal Register NPRM Notice of Proposed Rulemaking A. Regulatory History... Federal Register (77 FR 82). We received no comments on the proposed rule. No public meeting was requested... River, National Harbor Access Channel, MD AGENCY: Coast Guard, DHS. ACTION: Temporary final...

  3. 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 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY REGATTAS AND MARINE PARADES SAFETY OF LIFE ON NAVIGABLE WATERS § 100.35T05-0276 Special Local Regulations for Marine Events;...

  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 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY REGATTAS AND MARINE PARADES SAFETY OF LIFE ON NAVIGABLE WATERS § 100.35T05-0276 Special Local Regulations for Marine Events;...

  5. 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

    ... INFORMATION: Table of Acronyms DHS Department of Homeland Security FR Federal Register NPRM Notice of Proposed... Access Channel, MD'' in the Federal Register (78 FR 67). We received no comments on the proposed rule. No... rule, call or email Mr. Ronald Houck, U.S. Coast Guard Sector Baltimore, MD; telephone...

  6. Multiple-access channels without synchronization

    NASA Technical Reports Server (NTRS)

    Mceliece, R. J.; Posner, E. C.

    1977-01-01

    This paper discusses models for multiple-access communications which take into account the fact that the channel users may not be able to synchronize their transmissions. It is shown that for a broad class of such channels, the capacity region is the same as it would be with user synchronization. Some open problems are discussed.

  7. 47 CFR 76.701 - Leased access channels.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 4 2011-10-01 2011-10-01 false Leased access channels. 76.701 Section 76.701... CABLE TELEVISION SERVICE Cable Television Access § 76.701 Leased access channels. (a) Notwithstanding 47... leased access program or portion of a leased access program that the operator reasonably...

  8. 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...

  9. 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.

  10. 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

    ... DHS Department of Homeland Security FR Federal Register NPRM Notice of Proposed Rulemaking A. Public... Act notice regarding our public dockets in the January 17, 2008, issue of the Federal Register (73 FR... 38 47'35'' N, longitude 077 02'22'' W, thence east to latitude 38 47'12'' N, longitude 077 00'58''...

  11. 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

    ..., 2008, issue of the Federal Register (73 FR 3316). Public Meeting We do not now plan to hold a public... Potomac River in Prince George's County, Maryland on August 5, 2012. These special local regulations are... Ground Floor, Room W12-140, 1200 New Jersey Avenue SE., Washington, DC 20590-0001. (4) Hand...

  12. 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

    ... FR 20750, is withdrawn as of July 19, 2012. ADDRESSES: The docket for this withdrawn rulemaking is... Federal Register (77 FR 20750). The rulemaking ] concerned the Coast Guard's proposal to establish... Potomac River in Prince George's County, Maryland on August 5, 2012. The Coast Guard was notified on...

  13. 76 FR 70647 - Safety Zone; Fireworks Display, Potomac River, National Harbor Access Channel, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-15

    ... relationship between the Federal Government and Indian Tribes, or on the distribution of power and... Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution... effect on the supply, distribution, or use of energy. The Administrator of the Office of Information...

  14. 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…

  15. Omega currents in voltage-gated ion channels: what can we learn from uncovering the voltage-sensing mechanism using MD simulations?

    PubMed

    Tarek, Mounir; Delemotte, Lucie

    2013-12-17

    Ion channels conduct charged species through otherwise impermeable biological membranes. Their activity supports a number of physiological processes, and genetic mutations can disrupt their function dramatically. Among these channels, voltage gated cation channels (VGCCs) are ubiquitous transmembrane proteins involved in electrical signaling. In addition to their selectivity for ions, their function requires membrane-polarization-dependent gating. Triggered by changes in the transmembrane voltage, the activation and deactivation of VGCCs proceed through a sensing mechanism that prompts motion of conserved positively charged (basic) residues within the S4 helix of a four-helix bundle, the voltage sensor domain (VSD). Decades of experimental investigations, using electrophysiology, molecular biology, pharmacology, and spectroscopy, have revealed details about the function of VGCCs. However, in 2005, the resolution of the crystal structure of the activated state of one member of the mammalian voltage gated potassium (Kv) channels family (the Kv1.2) enabled researchers to make significant progress in understanding the structure-function relationship in these proteins on a molecular level. In this Account, we review the use of a complementary technique, molecular dynamics (MD) simulations, that has offered new insights on this timely issue. Starting from the "open-activated state" crystal structure, we have carried out large-scale all atom MD simulations of the Kv1.2 channel embedded in its lipidic environment and submitted to a hyperpolarizing (negative) transmembrane potential. We then used steered MD simulations to complete the full transition to the resting-closed state. Using these procedures, we have followed the operation of the VSDs and uncovered three intermediate states between their activated and deactivated conformations. Each conformational state is characterized by its network of salt bridges and by the occupation of the gating charge transfer center by a

  16. News and Information on Community Access Channels: Market Concerns amidst the Marketplace of Ideas.

    ERIC Educational Resources Information Center

    Atkin, David; LaRose, Robert

    Utilizing a regionally diversified sample of cable viewers to investigate viewer patronage of community channels--defined to include public, educational, and government (PEG) access as well as community (or leased) access channels, a study examined a quarterly national survey of homes serviced by cable in the United States. Each quarter, 1,000…

  17. Selectivity of a Singly Permeating Ion in Nonselective NaK Channel: Combined QM and MD Based Investigations.

    PubMed

    Sadhu, Biswajit; Sundararajan, Mahesh; Bandyopadhyay, Tusar

    2015-10-01

    Ion channels, such as potassium channels are known to discriminate ions to achieve remarkable selective transportation of K(+) over Na(+) through the membrane. The recently reported NaK ion channel, on the contrary, seems to be an exception, as it is observed to permeate most of the group IA alkali metal cations and hence is suggested to be nonselective in nature. However, does that correspond to a complete annihilation of selectivity inside the selectivity filter (SF) of the channel? What is the origin of such nonselectivity/selectivity, if any? The present computational study is an extensive multiscale modeling approach to find the probable answers to these intriguing questions. Here, we have used density functional theory (DFT) based calculations using a realistic truncated model of SF from the crystal structures of the NaK ion channel to evaluate the binding of various alkali metal ions (Na(+), K(+) and Cs(+)), free from "contamination" due to the absence any other "rivalry" cations, in its different binding sites. Among all of the possible binding sites, a vestibule is noticed to be nonselective and seen to act as a probable binding site only in the presence of multiple ions. Binding sites S3 and S4 are found to be selective for K(+) and Na(+), respectively. As an important observation, we find that calculations on oversimplified models using an isolated ion binding site may lead to an erroneous selectivity trend as it neglects the synergetics of consecutive binding sites on the final outcome. Energy decomposition analysis revealed ion-dipole electrostatics as the major contributing interaction in metal-bound binding sites. Our investigations find that although NaK is permeable to monovalent alkali metal ions, strongly "site specific" selectivity does exist at the three well-defined noncontiguous binding sites of the SF. Different important physicomechanical parameters (such as ligating environment, synergistic influence of binding sites, and topological

  18. Structural and dynamic basis of human cytochrome P450 7B1: a survey of substrate selectivity and major active site access channels.

    PubMed

    Cui, Ying-Lu; Zhang, Ji-Long; Zheng, Qing-Chuan; Niu, Rui-Juan; Xu, Yu; Zhang, Hong-Xing; Sun, Chia-Chung

    2013-01-01

    Cytochrome P450 (CYP) 7B1 is a steroid cytochrome P450 7α-hydroxylase that has been linked directly with bile salt synthesis and hereditary spastic paraplegia type 5 (SPG5). The enzyme provides the primary metabolic route for neurosteroids dehydroepiandrosterone (DHEA), cholesterol derivatives 25-hydroxycholesterol (25-HOChol), and other steroids such as 5α-androstane-3β,17β-diol (anediol), and 5α-androstene-3β,17β-diol (enediol). A series of investigations including homology modeling, molecular dynamics (MD), and automatic docking, combined with the results of previous experimental site-directed mutagenesis studies and access channels analysis, have identified the structural features relevant to the substrate selectivity of CYP7B1. The results clearly identify the dominant access channels and critical residues responsible for ligand binding. Both binding free energy analysis and total interaction energy analysis are consistent with the experimental conclusion that 25-HOChol is the best substrate. According to 20 ns MD simulations, the Phe cluster residues that lie above the active site, particularly Phe489, are proposed to merge the active site with the adjacent channel to the surface and accommodate substrate binding in a reasonable orientation. The investigation of CYP7B1-substrate binding modes provides detailed insights into the poorly understood structural features of human CYP7B1 at the atomic level, and will be valuable information for drug development and protein engineering. PMID:23180418

  19. Multi-channel access technology based on wavelength division multiplexing in wireless UV communication mesh network

    NASA Astrophysics Data System (ADS)

    Zhao, Tai-fei; Zhang, Ai-li; Xue, Rong-li

    2013-05-01

    In this paper, the multi-channel access technology of wavelength division multiplexing (WDM) in the wireless ultraviolet (UV) scattering communication is studied. A multi-interface and multi-channel device is deployed in each UV transceiver node. The band-pass filter is configured in the receiving node so as to realize the multi-channel access by use of the UV WDM technology. Both the UV communication node model and the UV channel model are established. Three types of UV no-line-of-sight (NLOS) multi-channel communications are simulated in the mesh topologies with NS2. The results show that the UV multi-channel access technology can increase network throughput effectively with using WDM.

  20. State-dependent access of anions to the cystic fibrosis transmembrane conductance regulator chloride channel pore.

    PubMed

    Fatehi, Mohammad; Linsdell, Paul

    2008-03-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is gated by intracellular factors; however, conformational changes in the channel pore associated with channel activation have not been identified. We have used patch clamp recording to investigate the state-dependent accessibility of substituted cysteine residues in the CFTR channel pore to a range of cysteine-reactive reagents applied to the extracellular side of the membrane. Using functional modification of the channel current-voltage relationship as a marker of modification, we find that several positively charged reagents are able to penetrate deeply into the pore from the outside irrespective of whether or not the channels have been activated. In contrast, access of three anionic cysteine-reactive reagents, the methanesulfonate sodium (2-sulfonatoethyl)methanesulfonate, the organic mercurial p-chloromercuriphenylsulfonic acid, and the permeant anion Au(CN)(2)(-), to several different sites in the pore is strictly limited prior to channel activation. This suggests that in nonactivated channels some ion selectivity mechanism exists to exclude anions yet permit cations into the channel pore from the extracellular solution. We suggest that activation of CFTR channels involves a conformational change in the pore that removes a strong selectivity against anion entry from the extracellular solution. We propose further that this conformational change occurs in advance of channel opening, suggesting that multiple distinct closed pore conformations exist. PMID:18167343

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

    PubMed

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

    2015-01-01

    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. PMID:26633421

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

    PubMed Central

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

    2015-01-01

    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. PMID:26633421

  3. 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

    ... Department of Homeland Security FR Federal Register NPRM Notice of Proposed Rulemaking A. Regulatory History... ground floor of the Department of Transportation West Building, 1200 New Jersey Avenue SE.,...

  4. 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

    ...: Table of Acronyms DHS Department of Homeland Security FR Federal Register NPRM Notice of Proposed... on navigable waters. Such hazards include premature detonations, dangerous projectiles and falling...

  5. Access channels and methanol binding site to the CaMn4 cluster in Photosystem II based on solvent accessibility simulations, with implications for substrate water access.

    PubMed

    Ho, Felix M; Styring, Stenbjörn

    2008-02-01

    Given the tightly packed environment of Photosystem II (PSII), channels are expected to exist within the protein to allow the movement of small molecules to and from the oxygen evolving centre. In this report, we calculate solvent contact surfaces from the PSII crystal structures to identify such access channels for methanol and water molecules. In a previous study of the effects of methanol on the EPR split S1-, S3-, and S0-signals [Su et al. (2006) Biochemistry 45, 7617-7627], we proposed that methanol binds to one and the same Mn ion in all S-states. We find here that while channels of methanol dimensions were able to make contact with the CaMn4 cluster, only 3Mn and 4Mn were accessible to methanol. Combining this observation with spectroscopic data in the literature, we propose that 3Mn is the ion to which methanol binds. Furthermore, by calculating solvent contact surfaces for water, we found analogous and more extensive water accessible channels within PSII. On the basis of their structure, orientation, and electrostatic properties, we propose functional assignments of these channels as passages for substrate water access to the CaMn4 cluster, and for the exit of O2 and H+ that are released during water oxidation. Finally, we discuss the possible existence of a gating mechanism for the control of substrate water access to the CaMn4 cluster, based on the observation of a gap within the channel system that is formed by Ca2+ and several mechanistically very significant residues in the vicinity of the cluster. PMID:17964532

  6. 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).

  7. 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. PMID:26794698

  8. An upper bound for codes in a two-access binary erasure channel

    NASA Technical Reports Server (NTRS)

    Van Tilborg, H. C. A.

    1978-01-01

    A method for determining an upper bound for the size of a code for a two-access binary erasure channel is presented. For uniquely decodable codes, this bound gives a combinatorial proof of a result by Liao. Examples of the bound are given for codes with minimum distance 4.

  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. PMID:16779415

  10. 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

  11. Q-ary collision resolution algorithms in random-access systems with free or blocked channel access

    NASA Astrophysics Data System (ADS)

    Mathys, P.; Flajolet, P.

    1985-03-01

    The throughput characteristics of contention-based random-access systems (RAS's) which use Q-ary tree algorithms (where Q equal to or greater than 2 is the number of groups into which contending users are split) of the Capetanakis-Tsybakov-Mikhailov-Vvedenskaya type are analyzed for an infinite population of identical users generating packets according to a Poisson process. Both free and blocked channel-access protocols are considered in combination with Q-ary collision resoluton algorithms that exploit either binary ('collision/no collision') or ternary ('collision/success/idle') feedback. For the resulting RAS's, functional equations for transformed generating functions of the first two moments of the collision resolution interval length are obtained and solved. The maximum stable throughput as a function of Q is given. The results of a packet-delay analysis are also given, and the analyzed RAS's are compared among themselves and with the slotted ALOHA system in terms of both system throughput and packet delay. It is concluded that the 'practical optimum' RAS (in terms of ease of implementation combined with good performance) uses free (i.e., immediate) channel access and ternary splitting (i.e., Q = 3) with binary feedback.

  12. Performance of Multiple Pulse Multiple Delay Modulated UWB Signals in a Multiple Access Indoor Wireless Channel

    SciTech Connect

    Nekoogar, F

    2003-06-12

    In this paper, the performance of a two user UWB multiple access (UWB-MA) system based on multiple-pulse multiple-delay (MPMD) modulation scheme in an indoor wireless channel is evaluated by computer simulations. The indoor multipath propagation channel model used in this study is based on the modified statistical Saleh-Valenzuela model proposed by Foerester and Li from Intel. The simulation results indicate that the multipath performance of MPMD modulated signals in a multiple access system outperforms the nonmultipath case as the number of autocorrelation function (ACF) sampling points increases for each user. This is an unusual but important result, since MPMD receiver exploits multipath phenomenon in indoor wireless channels to increase the BER performance, hence the transmission rate in a UWB-MA system.

  13. A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom

    NASA Astrophysics Data System (ADS)

    Lee, Seok-Yong; MacKinnon, Roderick

    2004-07-01

    Venomous animals produce small protein toxins that inhibit ion channels with high affinity. In several well-studied cases the inhibitory proteins are water-soluble and bind at a channel's aqueous-exposed extracellular surface. Here we show that a voltage-sensor toxin (VSTX1) from the Chilean Rose Tarantula (Grammostola spatulata) reaches its target by partitioning into the lipid membrane. Lipid membrane partitioning serves two purposes: to localize the toxin in the membrane where the voltage sensor resides and to exploit the free energy of partitioning to achieve apparent high-affinity inhibition. VSTX1, small hydrophobic poisons and anaesthetic molecules reveal a common theme of voltage sensor inhibition through lipid membrane access. The apparent requirement for such access is consistent with the recent proposal that the sensor in voltage-dependent K+ channels is located at the membrane-protein interface.

  14. Accessibility of cysteines in the native bovine rod cGMP-gated channel.

    PubMed

    Bauer, Paul J; Krause, Eberhard

    2005-02-01

    Cyclic nucleotide-gated channels of photoreceptors and olfactory sensory neurons are tetramers consisting of A and B subunits. Here, the accessibility of the cysteines of the bovine rod cyclic nucleotide-gated channel is examined as a function of ligand binding. N-Ethylmaleimide-modified cysteines of both subunits were identified by mass spectrometry after trypsin digestion. In the absence of ligand, the intracellular carboxy-terminal cysteines of both subunits were accessible to N-ethylmaleimide. Activation of the channel abolished the accessibility of Cys505 of the A subunit and Cys1104 of the B subunit, with both being conserved cysteines of the cyclic nucleotide-binding sites. The cysteine of the pore loop of the B subunit was also found to be modified by this reagent in the absence of ligand. The total number of accessible cysteines of each subunit was determined by mass shifting upon modification with polyethylene glycol maleimide. In the absence of cyclic nucleotides, this hydrophilic reagent only weakly labeled cysteines of the A subunit but readily labeled at least three cysteines of the B subunit. Ligand binding exposed two cysteines of the A subunit and one cysteine of the B subunit to chemical modification. Double-modification experiments suggest that some of these cysteines are in or close to membrane-spanning domains. However, these cysteines could not yet be identified. Together, the cysteine accessibility of the native rod cyclic nucleotide-gated channel varies markedly upon ligand binding, thus indicating major structural rearrangements, which are of functional importance for channel activation. PMID:15683246

  15. Accessibility, reactivity, and selectivity of side chains within a channel of de novo peptide assembly.

    PubMed

    Burton, Antony J; Thomas, Franziska; Agnew, Christopher; Hudson, Kieran L; Halford, Stephen E; Brady, R Leo; Woolfson, Derek N

    2013-08-28

    Ab initio design of enzymes requires precise and predictable positioning of reactive functional groups within accessible and controlled environments of de novo protein scaffolds. Here we show that multiple thiol moieties can be placed within a central channel, with approximate dimensions 6 × 42 Å, of a de novo, six-helix peptide assembly (CC-Hex). Layers of six cysteine residues are introduced at two different sites ~6 (the "L24C" mutant) and ~17 Å (L17C) from the C-terminal opening of the channel. X-ray crystal structures confirm the mutant structures as hexamers with internal free thiol, rather than disulfide-linked cysteine residues. Both mutants are hexa-alkylated upon addition of iodoacetamide, demonstrating accessibility and full reactivity of the thiol groups. Comparison of the alkylation and unfolding rates of the hexamers indicates that access is directly through the channel and not via dissociation and unfolding of the assembly. Moreover, neither mutant reacts with iodoacetic acid, demonstrating selectivity of the largely hydrophobic channel. These studies show that it is possible to engineer reactive side chains with both precision and control into a de novo scaffold to produce protein-like structures with chemoselective reactivity. PMID:23924058

  16. Molecular dioxygen enters the active site of 12/15-lipoxygenase via dynamic oxygen access channels.

    PubMed

    Saam, Jan; Ivanov, Igor; Walther, Matthias; Holzhütter, Hermann-Georg; Kuhn, Hartmut

    2007-08-14

    Cells contain numerous enzymes that use molecular oxygen for their reactions. Often, their active sites are buried deeply inside the protein, which raises the question whether there are specific access channels guiding oxygen to the site of catalysis. Choosing 12/15-lipoxygenase as a typical example for such oxygen-dependent enzymes, we determined the oxygen distribution within the protein and defined potential routes for oxygen access. For this purpose, we have applied an integrated strategy of structural modeling, molecular dynamics simulations, site-directed mutagenesis, and kinetic measurements. First, we computed the 3D free-energy distribution for oxygen, which led to identification of four oxygen channels in the protein. All channels connect the protein surface with a region of high oxygen affinity at the active site. This region is localized opposite to the nonheme iron providing a structural explanation for the reaction specificity of this lipoxygenase isoform. The catalytically most relevant path can be obstructed by L367F exchange, which leads to a strongly increased Michaelis constant for oxygen. The blocking mechanism is explained in detail by reordering the hydrogen-bonding network of water molecules. Our results provide strong evidence that the main route for oxygen access to the active site of the enzyme follows a channel formed by transiently interconnected cavities whereby the opening and closure are governed by side chain dynamics. PMID:17675410

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

    PubMed Central

    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. PMID:27347526

  18. Quantum superadditivity in linear optics networks: Sending bits via multiple-access Gaussian channels

    SciTech Connect

    Czekaj, L.; Horodecki, P.; Korbicz, J. K.; Chhajlany, R. W.

    2010-08-15

    Superadditivity effects of communication capacities are known in the case of discrete variable quantum channels. We describe the continuous variable analog of one of these effects in the framework of Gaussian multiple access channels (MACs). Classically, superadditivity-type effects are strongly restricted: For example, adding resources to one sender is never advantageous to other senders in sending their respective information to the receiver. We show that this rule can be surpassed using quantum resources, giving rise to a type of truly quantum superadditivity. This is illustrated here for two examples of experimentally feasible Gaussian MACs.

  19. Fairness of channel access for non-time-critical traffic using the FDDI token ring protocol

    NASA Technical Reports Server (NTRS)

    Johnson, M. J.

    1986-01-01

    The Fiber Distributed Data Interface (FDDI) is an ANSI draft proposed standard for a 100 megabit per second fiber optic token ring. FDDI supports two types of traffic, synchronous and asynchronous. Synchronous traffic is time critical traffic; stations are assigned guaranteed bandwidth to support their synchronous needs. Asynchronous traffic is lower priority and is sent only if time permits. It is proved analytically that the FDDI access protocol provides all stations on the ring with equal access to the channel to transmit asynchronous frames, regardless of the relative sizes of synchronous bandwidth allocations for individual stations. Analytic results are supported with data from simulation runs.

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

    PubMed

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

    2014-09-01

    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

  1. 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

    ... other than channel terminations between LEC end offices and customer premises. 69.709 Section 69.709... terminations between LEC end offices and customer premises. (a) Scope. This paragraph governs requests for... transport and special access services other than channel terminations between LEC end offices and...

  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

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

    2012-02-01

    Alzheimer's disease (AD) is a protein misfolding disease characterized by a buildup 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 Aβ(1-42) 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. Previously, we have shown that D-Aβ(1-42) channels conduct ions similarly to their L- counterparts. 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. 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…

  4. 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.

  5. MD-2 binds cholesterol.

    PubMed

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I

    2016-02-19

    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis. PMID:26806306

  6. Role of an isoform-specific substrate access channel residue in CO ligand accessibilities of neuronal and inducible nitric oxide synthase isoforms.

    PubMed

    Feng, Changjian; Fan, Weihong; Ghosh, Dipak K; Tollin, Gordon

    2011-03-01

    The rates of the bimolecular CO rebinding to the oxygenase domains of inducible and neuronal NOS proteins (iNOSoxy and nNOSoxy, respectively) after photolytic dissociation have been determined by laser flash photolysis. The following mutants at the isoform-specific sites (murine iNOSoxy N115L and rat nNOSoxy L337N, L337F) have been constructed to investigate role of the residues in the CO ligand accessibilities of the NOS isoforms. These residues are in the NOS distal substrate access channel. The effect of the (6R)-5,6,7,8-tetrahydrobiopterin (H(4)B) cofactor and l-arginine (Arg) substrate on the rates of CO rebinding have also been assessed. Addition of l-Arg to the iNOSoxy N115L mutant results in much faster CO rebinding rates, compared to the wild type. The results indicate that modifications to the iNOS channel in which the hydrophilic residue N115 is replaced by leucine (to resemble its nNOS cognate) open the channel somewhat, thereby improving access to the axial heme ligand binding position. On the other hand, introduction of a hydrophilic residue (L337N) or a bulky rigid aromatic residue (L337F) in the nNOS isoform does not significantly affect the kinetics profile, suggesting that the geometry of the substrate access pocket is not greatly altered. The bimolecular CO rebinding rate data indicate that the opening of the substrate access channel in the iNOS N115L mutant may be due to more widespread structural alterations induced by the mutation. PMID:21146639

  7. 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...

  8. Performance analysis of 2D asynchronous hard-limiting optical code-division multiple access system through atmospheric scattering channel

    NASA Astrophysics Data System (ADS)

    Zhao, Yaqin; Zhong, Xin; Wu, Di; Zhang, Ye; Ren, Guanghui; Wu, Zhilu

    2013-09-01

    Optical code-division multiple access (OCDMA) systems usually allocate orthogonal or quasi-orthogonal codes to the active users. When transmitting through atmospheric scattering channel, the coding pulses are broadened and the orthogonality of the codes is worsened. In truly asynchronous case, namely both the chips and the bits are asynchronous among each active user, the pulse broadening affects the system performance a lot. In this paper, we evaluate the performance of a 2D asynchronous hard-limiting wireless OCDMA system through atmospheric scattering channel. The probability density function of multiple access interference in truly asynchronous case is given. The bit error rate decreases as the ratio of the chip period to the root mean square delay spread increases and the channel limits the bit rate to different levels when the chip period varies.

  9. Accessibility

    MedlinePlus

    ... www.nlm.nih.gov/medlineplus/accessibility.html MedlinePlus Accessibility To use the sharing features on this page, ... Subscribe to RSS Follow us Disclaimers Copyright Privacy Accessibility Quality Guidelines Viewers & Players MedlinePlus Connect for EHRs ...

  10. FURSMASA: a new approach to rapid scoring functions that uses a MD-averaged potential energy grid and a solvent-accessible surface area term with parameters GA fit to experimental data.

    PubMed

    Pearlman, David A; Rao, B Govinda; Charifson, Paul

    2008-05-15

    We demonstrate a new approach to the development of scoring functions through the formulation and parameterization of a new function, which can be used both for rapidly ranking the binding of ligands to proteins and for estimating relative aqueous molecular solubilities. The intent of this work is to introduce a new paradigm for creation of scoring functions, wherein we impose the following criteria upon the function: (1) simple; (2) intuitive; (3) requires no postparameterization tweaking; (4) can be applied (without reparameterization) to multiple target systems; and (5) can be rapidly evaluated for any potential ligand. Following these criteria, a new function, FURSMASA (function for rapid scoring using an MD-averaged grid and the accessible surface area) has been developed. Three novel features of the function include: (1) use of an MD-averaged potential energy grid for ligand-protein interactions, rather than a simple static grid; (2) inclusion of a term that depends on the change in the solvent-accessible surface area changes on an atomic (not molecular) basis; and (3) use of the recently derived predictive index (PI) target when optimizing the function, which focuses the function on its intended purpose of relative ranking. A genetic algorithm is used to optimize the function against test data sets that include ligands for the following proteins: IMPDH, p38, gyrase B, HIV-1, and TACE, as well as the Syracuse Research solubility database. We find that the function is predictive, and can simultaneously fit all the test data sets with cross-validated predictive indices ranging from 0.68 to 0.82. As a test of the ability of this function to predict binding for systems not in the training set, the resulting fitted FURSAMA function is then applied to 23 ligands of the COX-2 enzyme. Comparing the results for COX-2 against those obtained using a variety of well-known rapid scoring functions demonstrates that FURSMASA outperforms all of them in terms of the PI and

  11. 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.

  12. The ability to create NTD silicon technology in the IRT-T reactor in a horizontal experimental channel with one-side access

    NASA Astrophysics Data System (ADS)

    Varlachev, V. A.; Golovatsky, A. V.; Emets, E. G.; Butko, Ya A.

    2016-06-01

    The article shows the ability of creation of neutron transmutation doping (NTD) of monocrystalline silicon technology in the reactor's channel, which has a one-side access. In the article a distribution of thermal neutron flux through the length of channel and it's radius, neutron spectrum were obtained which confirmed that horizontal experimental channel HEC-1 is suitable for NTD.

  13. Clinical Outcomes After Cervical Transcorporeal Microdecompression and Vertebral Body Access Channel Repair

    PubMed Central

    Lowry, David W.; Tuinstra, Scott M.; Liang, Kevin

    2015-01-01

    Background Although anterior cervical decompression and fusion (ACDF) can be performed using minimally invasive techniques, the extensive removal of anatomical keystones during decompression requires a segmental fusion to restore biomechanical stability. Treatment with arthrodesis techniques may result in a prolonged recovery time, loss of motion, and the need for further treatment if a pseudarthosis or adjacent segment disease occur. Transcorporeal micro decompression (TCMD) is a newly developed motion sparing, minimally invasive anterior cervical spine decompression procedure that utilizes a small channel through the cervical vertebral body to decompress areas of central or foraminal stenosis while preserving the native disc. Cervical decompression with TCMD can be performed as a stand-alone or hybrid procedure with ACDF at the adjacent levels. This study retrospectively assesses patient based clinical outcome measures in patients treated with TCMD. Methods A retrospective, non-randomized, single-center chart review of single surgeon experience with patients undergoing TCMD both with and without adjacent level ACDF using both a trajectory control guide and access channel repair. Statistical analyses were performed on pre and post-operative data collected using visual analog scale (VAS) and neck disability index (NDI) outcome measures. Results Among 62 patients, there were no cases of neurovascular injury, CSF leak, transfusion, or migration of repair implement. Revision surgery was required in 6.4% (n=4) patients. A subanalysis of outcome metrics was performed for patients that underwent standalone TCMD (TCMD group, n=42) and TCMD with concurrent ACDF at one or more levels (TCMD+ACDF group, n=20). TCMD group NDI improved from 20.0 to 2.7 at 1 year (p=0.0001); Axial VAS improved from 5.5 to 0.6 (p=0.0001); and Radiating VAS improved from 7.0 to 0.7 (p=0.0001). TCMD+ACDF group NDI improved from 22.0 to 4.0 at 1 year (p=0.004); Axial VAS improved from 7.1 to 1.2 (p

  14. Cysteine accessibility probes timing and extent of NBD separation along the dimer interface in gating CFTR channels

    PubMed Central

    Chaves, Luiz A. Poletto

    2015-01-01

    Cystic fibrosis transmembrane conductance regulator (CFTR) channel opening and closing are driven by cycles of adenosine triphosphate (ATP) binding–induced formation and hydrolysis-triggered disruption of a heterodimer of its cytoplasmic nucleotide-binding domains (NBDs). Although both composite sites enclosed within the heterodimer interface contain ATP in an open CFTR channel, ATP hydrolysis in the sole catalytically competent site causes channel closure. Opening of the NBD interface at that site then allows ADP–ATP exchange. But how frequently, and how far, the NBD surfaces separate at the other, inactive composite site remains unclear. We assessed separation at each composite site by monitoring access of nucleotide-sized hydrophilic, thiol-specific methanothiosulfonate (MTS) reagents to interfacial target cysteines introduced into either LSGGQ-like ATP-binding cassette signature sequence (replacing equivalent conserved serines: S549 and S1347). Covalent MTS-dependent modification of either cysteine while channels were kept closed by the absence of ATP impaired subsequent opening upon ATP readdition. Modification while channels were opening and closing in the presence of ATP caused macroscopic CFTR current to decline at the same speed as when the unmodified channels shut upon sudden ATP withdrawal. These results suggest that the target cysteines can be modified only in closed channels; that after modification the attached MTS adduct interferes with ATP-mediated opening; and that modification in the presence of ATP occurs rapidly once channels close, before they can reopen. This interpretation was corroborated by the finding that, for either cysteine target, the addition of the hydrolysis-impairing mutation K1250R (catalytic site Walker A Lys) similarly slowed, by an order of magnitude, channel closing on ATP removal and the speed of modification by MTS reagent in ATP. We conclude that, in every CFTR channel gating cycle, the NBD dimer interface separates

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

    SciTech Connect

    Grudka, Andrzej; 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.

  16. 18 CFR 1304.207 - Channel excavation on TVA-owned residential access shoreland.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... reservoir drawdown periods. (g) Channel excavations must be accomplished during the reservoir drawdown when the reservoir bottom is exposed and dry. (h) Spoil material from channel excavations must be placed in... Risk Profile elevation. For those reservoirs that have no flood control storage, dredge spoil must...

  17. 18 CFR 1304.207 - Channel excavation on TVA-owned residential access shoreland.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... reservoir drawdown periods. (g) Channel excavations must be accomplished during the reservoir drawdown when the reservoir bottom is exposed and dry. (h) Spoil material from channel excavations must be placed in... Risk Profile elevation. For those reservoirs that have no flood control storage, dredge spoil must...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... reservoir drawdown periods. (g) Channel excavations must be accomplished during the reservoir drawdown when the reservoir bottom is exposed and dry. (h) Spoil material from channel excavations must be placed in... Risk Profile elevation. For those reservoirs that have no flood control storage, dredge spoil must...

  19. Congruent pattern of accessibility identifies minimal pore gate in a non-symmetric voltage-gated sodium channel

    PubMed Central

    Oelstrom, Kevin; Chanda, Baron

    2016-01-01

    Opening and closing of the central ion-conducting pore in voltage-dependent ion channels is gated by changes in membrane potential. Although a gate residue in the eukaryotic voltage-gated sodium channel has been identified, the minimal molecular determinants of this gate region remain unknown. Here, by measuring the closed- and open-state reactivity of MTSET to substituted cysteines in all the pore-lining helices, we show that the state-dependent accessibility is delineated by four hydrophobic residues at homologous positions in each domain. Introduced cysteines above these sites do not react with intracellular MTSET while the channels are closed and yet are rapidly modified while the channels are open. These findings, in conjunction with state-dependent metal cross-bridging, support the notion that the gate residues in each of the four S6 segments of the eukaryotic sodium channel form an occlusion for ions in the closed state and are splayed open on activation. PMID:27186888

  20. Congruent pattern of accessibility identifies minimal pore gate in a non-symmetric voltage-gated sodium channel.

    PubMed

    Oelstrom, Kevin; Chanda, Baron

    2016-01-01

    Opening and closing of the central ion-conducting pore in voltage-dependent ion channels is gated by changes in membrane potential. Although a gate residue in the eukaryotic voltage-gated sodium channel has been identified, the minimal molecular determinants of this gate region remain unknown. Here, by measuring the closed- and open-state reactivity of MTSET to substituted cysteines in all the pore-lining helices, we show that the state-dependent accessibility is delineated by four hydrophobic residues at homologous positions in each domain. Introduced cysteines above these sites do not react with intracellular MTSET while the channels are closed and yet are rapidly modified while the channels are open. These findings, in conjunction with state-dependent metal cross-bridging, support the notion that the gate residues in each of the four S6 segments of the eukaryotic sodium channel form an occlusion for ions in the closed state and are splayed open on activation. PMID:27186888

  1. Access channel residues Ser315 and Asp137 in Mycobacterium tuberculosis catalase-peroxidase (KatG) control peroxidatic activation of the pro-drug isoniazid

    PubMed Central

    Zhao, Xiangbo; Hersleth, Hans-Petter; Zhu, Janan; Andersson, K. Kristoffer; Magliozzo, Richard S.

    2013-01-01

    Peroxidatic activation of the anti-tuberculosis pro-drug isoniazid by Mycobacterium tuberculosis catalase-peroxidase (KatG) is regulated by gating residues of a heme access channel. The steric restriction at the bottleneck of this channel is alleviated by replacement of residue Asp137 with Ser, according to crystallographic and kinetic studies. PMID:24185282

  2. Harold E. Varmus, MD.

    PubMed

    Varmus, H E

    1995-06-01

    On November 19, 1993, the Senate approved the nomination of Harold E. Varmus, MD, as Director of the National Institutes of Health (NIH). Varmus, who received the 1989 Nobel Prize in Medicine, brought unquestioned credentials as a scientist to the NIH. Despite his limited background as an administrator, Varmus has received high marks from most observers for improving the morale of NIH staffers and implementing streamlined procedures in the grant review process. His tenure has not been free of controversy, however. Many clinical researchers have long felt there is a bias in NIH study sections against patient-oriented research. A recent study sponsored by the Division of Research Grants confirmed the lower success rate of patient-oriented research proposals, but the outcome of these findings remains unclear. Faced with mounting political pressure for a balanced budget, and the resultant reduction of funding to many branches of government, Varmus has been a strong voice for non-targeted investigator initiated research. Interviewed in his office in Building One on the NIH campus in Bethesda, Maryland, Varmus discussed the state of patient oriented research, the evolving role of the NIH in supporting science, and just where the money to pay for it should be found. PMID:7614067

  3. Functionally Active T1-T1 Interfaces Revealed by the Accessibility of Intracellular Thiolate Groups in Kv4 Channels

    PubMed Central

    Wang, Guangyu; Shahidullah, Mohammad; Rocha, Carmen A.; Strang, Candace; Pfaffinger, Paul J.; Covarrubias, Manuel

    2005-01-01

    Gating of voltage-dependent K+ channels involves movements of membrane-spanning regions that control the opening of the pore. Much less is known, however, about the contributions of large intracellular channel domains to the conformational changes that underlie gating. Here, we investigated the functional role of intracellular regions in Kv4 channels by probing relevant cysteines with thiol-specific reagents. We find that reagent application to the intracellular side of inside-out patches results in time-dependent irreversible inhibition of Kv4.1 and Kv4.3 currents. In the absence or presence of Kv4-specific auxiliary subunits, mutational and electrophysiological analyses showed that none of the 14 intracellular cysteines is essential for channel gating. C110, C131, and C132 in the intersubunit interface of the tetramerization domain (T1) are targets responsible for the irreversible inhibition by a methanethiosulfonate derivative (MTSET). This result is surprising because structural studies of Kv4-T1 crystals predicted protection of the targeted thiolate groups by constitutive high-affinity Zn2+ coordination. Also, added Zn2+ or a potent Zn2+ chelator (TPEN) does not significantly modulate the accessibility of MTSET to C110, C131, or C132; and furthermore, when the three critical cysteines remained as possible targets, the MTSET modification rate of the activated state is ∼200-fold faster than that of the resting state. Biochemical experiments confirmed the chemical modification of the intact α-subunit and the purified tetrameric T1 domain by MTS reagents. These results conclusively demonstrate that the T1–T1 interface of Kv4 channels is functionally active and dynamic, and that critical reactive thiolate groups in this interface may not be protected by Zn2+ binding. PMID:15955876

  4. 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.

  5. 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

  6. Coenzyme Q Biosynthesis: Evidence for a Substrate Access Channel in the FAD-Dependent Monooxygenase Coq6

    PubMed Central

    Ismail, Alexandre; Leroux, Vincent; Smadja, Myriam; Gonzalez, Lucie; Lombard, Murielle; Pierrel, Fabien; Mellot-Draznieks, Caroline; Fontecave, Marc

    2016-01-01

    Coq6 is an enzyme involved in the biosynthesis of coenzyme Q, a polyisoprenylated benzoquinone lipid essential to the function of the mitochondrial respiratory chain. In the yeast Saccharomyces cerevisiae, this putative flavin-dependent monooxygenase is proposed to hydroxylate the benzene ring of coenzyme Q (ubiquinone) precursor at position C5. We show here through biochemical studies that Coq6 is a flavoprotein using FAD as a cofactor. Homology models of the Coq6-FAD complex are constructed and studied through molecular dynamics and substrate docking calculations of 3-hexaprenyl-4-hydroxyphenol (4-HP6), a bulky hydrophobic model substrate. We identify a putative access channel for Coq6 in a wild type model and propose in silico mutations positioned at its entrance capable of partially (G248R and L382E single mutations) or completely (a G248R-L382E double-mutation) blocking access to the channel for the substrate. Further in vivo assays support the computational predictions, thus explaining the decreased activities or inactivation of the mutated enzymes. This work provides the first detailed structural information of an important and highly conserved enzyme of ubiquinone biosynthesis. PMID:26808124

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

    PubMed

    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

  8. 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.

  9. Release notice of MD 9ne and MD25 high fiber quality cotton germplasm lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    MD 9ne and MD 25 are non-commercial breeding lines of cotton (Gossypium hirsutum L.) released by the USDA-ARS at Stoneville, MS. One parent of MD 9ne was a strain of MD 51ne that had high fiber quality genes introduced from the Species Polycross. The other parent was MD 15. The parents of MD 25 a...

  10. Channel

    NASA Technical Reports Server (NTRS)

    2006-01-01

    [figure removed for brevity, see original site] Context image for PIA03693 Channel

    This channel is located south of Iani Chaos.

    Image information: VIS instrument. Latitude -10.9N, Longitude 345.5E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  11. 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

    ... Praxedes E. Alverez Santiago, M.D., Daniel Perez Brisebois, M.D., Jorge Grillasca Palou, M.D., Rafael Garcia Nieves, M.D., Francis M. Vazques Roura, M.D., Angel B. Rivera Santos, M.D., Cosme D. Santos Torres, M.D., and Juan L. Vilaro Chardon, M.D.; Analysis of Agreement Containing Consent Order To Aid...

  12. Different pH-sensitivity patterns of 30 sodium channel inhibitors suggest chemically different pools along the access pathway.

    PubMed

    Lazar, Alexandra; Lenkey, Nora; Pesti, Krisztina; Fodor, Laszlo; Mike, Arpad

    2015-01-01

    The major drug binding site of sodium channels is inaccessible from the extracellular side, drug molecules can only access it either from the membrane phase, or from the intracellular aqueous phase. For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein interactions. One-way to probe this is to modify the pH of the extracellular fluid, which alters the ratio of charged vs. uncharged forms of some compounds, thereby changing their interaction with the membrane. In this electrophysiology study we used three different pH values: 6.0, 7.3, and 8.6 to test the significance of the protonation-deprotonation equilibrium in drug access and affinity. We investigated drugs of several different indications: carbamazepine, lamotrigine, phenytoin, lidocaine, bupivacaine, mexiletine, flecainide, ranolazine, riluzole, memantine, ritanserin, tolperisone, silperisone, ambroxol, haloperidol, chlorpromazine, clozapine, fluoxetine, sertraline, paroxetine, amitriptyline, imipramine, desipramine, maprotiline, nisoxetine, mianserin, mirtazapine, venlafaxine, nefazodone, and trazodone. We recorded the pH-dependence of potency, reversibility, as well as onset/offset kinetics. As expected, we observed a strong correlation between the acidic dissociation constant (pKa) of drugs and the pH-dependence of their potency. Unexpectedly, however, the pH-dependence of reversibility or kinetics showed diverse patterns, not simple correlation. Our data are best explained by a model where drug molecules can be trapped in at least two chemically different environments: A hydrophilic trap (which may be the aqueous cavity within the inner vestibule), which favors polar and less lipophilic compounds, and a lipophilic trap (which may be the membrane phase itself, and/or lipophilic binding sites on the channel). Rescue from the hydrophilic and lipophilic traps can be promoted by alkalic and acidic extracellular pH, respectively. PMID:26441665

  13. Different pH-sensitivity patterns of 30 sodium channel inhibitors suggest chemically different pools along the access pathway

    PubMed Central

    Lazar, Alexandra; Lenkey, Nora; Pesti, Krisztina; Fodor, Laszlo; Mike, Arpad

    2015-01-01

    The major drug binding site of sodium channels is inaccessible from the extracellular side, drug molecules can only access it either from the membrane phase, or from the intracellular aqueous phase. For this reason, ligand-membrane interactions are as important determinants of inhibitor properties, as ligand-protein interactions. One-way to probe this is to modify the pH of the extracellular fluid, which alters the ratio of charged vs. uncharged forms of some compounds, thereby changing their interaction with the membrane. In this electrophysiology study we used three different pH values: 6.0, 7.3, and 8.6 to test the significance of the protonation-deprotonation equilibrium in drug access and affinity. We investigated drugs of several different indications: carbamazepine, lamotrigine, phenytoin, lidocaine, bupivacaine, mexiletine, flecainide, ranolazine, riluzole, memantine, ritanserin, tolperisone, silperisone, ambroxol, haloperidol, chlorpromazine, clozapine, fluoxetine, sertraline, paroxetine, amitriptyline, imipramine, desipramine, maprotiline, nisoxetine, mianserin, mirtazapine, venlafaxine, nefazodone, and trazodone. We recorded the pH-dependence of potency, reversibility, as well as onset/offset kinetics. As expected, we observed a strong correlation between the acidic dissociation constant (pKa) of drugs and the pH-dependence of their potency. Unexpectedly, however, the pH-dependence of reversibility or kinetics showed diverse patterns, not simple correlation. Our data are best explained by a model where drug molecules can be trapped in at least two chemically different environments: A hydrophilic trap (which may be the aqueous cavity within the inner vestibule), which favors polar and less lipophilic compounds, and a lipophilic trap (which may be the membrane phase itself, and/or lipophilic binding sites on the channel). Rescue from the hydrophilic and lipophilic traps can be promoted by alkalic and acidic extracellular pH, respectively. PMID:26441665

  14. Enhancing Access to Land Remote Sensing Data through Mainstream Social Media Channels

    NASA Astrophysics Data System (ADS)

    Sohre, T.; Maiersperger, T.

    2011-12-01

    Social media tools are changing the way that people discover information, communicate, and collaborate. Government agencies supporting the Land Remote Sensing user community have begun taking advantage of standard social media tools and capabilities. National Aeronautics and Space Administration (NASA) Earth Observing System (EOS) data centers have started providing outreach utilizing services including Facebook, Twitter, and YouTube videos. Really Simple Syndication (RSS) Feeds have become more standard means of sharing information, and a DataCasting tool was created as a NASA Technology Infusion effort to make RSS-based technology for accessing Earth Science information available. The United States Geological Survey (USGS) has also started using social media to allow the community access to news feeds and real-time earthquake alerts; listen to podcasts; get updates on new USGS publications, videos, and photographs; and more. Twitter feeds have been implemented in 2011 for the USGS Land Cover and Landsat user communities. In early 2011, the NASA Land Processes Distributed Active Archive Center (LP DAAC) user working group suggested the investigation of concepts for creating and distributing "bundles" of data, which would aggregate theme-based data sets from multiple sources. The LP DAAC is planning to explore the use of standard social bookmarking tools to support community developed bundles through the use of tools such as Delicious, Digg, or StumbleUpon. This concept would allow science users to organize and discover common links to data resources based on community developed tags, or a folksonomy. There are challenges that will need to be addressed such as maintaining the quality of tags but a social bookmarking system may have advantages over traditional search engines or formal ontologies for identifying and labeling various data sets relevant to a theme. As classification is done by the community of scientists who understand the data, the tagged data sets

  15. Changes in accessibility of cytoplasmic substances to the pore associated with activation of the cystic fibrosis transmembrane conductance regulator chloride channel.

    PubMed

    El Hiani, Yassine; Linsdell, Paul

    2010-10-15

    Opening of the cystic fibrosis transmembrane conductance regulator Cl(-) channel is dependent both on phosphorylation and on ATP binding and hydrolysis. However, the mechanisms by which these cytoplasmic regulatory factors open the Cl(-) channel pore are not known. We have used patch clamp recording to investigate the accessibility of cytoplasmically applied cysteine-reactive reagents to cysteines introduced along the length of the pore-lining sixth transmembrane region (TM6) of a cysteine-less variant of cystic fibrosis transmembrane conductance regulator. We find that methanethiosulfonate (MTS) reagents modify irreversibly cysteines substituted for TM6 residues Phe-337, Thr-338, Ser-341, Ile-344, Val-345, Met-348, Ala-349, Arg-352, and Gln-353 when applied to the cytoplasmic side of open channels. However, the apparent rate of modification by internal [2-sulfonatoethyl] methanethiosulfonate (MTSES), a negatively charged MTS reagent, is dependent on the activation state of the channels. In particular, cysteines introduced far along the axis of TM6 from the inside (T338C, S341C, I344C) showed no evidence of significant modification even after prolonged pretreatment of non-activated channels with internal MTSES. In contrast, cysteines introduced closer to the inside of TM6 (V345C, M348C) were readily modified in both activated and non-activated channels. Access of a permeant anion, Au(CN)(2)(-), to T338C was similarly dependent upon channel activation state. The pattern of MTS modification we observe allows us to designate different pore-lining amino acid side chains to distinct functional regions of the channel pore. One logical interpretation of these findings is that cytoplasmic access to residues at the narrowest region of the pore changes concomitant with activation. PMID:20675380

  16. Changes in Accessibility of Cytoplasmic Substances to the Pore Associated with Activation of the Cystic Fibrosis Transmembrane Conductance Regulator Chloride Channel*

    PubMed Central

    El Hiani, Yassine; Linsdell, Paul

    2010-01-01

    Opening of the cystic fibrosis transmembrane conductance regulator Cl− channel is dependent both on phosphorylation and on ATP binding and hydrolysis. However, the mechanisms by which these cytoplasmic regulatory factors open the Cl− channel pore are not known. We have used patch clamp recording to investigate the accessibility of cytoplasmically applied cysteine-reactive reagents to cysteines introduced along the length of the pore-lining sixth transmembrane region (TM6) of a cysteine-less variant of cystic fibrosis transmembrane conductance regulator. We find that methanethiosulfonate (MTS) reagents modify irreversibly cysteines substituted for TM6 residues Phe-337, Thr-338, Ser-341, Ile-344, Val-345, Met-348, Ala-349, Arg-352, and Gln-353 when applied to the cytoplasmic side of open channels. However, the apparent rate of modification by internal [2-sulfonatoethyl] methanethiosulfonate (MTSES), a negatively charged MTS reagent, is dependent on the activation state of the channels. In particular, cysteines introduced far along the axis of TM6 from the inside (T338C, S341C, I344C) showed no evidence of significant modification even after prolonged pretreatment of non-activated channels with internal MTSES. In contrast, cysteines introduced closer to the inside of TM6 (V345C, M348C) were readily modified in both activated and non-activated channels. Access of a permeant anion, Au(CN)2−, to T338C was similarly dependent upon channel activation state. The pattern of MTS modification we observe allows us to designate different pore-lining amino acid side chains to distinct functional regions of the channel pore. One logical interpretation of these findings is that cytoplasmic access to residues at the narrowest region of the pore changes concomitant with activation. PMID:20675380

  17. Theoretical Characterization of Substrate Access/Exit Channels in the Human Cytochrome P450 3A4 Enzyme: Involvement of Phenylalanine Residues in the Gating Mechanism

    PubMed Central

    2009-01-01

    The human cytochrome P450 3A4 mono-oxygenates ∼50% of all drugs. Its substrates/products enter/leave the active site by access/exit channels. Here, we perform steered molecular dynamics simulations, pulling the products temazepam and testosterone-6βOH out of the P450 3A4 enzyme in order to identify the preferred substrate/product pathways and their gating mechanism. We locate six different egress pathways of products from the active site with different exit preferences for the two products and find that there is more than just one access/exit channel in CYP3A4. The so-called solvent channel manifests the largest opening for both tested products, thereby identifying this channel as a putative substrate channel. Most channels consist of one or two π-stacked phenylalanine residues that serve as gate keepers. The oxidized drug breaks the hydrophobic interactions of the gating residues and forms mainly hydrophobic contacts with the gate. We argue that product exit preferences in P450s are regulated by protein−substrate specificity. PMID:19728720

  18. 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

  19. Crystal Structure of Inhibitor-Bound P450BM-3 Reveals Open Conformation of Substrate Access Channel

    SciTech Connect

    Haines, Donovan C.; Chen, Baozhi; Tomchick, Diana R.; Bondlela, Muralidhar; Hegde, Amita; Machius, Mischa; Peterson, Julian A.

    2008-08-19

    P450BM-3 is an extensively studied P450 cytochrome that is naturally fused to a cytochrome P450 reductase domain. Crystal structures of the heme domain of this enzyme have previously generated many insights into features of P450 structure, substrate binding specificity, and conformational changes that occur on substrate binding. Although many P450s are inhibited by imidazole, this compound does not effectively inhibit P450BM-3. {omega}-Imidazolyl fatty acids have previously been found to be weak inhibitors of the enzyme and show some unusual cooperativity with the substrate lauric acid. We set out to improve the properties of these inhibitors by attaching the {omega}-imidazolyl fatty acid to the nitrogen of an amino acid group, a tactic that we used previously to increase the potency of substrates. The resulting inhibitors were significantly more potent than their parent compounds lacking the amino acid group. A crystal structure of one of the new inhibitors bound to the heme domain of P450BM-3 reveals that the mode of interaction of the amino acid group with the enzyme is different from that previously observed for acyl amino acid substrates. Further, required movements of residues in the active site to accommodate the imidazole group provide an explanation for the low affinity of imidazole itself. Finally, the previously observed cooperativity with lauric acid is explained by a surprisingly open substrate-access channel lined with hydrophobic residues that could potentially accommodate lauric acid in addition to the inhibitor itself.

  20. 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.

  1. Chip-interleaved optical code division multiple access relying on a photon-counting iterative successive interference canceller for free-space optical channels.

    PubMed

    Zhou, Xiaolin; Zheng, Xiaowei; Zhang, Rong; Hanzo, Lajos

    2013-07-01

    In this paper, we design a novel Poisson photon-counting based iterative successive interference cancellation (SIC) scheme for transmission over free-space optical (FSO) channels in the presence of both multiple access interference (MAI) as well as Gamma-Gamma atmospheric turbulence fading, shot-noise and background light. Our simulation results demonstrate that the proposed scheme exhibits a strong MAI suppression capability. Importantly, an order of magnitude of BER improvements may be achieved compared to the conventional chip-level optical code-division multiple-access (OCDMA) photon-counting detector. PMID:23842379

  2. Binding of the antitubercular pro-drug isoniazid in the heme access channel of catalase-peroxidase (KatG). A combined structural and metadynamics investigation.

    PubMed

    Vidossich, Pietro; Loewen, Peter C; Carpena, Xavi; Fiorin, Giacomo; Fita, Ignacio; Rovira, Carme

    2014-03-20

    Isonicotinic acid hydrazide (isoniazid or INH) is a front line antitubercular pro-drug that is converted to its active form, isonicotinyl-NAD, by the bacterial catalase-peroxidase KatG. Understanding the role of KatG in the INH activation process has been hampered by a lack of knowledge of the actual drug binding site. In this work, we have investigated the binding of INH in the main access channel of KatG with a combination of molecular dynamics, using an enhanced-sampling technique (metadynamics), X-ray crystallography, and site-directed mutagenesis. The metadynamics simulations show that there are several weak drug binding sites along the access channel. Moreover, the simulations evidence that complete entrance to the heme active site is impeded by an aspartate residue (D141) located above the heme. This has been confirmed by structural and functional analysis of the D141A mutant, leading to the first X-ray crystallography evidence of INH at the heme access channel. PMID:24568093

  3. Proportional Data Rate Fairness Resource Allocation for MIMO-OFDM Multiple Access Channel by Considering the Correlation Effect of Line of Sight and Non Line of Sight Channel Conditions

    NASA Astrophysics Data System (ADS)

    Maung, Sann Maw; Sasase, Iwao

    In the MIMO-OFDM multiple access channel (MIMO-OFDM-MAC) uplink scenario, the base station decides the uplink parameters for multiple users based on channel state information (CSI) from each user in the system. The performance of MIMO-OFDM-MAC systems can be significantly improved by using an adaptive transmission and resource allocation schemes which consider the correlation effect of line of sight (LOS) and non line of sight (NLOS) channel conditions for different users in the system. A lot of papers have been published on resource allocation schemes for MIMO-OFDM systems. However, most of these resource allocation schemes have been considered for MIMO-OFDMA systems, where users are separated in the frequency domain and each user uses the same uplink and downlink channels in the same channel conditions. On the other hand, in the mulituser MIMO-OFDM systems, more than one user can be assigned the same frequency and channel conditions for the MIMO-OFDM broadcast channel (downlink) and MIMO-OFDM-MAC channel (uplink) are not the same. Therefore, the same resource allocation schemes for the conventional MIMO-OFDM systems can not be applied to multiuser MIMO-OFDM systems with different uplink and downlink channel conditions. Until now, most of the resource allocation schemes have been considered only for downlink MIMO-OFDM broadcast (MIMO-OFDM-BC) channel and very few papers tackle the fairness among users. Moreover, no paper considers a scheme to realize proportional data rate fairness among users in the MIMO-OFDM-MAC condition. In this paper, we propose a proportional data rate fairness resource allocation scheme with adaptive bit loading for MIMO-ODFM-MAC systems by considering the correlation effects of LOS and NLOS channel conditions in both spatial and frequency domains. Computer simulation results show that the proposed scheme can give larger system capacity while maintaining the proportional data rate fairness requirements among users in the system under the

  4. Physical Properties of Near-Earth Asteroid 2011 MD

    NASA Astrophysics Data System (ADS)

    Mommert, M.; Farnocchia, D.; Hora, J. L.; Chesley, S. R.; Trilling, D. E.; Chodas, P. W.; Mueller, M.; Harris, A. W.; Smith, H. A.; Fazio, G. G.

    2014-07-01

    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+4-2) m in diameter with a geometric albedo of 0.3+0.4-0.2 (uncertainties are 1σ). We find the asteroid's most probable bulk density to be (1.1+0.7-0.5) g cm-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.

  5. 33 CFR 334.170 - Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range, Naval Research Laboratory.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... of Chesapeake Beach, Md.; firing range, Naval Research Laboratory. 334.170 Section 334.170 Navigation... RESTRICTED AREA REGULATIONS § 334.170 Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range...-west line through Chesapeake Beach Light 2 at the entrance channel to Fishing Creek; on the south by...

  6. 33 CFR 334.170 - Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range, Naval Research Laboratory.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... of Chesapeake Beach, Md.; firing range, Naval Research Laboratory. 334.170 Section 334.170 Navigation... RESTRICTED AREA REGULATIONS § 334.170 Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range...-west line through Chesapeake Beach Light 2 at the entrance channel to Fishing Creek; on the south by...

  7. 33 CFR 334.170 - Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range, Naval Research Laboratory.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... of Chesapeake Beach, Md.; firing range, Naval Research Laboratory. 334.170 Section 334.170 Navigation... RESTRICTED AREA REGULATIONS § 334.170 Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range...-west line through Chesapeake Beach Light 2 at the entrance channel to Fishing Creek; on the south by...

  8. 33 CFR 334.170 - Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range, Naval Research Laboratory.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... of Chesapeake Beach, Md.; firing range, Naval Research Laboratory. 334.170 Section 334.170 Navigation... RESTRICTED AREA REGULATIONS § 334.170 Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range...-west line through Chesapeake Beach Light 2 at the entrance channel to Fishing Creek; on the south by...

  9. 33 CFR 334.170 - Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range, Naval Research Laboratory.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... of Chesapeake Beach, Md.; firing range, Naval Research Laboratory. 334.170 Section 334.170 Navigation... RESTRICTED AREA REGULATIONS § 334.170 Chesapeake Bay, in the vicinity of Chesapeake Beach, Md.; firing range...-west line through Chesapeake Beach Light 2 at the entrance channel to Fishing Creek; on the south by...

  10. 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

  11. Exploring accessibility of structural elements of the mammalian 40S ribosomal mRNA entry channel at various steps of translation initiation.

    PubMed

    Sharifulin, Dmitri E; Bartuli, Yulia S; Meschaninova, Maria I; Ven'yaminova, Aliya G; Graifer, Dmitri M; Karpova, Galina G

    2016-10-01

    In this work, we studied how the accessibility of structural elements of the mammalian 40S ribosomal mRNA entry channel, ribosomal protein (rp) uS3 and helix (h) 16 of the 18S rRNA, changes upon the translation initiation. In particular, we examined the accessibility of rp uS3 for binding of unstructured RNAs and of riboses in h16 towards attack with benzoyl cyanide (BzCN) in complexes assembled in rabbit reticulocyte lysate utilizing synthetic oligoribonucleotides as well as full-length and truncated up to the initiation AUG codon hepatitis C virus IRES as model mRNAs. With both mRNA types, the rp uS3 peptide recognizing single-stranded RNAs was shown to become shielded only in those 48S preinitiation complexes (PICs) that contained eIF3j bound to 40S subunit in the area between the decoding site and the mRNA entry channel. Chemical probing with BzCN revealed that h16 in the 48S PICs containing eIF3j or scanning factor DHX29 is strongly shielded; the effect was observed with all the mRNAs used, and h16 remained protected as well in 80S post-initiation complexes lacking these factors. Altogether, the obtained results allowed us to suggest that eIF3j bound at the 48S PICs makes the rp uS3 inaccessible for binding of RNAs and this factor subunit is responsible for the decrease of h16 conformational flexibility; the latter is manifested as reduced accessibility of h16 to BzCN. Thus, our findings provide new insights into how eIF3j is implicated in ensuring the proper conformation of the mRNA entry channel, thereby facilitating mRNA loading. PMID:27346718

  12. An Investigation of How the Channel of Input and Access to Test Questions Affect L2 Listening Test Performance

    ERIC Educational Resources Information Center

    Wagner, Elvis

    2013-01-01

    The use of video technology has become widespread in the teaching and testing of second-language (L2) listening, yet research into how this technology affects the learning and testing process has lagged. The current study investigated how the channel of input (audiovisual vs. audio-only) used on an L2 listening test affected test-taker…

  13. [MD-NET--muscular dystrophy network].

    PubMed

    Lochmüller, H; Straub, V

    2007-12-01

    Muscular dystrophies (MD) constitute a group of inherited disorders characterized by progressive weakness of skeletal and sometimes cardiac muscle. MD are rare disorders affecting approximately 26,000 to 40,000 people in Germany based on a pre valence of 1:2000 to 1:3000 (estimate of the Association Française contre les Myopathies, AFM) and a population of 80 million people residing in Germany. More than 30 forms of MD are recognized today caused by different genetic defects. Based on the symptoms of an individual patient the underlying genetic defect cannot be determined, since all MD have the following in common: Muscle fibers are destroyed and become replaced by fatty and fibrous tissue. Various forms of MD are caused by defects of proteins residing in the sarcolemma, the cell membrane of muscle fibers. Other forms are caused by defects of proteins that are associated to the nucleus, to the sarcomer or the cytoplasm. Moreover, there are numerous forms where the exact molecular defect is unknown to date. Even though the underlying defect is known for many MD, the pathogenic process that leads to the decay of musculature is poorly understood. At present, MD cannot be cured. MD are treated by physiotherapy, surgery and medication that may delay progression. Symptomatic therapy such as cardiac pace makers may be life-saving and improve quality of life in many patients. For optimizing research into the MD, a network, the muscular dystrophy network or MD-NET, was initiated and has been supported by the German ministry of education and research (BMBF) since 2003. PMID:18026885

  14. A hybrid MD-DSMC coupling method to investigate flow characteristics of micro-devices

    NASA Astrophysics Data System (ADS)

    Watvisave, D. S.; Puranik, B. P.; Bhandarkar, U. V.

    2015-12-01

    A new methodology is proposed to couple Molecular Dynamics (MD) and Direct Simulation Monte Carlo (DSMC) methods to simulate high Knudsen number (Kn) flows. For this purpose a two-dimensional hybrid MD-DSMC code is developed. In this method gas-surface interactions are modeled using MD, and gas-gas interactions are modeled using DSMC method. Two-way coupling between MD and DSMC is implemented by employing buffer zones for both MD and DSMC regions. Bootstrap sampling and energy minimization algorithms are employed for dynamic coupling of these two methods since MD utilizes real number of molecules during simulation whereas DSMC utilizes a lesser number of simulated molecules. The hybrid methodology combines the advantages of both methods; it has the capability of modeling the gas-surface interaction accurately considering the effect of the presence of neighboring real number of gas molecules, while in the bulk it utilizes DSMC with only the simulated number of molecules thus increasing the computational efficiency significantly compared to pure MD codes. As a result comparatively large domain sizes can be simulated with realistic behavior at the walls. The utility of the hybrid method is demonstrated by simulating high Kn flows through a micro-channel, micro-nozzle and micro-scale shock tube. The effect of partial accommodation of gas molecules with the wall is seen to be captured dynamically with this approach.

  15. IUPHAR-DB: An Open-Access, Expert-Curated Resource for Receptor and Ion Channel Research

    PubMed Central

    2011-01-01

    This contribution highlights efforts by the International Union of Basic and Clinical Pharmacology (IUPHAR) Nomenclature Committee (NC-IUPHAR) to classify human receptors and ion channels, to document their properties, and to recommend ligands that are useful for characterization. This effort has inspired the creation of an online database (IUPHAR-DB), which is intended to provide free information to all scientists, summarized from primary literature by experts. PMID:22778867

  16. Harvesting graphics power for MD simulations

    NASA Astrophysics Data System (ADS)

    van Meel, J.; Arnold, A.; Frenkel, D.; Portegies Zwart, S. F.; Belleman, R.

    2008-05-01

    We discuss an implementation of molecular dynamics (MD) simulations on a graphic processing unit (GPU) in the NVIDIA CUDA language. We tested our code on a modern GPU, the NVIDIA GeForce 8800 GTX. Results for two MD algorithms suitable for short-ranged and long-ranged interactions, and a congruential shift random number generator are presented. The performance of the GPU's is compared to their main processor counterpart. We achieve speedups of up to 40, 80 and 150 fold, respectively. With the latest generation of GPU's one can run standard MD simulations at 107 flops/s.

  17. Registration of MD25-26ne, MD25-27, and MD25-87 germplasm lines of cotton with superior yield, fiber quality, and pest resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Three non-commercial cotton (Gossypium hirsutum L.) lines which were released by the USDA-ARS are MD25-26ne (PI 666042), MD25-27 (PI 666043), and MD25-87 (PI 666044). The three lines are reselections out of MD25 (Reg. No GP-929; PI 659505). The objective of this research was to select lines that h...

  18. MD-11 PCA - landing at DFRC

    NASA Technical Reports Server (NTRS)

    1995-01-01

    On August 29, 1995, aided by NASA-developed propulsion controlled aircraft (PCA) system, a McDonnell-Douglas MD-11 made the first-ever, safe landings of an actual transport aircraft using only engine power for control. Later, on November 30, 1995, improved software enabled a McDonnell-Douglas MD-11 to make a final landing at Edwards without the need for the pilot to manipulate the flight controls while using only engine power for control.

  19. 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

  20. 1-Tb/s single-channel coherent optical OFDM transmission over 600-km SSMF fiber with subwavelength bandwidth access.

    PubMed

    Ma, Yiran; Yang, Qi; Tang, Yan; Chen, Simin; Shieh, William

    2009-05-25

    A 1-Tb/s single-channel coherent optical OFDM (CO-OFDM) signal consisting of continuous 4,104 spectrally-overlapped subcarriers is generated using a novel device of recirculating frequency shifter (RFS). The RFS produces 320.6-GHz wide spectrum using a single laser with superior flatness and tone-to-noise ratio (TNR). The 1-Tb/s CO-OFDM signal is comprised of 36 uncorrelated orthogonal bands achieved by adjusting the delay of the RFS to an integer number of OFDM symbol periods. The 1- Tb/s CO-OFDM signal with a spectral efficiency of 3.3 bit/s/Hz is successfully received after transmission over 600-km SSMF fiber without either Raman amplification or dispersion compensation. PMID:19466194

  1. Four-Channel, 8 x 8 Bit, Two-Dimensional Parallel Transmission by use of Space-Code-Division Multiple-Access Encoder and Decoder Modules.

    PubMed

    Nakamura, M; Kitayama, K; Igasaki, Y; Kaneda, K

    1998-07-10

    We experimentally demonstrate four-channel multiplexing of 64-bit (8 x 8) two-dimensional (2-D) parallel data links on the basis of optical space-code-division multiple access (CDMA) by using new modules of optical spatial encoders and a decoder with a new high-contrast 9-m-long image fiber with 3 x 10(4) cores. Each 8 x 8 bit plane (64-bit parallel data) is optically encoded with an 8 x 8, 2-D optical orthogonal signature pattern. The encoded bit planes are spatially multiplexed and transmitted through an image fiber. A receiver can recover the intended input bit plane by means of an optical decoding process. This result should encourage the application of optical space-CDMA to future high-throughput 2-D parallel data links connecting massively parallel processors. PMID:18285889

  2. Near-Collision Attacks on MD4: Applied to MD4-Based Protocols

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Ohta, Kazuo; Kunihiro, Noboru

    The most widely used hash functions from MD4 family have been broken, which lead to a public competition on designing new hash functions held by NIST. This paper focuses on one concept called near-collision resistance: computationally difficult to find a pair of messages with hash values differing in only few bits, which new hash functions should satisfy. In this paper, we will give a model of near-collisions on MD4, and apply it to attack protocols including HMAC/NMAC-MD4 and MD4(Password||Challenge). Our new outer-key recovery attacks on HMAC/NMAC-MD4 has a complexity of 272 online queries and 277 MD4 computations, while previous result was 288 online queries and 295 MD4 computations. Our attack on MD4(Password||Challenge) can recover 16 password characters with a complexity of 237 online queries and 221 MD4 computations, which is the first approach to attack such protocols.

  3. 33 CFR 165.513 - Safety Zone; Magothy River, Sillery Bay, MD.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... zones found in 33 CFR 165.23. (2) All vessels and persons are prohibited from entering and accessing... 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:...

  4. 33 CFR 165.513 - Safety Zone; Magothy River, Sillery Bay, MD.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... zones found in 33 CFR 165.23. (2) All vessels and persons are prohibited from entering and accessing... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Safety Zone; Magothy River... Safety Zone; Magothy River, Sillery Bay, MD. (a) Regulated area. The following area is a safety zone:...

  5. 33 CFR 165.513 - Safety Zone; Magothy River, Sillery Bay, MD.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... zones found in 33 CFR 165.23. (2) All vessels and persons are prohibited from entering and accessing... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Safety Zone; Magothy River... Safety Zone; Magothy River, Sillery Bay, MD. (a) Regulated area. The following area is a safety zone:...

  6. Registration of cotton germplasm line md 10-5

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. 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. PMID:22621202

  8. Free Thiol Group of MD-2 as the Target for Inhibition of the Lipopolysaccharide-induced Cell Activation*

    PubMed Central

    Manček-Keber, Mateja; Gradišar, Helena; Pestaña, Melania Iñigo; de Tejada, Guillermo Martinez; Jerala, Roman

    2009-01-01

    MD-2 is a part of the Toll-like 4 signaling complex with an indispensable role in activation of the lipopolysaccharide (LPS) signaling pathway and thus a suitable target for the therapeutic inhibition of TLR4 signaling. Elucidation of MD-2 structure provides a foundation for rational design of inhibitors that bind to MD-2 and inhibit LPS signaling. Since the hydrophobic binding pocket of MD-2 provides little specificity for inhibitors, we have investigated targeting the solvent-accessible cysteine residue within the hydrophobic binding pocket of MD-2. Compounds with affinity for the hydrophobic pocket that contain a thiol-reactive group, which mediates covalent bond formation with the free cysteine residue of MD-2, were tested. Fluorescent compounds 2-(4′-(iodoacetamido)anilino)naphthalene-6-sulfonic acid and N-pyrene maleimide formed a covalent bond with MD-2 through Cys133 and inhibited LPS signaling. Cell activation was also inhibited by thiol-reactive compounds JTT-705 originally targeted against cholesterol ester transfer protein and antirheumatic compound auranofin. Oral intake of JTT-705 significantly inhibited endotoxin-triggered tumor necrosis factor α production in mice. The thiol group of MD-2 also represents the target of environmental or endogenous thiol-reactive compounds that are produced in inflammation. PMID:19473973

  9. 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…

  10. 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. |

  11. 78 FR 2707 - Maryland Disaster # MD-00026

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-14

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Maryland Disaster MD-00026 AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY... Deadline Date: 10/02/2013. ADDRESSES: Submit completed loan applications to: U.S. Small...

  12. 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.

  13. 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

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

    PubMed

    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

  15. Blocking the passage: C60 geometrically clogs K(+) channels.

    PubMed

    Calvaresi, Matteo; Furini, Simone; Domene, Carmen; Bottoni, Andrea; Zerbetto, Francesco

    2015-05-26

    Classical molecular dynamics (MD) simulations combined with docking calculations, potential of mean force estimates with the umbrella sampling method, and molecular mechanic/Poisson-Boltzmann surface area (MM-PBSA) energy calculations reveal that C60 may block K(+) channels with two mechanisms: a low affinity blockage from the extracellular side, and an open-channel block from the intracellular side. The presence of a low affinity binding-site at the extracellular entrance of the channel is in agreement with the experimental results showing a fast and reversible block without use-dependence, from the extracellular compartment. Our simulation protocol suggests the existence of another binding site for C60 located in the channel cavity at the intracellular entrance of the selectivity filter. The escape barrier from this binding site is ∼21 kcal/mol making the corresponding kinetic rate of the order of minutes. The analysis of the change in solvent accessible surface area upon C60 binding shows that binding at this site is governed purely by shape complementarity, and that the molecular determinants of binding are conserved in the entire family of K(+) channels. The presence of this high-affinity binding site conserved among different K(+) channels may have serious implications for the toxicity of carbon nanomaterials. PMID:25873341

  16. Theory and MD Simulation of Polyolefin Blends

    NASA Astrophysics Data System (ADS)

    Curro, John G.; Grest, Gary S.; Jaramillo, Eugenio; Wu, David T.; Li, Huimin

    2004-03-01

    Molecular dynamics (MD) simulations and PRISM theory calculations were carried out on various polyolefin homopolymer and copolymer blends. These polyolefins were modeled at the united atom level at 453K using the TRaPPE potential between pairs of sites. The chi parameters from the simulations were estimated from the structure factors using the random phase approximation (RPA) in analogy with neutron scattering (SANS) experiments. The heats of mixing were computed from both simulation and PRISM theory. The MD simulations predicted temperature dependent chi parameters in good agreement with SANS measurements previously reported on hhPP/PIB, hhPP/PP, and hhPP/PE. PRISM theory calculations on the PE(x)PEE(1-x)/PP blend suggest a miscibility window for a range of copolymer compositions x in agreement with SANS experiments.

  17. Direct NOE simulation from long MD trajectories

    NASA Astrophysics Data System (ADS)

    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.

  18. Toxic wastes discovered in Cecil County, MD

    SciTech Connect

    Not Available

    1994-01-01

    This report focuses on the clean-up activities following toxic waste contamination in Cecil County, MD. The potentially hazardous leakage from waste containers buried in a quarry was addressed before it was turned into a civil emergency of the magnitude of Love Canal. US Superfund is a federal government trust fund largely comprised of taxes on the chemical and petrochemical industries. Local governments share in the cost of removing the waste and other aspects of emergency management.

  19. Toxic wastes discovered in Cecil County, MD

    SciTech Connect

    1994-12-31

    This report focuses on the clean-up activities following toxic waste contamination in Cecil County, MD. The potentially hazardous leakage from waste containers buried in a quarry was addressed before it was turned into a civil emergency of the magnitude of Love Canal. US Superfund is a federal government trust fund largely comprised of taxes on the chemical and petrochemical industries. Local governments share in the cost of removing the waste and other aspects of emergency management.

  20. 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 the National Cancer Institute, Dr. Szabo led a laboratory effort studying lung cancer biology. |

  1. Susquehanna River Bridge. Havre de Grace, Hareford Co., MD. Sec. ...

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

    Susquehanna River Bridge. Havre de Grace, Hareford Co., MD. Sec. 1201, MP 60.07. - Northeast Railroad Corridor, Amtrak route between District of Columbia/Maryland state line & Maryland/Delaware state line, Baltimore, Independent City, MD

  2. Juniata Street Culvert. Havre de Grace, Hareford Co., MD. Sec. ...

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

    Juniata Street Culvert. Havre de Grace, Hareford Co., MD. Sec. 1201, MP 60.77. - Northeast Railroad Corridor, Amtrak route between District of Columbia/Maryland state line & Maryland/Delaware state line, Baltimore, Independent City, MD

  3. Local Legends of Medicine: Janelle Goetcheus, M.D.

    MedlinePlus

    ... Issues Local Legends of Medicine: Janelle Goetcheus, M.D. Past Issues / Spring 2007 Table of Contents For ... and photos by Christopher Klose Janelle Goetcheus, M.D., Caring for and about Washington, DC's Homeless "The ...

  4. 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.

  5. 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

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-27

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Sassafras River, Georgetown, MD... of the Sassafras River (Route 213) Bridge, mile 10.0, in Georgetown, MD. The deviation is necessary... Sassafras River Bridge (Route 213), at mile 10.0, in Georgetown, MD has a vertical clearance in the...

  7. Discovery of /sup 260/Md and the decay properties of /sup 258/Fm, /sup 258m,g/Md, and /sup 259/Md

    SciTech Connect

    Lougheed, R.W.; Hulet, E.K.; Dougan, R.J.; Wild, J.F.; Dupzyk, R.J.; Henderson, C.M.; Moody, K.J.; Hahn, R.L.; Suemmerer, K.; Bethune, G.

    1985-08-01

    We have discovered a new neutron-rich isotope, /sup 260/Md, from /sup 18/O and /sup 22/Ne bombardments of /sup 254/Es. We observed a spontaneous-fission (SF) activity with a 32-day half-life in electromagnetically separated mass-260 fractions from these bombardments and we have measured the mass and kinetic energy distributions of this SF activity. The mass distribution was symmetric with the principal energy peak at 234-MeV total kinetic energy (TKE), similar to previous observations for heavy Fm isotopes. Surprisingly, we also observed a smaller symmetric component with 195-MeV TKE. We interpret these two peaks in the TKE distribution as arising from two types of fission in the same nucleus, or bimodal fission. The observed fission activity may be either from the SF decay of /sup 260/Md or /sup 260/Fm which would arise from electron capture (EC) decay of /sup 260/Md. We have eliminated the possible ..beta../sup -/ decay of /sup 260/Md by measuring ..beta../sup -/-SF time correlations for the decay of /sup 260/Md and we plan to determine if /sup 260/Md decays by EC by measuring time correlations between Fm x-rays and SF events. We also measured properties for heavy Fm and Md isotopes which include: (1) more accurate cross sections for the neutron-rich Md isotopes which we use to predict the production rates of yet undiscovered nuclides; (2) improved half-live measurements for /sup 258m,g/Md and /sup 259/Md; (3) confirmation of the EC decay of /sup 258m/Md by measuring Fm x-rays preceding the SF decay of /sup 258/Fm; and (4) very substantially improved mass and TKE distributions for the SF decay of /sup 258/Fm and /sup 259/Md.

  8. Identification of a novel transcript of human MD2 gene.

    PubMed

    Shen, Chen; Shen, A-Dong

    2016-09-15

    Myeloid differentiation protein 2 (MD2) regulates bacterial lipopolysaccharide (LPS) triggered anti-bacterial immune response as a broker between LPS and Toll-like receptor 4 (TLR4). In this study, we identified a novel naturally occurring spliceosome of human MD2, termed as MD2-T3. This transcript lacked two exons of MD2 gene. By protein structure analysis and literature review, we predicted that MD2-T3 isoform might execute regulatory biological effects such as limiting LPS-triggered TLR4 signaling. PMID:27317890

  9. 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%). PMID:27069559

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

    PubMed Central

    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%). PMID:27069559

  11. Domain-swapped chain connectivity and gated membrane access in a Fab-mediated crystal of the human TRAAK K+ channel

    PubMed Central

    Brohawn, Stephen G.; Campbell, Ernest B.; MacKinnon, Roderick

    2013-01-01

    TRAAK (TWIK-related arachidonic acid-stimulated K+ channel, K2P4.1) K+ ion channels are expressed predominantly in the nervous system to control cellular resting membrane potential and are regulated by mechanical and chemical properties of the lipid membrane. TRAAK channels are twofold symmetric, which precludes a direct extension of gating mechanisms that close canonical fourfold symmetric K+ channels. We present the crystal structure of human TRAAK in complex with antibody antigen-binding fragments (Fabs) at 2.75-Å resolution. In contrast to a previous structure, this structure reveals a domain-swapped chain connectivity enabled by the helical cap that exchanges two opposing outer helices 180° around the channel. An unrelated conformational change of an inner helix seals a side opening to the membrane bilayer and is associated with structural changes around the K+-selectivity filter that may have implications for mechanosensitivity and gating of TRAAK channels. PMID:23341632

  12. 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.

  13. Dawbeney Turbervile, MD (1612-1696).

    PubMed

    Simunovic, Matthew P

    2012-03-01

    The year 2012 marks the quatercentenary of the birth of Dawbeney Turbervile,MD(1612-1696), one-time Royalist soldier and later ophthalmologist to England’s Princess Anne, the diarist Samuel Pepys, the natural philosopher Robert Boyle, and the astronomer Walter Pope. Turbervile is remarkable for many reasons: He specialized at a time when generalization was prized; though he was a qualified physician, he also practiced the trade of surgery. Furthermore, he provided in his communications with the Royal Society early descriptions of achromatopsia, ocular foreign body removal with a magnet, and tic doloreaux. He is a forebear worth remembering PMID:22411681

  14. 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.

  15. Easily Accessible Polycyclic Amines that Inhibit the Wild-Type and Amantadine-Resistant Mutants of the M2 Channel of Influenza A Virus

    PubMed Central

    2015-01-01

    Amantadine inhibits the M2 proton channel of influenza A virus, yet most of the currently circulating strains of the virus carry mutations in the M2 protein that render the virus amantadine-resistant. While most of the research on novel amantadine analogues has revolved around the synthesis of novel adamantane derivatives, we have recently found that other polycyclic scaffolds effectively block the M2 proton channel, including amantadine-resistant mutant channels. In this work, we have synthesized and characterized a series of pyrrolidine derivatives designed as analogues of amantadine. Inhibition of the wild-type M2 channel and the A/M2-S31N, A/M2-V27A, and A/M2-L26F mutant forms of the channel were measured in Xenopus oocytes using two-electrode voltage clamp assays. Most of the novel compounds inhibited the wild-type ion channel in the low micromolar range. Of note, two of the compounds inhibited the amantadine-resistant A/M2-V27A and A/M2-L26F mutant ion channels with submicromolar and low micromolar IC50, respectively. None of the compounds was found to inhibit the S31N mutant ion channel. PMID:24941437

  16. PHYSICAL PROPERTIES OF NEAR-EARTH ASTEROID 2011 MD

    SciTech Connect

    Mommert, M.; Trilling, D. E.; Farnocchia, D.; Chesley, S. R.; Chodas, P. W.; Hora, J. L.; Smith, H. A.; Fazio, G. G.; Mueller, M.; Harris, A. W.

    2014-07-01

    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 probable 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.

  17. 76 FR 41662 - Airworthiness Directives; MD Helicopters, Inc. Model MD900 Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-15

    ... Executive Order 12866, (2) Is not a ``significant rule'' under DOT Regulatory Policies and Procedures (44 FR.... 39.13 by removing airworthiness directive (AD) 2010-18-52, Amendment 39-16515 (75 FR 69862, November... the flex beam bolt hole locations during maintenance on two MDHI Model MD900 helicopters. Since...

  18. 75 FR 69862 - Airworthiness Directives; MD Helicopters, Inc. Model MD900 Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... Privacy Act Statement in the Federal Register published on April 11, 2000 (65 FR 19477-78). Regulatory... Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3. Will not have a significant... beam bolt hole locations during maintenance on two MDHI Model MD900 helicopters. The actions...

  19. 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

  20. Benjamin Rush, MD: assassin or beloved healer?

    PubMed

    North, R L

    2000-01-01

    Benjamin Rush, MD (1745-1813), was not only the most well known physician in 18th-century America, he was also a patriot, philosopher, author, lecturer, fervent evangelist, politician, and dedicated social reformer. He was unshakable in his convictions, as well as self-righteous, caustic, satirical, humorless, and polemical. Unquestionably brilliant, he graduated from what later became Princeton University at age 14. He translated Hippocrates' Aphorisms from the Greek at age 17. He wrote the first textbook of chemistry to be published in America. He was by all accounts a devoted, if highly paternalistic, medical practitioner, who cared deeply for his patients' welfare. His principles or theories and his championship of extreme purging and bleeding ("depletion therapy") have engendered 200 years of controversy and debate that continue today. The contradiction in his character is particularly well illustrated by his behavior during the Philadelphia yellow fever epidemic of 1793, as is briefly examined in this essay. PMID:16389324

  1. Ashley W. Oughterson, MD: Surgeon, Soldier, Leader

    PubMed Central

    Kunstman, John W.; Longo, Walter E.

    2015-01-01

    Ashley W. Oughterson, MD, (1895-1956) was a longtime faculty surgeon at Yale University. He performed some of the earliest pancreatic resections in the United States. During World War II, Colonel Oughterson was the primary “Surgical Consultant” in the South Pacific and present at nearly every major battle. His meticulously kept diary is regarded as the foremost source detailing wartime surgical care. Colonel Oughterson led the initial Army team to survey Hiroshima and Nagasaki following the nuclear attacks. Thoughout his academic career at Yale, Oughterson was a key leader in several medical and surgical societies. As scientific director of the American Cancer Society, Oughterson lectured widely and guided research priorities in oncology following World War II. Oughterson also authored numerous benchmark papers in surgical oncology that continue to be cited today. These extensive contributions are examined here and demonstrate the wide-ranging impact Oughterson exerted during a formative period of American surgery. PMID:26029018

  2. MD-11 PCA - First Landing at Edwards

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This McDonnell Douglas MD-11 transport aircraft approaches its first landing under engine power only on Aug. 29, 1995, at NASA's Dryden Flight Research Center, Edwards, California. The milestone flight, flown by NASA research pilot and former astronaut Gordon Fullerton, was part of a NASA project to develop a computer-assisted engine control system that enables a pilot to land a plane safely when its normal control surfaces are disabled. The Propulsion-Controlled Aircraft (PCA) system uses standard autopilot controls already present in the cockpit, together with the new programming in the aircraft's flight control computers. The PCA concept is simple--for pitch control, the program increases thrust to climb and reduces thrust to descend. To turn right, the autopilot increases the left engine thrust while decreasing the right engine thrust. The initial Propulsion-Controlled Aircraft studies by NASA were carried out at Dryden with a modified twin-engine F-15 research aircraft.

  3. MD-11 PCA - Research flight team egress

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This McDonnell Douglas MD-11 has parked on the flightline at NASA's Dryden Flight Research Center, Edwards, California, following its completion of the first and second landings ever performed by a transport aircraft under engine power only (on Aug. 29, 1995). The milestone flight, with NASA research pilot and former astronaut Gordon Fullerton at the controls, was part of a NASA project to develop a computer-assisted engine control system that enables a pilot to land a plane safely when its normal control surfaces are disabled. Coming down the steps from the aircraft are Gordon Fullerton (in front), followed by Bill Burcham, Propulsion Controlled Aircraft (PCA) project engineer at Dryden; NASA Dryden controls engineer John Burken; John Feather of McDonnell Douglas; and Drew Pappas, McDonnell Douglas' project manager for PCA.

  4. MD-11 PCA - First Landing at Edwards

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This McDonnell Douglas MD-11 approaches the first landing ever of a transport aircraft under engine power only on Aug. 29, 1995, at NASA's Dryden Flight Research Center, Edwards, California. The milestone flight, flown by NASA research pilot and former astronaut Gordon Fullerton, was part of a NASA project to develop a computer-assisted engine control system that enables a pilot to land a plane safely when it normal control surfaces are disabled. The Propulsion-Controlled Aircraft (PCA) system uses standard autopilot controls already present in the cockpit, together with the new programming in the aircraft's flight control computers. The PCA concept is simple--for pitch control, the program increases thrust to climb and reduces thrust to descend. To turn right, the autopilot increases the left engine thrust while decreasing the right engine thrust. The initial Propulsion-Controlled Aircraft studies by NASA were carried out at Dryden with a modified twin-engine F-15 research aircraft.

  5. 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.

  6. Bacterial Ion Channels.

    PubMed

    Compton, Emma L R; Mindell, Joseph A

    2010-09-01

    Bacterial ion channels were known, but only in special cases, such as outer membrane porins in Escherichia coli and bacterial toxins that form pores in their target (bacterial or mammalian) membranes. The exhaustive coverage provided by a decade of bacterial genome sequencing has revealed that ion channels are actually widespread in bacteria, with homologs of a broad range of mammalian channel proteins coded throughout the bacterial and archaeal kingdoms. This review discusses four groups of bacterial channels: porins, mechano-sensitive (MS) channels, channel-forming toxins, and bacterial homologs of mammalian channels. The outer membrane (OM) of gram-negative bacteria blocks access of essential nutrients; to survive, the cell needs to provide a mechanism for nutrients to penetrate the OM. Porin channels provide this access by forming large, nonspecific aqueous pores in the OM that allow ions and vital nutrients to cross it and enter the periplasm. MS channels act as emergency release valves, allowing solutes to rapidly exit the cytoplasm and to dissipate the large osmotic disparity between the internal and external environments. MS channels are remarkable in that they do this by responding to forces exerted by the membrane itself. Some bacteria produce toxic proteins that form pores in trans, attacking and killing other organisms by virtue of their pore formation. The review focuses on those bacterial toxins that kill other bacteria, specifically the class of proteins called colicins. Colicins reveal the dangers of channel formation in the plasma membrane, since they kill their targets with exactly that approach. PMID:26443789

  7. 77 FR 42459 - Airworthiness Directives; MD Helicopters, Inc. (MDHI) Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-19

    ... (expiration date). For the MDHI Model MD900 helicopters, AD 2006-18-01 (71 FR 51095, August 29, 2006) already... Policies and Procedures (44 FR 11034, February 26, 1979); 3. Will not affect intrastate aviation in Alaska... the MDHI Model MD900 helicopters, AD 2006-18-01 (71 FR 51095, August 29, 2006) contains additional...

  8. 77 FR 24838 - Safety Zone; Magothy River, Sillery Bay, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-26

    ... ``Safety Zone; Magothy River, Sillery Bay, MD'' in the Federal Register (77 FR 11423). We received no... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Magothy River, Sillery Bay, MD AGENCY... waters of the Magothy River, in Sillery Bay, Maryland. This safety zone is necessary to provide for...

  9. 76 FR 51887 - Safety Zone; Patuxent River, Patuxent River, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ...) entitled ``Safety Zone; Patuxent River, Patuxent River, MD'' in the Federal Register (76 FR 36447). We... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Patuxent River, Patuxent River, MD AGENCY... safety zone during the ``NAS Patuxent River Air Expo '11,'' which consists of aerial...

  10. 78 FR 35773 - Airworthiness Directives; MD Helicopters, Inc. (MDHI), Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... the MDHI Model MD900 helicopters with certain main rotor blade (MRB) retention bolts (bolts) installed...'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); 3. Will not affect... MD 900 helicopters with a main rotor blade retention bolt (bolt), part number (P/N)...

  11. DFT-MD simulations of shocked Xenon

    NASA Astrophysics Data System (ADS)

    Magyar, Rudolph J.; Mattsson, Thomas R.

    2009-03-01

    Xenon is not only a technologically important element used in laser technologies, jet propulsion and dental anesthesia, but it is also arguably the simplest material in which to study the metal-insulator transition at high pressure. Because of its closed shell electronic configuration, Xenon is often assumed to be chemically inert, interacting almost entirely through the van der Waals interaction, and at liquid density, is typically modeled well using Leonard-Jones potentials. However, such modeling has a limited range of validity as Xenon is known to form compounds at normal conditions and likely exhibits considerably more chemistry at higher densities when hybridization of occupied orbitals becomes significant. In this talk, we present DFT-MD simulations of shocked liquid Xenon with the goal of developing an improved equation of state. The relative importance of the van der Waals interaction compared to other Coulomb interactions is considered, and estimates of the relative accuracy of various density functionals are quantified. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the United States Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

  12. MD-11 PCA - First Landing at Edwards

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A transport aircraft lands for the first time under engine power only, as this McDonnell Douglas MD-11 touches down at 11:38 a.m., Aug. 29, 1995, at NASA's Dryden Flight Research Center, Edwards, California. The milestone flight, flown by NASA research pilot and former astronaut Gordon Fullerton, was part of a NASA project to develop a computer-assisted engine control system that enables a pilot to land a plane safely when its normal control surfaces are disabled. The propulsion-Controlled Aircraft (PCA) system uses standard autopilot controls already present in the cockpit, together with the new programming in the aircraft's flight control computers. The PCA concept is simple--for pitch control, the program increases thrust to climb and reduces thrust to descend. To turn right, the autopilot increases the left engine thrust while decreasing the right engine thrust. The initial Propulsion-Controlled Aircraft studies by NASA were carried out at Dryden with a modified twin-engine F-15 research aircraft.

  13. MD-11 PCA - First Landing at Edwards

    NASA Technical Reports Server (NTRS)

    1995-01-01

    A transport aircraft lands for the first time under engine power only, as this McDonnell Douglas MD-11 touches down at 11:38 a.m., Aug. 29, 1995, at NASA's Dryden Flight Research Center, Edwards, California. The milestone flight, flown by NASA research pilot and former astronaut Gordon Fullerton, was part of a NASA project to develop a computer-assisted engine control system that enables a pilot to land a plane safely when its normal control surfaces are disabled. The Propulsion-Controlled Aircraft (PCA) system uses standard autopilot controls already present in the cockpit, together with the new programming in the aircraft's flight control computers. The PCA concept is simple--for pitch control, the program increases thrust to climb and reduces thrust to descend. To turn right, the autopilot increases the left engine thrust while decreasing the right engine thrust. The initial Propulsion-Controlled Aircraft studies by NASA were carried out at Dryden with a modified twin-engine F-15 research aircraft.

  14. MD-Logic Artificial Pancreas System

    PubMed Central

    Atlas, Eran; Nimri, Revital; Miller, Shahar; Grunberg, Eli A.; Phillip, Moshe

    2010-01-01

    OBJECTIVE Current state-of-the-art artificial pancreas systems are either based on traditional linear control theory or rely on mathematical models of glucose-insulin dynamics. Blood glucose control using these methods is limited due to the complexity of the biological system. The aim of this study was to describe the principles and clinical performance of the novel MD-Logic Artificial Pancreas (MDLAP) System. RESEARCH DESIGN AND METHODS The MDLAP applies fuzzy logic theory to imitate lines of reasoning of diabetes caregivers. It uses a combination of control-to-range and control-to-target strategies to automatically regulate individual glucose levels. Feasibility clinical studies were conducted in seven adults with type 1 diabetes (aged 19–30 years, mean diabetes duration 10 ± 4 years, mean A1C 6.6 ± 0.7%). All underwent 14 full, closed-loop control sessions of 8 h (fasting and meal challenge conditions) and 24 h. RESULTS The mean peak postprandial (overall sessions) glucose level was 224 ± 22 mg/dl. Postprandial glucose levels returned to <180 mg/dl within 2.6 ± 0.6 h and remained stable in the normal range for at least 1 h. During 24-h closed-loop control, 73% of the sensor values ranged between 70 and 180 mg/dl, 27% were >180 mg/dl, and none were <70 mg/dl. There were no events of symptomatic hypoglycemia during any of the trials. CONCLUSIONS The MDLAP system is a promising tool for individualized glucose control in patients with type 1 diabetes. It is designed to minimize high glucose peaks while preventing hypoglycemia. Further studies are planned in the broad population under daily-life conditions. PMID:20150292

  15. MD-PhD training: looking back and looking forward.

    PubMed

    Bonham, Ann C

    2014-01-01

    MD-PhD programs provide rigorous, integrated training for physician-scientists, enabling them to frame scientific questions in unique ways and to apply clinical insight to fundamental science. Few would question the influential contributions of MD-PhD physician-scientists in advancing medical science. In this issue of Academic Medicine, Jeffe et al affirm high levels of excellence in educational outcomes from MD-PhD training programs at U.S. MD-granting medical schools, especially programs that receive funding from the NIH Medical Scientist Training Program (MSTP). The author of this commentary observes that, in the face of current economic pressures, comprehensive, longitudinal national outcomes data from MSTP- and non-MSTP-funded MD-PhD programs will help verify the value provided by MD-PhD physician-scientists. She proposes that MD-PhD programs should better prepare the next generation of physician-scientists for future research environments, which will provide new technologies, venues, and modalities. These research environments will be more closely integrated within health care delivery systems, extend into diverse communities and regions, and employ complex technologies. MD-PhD physician-scientists also will train and gain expertise in broadening areas of research, such as health policy, health economics, clinical epidemiology, and medical informatics. Program leaders are ideally situated to foster innovative learning environments and methodologies. By sharing their innovations, they can help ensure production of a diverse MD-PhD physician-scientist workforce, prepared to engage in myriad research opportunities to meet patient and population needs in a new environment. PMID:24280863

  16. 77 FR 73967 - Drawbridge Operation Regulation; Bear Creek, Dundalk, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-12

    ... Regulation; Bear Creek, Dundalk, MD'' in the Federal Register (77 FR 5201). The rulemaking concerned would... to http://www.regulations.gov , inserting USCG-2011-1062 in the ``Search'' box, and then...

  17. Find an Orthopaedic Foot and Ankle MD/DO

    MedlinePlus

    ... AOFAS / FootCareMD / Find a Surgeon Find an Orthopaedic Foot & Ankle Surgeon Page Content The Orthopaedic Distinction Who are Orthopaedic Foot & Ankle Surgeons? Orthopaedic foot and ankle surgeons are ...

  18. 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

  19. 76 FR 53346 - Airworthiness Directives; The Boeing Company Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-26

    ... proposed AD affects Model MD-80 series airplanes. We issued AD 2011-01-11, Amendment 39-16565 (76 FR 430... under Executive Order 13132. This proposed AD would not have a substantial direct effect on the States... 12866, (2) Is not a ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR...

  20. MdSOS2L1 forms a complex with MdMYB1 to control vacuolar pH by transcriptionally regulating MdVHA-B1 in apples.

    PubMed

    Sun, Cui-Hui; Zhang, Quan-Yan; Sun, Mei-Hong; Hu, Da-Gang

    2016-03-01

    Vacuolar pH is important and involves in many different physiological processes in plants. A recent paper published in Plant Physiology reveals that MdMYB1 regulates vacuolar pH by directly transcriptionally regulating proton pump genes and malate transporters genes, such as V-ATPase subunit gene MdVHA-B1. Here, we found that MdSOS2L1 in vitro did not directly interact with MdMYB1, however, in vivo formed a complex with MdMYB1 in the nucleus to regulate MdVHA-B1-mediated vacuolar acidification. This finding shed light on the role of MdSOS2L1 in transcriptionally regulating MdVHA-B1 in addition to its post-modified function in apples. PMID:26910596

  1. Channel Networks

    NASA Astrophysics Data System (ADS)

    Rinaldo, Andrea; Rodriguez-Iturbe, Ignacio; Rigon, Riccardo

    This review proceeds from Luna Leopold's and Ronald Shreve's lasting accomplishments dealing with the study of random-walk and topologically random channel networks. According to the random perspective, which has had a profound influence on the interpretation of natural landforms, nature's resiliency in producing recurrent networks and landforms was interpreted to be the consequence of chance. In fact, central to models of topologically random networks is the assumption of equal likelihood of any tree-like configuration. However, a general framework of analysis exists that argues that all possible network configurations draining a fixed area are not necessarily equally likely. Rather, a probability P(s) is assigned to a particular spanning tree configuration, say s, which can be generally assumed to obey a Boltzmann distribution: P(s) % e^-H(s)/T, where T is a parameter and H(s) is a global property of the network configuration s related to energetic characters, i.e. its Hamiltonian. One extreme case is the random topology model where all trees are equally likely, i.e. the limit case for T6 4 . The other extreme case is T 6 0, and this corresponds to network configurations that tend to minimize their total energy dissipation to improve their likelihood. Networks obtained in this manner are termed optimal channel networks (OCNs). Observational evidence suggests that the characters of real river networks are reproduced extremely well by OCNs. Scaling properties of energy and entropy of OCNs suggest that large network development is likely to effectively occur at zero temperature (i.e. minimizing its Hamiltonian). We suggest a corollary of dynamic accessibility of a network configuration and speculate towards a thermodynamics of critical self-organization. We thus conclude that both chance and necessity are equally important ingredients for the dynamic origin of channel networks---and perhaps of the geometry of nature.

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

    SciTech Connect

    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 systems 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.

  3. Expression pattern and function of alternative splice variants of glutamate-gated chloride channel in the housefly Musca domestica.

    PubMed

    Kita, Tomo; Ozoe, Fumiyo; Ozoe, Yoshihisa

    2014-02-01

    Glutamate-gated chloride channels (GluCls) mediate fast inhibitory neurotransmission in invertebrate nervous systems. cDNAs encoding two alternative splice variants (MdGluClB and C) of the GluCl subunit were cloned from the housefly Musca domestica. The expression patterns of three variants, including the previously reported MdGluClA, differed among the body parts (head, thorax, abdomen, and leg) of the adult housefly and among developmental stages (embryo, larva, pupa, and adult). The MdGluClA and B transcripts were abundant in the central nervous system of the adult, whereas the MdGluClC transcript was expressed in the central nervous system and as the predominant variant in the peripheral tissues. The sensitivities to the agonist glutamate and the allosteric activator ivermectin B1a did not differ between channels containing MdGluCl variants when they were singly or co-expressed in Xenopus oocytes. By contrast, MdGluClA and B channels were more sensitive to the channel blockers fipronil and picrotoxinin than was MdGluClC channels. Heteromeric channels containing different subunit variants were more sensitive to picrotoxinin than were homomeric channels. Heteromeric channels were more sensitive to fipronil than were homomeric MdGluClC channels but not than homomeric MdGluClA and B channels. These results suggest that functionally indistinguishable but pharmacologically distinct GluCls are expressed in a spatially and temporally distinct manner in the housefly. PMID:24291284

  4. 76 FR 60889 - Stephen L. Reitman, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-30

    ... substances properly if entrusted with a DEA registration.''' Id. (quoting Leonardo v. Lopez, M.D., 54 FR... has demonstrated his sobriety for only one year. See Lopez, 54 FR 36915; see also Robert L. Dougherty, M.D., 76 FR 16823 (2011); Robert A. Leslie, M.D., 64 FR 25908 (1999); Mary M. Miller, M.D., 63...

  5. CoMD Implementation Suite in Emerging Programming Models

    2014-09-23

    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 molecularmore » 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 to 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

  6. CoMD Implementation Suite in Emerging Programming Models

    SciTech Connect

    Haque, Riyaz; Reeve, Sam; Juallmes, Luc; Asal, Sameer Abu; Landmehr, Aaron; Gaffer, Sanian; Teodor Bercea, Gheorghe; Rubinstein, Zach

    2014-09-23

    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 to 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.

  7. 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

  8. Molecular Dynamical Study on Ion Channeling through Peptide Nanotube

    NASA Astrophysics Data System (ADS)

    Sumiya, Norihito; Igami, Daiki; Takeda, Kyozaburo

    2011-12-01

    We theoretically study the possibility of ion channeling through peptide nanotubes (PNTs). After designing the minimal peptide nanorings (PNRs) and their aggregated form (peptide nanotubes, PNT) computationally, we carry out molecular dynamics (MD) calculations for cation channeling. The present MD calculations show that cation channeling through PNTs occurs. Furthermore, inter-ring hydrogen bonds (HBs) survive and maintain the tubular form of PNTs during cation channeling. We introduce mobility such that cation channeling can be evaluated quantitatively. As the ionic radius of the cation becomes smaller, the effective relaxation time τ becomes larger. Accordingly, mobilities of 10-2˜10-3[cm2/volt/sec] are calculated. In contrast, when an anion (F-) passes through the PNT, the inter-ring HBs are broken, thus inducing breakdown of the peptide backbone. Consequently, H atoms from the broken HBs surround the channeling anion (F-) and halt its motion.

  9. An optimized MD program for the vector computer cyber 205

    NASA Astrophysics Data System (ADS)

    Brode, Stefan; Ahlrichs, Reinhart

    1986-09-01

    The potential of supercomputers for MD simulation runs is explored for the CYBER 205 vectorcomputer in the treatment of molecular liquids with site-site interaction potentials. Careful vectorization and optimization of remaining scalar codes is shown to reduce the CPU time to 7% as compared to the original code. The advantage of avoiding IO completely by computing time correlation functions in the course of the MD run is demostrated. Special emphasis is given to optimized data structures and data flow in order to minimize start up times and to exploit the hardware features of the CYBER 205.

  10. In memoriam: Wolfgang Kiowski, M.D. (1949-2012)--pioneer in clinical endothelin research.

    PubMed

    Barton, Matthias; Schiffrin, Ernesto L

    2014-11-24

    Wolfgang Kiowski, M.D. (1949-2012) was a German physician-scientist who made exemplary contributions to clinical research in human physiology, heart failure, arterial hypertension, and endothelin science. His academic career took him from Heinz Losse, M.D. at the University of Münster, Germany, to the University of Michigan, U.S.A., to work with Stevo Julius, M.D. In 1979, Kiowski was recruited to the University of Basel in Switzerland and ultimately moved to the Hospital of the University of Zürich in Switzerland. Twenty years ago, Kiowski published a landmark study pioneering the use of endothelin receptor antagonists (ERAs) in patients (Lancet 1995; 346: 732-736), which introduced a new therapeutic principle to human medicine. During his career, he published numerous studies in the area of pathophysiology, clinical pharmacology (particularly calcium channel blockers, ERAs, and PDE5 inhibitors), heart failure, cardiac transplantation, coronary artery disease, and many case reports from his clinical work. Kiowski was an active mentor and trained many young physicians and physician-scientists. He died unexpectedly in Zürich during the planning stages of the Thirteenth International Conference on Endothelin to be held in Tokyo in 2013. This article summarizes Kiowski's achievements, his role as a mentor and as the human being he was. He will be remembered as a role model of an outstanding, curious clinician who was highly successful as a physician, scientist, and teacher, and at the same time managed to enjoy many hobbies and life with his family. Referring to Wolfgang Kiowski, the article closes with a "It can be done!"-message to young physician-scientists by Dr. Stevo Julius. PMID:25152472

  11. 77 FR 64709 - Airworthiness Directives; MD Helicopters, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-23

    ...), Model MD900 helicopters. The existing AD requires a visual inspection, and if necessary, an eddy current..., at 77 FR 18963, the Federal Register published our notice of proposed rulemaking (NPRM), which...-117, dated January 14, 2011 (SB). The SB specifies an initial 100-hour and recurring 300-hour...

  12. 77 FR 74908 - Maryland Disaster Number MD-00025

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-18

    ... ADMINISTRATION Maryland Disaster Number MD-00025 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1... completed loan applications to: U.S. Small Business Administration, Processing and Disbursement Center... Disaster Assistance, U.S. Small Business Administration, 409 3rd Street SW., Suite 6050, Washington,...

  13. 78 FR 3496 - Maryland Disaster Number MD-00025

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-16

    ... ADMINISTRATION Maryland Disaster Number MD-00025 AGENCY: U.S. Small Business Administration. ACTION: Amendment 3... completed loan applications to: U.S. Small Business Administration, Processing and Disbursement Center... Disaster Assistance, U.S. Small Business Administration, 409 3rd Street SW., Suite 6050, Washington,...

  14. 75 FR 10172 - Drawbridge Operation Regulation; Chester River, Chestertown, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-05

    ... Operation Regulations; Chester River, Chestertown, MD'' in the Federal Register (74 FR 48889). We received... SECURITY Coast Guard 33 CFR Part 117 RIN 1625-AA09 Drawbridge Operation Regulation; Chester River... drawbridge operation regulations of the S213 Bridge, at mile 26.8, across Chester River at Chestertown,...

  15. 77 FR 5201 - Drawbridge Operation Regulation; Bear Creek, Dundalk, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-02

    ... Federal Register (73 FR 3316). Public Meeting We do not now plan to hold a public meeting. But you may... SECURITY Coast Guard 33 CFR Part 117 RIN 1625-AA09 Drawbridge Operation Regulation; Bear Creek, Dundalk, MD... change the regulation governing the operation of the Baltimore County highway bridge at Wise...

  16. 76 FR 9225 - Drawbridge Operation Regulation; Curtis Creek, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ... Regulations; Curtis Creek, Baltimore, MD'' in the Federal Register (74 FR 50707). The temporary deviation... complete structural repairs and replacement of the grid deck, floor beams and stringers. DATES: This... February 17, 2011 to November 30, 2011. During the replacement of the grid deck, floor beams and...

  17. 76 FR 36447 - Safety Zone; Patuxent River, Patuxent River, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-22

    ..., 2008, issue of the Federal Register (73 FR 3316). Public meeting We do not now plan to hold a public... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Patuxent River, Patuxent River, MD AGENCY... a temporary safety zone during the ``NAS Patuxent River Air Expo '11'', which consists of...

  18. 75 FR 1705 - Drawbridge Operation Regulations; Curtis Creek, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-13

    ...The Commander, Fifth Coast Guard District, has issued a temporary deviation from the regulations governing the operation of the I695 Bridge across Curtis Creek, mile 0.9, at Baltimore, MD. The deviation is necessary to facilitate mechanical repairs to the bridge. This temporary deviation allows the drawbridge to remain in the closed position during the deviation...

  19. 78 FR 11725 - Maryland Disaster Number MD-00024

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-19

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Maryland Disaster Number MD-00024 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1... Federal Domestic Assistance Numbers 59002 and 59008) James E. Rivera, Associate Administrator for...

  20. 76 FR 70527 - Maryland Disaster Number MD-00018

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Maryland Disaster Number MD-00018 AGENCY: U.S. Small Business Administration. ACTION: Amendment 1... Assistance Numbers 59002 and 59008) James E. Rivera, Associate Administrator for Disaster Assistance....

  1. 76 FR 70528 - Maryland Disaster Number MD-00018

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Maryland Disaster Number MD-00018 AGENCY: U.S. Small Business Administration. ACTION: Amendment 2... Numbers 59002 and 59008) James E. Rivera, Associate Administrator for Disaster Assistance. BILLING...

  2. RFI channels

    NASA Technical Reports Server (NTRS)

    Mceliece, R. J.

    1980-01-01

    A class of channel models is presented which exhibit varying burst error severity much like channels encountered in practice. An information-theoretic analysis of these channel models is made, and conclusions are drawn that may aid in the design of coded communication systems for realistic noisy channels.

  3. Synchronization strategies for RFI channels

    NASA Technical Reports Server (NTRS)

    Mceliece, R. J.; Vantilborg, H.; Tung, S.

    1977-01-01

    An RFI channel to be a multiple-access channel is defined in which no sender can know when any other starts, and the problem of determining the relative phases of the senders at the receiver is studied. A new result is proved about binary DEBruijn sequences.

  4. Spectroscopic studies beyond N = 152 neutron gap : decay of {sup 255 ovr sub 101}Md and {sup 256 ovr sub 101}Md.

    SciTech Connect

    Ahmad, I.; Chasman, R. R.; Fields, P. R.

    2000-01-01

    The isotopes {sup 255}Md and {sup 256}Md were produced by the irradiation of {sup 253}Es with 35-45 MeV {alpha} particles by ({alpha},n) and ({alpha},2n) reactions and were removed from the target by a helium jet system. {alpha}, {gamma}, and {alpha}-{gamma} coincidence spectra were measured with Si and Ge(Li) detectors. From the EC decays of {sup 255}Md and {sup 256}Md, levels in {sup 255}Fm and {sup 256}Fm were deduced. Favored {alpha} decay of {sup 255}Md was found to populate the 7/2{sup -}[514] single-particle state in {sup 251}Es, thus establishing the 7/2{sup -}[514] as the {sup 255}Md ground state. Several {gamma} rays were observed in the {sub 256}Md {alpha}-{gamma} coincidence spectrum. {sup 256}Fm is the heaviest nucleus in which excited intrinsic states have been identified.

  5. Spectroscopic studies beyond the N=152 neutron gap: Decay of {sub 101}{sup 255}Md and {sub 101}{sup 256}Md

    SciTech Connect

    Ahmad, I.; Chasman, R. R.; Fields, P. R.

    2000-04-01

    The isotopes {sup 255}Md and {sup 256}Md were produced by the irradiation of {sup 253}Es with 35-45 MeV {alpha} particles by ({alpha},n) and ({alpha},2n) reactions and were removed from the target by a helium jet system. {alpha}, {gamma}, and {alpha}-{gamma} coincidence spectra were measured with Si and Ge(Li) detectors. From the EC decays of {sup 255}Md and {sup 256}Md, levels in {sup 255}Fm and {sup 256}Fm were deduced. Favored {alpha} decay of {sup 255}Md was found to populate the 7/2{sup -}[514] single-particle state in {sup 251}Es, thus establishing the 7/2{sup -}[514] as the {sup 255}Md ground state. Several {gamma} rays were observed in the {sup 256}Md {alpha}-{gamma} coincidence spectrum. {sup 256}Fm is the heaviest nucleus in which excited intrinsic states have been identified. (c) 2000 The American Physical Society.

  6. 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

  7. Routine Access to Millisecond Time Scale Events with Accelerated Molecular Dynamics

    PubMed Central

    2012-01-01

    In this work, we critically assess the ability of the all-atom enhanced sampling method accelerated molecular dynamics (aMD) to investigate conformational changes in proteins that typically occur on the millisecond time scale. We combine aMD with the inherent power of graphics processor units (GPUs) and apply the implementation to the bovine pancreatic trypsin inhibitor (BPTI). A 500 ns aMD simulation is compared to a previous millisecond unbiased brute force MD simulation carried out on BPTI, showing that the same conformational space is sampled by both approaches. To our knowledge, this represents the first implementation of aMD on GPUs and also the longest aMD simulation of a biomolecule run to date. Our implementation is available to the community in the latest release of the Amber software suite (v12), providing routine access to millisecond events sampled from dynamics simulations using off the shelf hardware. PMID:22984356

  8. pMD-Membrane: A Method for Ligand Binding Site Identification in Membrane-Bound Proteins

    PubMed Central

    Gorfe, Alemayehu A.

    2015-01-01

    Probe-based or mixed solvent molecular dynamics simulation is a useful approach for the identification and characterization of druggable sites in drug targets. However, thus far the method has been applied only to soluble proteins. A major reason for this is the potential effect of the probe molecules on membrane structure. We have developed a technique to overcome this limitation that entails modification of force field parameters to reduce a few pairwise non-bonded interactions between selected atoms of the probe molecules and bilayer lipids. We used the resulting technique, termed pMD-membrane, to identify allosteric ligand binding sites on the G12D and G13D oncogenic mutants of the K-Ras protein bound to a negatively charged lipid bilayer. In addition, we show that differences in probe occupancy can be used to quantify changes in the accessibility of druggable sites due to conformational changes induced by membrane binding or mutation. PMID:26506102

  9. 76 FR 22922 - JLG Industries, Inc., Access Division, A Subsidiary of Oshkosh Corporation, Hagerstown, MD...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-25

    ... of Determination was published in the Federal Register on March 23, 2011 (76 FR 16450). The workers are engaged in activities related to the supply of design engineering, global procurement supply...

  10. 77 FR 3118 - Security Zone; Choptank River and Cambridge Channel, Cambridge, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-23

    ... 3118-3121] [FR Doc No: 2012-1172] DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 165 [Docket..., U.S. Coast Guard, Captain of the Port Baltimore. [FR Doc. 2012-1172 Filed 1-20-12; 8:45 am] BILLING... will be held at the Hyatt Regency Chesapeake Bay Golf Resort, Spa and Marina in Cambridge,...

  11. 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. PMID:25378687

  12. Enhancing MD simulations of proteins using vague and combinatorics information

    NASA Astrophysics Data System (ADS)

    Dill, Ken

    We have developed MELD, a method that `melds' together replica-exchange molecular dynamics simulations with external information. Traditionally, accelerating MD simulations has only been possible by using information that is precise and correct. In contrast, MELD allows us to leverage information that is vague or corrupted. For example, we give generic instructives, such as `make a hydrophobic core', `make good secondary structures', or `search only compact structures'. Normally, such information implies a loss of ability to compute free energies and populations. But, MELD satisfies detailed balance. We show that it can fold small proteins much faster than brute-force MD can, that it gives reasonable populations, and that it can succeed in CASP, the blind protein-structure prediction event.

  13. Can maitake MD-fraction aid cancer patients?

    PubMed

    Kodama, Noriko; Komuta, Kiyoshi; Nanba, Hiroaki

    2002-06-01

    Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan with beta-1,3 branched chains has previously exhibited strong anticancer activity by increasing immune-competent cell activity.1,2 In this non-random case series, a combination of MD-fraction and whole maitake powder was investigated to determine its effectiveness for 22- to 57-year-old cancer patients in stages II-IV. Cancer regression or significant symptom improvement was observed in 58.3 percent of liver cancer patients, 68.8 percent of breast cancer patients, and 62.5 percent of lung cancer patients. The trial found a less than 10-20 percent improvement for leukemia, stomach cancer, and brain cancer patients. Furthermore, when maitake was taken in addition to chemotherapy, immune-competent cell activities were enhanced 1.2-1.4 times, compared with chemotherapy alone. Animal studies have supported the use of maitake MD-fraction for cancer. PMID:12126464

  14. Structure and Properties of HELICAL CARBON NANOTUBES through MD Simulations

    NASA Astrophysics Data System (ADS)

    Dahiya, Akshay; Verma, Deepti; Gupta, Shakti S.

    Helical Carbon Nanotubes (HCNTs) are coiled 3-valent carbon networks which represent pure carbon helix. Here we study the geometries of two classes: hexagonal helix containing purely polyhex networks and the second class with 5-and 7-membered rings besides hexagons. We followed a model of hexagonal, single wall HCNTs, and determined their relaxed configuration using MD simulations based on Tersoff potential. A race-track like structure is observed in the cross-section of HCNTs upon minimization. For generating class two helix, the adjacency matrix eigenvector's (AME) method is applied which utilizes 3-coordinated tiling of the plane by 5-,6-,and 7-membered ring for the construction of helical structures. The application of the AME method to torusenes is crucial for class two helix generation as it is based on an appropriate choice of bi-lobial eigenvectors triplet which can be selected on the basis of their nodal properties as verified here. After 3-D transformations the final structure was obtained with the help of MM3-potential based MD simulations on Tinker commercial code. The spring constants of HCNTs are computed through MD simulations.

  15. 77 FR 67669 - Wayne D. Longmore, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    .... Edwards, M.D., 75 FR 49,991 (DEA 2010); Joseph Baumstarck, M.D., 74 FR 17,525 (DEA 2009). In this case... Baumstarck, M.D., 74 FR at 17,527 (DEA 2009). Thus, because there is no dispute that the Respondent lacks... cancellation); William R. Lockridge, M.D., 71 FR 77,791, 77,797 (DEA 2006) (interpreting 21 CFR 1301.52(a)...

  16. 78 FR 7813 - Sanjay Trivedi, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ... authority''); Beverley P. Edwards, M.D., 75 FR 49,991 (DEA 2010); Joseph Baumstarck, M.D., 74 FR 17,525 (DEA... Florida. Consequently, his DEA registration must be revoked. See Joseph Baumstarck, M.D., 74 FR 17,525, 17... Coast Specialty Pharmacy, 76 FR 66,965 (DEA 2011); Roy Chi Lung, M.D., 74 FR 20,346 (DEA 2009);...

  17. 76 FR 71370 - Silviu Ziscovici, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... the state in which he does business. See Scott Sandarg, D.M.D., 74 FR 17,528 (DEA 2009); David W. Wang, M.D., 72 FR 54,297 (DEA 2007); Sheran ] Arden Yeates, M.D., 71 FR 39,130 (DEA 2006); Dominick A. Ricci, M.D., 58 FR 51,104 (DEA 1993); Bobby Watts M.D., 53 Fed. Reg. 11,919 (DEA 1988)....

  18. 76 FR 71374 - Joseph Giacchino, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ...); Agostino Carlucci, M.D., 49 FR 33,184, 33,184-85 (1984). Rather, what matters--as DEA has repeatedly held... does business. See Scott Sandarg, DMD, 74 FR 17528 (DEA 2009); David W. Wang, M.D., 72 FR 54297 (DEA 2007); Sheran Arden Yeates, M.D., 71 FR 39130 (DEA 2006); Dominick A. Ricci, M.D., 58 FR 51104...

  19. 76 FR 71369 - Robert G. Crummie, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... authority under the laws of the state in which he does business. See Scott Sandarg, D.M.D., 74 FR 17528 (DEA 2009); David W. Wang, M.D., 72 FR 54297 (DEA 2007); Sheran Arden Yeates, M.D., 71 FR 39130 (DEA 2006); Dominick A. Ricci, M.D., 58 FR 51104 (DEA 1993); Bobby Watts M.D., 53 FR 11919 (DEA 1988). In the...

  20. Molecular Basis of the Functional Differences between Soluble Human Versus Murine MD-2: Role of Val135 in Transfer of Lipopolysaccharide from CD14 to MD-2.

    PubMed

    Vašl, Jožica; Oblak, Alja; Peternelj, Tina T; Klett, Javier; Martín-Santamaría, Sonsoles; Gioannini, Theresa L; Weiss, Jerrold P; Jerala, Roman

    2016-03-01

    Myeloid differentiation factor 2 (MD-2) is an extracellular protein, associated with the ectodomain of TLR4, that plays a critical role in the recognition of bacterial LPS. Despite high overall structural and functional similarity, human (h) and murine (m) MD-2 exhibit several species-related differences. hMD-2 is capable of binding LPS in the absence of TLR4, whereas mMD-2 supports LPS responsiveness only when mMD-2 and mTLR4 are coexpressed in the same cell. Previously, charged residues at the edge of the LPS binding pocket have been attributed to this difference. In this study, site-directed mutagenesis was used to explore the hydrophobic residues within the MD-2 binding pocket as the source of functional differences between hMD-2 and mMD-2. Whereas decreased hydrophobicity of residues 61 and 63 in the hMD-2 binding pocket retained the characteristics of wild-type hMD-2, a relatively minor change of valine to alanine at position 135 completely abolished the binding of LPS to the hMD-2 mutant. The mutant, however, retained the LPS binding in complex with TLR4 and also cell activation, resulting in a murine-like phenotype. These results were supported by the molecular dynamics simulation. We propose that the residue at position 135 of MD-2 governs the dynamics of the binding pocket and its ability to accommodate lipid A, which is allosterically affected by bound TLR4. PMID:26826249

  1. The Application Research of MD5 Encryption Algorithm in DCT Digital Watermarking

    NASA Astrophysics Data System (ADS)

    Xijin, Wang; Linxiu, Fan

    This article did the preliminary study of the application of algorithm for MD5 in the digital watermark. It proposed that copyright information will be encrypted using an algorithm MD5, and made rules for the second value image watermarks, through DCT algorithm that embeds an image by the carrier. The extraction algorithms can pick up the watermark and restore MD5 code.

  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. Crystal structure of soluble MD-1 and its interaction with lipid IVa

    SciTech Connect

    Yoon, Sung-il; Hong, Minsun; Han, Gye Won; Wilson, Ian A.

    2010-07-22

    Lipopolysaccharide (LPS) of Gram-negative bacteria is a common pathogen-associated molecular pattern (PAMP) that induces potent innate immune responses. The host immune response against LPS is triggered by myeloid differentiation factor 2 (MD-2) in association with Toll-like receptor 4 (TLR4) on the cell surface. The MD-2/TLR4-mediated LPS response is regulated by the evolutionarily related complex of MD-1 and Toll-like receptor homolog RP105. Here, we report crystallographic and biophysical data that demonstrate a previously unidentified direct interaction of MD-1 with LPS. The crystal structure of chicken MD-1 (cMD-1) at 2.0 {angstrom} resolution exhibits a {beta}-cup-like fold, similar to MD-2, that encloses a hydrophobic cavity between the two {beta}-sheets. A lipid-like moiety was observed inside the cavity, suggesting the possibility of a direct MD-1/LPS interaction. LPS was subsequently identified as an MD-1 ligand by native gel electrophoresis and gel filtration analyses. The crystal structure of cMD-1 with lipid IVa, an LPS precursor, at 2.4 {angstrom} resolution revealed that the lipid inserts into the deep hydrophobic cavity of the {beta}-cup-like structure, but with some important differences compared with MD-2. These findings suggest that soluble MD-1 alone, in addition to its complex with RP105, can regulate host LPS sensitivity.

  4. 76 FR 5686 - Drawbridge Operation Regulation; Pocomoke River, Pocomoke City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-02

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Pocomoke River, Pocomoke City, MD... operation of the Route 675 Bridge across Pocomoke River, mile 15.6, at Pocomoke City, MD. The deviation... at Pocomoke City MD, has a vertical clearance in the closed position of three feet above mean...

  5. 76 FR 81826 - Drawbridge Operation Regulation; Pocomoke River, Pocomoke City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-29

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Pocomoke River, Pocomoke City, MD... operation of the Route 675 Bridge across Pocomoke River, mile 15.6, at Pocomoke City, MD. The deviation... across Pocomoke River, mile 15.6 at Pocomoke City, MD, has a vertical clearance in the closed position...

  6. 76 FR 23185 - Drawbridge Operation Regulation; Isle of Wight (Sinepuxent) Bay, Ocean City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-26

    ... (Sinepuxent) Bay, Ocean City, MD in the Federal Register (75 FR 236). We received no comments on the proposed... (Sinepuxent) Bay, Ocean City, MD AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: The Coast Guard is..., mile 0.5, at Ocean City, MD. This rule will require any mariner requesting an opening in the ]...

  7. 78 FR 39604 - Safety Zone; Northside Park Pier Fireworks Display, Assawoman Bay, Ocean City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    ..., Assawoman Bay, Ocean City, MD AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone on the navigable waters of Assawoman Bay in Ocean City, MD... pier at Northside Park in Ocean City, MD. The fireworks debris fallout area will extend over...

  8. 78 FR 76322 - Thomas Neuschatz, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-17

    ...(f). ``These factors are . . . considered in the disjunctive.'' Robert A. Leslie, M.D., 68 FR 15227... Kevin Dennis, M.D., 78 FR 52787, 52794 (2013); MacKay v. DEA, 664 F.3d 808, 816 (10th Cir. 2010). The...-contested case. Gabriel Sanchez, M.D., 78 FR 59060, 59063 (2013). Having considered all of the factors,\\3\\...

  9. 75 FR 52461 - Drawbridge Operation Regulation; Pocomoke River, Snow Hill, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-26

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Pocomoke River, Snow Hill, MD AGENCY... the S12 ] Bridge across the Pocomoke River, mile 29.9, at Snow Hill, MD. The deviation restricts the... hours advance notice is given. The S12 Bridge across Pocomoke River, mile 29.9 at Snow Hill MD, has...

  10. TRP Channels

    PubMed Central

    Venkatachalam, Kartik; Montell, Craig

    2011-01-01

    The TRP (Transient Receptor Potential) superfamily of cation channels is remarkable in that it displays greater diversity in activation mechanisms and selectivities than any other group of ion channels. The domain organizations of some TRP proteins are also unusual, as they consist of linked channel and enzyme domains. A unifying theme in this group is that TRP proteins play critical roles in sensory physiology, which include contributions to vision, taste, olfaction, hearing, touch, and thermo- and osmosensation. In addition, TRP channels enable individual cells to sense changes in their local environment. Many TRP channels are activated by a variety of different stimuli and function as signal integrators. The TRP superfamily is divided into seven subfamilies: the five group 1 TRPs (TRPC, TRPV, TRPM, TRPN, and TRPA) and two group 2 subfamilies (TRPP and TRPML). TRP channels are important for human health as mutations in at least four TRP channels underlie disease. PMID:17579562

  11. 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. PMID:25354071

  12. Molecular Dynamics (MD) Simulation Directed Rational Design of Inhibitors Targeting Drug-Resistant Mutants of Influenza A Virus M2

    PubMed Central

    Wang, Jun; Ma, Chunlong; Fiorin, Giacomo; Carnevale, Vincenzo; Wang, Tuo; Hu, Fanghao; Lamb, Robert A.; Pinto, Lawrence H.; Hong, Mei; Klein, Michael L.; DeGrado, William F.

    2012-01-01

    Influenza A virus M2 (A/M2) forms a homotetrameric proton selective channel in the viral membrane. It has been the drug targets of antiviral drugs such as amantadine and rimantadine. However, most of the current virulent influenza A viruses carry drug resistant mutations alongside the drug binding site, such as S31N, V27A, and L26F etc., each of which might be dominant in a given flu season. Among these mutations, the V27A mutation was prevalent among transmissible viruses under drug selection pressure. Until now, V27A has not been successfully targeted by small molecule inhibitors, despite years of extensive medicinal chemistry research efforts and high throughput screening. Guided by molecular dynamics (MD) simulation of drug binding and the influence of drug binding on the dynamics of A/M2 from earlier experimental studies, we designed a series of potent spirane amine inhibitors targeting not only WT, but also both A/M2-27A and L26F mutants with IC50s similar to that seen for amantadine's inhibition of the WT channel. The potencies of these inhibitors were further demonstrated in experimental binding and plaque reduction assays. These results demonstrate the power of MD simulations to probe the mechanism of drug binding as well as the ability to guide design of inhibitors of targets that had previously appeared to be undruggable. PMID:21744829

  13. 16. STRUCTURAL DETAILS: CHANNEL, BIT & CLEAT, ANCHOR BOLTS & ...

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

    16. STRUCTURAL DETAILS: CHANNEL, BIT & CLEAT, ANCHOR BOLTS & PLATES FOR PIERS 4, 5, AND 6, DWG. NO. 97, 1-1/2" = 1', MADE BY A.F., JUNE 13, 1908 - Baltimore Inner Harbor, Pier 5, South of Pratt Street between Market Place & Concord Street, Baltimore, Independent City, MD

  14. Repair materials and processes for the MD-11 Composite Tailcone

    NASA Astrophysics Data System (ADS)

    Yamamoto, Tetsuya; Bonnar, Gerard R.

    This paper describes field and depot level repair methods for the MD-11 Composite Tailcone. The repair materials, processing methods, and mechanical properties of the test specimens and subcomponents are discussed. According to recent tests, the dry carbon cloth and the liquid resin matrix that can be cured under 93 C have better processing and mechanical properties than the 121 C curing prepregs and film adhesives. The moisture in the parent CFRP is the main cause of creating voids in the adhesive layer during the 121 C/vacuum pressure cure cycle. The lower processing temperature (wet layup) showed better results than higher processing temperature (prepreg/adhesive layup) for composite repair.

  15. Web Accessibility and Accessibility Instruction

    ERIC Educational Resources Information Center

    Green, Ravonne A.; Huprich, Julia

    2009-01-01

    Section 508 of the Americans with Disabilities Act (ADA) mandates that programs and services be accessible to people with disabilities. While schools of library and information science (SLIS*) and university libraries should model accessible Web sites, this may not be the case. This article examines previous studies about the Web accessibility of…

  16. 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

  17. Md-ACS1 and Md-AC01 genotyping of apple breeding parents and suitability for marker-assisted selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fruit ethylene production genotypes for Md-ACS1 and Md-ACO1 were determined for 60 apple cultivars/selections and 35 advanced breeding selections. Two alleles for each gene are commonly found in cultivated apple. Earlier studies showed that genotypes homozygous for the ACS1-2 allele produce less eth...

  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. PMID:15022542

  19. The first/last access protocol

    NASA Astrophysics Data System (ADS)

    Karol, M. J.; Schwartz, S. C.

    When a random access protocol is used to share a communications channel, conflicts arising from simultaneous transmissions must be resolved. Listening to feedback on a broadcast channel, and using knowledge of round trip propagation delays, the First/Last Access Protocol (FLAP) reserves time for retransmissions of the 'first' and 'last' packets involved in a channel collision. Time slots of duration greater than a packet transmission time exploit the advantages of both slotted access protocols. The maximum achievable system throughput is 0.673 as the input rate increases. Extensions of FLAP yield system throughputs greater than 0.80.

  20. 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.

  1. MLKL forms cation channels

    PubMed Central

    Xia, Bingqing; Fang, Sui; Chen, Xueqin; Hu, Hong; Chen, Peiyuan; Wang, Huayi; Gao, Zhaobing

    2016-01-01

    The mixed lineage kinase domain-like (MLKL) protein is a key factor in tumor necrosis factor-induced necroptosis. Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption. However, our knowledge of how MLKL functions on membrane remains very limited. Here we demonstrate that MLKL forms cation channels that are permeable preferentially to Mg2+ rather than Ca2+ in the presence of Na+ and K+. Moreover, the N-terminal domain containing six helices (H1-H6) is sufficient to form channels. Using the substituted cysteine accessibility method, we further determine that helix H1, H2, H3, H5 and H6 are transmembrane segments, while H4 is located in the cytoplasm. Finally, MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity. The Mg2+-preferred permeability and five transmembrane segment topology distinguish MLKL from previously identified Mg2+-permeable channels and thus establish MLKL as a novel class of cation channels. PMID:27033670

  2. [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. PMID:21250499

  3. 78 FR 28229 - Prospective Grant of Exclusive License: Device and System for Expression Microdissection (xMD)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-14

    ... for Expression Microdissection (xMD) AGENCY: National Institutes of Health, HHS. ACTION: Notice... Activated Microtransfer;'' and all continuing applications and foreign counterparts to xMD Diagnostics, LLC... Field''). xMD Diagnostics, LLC (xMD) shall be the only entity granted rights in the Exclusive Field...

  4. The role of cultivar-specific expression patterns of MdACS3 gene on apple fruit ripening and quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ethylene plays an important role in diverse physiological and developmental processes of plants. In apple, two ethylene biosynthesis genes, MdACS1 and MdACS3, are expressed in fruit tissues. While MdACS1 expresses at late ripening stages, expression of MdACS3 can be detected as early as 6 weeks befo...

  5. The cultivar-specific expression patterns of MdACS3 gene and apple fruit ripening and quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ethylene plays an important role in diverse physiological and developmental processes of plants. In apple, two ethylene biosynthesis genes, MdACS1 and MdACS3, are expressed in fruit tissues. While MdACS1 expresses at late ripening stages, expression of MdACS3 can be detected as early as 6 weeks bef...

  6. Open Access

    ERIC Educational Resources Information Center

    Suber, Peter

    2012-01-01

    The Internet lets us share perfect copies of our work with a worldwide audience at virtually no cost. We take advantage of this revolutionary opportunity when we make our work "open access": digital, online, free of charge, and free of most copyright and licensing restrictions. Open access is made possible by the Internet and copyright-holder…

  7. Access Denied

    ERIC Educational Resources Information Center

    Villano, Matt

    2008-01-01

    Building access control (BAC)--a catchall phrase to describe the systems that control access to facilities across campus--has traditionally been handled with remarkably low-tech solutions: (1) manual locks; (2) electronic locks; and (3) ID cards with magnetic strips. Recent improvements have included smart cards and keyless solutions that make use…

  8. Fred Loe, MD, and the history of trachoma.

    PubMed

    Feibel, Robert M

    2011-04-01

    Trachoma has been one of the most blinding diseases in the history of ophthalmology. From its initial description in antiquity until the late 1930s, no specific treatment or effective cure had been known, and the only expedient had been to destroy the diseased tissue containing the infectious agent, rendering the disease inactive. Virtually all medical, mechanical, and surgical treatments were unsatisfactory, with cure rates of approximately 20%. Therapy for trachoma had barely advanced from the measures used by the ancient Egyptian, Greek, and Roman physicians. All prior therapies became obsolete in 1938 when Fred Loe, MD, working on an American Indian reservation, introduced sulfanilamide as a treatment of trachoma, achieving a 90% cure rate. One of the most unusual aspects of Loe's career was that he had no formal training in ophthalmology and was completely self-taught as an ophthalmologist. PMID:21482877

  9. Thermal Sensitivity of MD Hematite: Implication for Magnetic Anomalies

    NASA Technical Reports Server (NTRS)

    Kletetschka, Gunther; Wasilewski, Peter J.; Taylor, Patrick T.

    1999-01-01

    Magnetic remanence of crustal rocks can reside in three common rock-forming magnetic minerals: magnetite, pyrrhotite, and hematite. Thermoremanent magnetization (TRM) of magnetite and pyrrhotite is carried mostly by single domain (SD) grains. The TRM of hematite grains, however, is carried mostly by multidomain (NM) grains. This characteristic is illustrated by TRM acquisition curves for hematite of variable grainsizes. The transition between truly NM behavior and tendency towards SD behavior his been established between hematite grainsizes of 0. 1 and 0.05 mm. Coarse grainsize of lower crustal rocks and the large sensitivity of MD hematite grains to acquire TRM indicates that hematite could be a significant contributor to long-wavelength magnetic anomalies.

  10. RADIATION PRESSURE DETECTION AND DENSITY ESTIMATE FOR 2011 MD

    SciTech Connect

    Micheli, Marco; Tholen, David J.; Elliott, Garrett T. E-mail: tholen@ifa.hawaii.edu

    2014-06-10

    We present our astrometric observations of the small near-Earth object 2011 MD (H ∼ 28.0), obtained after its very close fly-by to Earth in 2011 June. Our set of observations extends the observational arc to 73 days, and, together with the published astrometry obtained around the Earth fly-by, allows a direct detection of the effect of radiation pressure on the object, with a confidence of 5σ. The detection can be used to put constraints on the density of the object, pointing to either an unexpectedly low value of ρ=(640±330)kg m{sup −3} (68% confidence interval) if we assume a typical probability distribution for the unknown albedo, or to an unusually high reflectivity of its surface. This result may have important implications both in terms of impact hazard from small objects and in light of a possible retrieval of this target.

  11. Angular Effects on F+ Etching SiC: MD Study

    NASA Astrophysics Data System (ADS)

    Chen, Xu; Tian, Shuping; He, Pingni; Zhao, Chengli; Sun, Weizhong; Zhang, Junyuan; Chen, Feng; Gou, Fujun

    2012-12-01

    Molecular dynamics (MD) simulations were performed to investigate F+ continuously bombarding SiC surfaces with energies of 100 eV at different incident angles at 300 K. The simulated results show that the steady-state uptake of F atoms increases with increasing incident angle. With the steady-state etching established, a Si-C-F reactive layer is formed. It is found that the etching yield of Si is greater than that of C. In the F-containing reaction layer, the SiF species is dominant with incident angles less than 30°. For all incident angles, the CF species is dominant over CF2 and CF3.

  12. Plasticity and Failure in Nanocrystalline BCC Metals via MD Simulation

    SciTech Connect

    Rudd, R E

    2010-02-12

    Advances in the ability to generate extremely high pressures in dynamic experiments such as at the National Ignition Facility has motivated the need for special materials optimized for those conditions as well as ways to probe the response of these materials as they are deformed. We need to develop a much deeper understanding of the behavior of materials subjected to high pressure, especially the effect of rate at the extremely high rates encountered in those experiments. Here we use large-scale molecular dynamics (MD) simulations of the high-rate deformation of nanocrystalline tantalum at pressures less than 100 GPa to investigate the processes associated with plastic deformation for strains up to 100%. We focus on 3D polycrystalline systems with typical grain sizes of 10-20 nm. We also study a rapidly quenched liquid (amorphous solid) tantalum. We apply a constant volume (isochoric), constant temperature (isothermal) shear deformation over a range of strain rates, and compute the resulting stress-strain curves to large strains for both uniaxial and biaxial compression. We study the rate dependence and identify plastic deformation mechanisms. The identification of the mechanisms is facilitated through a novel technique that computes the local grain orientation, returning it as a quaternion for each atom. This analysis technique is robust and fast, and has been used to compute the orientations on the fly during our parallel MD simulations on supercomputers. We find both dislocation and twinning processes are important, and they interact in the weak strain hardening in these extremely fine-grained microstructures. We also present some results on void growth in nanocrystalline BCC metals under tension.

  13. Channel catfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book chapter provides a comprehensive overview of channel catfish aquaculture. Sections include fish biology; commercial culture; culture facilities; production practices; water quality management; nutrition, feeding and feed formulation; infectious diseases; harvesting and processing; and the...

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

    NASA Astrophysics Data System (ADS)

    Timko, Jeff; Kuyucak, Serdar

    2012-11-01

    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.

  15. Characterization of an Autophagy-Related Gene MdATG8i from Apple

    PubMed Central

    Wang, Ping; Sun, Xun; Jia, Xin; Wang, Na; Gong, Xiaoqing; Ma, Fengwang

    2016-01-01

    Nutrient deficiencies restrict apple (Malus sp.) tree growth and productivity in Northwest China. The process of autophagy, a conserved degradation pathway in eukaryotic cells, has important roles in nutrient-recycling and helps improve plant performance during periods of nutrient-starvation. Little is known about the functioning of autophagy-related genes (ATGs) in apple. In this study, one of the ATG8 gene family members MdATG8i was isolated from Malus domestica. MdATG8i has conserved putative tubulin binding sites and ATG7 interaction domains. A 1865-bp promoter region cloned from apple genome DNA was predicated to have cis-regulatory elements responsive to light, environmental stresses, and hormones. MdATG8i transcriptions were induced in response to leaf senescence, nitrogen depletion, and oxidative stress. At cellular level, MdATG8i protein was expressed in the nucleus and cytoplasm of onion epidermal cells. Yeast two-hybrid tests showed that MdATG8i could interact with MdATG7a and MdATG7b. In Arabidopsis, its heterologous expression was associated with enhanced vegetative growth, leaf senescence, and tolerance to nitrogen- and carbon-starvation. MdATG8i-overexpressing “Orin” apple callus lines also displayed improved tolerance to nutrient-limited conditions. Our results demonstrate that MdATG8i protein could function in autophagy in a conserved way, as a positive regulator in the response to nutrient-starvation. PMID:27252732

  16. Characterization of an Autophagy-Related Gene MdATG8i from Apple.

    PubMed

    Wang, Ping; Sun, Xun; Jia, Xin; Wang, Na; Gong, Xiaoqing; Ma, Fengwang

    2016-01-01

    Nutrient deficiencies restrict apple (Malus sp.) tree growth and productivity in Northwest China. The process of autophagy, a conserved degradation pathway in eukaryotic cells, has important roles in nutrient-recycling and helps improve plant performance during periods of nutrient-starvation. Little is known about the functioning of autophagy-related genes (ATGs) in apple. In this study, one of the ATG8 gene family members MdATG8i was isolated from Malus domestica. MdATG8i has conserved putative tubulin binding sites and ATG7 interaction domains. A 1865-bp promoter region cloned from apple genome DNA was predicated to have cis-regulatory elements responsive to light, environmental stresses, and hormones. MdATG8i transcriptions were induced in response to leaf senescence, nitrogen depletion, and oxidative stress. At cellular level, MdATG8i protein was expressed in the nucleus and cytoplasm of onion epidermal cells. Yeast two-hybrid tests showed that MdATG8i could interact with MdATG7a and MdATG7b. In Arabidopsis, its heterologous expression was associated with enhanced vegetative growth, leaf senescence, and tolerance to nitrogen- and carbon-starvation. MdATG8i-overexpressing "Orin" apple callus lines also displayed improved tolerance to nutrient-limited conditions. Our results demonstrate that MdATG8i protein could function in autophagy in a conserved way, as a positive regulator in the response to nutrient-starvation. PMID:27252732

  17. Town + Gown + CATV = Community Access.

    ERIC Educational Resources Information Center

    Clemens, Donald J.

    1980-01-01

    Describes a cooperative venture between Paducah Community College, Comcast Cable, and Paducah, Kentucky, and the roles each of these organizations played in establishing a public access channel which would provide informational and general interest programs, as well as college courses. Offers information on programing, financial support, and…

  18. 76 FR 72403 - Access to Confidential Business Information by Primus Solutions, Inc.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-23

    ... AGENCY Access to Confidential Business Information by Primus Solutions, Inc. AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: EPA has authorized its contractor, Primus Solutions, Inc., (Primus) of Greenbelt, MD, to access information which has been submitted to EPA under all sections of...

  19. Methodologies for the Analysis of Instantaneous Lipid Diffusion in MD Simulations of Large Membrane Systems

    PubMed Central

    Chavent, Matthieu; Reddy, Tyler; Goose, Joseph; Dahl, Anna Caroline E.; Stone, John E.; Jobard, Bruno; Sansom, Mark S.P.

    2014-01-01

    Interactions between lipids and membrane proteins play a key role in determining the nanoscale dynamic and structural properties of biological membranes. Molecular dynamics (MD) simulations provide a valuable tool for studying membrane models, complementing experimental approaches. It is now possible to simulate large membrane systems, such as simplified models of bacterial and viral envelope membranes. Consequently, there is a pressing need to develop tools to visualize and quantify the dynamics of these immense systems, which typically are comprised of millions of particles. To tackle this issue, we have developed visual and quantitative analyses of molecular positions and their velocity field using path line, vector field and streamline techniques. This allows us to highlight large, transient flow-like movements of lipids and to better understand crowding within the lipid bilayer. The current study focuses on visualization and analysis of lipid dynamics. However, the methods are flexible and can be readily applied to e.g. proteins and nanoparticles within large complex membranes. The protocols developed here are readily accessible both as a plugin for the molecular visualization program VMD and as a module for the MDAnalysis library. PMID:25341001

  20. 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. PMID:23583403

  1. A baccalaureate-MD program for students from medically underserved communities: 15-year outcomes.

    PubMed

    Thomson, William A; Ferry, Pamela; King, Jason; Wedig, Cindy Martinez; Villarreal, Graciela B

    2010-04-01

    Liaison Committee on Medical Education standard MS-8 requires medical schools to partner with other educational institutions or develop programs to make medical education more accessible to potential applicants from diverse backgrounds. From 1994 to the present, Baylor College of Medicine and the University of Texas-Pan American (UTPA) have partnered to offer a BS-MD program to increase access to medical education for students from South Texas, a predominantly Latino, largely medically underserved region. Since its inception in 1994, the Premedical Honors College (PHC) has produced 134 medical school matriculants (as of 2008), an average of 12 students per year since 1998, when the first program graduates matriculated to medical school. This represents a significant increase; only 10 students entered medical school from the region's five undergraduate institutions at baseline year 1994, including six from UTPA. Of those matriculating to medical school, through the PHC 110 (82%) are from underrepresented minority backgrounds, and 106 (79%) are Latino. In addition, the program has produced 65 MDs to date; 55 (85%) are Latino. Twenty PHC participants have already completed residency training and are practicing, 12 of those in or near South Texas. As of 2008, 44 were completing residencies or fellowships, 9 in South Texas, and several have expressed a desire to return to South Texas eventually to practice. Six PHC graduates are academic faculty members (four clinical instructors and two assistant professors), all of them Latino. These results suggest that pipeline strategies involving academic partnerships can have a meaningful impact on diversity in medical education. PMID:20354387

  2. TRP channels.

    PubMed

    Benemei, Silvia; Patacchini, Riccardo; Trevisani, Marcello; Geppetti, Pierangelo

    2015-06-01

    Evidence is accumulating on the role of transient receptor potential (TRP) channels, namely TRPV1, TRPA1, TRPV4 and TRPM8, expressed by C- and Aδ-fibres primary sensory neurons, in cough mechanism. Selective stimuli for these channels have been proven to provoke and, more rarely, to inhibit cough. More importantly, cough threshold to TRP agonists is increased by proinflammatory conditions, known to favour cough. Off-target effects of various drugs, such as tiotropium or desflurane, seem to produce their protective or detrimental actions on airway irritation and cough via TRPV1 and TRPA1, respectively. Thus, TRPs appear to encode the process that initiates or potentiates cough, activated by exogenous irritants and endogenous proinflammatory mediators. More research on TRP channels may result in innovative cough medicines. PMID:25725213

  3. Theoretical and computational studies of microscopic water channels

    NASA Astrophysics Data System (ADS)

    Zhu, Fangqiang

    Water channels are ubiquitous in all life forms. A notable example is aquaporins (AQPs), a family of proteins which mainly function as passive water channels in cell membranes. The availability of the crystal structures of several AQPs in recent years allowed us to study them in atomic details. We performed molecular dynamics (MD) simulations on AQPs in lipid bilayers to study water permeation through these channels. We also simulated water conduction in carbon nanotubes, serving as simplified models for biological channels. We developed theories and methodologies aimed to reproduce and predict important experimental quantities of water channels from simulations. We showed that the diffusion permeability (pd), which is measured by tracer diffusion in experiments, can be calculated from equilibrium MD simulations. In order to calculate the osmotic permeability (p f), which is experimentally measured in the presence of a solute concentration difference, we developed a method to induce a hydrostatic pressure difference across the membrane under periodic boundary conditions. We calculated the osmotic permeability for aquaporin-1 using this method, which agrees with experiments. Using a continuous-time random-walk model, we showed that for single-file water channels, the ratio of p f to pd is roughly equal to the number of water molecules in the channel. Proton transfer through single water file was studied theoretically using network thermodynamics. Finally, we proposed a new model for general water channels, which gives a quantitative relationship between water permeations under equilibrium and non-equilibrium conditions, and therefore allows one to calculate pf from equilibrium MD simulations.

  4. 78 FR 52802 - Tin T. Win, M.D., Dismissal of Proceeding

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Tin T. Win, M.D., Dismissal of Proceeding On February 27, 2013, I, the Administrator of the Drug Enforcement Administration, issued an Order to Show Cause and Immediate Suspension of Registration to Tin T. Win, M.D....

  5. 33 CFR 165.507 - Security Zone; Chesapeake Bay, between Sandy Point and Kent Island, MD.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., between Sandy Point and Kent Island, MD. 165.507 Section 165.507 Navigation and Navigable Waters COAST... Guard District § 165.507 Security Zone; Chesapeake Bay, between Sandy Point and Kent Island, MD. (a... to the eastern shore at Kent Island, Maryland. (c) Regulations. (1) All persons are required...

  6. 33 CFR 165.507 - Security Zone; Chesapeake Bay, between Sandy Point and Kent Island, MD.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., between Sandy Point and Kent Island, MD. 165.507 Section 165.507 Navigation and Navigable Waters COAST... Guard District § 165.507 Security Zone; Chesapeake Bay, between Sandy Point and Kent Island, MD. (a... to the eastern shore at Kent Island, Maryland. (c) Regulations. (1) All persons are required...

  7. 33 CFR 165.507 - Security Zone; Chesapeake Bay, between Sandy Point and Kent Island, MD.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., between Sandy Point and Kent Island, MD. 165.507 Section 165.507 Navigation and Navigable Waters COAST... Guard District § 165.507 Security Zone; Chesapeake Bay, between Sandy Point and Kent Island, MD. (a... to the eastern shore at Kent Island, Maryland. (c) Regulations. (1) All persons are required...

  8. Regulation of TLR4-associated MD-2 in intestinal epithelial cells: a comprehensive analysis

    PubMed Central

    Vamadevan, Arunan S.; Fukata, Masayuki; Arnold, Elizabeth T.; Thomas, Lisa S.; Hsu, David; Abreu, Maria T.

    2009-01-01

    The intestinal epithelium maintains a state of controlled inflammation despite continuous contact with Gram-negative commensal bacteria and lipopolysaccharide (LPS) on its luminal surface. Recognition of LPS by the TLR4/MD-2 complex results in proinflammatory gene expression and cytokine secretion in intestinal epithelial cells (IEC). We have shown that IEC express low levels of MD-2 and TLR4 and are poorly responsive to LPS. In this study, we did a comprehensive analysis to understand the immune-mediated and epigenetic mechanisms by which IEC down-regulate MD-2 expression. Expression of MD-2 and TLR4 mRNA was examined in human inflammatory bowel disease and intestinal epithelial cell lines (T84, HT-29, Caco-2). Nuclear factor-κB transcriptional activation was used as a measure of LPS responsiveness. Intestinal epithelial cellsin patients with IBD exhibited increased expression of MD-2 and TLR4 mRNA. Lipopolysaccharide responsiveness in IEC was polarized to the basolateral membrane. Bisulfite sequencing of the MD-2 promoter demonstrated methylation of CpG dinucleotides. Inhibition of methylation by 5-azacytidine and histone deactylation by trichostatin A, two forms of epigenetic silencing, resulted in increased mRNA expression of MD-2 in IEC. These results demonstrate various molecular mechanisms by which IEC down-regulate MD-2 and thereby protect against dysregulated inflammation to commensal bacteria in the intestinal lumen. PMID:19710105

  9. DNA methylation fluctuation induced by virus infection differs between MD-resistant and -susceptible chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a lymphoproliferative disease induced by Marek’s disease virus (MDV). To augment vaccination, the host genetic resistance is of importance in MD control. While researchers have been largely focused on exploring the genetic differences between resistant and susceptible chicken...

  10. 78 FR 71660 - Zizhuang Li, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Zizhuang Li, M.D.; Decision and Order On June 10, 2013, the Deputy Assistant Administrator, Office of Diversion Control, Drug Enforcement Administration, issued an Order to Show Cause to Zizhuang Li, M.D. (Applicant),...

  11. 78 FR 38363 - David A. Ruben, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration David A. Ruben, M.D.; Decision and Order On February 7, 2011, the Deputy Assistant Administrator, Office of Diversion Control, Drug Enforcement Administration, issued an Order to Show Cause to David A. Ruben, M.D....

  12. 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... ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water area of Jacobs Nose Cove, on the west side of the mouth of Elk River, Maryland, comprising the...

  13. 76 FR 50950 - Drawbridge Operation Regulation; Isle of Wight (Sinepuxent) Bay, Ocean City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... Federal Register (73 FR 3316). Public Meeting We do not now plan to hold a public meeting. But you may... (Sinepuxent) Bay, Ocean City, MD AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The... of Wight (Sinepuxent) Bay, mile 0.5, at Ocean City, MD. The proposed change will alter the dates...

  14. 76 FR 70346 - Drawbridge Operation Regulation; Isle of Wight (Sinepuxent) Bay, Ocean City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-14

    ... FR 50950). We have not received any comments on the proposed rule. No public meeting was requested... (Sinepuxent) Bay, Ocean City, MD AGENCY: Coast Guard, DHS. ACTION: Final rule. SUMMARY: The Coast Guard is..., mile 0.5, at Ocean City, MD. This rule will add dates that the bridge is allowed to remain in...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ...'s action at which he may ultimately prevail.'' Kamal Tiwari, M.D., 76 FR 71604, 71606 (2011); see also Bourne Pharmacy, Inc., 72 FR 18273, 18274 (2007); Anne Lazar Thorn, 62 FR 12847 (1997...., 67 FR 35,582 (DEA 2002); Michael G. Dolin, M.D., 65 Fed. Reg. 5661 (DEA 2000); see also Philip...

  17. 75 FR 21528 - Airworthiness Directives; McDonnell Douglas Corporation Model MD-90-30 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... Policies and Procedures (44 FR 11034, February 26, 1979), and 3. Will not have a significant economic... Douglas Corporation Model MD- 90-30 Airplanes AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... certain Model MD-90-30 airplanes. This proposed AD would require inspecting for corrosion of the...

  18. 78 FR 67086 - Safety Zone, Submarine Cable Replacement Operations, Kent Island Narrows; Queen Anne's County, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ...The Coast Guard proposes to establish a temporary safety zone encompassing certain waters of Kent Island Narrows in Queen Anne's County, MD. This action is necessary to provide for the safety of mariners and their vessels on navigable waters during submarine cable replacement operations at the Kent Island Narrows (MD-18B) Bridge. This action is intended to restrict vessel traffic movement to......

  19. Registration of mutant population of MD 15 M4 Gossypium hirsutum L. with enhanced fiber quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mutant population of MD 15 M4 (Reg. No. ,PI ) is a unique germplasm population of upland cotton (Gossypium hirsutum L.). This germplasm was developed by USDA-ARS, Stoneville, MS in 2008 and released in June, 2012. About 5000 seeds of a Mississippi Delta line, MD 15 were chemically mutagenized with 3...

  20. 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... ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water area of Jacobs Nose Cove, on the west side of the mouth of Elk River, Maryland, comprising the...

  1. 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... ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water area of Jacobs Nose Cove, on the west side of the mouth of Elk River, Maryland, comprising the...

  2. 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... ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water area of Jacobs Nose Cove, on the west side of the mouth of Elk River, Maryland, comprising the...

  3. 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... ANCHORAGES ANCHORAGE REGULATIONS Special Anchorage Areas § 110.71 Jacobs Nose Cove, Elk River, Md. The water area of Jacobs Nose Cove, on the west side of the mouth of Elk River, Maryland, comprising the...

  4. 77 FR 57126 - Henri Wetselaar, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Henri Wetselaar, M.D.; Decision and Order On September 27, 2011, I, the Administrator of the Drug Enforcement Administration, issued an Order to Show Cause and Immediate Suspension of Registration to Henri Wetselaar, M.D....

  5. 76 FR 29640 - Special Local Regulations for Marine Events; Chester River, Chestertown, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-23

    ... Regulations for Marine Events; Chester River, Chestertown, MD'' in the Federal Register (76 FR 54). We... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations for Marine Events; Chester... Party Festival,'' a marine event to be held on the waters of the Chester River, Chestertown, MD on...

  6. 75 FR 21167 - Special Local Regulations for Marine Events; Chester River, Chestertown, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... Regulations for Marine Events; Chester River, Chestertown, MD'' in the Federal Register (75 FR 043). We... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA08 Special Local Regulations for Marine Events; Chester... Party Festival'', a marine event to be held on the waters of the Chester River, Chestertown, MD on...

  7. 75 FR 57388 - Special Local Regulations for Marine Events; Patuxent River, Solomons, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-21

    ... Marine Events; Patuxent River, Solomons, MD'' in the Federal Register (75 FR 32866). Additionally, on... Local Regulations for Marine Events; Patuxent River, Solomons, MD'' in the Federal Register (75 FR 41789... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations for Marine Events;...

  8. 77 FR 73677 - Stephanie A. Tarapchak, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-11

    ... (quoting Calvin Ramsey, M.D., 76 FR 20034, 20036 (2011)). See also Kamal Tiwari, M.D., 76 FR 71604, 71606... . . . dispensing of controlled substances.'' See, e.g., Richard H. Ng, 77 FR 29694 (2012); Segun M. Rasaki, 77 FR 29692 (2012); David W. Wang, 72 FR 54297 (2007). Rather, DEA's rule derives primarily from two...

  9. 76 FR 17673 - Bienvenido Tan, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-30

    ... Enforcement Administration Bienvenido Tan, M.D.; Denial of Application On October 31, 2008, the Deputy... Show Cause to Bienvenido Tan, M.D. (Respondent), of Newhall, California. The Show Cause Order proposed..., contains manufacturers' recommendations as to the dosing of drug products. RX D, at 3. On January 28,...

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... Respondent's registration.'' Id. (citing Harrell E. Robinson, M.D., 74 FR 61370, 61376-77 (2010)). The ALJ... Jeri Hassman, M.D., 75 FR 8194, 8227 (2010); Gonzales v. Oregon, 546 U.S. 243, 274 (2006)). Noting that... continuation of a registration is consistent with the public interest.'' Id. (citing Patrick W. Stodola, 74...

  11. 75 FR 66138 - George Mathew, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-27

    ... Purchasing Controlled Substances over the Internet, 66 FR 21181. Therein, the Agency explained that ``Federal... Enforcement Administration George Mathew, M.D.; Denial of Application On September 19, 2005, I, the Deputy... Registration to George Mathew, M.D. (Respondent), of Seattle, Washington. The Order proposed the revocation...

  12. 78 FR 52787 - Kevin Dennis, M.D., Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Kevin Dennis, M.D., Decision and Order On April 12, 2011, the Deputy Assistant Administrator, Office of Diversion Control, issued an Order to Show Cause to Kevin Dennis, M.D....

  13. 77 FR 67673 - Fernando Valle, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-13

    ...); Sheran Arden Yeates, 71 FR 39130, 39131 (2006); Dominick A. Ricci, M.D., 58 FR 51104 (1993); Bobby Watts, M.D., 53 FR 11919 (1988). Notwithstanding the foregoing, the Respondent contends that the Emergency..., 20347 (2009); see also Scott Sandarg, D.M.D., 74 FR 17528, 174529 (2009); John B. Freitas, D.O., 74...

  14. 76 FR 75448 - Establishment of Class D and E Airspace; Frederick, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-02

    ... Class D and E airspace at Frederick, MD, to accommodate new Area Navigation (RNAV) Global Positioning... and E airspace for the new Frederick Municipal Airport, Frederick, MD (76 FR 50156) Docket No. FAA... Executive Order 12866; (2) is not a ``significant rule'' under DOT Regulatory Policies and Procedures (44...

  15. 76 FR 53942 - Richard A. Herbert, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... deliberate ignorance as to the likelihood the drugs were being diverted. See Jeri Hassman, M.D., 75 FR 8194... [a registration] would be in the public interest.'' Mortimer B. Levin, D.O., 55 FR 8209, 8210 (1990..., M.D., 75 FR 66138, 66146 (2010) (under Federal law, where a physician issues a prescription...

  16. 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

    ...; St. Mary's County, Leonardtown, MD'' in the Federal Register (78 FR 21864). The rulemaking concerned... Breton Bay, in St. Mary's County, MD, effective from 8 a.m. on July 13, 2013 to 5 p.m. on July 14, 2013... SECURITY Coast Guard 33 CFR Part 100 RIN 1625-AA08 Special Local Regulations; Marine Events, Breton Bay;...

  17. 75 FR 27430 - Special Local Regulations for Marine Events; Patapsco River, Northwest Harbor, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-17

    ...; Patapsco River, Northwest Harbor, Baltimore, MD'' in the Federal Register (75 FR 16374). We received no... River, Northwest Harbor, Baltimore, MD AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing special local regulations during the ``Baltimore Dragon Boat...

  18. Breast reconstruction at the MD Anderson Cancer Center.

    PubMed

    Yu, Peirong

    2016-08-01

    The introduction of the transverse rectus abdominis myocutaneous flap in the 1970s marks the beginning of modern breast reconstruction although implants were available even earlier mainly for breast augmentation. Mastectomy techniques have evolved from the early Halsted radical mastectomy to the modern skin sparing mastectomy. The latter made possible using implants for breast reconstruction. Although prosthetic reconstruction provides a simpler procedure with quick recovery, autologous reconstruction offers more natural and long-lasting results especially in the setting of radiotherapy. Both forms have been extensively used at the MD Anderson Cancer Center (MDACC) while microsurgical breast reconstruction has been the hallmark of the MDACC experience. One of the most challenging areas of breast reconstruction is how to achieve good results without compromising adjuvant therapy when post-mastectomy radiotherapy is required. Managing upper extremity lymphedema following breast cancer treatment is another difficult issue which has gained great attention in recent years. This article highlights the important work in various aspects of breast reconstruction that has been done at the MDACC. PMID:27563563

  19. The value circle. A profile of J. Richard Gaintner, MD.

    PubMed

    Howard, R

    1999-01-01

    This article describes how the arrival of CEO J. Richard Gaintner, MD, at Shands HealthCare signaled a time for refocusing the organization's direction and helping physicians to cope with the changes buffeting the industry. He saw angst and disenfranchisement, sentiments that characterized not only Shands and the University of Florida Health Science Center, but also the entire establishment of American scientific medicine. Gaintner believes--and continually preaches--that practicing medicine in a cost-effective manner will improve, not harm, the quality of care. His willingness to face reality objectively is perhaps his greatest asset in helping physicians deal with managed care. He conveys heartfelt empathy with the day-to-day conflicts they face. But he does not allow himself the temporary luxury of cynicism, and he refuses to accept negativity and pessimism in others. Rather, he asks that physicians and managers understand the system and develop the capacity to work within it and take responsibility for improving it. Beyond exhorting physicians to be accountable for the success of the enterprise, Gaintner creates mechanisms for meaningful physician participation in enterprise management. PMID:10351728

  20. John Call Dalton, Jr., MD: America's first neurophysiologist.

    PubMed

    Fine, E J; Manteghi, T; Sobel, S H; Lohr, L A

    2000-09-26

    Before the discoveries of John Call Dalton, Jr., MD (1824-1889), innervation of laryngeal muscles, long-term effects of cerebellar lesions, and consequences of raised intracranial pressure were poorly understood. Dalton discovered that the posterior cricoarytenoid muscles adducted the vocal cords during inspiration. He confirmed Flourens' observations that acute ablation of the cerebellum of pigeons caused loss of coordination. Dalton observed that properly cared for pigeons gradually recovered "coordinating power." Dalton observed that prolonged raised intracranial pressure caused tachycardia and then fatal bradycardia in dogs. Before Dalton published his photographic atlas of the human brain, neuroanatomy atlases were sketched by Europeans and imported into the United States. Dalton's atlas of the human brain contained precise photographs of vertical and horizontal sections that equal modern works. Before Dalton introduced live demonstrations of animals, physiology was taught by recitation of texts only. Dalton was the first American-born professor to teach physiology employing demonstrations of live animals operated on under ether anesthesia. He wrote an essay advocating experimentation on animals as the proper method of acquiring knowledge of function and that humane animal experimentation would ultimately improve the health of man and animals. His eloquent advocacy for humane experimental physiology quelled attacks by contemporaneous antivivisectionists. Dalton was America's first experimental neurophysiologist. PMID:10994009

  1. Using MD Simulations To Calculate How Solvents Modulate Solubility.

    PubMed

    Liu, Shuai; Cao, Shannon; Hoang, Kevin; Young, Kayla L; Paluch, Andrew S; Mobley, David L

    2016-04-12

    Here, our interest is in predicting solubility in general, and we focus particularly on predicting how the solubility of particular solutes is modulated by the solvent environment. Solubility in general is extremely important, both for theoretical reasons - it provides an important probe of the balance between solute-solute and solute-solvent interactions - and for more practical reasons, such as how to control the solubility of a given solute via modulation of its environment, as in process chemistry and separations. Here, we study how the change of solvent affects the solubility of a given compound. That is, we calculate relative solubilities. We use MD simulations to calculate relative solubility and compare our calculated values with experiment as well as with results from several other methods, SMD and UNIFAC, the latter of which is commonly used in chemical engineering design. We find that straightforward solubility calculations based on molecular simulations using a general small-molecule force field outperform SMD and UNIFAC both in terms of accuracy and coverage of the relevant chemical space. PMID:26878198

  2. MD Study of Stokes Shifts in Ionic Liquids: Temperature Dependence.

    PubMed

    Wu, Eric C; Kim, Hyung J

    2016-05-26

    Effects of temperature on Stokes shifts, solvation structure, and dynamics in ionic liquids EMI(+)Tf2N(-), EMI(+)PF6(-), and BMI(+)PF6(-) (EMI(+) = 1-ethyl-3-methylimidazolium, BMI(+) = 1-butyl-3-methylimidazolium, Tf2N(-) = bis(trifluoromethylsulfonyl)imide, and PF6(-) = hexafluorophosphate) are investigated via molecular dynamics (MD) computer simulations in the temperature range 350 K ≤ T ≤ 500 K. Two different types of solutes are considered: a simple model diatomic solute and realistic coumarin 153, both of which are characterized by more polar S1 and less polar S0 states. In all three ionic liquids studied, the Stokes shift tends to decrease with increasing temperature. For coumarin 153, as T increases, the Franck-Condon energy for steady-state absorption decreases, whereas that for steady-state emission increases. Our findings indicate that the effective polarity of ionic liquids decreases as T increases. Their solvation dynamics are characterized by an ultrafast initial decay in the subpicosecond time scale, followed by slow dissipative relaxation, regardless of temperature. For both solutes, the solvent frequency that quantifies initial ultrafast dynamics shows little temperature dependence. By contrast, the long-time dissipative dynamics become significantly faster with rising T. Variations of solvation structure with temperature and their connection to Stokes shift and solvation dynamics are briefly examined. PMID:27133895

  3. Predicting nematic coupling constants of semiflexible polymers from MD simulations

    NASA Astrophysics Data System (ADS)

    Zhang, Wenlin; Gomez, Enrique; Milner, Scott

    2015-03-01

    The nematic phase is important for many semiflexible polymers. For example, semiflexible polymers with nematic phase can be directly used in many applications, including displays and high strength fibers. The existence of nematic phases also enables better processing of functional semiflexible polymers including conducting conjugated polymers. The nematic coupling constant α, together with the chain stiffness κ, governs chain alignment and the isotropic-to-nematic (IN) transition temperature TIN for semiflexible polymers. For many semiflexible chains, crystallization or thermal degradation can preclude the IN transition, so that TIN cannot be used to estimate α. We combine self-consistent field theory (SCFT) with atomistic molecular dynamics (MD) simulations of semiflexible chains under external tension in the isotropic phase to estimate the nematic coupling constant α. Using our mean-field model, we can obtain the variational free energy of a given polymer, from which the IN transition temperature TIN can be determined. We apply our method to estimate α and TIN of a commonly studied conjugated polymer, poly(3-hexylthiophene) (P3HT). Using the estimated TIN, we predict P3HT is nematic after melting from crystal.

  4. MD studies on conformational behavior of a DNA photolyase enzyme

    NASA Astrophysics Data System (ADS)

    Dushanov, E.; Kholmurodov, Kh.; Yasuoka, K.; Krasavin, E.

    2013-11-01

    In this work, molecular dynamics (MD) simulations were performed on a DNA photolyase protein with two cofactors, FAD (flavin adenine dinucleotide) and MTHF (methenyltetrahydrofolate), inside the enzyme pocket. A DNA photolyase is a highly efficient light-driven enzyme that repairs the UV-induced cyclobutane-pyrimidine dimer in damaged DNA. We were aimed to compare the conformational changes of the FAD cofactor and other constituent fragments of the molecular system under consideration. The conformational behavior of the FAD molecule is very important for understanding the functional and structural properties of the DNA repair protein photolyase. The photoactive FAD is an essential cofactor both for specificial binding to damaged DNA and for catalysis. The second chromophore (MTHF or 8-HDF) is not necessary for catalysis and has no effect on specific enzyme—substrate binding. The obtained results were discussed to gain insight into the light-driven mechanism of DNA repair by a DNA photolyase enzyme—based on the enzyme structure, the FAD mobility, and conformation shape.

  5. [A tribute to Richard V. Lee, M.D].

    PubMed

    Reyes B, Humberto

    2013-10-01

    Richard V Lee, MD, MACP, FRGS, Professor of Medicine and Pediatrics and Obstetrics, Adjunct Professor of Anthropology and Social and Preventive Medicine. Director, Division of Maternal & Adolescent Medicine, and Director, Division of Geographic Medicine, Department of Medicine, State University of New York at Buffalo, USA, passed away on May 7,2013. His academic degrees and university positions are a vivid testimony of his wide professional interests and capabilities. As a humanist and ecologist, he became involved in a broad range of medical and research activities in the Brazilian Amazon, the Chilean Southern Andes, the African deserts and highlands, India, the Himalayas, and China. His extensive bibliography on ecology, the health status of geographically isolated populations and the role of physicians on cultural and macro environmental factors, has been summarized in his posthumous book "Out of Bounds. Medicine and The Hundred Acre Wood", recently published by the Royal Society of Medicine, London. The Sociedad Médica de Santiago-Chilean Society of Internal Medicine and its journal Revista Médica de Chile are indebted to his enthusiastic contributions and advice. PMID:24522368

  6. Breast reconstruction at the MD Anderson Cancer Center

    PubMed Central

    2016-01-01

    The introduction of the transverse rectus abdominis myocutaneous flap in the 1970s marks the beginning of modern breast reconstruction although implants were available even earlier mainly for breast augmentation. Mastectomy techniques have evolved from the early Halsted radical mastectomy to the modern skin sparing mastectomy. The latter made possible using implants for breast reconstruction. Although prosthetic reconstruction provides a simpler procedure with quick recovery, autologous reconstruction offers more natural and long-lasting results especially in the setting of radiotherapy. Both forms have been extensively used at the MD Anderson Cancer Center (MDACC) while microsurgical breast reconstruction has been the hallmark of the MDACC experience. One of the most challenging areas of breast reconstruction is how to achieve good results without compromising adjuvant therapy when post-mastectomy radiotherapy is required. Managing upper extremity lymphedema following breast cancer treatment is another difficult issue which has gained great attention in recent years. This article highlights the important work in various aspects of breast reconstruction that has been done at the MDACC. PMID:27563563

  7. MD-11 PCA - View of aircraft on ramp

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This McDonnell Douglas MD-11 is taxiing to a position on the flightline at NASA's Dryden Flight Research Center, Edwards, California, following its completion of the first and second landings ever performed by a transport aircraft under engine power only (on Aug. 29, 1995). The milestone flight, with NASA research pilot and former astronaut Gordon Fullerton at the controls, was part of a NASA project to develop a computer-assisted engine control system that enables a pilot to land a plane safely when its normal control surfaces are disabled. The Propulsion-Controlled Aircraft (PCA) system uses standard autopilot controls already present in the cockpit, together with the new programming in the aircraft's flight control computers. The PCA concept is simple. For pitch control, the program increases thrust to climb and reduces thrust to descend. To turn right, the autopilot increases the left engine thrust while decreasing the right engine thrust. The initial Propulsion-Controlled Aircraft studies by NASA were carried out at Dryden with a modified twin-engine F-15 research aircraft.

  8. MD-11 PCA - Closeup view of aircraft on ramp

    NASA Technical Reports Server (NTRS)

    1995-01-01

    This McDonnell Douglas MD-11 has taxied to a position on the flightline at NASA's Dryden Flight Research Center, Edwards, California, following its completion of the first and second landings ever performed by a transport aircraft under engine power only (on Aug. 29, 1995). The milestone flight, with NASA research pilot and former astronaut Gordon Fullerton at the controls, was part of a NASA project to develop a computer-assisted engine control system that enables a pilot to land a plane safely when its normal control surfaces are disabled. The Propulsion-Controlled Aircraft (PCA) system uses standard autopilot controls already present in the cockpit, together with the new programming in the aircraft's flight control computers. The PCA concept is simple. For pitch control, the program increases thrust to climb and reduces thrust to descend. To turn right, the autopilot increases the left engine thrust while decreasing the right engine thrust. The initial Propulsion-Controlled Aircraft studies by NASA were carried out at Dryden with a modified twin-engine F-15 research aircraft.

  9. 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. PMID:26555017

  10. H5MD: A structured, efficient, and portable file format for molecular data

    NASA Astrophysics Data System (ADS)

    de Buyl, Pierre; Colberg, Peter H.; Höfling, Felix

    2014-06-01

    We propose a new file format named "H5MD" for storing molecular simulation data, such as trajectories of particle positions and velocities, along with thermodynamic observables that are monitored during the course of the simulation. H5MD files are HDF5 (Hierarchical Data Format) files with a specific hierarchy and naming scheme. Thus, H5MD inherits many benefits of HDF5, e.g., structured layout of multi-dimensional datasets, data compression, fast and parallel I/O, and portability across many programming languages and hardware platforms. H5MD files are self-contained, and foster the reproducibility of scientific data and the interchange of data between researchers using different simulation programs and analysis software. In addition, the H5MD specification can serve for other kinds of data (e.g. experimental data) and is extensible to supplemental data, or may be part of an enclosing file structure.

  11. Hemodialysis access - self care

    MedlinePlus

    Kidney failure - chronic-hemodialysis access; Renal failure - chronic-hemodialysis access; Chronic renal insufficiency - hemodialysis access; Chronic kidney failure - hemodialysis access; Chronic renal failure - hemodialysis access; dialysis - hemodialysis access

  12. 47 CFR 76.978 - Leased access annual reporting requirement.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... rate and actual rates. (5) The programmers using each commercial leased access channel and whether each programmer is using the channel on a full-time or part-time basis. (6) The number of requests received for... different rates, terms, or conditions on commercial leased access programmers (such as with respect...

  13. 47 CFR 76.978 - Leased access annual reporting requirement.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... rate and actual rates. (5) The programmers using each commercial leased access channel and whether each programmer is using the channel on a full-time or part-time basis. (6) The number of requests received for... different rates, terms, or conditions on commercial leased access programmers (such as with respect...

  14. 47 CFR 76.978 - Leased access annual reporting requirement.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... rate and actual rates. (5) The programmers using each commercial leased access channel and whether each programmer is using the channel on a full-time or part-time basis. (6) The number of requests received for... different rates, terms, or conditions on commercial leased access programmers (such as with respect...

  15. Md1 and Rp105 regulate innate immunity and viral resistance in zebrafish.

    PubMed

    Candel, Sergio; Sepulcre, María P; Espín-Palazón, Raquel; Tyrkalska, Sylwia D; de Oliveira, Sofía; Meseguer, José; Mulero, Victoriano

    2015-06-01

    TLR4 was the first TLR family member identified in mammals and is responsible for the activation of the immune response by bacterial LPS. Later, MD1 and RP105 were shown to form complexes that directly interact with the MD2-TLR4 complex, acting as physiological negative regulators of LPS signaling. Despite the general conservation of various TLR families from fish to mammals, several differences can be appreciated, such as the high tolerance of fish to LPS, the absence of the crucial accessory molecules Md2 and Cd14 for Tlr4 signaling in fish, the absence of Tlr4 in some fish species, and the confirmation that LPS does not signal through Tlr4 in zebrafish. The present study has identified the Rp105 and Md1 homologs in zebrafish, confirming (i) Rp105 and Tlr4 evolved from a common ancestor before the divergence between fish and tetrapods and (ii) the presence of Md1 in teleost fish and the lack of Md2, suggesting that the divergence of these accessory molecules occurred in the tetrapod lineage. Biochemical and functional studies indicate that Md1 binds both Rp105 and Tlr4 in zebrafish. Genetic inhibition of zebrafish Md1 and Rp105 reveals that Md1 or Rp105 deficiency impairs the expression of genes encoding pro-inflammatory and antiviral molecules, leading to increased susceptibility to viral infection. These results shed light on the evolutionary history of Md1 and Rp105 and uncover a previously unappreciated function of these molecules in the regulation of innate immunity. PMID:25681741

  16. Hemodialysis access - self care

    MedlinePlus

    Kidney failure - chronic-hemodialysis access; Renal failure - chronic-hemodialysis access; Chronic renal insufficiency - hemodialysis access; Chronic kidney failure - hemodialysis access; Chronic renal failure - ...

  17. Expanding Access

    ERIC Educational Resources Information Center

    Roach, Ronald

    2007-01-01

    There is no question that the United States lags behind most industrialized nations in consumer access to broadband Internet service. For many policy makers and activists, this shortfall marks the latest phase in the struggle to overcome the digital divide. To remedy this lack of broadband affordability and availability, one start-up firm--with…

  18. Access Denied

    ERIC Educational Resources Information Center

    Raths, David

    2012-01-01

    As faculty members add online and multimedia elements to their courses, colleges and universities across the country are realizing that there is a lot of work to be done to ensure that disabled students (and employees) have equal access to course material and university websites. Unfortunately, far too few schools consider the task a top priority.…

  19. Easy Access

    ERIC Educational Resources Information Center

    Gettelman, Alan

    2009-01-01

    School and university restrooms, locker and shower rooms have specific ADA accessibility requirements that serve the needs of staff, students and campus visitors who are disabled as a result of injury, illness or age. Taking good care of them is good for the reputation of a sensitive community institution, and fosters positive public relations.…

  20. 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

    2016-04-01

    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. PMID:26208676

  1. Electroporation of archaeal lipid membranes using MD simulations.

    PubMed

    Polak, Andraž; Tarek, Mounir; Tomšič, Matija; Valant, Janez; Ulrih, Nataša Poklar; Jamnik, Andrej; Kramar, Peter; Miklavčič, Damijan

    2014-12-01

    Molecular dynamics (MD) simulations were used to investigate the electroporation of archaeal lipid bilayers when subjected to high transmembrane voltages induced by a charge imbalance, mimicking therefore millisecond electric pulse experiments. The structural characteristics of the bilayer, a 9:91 mol% 2,3-di-O-sesterterpanyl-sn-glicerol-1-phospho-myo-inositol (AI) and 2,3-di-O-sesterterpanyl-sn-glicerol-1-phospho-1'(2'-O-α-D-glucosyl)-myo-inositol (AGI) were compared to small angle X-ray scattering data. A rather good agreement of the electron density profiles at temperatures of 298 and 343 K was found assessing therefore the validity of the protocols and force fields used in simulations. Compared to dipalmitoyl-phosphatidylcholine (DPPC), the electroporation threshold for the bilayer was found to increase from ~2 V to 4.3 V at 323 K, and to 5.2 V at 298 K. Comparing the electroporation thresholds of the archaeal lipids to those of simple diphytanoyl-phosphatidylcholine (DPhPC) bilayers (2.5 V at 323 K) allowed one to trace back the stability of the membranes to the structure of their lipid head groups. Addition of DPPC in amounts of 50 mol% to the archaeal lipid bilayers decreases their stability and lowers the electroporation thresholds to 3.8 V and 4.1 V at respectively 323 and 298 K. The present study therefore shows how membrane compositions can be selected to cover a wide range of responses to electric stimuli. This provides new routes for the design of liposomes that can be efficiently used as drug delivery carriers, as the selection of their composition allows one to tune in their electroporation threshold for subsequent release of their load. PMID:24461702

  2. The channels of Mars

    NASA Technical Reports Server (NTRS)

    Baker, Victor R.

    1988-01-01

    The geomorphology of Mars is discussed, focusing on the Martian channels. The great flood channels of Mars, the processes of channel erosion, and dendritic channel networks, are examined. The topography of the Channeled Scabland region of the northwestern U.S. is described and compared to the Martian channels. The importance of water in the evolution of the channel systems is considered.

  3. Starburst Channels

    NASA Technical Reports Server (NTRS)

    2007-01-01

    [figure removed for brevity, see original site] Figure 1

    Translucent carbon dioxide ice covers the polar regions of Mars seasonally. It is warmed and sublimates (evaporates) from below, and escaping gas carves a numerous channel morphologies.

    In this example (figure 1) the channels form a 'starburst' pattern, radiating out into feathery extensions. The center of the pattern is being buried with dust and new darker dust fans ring the outer edges. This may be an example of an expanding morphology, where new channels are formed as the older ones fill and are no longer efficiently channeling the subliming gas out.

    Observation Geometry Image PSP_003443_0980 was taken by the High Resolution Imaging Science Experiment (HiRISE) camera onboard the Mars Reconnaissance Orbiter spacecraft on 21-Apr-2007. The complete image is centered at -81.8 degrees latitude, 76.2 degrees East longitude. The range to the target site was 247.1 km (154.4 miles). At this distance the image scale is 24.7 cm/pixel (with 1 x 1 binning) so objects 74 cm across are resolved. The image shown here has been map-projected to 25 cm/pixel. The image was taken at a local Mars time of 04:52 PM and the scene is illuminated from the west with a solar incidence angle of 71 degrees, thus the sun was about 19 degrees above the horizon. At a solar longitude of 223.4 degrees, the season on Mars is Northern Autumn.

  4. 78 FR 77074 - Accessibility of User Interfaces, and Video Programming Guides and Menus; Accessible Emergency...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-20

    ... COMMISSION 47 CFR Part 79 Accessibility of User Interfaces, and Video Programming Guides and Menus... authority for requiring MVPDs to ensure that video programming guides and menus that ] provide channel and... video programming guides and menus that provide channel and program information include high...

  5. Expression profiles of MdACS3 gene suggest function as an accelerator of apple (Malus x domestica) fruit ripening.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ethylene plays an important role in diverse physiological and developmental processes of plants. Ethylene is synthesized by a short pathway and catalyzed by two enzymes, i.e. ACS and ACO. In apple fruit tissues, at least two ACS genes, MdACS1 and MdACS3, are expressed. While MdACS1 expresses only at...

  6. Chemotherapy for bone sarcomas in adults: the MD anderson experience.

    PubMed

    Benjamin, Robert S; Wagner, Michael J; Livingston, J Andrew; Ravi, Vinod; Patel, Shreyaskumar R

    2015-01-01

    Increasing age is an adverse prognostic factor in the treatment of primary bone tumors. There are few published data on treatment of primary bone tumors in adults. This paper presents data from the Department of Sarcoma Medical Oncology at The University of Texas MD Anderson Cancer Center, summarizing our treatment results. To treat primary osteosarcoma, we used 90 mg/m2 of doxorubicin as a continuous intravenous infusion over 48 to 96 hours and 120 to 160 mg/m2 of cisplatin intravenously or intra-arterially. Initially, we found a marked difference in postoperative continuous disease-free survival (CDFS) between those with 90% or greater (i.e., good response) tumor necrosis and those with less than 90% (i.e., poor response) tumor necrosis. The sequential addition of high-dose methotrexate and ifosfamide to patients with poorly responding disease improved their CDFS to that of patients with good response. Older patients and those who have tumors with variant histology have inferior outcomes. Evaluation of subsequent patients revealed similar outcomes for those with good or poor response to induction therapy, supporting our practice of adaptation of postoperative chemotherapy to the results of preoperative chemotherapy. PET-CT is the best imaging modality to screen for a response with tumors inside bone. To treat Ewing sarcoma, we have employed 2 mg of vincristine, 75 to 90 mg/m2 of doxorubicin as a 72-hour infusion, and 2.5 g/m2 of ifosfamide over 3 hours daily for 4 doses (i.e., vincristine, doxorubicin, and ifosfamide [VAI]). Preliminary analysis indicates a higher CDFS when adjusted for patient age than seen with the standard alternating regimen used in pediatrics. A screening MRI of the pelvis and spine can detect subtle metastatic disease in bone or bone marrow that is missed by other imaging modalities or blind biopsy. Chondrosarcoma is treated surgically or on investigational protocols. Giant cell tumor of bone is usually managed surgically, but multiple

  7. The core competencies of James Marion Sims, MD.

    PubMed

    Straughn, J Michael; Gandy, Roy E; Rodning, Charles B

    2012-07-01

    The concept of core competencies in graduate medical education was introduced by the Accreditation Council for Graduate Medical Education of the American Medical Association to semiquantitatively assess the professional performance of students, residents, practitioners, and faculty. Many aspects of the career of J. Marion Sims, MD, are exemplary of those core competencies: MEDICAL KNOWLEDGE: Author of the first American textbook related to gynecology. MEDICAL CARE: Innovator of the Sims' Vaginal Speculum, Sims' Position, Sims' Test, and vesico-/rectovaginal fistulorrhaphy; advocated abdominal exploration for penetrating wounds; performed the first cholecystostomy. PROFESSIONALISM: Served as President of the New York Academy of Medicine, the American Medical Association, and the American Gynecologic Society. INTERPERSONAL RELATIONSHIPS/COMMUNICATION: Cared for the indigent, hearthless, indentured, disenfranchised; served as consulting surgeon to the Empress Eugénie (France), the Duchess of Hamilton (Scotland), the Empress of Austria, and other royalty of the aristocratic Houses of Europe; accorded the National Order of the Legion of Honor. PRACTICE-BASED LEARNING: Introduction of silver wire sutures; adoption of the principles of asepsis/antisepsis; adoption of the principles of general anesthesia. SYSTEMS-BASED PRACTICE: Established the Woman's Hospital, New York City, New York, the predecessor of the Memorial Sloan-Kettering Center for the Treatment of Cancer and Allied Diseases; organized the Anglo-American Ambulance Corps under the patronage of Napoleon III. What led him to a life of clinical and humanitarian service? First, he was determined to succeed. His formal medical/surgical education was perhaps the best available to North Americans during that era. Second, he was courageous in experimentation and innovation, applying new developments in operative technique, asepsis/antisepsis, and general anesthesia. Third, his curiosity was not burdened by rigid

  8. Hemodialysis access procedures

    MedlinePlus

    Kidney failure - chronic-dialysis access; Renal failure - chronic-dialysis access; Chronic renal insufficiency-dialysis access; Chronic kidney failure-dialysis access; Chronic renal failure-dialysis access

  9. 75 FR 70126 - Safety Zone; Fireworks Displays, Potomac River, National Harbor, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-17

    ..., Potomac River, National Harbor, MD'' in the Federal Register (75 FR 169). We received one comment on the...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. FOR...

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

    PubMed Central

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

    2013-01-01

    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. PMID:26462530

  11. 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

    2013-01-01

    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. PMID:26462530

  12. 78 FR 19009 - Gary Alfred Shearer, M.D.; Decision And Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-28

    ... proceeding under section 304, 21 U.S.C. 824, of the CSA.'' Zhiwei Lin, 77 FR 18862, 18864 (2012) (citing... Kentucky, not Florida.) \\16\\ See Michael G. Dolin, M.D., 65 FR 5661 (2000); see also Philip E. Kirk, M.D., 48 FR 32887 (1983), aff'd sub nom. Kirk v. Mullen, 749 F.2d 297 (6th Cir. 1984). \\17\\ See 28...

  13. 78 FR 19012 - Pawan Kumar Jain, M.D.; Decision And Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-28

    .... Edwards, M.D., 75 FR 49,991 (DEA 2010); Joseph Baumstarck, M.D., 74 FR 17,525 (DEA 2009). In this case... practice medicine, his DEA registration must be revoked. See 21 U.S.C. 824(a)(3); Edwards, 75 FR 49,991; Baumstarck, 74 FR 17,525. \\4\\ In Respondent's January 16, 2012 Request for Hearing, he contends that he has...

  14. Practical Password Recovery Attacks on MD4 Based Prefix and Hybrid Authentication Protocols

    NASA Astrophysics Data System (ADS)

    Sasaki, Yu; Wang, Lei; Ohta, Kazuo; Aoki, Kazumaro; Kunihiro, Noboru

    In this paper, we present practical password recovery attacks against two challenge and response authentication protocols using MD4. For attacks on protocols, the number of queries is one of the most important factors because the opportunity where an attacker can ask queries is very limited in real protocols. When responses are computed as MD4(Password||Challenge), which is called prefix approach, previous work needs to ask 237 queries to recover a password. Asking 237 queries in real protocols is almost impossible. In our attack, to recover up to 8-octet passwords, we only need 1 time the amount of eavesdropping, 17 queries, and 234 MD4 off-line computations. To recover up to 12-octet passwords, we only need 210 times the amount of eavesdropping, 210 queries, and 241 off-line MD4 computations. When responses are computed as MD4(Password||Challenge||Password), which is called hybrid approach, previous work needs to ask 263 queries, while in our attack, up to 8-octet passwords are practically recovered by 28 times the amount of eavesdropping, 28 queries, and 239 off-line MD4 computations. Our idea is guessing a part of passwords so that we can simulate values of intermediate chaining variables from observed hash values. This enables us to use a short local collision that occurs with a very high probability, and thus the number of queries becomes practical.

  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. 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

  17. Comparative Global Gene Expression Profiling Between rMd5- and rMd5deltaMeq-Infected Chickens: Host-Pathogen Interaction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease virus (MDV), an oncogenic alpha-herpesvirus, is the etiological agent of Marek’s disease (MD), a highly contagious lymphoproliferative disease of domestic chickens. MDV encodes a basic leucine zipper protein, meq (MDV Eco Q), which is homologous to the Jun/Fos family of transcriptio...

  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. The Channel Acquisition Slot Protocol

    NASA Astrophysics Data System (ADS)

    Milian, Arturo Valencia; Tamura, Shinsuke; Yanase, Tatsuro

    This paper discusses the Channel Acquisition Slot Protocol (CASP), a new protocol for the Media Access Control (MAC) of wireless networks. The CASP is intended to provide a more efficient use of communication channels; this is achieved by mechanisms for eliminating contentions among network stations and by an implicit handling of acknowledge messages. To avoid collisions of messages, the protocol divides the time into short slots, each of which is assigned to a single station, and any station must wait its own slot to start its transmission. However once a transmission is started the slot can be extended and no other station can make use of the channel. The use of an implicit acknowledge mechanism removes the necessity of an acknowledge message exchange for every transmission. In various simulated scenarios the CASP shows a 25% better throughput efficiency compared with the one of the IEEE802.11 protocol.

  20. Localization of Millisecond Dynamics: Dihedral Entropy from Accelerated MD.

    PubMed

    Kamenik, Anna S; Kahler, Ursula; Fuchs, Julian E; Liedl, Klaus R

    2016-08-01

    Here, we demonstrate a method to capture local dynamics on a time scale 3 orders of magnitude beyond state-of-the-art simulation approaches. We apply accelerated molecular dynamics simulations for conformational sampling and extract reweighted backbone dihedral distributions. Local dynamics are characterized by torsional probabilities, resulting in residue-wise dihedral entropies. Our approach is successfully validated for three different protein systems of increasing size: alanine dipeptide, bovine pancreatic trypsin inhibitor (BPTI), and the major birch pollen allergen Bet v 1a. We demonstrate excellent agreement of flexibility profiles with both large-scale computer simulations and NMR experiments. Thus, our method provides efficient access to local protein dynamics on extended time scales of high biological relevance. PMID:27322931

  1. Localization of Millisecond Dynamics: Dihedral Entropy from Accelerated MD

    PubMed Central

    2016-01-01

    Here, we demonstrate a method to capture local dynamics on a time scale 3 orders of magnitude beyond state-of-the-art simulation approaches. We apply accelerated molecular dynamics simulations for conformational sampling and extract reweighted backbone dihedral distributions. Local dynamics are characterized by torsional probabilities, resulting in residue-wise dihedral entropies. Our approach is successfully validated for three different protein systems of increasing size: alanine dipeptide, bovine pancreatic trypsin inhibitor (BPTI), and the major birch pollen allergen Bet v 1a. We demonstrate excellent agreement of flexibility profiles with both large-scale computer simulations and NMR experiments. Thus, our method provides efficient access to local protein dynamics on extended time scales of high biological relevance. PMID:27322931

  2. Quantum internet using code division multiple access.

    PubMed

    Zhang, Jing; Liu, Yu-xi; Ozdemir, Sahin 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

  3. Quantum internet using code division multiple access

    NASA Astrophysics Data System (ADS)

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

    2013-07-01

    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.

  4. 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.

  5. Quantum channel capacities: Multiparty communication

    NASA Astrophysics Data System (ADS)

    Demianowicz, Maciej; Horodecki, Paweł

    2006-10-01

    We analyze different aspects of multiparty communication over quantum memoryless channels and generalize some of the key results known from bipartite channels to the multiparty scenario. In particular, we introduce multiparty versions of subspace and entanglement transmission fidelities. We also provide alternative, local, versions of fidelities and show their equivalence to the global ones in context of capacity regions defined. An equivalence of two different capacity notions with respect to two types of fidelities is proven. In analogy to the bipartite case it is shown, via sufficiency of isometric encoding theorem, that additional classical forward side channel does not increase capacity region of any quantum channel with k senders and m receivers which represents a compact unit of general quantum networks theory. The result proves that recently provided capacity region of a multiple access channel [M. Horodecki , Nature 436, 673 (2005); J. Yard , e-print quant-ph/0501045], is optimal also in a scenario of an additional support of forward classical communication.

  6. An unusual dimeric structure and assembly for TLR4 regulator RP105-MD-1

    SciTech Connect

    Yoon, Sung-il; Hong, Minsun; Wilson, Ian A

    2011-11-16

    RP105-MD-1 modulates the TLR4-MD-2-mediated, innate immune response against bacterial lipopolysaccharide (LPS). The crystal structure of the bovine 1:1 RP105-MD-1 complex bound to a putative endogenous lipid at 2.9 Å resolution shares a similar overall architecture to its homolog TLR4-MD-2 but assembles into an unusual 2:2 homodimer that differs from any other known TLR-ligand assembly. The homodimer is assembled in a head-to-head orientation that juxtaposes the N-terminal leucine-rich repeats (LRRs) of the two RP105 chains, rather than the usual tail-to-tail configuration of C-terminal LRRs in ligand-activated TLR dimers, such as TLR1-TRL2, TLR2-TLR6, TLR3-TLR3 and TLR4-TLR4. Another unusual interaction is mediated by an RP105-specific asparagine-linked glycan, which wedges MD-1 into the co-receptor binding concavity on RP105. This unique mode of assembly represents a new paradigm for TLR complexes and suggests a molecular mechanism for regulating LPS responses.

  7. 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. PMID:26695055

  8. Chosen-Prefix Collisions for MD5 and Colliding X.509 Certificates for Different Identities

    NASA Astrophysics Data System (ADS)

    Stevens, Marc; Lenstra, Arjen; de Weger, Benne

    We present a novel, automated way to find differential paths for MD5. As an application we have shown how, at an approximate expected cost of 250 calls to the MD5 compression function, for any two chosen message prefixes P and P', suffixes S and S' can be constructed such that the concatenated values P||S and P'||S' collide under MD5. Although the practical attack potential of this construction of chosen-prefix collisions is limited, it is of greater concern than random collisions for MD5. To illustrate the practicality of our method, we constructed two MD5 based X.509 certificates with identical signatures but different public keys and different Distinguished Name fields, whereas our previous construction of colliding X.509 certificates required identical name fields. We speculate on other possibilities for abusing chosen-prefix collisions. More details than can be included here can be found on www.win.tue.nl/hashclash/ChosenPrefixCollisions/.

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

    SciTech Connect

    Kylasa, S.B.; Aktulga, H.M.; Grama, A.Y.

    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 we 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.

  10. Molecular Dynamics/Order Parameter eXtrapolation (MD/OPX) for Bionanosystem Simulations

    PubMed Central

    Miao, Yinglong; Ortoleva, Peter J.

    2012-01-01

    A multiscale approach, Molecular Dynamics/Order Parameter eXtrapolation (MD/OPX), to the all-atom simulation of large bionanosystems is presented. The approach starts with the introduction of a set of order parameters (OPs) automatically generated with orthogonal polynomials to characterize the nanoscale features of bionanosystems. The OPs are shown to evolve slowly via Newton’s equations and the all-atom multiscale analysis (AMA) developed earlier1 demonstrates the existence of their stochastic dynamics, which serve as the justification for our MD/OPX approach. In MD/OPX, a short MD run estimates the rate of change of the OPs, which is then used to extrapolate the state of the system over time that is much longer than the 10−14 second timescale of fast atomic vibrations and collisions. The approach is implemented in NAMD and demonstrated on cowpea chlorotic mottle virus (CCMV) capsid structural transitions (STs). It greatly accelerates the MD code and its underlying all-atom description of the nanosystems enables the use of a universal inter-atomic force field, avoiding recalibration with each new application as needed for coarse-grained models. PMID:18636559

  11. 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.

  12. The roles of K(+) channels in cancer.

    PubMed

    Pardo, Luis A; Stühmer, Walter

    2014-01-01

    Potassium channels are transmembrane proteins that selectively facilitate the flow of potassium ions down an electrochemical gradient. These molecules have been studied in great detail in the context of cell excitability, but their roles in less cell type-specific functions, such as cell proliferation, angiogenesis or cell migration, have only recently been assessed. Moreover, the importance of these channels for tumour biology has become evident. This, coupled with the fact that they are accessible proteins and that their pharmacology is well characterized, has increased the interest in investigating potassium channels as therapeutic targets in cancer patients. PMID:24336491

  13. The protective efficacy of rMd5deltaMeq against challenge with a very virulent plus strain of MDV in relatively resistant lines of chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a T-cell lymphoma of domestic chickens induced by MD virus (MDV), a naturally oncogenic and highly contagious cell-associated alpha-herpesvirus. A recombinant MDV lacking both copies of Meq oncogene, rMd5deltaMeq, was tested as a candidate vaccine against MD in a series of 19...

  14. Dynamics and energetics of water permeation through the aquaporin channel.

    PubMed

    Vidossich, Pietro; Cascella, Michele; Carloni, Paolo

    2004-06-01

    Structural properties of water inside bovine aquaporin-1 are investigated by molecular simulation. The calculations, which are based on the recently determined X-ray structure at 2.2 A resolution (Sui et al., Nature 2001;414:872-878), are carried out on one monomeric subunit immersed in a water-n-octane-water bilayer. Molecular dynamics (MD) simulations suggest that His182, a fully conserved residue in the channel pore, is protonated in the delta position. Furthermore, they reveal a highly ordered water structure in the channel, induced by the electrostatic properties of the protein. Multiple-steering MD simulations are used to calculate the free-energy of water diffusion. To the best of our knowledge, this represents the first free-energy calculation based on the new, high-resolution structure of the pore. The calculated barrier is 2.5 kcal/mol, and it is associated to water permeation through the Asn-Pro-Ala (NPA) region of the pore, where water molecules are only hydrogen-bonded with themselves. These findings are fully consistent with those based on the previous MD studies on the human protein (de Groot and Grubmüller, Science 2001;294:2353-2357). PMID:15146490

  15. ICEPO: the ion channel electrophysiology ontology

    PubMed Central

    Hinard, V.; Britan, A.; Rougier, J.S.; Bairoch, A.; Abriel, H.; Gaudet, P.

    2016-01-01

    Ion channels are transmembrane proteins that selectively allow ions to flow across the plasma membrane and play key roles in diverse biological processes. A multitude of diseases, called channelopathies, such as epilepsies, muscle paralysis, pain syndromes, cardiac arrhythmias or hypoglycemia are due to ion channel mutations. A wide corpus of literature is available on ion channels, covering both their functions and their roles in disease. The research community needs to access this data in a user-friendly, yet systematic manner. However, extraction and integration of this increasing amount of data have been proven to be difficult because of the lack of a standardized vocabulary that describes the properties of ion channels at the molecular level. To address this, we have developed Ion Channel ElectroPhysiology Ontology (ICEPO), an ontology that allows one to annotate the electrophysiological parameters of the voltage-gated class of ion channels. This ontology is based on a three-state model of ion channel gating describing the three conformations/states that an ion channel can adopt: closed, open and inactivated. This ontology supports the capture of voltage-gated ion channel electrophysiological data from the literature in a structured manner and thus enables other applications such as querying and reasoning tools. Here, we present ICEPO (ICEPO ftp site: ftp://ftp.nextprot.org/pub/current_release/controlled_vocabularies/), as well as examples of its use. PMID:27055825

  16. ICEPO: the ion channel electrophysiology ontology.

    PubMed

    Hinard, V; Britan, A; Rougier, J S; Bairoch, A; Abriel, H; Gaudet, P

    2016-01-01

    Ion channels are transmembrane proteins that selectively allow ions to flow across the plasma membrane and play key roles in diverse biological processes. A multitude of diseases, called channelopathies, such as epilepsies, muscle paralysis, pain syndromes, cardiac arrhythmias or hypoglycemia are due to ion channel mutations. A wide corpus of literature is available on ion channels, covering both their functions and their roles in disease. The research community needs to access this data in a user-friendly, yet systematic manner. However, extraction and integration of this increasing amount of data have been proven to be difficult because of the lack of a standardized vocabulary that describes the properties of ion channels at the molecular level. To address this, we have developed Ion Channel ElectroPhysiology Ontology (ICEPO), an ontology that allows one to annotate the electrophysiological parameters of the voltage-gated class of ion channels. This ontology is based on a three-state model of ion channel gating describing the three conformations/states that an ion channel can adopt: closed, open and inactivated. This ontology supports the capture of voltage-gated ion channel electrophysiological data from the literature in a structured manner and thus enables other applications such as querying and reasoning tools. Here, we present ICEPO (ICEPO ftp site:ftp://ftp.nextprot.org/pub/current_release/controlled_vocabularies/), as well as examples of its use. PMID:27055825

  17. The Emerging Physician-Scientist Workforce: Demographic, Experiential, and Attitudinal Predictors of MD-PhD Program Enrollment

    PubMed Central

    Jeffe, Donna B.; Andriole, Dorothy A.; Wathington, Heather D.; Tai, Robert H.

    2014-01-01

    Purpose MD-PhD scientists are a very successful, but small and fairly homogenous group of biomedical researchers. The authors conducted a retrospective cohort study to identify predictors of MD-PhD program enrollment to inform the development of evidence-based strategies to increase the size and diversity of the biomedical research workforce. Method Using de-identified data from all 2001–2006 Pre-Medical College Admission Test Questionnaire (PMQ) respondents, the authors developed multivariate logistic regression models to identify the demographic, experiential, and attitudinal variables associated with MD-PhD program enrollment at matriculation compared with all other MD program enrollment at matriculation and with not enrolling in medical school by August 2012. Results Of 207,436 PMQ respondents with complete data for all variables of interest, 2,575 (1.2%) were MD-PhD program enrollees, 80,856 (39.0%) were other MD program enrollees, and 124,005 (59.8%) were non-medical school matriculants. Respondents who were black (vs. white), high school and college laboratory research apprenticeship participants, and highly endorsed the importance of research/finding cures as reasons to study medicine were more likely to be MD-PhD program enrollees, whereas respondents who highly endorsed the status of medicine as a reason to study medicine were less likely to be MD-PhD program enrollees than either other MD program enrollees or non-medical school matriculants. Conclusions MD-PhD program directors appear to be successful in enrolling students whose attitudes and interests align with MD-PhD program goals. Continued efforts are needed to promote MD-PhD workforce diversity and the value of both high school and college research apprenticeships for students considering careers as physician-scientists. PMID:25006709

  18. An MD2 Hot-Spot Mimicking Peptide that Suppresses TLR4-Mediated Inflammatory Response In Vitro and In Vivo

    PubMed Central

    Liu, Liping; Ghosh, Nilanjan; Slivka, Peter F.; Fiorini, Zeno; Hutchinson, Mark R.; Watkins, Linda R.

    2012-01-01

    A truncated peptide was shown to retain the structure of the TLR4-binding hot-spot region of MD2, disrupting with the TLR4/MD2 interactions. The peptide not only demonstrated strong binding affinity in the fluorescence polarization assay, but also showed high specificity in macrophage cells. Furthermore, MD2-I was able to suppress neuropathic pain in animal models. PMID:21678541

  19. Relationships among Land-Use, In-Stream Stressors, and Biological Condition in Prince George's County, MD

    NASA Astrophysics Data System (ADS)

    Lessard, J. L.; Stribling, S.; Leppo, E.

    2005-05-01

    As human disturbance increases in watersheds there is a resulting change in hydrologic stability that leads to alterations of in-stream habitat conditions. These in-stream alterations are called stressors because they represent sub-optimal to lethal conditions for aquatic organisms. The linkages and mechanisms that relate multiple stressors with complex landscape features (sources) are currently the focus of research across North America. The objective of this project was to illustrate the linkages and biological responses for coastal plain watersheds that contain a gradient of severity and types of human disturbance. Stepwise multiple-regression was performed on a routine biological monitoring database from Prince George's County, MD. Results demonstrated that urban land-use sources (medium-density residential, commercial, and industrial) and in-stream stressors of reduced physical habitat complexity (e.g., decreased gravel substrate, reduced channel sinuosity etc.) were most related to biological degradation. The biological response variables that had the strongest relationships with these sources and stressors were: the indexes of biotic integrity, EPT Index, Beck's Biotic Index, % Dominant Fish Species, and % generalists, omnivores, and invertivores. These types of analyses need to be conducted in a variety of ecoregions to understand the dynamics of the relationship between human disturbance and the biological condition of streams.

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

    SciTech Connect

    Laganapan, A. M. K.; Videcoq, A. Bienia, M.; Ala-Nissila, T.; Bochicchio, D.; Ferrando, R.

    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.

  1. Study on the structure of Bayer liquor with spectroscopy and MD simulation

    NASA Astrophysics Data System (ADS)

    Chen, Yun; Feng, Qiming; Liu, Kun; Chen, Yuandao; Zhang, Guofan

    2006-05-01

    The combination of spectroscopy analysis (Raman and IR) and MD simulation was applied to explore the structure characters of Bayer liquor. In this work, MD simulation had been used to probe the nature of sodium metal-aluminate ion pairing and its role in the stabilization of clusters. It was found that the maximum concentration of Al(OH)4- occurs in low caustic solutions, but in high caustic solution, the appearance of Al(OH)63- was found. Results of molecular dynamic simulation indicated that the formation of clustering of aluminates in solution, and the clusters stabilized by sodium ions made a contribution to the formation of polyaluminate.

  2. Simulating picosecond X-ray diffraction from crystals using FFT methods on MD output

    SciTech Connect

    Kimminau, Giles; Nagler, Bob; Higginbotham, Andrew; Murphy, William; Wark, Justin; Park, Nigel; Hawreliak, James; Kalantar, Dan; Lorenzana, Hector; Remington, Bruce

    2007-12-12

    Multi-million atom non-equilibrium molecular dynamics (MD) simulations give significant insight into the transient processes that occur under shock compression. Picosecond X-ray diffraction enables the probing of materials on a timescale fast enough to test such effects. In order to simulate diffraction patterns, Fourier methods are required to gain a picture of reciprocal lattice space. We present here results of fast Fourier transforms of atomic coordinates of shocked crystals simulated by MD, and comment on the computing power required as a function of problem size. The relationship between reciprocal space and particular experimental geometries is discussed.

  3. 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.

  4. 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. PMID:23022687

  5. Regulation of channel function due to physical energetic coupling with a lipid bilayer

    SciTech Connect

    Ashrafuzzaman, Md.; Tseng, C.-Y.; Tuszynski, J.A.

    2014-03-07

    Highlights: • Lipid membrane regulation of membrane protein functions has been addressed. • Energetics behind ion channel-membrane coupling phenomena has been investigated. • Charge based interactions stabilize peptide–lipid complex. • Screened Coulomb interaction model explains the energetics. • Van der Waals and electrostatic forces drive peptides and lipids to close proximity. - Abstract: Regulation of membrane protein functions due to hydrophobic coupling with a lipid bilayer has been investigated. An energy formula describing interactions between lipid bilayer and integral ion channels with different structures, which is based on the screened Coulomb interaction approximation, has been developed. Here the interaction energy is represented as being due to charge-based interactions between channel and lipid bilayer. The hydrophobic bilayer thickness channel length mismatch is found to induce channel destabilization exponentially while negative lipid curvature linearly. Experimental parameters related to channel dynamics are consistent with theoretical predictions. To measure comparable energy parameters directly in the system and to elucidate the mechanism at an atomistic level we performed molecular dynamics (MD) simulations of the ion channel forming peptide–lipid complexes. MD simulations indicate that peptides and lipids experience electrostatic and van der Waals interactions for short period of time when found within each other’s proximity. The energies from these two interactions are found to be similar to the energies derived theoretically using the screened Coulomb and the van der Waals interactions between peptides (in ion channel) and lipids (in lipid bilayer) due to mainly their charge properties. The results of in silico MD studies taken together with experimental observable parameters and theoretical energetic predictions suggest that the peptides induce ion channels inside lipid membranes due to peptide–lipid physical interactions

  6. 47 CFR 76.971 - Commercial leased access terms and conditions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... access terms and conditions. (a)(1) Cable operators shall place leased access programmers that request... select from among leased access programmers using objective, content-neutral criteria. (4) Cable... a channel already carrying an existing full-time non-leased access programmer, the operator does...

  7. 47 CFR 76.971 - Commercial leased access terms and conditions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... access terms and conditions. (a)(1) Cable operators shall place leased access programmers that request... select from among leased access programmers using objective, content-neutral criteria. (4) Cable... a channel already carrying an existing full-time non-leased access programmer, the operator does...

  8. 47 CFR 76.971 - Commercial leased access terms and conditions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... access terms and conditions. (a)(1) Cable operators shall place leased access programmers that request... select from among leased access programmers using objective, content-neutral criteria. (4) Cable... a channel already carrying an existing full-time non-leased access programmer, the operator does...

  9. 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.

  10. The Discovery Channel Telescope

    NASA Astrophysics Data System (ADS)

    Millis, R. L.; Dunham, E. W.; Sebring, T. A.; Smith, B. W.; de Kock, M.; Wiecha, O.

    2004-11-01

    The Discovery Channel Telescope (DCT) is a 4.2-m telescope to be built at a new site near Happy Jack, Arizona. The DCT features a large prime focus mosaic CCD camera with a 2-degree-diameter field of view especially designed for surveys of KBOs, Centaurs, NEAs and other moving or time-variable targets. The telescope can be switched quickly to a Ritchey-Chretien configuration for optical/IR spectroscopy or near-IR imaging. This flexibility allows timely follow-up physical studies of high priority objects discovered in survey mode. The ULE (ultra-low-expansion) meniscus primary and secondary mirror blanks for the telescope are currently in fabrication by Corning Glass. Goodrich Aerospace, Vertex RSI, M3 Engineering and Technology Corp., and e2v Technologies have recently completed in-depth conceptual design studies of the optics, mount, enclosure, and mosaic focal plane, respectively. The results of these studies were subjected to a formal design review in July, 2004. Site testing at the 7760-ft altitude Happy Jack site began in 2001. Differential image motion observations from 117 nights since January 1, 2003 gave median seeing of 0.84 arcsec FWHM, and the average of the first quartile was 0.62 arcsec. The National Environmental Policy Act (NEPA) process for securing long-term access to this site on the Coconino National Forest is nearing completion and ground breaking is expected in the spring of 2005. The Discovery Channel Telescope is a project of the Lowell Observatory with major financial support from Discovery Communications, Inc. (DCI). DCI plans ongoing television programming featuring the construction of the telescope and the research ultimately undertaken with the DCT. An additional partner can be accommodated in the project. Interested parties should contact the lead author.

  11. 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

    2015-07-01

    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

  12. 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

  13. 47 CFR 76.1505 - Public, educational and governmental access.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...) If an open video system operator maintains an institutional network, as defined in Section 611(f) of... access channels be designated on that institutional network to the extent such channels are designated on the institutional network of the local cable operator. (f) An open video system operator shall...

  14. Membrane association of the PTEN tumor suppressor: Neutron scattering and MD simulations reveal the structure of protein-membranes complexes

    PubMed Central

    Nanda, Hirsh; Heinrich, Frank; Lösche, Mathias

    2014-01-01

    Neutron reflection (NR) from planar interfaces is an emerging technology that provides unique and otherwise inaccessible structural information on disordered molecular systems such as membrane proteins associated with fluid bilayers, thus addressing one of the remaining challenges of structural biology. Although intrinsically a low-resolution technique, using structural information from crystallography or NMR allows the construction of NR models that describe the architecture of protein-membrane complexes at high resolution. In addition, a combination of these methods with molecular dynamics (MD) simulations has the potential to reveal the dynamics of protein interactions with the bilayer in atomistic detail. We review recent advances in this area by discussing the application of these techniques to the complex formed by the PTEN phosphatase with the plasma membrane. These studies provide insights in the cellular regulation of PTEN, its interaction with PI(4,5)P2 in the inner plasma membrane and the pathway by which its substrate, PI(3,4,5)P3, accesses the PTEN catalytic site. PMID:25461777

  15. Unraveling the Conformational Landscape of Ligand Binding to Glucose/Galactose-Binding Protein by Paramagnetic NMR and MD Simulations.

    PubMed

    Unione, Luca; Ortega, Gabriel; Mallagaray, Alvaro; Corzana, Francisco; Pérez-Castells, Javier; Canales, Angeles; Jiménez-Barbero, Jesús; Millet, Oscar

    2016-08-19

    Protein dynamics related to function can nowadays be structurally well characterized (i.e., instances obtained by high resolution structures), but they are still ill-defined energetically, and the energy landscapes are only accessible computationally. This is the case for glucose-galactose binding protein (GGBP), where the crystal structures of the apo and holo states provide structural information for the domain rearrangement upon ligand binding, while the time scale and the energetic determinants for such concerted dynamics have been so far elusive. Here, we use GGBP as a paradigm to define a functional conformational landscape, both structurally and energetically, by using an innovative combination of paramagnetic NMR experiments and MD simulations. Anisotropic NMR parameters induced by self-alignment of paramagnetic metal ions was used to characterize the ensemble of conformations adopted by the protein in solution while the rate of interconversion between conformations was elucidated by long molecular dynamics simulation on two states of GGBP, the closed-liganded (holo_cl) and open-unloaded (apo_op) states. Our results demonstrate that, in its apo state, the protein coexists between open-like (68%) and closed-like (32%) conformations, with an exchange rate around 25 ns. Despite such conformational heterogeneity, the presence of the ligand is the ultimate driving force to unbalance the equilibrium toward the holo_cl form, in a mechanism largely governed by a conformational selection mechanism. PMID:27219646

  16. 76 FR 77580 - Maryland Disaster #MD-00020 Declaration of Economic Injury

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-13

    ... ADMINISTRATION Maryland Disaster MD-00020 Declaration of Economic Injury AGENCY: U.S. Small Business Administration. ACTION: Notice. SUMMARY: This is a notice of an Economic Injury Disaster Loan (EIDL) declaration... of Disaster Assistance, U.S. Small Business Administration, 409 3rd Street SW., Suite...

  17. 75 FR 41789 - Special Local Regulations for Marine Events; Patuxent River, Solomons, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-19

    ... public dockets in the January 17, 2008, issue of the Federal Register (73 FR 3316). Public Meeting We do... for Marine Events; Patuxent River, Solomons, MD'' in the Federal Register (75 FR 111). The NPRM stated... positions: From latitude 38 19'45'' N, longitude 076 28'06'' W, thence to latitude 38 19'24'' N,...

  18. 77 FR 47279 - Special Local Regulations for Marine Events, Patuxent River; Solomons, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-08

    .... SUPPLEMENTARY INFORMATION: Table of Acronyms DHS Department of Homeland Security FR Federal Register NPRM Notice..., Solomons, MD'' in the Federal Register (77 FR 25649). We received no comments on the proposed rule. No... latitude 38 19'45'' N, longitude 076 28'06'' W, thence to latitude 38 19'24'' N, longitude 076 28'30''...

  19. 78 FR 38000 - Special Local Regulations; Marine Events, Spa Creek and Annapolis Harbor; Annapolis, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-25

    ...; Annapolis, MD'' in the Federal Register (78 FR 20066). The rulemaking concerned the Coast Guard's proposal... near the entrance of Spa Creek originating at latitude 38 58'40'' N, longitude 076 28'49'' W, thence south to latitude 38 58'32'' N, longitude 076 28'45'' W. The regulated area is bounded to the...

  20. 76 FR 52865 - Special Local Regulations for Marine Events; Patuxent River, Solomons, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ... Marine Events; Patuxent River, Solomons, MD'' in the Federal Register (76 FR 118). We received no... following positions: from latitude 38 19 45 N, longitude 076 28 06 W, thence to latitude 38 19 24 N, longitude 076 28 30 W, thence to latitude 38 18 32 N, longitude 076 28 14 W; and from latitude 38 17 38...

  1. 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. PMID:27152458

  2. 76 FR 9407 - Fraternity Federal Savings & Loan Association, Baltimore, MD; Approval of Conversion Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Office of Thrift Supervision Fraternity Federal Savings & Loan Association, Baltimore, MD; Approval of Conversion Application Notice is hereby given that on February 10, 2011, the Office of Thrift...

  3. 75 FR 18056 - Safety Zone; Fireworks Display, Patuxent River, Solomons Island Harbor, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ... Island Harbor, MD AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing a temporary safety zone upon specified waters of Solomons Island Harbor, a tributary of the... fireworks display launched from discharge barge located in Solomons Island, Calvert County, Maryland....

  4. 76 FR 53961 - Harold Edward Smith, M.D.; Revocation Of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... * * * are considered in the disjunctive.'' Robert A. Leslie, 68 FR 15227, 15230 (2003). I may rely on any... interpretation of the law.'' Id. at 772 (int. quotations and citations omitted). See also Craig H. Bammer, 73 FR...\\ See Kenneth Wayne Green, Jr., M.D., 59 FR 51453, 51454 (1994) (registrant's ``continued drug usage...

  5. PERSONAL EXPOSURE TO PM2.5 MASS AND TRACE ELEMENTS IN BALTIMORE, MD, USA

    EPA Science Inventory

    In a recent study, EPA found significant relationships between PM2.5 mass measurements at a community site and personal exposure samples in a Towson, MD retirement facility. This manuscript builds upon these results by evaluating the exposure relationships with the elemental c...

  6. 75 FR 49979 - Tony T. Bui, M.D.; Revocation of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ....'' Robert A. Leslie, M.D., 68 FR 15227, 15230 (2003). I ``may rely on any one or a combination of factors..., a human growth hormone, which the Food and Drug Administration has not approved for use in the... to Respondent's prescribing of human growth hormone including Jintropin, a substance which has...

  7. 76 FR 63117 - Carlos Gonzalez, M.D., Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-11

    ... From the Federal Register Online via the Government Publishing Office ] Vol. 76 Tuesday, No. 196 October 11, 2011 Part VII Department of Justice Drug Enforcement Administration Carlos Gonzalez, M.D., Decision and Order; Notice #0;#0;Federal Register / Vol. 76 , No. 196 / Tuesday, October 11, 2011 / Notices#0;#0; ] DEPARTMENT OF JUSTICE Drug...

  8. 76 FR 20008 - Notice of Temporary Concession Contract for Assateague Island National Seashore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... National Park Service Notice of Temporary Concession Contract for Assateague Island National Seashore, MD AGENCY: National Park Service, Interior. ACTION: Notice of proposed award of temporary concession... to 36 CFR 51.24, public notice is hereby given that the National Park Service proposes to award...

  9. 75 FR 31511 - Ideal Federal Savings Bank, Baltimore, MD; Approval of Conversion Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE TREASURY Office of Thrift Supervision Ideal Federal Savings Bank, Baltimore, MD; Approval of Conversion... application of Ideal Federal Savings Bank, Baltimore, Maryland, to convert to the stock form of...

  10. 75 FR 49992 - Peter W.S. Grigg, M.D.; Revocation of Registration

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ... * * * considered in the disjunctive.'' Robert A. Leslie, M.D., 68 FR 15227, 15230 (2003). I ``may rely on any one...). However, under Agency precedent, neither of these findings is dispositive. See Edmund Chein, 72 FR 6580, 6590 n.22 (2007); Mortimer B. Levin, 55 FR 8209, 8210 (1990). Moreover, the evidence with respect...

  11. 76 FR 19420 - Michael J. Aruta, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-07

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF JUSTICE Drug Enforcement Administration Michael J. Aruta, M.D.; Decision and Order On August 10, 2010, Administrative Law Judge (ALJ) John J. Mulrooney, II, issued the attached recommended decision.\\1\\ The Respondent did not file exceptions to the decision....

  12. Infant motion: detection (M:D) ratios for chromatically defined and luminance-defined moving stimuli.

    PubMed

    Dobkins, K R; Teller, D Y

    1996-10-01

    In order to assess the relative contributions of chromatic vs luminance information to motion processing in infants, we employed a motion:detection (M:D) paradigm. Stimuli consisted of 27 deg by 40 deg, 0.25 c/deg sinusoidal gratings moving at 22 deg/sec (5.6 Hz), and were either chromatically defined or luminance-defined. Contrast thresholds for direction-of-motion (M) were obtained using a directional eye movement technique. Contrast thresholds for detection (D) were obtained using forced-choice preferential looking. M:D threshold ratios were obtained for individual infant subjects, and results were compared to those of adults. As expected, adult M:D threshold ratios were near 1:1 for luminance-defined stimuli, but greater than 1:1 for chromatically defined stimuli. This suggests that, for adults, luminance-defined, but not chromatically defined, stimuli are detected by mechanisms labeled for direction of motion. By contrast, infant M:D ratios for chromatically and luminance-defined stimuli were approximately equal and close to 1:1, suggesting that, for infants, luminance- as well as chromatically defined stimuli are detected by mechanisms that are labeled for direction of motion. PMID:8944288

  13. 76 FR 9965 - Amendment of Class E Airspace and Revocation of Class E Airspace; Easton, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-23

    ... surface, and remove Class E airspace designated as an extension to Class D airspace at Easton, MD (75 FR... Executive Order 12866; (2) is not a ``significant rule'' under DOT Regulatory Policies and Procedures (44 FR... FR 9565, 3 CFR, 1959-1963 Comp., p. 389. Sec. 71.1 0 2. The incorporation by reference in 14 CFR...

  14. 76 FR 16823 - Robert L. Dougherty, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... prescribing of controlled substances to three patients. Id. (citing 60 FR 55047). More specifically, the Show... treatment record of Patient 1 could have ultimately jeopardized that patient's welfare.'' 60 FR at 55051. \\2... previously held a DEA Certificate of Registration as a practitioner. Robert L. Dougherty, Jr., M.D., 60...

  15. 75 FR 26993 - Alvin Darby, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-13

    ... factors are * * * considered in the disjunctive.'' Robert A. Leslie, M.D., 68 FR 15227, 15230 (2003). I... application under section 303. See The Lawsons, Inc., 72 FR 74334, 74337 (2007); Anthony D. Funches, 64 FR 14267, 14268 (1999); Alan R. Schankman, 63 FR 45260 (1998); Kuen H. Chen, 58 FR 65401, 65402...

  16. 76 FR 60873 - Jeffery M. Freesemann, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-30

    ... will not engage in future misconduct. Cf. Ronald Lynch, M.D., 75 FR 78745, 78749 (2010). Order Pursuant... evidence is the October 20, 2010 Decision and Order (Order) of the Medical Board of California (Medical.... In its Order, the Medical Board, adopting the recommended decision issued by the state...

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-16

    ... or revoked. David W. Wang, 72 FR 54297, 54298 (2007); Sheran Arden Yeates, 71 FR 39130, 39131 (2006); Dominick A. Ricci, 58 FR 51104, 51105 (1993); Bobby Watts, 53 FR 11919, 11920 (1988). Respondent's loss of... Enforcement Administration Hung Thien Ly, M.D.; Revocation of Registration On August 28, 2009, the...

  18. 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

    ...The Coast Guard is establishing a temporary safety zone on the navigable waters of the Atlantic Ocean in the vicinity of Ocean City, MD to support the Ocean City Air Show. This action is intended to restrict vessel traffic movement in the restricted area in order to protect mariners from the hazards associated with air show...

  19. 75 FR 18778 - Safety Zone; Ocean City Air Show 2010, Atlantic Ocean, Ocean City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-13

    ... public dockets in the January 17, 2008, issue of the Federal Register (73 FR 3316). Public Meeting We do... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; Ocean City Air Show 2010, Atlantic Ocean, Ocean City, MD AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast...

  20. 75 FR 60665 - Airworthiness Directives; McDonnell Douglas Corporation Model MD-90-30 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-01

    ... MD-90-30 airplanes. This proposed AD would require repetitive high frequency eddy current inspections... 17, 2010, describes procedures for doing repetitive high frequency eddy current (HFEC) inspections... Order 12866, 2. Is not a ``significant rule'' under the DOT Regulatory Policies and Procedures (44...

  1. 75 FR 12563 - Patuxent Research Refuge, Anne Arundel and Prince George's Counties, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-16

    ... Fish and Wildlife Service Patuxent Research Refuge, Anne Arundel and Prince George's Counties, MD... process for developing a CCP for Patuxent Research Refuge, in Anne Arundel and Prince George's Counties... the Patuxent and Little Patuxent Rivers between Washington, DC, and Baltimore, Maryland, the...

  2. 77 FR 61624 - Patuxent Research Refuge, Prince George's and Anne Arundel Counties, MD; Draft Comprehensive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-10

    ... Federal Register (75 FR 12563; March 16, 2010). Patuxent RR was established in 1936 by Executive Order by... Fish and Wildlife Service Patuxent Research Refuge, Prince George's and Anne Arundel Counties, MD... environmental assessment (CCP/EA) for Patuxent Research Refuge (Patuxent RR), located in Prince George's...

  3. 78 FR 68002 - Safety Zone for Fireworks Display, Baltimore Harbor, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ...The Coast Guard proposes to establish a temporary safety zone encompassing certain waters of Baltimore Harbor. This action is necessary to provide for the safety of life on navigable waters during a fireworks display launched from a barge located in Baltimore's Inner Harbor at Baltimore, MD on December 31, 2013. This safety zone is intended to protect the maritime public in a portion of......

  4. Novel plasmid conferring kanamycin and tetracycline resistance in turkey-derived Campylobacter jejuni strain 11601MD

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Campylobacter spp., resistance to the antibiotics kanamycin and tetracycline is frequently associated with plasmid-borne genes. However, relatively few plasmids of Campylobacter jejuni have been fully characterized to date. A novel plasmid (p11601MD; 44,095 bp.) harboring tet(O) was identified in...

  5. 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

    ... Federal Register (73 FR 3316). ] Public Meeting We do not now plan to hold a public meeting. But you may... SECURITY Coast Guard 33 CFR Part 165 RIN 1625-AA00 Safety Zone; 2012 Ocean City Air Show; Atlantic Ocean, Ocean City, MD AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast...

  6. 78 FR 62666 - Kenneth Harold Bull, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... factors are . . . considered in the disjunctive.'' Robert A. Leslie, M.D., 68 FR 15227, 15230 (2003). It... Krishna-Iyer, 74 FR 459, 462 (2009). Accordingly, as the Tenth Circuit has recognized, findings under a...-Jonesborough, 73 FR 364, 387 (2008) (citing cases)). Factor One--The Recommendation of the State...

  7. James McHenry, M.D. of Fort McHenry in Baltimore Towne.

    PubMed

    Miller, J M

    1992-05-01

    James McHenry, M.D., whose name is best known for the fort immortalized in the Star Spangled Banner, was one of the early members of Med Chi. In addition, he was secretary to George Washington; aide to Lafayette; member of the Maryland Senate, the General Assembly of Maryland, and the US Congress; and signer of the Constitution. PMID:1625535

  8. 75 FR 31835 - Environmental Impact Statement: Calvert and St. Mary's Counties, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-04

    ... Counties, Maryland (Federal Register Vol. 72, No. 203; FR Doc. 07-5190) is being withdrawn and an... Federal Highway Administration Environmental Impact Statement: Calvert and St. Mary's Counties, MD AGENCY... this notice to advise the public that a prior Notice of Intent to prepare an Environmental...

  9. Electrochemical endotoxin sensors based on TLR4/MD-2 complexes immobilized on gold electrodes.

    PubMed

    Yeo, Tae Yun; Choi, Ji Suk; Lee, Byung Kook; Kim, Beob Soo; Yoon, Hwa In; Lee, Hyeong Yun; Cho, Yong Woo

    2011-10-15

    Even low concentrations of endotoxins can be life-threatening. As such, continuous effort has been directed toward the development of sensitive and specific endotoxin detection systems. In this paper, we report the design and fabrication of a new electrochemical endotoxin sensor based on a human recombinant toll-like receptor 4 (rhTLR4) and myeloid differentiation-2 (MD-2) complex. The rhTLR4/MD-2 complex, which specifically binds to endotoxin, was immobilized on gold electrodes through a self-assembled monolayer (SAM) technique involving the use of dithiobis(succinimidyl undecanoate) (DSU). The surface topography of the electrodes at each fabrication stage was characterized with a nanosurface profiler and atomic force microscope (AFM). The electrochemical signals generated from interactions between the rhTLR4/MD-2 complex and the endotoxin were characterized by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). A linear relationship between the peak current and endotoxin concentration was obtained in the range of 0.0005 to 5 EU/mL with a correlation coefficient (R(2)) of 0.978. The estimated limit of detection (LOD) was fairly low, 0.0002 EU/mL. The rhTLR4/MD-2 based sensors exhibited no current responses to dipalmitoylphosphatidylcholine (DPPC) bearing two lipid chains, which is structurally similar to endotoxin, indicating the high specificity of the sensors to endotoxin. PMID:21816600

  10. 77 FR 64128 - Jose Gonzalo Zavaleta, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-18

    ... of the first Show Cause Order. See Jose Gonzalo Zavaleta, M.D., 76 FR 49506 (Aug. 10, 2011). Therein...., Alexandria, Louisiana. 76 FR 49506. However, on March 26, 2008, concurrent with Applicant's arrest on state... allowed.'' 76 FR at 49506. Upon receipt of this information, an undercover state trooper (UC1)...

  11. 76 FR 21406 - Michael J. Aruta, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... at 76 FR 19420 under the third column. Dated: April 8, 2011. Michele M. Leonhart, Administrator... Decision of the Administrative Law Judge (76 FR 19420). In preparing the document for publication, the... Enforcement Administration Michael J. Aruta, M.D.; Decision and Order ACTION: Correction. On Thursday, April...

  12. 76 FR 21406 - Cynthia M. Cadet, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... at 76 FR 19451 under the second column. Dated: April 8, 2011. Michele M. Leonhart, Administrator... Decision of the Administrative Law Judge (76 FR 19450). In preparing the document for publication, the... Enforcement Administration Cynthia M. Cadet, M.D.; Decision and Order ACTION: Correction. On Thursday, April...

  13. 76 FR 66968 - Abelardo E. Lecompte-Torres, M.D. Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-28

    ... registration. Steven B. Brown, 75 FR 65660, 65663 (2010) (citing John B. Freitas, 74 FR 17524, 17525 (2009)); Dominick A. Ricci, 58 FR 51104, 51105 (1993); Bobby Watts, 53 FR 11919, 11920 (1988). It is undisputed that... Enforcement Administration Abelardo E. Lecompte-Torres, M.D. Decision and Order On April 29, 2010, the...

  14. China eastern MD-11 mass casualty--expect the unexpected: a case report.

    PubMed

    Towne, L E

    1995-10-01

    On April 5, 1993, a China Eastern MD-11 underwent three violent pitch-up maneuvers, injuring over 100 passengers. The pilot made an emergency landing at 3:20 a.m. at Shemya, a tiny Aleutian Island with minimal medical facilities and personnel. The author describes their medical response, problems encountered and lessons learned. PMID:8526838

  15. Ab Initio ONIOM-Molecular Dynamics (MD) Study on the Deamination Reaction by Cytidine Deaminase

    SciTech Connect

    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 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-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.

  16. 77 FR 25592 - Safety Zone; Patapsco River, Northwest and Inner Harbors, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-01

    ...; Patapsco River, Northwest and Inner Harbors, Baltimore, MD'' in the Federal Register (77 FR 11434). We... Harbor during the movement of the historic sloop-of-war USS CONSTELLATION on May 24, 2012. This action is...-of-war USS CONSTELLATION in Baltimore, Maryland on May 24, 2012. Planned events include a three-...

  17. 77 FR 34998 - Darryl J. Mohr, M.D.; Affirmance of Immediate Suspension Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-12

    ... decision'' of the Agency as to whether to grant his application. See Scott C. Bickman, 76 FR 17694, 17701... doctrine. See Gov. Note. Regarding Resp.'s DEA Registration, at 1-2 (citing William Lockridge, 71 FR 77,791... entitled to be registered. See, e.g., Jovencio L. Raneses, M.D., 75 FR 11563 (2010). Moreover,...

  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. 76 FR 78695 - Barry M. Schultz, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-19

    ... Pain, 76 FR 52,715, 52717 (2006) (stating ``although DEA is the agency responsible for administering... ordered approximately 281,000 dosage units of oxycodone to be delivered to his pain management clinic in... 1 (citing 21 U.S.C. 801(21), 823(f), 824(a)(3); Layfe Robert Anthony, M.D., 67 FR 20,346...

  20. 76 FR 71371 - James L. Hooper, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ...); Shatz v. U.S. Dept. of Justice, 873 F.2d 1089, 1091 (8th Cir. 1989); Thomas E. Johnston, 45 FR 72311... decision in Anne Lazar Thorn, M.D., 62 FR 12847 (1997), stands for the proposition that the Agency's... this case. Id. at 2 (quoting 62 FR at 12848). Notwithstanding the implication of the above passage,...

  1. 76 FR 72837 - Amendment of Class D and Class E Airspace; Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-28

    ... Policies and Procedures (44 FR 11034; February 26, 1979); and (3) does not warrant preparation of a..., Baltimore, MD (76 FR 54153). Interested parties were invited to participate in this rulemaking effort by...: Authority: 49 U.S.C. 106(g); 40103, 40113, 40120; E.O. 10854, 24 FR 9565, 3 CFR, 1959-1963 Comp., p....

  2. 75 FR 11563 - Jovencio L. Raneses, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-11

    ... Carino, M.D., 72 FR 71955, 71956 (2007). Accordingly, his application for a new DEA registration must be... residence in San Marcos, California. GX B. Since that time, neither Respondent, nor anyone purporting to... practitioner, at the registered location of 1666 Garnet Avenue, 708, San Diego, California. GX E, at 1. On...

  3. 77 FR 45675 - Margy Temponeras, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-01

    ... encompasses the factors listed in Section 824(a).'' ALJ at 19 n.24 (citing Kuen H. Chen, M.D., 58 FR 65401... 21 U.S.C. 824(a).'' 58 FR at 65402. However, whether this constitutes a holding or merely dictum...., 40 FR 11918, 11919 (1975). See also John R. Amato, 40 FR 22852 (1975) (Denying application...

  4. 76 FR 71375 - Scott D. Fedosky, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... or otherwise engaged in an unlawful distribution to others. See Tony T. Bui, M.D., 75 FR 49979, 49989... FR 21931, 21932 (1988))), aff'd, Medicine Shoppe- Jonesborough v. DEA, 300 Fed. Appx. 409 (6th Cir.... Leslie, 68 FR 15227, 15230 (2003). I may rely on any one or a combination of factors and may give...

  5. 76 FR 21406 - Roni Dreszer, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... Decision of the Administrative Law Judge (76 FR 19434). In preparing the document for publication, the... at 76 FR 19437 under the second column. Dated: April 8, 2011. Michele M. Leonhart, Administrator... Enforcement Administration Roni Dreszer, M.D.; Decision and Order ACTION: Correction. On Thursday, April...

  6. 76 FR 21406 - Beau Boshers, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... Decision of the Administrative Law Judge (76 FR 19401). In preparing the document for publication, the... at 76 FR 19404 under the third column. Dated: April 8, 2011. Michele M. Leonhart, Administrator... Enforcement Administration Beau Boshers, M.D.; Decision and Order ACTION: Correction. On Thursday, April...

  7. 77 FR 36003 - Patrick K. Chau, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... do not establish a violation of 21 CFR 1306.04(a). But see George Mathew, M.D., 75 FR 66138, 66146.... Leslie, 68 FR 15227, 15230 (2003). I may rely on any one or a combination of factors and may give each... why he can be entrusted with a registration. Medicine Shoppe-Jonesborough, 73 FR 363, 380...

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... 304 of the CSA.' '' Hicham K. Riba, 73 FR 75773, 75774 (2008) (quoting Brenton D. Glisson, 72 FR 54296..., M.D., 66 FR 18305 (2001); Vincent J. Scolaro, 67 FR 42060 (2002)). Neither of these case support... a registration issued to a practitioner who lacks .' '' Id. at 3 (quoting Roy Chi Lung, 74 FR...

  9. 76 FR 21406 - Jacobo Dreszer, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-15

    ... Decision of the Administrative Law Judge (76 FR 19386). In preparing the document for publication, the... at 76 FR 19390 under the first column. Dated: April 8, 2011. Michele M. Leonhart, Administrator... Enforcement Administration Jacobo Dreszer, M.D.; Decision and Order ACTION: Correction. On Thursday, April...

  10. 76 FR 19401 - Beau Boshers, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF JUSTICE Drug Enforcement Administration Beau Boshers, M.D.; Decision and Order On August 10, 2010, Administrative Law Judge (ALJ) John J. Mulrooney, II, issued the attached recommended decision.\\1\\ Thereafter, Respondent filed exceptions to the decision. \\1\\...

  11. 77 FR 7182 - Scott W. Houghton, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-10

    ... Respondent lacks such state authority, both the plain language of applicable federal statutory provisions and... practitioner who lacks .'' Roy Chi Lung, 74 FR 20346, 20347 (2009); Scott Sandarg, D.M.D., 74 FR 17528, 174529 (2009); John B. Freitas, D.O., 74 FR 17524, 17525 (2009); Roger A. Rodriguez, M.D., 70 FR 33206,...

  12. Vienna-PTM web server: a toolkit for MD simulations of protein post-translational modifications.

    PubMed

    Margreitter, Christian; Petrov, Drazen; Zagrovic, Bojan

    2013-07-01

    Post-translational modifications (PTMs) play a key role in numerous cellular processes by directly affecting structure, dynamics and interaction networks of target proteins. Despite their importance, our understanding of protein PTMs at the atomistic level is still largely incomplete. Molecular dynamics (MD) simulations, which provide high-resolution insight into biomolecular function and underlying mechanisms, are in principle ideally suited to tackle this problem. However, because of the challenges associated with the development of novel MD parameters and a general lack of suitable computational tools for incorporating PTMs in target protein structures, MD simulations of post-translationally modified proteins have historically lagged significantly behind the studies of unmodified proteins. Here, we present Vienna-PTM web server (http://vienna-ptm.univie.ac.at), a platform for automated introduction of PTMs of choice to protein 3D structures (PDB files) in a user-friendly visual environment. With 256 different enzymatic and non-enzymatic PTMs available, the server performs geometrically realistic introduction of modifications at sites of interests, as well as subsequent energy minimization. Finally, the server makes available force field parameters and input files needed to run MD simulations of modified proteins within the framework of the widely used GROMOS 54A7 and 45A3 force fields and GROMACS simulation package. PMID:23703210

  13. Vienna-PTM web server: a toolkit for MD simulations of protein post-translational modifications

    PubMed Central

    Margreitter, Christian; Petrov, Drazen; Zagrovic, Bojan

    2013-01-01

    Post-translational modifications (PTMs) play a key role in numerous cellular processes by directly affecting structure, dynamics and interaction networks of target proteins. Despite their importance, our understanding of protein PTMs at the atomistic level is still largely incomplete. Molecular dynamics (MD) simulations, which provide high-resolution insight into biomolecular function and underlying mechanisms, are in principle ideally suited to tackle this problem. However, because of the challenges associated with the development of novel MD parameters and a general lack of suitable computational tools for incorporating PTMs in target protein structures, MD simulations of post-translationally modified proteins have historically lagged significantly behind the studies of unmodified proteins. Here, we present Vienna-PTM web server (http://vienna-ptm.univie.ac.at), a platform for automated introduction of PTMs of choice to protein 3D structures (PDB files) in a user-friendly visual environment. With 256 different enzymatic and non-enzymatic PTMs available, the server performs geometrically realistic introduction of modifications at sites of interests, as well as subsequent energy minimization. Finally, the server makes available force field parameters and input files needed to run MD simulations of modified proteins within the framework of the widely used GROMOS 54A7 and 45A3 force fields and GROMACS simulation package. PMID:23703210

  14. A mathematic model that describes modes of MdSGHV transmission within house fly populations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 h...

  15. Large-scale MD simulations investigating H plasma interactions with Tungsten surfaces

    NASA Astrophysics Data System (ADS)

    Cusentino, Mary Alice; Wirth, Brian

    2015-11-01

    Tungsten is a prime candidate material for the divertor in future fusion reactors such as ITER. However, the tungsten divertor will need to be able to withstand high fluxes, on the order of 1024m-2s-1, of low energy hydrogen. It is crucial to understand both the tungsten surface response as well as the hydrogen retention and recycling for the divertor region. Molecular dynamics (MD) is a useful tool to study these effects. One issue with MD is that implantation fluxes tend to be very high, on the order of 1027 m-2s-1, due to time and computational limitations. By performing large scale MD on supercomputers, it is possible to reach more realistic fluxes of 1025 m-2s-1. Results will be presented from MD simulations from a 50 nm x 50 nm x 25 nm tungsten box at 1200 K and 2000 K. Hydrogen is implanted every 10 ps based on the 60 eV depth distribution calculated by SRIM, which amounts to a flux of 4 x 1025 m-2s-1. A modified version of the Juslin bond order W-H potential is used to describe the W-H interactions. Preliminary results show an initially high retention of hydrogen that accumulates in a sub-surface region. These simulations provide insight into the early stages of surface deformation as well as hydrogen retention for the tungsten divertor.

  16. 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.

  17. 78 FR 59060 - Gabriel Sanchez, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-25

    ... was no ``compression of the nerves of the spinal cord. . . .'' GX 4, at 10-11. Despite this finding... that he did not ``see too much of the problem,'' and when examining the TFO's purported injury... sufficiently reliable to be accepted and relied upon in this .'' See Cynthia M. Cadet, M.D., 76 FR 19450,...

  18. 78 FR 61591 - Decision and Order: Clair L. Pettinger, M.D.

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-03

    ..., 54 F.3d 450, 452 (7th Cir. 1995); see also, e.g., Medicine Shoppe-Jonesborough, 73 FR 364, 387 (2008... David A. Ruben 78 FR 38363, 38385 n.47 (2013)), the Agency has long considered an applicant's record of compliance with laws related to controlled substances under this factor. See Albert Lepis, M.D., 51 FR...

  19. 75 FR 36577 - Airworthiness Directives; McDonnell Douglas Corporation Model MD-90-30 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ...-07-04, Amendment 39-15863 (74 FR 14460, March 31, 2009), for certain Model MD-90-30 airplanes. That... ``significant rule'' under the DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979); and 3... Amendment 39-15863 (74 FR 14460, March 31, 2009) and adding the following new AD: McDonnell...

  20. 76 FR 20025 - Alan H. Olefsky, M.D.; Denial of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-11

    ... entirety and revoked Respondent's registration. GX 4, at 3 (57 FR 928 (1992)). The Administrator expressly.... Olefsky, M.D., 72 FR 42127 (2007) (GX 3B, at 1). Among the conditions imposed by the order were that....'' See 72 FR at 42128 (citing 21 U.S.C. 802(21), 823(f), and 843(a)(3)). Following his...

  1. 76 FR 16821 - Gregory F. Saric, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... similar to that of Respondent's.'' Exceptions at 1 (citing Stuart A. Bergman, M.D., 70 FR 33193 (2005... Health Servs., 72 FR 42126 (2007) (quoting Bourne Pharmacy, Inc., 72 FR 18273, 18274 (2007) (quoting 21 U... * * * controlled substances under the laws of the State in which he practices.''); Bourne Pharmacy, 72 FR at...

  2. 75 FR 8465 - Airworthiness Directives; McDonnell Douglas Corporation Model MD-90-30 Airplanes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-25

    ... Model MD-90-30 airplanes. That NPRM was published in the Federal Register on September 4, 2009 (74 FR... ``significant rule'' under DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979), and (3) Will... airplane to which the AMOC applies, notify your principal maintenance inspector (PMI) or principal...

  3. Comments on ""Lake Woebegone," Twenty Years Later" by J. J. Cannell, MD

    ERIC Educational Resources Information Center

    McRae, D. J.

    2006-01-01

    This article presents the author's comments on ""Lake Woebegone," Twenty Years Later" by J. J. Cannell, MD. J. J. Cannell's article on the so-called "Lake Woebegone" effect for K-12 educational testing systems is mostly an historical account of technical issues and policy considerations that led in part to development of new types of test…

  4. 75 FR 16374 - Special Local Regulations for Marine Events; Patapsco River, Northwest Harbor, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-01

    ... Federal Register (73 FR 3316). Public Meeting We do not now plan to hold a public meeting. But you may... June 2, 2009 (74 FR 26326), and the Temporary Final Rule published on August 6, 2009 (74 Fed. Reg... River, Northwest Harbor, Baltimore, MD AGENCY: Coast Guard, DHS. ACTION: Notice of proposed...

  5. 76 FR 30823 - Special Local Regulations for Marine Events; Patapsco River, Northwest Harbor, Baltimore, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-27

    ... FR 69). We received no comments on the proposed rule. No public meeting was requested, and none was... River, Northwest Harbor, Baltimore, MD AGENCY: Coast Guard, DHS. ACTION: Temporary final rule. SUMMARY: The Coast Guard is establishing special local regulations during the ``Baltimore Dragon Boat...

  6. Identification of Evolutionarily Conserved Md1 Splice Variants That Regulate Innate Immunity through Differential Induction of NF-кB.

    PubMed

    Candel, Sergio; Tyrkalska, Sylwia D; García-Moreno, Diana; Meseguer, José; Mulero, Victoriano

    2016-08-15

    Although in mammals the TLR4/myeloid differentiation factor (MD)2/CD14 complex is responsible for the recognition of bacterial LPS, and it is known that the RP105/MD1 complex negatively regulates TLR4 signaling, the evolutionary history of LPS recognition remains enigmatic. Thus, zebrafish has orthologs of mammalian TLR4 (Tlr4a and Tlr4b), RP105, and MD1, but MD2 and CD14 seem to be absent from all fish genomes available to date. In addition, and to make the story more intriguing, zebrafish Tlr4a and Tlr4b do not recognize LPS, whereas the zebrafish Rp105/Md1 complex unexpectedly participates in the regulation of innate immunity and viral resistance. In this work, we report the identification of two novel splice variants of Md1, which are expressed at similar levels as full-length Md1 in the main immune-related organs of zebrafish and are highly induced upon viral infection. One of these splice variants, which is also expressed by mouse macrophages, lacks three conserved cysteine residues that have been shown to form disulfide bonds that are crucial for the three-dimensional structure of the MD-2-related lipid recognition domain of Md1. Functional studies in zebrafish demonstrate that this evolutionarily conserved splice variant shows higher antiviral activity than full-length Md1, but reduced proinflammatory activity, due to an impaired ability to activate the master regulator of inflammation, NF-κB. These results uncover a previously unappreciated evolutionarily conserved Md1 splice variant with important functions in the regulation of innate immunity and the antiviral response in zebrafish, and point to the need for additional functional studies in mammals on this little explored molecule. PMID:27402697

  7. Equalization in redundant channels

    NASA Technical Reports Server (NTRS)

    Tulpule, Bhalchandra R. (Inventor); Collins, Robert E. (Inventor); Cominelli, Donald F. (Inventor); O'Neill, Richard D. (Inventor)

    1988-01-01

    A miscomparison between a channel's configuration data base and a voted system configuration data base in a redundant channel system having identically operating, frame synchronous channels triggers autoequalization of the channel's historical signal data bases in a hierarchical, chronological manner with that of a correctly operating channel. After equalization, symmetrization of the channel's configuration data base with that of the system permits upgrading of the previously degraded channel to full redundancy. An externally provided equalization command, e.g., manually actuated, can also trigger equalization.

  8. Commercialism in Public Schools: Focusing on Channel One.

    ERIC Educational Resources Information Center

    Aiken, Margaret Putman

    A study measured the effectiveness of the Channel One news program on student achievement in current events. Data were collected to measure the difference in current events knowledge between those students who viewed and discussed Channel One, and those students who had no access to the program. Data based on gender differences in student…

  9. High-Resolution Magnetostratigraphy of Core MD99-2236 (Cartwright Saddle, Offshore Labrador) Since the Last Deglaciation

    NASA Astrophysics Data System (ADS)

    St-Onge, M.; Guillaume, S.; Jennings, A.; Andrews, J. T.

    2009-05-01

    The magnetic properties of a long and well-dated (18 AMS 14C dates) piston core (MD99-2236) sampled offshore Labrador (Cartwright Saddle) on board the R/V Marion Dufresne II in 1999 were analyzed at high- resolution in order to reconstruct the geomagnetic field behavior and to characterize several detrital carbonate events. The Natural, Anhysteretic, Isothermal and Saturated Isothemal Remanent Magnetizations were studied by progressives stepwise alternating field (AF) demagnetization at 1 cm intervals on u-channel samples using a cryogenic magnetometer at the Institut des sciences de la mer de Rimouski (ISMER). Hysteresis curves were also determined with an alternating gradient force magnetometer in order to characterize the magnetic mineralogy and grain size. The results indicate that the NRM is characterized by a strong, stable and single component magnetization most likely carried low coercivity minerals such as magnetite in the pseudo-single domain grain size range. The component inclination and declination were calculated by principal component analysis and exhibit maximum angular deviation values generally lower than 5°, highlighting well-defined directional data, except for some specific intervals characterized by higher carbonate content and multi-domain grains. Moreover, the component inclinations vary around the expected inclination (70.3°) for the latitude of the coring site based on a geocentric axial dipole (GAD) model. Component inclination and declination are presented and compared with other high-resolution paleomagnetic records from Eastern Canada, Iceland (MD99-2322 and -2269) and Europe. This comparison reveals that the sediments recorded coherent paleomagnetic secular variations (PSV), especially from 8 to 14 ka, where sedimentation rates are higher, the data of high quality and where previously published high-resolution RPI and PSV records for this period are rare. In addition, relative paleointensity (RPI) proxies were constructed by

  10. Identification of key residues that confer Rhodobacter sphaeroides LPS activity at horse TLR4/MD-2.

    PubMed

    Irvine, Katherine L; Gangloff, Monique; Walsh, Catherine M; Spring, David R; Gay, Nicholas J; Bryant, Clare E

    2014-01-01

    The molecular determinants underpinning how hexaacylated lipid A and tetraacylated precursor lipid IVa activate Toll-like receptor 4 (TLR4) are well understood, but how activation is induced by other lipid A species is less clear. Species specificity studies have clarified how TLR4/MD-2 recognises different lipid A structures, for example tetraacylated lipid IVa requires direct electrostatic interactions for agonism. In this study, we examine how pentaacylated lipopolysaccharide from Rhodobacter sphaeroides (RSLPS) antagonises human TLR4/MD-2 and activates the horse receptor complex using a computational approach and cross-species mutagenesis. At a functional level, we show that RSLPS is a partial agonist at horse TLR4/MD-2 with greater efficacy than lipid IVa. These data suggest the importance of the additional acyl chain in RSLPS signalling. Based on docking analysis, we propose a model for positioning of the RSLPS lipid A moiety (RSLA) within the MD-2 cavity at the TLR4 dimer interface, which allows activity at the horse receptor complex. As for lipid IVa, RSLPS agonism requires species-specific contacts with MD-2 and TLR4, but the R2 chain of RSLA protrudes from the MD-2 pocket to contact the TLR4 dimer in the vicinity of proline 442. Our model explains why RSLPS is only partially dependent on horse TLR4 residue R385, unlike lipid IVa. Mutagenesis of proline 442 into a serine residue, as found in human TLR4, uncovers the importance of this site in RSLPS signalling; horse TLR4 R385G/P442S double mutation completely abolishes RSLPS activity without its counterpart, human TLR4 G384R/S441P, being able to restore it. Our data highlight the importance of subtle changes in ligand positioning, and suggest that TLR4 and MD-2 residues that may not participate directly in ligand binding can determine the signalling outcome of a given ligand. This indicates a cooperative binding mechanism within the receptor complex, which is becoming increasingly important in TLR

  11. Identification of Key Residues That Confer Rhodobacter sphaeroides LPS Activity at Horse TLR4/MD-2

    PubMed Central

    Walsh, Catherine M.; Spring, David R.; Gay, Nicholas J.; Bryant, Clare E.

    2014-01-01

    The molecular determinants underpinning how hexaacylated lipid A and tetraacylated precursor lipid IVa activate Toll-like receptor 4 (TLR4) are well understood, but how activation is induced by other lipid A species is less clear. Species specificity studies have clarified how TLR4/MD-2 recognises different lipid A structures, for example tetraacylated lipid IVa requires direct electrostatic interactions for agonism. In this study, we examine how pentaacylated lipopolysaccharide from Rhodobacter sphaeroides (RSLPS) antagonises human TLR4/MD-2 and activates the horse receptor complex using a computational approach and cross-species mutagenesis. At a functional level, we show that RSLPS is a partial agonist at horse TLR4/MD-2 with greater efficacy than lipid IVa. These data suggest the importance of the additional acyl chain in RSLPS signalling. Based on docking analysis, we propose a model for positioning of the RSLPS lipid A moiety (RSLA) within the MD-2 cavity at the TLR4 dimer interface, which allows activity at the horse receptor complex. As for lipid IVa, RSLPS agonism requires species-specific contacts with MD-2 and TLR4, but the R2 chain of RSLA protrudes from the MD-2 pocket to contact the TLR4 dimer in the vicinity of proline 442. Our model explains why RSLPS is only partially dependent on horse TLR4 residue R385, unlike lipid IVa. Mutagenesis of proline 442 into a serine residue, as found in human TLR4, uncovers the importance of this site in RSLPS signalling; horse TLR4 R385G/P442S double mutation completely abolishes RSLPS activity without its counterpart, human TLR4 G384R/S441P, being able to restore it. Our data highlight the importance of subtle changes in ligand positioning, and suggest that TLR4 and MD-2 residues that may not participate directly in ligand binding can determine the signalling outcome of a given ligand. This indicates a cooperative binding mechanism within the receptor complex, which is becoming increasingly important in TLR

  12. 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.

  13. Channel nut tool

    DOEpatents

    Olson, Marvin

    2016-01-12

    A method, system, and apparatus for installing channel nuts includes a shank, a handle formed on a first end of a shank, and an end piece with a threaded shaft configured to receive a channel nut formed on the second end of the shaft. The tool can be used to insert or remove a channel nut in a channel framing system and then removed from the channel nut.

  14. United States Access Board

    MedlinePlus

    ... disabilities through leadership in accessible design and the development of accessibility guidelines and standards for the built environment, transportation, communication, medical diagnostic equipment, and information technology. ...

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

    PubMed Central

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

    2014-01-01

    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. PMID:24759884

  16. 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

    ... areas, found in 33 CFR 165.13, apply to the regulated navigation area described in paragraph (a) of this...; 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:...

  17. 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

    ... areas, found in 33 CFR 165.13, apply to the regulated navigation area described in paragraph (a) of this...; 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:...

  18. 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

    ... areas, found in 33 CFR 165.13, apply to the regulated navigation area described in paragraph (a) of this...; 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:...

  19. 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

    ... areas, found in 33 CFR 165.13, apply to the regulated navigation area described in paragraph (a) of this...; 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:...

  20. Registration of the Soft Red Winter Wheat Germplasm MD01W233-06-1 Resistant to Fusarium Head Blight

    Technology Transfer Automated Retrieval System (TEKTRAN)

    MD01W233-06-1 (Reg. No., PI ) is a soft red winter wheat (SRWW) (Triticum aestivum L.) germplasm line developed at the University of Maryland and released by the Maryland Agricultural Experiment Station in 2009. MD01W233-06-1 was selected from a cross of ‘McCormick’/ ‘Choptank’ made in 2001. McCorm...

  1. 33 CFR 334.190 - Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. 334.190 Section 334.190 Navigation and Navigable Waters CORPS OF ENGINEERS... Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. (a) The areas—(1) Prohibited area....

  2. 33 CFR 334.190 - Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. 334.190 Section 334.190 Navigation and Navigable Waters CORPS OF ENGINEERS... Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. (a) The areas—(1) Prohibited area....

  3. 33 CFR 334.190 - Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. 334.190 Section 334.190 Navigation and Navigable Waters CORPS OF ENGINEERS... Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. (a) The areas—(1) Prohibited area....

  4. 33 CFR 334.190 - Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. 334.190 Section 334.190 Navigation and Navigable Waters CORPS OF ENGINEERS... Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. (a) The areas—(1) Prohibited area....

  5. 33 CFR 334.190 - Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. 334.190 Section 334.190 Navigation and Navigable Waters CORPS OF ENGINEERS... Chesapeake Bay, in vicinity of Bloodsworth Island, MD, U.S. Navy. (a) The areas—(1) Prohibited area....

  6. 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

    ... areas, found in 33 CFR 165.13, apply to the regulated navigation area described in paragraph (a) of this...; 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:...

  7. Pathogenesis and protective efficacy of attenuated Meq null rMd5 virus in maternal antibody negative and commercial chickens.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A serotype 1 Marek’s disease Meq null virus (rMd5'Meq) has been shown to be an excellent vaccine in maternal antibody positive (MAb+) chickens. The only drawback of this non-oncogenic virus is that, like parental rMd5, it retains the ability to induce bursa and thymus atrophy (BTA) in MAb- chickens....

  8. Characterizing a point mutation within the UL5 gene that reduces in vivo replication and MD incidence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. 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.;...

  10. 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.;...

  11. 77 FR 9228 - AP Gas & Electric (MD), LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-16

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission AP Gas & Electric (MD), LLC; Supplemental Notice That Initial Market-Based... above-referenced proceeding of AP Gas & Electric (MD), LLC's application for market-based rate...

  12. Draft Genome Sequence of Ralstonia sp. MD27, a Poly(3-Hydroxybutyrate)-Degrading Bacterium, Isolated from Compost

    PubMed Central

    Zhu, Morgan; McCully, Lucy M.; Silby, Mark W.; Charles-Ogan, Tamunonengiyeofori I.

    2015-01-01

    Ralstonia sp. strain MD27, a novel biopolymer-degrading betaproteobacterium, was isolated from compost samples. This organism has been shown to utilize the biopolymer poly(3-hydroxybutyrate) [P(3HB)] as a carbon source for growth. We report the draft genome sequence of MD27 with an estimated total sequence length of 5.9 Mb. PMID:26450738

  13. 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.…

  14. 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

    ... public comment (77 FR 39209, 7/2/2012). The FTZ Board has determined that no further review of the... Foreign-Trade Zones Board 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...

  15. 77 FR 39209 - Foreign-Trade Zone 74-Baltimore, MD, Notification of Proposed Production Activity, J.D. Neuhaus...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-02

    ... Foreign-Trade Zones Board Foreign-Trade Zone 74--Baltimore, MD, Notification of Proposed Production Activity, J.D. Neuhaus LP (Overhead Lifting Equipment Production) Sparks, MD The Baltimore Development Corporation, grantee of FTZ 74, submitted a notification of proposed production activity on behalf of...

  16. 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

    ... Surface Transportation Board MCM Rail Services LLC--Petition for Retroactive Exemption--In Sparrows Point... MCM Rail Services LLC (MCM) regarding 12 miles of rail line in Sparrows Point, Md. (the Line). DATES..., is located at 1430 Sparrows Point Boulevard, Sparrows Point, Baltimore County, Md. MCM...

  17. 47 CFR 76.970 - Commercial leased access rates.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... access programmer for a full-time channel on that particular tier. The average implicit fee shall be... programmer's cost or the fair market value, whichever is lower. The average implicit fee shall be based on... that the operator may charge the leased access programmer for placement as a full-time a la...

  18. 47 CFR 76.970 - Commercial leased access rates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... access programmer for a full-time channel on that particular tier. The average implicit fee shall be... programmer's cost or the fair market value, whichever is lower. The average implicit fee shall be based on... that the operator may charge the leased access programmer for placement as a full-time a la...

  19. A comparison of hydrology and channel hydraulics in headwater streams of the Central Oregon Cascades

    NASA Astrophysics Data System (ADS)

    Hempel, L. A.; Grant, G.; Lewis, S.

    2013-12-01

    Streams with distinctly different flow regimes can be found within close proximity of each other in the Central Oregon Cascades due to the unique hydrogeology of the region. Spring-fed streams with stable discharge regimes tend to have rectangular cross-sections, uniform grain sizes, and frequent channel-spanning wood. In contrast, flashier surface-runoff channels tend to have more variable cross-sections, a wider grain-size distribution, and woody debris accumulations along channel margins. To examine differences in channel hydraulics, we collected high-resolution 3-D maps of 12 channel reaches from tributaries of the McKenzie and Metolius Rivers, OR. Stream channel maps were then used to run a 2-D channel stability model (MD_SWMS). We also compared stream hydrology using 10+ years of stream gage data. We expect bed particles are mobilized more frequently in spring-fed systems, but the opportunity for channel form development-- which occurs when sediment is mobile and when flow reaches or exceeds the active channel flow--is higher in surface-runoff channels. Therefore, each channel-type is characterized by a unique set of hydraulic processes that lead to observed differences in channel form.

  20. Control with a random access protocol and packet dropouts

    NASA Astrophysics Data System (ADS)

    Wang, Liyuan; Guo, Ge

    2016-08-01

    This paper investigates networked control systems whose actuators communicate with the controller via a limited number of unreliable channels. The access to the channels is decided by a so-called group random access protocol, which is modelled as a binary Markov sequence. Data packet dropouts in the channels are modelled as independent Bernoulli processes. For such systems, a systematic characterisation for controller synthesis is established and stated in terms of the transition probabilities of the Markov protocol and the packet dropout probabilities. The results are illustrated via a numerical example.

  1. The Earliest Ion Channels

    NASA Astrophysics Data System (ADS)

    Pohorille, A.; Wilson, M. A.; Wei, C.

    2009-12-01

    Supplying protocells with ions required assistance from channels spanning their membrane walls. The earliest channels were most likely short proteins that formed transmembrane helical bundles surrounding a water-filled pore. These simple aggregates were capable of transporting ions with efficiencies comparable to those of complex, contemporary ion channels. Channels with wide pores exhibited little ion selectivity but also imposed only modest constraints on amino acid sequences of channel-forming proteins. Channels with small pores could have been selective but also might have required a more precisely defined sequence of amino acids. In contrast to modern channels, their protocellular ancestors had only limited capabilities to regulate ion flux. It is postulated that subsequent evolution of ion channels progressed primarily to acquire precise regulation, and not high efficiency or selectivity. It is further proposed that channels and the surrounding membranes co-evolved.

  2. Microfluidic channel fabrication method

    DOEpatents

    Arnold, Don W.; Schoeniger, Joseph S.; Cardinale, Gregory F.

    2001-01-01

    A new channel structure for microfluidic systems and process for fabricating this structure. In contrast to the conventional practice of fabricating fluid channels as trenches or grooves in a substrate, fluid channels are fabricated as thin walled raised structures on a substrate. Microfluidic devices produced in accordance with the invention are a hybrid assembly generally consisting of three layers: 1) a substrate that can or cannot be an electrical insulator; 2) a middle layer, that is an electrically conducting material and preferably silicon, forms the channel walls whose height defines the channel height, joined to and extending from the substrate; and 3) a top layer, joined to the top of the channels, that forms a cover for the channels. The channels can be defined by photolithographic techniques and are produced by etching away the material around the channel walls.

  3. Gramicidin Channels: Versatile Tools

    NASA Astrophysics Data System (ADS)

    Andersen, Olaf S.; Koeppe, Roger E., II; Roux, Benoît

    Gramicidin channels are miniproteins in which two tryptophan-rich subunits associate by means of transbilayer dimerization to form the conducting channels. That is, in contrast to other ion channels, gramicidin channels do not open and close; they appear and disappear. Each subunit in the bilayer-spanning channel is tied to the bilayer/solution interface through hydrogen bonds that involve the indole NH groups as donors andwater or the phospholipid backbone as acceptors. The channel's permeability characteristics are well-defined: gramicidin channels are selective for monovalent cations, with no measurable permeability to anions or polyvalent cations; ions and water move through a pore whose wall is formed by the peptide backbone; and the single-channel conductance and cation selectivity vary when the amino acid sequence is varied, even though the permeating ions make no contact with the amino acid side chains. Given the plethora of available experimental information—for not only the wild-type channels but also for channels formed by amino acid-substituted gramicidin analogues—gramicidin channels continue to provide important insights into the microphysics of ion permeation through bilayer-spanning channels. For similar reasons, gramicidin channels constitute a system of choice for evaluating computational strategies for obtaining mechanistic insights into ion permeation through the more complex channels formed by integral membrane proteins.

  4. Message passing with queues and channels

    SciTech Connect

    Dozsa, Gabor J; Heidelberger, Philip; Kumar, Sameer; Ratterman, Joseph D; Steinmacher-Burow, Burkhard; Wisniewski, Robert W

    2013-09-24

    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 send 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.

  5. Mitigation of Control Channel Jamming via Combinatorial Key Distribution

    NASA Astrophysics Data System (ADS)

    Falahati, Abolfazl; Azarafrooz, Mahdi

    The problem of countering control channel jamming against internal adversaries in wireless ad hoc networks is addressed. Using combinatorial key distribution, a new method to secure the control channel access is introduced. This method, utilizes the established keys in the key establishment phase to hide the location of control channels without the need for a secure BS. This is in obtained by combination of a collision free one-way function and a combinatorial key establishment method. The proposed scheme can be considered as a special case of the ALOHA random access schemes which uses the common established keys as its seeds to generate the pattern of transmission.

  6. 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

  7. 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. PMID:26637549

  8. Deletion of the BAC sequences from recombinant meq-null Marek's disease (MD) virus increases immunosuppression while maintaining protective efficacy against MD.

    PubMed

    Su, S; Cui, N; Li, J; Sun, P; Li, H; Li, Y; Cui, Z

    2016-07-01

    Marek's disease virus (MDV) GX0101 is a field strain of MDV with a naturally occurring insertion of the reticuloendotheliosis virus (REV) long terminal repeat (LTR) fragment. Both copies of the meq gene were knocked out in the GX0101 bacterial artificial chromosome (BAC) clone to construct the recombinant virus SC9-1, resulting in a complete lack of pathogenicity and providing better protection against MD than CVI988/Rispens. In the present study, the BAC sequences in SC9-1 were removed using a cre-loxP system, and the virus termed SC9-2. SC9-2 showed a significant increase in replication in vitro and in vivo. There was a significant decrease in chicken weight, immune organ index, and antibody levels compared with those of SC9-1-inoculated chickens. The immune protection index of SC9-2 was similar to that of SC9-1, and the difference was not significant. The results of our studies demonstrate that the SC9-2 virus provides protection in specific pathogen free (SPF) chickens when challenged with a very virulent MDV rMd5, but it induces immunosuppressive effects in SPF chickens. PMID:26957626

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

    PubMed Central

    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

  10. 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

  11. A Theory of Access

    ERIC Educational Resources Information Center

    Ribot, Jesse C.; Peluso, Nancy Lee

    2003-01-01

    The term "access" is frequently used by property and natural resource analysts without adequate definition. In this paper we develop a concept of access and examine a broad set of factors that differentiate access from property. We define access as "the "ability" to derive benefits from things," broadening from property's classical definition as…

  12. Baltimore, MD

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Baltimore is the largest city in Maryland and one of the busiest ports in the United States. Its economy focuses on research and development, especially in the areas of aquaculture, pharmaceuticals, and medical supplies and services. Before European settlement, the site of Baltimore was inhabited by Native Americans of the Susquehannock tribe. The town was founded in 1729 and named for the barons Baltimore, the British founders of the Maryland Colony. This ASTER image of Baltimore was acquired on April 4, 2000, covers an area of 17 by 20 km, and is located at 39.3 degrees north latitude and 76.7 degrees west longitude.

    The U.S. science team is located at NASA's Jet Propulsion Laboratory, Pasadena, Calif. The Terra mission is part of NASA's Science Mission Directorate.

  13. Fading channel simulator

    SciTech Connect

    Argo, P.E.; Fitzgerald, T.J.

    1991-12-31

    This invention relates to high frequency (HF) radio signal propagation through fading channels and, more particularly, to simulation of fading channels in order to characterize HF radio system performance in transmitting and receiving signals through such fading channels. Fading channel effects on a transmitted communication signal are simulated with both frequency and time variations using a channel scattering function to affect the transmitted signal. A conventional channel scattering function is converted to a series of channel realizations by multiplying the square root of the channel scattering function by a complex number of which the real and imaginary parts are each independent variables. The two-dimensional inverse-FFT of this complex-valued channel realization yields a matrix of channel coefficients that provide a complete frequency-time description of the channel. The transmitted radio signal is segmented to provide a series of transmitted signal and each segment is subject to FFT to generate a series of signal coefficient matrices. The channel coefficient matrices and signal coefficient matrices are then multiplied and subjected to inverse-FFT to output a signal representing the received affected radio signal. A variety of channel scattering functions can be used to characterize the response of a transmitter-receiver system to such atmospheric effects.

  14. Calcium channel blocker overdose

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002580.htm Calcium channel blocker overdose To use the sharing features on this page, please enable JavaScript. Calcium channel blockers are a type of medicine used ...

  15. Structure of Anion-Conducting Polymers from Waxs and MD Simulations

    NASA Astrophysics Data System (ADS)

    Frisken, Barbara; Tahmasebi, Sepehr; Schibli, Eric; Holdcroft, Steven

    The structure of novel polymers for anion exchange membranes (AEMs) is investigated using wide angle X-ray scattering (WAXS) combined with molecular dynamics (MD) simulations using a united-atom force field model based on the DREIDING force field. The polymers being studied are poly(benzimidazole) (PBI) derivatives including poly(dimethylbenzimidazole) (PDMBI), mesitylene poly(benzimidazole) (mes-PBI), and mesitylene poly(dimethylbenzimidazole) (mes-PDMBI). WAXS reveals an amorphous structure with two main length scales. By comparing simulation results to WAXS data, we attribute features observed in the scattering data to side-to-side spacing between polymer chains and to the parallel-ring stacking of the benzimidazole rings. Overall, we are able to validate the interpretation of scattering data by combining MD simulations and scattering experiments.

  16. CJDATS Co-Occurring Disorders Screening Instrument for Mental Disorders (CODSI-MD)

    PubMed Central

    Sacks, Stanley; Melnick, Gerald; Coen, Carrie; Banks, Steven; Friedmann, Peter D.; Grella, Christine; Knight, Kevin

    2011-01-01

    This article describes the development of an instrument to screen male and female offenders for co-occurring substance use and mental disorders. This phase developed and pilot tested (N = 100) the Criminal Justice Drug Abuse Treatment Studies (CJDATS) Co-occurring Disorders Screening Instrument for Mental Disorders (CODSI-MD), a 6-item instrument derived from three standard mental health screeners. The overall accuracy of the CODSI-MD (81%) compared favorably with the three standard instruments. A second 3-item instrument, developed to screen for severe mental disorders (the CODSI-SMD), had an overall accuracy of 82%. The results of this pilot study must be viewed cautiously, pending validation of the findings with a larger sample. PMID:22140276

  17. 75 FR 76688 - Drawbridge Operation Regulation; Isle of Wight (Sinepuxent) Bay, Ocean City, MD

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-09

    ...The Coast Guard proposes to change the regulations that govern the operation of the US 50 Bridge over Isle of Wight (Sinepuxent) Bay, mile 0.5, at Ocean City, MD. This proposed rule will require any mariner requesting an opening in the evening hours during the off- season, to do so before the tender office has vacated for the night. The proposed change will ensure draw tender availability for......

  18. 76 FR 17672 - Alfred E. Boyce, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-30

    ... v. U.S. Dept. of Justice, 873 F.2d 1089, 1091 (8th Cir. 1989); Thomas E. Johnston, 45 FR 72311 (1980... '' (emphasis supplied). Roy Chi Lung, 74 FR 20346, 20347 (2009); Scott Sandarg, D.M.D., 74 FR 17528, 174529 (2009); John B. Freitas, D.O., 74 FR 17524, 17525 (2009); Roger A. Rodriguez, M.D., 70 FR 33206,...

  19. 78 FR 47412 - Tyson D. Quy, M.D.; Decision and Order

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-05

    ... should be revoked. See Robert A. Leslie, M.D., 68 FR 15,227, 15,230 (DEA 2003). Moreover, the....'' Medicine Shoppe--Jonesborough, 73 FR at 387; see also Samuel S. Jackson, D.D.S., 72 FR 23,848, 23,853 (DEA... determination as to whether the granting of would be in the public interest.'' Mortimer B. Levin, D.O., 55 FR...

  20. Mimicking titration experiments with MD simulations: A protocol for the investigation of pH-dependent effects on proteins

    NASA Astrophysics Data System (ADS)

    Socher, Eileen; Sticht, Heinrich

    2016-03-01

    Protein structure and function are highly dependent on the environmental pH. However, the temporal or spatial resolution of experimental approaches hampers direct observation of pH-induced conformational changes at the atomic level. Molecular dynamics (MD) simulation strategies (e.g. constant pH MD) have been developed to bridge this gap. However, one frequent problem is the sampling of unrealistic conformations, which may also lead to poor pKa predictions. To address this problem, we have developed and benchmarked the pH-titration MD (pHtMD) approach, which is inspired by wet-lab titration experiments. We give several examples how the pHtMD protocol can be applied for pKa calculation including peptide systems, Staphylococcus nuclease (SNase), and the chaperone HdeA. For HdeA, pHtMD is also capable of monitoring pH-dependent dimer dissociation in accordance with experiments. We conclude that pHtMD represents a versatile tool for pKa value calculation and simulation of pH-dependent effects in proteins.

  1. Comparison of the SIMARD MD to Clinical Impression in Assessing Fitness to Drive in Patients with Cognitive Impairment

    PubMed Central

    Wernham, Madelaine; Jarrett, Pamela G.; Stewart, Connie; MacDonald, Elizabeth; MacNeil, Donna; Hobbs, Cynthia

    2014-01-01

    Background The assessment of fitness to drive in patients with cognitive impairment is complex. The SIMARD MD was developed to assist with assessing fitness to drive. This study compares the clinical decision made by a geriatrician regarding driving with the SIMARD MD score. Methods Patients with a diagnosis of mild dementia or mild cognitive impairment, who had a SIMARD MD test, were included in the sample. A retrospective chart review was completed to gather diagnosis, driving status, and cognitive and functional information. Results Sixty-three patients were identified and 57 met the inclusion criteria. The mean age was 77.1 years (SD 8.9). The most common diagnosis was Alzheimer’s disease in 22 (38.6%) patients. The mean MMSE score was 24.9 (SD 3.34) and the mean MoCA was 19.9 (SD 3.58). The mean SIMARD MD score was 37.2 (SD 19.54). Twenty-four patients had a SIMARD MD score ≤ 30, twenty-eight between 31–70, and five scored > 70. The SIMARD MD scores did not differ significantly compared to the clinical decision (ANOVA p value = 0.14). Conclusions There was no association between the SIMARD MD scores and the geriatricians’ clinical decision regarding fitness to drive in persons with mild dementia or mild cognitive impairment. PMID:24883164

  2. Mimicking titration experiments with MD simulations: A protocol for the investigation of pH-dependent effects on proteins

    PubMed Central

    Socher, Eileen; Sticht, Heinrich

    2016-01-01

    Protein structure and function are highly dependent on the environmental pH. However, the temporal or spatial resolution of experimental approaches hampers direct observation of pH-induced conformational changes at the atomic level. Molecular dynamics (MD) simulation strategies (e.g. constant pH MD) have been developed to bridge this gap. However, one frequent problem is the sampling of unrealistic conformations, which may also lead to poor pKa predictions. To address this problem, we have developed and benchmarked the pH-titration MD (pHtMD) approach, which is inspired by wet-lab titration experiments. We give several examples how the pHtMD protocol can be applied for pKa calculation including peptide systems, Staphylococcus nuclease (SNase), and the chaperone HdeA. For HdeA, pHtMD is also capable of monitoring pH-dependent dimer dissociation in accordance with experiments. We conclude that pHtMD represents a versatile tool for pKa value calculation and simulation of pH-dependent effects in proteins. PMID:26936826

  3. A new two dimensional spectral/spatial multi-diagonal code for noncoherent optical code division multiple access (OCDMA) systems

    NASA Astrophysics Data System (ADS)

    Kadhim, Rasim Azeez; Fadhil, Hilal Adnan; Aljunid, S. A.; Razalli, Mohamad Shahrazel

    2014-10-01

    A new two dimensional codes family, namely two dimensional multi-diagonal (2D-MD) codes, is proposed for spectral/spatial non-coherent OCDMA systems based on the one dimensional MD code. Since the MD code has the property of zero cross correlation, the proposed 2D-MD code also has this property. So that, the multi-access interference (MAI) is fully eliminated and the phase induced intensity noise (PIIN) is suppressed with the proposed code. Code performance is analyzed in terms of bit error rate (BER) while considering the effect of shot noise, PIIN, and thermal noise. The performance of the proposed code is compared with the related MD, modified quadratic congruence (MQC), two dimensional perfect difference (2D-PD) and two dimensional diluted perfect difference (2D-DPD) codes. The analytical and the simulation results reveal that the proposed 2D-MD code outperforms the other codes. Moreover, a large number of simultaneous users can be accommodated at low BER and high data rate.

  4. Optimal channels for channelized quadratic estimators.

    PubMed

    Kupinski, Meredith K; Clarkson, Eric

    2016-06-01

    We present a new method for computing optimized channels for estimation tasks that is feasible for high-dimensional image data. Maximum-likelihood (ML) parameter estimates are challenging to compute from high-dimensional likelihoods. The dimensionality reduction from M measurements to L channels is a critical advantage of channelized quadratic estimators (CQEs), since estimating likelihood moments from channelized data requires smaller sample sizes and inverting a smaller covariance matrix is easier. The channelized likelihood is then used to form ML estimates of the parameter(s). In this work we choose an imaging example in which the second-order statistics of the image data depend upon the parameter of interest: the correlation length. Correlation lengths are used to approximate background textures in many imaging applications, and in these cases an estimate of the correlation length is useful for pre-whitening. In a simulation study we compare the estimation performance, as measured by the root-mean-squared error (RMSE), of correlation length estimates from CQE and power spectral density (PSD) distribution fitting. To abide by the assumptions of the PSD method we simulate an ergodic, isotropic, stationary, and zero-mean random process. These assumptions are not part of the CQE formalism. The CQE method assumes a Gaussian channelized likelihood that can be a valid for non-Gaussian image data, since the channel outputs are formed from weighted sums of the image elements. We have shown that, for three or more channels, the RMSE of CQE estimates of correlation length is lower than conventional PSD estimates. We also show that computing CQE by using a standard nonlinear optimization method produces channels that yield RMSE within 2% of the analytic optimum. CQE estimates of anisotropic correlation length estimation are reported to demonstrate this technique on a two-parameter estimation problem. PMID:27409452

  5. Channel catfish pond fertilization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The most successful aquaculture enterprise in the U.S. is channel catfish Ictalurus punctatus production. In the U.S., 257 million kg of channel catfish were sold in 2007 at a value of $455 million. Large-scale commercial channel catfish culture began in the late 1950s and expanded rapidly from 1978...

  6. Identification and characterization of the cysteine protease inhibitor gene MdCPI from Musca domestica.

    PubMed

    Dong, X; Liu, Fengsong; Zhang, D; Tang, T; Ge, X

    2011-10-01

    Cysteine proteinase inhibitors (CPIs) are involved in many vital cellular processes such as signalling pathways, apoptosis, immune response and development; however, no CPIs have yet been reported from the housefly Musca domestica. Here we report the isolation and characterization of a housefly CPI gene designated MdCPI. The gene contains an open reading frame of 357 bp encoding a protein of 118 amino acid residues with a putative signal peptide of 17 amino acid residues. Protein alignment demonstrated a high homology to that of Sarcophaga crassipalpis (identity = 51%). Phylogenetic analysis suggested that all CPIs from dipterans, including the housefly, belong to the I25A family and may be descended from a single common ancestor. The gene was expressed in and purified from Escherichia coli. Biochemical studies showed that MdCPI exerts an inhibiting function on papain, which is a classical assay to confirm CPIs. Real-time quantitative PCR and immunolocalization analysis revealed that MdCPI is specifically expressed in haemocytes and fat bodies. It is highly down-regulated in larvae and markedly up-regulated in the pupal stage, suggesting that it may be related to development. PMID:21711401

  7. Solvation structure and dynamics of Na+ in liquid ammonia studied by ONIOM-XS MD simulations

    NASA Astrophysics Data System (ADS)

    Sripradite, Jarukorn; Tongraar, Anan; Kerdcharoen, Teerakiat

    2015-12-01

    The molecular dynamics (MD) technique based on the ONIOM-XS method, known as the ONIOM-XS MD, has been applied to investigate the solvation structure and dynamics of Na+ in liquid ammonia. Regarding the ONIOM-XS MD results, it is observed that Na+ is able to order the surrounding ammonia molecules to form its specific first and second solvation shells with the average coordination numbers of 5.1 and 11.2, respectively. The first solvation shell of Na+ is rather well-defined, forming a preferred 5-fold coordinated complex with a distorted square pyramidal geometry. In this respect, the most preferential Na+(NH3)5 species could convert back and forth to the lower probability Na+(NH3)6 and Na+(NH3)4 configurations. The second solvation shell of Na+ is detectable, in which a number of ammonia molecules, ranging from 7 to 14, are involved in this layer and they are arranged according to recognizable influence of the ion.

  8. Wettability of graphitic-carbon and silicon surfaces: MD modeling and theoretical analysis

    SciTech Connect

    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 provide 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.

  9. World Wide Access: Accessible Web Design.

    ERIC Educational Resources Information Center

    Washington Univ., Seattle.

    This brief paper considers the application of "universal design" principles to Web page design in order to increase accessibility for people with disabilities. Suggestions are based on the World Wide Web Consortium's accessibility initiative, which has proposed guidelines for all Web authors and federal government standards. Seven guidelines for…

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

    PubMed

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

    2012-03-13

    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 Zn(2+), 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 Ca(2+) leaking, unregulated channels in AD, and suggest that Aβ toxicity is mediated through a receptor-independent, nonstereoselective mechanism. PMID:22423218

  11. Accurate Evaluation of Ion Conductivity of the Gramicidin A Channel Using a Polarizable Force Field without Any Corrections.

    PubMed

    Peng, Xiangda; Zhang, Yuebin; Chu, Huiying; Li, Yan; Zhang, Dinglin; Cao, Liaoran; Li, Guohui

    2016-06-14

    Classical molecular dynamic (MD) simulation of membrane proteins faces significant challenges in accurately reproducing and predicting experimental observables such as ion conductance and permeability due to its incapability of precisely describing the electronic interactions in heterogeneous systems. In this work, the free energy profiles of K(+) and Na(+) permeating through the gramicidin A channel are characterized by using the AMOEBA polarizable force field with a total sampling time of 1 μs. Our results indicated that by explicitly introducing the multipole terms and polarization into the electrostatic potentials, the permeation free energy barrier of K(+) through the gA channel is considerably reduced compared to the overestimated results obtained from the fixed-charge model. Moreover, the estimated maximum conductance, without any corrections, for both K(+) and Na(+) passing through the gA channel are much closer to the experimental results than any classical MD simulations, demonstrating the power of AMOEBA in investigating the membrane proteins. PMID:27171823

  12. 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.

  13. Satellite multiple access systems for mobile communication

    NASA Technical Reports Server (NTRS)

    Lewis, J. L.

    1979-01-01

    This paper considers multiple access techniques for a mobile radio system which incorporates a geosynchronous orbiting satellite repeater through which mobile terminals communicate. The communication capacities of FDMA, TDMA and CDMA systems are examined for a 4 MHz bandwidth system to serve up to 10,000 users. An FDMA system with multibeam coverage is analyzed in detail. The system includes an order-wire network for demand-access control and reassignment of satellite channels. Satellite and terminal configurations are developed to a block diagram level and system costs and implementation requirements are discussed.

  14. Mechanically Activated Ion Channels.

    PubMed

    Ranade, Sanjeev S; Syeda, Ruhma; Patapoutian, Ardem

    2015-09-23

    Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels. PMID:26402601

  15. C. elegans TRP channels

    PubMed Central

    Xiao, Rui; Xu, X.Z. Shawn

    2010-01-01

    TRP (transient receptor potential) channels represent a superfamily of cation channels found in all eukaryotes. The C. elegans genome encodes seventeen TRP channels covering all of the seven TRP subfamilies. Genetic analyses in C. elegans have implicated TRP channels in a wide spectrum of behavioral and physiological processes, ranging from sensory transduction (e.g. chemosensation, touch sensation, proprioception and osmosensation) to fertilization, drug dependence, organelle biogenesis, apoptosis, gene expression, and neurotransmitter/hormone release. Many C. elegans TRP channels share similar activation and regulatory mechanisms with their vertebrate counterparts. Studies in C. elegans have also revealed some previously unrecognized functions and regulatory mechanisms of TRP channels. C. elegans represents an excellent genetic model organism for the study of function and regulation of TRP channels in vivo. PMID:21290304

  16. Salt-Excluding Artificial Water Channels Exhibiting Enhanced Dipolar Water and Proton Translocation.

    PubMed

    Licsandru, Erol; Kocsis, Istvan; Shen, Yue-Xiao; Murail, Samuel; Legrand, Yves-Marie; van der Lee, Arie; Tsai, Daniel; Baaden, Marc; Kumar, Manish; Barboiu, Mihail

    2016-04-27

    Aquaporins (AQPs) are biological water channels known for fast water transport (∼10(8)-10(9) molecules/s/channel) with ion exclusion. Few synthetic channels have been designed to mimic this high water permeability, and none reject ions at a significant level. Selective water translocation has previously been shown to depend on water-wires spanning the AQP pore that reverse their orientation, combined with correlated channel motions. No quantitative correlation between the dipolar orientation of the water-wires and their effects on water and proton translocation has been reported. Here, we use complementary X-ray structural data, bilayer transport experiments, and molecular dynamics (MD) simulations to gain key insights and quantify transport. We report artificial imidazole-quartet water channels with 2.6 Å pores, similar to AQP channels, that encapsulate oriented dipolar water-wires in a confined chiral conduit. These channels are able to transport ∼10(6) water molecules/s, which is within 2 orders of magnitude of AQPs' rates, and reject all ions except protons. The proton conductance is high (∼5 H(+)/s/channel) and approximately half that of the M2 proton channel at neutral pH. Chirality is a key feature influencing channel efficiency. PMID:27063409

  17. Hemodialysis access procedures

    MedlinePlus

    National Kidney and Urologic Diseases Information Clearinghouse. Vascular Access for Hemodialysis . Updated July 23, 2014. Available at: kidney.niddk.nih.gov/kudiseases/pubs/vascularaccess/index.aspx. Accessed: February 9, 2015. ...

  18. Calcium ions open a selectivity filter gate during activation of the MthK potassium channel

    NASA Astrophysics Data System (ADS)

    Posson, David J.; Rusinova, Radda; Andersen, Olaf S.; Nimigean, Crina M.

    2015-09-01

    Ion channel opening and closing are fundamental to cellular signalling and homeostasis. Gates that control K+ channel activity were found both at an intracellular pore constriction and within the selectivity filter near the extracellular side but the specific location of the gate that opens Ca2+-activated K+ channels has remained elusive. Using the Methanobacterium thermoautotrophicum homologue (MthK) and a stopped-flow fluorometric assay for fast channel activation, we show that intracellular quaternary ammonium blockers bind to closed MthK channels. Since the blockers are known to bind inside a central channel cavity, past the intracellular entryway, the gate must be within the selectivity filter. Furthermore, the blockers access the closed channel slower than the open channel, suggesting that the intracellular entryway narrows upon pore closure, without preventing access of either the blockers or the smaller K+. Thus, Ca2+-dependent gating in MthK occurs at the selectivity filter with coupled movement of the intracellular helices.

  19. 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

  20. Gating of the Mechanosensitive Channel Protein MscL: The Interplay of Membrane and Protein

    PubMed Central

    Jeon, Jonggu; Voth, Gregory A.

    2008-01-01

    The mechanosensitive channel of large conductance (MscL) belongs to a family of transmembrane channel proteins in bacteria and functions as a safety valve that relieves the turgor pressure produced by osmotic downshock. MscL gating can be triggered solely by stretching of the membrane. This work reports an effort to understand this mechanotransduction by means of molecular dynamics (MD) simulation on the MscL of mycobacterium tuberculosis embedded in a palmitoyloleoylphosphatidylethanolamine membrane. Equilibrium MD under zero membrane tension produced a more compact protein structure, as measured by its radii of gyration, compared to the crystal structure, in agreement with previous experimental findings. Even under a large applied tension up to 1000 dyn/cm, the MscL lateral dimension largely remained unchanged after up to 20 ns of simulation. A nonequilibrium MD simulation of 3% membrane expansion showed a significant increase in membrane rigidity upon MscL inclusion, which can contribute to efficient mechanotransduction. Direct observation of channel opening was possible only when an explicit lateral bias force was applied to each of the five subunits of MscL in the radially outward direction. Using this force, open structures with a large pore of radius 10 Å could be obtained. The channel opening takes place in a stepwise manner and concurrently with the water chain formation across the channel, which occurs without direct involvement of protein hydrophilic residues. The N-terminal S1 helices stabilize the open structure, and the membrane asymmetry (different lipid density on the two leaflets of membrane) promotes channel opening. PMID:18212020