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Fluid circulating pump operated by same incident solar energy which heats energy collection fluid

NASA Technical Reports Server (NTRS)

Collins, E. R.

1980-01-01

The application of using a spacecraft solar powered pump terrestrially to reduce or eliminate the need for fossil fuel generated electricity for domestic solar hot water systems was investigated. A breadboard prototype model was constructed utilizing bimetals to convert thermal energy into mechanical motion by means of a toggle operated shutter mechanism. Although it did not meet expected thermal efficiency, the prototype model was sufficient to demonstrate the mechanical concept.

News | Argonne National Laboratory

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Skip to main content Argonne National Laboratory Toggle Navigation Toggle Search Home Learning solvers Home Learning Center Undergraduates Graduates Faculty Partners News & Events News & Events -4114 Contact Us Argonne Educational Programs is committed to providing a learning environment that

Facilities | Argonne National Laboratory

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Skip to main content Argonne National Laboratory Toggle Navigation Toggle Search Research Facilities Advanced Powertrain Research Facility Center for Transportation Research Distributed Energy Research Center Engine Research Facility Heat Transfer Laboratory Materials Engineering Research Facility

Safety | Argonne National Laboratory

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laboratory's ongoing effort to provide a safe and productive environment for employees, users, other site Skip to main content Argonne National Laboratory Toggle Navigation Toggle Search Energy Environment Careers Education Community Diversity Directory Energy Environment National Security User Facilities

Increase Workshop | Argonne National Laboratory

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Skip to main content Argonne National Laboratory Toggle Navigation Toggle Search Home Learning solvers Home Learning Center Undergraduates Graduates Faculty Partners News & Events Faculty Visiting Us Argonne Educational Programs is committed to providing a learning environment that emphasizes the

Internship Opportunities | Argonne National Laboratory

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Skip to main content Argonne National Laboratory Toggle Navigation Toggle Search Home Learning -class research to tomorrow's STEM problem solvers Home Learning Center Undergraduates Graduates Faculty ) 252-4114 Contact Us Argonne Educational Programs is committed to providing a learning environment that

Voice/Natural Language Interfacing for Robotic Control.

DTIC Science & Technology

1987-11-01

THIS PAGE REPORT DOCUMENTATION PAGE Is. REPORT SECURITY CLASSIFICATION lb . RESTRICTIVE MARKINGS UNCLASSIFIED 2a. SECURITY CLASSIFICATION AUTHORITY 3...until major computing power can be profitably allocated to the speech recognition process, off-the- shelf units will never have sufficient intelligence to...coordinate transformation for a location, and opening or closing the gripper’s toggles. External to world operations, each joint may be rotated

A Compendium of Arctic Environmental Information

DTIC Science & Technology

1986-03-01

warn- ing of possible future ice invasions during petroleum drill - ing operations in open-water conditions. Development of sea ice Several basic...tubes, triple beam balance snow temperature thermistor and bridge ice ttiicl^ness hand auger, electric drill with auger, tape with toggle ice...fluids, 8 quarts daily. Acidify urine by drink- ing cranberry juice, taking Vitamin C, etc. Machines All machinery in the Arctic (engines, drills

Intracellular calcium dynamics permit a Purkinje neuron model to perform toggle and gain computations upon its inputs

PubMed Central

Forrest, Michael D.

2014-01-01

Without synaptic input, Purkinje neurons can spontaneously fire in a repeating trimodal pattern that consists of tonic spiking, bursting and quiescence. Climbing fiber input (CF) switches Purkinje neurons out of the trimodal firing pattern and toggles them between a tonic firing and a quiescent state, while setting the gain of their response to Parallel Fiber (PF) input. The basis to this transition is unclear. We investigate it using a biophysical Purkinje cell model under conditions of CF and PF input. The model can replicate these toggle and gain functions, dependent upon a novel account of intracellular calcium dynamics that we hypothesize to be applicable in real Purkinje cells. PMID:25191262

Toggle mechanism for pinching metal tubes

NASA Technical Reports Server (NTRS)

Stengard, E. O. (Inventor)

1979-01-01

A toggle mechanism pinches a metal tube and maintains the tube in a pinched condition, without fracturing. The toggle mechanism includes a plunger translatable along a longitudinal axis, as well as a pair of links pivoted about a common axis extending through an end of the plunger. One of the links also pivots about a fixed axis. A free end of the other link carries a push link which the other link translates at right angles to the plunger longitudinal axis. First and second sides of the tube bear against a first stop block and are engaged by the push link when a compression spring, attached to the plunger, is suddenly released to irreversibly drive the plunger along its longitudinal axis so the pivot point of the two links is driven to an over travel position.

Easily-wired toggle switch

NASA Technical Reports Server (NTRS)

Dean, W. T.; Stringer, E. J.

1979-01-01

Crimp-type connectors reduce assembly and disassembly time. With design, no switch preparation is necessary and socket contracts are crimped to wires inserted in module attached to back of toggle switch engaging pins inside module to make electrical connections. Wires are easily removed with standard detachment tool. Design can accommodate wires of any gage and as many terminals can be placed on switch as wire gage and switch dimensions will allow.

Variable-Reluctance Motor For Electric Vehicles

NASA Technical Reports Server (NTRS)

Lang, Jeffrey H.

1987-01-01

Report describes research on variable-reluctance electric-motor drive for eventual use in electric-vehicle propulsion. Primary design and performance criteria were torque and power output per unit mass of motor, cost, and drive efficiency. For each criterion, optimized drive design developed, and designs unified to yield single electric-vehicle drive. Scaled-down motor performed as expected. Prototype of paraplegic lift operated by toggle switch and joystick. Lift plugs into household electrical outlet for recharging when not in use.

Rapid convergence of optimal control in NMR using numerically-constructed toggling frames

NASA Astrophysics Data System (ADS)

Coote, Paul; Anklin, Clemens; Massefski, Walter; Wagner, Gerhard; Arthanari, Haribabu

2017-08-01

We present a numerical method for rapidly solving the Bloch equation for an arbitrary time-varying spin-1/2 Hamiltonian. The method relies on fast, vectorized computations such as summation and quaternion multiplication, rather than slow computations such as matrix exponentiation. A toggling frame is constructed in which the Hamiltonian is time-invariant, and therefore has a simple analytical solution. The key insight is that constructing this frame is faster than solving the system dynamics in the original frame. Rapidly solving the Bloch equations for an arbitrary Hamiltonian is particularly useful in the context of NMR optimal control. Optimal control theory can be used to design pulse shapes for a range of tasks in NMR spectroscopy. However, it requires multiple simulations of the Bloch equations at each stage of the algorithm, and for each relevant set of parameters (e.g. chemical shift frequencies). This is typically time consuming. We demonstrate that by working in an appropriate toggling frame, optimal control pulses can be generated much faster. We present a new alternative to the well-known GRAPE algorithm to continuously update the toggling-frame as the optimal pulse is generated, and demonstrate that this approach is extremely fast. The use and benefit of rapid optimal pulse generation is demonstrated for 19F fragment screening experiments.

A novel image toggle tool for comparison of serial mammograms: automatic density normalization and alignment-development of the tool and initial experience.

PubMed

Honda, Satoshi; Tsunoda, Hiroko; Fukuda, Wataru; Saida, Yukihisa

2014-12-01

The purpose is to develop a new image toggle tool with automatic density normalization (ADN) and automatic alignment (AA) for comparing serial digital mammograms (DMGs). We developed an ADN and AA process to compare the images of serial DMGs. In image density normalization, a linear interpolation was applied by taking two points of high- and low-brightness areas. The alignment was calculated by determining the point of the greatest correlation while shifting the alignment between the current and prior images. These processes were performed on a PC with a 3.20-GHz Xeon processor and 8 GB of main memory. We selected 12 suspected breast cancer patients who had undergone screening DMGs in the past. Automatic processing was retrospectively performed on these images. Two radiologists subjectively evaluated them. The process of the developed algorithm took approximately 1 s per image. In our preliminary experience, two images could not be aligned approximately. When they were aligned, image toggling allowed detection of differences between examinations easily. We developed a new tool to facilitate comparative reading of DMGs on a mammography viewing system. Using this tool for toggling comparisons might improve the interpretation efficiency of serial DMGs.

Whole-brain perfusion CT using a toggling table technique to predict final infarct volume in acute ischemic stroke.

PubMed

Schrader, I; Wilk, D; Jansen, O; Riedel, C

2013-09-01

To evaluate how accurately final infarct volume in acute ischemic stroke can be predicted with perfusion CT (PCT) using a 64-MDCT unit and the toggling table technique. Retrospective analysis of 89 patients with acute ischemic stroke who underwent CCT, CT angiography (CTA) and PCT using the "toggling table" technique within the first three hours after symptom onset. In patients with successful thrombolytic therapy (n = 48) and in those without effective thrombolytic therapy (n = 41), the infarct volume and the volume of the penumbra on PCT were compared to the infarct size on follow-up images (CT or MRI) performed within 8 days. The feasibility of complete infarct volume prediction by 8 cm cranio-caudal coverage was evaluated. The correlation between the volume of hypoperfusion on PCT defined by cerebral blood volume reduction and final infarct volume was strongest in patients with successful thrombolytic therapy with underestimation of the definite infarct volume by 8.5 ml on average. The CBV map had the greatest prognostic value. In patients without successful thrombolytic therapy, the final infarct volume was overestimated by 12.1 ml compared to the MTT map on PCT. All infarcts were detected completely. There were no false-positive or false-negative results. Using PCT and the "toggling table" technique in acute stroke patients is helpful for the rapid and accurate quantification of the minimal final infarct and is therefore a prognostic parameter which has to be evaluated in further studies to assess its impact on therapeutic decision. ▶ Using PCT and the “toggling table technique” allows accurate quantification of the infarct core and penumbra. ▶ It is possible to record dynamic perfusion parameters quickly and easily of almost the entire supratentorial brain volume on a 64-slice MDCT unit. ▶ The technique allows identification of those patients who could profit from thrombolytic therapy outside the established time intervals. © Georg Thieme Verlag KG Stuttgart · New York.

Toggling Bistable Atoms via Mechanical Switching of Bond Angle

NASA Astrophysics Data System (ADS)

Sweetman, Adam; Jarvis, Sam; Danza, Rosanna; Bamidele, Joseph; Gangopadhyay, Subhashis; Shaw, Gordon A.; Kantorovich, Lev; Moriarty, Philip

2011-04-01

We reversibly switch the state of a bistable atom by direct mechanical manipulation of bond angle using a dynamic force microscope. Individual buckled dimers at the Si(100) surface are flipped via the formation of a single covalent bond, actuating the smallest conceivable in-plane toggle switch (two atoms) via chemical force alone. The response of a given dimer to a flip event depends critically on both the local and nonlocal environment of the target atom—an important consideration for future atomic scale fabrication strategies.

Operating principles of tristable circuits regulating cellular differentiation

NASA Astrophysics Data System (ADS)

Jia, Dongya; Jolly, Mohit Kumar; Harrison, William; Boareto, Marcelo; Ben-Jacob, Eshel; Levine, Herbert

2017-06-01

Many cell-fate decisions during embryonic development are governed by a motif comprised of two transcription factors (TFs) A and B that mutually inhibit each other and may self-activate. This motif, called as a self-activating toggle switch (SATS), can typically have three stable states (phenotypes)—two corresponding to differentiated cell fates, each of which has a much higher level of one TF than the other—≤ft(A,~B\\right)=≤ft(1,~0\\right) or ≤ft(0,~1\\right) —and the third state corresponding to an ‘undecided’ stem-like state with similar levels of both A and B—≤ft(A,~B\\right)=≤ft(1/2,1/2\\right) . Furthermore, two or more SATSes can be coupled together in various topologies in different contexts, thereby affecting the coordination between multiple cellular decisions. However, two questions remain largely unanswered: (a) what governs the co-existence and relative stability of these three stable states? (b) What orchestrates the decision-making of coupled SATSes? Here, we first demonstrate that the co-existence and relative stability of the three stable states in an individual SATS can be governed by the relative strength of self-activation, external signals activating and/or inhibiting A and B, and mutual degradation between A and B. Simultaneously, we investigate the effects of these factors on the decision-making of two coupled SATSes. Our results offer novel understanding into the operating principles of individual and coupled tristable self-activating toggle switches (SATSes) regulating cellular differentiation and can yield insights into synthesizing three-way genetic circuits and understanding of cellular reprogramming.

Novel toggle-rate based energy-efficient scheme for heavy load real-time IM-DD OFDM-PON with ONU LLID identification in time-domain using amplitude decision.

PubMed

Qin, Youxiang; Zhang, Junjie

2017-07-10

A novel low complexity and energy-efficient scheme by controlling the toggle-rate of ONU with time-domain amplitude identification is proposed for a heavy load downlink in an intensity-modulation and direct-detection orthogonal frequency division multiplexing passive optical network (IM-DD OFDM-PON). In a conventional OFDM-PON downlink, all ONUs have to perform demodulation for all the OFDM frames in a broadcast way no matter whether the frames are targeted to or not, which causes a huge energy waste. However, in our scheme, the optical network unit (ONU) logical link identifications (LLIDs) are inserted into each downlink OFDM frame in time-domain at the optical line terminal (OLT) side. At the ONU side, the LLID is obtained with a low complexity and high precision amplitude identification method. The ONU sets the toggle-rate of demodulation module to zero when the frames are not targeted to, which avoids unnecessary digital signal processing (DSP) energy consumption. Compared with the sleep-mode methods consisting of clock recovery and synchronization, toggle-rate shows its advantage in fast changing, which is more suitable for the heavy load scenarios. Moreover, for the first time to our knowledge, the characteristics of the proposed scheme are investigated in a real-time IM-DD OFDM system, which performs well at the received optical power as low as -21dBm. The experimental results show that 25.1% energy consumption can be saved in the receiver compared to the conventional configurations.

Combining a Toggle Switch and a Repressilator within the AC-DC Circuit Generates Distinct Dynamical Behaviors.

PubMed

Perez-Carrasco, Ruben; Barnes, Chris P; Schaerli, Yolanda; Isalan, Mark; Briscoe, James; Page, Karen M

2018-04-25

Although the structure of a genetically encoded regulatory circuit is an important determinant of its function, the relationship between circuit topology and the dynamical behaviors it can exhibit is not well understood. Here, we explore the range of behaviors available to the AC-DC circuit. This circuit consists of three genes connected as a combination of a toggle switch and a repressilator. Using dynamical systems theory, we show that the AC-DC circuit exhibits both oscillations and bistability within the same region of parameter space; this generates emergent behaviors not available to either the toggle switch or the repressilator alone. The AC-DC circuit can switch on oscillations via two distinct mechanisms, one of which induces coherence into ensembles of oscillators. In addition, we show that in the presence of noise, the AC-DC circuit can behave as an excitable system capable of spatial signal propagation or coherence resonance. Together, these results demonstrate how combinations of simple motifs can exhibit multiple complex behaviors. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Dynamically variable spot size laser system

NASA Technical Reports Server (NTRS)

Gradl, Paul R. (Inventor); Hurst, John F. (Inventor); Middleton, James R. (Inventor)

2012-01-01

A Dynamically Variable Spot Size (DVSS) laser system for bonding metal components includes an elongated housing containing a light entry aperture coupled to a laser beam transmission cable and a light exit aperture. A plurality of lenses contained within the housing focus a laser beam from the light entry aperture through the light exit aperture. The lenses may be dynamically adjusted to vary the spot size of the laser. A plurality of interoperable safety devices, including a manually depressible interlock switch, an internal proximity sensor, a remotely operated potentiometer, a remotely activated toggle and a power supply interlock, prevent activation of the laser and DVSS laser system if each safety device does not provide a closed circuit. The remotely operated potentiometer also provides continuous variability in laser energy output.

Quickly Removable Valve

NASA Technical Reports Server (NTRS)

Robbins, John S.

1988-01-01

Unit removed with minimal disturbance. Valve inlet and outlet ports adjacent to each other on same side of valve body. Ports inserted into special manifold on fluid line. Valve body attached to manifold by four bolts or, alternatively, by toggle clamps. Electromechanical actuator moves in direction parallel to fluid line to open and close valve. When necessary to clean valve, removed simply by opening bolts or toggle clamps. No need to move or separate ports of fluid line. Valve useful where disturbance of fluid line detrimental or where fast maintenance essential - in oil and chemical industries, automotive vehicles, aircraft, and powerplants.

Membrane-bound MinDE complex acts as a toggle switch that drives Min oscillation coupled to cytoplasmic depletion of MinD

PubMed Central

Vecchiarelli, Anthony G.; Li, Min; Mizuuchi, Michiyo; Hwang, Ling Chin; Seol, Yeonee; Neuman, Keir C.; Mizuuchi, Kiyoshi

2016-01-01

The Escherichia coli Min system self-organizes into a cell-pole to cell-pole oscillator on the membrane to prevent divisions at the cell poles. Reconstituting the Min system on a lipid bilayer has contributed to elucidating the oscillatory mechanism. However, previous in vitro patterns were attained with protein densities on the bilayer far in excess of those in vivo and failed to recapitulate the standing wave oscillations observed in vivo. Here we studied Min protein patterning at limiting MinD concentrations reflecting the in vivo conditions. We identified “burst” patterns—radially expanding and imploding binding zones of MinD, accompanied by a peripheral ring of MinE. Bursts share several features with the in vivo dynamics of the Min system including standing wave oscillations. Our data support a patterning mechanism whereby the MinD-to-MinE ratio on the membrane acts as a toggle switch: recruiting and stabilizing MinD on the membrane when the ratio is high and releasing MinD from the membrane when the ratio is low. Coupling this toggle switch behavior with MinD depletion from the cytoplasm drives a self-organized standing wave oscillator. PMID:26884160

Membrane-bound MinDE complex acts as a toggle switch that drives Min oscillation coupled to cytoplasmic depletion of MinD.

PubMed

Vecchiarelli, Anthony G; Li, Min; Mizuuchi, Michiyo; Hwang, Ling Chin; Seol, Yeonee; Neuman, Keir C; Mizuuchi, Kiyoshi

2016-03-15

The Escherichia coli Min system self-organizes into a cell-pole to cell-pole oscillator on the membrane to prevent divisions at the cell poles. Reconstituting the Min system on a lipid bilayer has contributed to elucidating the oscillatory mechanism. However, previous in vitro patterns were attained with protein densities on the bilayer far in excess of those in vivo and failed to recapitulate the standing wave oscillations observed in vivo. Here we studied Min protein patterning at limiting MinD concentrations reflecting the in vivo conditions. We identified "burst" patterns--radially expanding and imploding binding zones of MinD, accompanied by a peripheral ring of MinE. Bursts share several features with the in vivo dynamics of the Min system including standing wave oscillations. Our data support a patterning mechanism whereby the MinD-to-MinE ratio on the membrane acts as a toggle switch: recruiting and stabilizing MinD on the membrane when the ratio is high and releasing MinD from the membrane when the ratio is low. Coupling this toggle switch behavior with MinD depletion from the cytoplasm drives a self-organized standing wave oscillator.

Tuning stochastic transition rates in a bistable genetic network.

NASA Astrophysics Data System (ADS)

Chickarmane, Vijay; Peterson, Carsten

2009-03-01

We investigate the stochastic dynamics of a simple genetic network, a toggle switch, in which the system makes transitions between the two alternative states. Our interest is in exploring whether such stochastic transitions, which occur due to the intrinsic noise such as transcriptional and degradation events, can be slowed down/speeded up, without changing the mean expression levels of the two genes, which comprise the toggle network. Such tuning is achieved by linking a signaling network to the toggle switch. The signaling network comprises of a protein, which can exist either in an active (phosphorylated) or inactive (dephosphorylated) form, and where its state is determined by one of the genetic network components. The active form of the protein in turn feeds back on the dynamics of the genetic network. We find that the rate of stochastic transitions from one state to the other, is determined essentially by the speed of phosphorylation, and hence the rate can be modulated by varying the phosphatase levels. We hypothesize that such a network architecture can be implemented as a general mechanism for controlling transition rates and discuss applications in population studies of two differentiated cell lineages, ex: the myeloid/erythroid lineage in hematopoiesis.

Infrared and Visual Image Fusion through Fuzzy Measure and Alternating Operators

PubMed Central

Bai, Xiangzhi

2015-01-01

The crucial problem of infrared and visual image fusion is how to effectively extract the image features, including the image regions and details and combine these features into the final fusion result to produce a clear fused image. To obtain an effective fusion result with clear image details, an algorithm for infrared and visual image fusion through the fuzzy measure and alternating operators is proposed in this paper. Firstly, the alternating operators constructed using the opening and closing based toggle operator are analyzed. Secondly, two types of the constructed alternating operators are used to extract the multi-scale features of the original infrared and visual images for fusion. Thirdly, the extracted multi-scale features are combined through the fuzzy measure-based weight strategy to form the final fusion features. Finally, the final fusion features are incorporated with the original infrared and visual images using the contrast enlargement strategy. All the experimental results indicate that the proposed algorithm is effective for infrared and visual image fusion. PMID:26184229

Infrared and Visual Image Fusion through Fuzzy Measure and Alternating Operators.

PubMed

Bai, Xiangzhi

2015-07-15

The crucial problem of infrared and visual image fusion is how to effectively extract the image features, including the image regions and details and combine these features into the final fusion result to produce a clear fused image. To obtain an effective fusion result with clear image details, an algorithm for infrared and visual image fusion through the fuzzy measure and alternating operators is proposed in this paper. Firstly, the alternating operators constructed using the opening and closing based toggle operator are analyzed. Secondly, two types of the constructed alternating operators are used to extract the multi-scale features of the original infrared and visual images for fusion. Thirdly, the extracted multi-scale features are combined through the fuzzy measure-based weight strategy to form the final fusion features. Finally, the final fusion features are incorporated with the original infrared and visual images using the contrast enlargement strategy. All the experimental results indicate that the proposed algorithm is effective for infrared and visual image fusion.

Parallel logic gates in synthetic gene networks induced by non-Gaussian noise.

PubMed

Xu, Yong; Jin, Xiaoqin; Zhang, Huiqing

2013-11-01

The recent idea of logical stochastic resonance is verified in synthetic gene networks induced by non-Gaussian noise. We realize the switching between two kinds of logic gates under optimal moderate noise intensity by varying two different tunable parameters in a single gene network. Furthermore, in order to obtain more logic operations, thus providing additional information processing capacity, we obtain in a two-dimensional toggle switch model two complementary logic gates and realize the transformation between two logic gates via the methods of changing different parameters. These simulated results contribute to improve the computational power and functionality of the networks.

Medial Patellofemoral Ligament Reconstruction Procedure Using a Suspensory Femoral Fixation System

PubMed Central

Nakagawa, Shuji; Arai, Yuji; Kan, Hiroyuki; Ueshima, Keiichiro; Ikoma, Kazuya; Terauchi, Ryu; Kubo, Toshikazu

2013-01-01

Recurrent patellar dislocation has recently been treated with anatomic medial patellofemoral ligament (MPFL) reconstruction using a semitendinosus muscle tendon. Although it is necessary to add tension to fix the tendon graft without loading excess stress on the patellofemoral joint, adjustment of the tension can be difficult. To resolve this problem, we developed an MPFL reconstruction procedure using the ToggleLoc Fixation Device (Biomet, Warsaw, IN), in which the semitendinosus muscle tendon is folded and used as a double-bundle tendon graft and 2 bone tunnels and 1 bone tunnel are made on the patellar and femoral sides, respectively. The patellar side of the tendon graft is fixed with an EndoButton (Smith & Nephew, London, England), and the femoral side is fixed with the ToggleLoc. Stepless adjustment of tension of the tendon graft is possible by reducing the size of the loop of the ToggleLoc hung onto the tendon graft. It may be useful to position the patella in the center of the femoral sulcus by confirming the patellofemoral joint fitting. Stability can be confirmed by loading lateral stress on the patella in the extended knee joint. This procedure is less invasive because opening of the lateral side of the femur is not necessary, and it may be useful for MPFL reconstruction. PMID:24892014

Immunization Program

Science.gov Websites

Department home page Immunizations Search: Search Toggle navigation Medical Services Disease Control Facebook Contacts CoverageRates Diseases Immunization Homepage Immunization Honor Roll HPV NDIIS Medical Providers

Broadband, Low-Loss Phase Shifters Based on Thin Ferroelectric Films

NASA Technical Reports Server (NTRS)

Romanofsky, Robert

2004-01-01

Several different types of microwave transmission line phase shifters based on thin ferroelectic films have been developed at the NASA Glenn Research Center. These include a series of coupled microstrip lines, slotline incorporating Marchand balms, odd-mode coplanar strips, and hybrid devices incorporating a switch to toggle the output termination between an open and virtual short circuit. A review of the theory of operation of each of these devices will be presented along with measured performance. Also, devices of the first variety have been subjected to total dose (proton) radiation exposure using a 200 MeV beam energy with a total dose up to nearly 1 kRad (Si). Results of these radiation tests will be discussed.

Spinal Infections

MedlinePlus

Toggle navigation CONDITIONS Low Back Pain Acute Low Back Pain Chronic Low Back Pain SI Joint Pain Other Scoliosis Back Pain and Emotional Distress Muscle Spasms Pinched Nerve Discitis Degenerative Conditions Bulge vs ...

Inclusion and Diversity | NREL

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deep-seeded belief held by our leadership team. Listen to NREL Director Martin Keller share his . Toggle navigation Overall Senior Leadership Research Management Research Staff Postdocs & Interns

Overcenter collet space station truss fastener

NASA Technical Reports Server (NTRS)

Sheridan, Philip L. (Inventor)

1991-01-01

A quick-connect fastener is arranged with a tubular body that is arranged to be engaged against the exterior surface of a hollow attachment fitting and coincidentally aligned with an opening in the fitting. A collet having normally-contracted fingers with outwardly-enlarged ends is operatively arranged in the body to be moved forwardly by an expander member mounted in the tubular body for advancing the collet fingers through the opening in the attachment fitting. Biasing means are arranged between the expander member and a toggle linkage in the tubular body which is selectively operated to urge the expander member forwardly into engagement with the collet fingers with an initial biasing force to advance their forward portions through the body opening and then expand them outwardly. The biasing means also provide a subsequent biasing force for retaining the collet members in their expanded positions once their enlarged forward end portions are on the opposite side of the body.

Sore Throats

MedlinePlus

... Marketplace ENT Careers Marketplace Log in b Search form Log in Toggle navigation b Join Now Donate ... matter in the air from the burning of fossil fuels, as well as common household chemicals, can ...

Lumbar (Open) Microscopic Discectomy

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Toggle navigation CONDITIONS Low Back Pain Acute Low Back Pain Chronic Low Back Pain SI Joint Pain Other Scoliosis Back Pain and Emotional Distress Muscle Spasms Pinched Nerve Discitis Degenerative Conditions Bulge vs ...

Down Syndrome: Education

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... content Toggle navigation Home Our Story Mission Say Hello to Our Team Financial Information NDSS History About ... Events Shop NDSS Home Our Story Mission Say Hello to Our Team Financial Information NDSS History About ...

NCIS publicdefault

Science.gov Websites

SERVICE SUBMIT A TIP CONNECT Facebook Logo Twitter Logo YouTube Logo Toggle navigation ABOUT NCIS MISSION Twitter Logo YouTube Logo CONNECT Privacy Policy Notice | Diversity Policy | Accessibility/Section 508

Types of Stem Cells

MedlinePlus

... Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

Learn About Stem Cells

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... Handbook Stem Cell Glossary Search Toggle Nav Stem Cell Basics Stem cells are the foundation from which ... Home > Learn About Stem Cells > Stem Cell Basics Cells in the human body The human body comprises ...

Retrospective evaluation of milk production and culling risk following either surgical, toggle-pin suture or conservative treatment of left displaced abomasum in Chilean dairy cows.

PubMed

Melendez, P; Romero, C; Pithua, P; Marin, M P; Pinedo, P; Duchens, M

2017-11-01

AIMS To describe milk yield and culling risk in cows diagnosed with left displacement of abomasum (LDA) treated either conservatively, by right flank pyloric omentopexy, or rolling and toggling, compared with normal herdmates from four Chilean dairy herds. METHODS Historical records were obtained from four commercial dairy farms located in Central Chile for cows with a history of LDA between 2010 and 2012, and healthy herdmates. Cows with LDA were categorised into three groups: cows treated with right omentopexy (ST, n=58), cows treated by toggle suturing (TT, n=15) and cows treated conservatively (CT, n=56). Control cows (n=129) were selected from unaffected cows, matched by days in milk (DIM), parity and herd with affected cows. Groups were compared for risk of culling up to 300 DIM and for milk production up to 5 months of lactation using survival and Cox proportional hazard models and mixed models for repeated measures, respectively. RESULTS Compared with cows in the Control group, the risk of being culled up to 300 DIM was 9.1 (SE 0.62) times greater in ST cows, 10.4 (SE 0.68) times greater in TT cows, and 37.3 (SE 0.61) times greater in CT cows (p<0.01). In the first 5 months of lactation, compared with cows in the Control group, mean daily milk production was 23.3 (SE 1.5) kg less in ST cows, 15.3 (SE 1.6) kg less in TT cows, and 30.1 (SE 1.3) kg less in CT cows (p<0.001). CONCLUSIONS AND CLINICAL RELEVANCE Cows in four dairy herds in central Chile diagnosed and treated for LDA produced significantly less milk and had a higher risk of culling than healthy herdmates. Although cows treated surgically or with toggle suture never recovered to the extent of healthy cows, they produced more milk than cows treated conservatively. However, the retrospective nature of the data, the inclusion of only four herds and the non-random allocation to treatments means that these conclusions cannot be extrapolated to the overall dairy cattle population in Chile.

Down Syndrome: Co-Occuring Conditions

MedlinePlus

... content Toggle navigation Home Our Story Mission Say Hello to Our Team Financial Information NDSS History About ... Events Shop NDSS Home Our Story Mission Say Hello to Our Team Financial Information NDSS History About ...

HubbleSite - Out of the ordinary...out of this world.

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Toggle navigation Home News Images Videos Blogs Explore Discoveries Astronomy Technology Education ! Email list: Inbox Astronomy Servicing Missions Reference Desk eBooks WebbTelescope Amazing Space

Interstitial Cystitis Association

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American Orthopaedic Society for Sports Medicine

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... Upcoming Meetings Online Education Archived Meetings Faculty Resources Sports Medicine Fellowships Traveling Fellowship Submit an Abstract Submit ... Support AOSSM Research Publications Toggle American Journal of Sports Medicine Sports Health: A Multidisciplinary Approach Orthopaedic Journal ...

An electrically actuated molecular toggle switch

NASA Astrophysics Data System (ADS)

Gerhard, Lukas; Edelmann, Kevin; Homberg, Jan; Valášek, Michal; Bahoosh, Safa G.; Lukas, Maya; Pauly, Fabian; Mayor, Marcel; Wulfhekel, Wulf

2017-03-01

Molecular electronics is considered a promising approach for future nanoelectronic devices. In order that molecular junctions can be used as electrical switches or even memory devices, they need to be actuated between two distinct conductance states in a controlled and reproducible manner by external stimuli. Here we present a tripodal platform with a cantilever arm and a nitrile group at its end that is lifted from the surface. The formation of a coordinative bond between the nitrile nitrogen and the gold tip of a scanning tunnelling microscope can be controlled by both electrical and mechanical means, and leads to a hysteretic switching of the conductance of the junction by more than two orders of magnitude. This toggle switch can be actuated with high reproducibility so that the forces involved in the mechanical deformation of the molecular cantilever can be determined precisely with scanning tunnelling microscopy.

Nine Things to Know About Stem Cell Treatments

MedlinePlus

... Toggle Nav Nine Things To Know About Stem Cell Treatments Home > Stem Cells and Medicine > Nine Things ... About Stem Cell Treatments Many clinics offering stem cell treatments make claims that are not supported by ...

Accelerated Cure Project for Multiple Sclerosis

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... main content Accelerating research toward a cure for multiple sclerosis Toggle navigation Search form Search Connect Volunteer Donate ... is to accelerate efforts toward a cure for multiple sclerosis by rapidly advancing research that determines its causes ...

Capacitive Trans-Impedance Amplifier Circuit with Charge Injection Compensation

NASA Technical Reports Server (NTRS)

Milkov, Mihail M. (Inventor); Gulbransen, David J. (Inventor)

2016-01-01

A capacitive trans-impedance amplifier circuit with charge injection compensation is provided. A feedback capacitor is connected between an inverting input port and an output port of an amplifier. A MOS reset switch has source and drain terminals connected between the inverting input and output ports of the amplifier, and a gate terminal controlled by a reset signal. The reset switch is open or inactive during an integration phase, and closed or active to electrically connect the inverting input port and output port of the amplifier during a reset phase. One or more compensation capacitors are provided that are not implemented as gate oxide or MOS capacitors. Each compensation capacitor has a first port connected to a compensation signal that is a static signal or a toggling compensation signal that toggles between two compensation voltage values, and a second port connected to the inverting input port of the amplifier.

Airport Traffic Conflict Detection and Resolution Algorithm Evaluation

NASA Technical Reports Server (NTRS)

Jones, Denise R.; Chartrand, Ryan C.; Wilson, Sara R.; Commo, Sean A.; Ballard, Kathryn M.; Otero, Sharon D.; Barker, Glover D.

2016-01-01

Two conflict detection and resolution (CD&R) algorithms for the terminal maneuvering area (TMA) were evaluated in a fast-time batch simulation study at the National Aeronautics and Space Administration (NASA) Langley Research Center. One CD&R algorithm, developed at NASA, was designed to enhance surface situation awareness and provide cockpit alerts of potential conflicts during runway, taxi, and low altitude air-to-air operations. The second algorithm, Enhanced Traffic Situation Awareness on the Airport Surface with Indications and Alerts (SURF IA), was designed to increase flight crew awareness of the runway environment and facilitate an appropriate and timely response to potential conflict situations. The purpose of the study was to evaluate the performance of the aircraft-based CD&R algorithms during various runway, taxiway, and low altitude scenarios, multiple levels of CD&R system equipage, and various levels of horizontal position accuracy. Algorithm performance was assessed through various metrics including the collision rate, nuisance and missed alert rate, and alert toggling rate. The data suggests that, in general, alert toggling, nuisance and missed alerts, and unnecessary maneuvering occurred more frequently as the position accuracy was reduced. Collision avoidance was more effective when all of the aircraft were equipped with CD&R and maneuvered to avoid a collision after an alert was issued. In order to reduce the number of unwanted (nuisance) alerts when taxiing across a runway, a buffer is needed between the hold line and the alerting zone so alerts are not generated when an aircraft is behind the hold line. All of the results support RTCA horizontal position accuracy requirements for performing a CD&R function to reduce the likelihood and severity of runway incursions and collisions.

Website Policies / Important Links | DOepatents

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Videos | NOAA Gulf Spill Restoration

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Slicing of silicon into sheet material. Silicon sheet growth development for the large area silicon sheet task of the low cost silicon solar array project

NASA Technical Reports Server (NTRS)

Holden, S. C.; Fleming, J. R.

1978-01-01

Fabrication of a prototype large capacity multiple blade slurry saw is considered. Design of the bladehead which will tension up to 1000 blades, and cut a 45 cm long silicon ingot as large as 12 cm in diameter is given. The large blade tensioning force of 270,000 kg is applied through two bolts acting on a pair of scissor toggles, significantly reducing operator set-up time. Tests with an upside-down cutting technique resulted in 100% wafering yields and the highest wafer accuracy yet experienced with MS slicing. Variations in oil and abrasives resulted only in degraded slicing results. A technique of continuous abrasive slurry separation to remove silicon debris is described.

Environmental Compliance | NOAA Gulf Spill Restoration

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Quick action clamp

NASA Technical Reports Server (NTRS)

Calco, Frank S. (Inventor)

1991-01-01

A quick release toggle clamp that utilizes a spring that requires a deliberate positive action for disengagement is presented. The clamp has a sliding bolt that provides a latching mechanism. The bolt is moved by a handle that tends to remain in an engaged position while under tension.

IARC - Illinois Accelerator Research Center | Pilot Program

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Toggle navigation Pilot Program Agenda Directions Registration Illinois Accelerator Research Center National Laboratory present Accelerator Stewardship Test Facility Pilot Program Use accelerator technology , energy and environment. With this pilot program, the DOE Office of Science National Laboratories are

Effect of Spinal Manipulation of Upper Cervical Vertebrae on Blood Pressure: Results of a Pilot Sham-Controlled Trial.

PubMed

Goertz, Christine M; Salsbury, Stacie A; Vining, Robert D; Long, Cynthia R; Pohlman, Katherine A; Weeks, William B; Lamas, Gervasio A

2016-06-01

The purpose of this pilot sham-controlled clinical trial was to estimate the treatment effect and safety of toggle recoil spinal manipulation for blood pressure management. Fifty-one participants with prehypertension or stage 1 hypertension (systolic blood pressure ranging from 135 to 159 mm Hg or diastolic blood pressure ranging from 85 to 99 mm Hg) were allocated by an adaptive design to 2 treatments: toggle recoil spinal manipulation or a sham procedure. Participants were seen by a doctor of chiropractic twice weekly for 6 weeks and remained on their antihypertensive medications, as prescribed, throughout the trial. Blood pressure was assessed at baseline and after study visits 1, 6 (week 3), and 12 (week 6), with the primary end point at week 6. Analysis of covariance was used to compare mean blood pressure changes from baseline between groups at each end point, controlling for sex, age, body mass index, and baseline blood pressure. Adjusted mean change from baseline to week 6 was greater in the sham group (systolic, -4.2 mm Hg; diastolic, -1.6 mm Hg) than in the spinal manipulation group (systolic, 0.6 mm Hg; diastolic, 0.7 mm Hg), but the difference was not statistically significant. No serious and few adverse events were noted. Six weeks of toggle recoil spinal manipulation did not lower systolic or diastolic blood pressure when compared with a sham procedure. No serious adverse events from either treatment were reported. Our results do not support a larger clinical trial. Further research to understand the potential mechanisms of action involving upper cervical manipulation on blood pressure is warranted before additional clinical investigations are conducted. Copyright © 2016. Published by Elsevier Inc.

Division of Agriculture

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Department of Natural Resources logo, color scheme Department of Natural Resources Division of Agriculture Search Search DNR's site DNR State of Alaska Toggle main menu visibility Agriculture Home Programs Asset Disposals Alaska Caps Progam Board of Agriculture & Conservation Farm To School Program Grants

Mojave Desert Ecosystem Program

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Toggle navigation logo garis Home About Search Contact About Us History The Mojave Desert Ecosystem providing dynamic, sustainable, land management decision-making at the ecosystem level. Its numerous mission of the Mojave Desert Ecosystem Program is to provide government agencies throughout the Mojave

Multi-scale kinetics of a field-directed colloidal phase transition.

PubMed

Swan, James W; Vasquez, Paula A; Whitson, Peggy A; Fincke, E Michael; Wakata, Koichi; Magnus, Sandra H; De Winne, Frank; Barratt, Michael R; Agui, Juan H; Green, Robert D; Hall, Nancy R; Bohman, Donna Y; Bunnell, Charles T; Gast, Alice P; Furst, Eric M

2012-10-02

Polarizable colloids are expected to form crystalline equilibrium phases when exposed to a steady, uniform field. However, when colloids become localized this field-induced phase transition arrests and the suspension persists indefinitely as a kinetically trapped, percolated structure. We anneal such gels formed from magneto-rheological fluids by toggling the field strength at varied frequencies. This processing allows the arrested structure to relax periodically to equilibrium--colloid-rich, cylindrical columns. Two distinct growth regimes are observed: one in which particle domains ripen through diffusive relaxation of the gel, and the other where the system-spanning structure collapses and columnar domains coalesce apparently through field-driven interactions. There is a stark boundary as a function of magnetic field strength and toggle frequency distinguishing the two regimes. These results demonstrate how kinetic barriers to a colloidal phase transition are subverted through measured, periodic variation of driving forces. Such directed assembly may be harnessed to create unique materials from dispersions of colloids.

Center for Interface Science and Catalysis | Theory

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& Stanford School of Engineering Toggle navigation Home Research Publications People About Academic to overcome challenges associated with the atomic-scale design of catalysts for chemical computational methods we are developing a quantitative description of chemical processes at the solid-gas and

HubbleSite: News

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Office of Diversity Management and Equal Opportunity

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Office of Water Prediction

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Defense Human Resources Activity > PERSEREC

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Department of Defense Senior Intelligence Oversight Official

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Defense Contract Management Agency

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Alaska Department of Natural Resources

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Information Information Resource Management Information Resource Management (IRM) maintains the department's DNR's site DNR State of Alaska Toggle main menu visibility Home Contact Us Information Resource Management Recorder's Office/UCC Recorder's Office Recorder's Office Search Uniform Commercial Code (UCC) UCC

III: Trying Something New

ERIC Educational Resources Information Center

Rosenfeld, Malke; Rufo, David; Makol, Suzanne; Greco, Ardina; Flores, Chio; Redman, Jeff

2014-01-01

The last two sections (EJ1039315 and EJ1039319) presented stories about specific moments or lessons. Also, situations infused with complexity where the writers had to toggle back and forth between providing the larger context and the details that support readers' understanding of that big picture were presented. In this section each story is…

X-ray ptychography, fluorescence microscopy combo sheds new light on trace

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Data from: Solving the Robot-World Hand-Eye(s) Calibration Problem with

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Iterative Methods | National Agricultural Library Skip to main content Home National Agricultural Library United States Department of Agriculture Ag Data Commons Beta Toggle navigation Datasets . License U.S. Public Domain Funding Source(s) National Science Foundation IOS-1339211 Agricultural Research

Clean Cities Technical Assistance | State, Local, and Tribal Governments |

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NREL Toggle navigation Menu Technical Assistance Technical Assistance States Tribes Clean » State, Local, and Tribal Governments » Clean Cities Technical Assistance Clean Cities Technical reduce petroleum use in transportation by providing technical assistance, educational and outreach

Positron Beam Characteristics at NEPOMUC Upgrade

NASA Astrophysics Data System (ADS)

Hugenschmidt, C.; Ceeh, H.; Gigl, T.; Lippert, F.; Piochacz, C.; Reiner, M.; Schreckenbach, K.; Vohburger, S.; Weber, J.; Zimnik, S.

2014-04-01

In 2012, the new neutron induced positron source NEPOMUC upgrade was put into operation at FRMII. Major changes have been made to the source which consists of a neutron-γ-converter out of Cd and a Pt foil structure for electron positron pair production and positron moderation. The new design leads to an improvement of both intensity and brightness of the mono-energetic positron beam. In addition, the application of highly enriched 113Cd as neutron-γ-converter extends the lifetime of the positron source to 25 years. A new switching and remoderation device has been installed in order to allow toggling from the high-intensity primary beam to a brightness enhanced remoderated positron beam. At present, an intensity of more than 109 moderated positrons per second is achieved at NEPOMUC upgrade. The main characteristics are presented which comprise positron yield and beam profile of both the primary and the remoderated positron beam.

Non-Lethal Weapons Program

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), 26th Marine Expeditionary Unit (MEU), practice non-lethal control techniques during a non-lethal Skip to main content (Press Enter). Toggle navigation Non-Lethal Weapons Program Search Search JNLWP: Search Search JNLWP: Search Non-Lethal Weapons Program U.S. Department of Defense Non-Lethal

Modulation of starch digestion for slow glucose release through "toggling" of activities of mucosal "alpha"-glucosidases

USDA-ARS?s Scientific Manuscript database

Starch digestion involves the breakdown by alpha-amylase to small linear and branched malto-oligosaccharides, which are in turn hydrolyzed to glucose by the mucosal alpha-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI). MGAM and SI are anchored to the small intestinal brush-bor...

U.S. Northern Command > Newsroom > Press Releases

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Skip to main content (Press Enter). Toggle navigation U.S. Northern Command Search Search USNORTHCOM: Search Search USNORTHCOM: Search U.S. Northern Command U.S. Northern Command Home Leadership , 2018 NORAD and USNORTHCOM to host change of command ceremony Nov. 30, 2017 United States, Mexico to

Crashworthy Troop Seat Testing Program

DTIC Science & Technology

1977-11-01

19 ’rest 4 . . . . . . . . . .. . 29 | Detail Design’Finalization. .... 29 Vertical Wire - Bending Energy Attenuator 32 Toggle Latch...Strut Wire - Bending Attenuator Force Deflection. . . . ................... 28 15 Notched Wire and Pin Anchorage Test Specimen . 30 16 Quick-Disconnect...and Hold-Down Cable ......... 31 17 Failed Hold-Down Cable ...... . . . . 31 18 Wire - Bending Tension/Compression Energy Attenuator

Chief Information Officer > DoDSection508

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Biographies of Senior Defense Officials

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Chief Information Officer > Library

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Chief Information Officer > In the News

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Chief Information Officer > About DoD CIO

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Ferguson Troubleshoots GPC 3

NASA Image and Video Library

2011-07-11

S135-E-007350 (11 July 2011) --- NASA astronaut Chris Ferguson, STS-135 mission commander, toggles switches on the overhead panel of the forward flight deck of the space shuttle Atlantis. The image was recorded during the mission's fourth day of activities in Earth orbit and second day while being docked with the International Space Station. Photo credit: NASA

outreach | News

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. Photo: Elliott McCrory On March 3, 71 local high school students graduated from the winter session of Figures STEM program for local students February 20, 2018 | Sarah Lawhun After watching short videos on Students and teachers Media News Navbar Toggle Newsroom News and features Press releases Fermilab in the

Gulf Dolphins Slideshow | NOAA Gulf Spill Restoration

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Skip to main content Home Home Toggle navigation Search form Search Search the web Search NOAA Gulf Spill Restoration Search Home About Us Trustees Contact Us How We Restore Planning Damage Assessment Archive Home Gulf Dolphins Slideshow Gulf Dolphins Slideshow share Posted on March 23, 2012 | Assessment

Christmas Light Display

NASA Astrophysics Data System (ADS)

Ross, Arthur; Renfro, Timothy

2012-03-01

The Digital Electronics class at McMurry University created a Christmas light display that toggles the power of different strands of lights, according to what frequencies are played in a song, as an example of an analog to digital circuit. This was accomplished using a BA3830S IC six-band audio filter and six solid-state relays.

The Better World Project - Home

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Toggle navigation Featured Stories Past Reports FAQ Background Information 500 Better World Stories ... and Counting! Thanks to the hard work of AUTM members around the world, the Better World Project Better World Project Database. Simply type in the criteria you're looking for. Add Your Story to the

The Relationship between Software Design and Children's Engagement

ERIC Educational Resources Information Center

Buckleitner, Warren

2006-01-01

This study was an attempt to measure the effects of praise and reinforcement on children in a computer learning setting. A sorting game was designed to simulate 2 interaction styles. One style, called high computer control, provided frequent praise and coaching. The other, called high child control, had narration and praise toggled off. A…

::: American Indians of the Pacific Northwest Collection :::

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Ask Us! University of Washington Libraries Digital Collections Toggle navigation Browse Special learn from the images and writings of the time...This site provides an extensive digital collection of digital databases includes over 2,300 original photographs as well as over 1,500 pages from the Annual

Aversive Learning and Appetitive Motivation Toggle Feed-Forward Inhibition in the Drosophila Mushroom Body.

PubMed

Perisse, Emmanuel; Owald, David; Barnstedt, Oliver; Talbot, Clifford B; Huetteroth, Wolf; Waddell, Scott

2016-06-01

In Drosophila, negatively reinforcing dopaminergic neurons also provide the inhibitory control of satiety over appetitive memory expression. Here we show that aversive learning causes a persistent depression of the conditioned odor drive to two downstream feed-forward inhibitory GABAergic interneurons of the mushroom body, called MVP2, or mushroom body output neuron (MBON)-γ1pedc>α/β. However, MVP2 neuron output is only essential for expression of short-term aversive memory. Stimulating MVP2 neurons preferentially inhibits the odor-evoked activity of avoidance-directing MBONs and odor-driven avoidance behavior, whereas their inhibition enhances odor avoidance. In contrast, odor-evoked activity of MVP2 neurons is elevated in hungry flies, and their feed-forward inhibition is required for expression of appetitive memory at all times. Moreover, imposing MVP2 activity promotes inappropriate appetitive memory expression in food-satiated flies. Aversive learning and appetitive motivation therefore toggle alternate modes of a common feed-forward inhibitory MVP2 pathway to promote conditioned odor avoidance or approach. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Analysis and design of a genetic circuit for dynamic metabolic engineering.

PubMed

Anesiadis, Nikolaos; Kobayashi, Hideki; Cluett, William R; Mahadevan, Radhakrishnan

2013-08-16

Recent advances in synthetic biology have equipped us with new tools for bioprocess optimization at the genetic level. Previously, we have presented an integrated in silico design for the dynamic control of gene expression based on a density-sensing unit and a genetic toggle switch. In the present paper, analysis of a serine-producing Escherichia coli mutant shows that an instantaneous ON-OFF switch leads to a maximum theoretical productivity improvement of 29.6% compared to the mutant. To further the design, global sensitivity analysis is applied here to a mathematical model of serine production in E. coli coupled with a genetic circuit. The model of the quorum sensing and the toggle switch involves 13 parameters of which 3 are identified as having a significant effect on serine concentration. Simulations conducted in this reduced parameter space further identified the optimal ranges for these 3 key parameters to achieve productivity values close to the maximum theoretical values. This analysis can now be used to guide the experimental implementation of a dynamic metabolic engineering strategy and reduce the time required to design the genetic circuit components.

Off and back-on again: a tumor suppressor's tale.

PubMed

Acosta, Jonuelle; Wang, Walter; Feldser, David M

2018-06-01

Tumor suppressor genes play critical roles orchestrating anti-cancer programs that are both context dependent and mechanistically diverse. Beyond canonical tumor suppressive programs that control cell division, cell death, and genome stability, unexpected tumor suppressor gene activities that regulate metabolism, immune surveillance, the epigenetic landscape, and others have recently emerged. This diversity underscores the important roles these genes play in maintaining cellular homeostasis to suppress cancer initiation and progression, but also highlights a tremendous challenge in discerning precise context-specific programs of tumor suppression controlled by a given tumor suppressor. Fortunately, the rapid sophistication of genetically engineered mouse models of cancer has begun to shed light on these context-dependent tumor suppressor activities. By using techniques that not only toggle "off" tumor suppressor genes in nascent tumors, but also facilitate the timely restoration of gene function "back-on again" in disease specific contexts, precise mechanisms of tumor suppression can be revealed in an unbiased manner. This review discusses the development and implementation of genetic systems designed to toggle tumor suppressor genes off and back-on again and their potential to uncover the tumor suppressor's tale.

Programmable cells: Interfacing natural and engineered gene networks

NASA Astrophysics Data System (ADS)

Kobayashi, Hideki; Kærn, Mads; Araki, Michihiro; Chung, Kristy; Gardner, Timothy S.; Cantor, Charles R.; Collins, James J.

2004-06-01

Novel cellular behaviors and characteristics can be obtained by coupling engineered gene networks to the cell's natural regulatory circuitry through appropriately designed input and output interfaces. Here, we demonstrate how an engineered genetic circuit can be used to construct cells that respond to biological signals in a predetermined and programmable fashion. We employ a modular design strategy to create Escherichia coli strains where a genetic toggle switch is interfaced with: (i) the SOS signaling pathway responding to DNA damage, and (ii) a transgenic quorum sensing signaling pathway from Vibrio fischeri. The genetic toggle switch endows these strains with binary response dynamics and an epigenetic inheritance that supports a persistent phenotypic alteration in response to transient signals. These features are exploited to engineer cells that form biofilms in response to DNA-damaging agents and cells that activate protein synthesis when the cell population reaches a critical density. Our work represents a step toward the development of "plug-and-play" genetic circuitry that can be used to create cells with programmable behaviors. heterologous gene expression | synthetic biology | Escherichia coli

Action of Molecular Switches in GPCRs - Theoretical and Experimental Studies

PubMed Central

Trzaskowski, B; Latek, D; Yuan, S; Ghoshdastider, U; Debinski, A; Filipek, S

2012-01-01

G protein coupled receptors (GPCRs), also called 7TM receptors, form a huge superfamily of membrane proteins that, upon activation by extracellular agonists, pass the signal to the cell interior. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. Biochemical and crystallographic methods together with molecular dynamics simulations and other theoretical techniques provided models of the receptor activation based on the action of so-called “molecular switches” buried in the receptor structure. They are changed by agonists but also by inverse agonists evoking an ensemble of activation states leading toward different activation pathways. Switches discovered so far include the ionic lock switch, the 3-7 lock switch, the tyrosine toggle switch linked with the nPxxy motif in TM7, and the transmission switch. The latter one was proposed instead of the tryptophan rotamer toggle switch because no change of the rotamer was observed in structures of activated receptors. The global toggle switch suggested earlier consisting of a vertical rigid motion of TM6, seems also to be implausible based on the recent crystal structures of GPCRs with agonists. Theoretical and experimental methods (crystallography, NMR, specific spectroscopic methods like FRET/BRET but also single-molecule-force-spectroscopy) are currently used to study the effect of ligands on the receptor structure, location of stable structural segments/domains of GPCRs, and to answer the still open question on how ligands are binding: either via ensemble of conformational receptor states or rather via induced fit mechanisms. On the other hand the structural investigations of homo- and heterodimers and higher oligomers revealed the mechanism of allosteric signal transmission and receptor activation that could lead to design highly effective and selective allosteric or ago-allosteric drugs. PMID:22300046

Action of molecular switches in GPCRs--theoretical and experimental studies.

PubMed

Trzaskowski, B; Latek, D; Yuan, S; Ghoshdastider, U; Debinski, A; Filipek, S

2012-01-01

G protein coupled receptors (GPCRs), also called 7TM receptors, form a huge superfamily of membrane proteins that, upon activation by extracellular agonists, pass the signal to the cell interior. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. Biochemical and crystallographic methods together with molecular dynamics simulations and other theoretical techniques provided models of the receptor activation based on the action of so-called "molecular switches" buried in the receptor structure. They are changed by agonists but also by inverse agonists evoking an ensemble of activation states leading toward different activation pathways. Switches discovered so far include the ionic lock switch, the 3-7 lock switch, the tyrosine toggle switch linked with the nPxxy motif in TM7, and the transmission switch. The latter one was proposed instead of the tryptophan rotamer toggle switch because no change of the rotamer was observed in structures of activated receptors. The global toggle switch suggested earlier consisting of a vertical rigid motion of TM6, seems also to be implausible based on the recent crystal structures of GPCRs with agonists. Theoretical and experimental methods (crystallography, NMR, specific spectroscopic methods like FRET/BRET but also single-molecule-force-spectroscopy) are currently used to study the effect of ligands on the receptor structure, location of stable structural segments/domains of GPCRs, and to answer the still open question on how ligands are binding: either via ensemble of conformational receptor states or rather via induced fit mechanisms. On the other hand the structural investigations of homoand heterodimers and higher oligomers revealed the mechanism of allosteric signal transmission and receptor activation that could lead to design highly effective and selective allosteric or ago-allosteric drugs.

Toggling of seismicity by the 1997 Kagoshima earthquake couplet: A demonstration of time-dependent stress transfer

USGS Publications Warehouse

Toda, S.; Stein, R.

2003-01-01

Two M ??? 6 well-recorded strike-slip earthquakes struck just 4 km and 48 days apart in Kagoshima prefecture, Japan, in 1997, providing an opportunity to study earthquake interaction. Aftershocks are abundant where the Coulomb stress is calculated to have been increased by the first event, and they abruptly stop where the stress is dropped by the second event. This ability of the main shocks to toggle seismicity on and off argues that static stress changes play a major role in exciting aftershocks, whereas the dynamic Coulomb stresses, which should only promote seismicity, appear to play a secondary role. If true, the net stress changes from a sequence of earthquakes might be expected to govern the subsequent seismicity distribution. However, adding the stress changes from the two Kagoshima events does not fully capture the ensuing seismicity, such as its rate change, temporal decay, or migration away from the ends of the ruptures. We therefore implement a stress transfer model that incorporates rate/state friction, in which seismicity is treated as a sequence of independent nucleation events that are dependent on the fault slip, slip rate, and elapsed time since the last event. The model reproduces the temporal response of seismicity to successive stress changes, including toggling, decay, and aftershock migration. Nevertheless, the match of observed to predicted seismicity is quite imperfect, due perhaps to inadequate knowledge of several model parameters. However, to demonstrate the potential of this approach, we build a probabilistic forecast of larger earthquakes on the expected rate of small aftershocks, taking advantage of the large statistical sample the small shocks afford. Not surprisingly, such probabilities are highly time- and location-dependent: During the first decade after the main shocks, the seismicity rate and the chance of successive large shocks are about an order of magnitude higher than the background rate and are concentrated exclusively in the stress triggering zones. Copyright 2003 by the American Geophysical Uion.

Chief Information Officer > About DoD CIO > Organization > DCIO R&A

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provide strategy, leadership, and guidance to create a unified information management and technology Skip to main content (Press Enter). Toggle navigation Chief Information Officer Search Search Chief Information Officer: Search Search Chief Information Officer: Search Chief Information Officer U.S. Department

49 CFR Appendix A to Part 180 - Internal Self-closing Stop Valve Emergency Closure Test for Liquefied Compressed Gases

Code of Federal Regulations, 2010 CFR

2010-10-01

... Test for Liquefied Compressed Gases A Appendix A to Part 180 Transportation Other Regulations Relating... Compressed Gases 1. In performing this test, all internal self-closing stop valves must be opened. Each.... 2. On pump-actuated pressure differential internal valves, the three-way toggle valve handle or its...

Information Technology Exchange Program (ITEP) - U.S. Department of Defense

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Web and Internet-based Capabilities (IbC) Policies - U.S. Department of

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Defense Skip to main content (Press Enter). Toggle navigation Chief Information Officer Search Search Chief Information Officer: Search Search Chief Information Officer: Search Chief Information Officer U.S. Department of Defense Chief Information Officer Home About DoD CIO Bios Organization DCIO C4

Chief Information Officer > About DoD CIO > Organization > DCIO IE

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Learn More at Public Meetings | NOAA Gulf Spill Restoration

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Skip to main content Home Home Toggle navigation Search form Search Search the web Search NOAA Gulf Spill Restoration Search Home About Us Trustees Contact Us How We Restore Planning Damage Assessment Archive Home Learn More at Public Meetings Learn More at Public Meetings Get Involved in Restoring the

Study of Man-Machine Communications Systems for Disabled Persons (The Handicapped). Volume VII. Final Report.

ERIC Educational Resources Information Center

Kafafian, Haig

Teaching instructions, lesson plans, and exercises are provided for severely physically and/or neurologically handicapped persons learning to use the Cybertype electric writing machine with a tongue-body keyboard. The keyboard, which has eight double-throw toggle switches and a three-position state-selector switch, is designed to be used by…

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76 FR 73667 - Notice of Inventory Completion: U.S. Department of Defense, Army Corps of Engineers, Walla Walla...

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2011-11-29

.... No known individuals were identified. The three associated funerary objects are 1 bone whistle from... associated funerary objects are 4 adze blades, 1 awl, 2 beaver incisors, 2 bone needles, 1 bone point, 1 bone toggle, 1 incised bird bone, 3 pieces of incised bone, 3 pestles, 3 polished bone items, 3 polished...

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Radar channel balancing with commutation

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

Doerry, Armin Walter

2014-02-01

When multiple channels are employed in a pulse-Doppler radar, achieving and maintaining balance between the channels is problematic. In some circumstances the channels may be commutated to achieve adequate balance. Commutation is the switching, trading, toggling, or multiplexing of the channels between signal paths. Commutation allows modulating the imbalance energy away from the balanced energy in Doppler, where it can be mitigated with filtering.

The bacterial nanorecorder: engineering E. coli to function as a chemical recording device.

PubMed

Bhomkar, Prasanna; Materi, Wayne; Wishart, David S

2011-01-01

Synthetic biology is an emerging branch of molecular biology that uses synthetic genetic constructs to create man-made cells or organisms that are capable of performing novel and/or useful applications. Using a synthetic chemically sensitive genetic toggle switch to activate appropriate fluorescent protein indicators (GFP, RFP) and a cell division inhibitor (minC), we have created a novel E. coli strain that can be used as a highly specific, yet simple and inexpensive chemical recording device. This biological "nanorecorder" can be used to determine both the type and the time at which a brief chemical exposure event has occurred. In particular, we show that the short-term exposure (15-30 min) of cells harboring this synthetic genetic circuit to small molecule signals (anhydrotetracycline or IPTG) triggered long-term and uniform cell elongation, with cell length being directly proportional to the time elapsed following a brief chemical exposure. This work demonstrates that facile modification of an existing genetic toggle switch can be exploited to generate a robust, biologically-based "nanorecorder" that could potentially be adapted to detect, respond and record a wide range of chemical stimuli that may vary over time and space.

Finite Element Analysis and Vibration Control of Lorry’s Shift Mechanism

NASA Astrophysics Data System (ADS)

Qiangwei, Li

2017-11-01

The transmission is one of the important parts of the automobile’s transmission system, Shift mechanism’s main function of transmission is to adjust the position of the shift fork, toggle the synchronizer’s tooth ring, so that the gears are separated and combined to achieve the shift. Therefore, in order to ensure the reliability and stability of the shift process, the vibration characteristics of the shift mechanism cannot be ignored. The static analysis of the shift fork is carried out, and the stress distribution of the shift fork is obtained according to the operating characteristics of the shift mechanism of the lorry transmission in this paper. The modal analysis of the shift mechanism shows the low-order vibration frequencies and the corresponding modal vibration shapes, and the vibration control analysis is carried out according to the simulation results. The simulation results provide the theoretical basis for the reasonable optimization design of the shift mechanism of the lorry transmission.

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Walheim Troubleshoots GPC 3

NASA Image and Video Library

2011-07-11

S135-E-007351 (11 July 2011) --- NASA astronaut Rex Walheim, STS-135 mission specialist, watches as astronaut Chris Ferguson (out of frame at right) toggles switches on the overhead panel of the forward flight deck of the space shuttle Atlantis. The action came during the mission's fourth day of activities in Earth orbit and second day while being docked with the International Space Station. Photo credit: NASA

Single event effects in pulse width modulation controllers

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

Penzin, S.H.; Crain, W.R.; Crawford, K.B.

1996-12-01

SEE testing was performed on pulse width modulation (PWM) controllers which are commonly used in switching mode power supply systems. The devices are designed using both Set-Reset (SR) flip-flops and Toggle (T) flip-flops which are vulnerable to single event upset (SEU) in a radiation environment. Depending on the implementation of the different devices the effect can be significant in spaceflight hardware.

Mind the GAP: A Novel Tumor-Promoting Mechanism | Center for Cancer Research

Cancer.gov

RAS proteins, like light switches, toggle between an “on” conformation where they promote cell growth, survival, and/or the formation of blood vessels (known as angiogenesis) and an “off” conformation in which they are unable to stimulate their target effector proteins. Nearly one-third of human tumors express a mutated RAS gene, which encodes a protein locked permanently in

Enhancing poly-γ-glutamic acid production in Bacillus amyloliquefaciens by introducing the glutamate synthesis features from Corynebacterium glutamicum.

PubMed

Feng, Jun; Quan, Yufen; Gu, Yanyan; Liu, Fenghong; Huang, Xiaozhong; Shen, Haosheng; Dang, Yulei; Cao, Mingfeng; Gao, Weixia; Lu, Xiaoyun; Wang, Yi; Song, Cunjiang; Wang, Shufang

2017-05-22

Poly-γ-glutamic acid (γ-PGA) is a valuable polymer with glutamate as its sole precursor. Enhancement of the intracellular glutamate synthesis is a very important strategy for the improvement of γ-PGA production, especially for those glutamate-independent γ-PGA producing strains. Corynebacterium glutamicum has long been used for industrial glutamate production and it exhibits some unique features for glutamate synthesis; therefore introduction of these metabolic characters into the γ-PGA producing strain might lead to increased intracellular glutamate availability, and thus ultimate γ-PGA production. In this study, the unique glutamate synthesis features from C. glutamicum was introduced into the glutamate-independent γ-PGA producing Bacillus amyloliquefaciens NK-1 strain. After introducing the energy-saving NADPH-dependent glutamate dehydrogenase (NADPH-GDH) pathway, the NK-1 (pHT315-gdh) strain showed slightly increase (by 9.1%) in γ-PGA production. Moreover, an optimized metabolic toggle switch for controlling the expression of ɑ-oxoglutarate dehydrogenase complex (ODHC) was introduced into the NK-1 strain, because it was previously shown that the ODHC in C. glutamicum was completely inhibited when glutamate was actively produced. The obtained NK-PO1 (pHT01-xylR) strain showed 66.2% higher γ-PGA production than the NK-1 strain. However, the further combination of these two strategies (introducing both NADPH-GDH pathway and the metabolic toggle switch) did not lead to further increase of γ-PGA production but rather the resultant γ-PGA production was even lower than that in the NK-1 strain. We proposed new metabolic engineering strategies to improve the γ-PGA production in B. amyloliquefaciens. The NK-1 (pHT315-gdh) strain with the introduction of NADPH-GDH pathway showed 9.1% improvement in γ-PGA production. The NK-PO1 (pHT01-xylR) strain with the introduction of a metabolic toggle switch for controlling the expression of ODHC showed 66.2% higher γ-PGA production than the NK-1 strain. This work proposed a new strategy for improving the target product in microbial cell factories.

A Circadian Clock-Regulated Toggle Switch Explains AtGRP7 and AtGRP8 Oscillations in Arabidopsis thaliana

PubMed Central

Schmal, Christoph; Reimann, Peter; Staiger, Dorothee

2013-01-01

The circadian clock controls many physiological processes in higher plants and causes a large fraction of the genome to be expressed with a 24h rhythm. The transcripts encoding the RNA-binding proteins AtGRP7 (Arabidopsis thaliana Glycine Rich Protein 7) and AtGRP8 oscillate with evening peaks. The circadian clock components CCA1 and LHY negatively affect AtGRP7 expression at the level of transcription. AtGRP7 and AtGRP8, in turn, negatively auto-regulate and reciprocally cross-regulate post-transcriptionally: high protein levels promote the generation of an alternative splice form that is rapidly degraded. This clock-regulated feedback loop has been proposed to act as a molecular slave oscillator in clock output. While mathematical models describing the circadian core oscillator in Arabidopsis thaliana were introduced recently, we propose here the first model of a circadian slave oscillator. We define the slave oscillator in terms of ordinary differential equations and identify the model's parameters by an optimization procedure based on experimental results. The model successfully reproduces the pertinent experimental findings such as waveforms, phases, and half-lives of the time-dependent concentrations. Furthermore, we obtain insights into possible mechanisms underlying the observed experimental dynamics: the negative auto-regulation and reciprocal cross-regulation via alternative splicing could be responsible for the sharply peaking waveforms of the AtGRP7 and AtGRP8 mRNA. Moreover, our results suggest that the AtGRP8 transcript oscillations are subordinated to those of AtGRP7 due to a higher impact of AtGRP7 protein on alternative splicing of its own and of the AtGRP8 pre-mRNA compared to the impact of AtGRP8 protein. Importantly, a bifurcation analysis provides theoretical evidence that the slave oscillator could be a toggle switch, arising from the reciprocal cross-regulation at the post-transcriptional level. In view of this, transcriptional repression of AtGRP7 and AtGRP8 by LHY and CCA1 induces oscillations of the toggle switch, leading to the observed high-amplitude oscillations of AtGRP7 mRNA. PMID:23555221

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Influenza (Flu) | North Carolina Department of Health and Human Services

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Toggle navigation Home Statistics Providers FAQs Information Contact Don't Be a Shot Dodger! Meet , the flu knocks everyone off their game. Don't be a Shot Dodger! Contact your health care provider or Clinicians (PDF, 31KB) - UPDATED 09/27/17 Novel Influenza Information N.C. Memo to Clinicians on Influenza A

Robotic Vehicle Communications Interoperability

DTIC Science & Technology

1988-08-01

starter (cold start) X X Fire suppression X Fording control X Fuel control X Fuel tank selector X Garage toggle X Gear selector X X X X Hazard warning...optic Sensors Sensor switch Video Radar IR Thermal imaging system Image intensifier Laser ranger Video camera selector Forward Stereo Rear Sensor control...optic sensors Sensor switch Video Radar IR Thermal imaging system Image intensifier Laser ranger Video camera selector Forward Stereo Rear Sensor

Fermilab | Science | Questions for the Universe | The Particle World | What

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is dark matter? How can we make it in the laboratory? Fermilab Search Toggle Fermilab Navbar Fermilab and the LHC Dark matter and dark energy ADMX Muons More fundamental particles and forces Theory there so many kinds of particles? What is dark matter? How can we make it in the laboratory? What are

Stability and Multiattractor Dynamics of a Toggle Switch Based on a Two-Stage Model of Stochastic Gene Expression

PubMed Central

Strasser, Michael; Theis, Fabian J.; Marr, Carsten

2012-01-01

A toggle switch consists of two genes that mutually repress each other. This regulatory motif is active during cell differentiation and is thought to act as a memory device, being able to choose and maintain cell fate decisions. Commonly, this switch has been modeled in a deterministic framework where transcription and translation are lumped together. In this description, bistability occurs for transcription factor cooperativity, whereas autoactivation leads to a tristable system with an additional undecided state. In this contribution, we study the stability and dynamics of a two-stage gene expression switch within a probabilistic framework inspired by the properties of the Pu/Gata toggle switch in myeloid progenitor cells. We focus on low mRNA numbers, high protein abundance, and monomeric transcription-factor binding. Contrary to the expectation from a deterministic description, this switch shows complex multiattractor dynamics without autoactivation and cooperativity. Most importantly, the four attractors of the system, which only emerge in a probabilistic two-stage description, can be identified with committed and primed states in cell differentiation. To begin, we study the dynamics of the system and infer the mechanisms that move the system between attractors using both the quasipotential and the probability flux of the system. Next, we show that the residence times of the system in one of the committed attractors are geometrically distributed. We derive an analytical expression for the parameter of the geometric distribution, therefore completely describing the statistics of the switching process and elucidate the influence of the system parameters on the residence time. Moreover, we find that the mean residence time increases linearly with the mean protein level. This scaling also holds for a one-stage scenario and for autoactivation. Finally, we study the implications of this distribution for the stability of a switch and discuss the influence of the stability on a specific cell differentiation mechanism. Our model explains lineage priming and proposes the need of either high protein numbers or long-term modifications such as chromatin remodeling to achieve stable cell fate decisions. Notably, we present a system with high protein abundance that nevertheless requires a probabilistic description to exhibit multistability, complex switching dynamics, and lineage priming. PMID:22225794

A visualization system for CT based pulmonary fissure analysis

NASA Astrophysics Data System (ADS)

Pu, Jiantao; Zheng, Bin; Park, Sang Cheol

2009-02-01

In this study we describe a visualization system of pulmonary fissures depicted on CT images. The purpose is to provide clinicians with an intuitive perception of a patient's lung anatomy through an interactive examination of fissures, enhancing their understanding and accurate diagnosis of lung diseases. This system consists of four key components: (1) region-of-interest segmentation; (2) three-dimensional surface modeling; (3) fissure type classification; and (4) an interactive user interface, by which the extracted fissures are displayed flexibly in different space domains including image space, geometric space, and mixed space using simple toggling "on" and "off" operations. In this system, the different visualization modes allow users not only to examine the fissures themselves but also to analyze the relationship between fissures and their surrounding structures. In addition, the users can adjust thresholds interactively to visualize the fissure surface under different scanning and processing conditions. Such a visualization tool is expected to facilitate investigation of structures near the fissures and provide an efficient "visual aid" for other applications such as treatment planning and assessment of therapeutic efficacy as well as education of medical professionals.

Business Planning Model Programmer’s Guide

DTIC Science & Technology

1993-12-01

BPMREPI.PRG 847 temnpupgrade BPMOPEN.PRG 163 te - da -org BPMWHA2.PRG 1949 te tot BPMWHA2.PRG 1912 tgzzoggle BPMWHA2.PRG 349 tlbr UTILITY.PRG 921 toggle...closewindowIdispcapital get-totals disp capital. openwindow disp capital pad disp capital showeditinsg disp__capital tlbr disp capital wr-arr disp capital wr-dulsUdisp_...showeditnisg disp__contract tlbr disp contract wr -arrIdisp_ contract wr -duls disp contract wr uls disp__contract wrjyears disp expense closewindow

Optomechanically induced spontaneous symmetry breaking

NASA Astrophysics Data System (ADS)

Miri, Mohammad-Ali; Verhagen, Ewold; Alú, Andrea

2017-05-01

We explore the dynamics of spontaneous breakdown of mirror symmetry in a pair of identical optomechanical cavities symmetrically coupled to a waveguide. Large optical intensities enable optomechanically induced nonlinear detuning of the optical resonators, resulting in a pitchfork bifurcation. We investigate the stability of this regime and explore the possibility of inducing multistability. By injecting proper trigger pulses, the proposed structure can toggle between two asymmetric stable states, thus serving as a low-noise nanophotonic all-optical switch or memory element.

Glove box on vehicular instrument panel

DOEpatents

Atarashi, Kazuya

1985-01-01

A glove box for the upper surface of an automobile dashboard whereby it may be positioned close to the driver. The glove box lid is pivotally supported by arms extending down either side to swing forwardly for opening. A hook is pivotally support adjacent an arm and weighted to swing into engagement with the arm to prevent opening of the lid during abrupt deceleration. A toggle spring assists in maintaining the lid in either the open or closed position.

A Multistate Toggle Switch Defines Fungal Cell Fates and Is Regulated by Synergistic Genetic Cues

PubMed Central

Anderson, Matthew Z.; Porman, Allison M.; Wang, Na; Mancera, Eugenio; Bennett, Richard J.

2016-01-01

Heritable epigenetic changes underlie the ability of cells to differentiate into distinct cell types. Here, we demonstrate that the fungal pathogen Candida tropicalis exhibits multipotency, undergoing stochastic and reversible switching between three cellular states. The three cell states exhibit unique cellular morphologies, growth rates, and global gene expression profiles. Genetic analysis identified six transcription factors that play key roles in regulating cell differentiation. In particular, we show that forced expression of Wor1 or Efg1 transcription factors can be used to manipulate transitions between all three cell states. A model for tristability is proposed in which Wor1 and Efg1 are self-activating but mutually antagonistic transcription factors, thereby forming a symmetrical self-activating toggle switch. We explicitly test this model and show that ectopic expression of WOR1 can induce white-to-hybrid-to-opaque switching, whereas ectopic expression of EFG1 drives switching in the opposite direction, from opaque-to-hybrid-to-white cell states. We also address the stability of induced cell states and demonstrate that stable differentiation events require ectopic gene expression in combination with chromatin-based cues. These studies therefore experimentally test a model of multistate stability and demonstrate that transcriptional circuits act synergistically with chromatin-based changes to drive cell state transitions. We also establish close mechanistic parallels between phenotypic switching in unicellular fungi and cell fate decisions during stem cell reprogramming. PMID:27711197

Stochastic models for regulatory networks of the genetic toggle switch.

PubMed

Tian, Tianhai; Burrage, Kevin

2006-05-30

Bistability arises within a wide range of biological systems from the lambda phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks.

Stochastic models for regulatory networks of the genetic toggle switch

PubMed Central

Tian, Tianhai; Burrage, Kevin

2006-01-01

Bistability arises within a wide range of biological systems from the λ phage switch in bacteria to cellular signal transduction pathways in mammalian cells. Changes in regulatory mechanisms may result in genetic switching in a bistable system. Recently, more and more experimental evidence in the form of bimodal population distributions indicates that noise plays a very important role in the switching of bistable systems. Although deterministic models have been used for studying the existence of bistability properties under various system conditions, these models cannot realize cell-to-cell fluctuations in genetic switching. However, there is a lag in the development of stochastic models for studying the impact of noise in bistable systems because of the lack of detailed knowledge of biochemical reactions, kinetic rates, and molecular numbers. In this work, we develop a previously undescribed general technique for developing quantitative stochastic models for large-scale genetic regulatory networks by introducing Poisson random variables into deterministic models described by ordinary differential equations. Two stochastic models have been proposed for the genetic toggle switch interfaced with either the SOS signaling pathway or a quorum-sensing signaling pathway, and we have successfully realized experimental results showing bimodal population distributions. Because the introduced stochastic models are based on widely used ordinary differential equation models, the success of this work suggests that this approach is a very promising one for studying noise in large-scale genetic regulatory networks. PMID:16714385

Conformational Toggling of Yeast Iso-1-Cytochrome c in the Oxidized and Reduced States

PubMed Central

Yang, Zhongzheng; Zhu, Jing; Ying, Tianlei; Jiang, Xianwang; Zhang, Xu; Wu, Houming; Liu, Maili; Tan, Xiangshi; Cao, Chunyang; Huang, Zhong-Xian

2011-01-01

To convert cyt c into a peroxidase-like metalloenzyme, the P71H mutant was designed to introduce a distal histidine. Unexpectedly, its peroxidase activity was found even lower than that of the native, and that the axial ligation of heme iron was changed to His71/His18 in the oxidized state, while to Met80/His18 in the reduced state, characterized by UV-visible, circular dichroism, and resonance Raman spectroscopy. To further probe the functional importance of Pro71 in oxidation state dependent conformational changes occurred in cyt c, the solution structures of P71H mutant in both oxidation states were determined. The structures indicate that the half molecule of cyt c (aa 50–102) presents a kind of “zigzag riveting ruler” structure, residues at certain positions of this region such as Pro71, Lys73 can move a big distance by altering the tertiary structure while maintaining the secondary structures. This finding provides a molecular insight into conformational toggling in different oxidation states of cyt c that is principle significance to its biological functions in electron transfer and apoptosis. Structural analysis also reveals that Pro71 functions as a key hydrophobic patch in the folding of the polypeptide of the region (aa 50–102), to prevent heme pocket from the solvent. PMID:22087268

Advances in methods to characterize ligand-induced ionic lock and rotamer toggle molecular switch in G protein-coupled receptors.

PubMed

Xie, Xiang-Qun; Chowdhury, Ananda

2013-01-01

Structural biology of GPCRs has made significant progress upon recently developed technologies for GPCRs expression/purification and elucidation of GPCRs crystal structures. The crystal structures provide a snapshot of the receptor structural disposition of GPCRs itself or with cocrystallized ligands, and the results are congruent with biophysical and computer modeling studies reported about GPCRs conformational and dynamics flexibility, regulated activation, and the various stabilizing interactions, such as "molecular switches." The molecular switches generally constitute the most conserved domains within a particular GPCR superfamily. Often agonist-induced receptor activation proceeds by the disruption of majority of these interactions, while antagonist and inverse agonist act as blockers and structural stabilizers, respectively. Several elegant studies, particularly for the β2AR, have demonstrated the relationship between ligand structure, receptor conformational changes, and corresponding pharmacological outcomes. Thus, it is of great importance to understand GPCRs activation related to cell signaling pathways. Herein, we summarize the steps to produce functional GPCRs, generate suitably fluorescent labeled GPCRs and the procedure to use that to understand if ligand-induced activation can proceed by activation of the GPCRs via ionic lock switch and/or rotamer toggle switch mechanisms. Such understanding of ligand structure and mechanism of receptor activation will provide great insight toward uncovering newer pathways of GPCR activation and aid in structure-based drug design. Copyright © 2013 Elsevier Inc. All rights reserved.

Camarada on middeck

NASA Image and Video Library

2005-08-04

S114-E-7003 (4 August 2005) --- Astronaut Charles J. Camarda, STS-114 mission specialist, performs a middeck evaluation of the mechanical "plug" option for Reinforced Carbon-Carbon (RCC) repair aboard the Space Shuttle Discovery. Camarda used special pre-designated tools to accomplish the procedure, along with round thin, flexible 7-inch-diamter carbon-silicon cover plates designed to flex up to 0.25 inch to conform to the wing leading edge RCC panels, a hardware attachment mechanism similar to a toggle bolt and sealant.

Let's Use Cognitive Science to Create Collaborative Workstations.

PubMed

Reicher, Murray A; Wolfe, Jeremy M

2016-05-01

When informed by an understanding of cognitive science, radiologists' workstations could become collaborative to improve radiologists' performance and job satisfaction. The authors review relevant literature and present several promising areas of research, including image toggling, eye tracking, cognitive computing, intelligently restricted messaging, work habit tracking, and innovative input devices. The authors call for more research in "perceptual design," a promising field that can complement advances in computer-aided detection. Copyright © 2016 American College of Radiology. Published by Elsevier Inc. All rights reserved.

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

Milkov, Mihail M.

A comparator circuit suitable for use in a column-parallel single-slope analog-to-digital converter comprises a comparator, an input voltage sampling switch, a sampling capacitor arranged to store a voltage which varies with an input voltage when the sampling switch is closed, and a local ramp buffer arranged to buffer a global voltage ramp applied at an input. The comparator circuit is arranged such that its output toggles when the buffered global voltage ramp exceeds the stored voltage. Both DC- and AC-coupled comparator embodiments are disclosed.

Nonlatching positive feedback enables robust bimodality by decoupling expression noise from the mean

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

Razooky, Brandon S.; Cao, Youfang; Hansen, Maike M. K.

Fundamental to biological decision-making is the ability to generate bimodal expression patterns where two alternate expression states simultaneously exist. Here in this study, we use a combination of single-cell analysis and mathematical modeling to examine the sources of bimodality in the transcriptional program controlling HIV’s fate decision between active replication and viral latency. We find that the HIV Tat protein manipulates the intrinsic toggling of HIV’s promoter, the LTR, to generate bimodal ON-OFF expression, and that transcriptional positive feedback from Tat shifts and expands the regime of LTR bimodality. This result holds for both minimal synthetic viral circuits and full-lengthmore » virus. Strikingly, computational analysis indicates that the Tat circuit’s non-cooperative ‘non-latching’ feedback architecture is optimized to slow the promoter’s toggling and generate bimodality by stochastic extinction of Tat. In contrast to the standard Poisson model, theory and experiment show that non-latching positive feedback substantially dampens the inverse noise-mean relationship to maintain stochastic bimodality despite increasing mean-expression levels. Given the rapid evolution of HIV, the presence of a circuit optimized to robustly generate bimodal expression appears consistent with the hypothesis that HIV’s decision between active replication and latency provides a viral fitness advantage. More broadly, the results suggest that positive-feedback circuits may have evolved not only for signal amplification but also for robustly generating bimodality by decoupling expression fluctuations (noise) from mean expression levels.« less

NTM stabilization by alternating O-point EC current drive using a high-power diplexer

NASA Astrophysics Data System (ADS)

Kasparek, W.; Doelman, N.; Stober, J.; Maraschek, M.; Zohm, H.; Monaco, F.; Eixenberger, H.; Klop, W.; Wagner, D.; Schubert, M.; Schütz, H.; Grünwald, G.; Plaum, B.; Munk, R.; Schlüter, K. H.; ASDEX Upgrade Team

2016-12-01

At the tokamak ASDEX Upgrade, experiments to stabilize neoclassical tearing modes (NTMs) by electron cyclotron (EC) heating and current drive in the O-points of the magnetic islands were performed. For the first time, injection into the O-points of the revolving islands was performed via a fast directional switch, which toggled the EC power between two launchers synchronously to the island rotation. The switching was performed by a resonant diplexer employing a sharp resonance in the transfer function, and a small frequency modulation of the feeding gyrotron around the slope of the resonance. Thus, toggling of the power between the two outputs of the diplexer connected to two articulating launchers was possible. Phasing and control of the modulation were performed via a set of Mirnov coils and appropriate signal processing. In the paper, technological issues, the design of the diplexer, the tracking of the diplexer resonance to the gyrotron frequency, the generation and processing of control signals for the gyrotron, and the typical performance concerning switching contrast and efficiency are discussed. The plasma scenario is described, and plasma experiments are presented, where the launchers scanned the region of the resonant surface continuously and also where the launchers were at a fixed position near to the q  =  1.5-surface. In the second case, complete stabilization of a 3/2 NTM could be reached. These experiments are also seen as a technical demonstration for the applicability of diplexers in large-scale ECRH systems.

Comparison of design and torque measurements of various manual wrenches.

PubMed

Neugebauer, Jörg; Petermöller, Simone; Scheer, Martin; Happe, Arndt; Faber, Franz-Josef; Zoeller, Joachim E

2015-01-01

Accurate torque application and determination of the applied torque during surgical and prosthetic treatment is important to reduce complications. A study was performed to determine and compare the accuracy of manual wrenches, which are available in different designs with a large range of preset torques. Thirteen different wrench systems with a variety of preset torques ranging from 10 to 75 Ncm were evaluated. Three different designs were available, with a spring-in-coil or toggle design as an active mechanism or a beam as a passive mechanism, to select the preset torque. To provide a clinically relevant analysis, a total of 1,170 torque measurements in the range of 10 to 45 Ncm were made in vitro using an electronic torque measurement device. The absolute deviations in Ncm and percent deviations across all wrenches were small, with a mean of -0.24 ± 2.15 Ncm and -0.84% ± 11.72% as a shortfall relative to the preset value. The greatest overage was 8.2 Ncm (82.5%), and the greatest shortfall was 8.47 Ncm (46%). However, extreme values were rare, with 95th-percentile values of -1.5% (lower value) and -0.16% (upper value). A comparison with respect to wrench design revealed significantly higher deviations for coil and toggle-style wrenches than for beam wrenches. Beam wrenches were associated with a lower risk of rare extreme values thanks to their passive mechanism of achieving the selected preset torque, which minimizes the risk of harming screw connections.

Camarada and Thomas on middeck

NASA Image and Video Library

2005-08-07

S114-E-7001 (4 August 2005) --- Astronaut Andrew S. W. Thomas, STS-114 mission specialist, photographs a middeck evaluation of the mechanical "plug" option for Reinforced Carbon-Carbon (RCC) repair aboard the Space Shuttle Discovery. Astronaut Charles J. Camarda, mission specialist, uses special pre-designated tools to accomplish the procedure, along with round thin, flexible 7-inch-diamter carbon-silicon cover plates designed to flex up to 0.25 inch to conform to the wing leading edge RCC panels, a hardware attachment mechanism similar to a toggle bolt and sealant.

Thomas and Camarda on middeck

NASA Image and Video Library

2005-08-04

S114-E-7005 (4 August 2005) --- Astronaut Andrew S. W. Thomas, STS-114 mission specialist, photographs a middeck evaluation of the mechanical "plug" option for Reinforced Carbon-Carbon (RCC) repair aboard the Space Shuttle Discovery. Astronaut Charles J. Camarda, mission specialist, uses special pre-designated tools to accomplish the procedure, along with round thin, flexible 7-inch-diamter carbon-silicon cover plates designed to flex up to 0.25 inch to conform to the wing leading edge RCC panels, a hardware attachment mechanism similar to a toggle bolt and sealant.

Mind the GAP: A Novel Tumor-Promoting Mechanism | Center for Cancer Research

Cancer.gov

RAS proteins, like light switches, toggle between an “on” conformation where they promote cell growth, survival, and/or the formation of blood vessels (known as angiogenesis) and an “off” conformation in which they are unable to stimulate their target effector proteins. Nearly one-third of human tumors express a mutated RAS gene, which encodes a protein locked permanently in the active state. Other tumors, including liver hepatocellular carcinomas (HCCs), display aberrant RAS pathway signaling but lack RAS gene mutations, suggesting alternative mechanisms for this excessive RAS activity.

Embedded neural recording with TinyOS-based wireless-enabled processor modules.

PubMed

Farshchi, Shahin; Pesterev, Aleksey; Nuyujukian, Paul; Guenterberg, Eric; Mody, Istvan; Judy, Jack W

2010-04-01

To create a wireless neural recording system that can benefit from the continuous advancements being made in embedded microcontroller and communications technologies, an embedded-system-based architecture for wireless neural recording has been designed, fabricated, and tested. The system consists of commercial-off-the-shelf wireless-enabled processor modules (motes) for communicating the neural signals, and a back-end database server and client application for archiving and browsing the neural signals. A neural-signal-acquisition application has been developed to enable the mote to either acquire neural signals at a rate of 4000 12-bit samples per second, or detect and transmit spike heights and widths sampled at a rate of 16670 12-bit samples per second on a single channel. The motes acquire neural signals via a custom low-noise neural-signal amplifier with adjustable gain and high-pass corner frequency that has been designed, and fabricated in a 1.5-microm CMOS process. In addition to browsing acquired neural data, the client application enables the user to remotely toggle modes of operation (real-time or spike-only), as well as amplifier gain and high-pass corner frequency.

Comparative short-term effects of two thoracic spinal manipulation techniques in subjects with chronic mechanical neck pain: a randomized controlled trial.

PubMed

Casanova-Méndez, Amaloha; Oliva-Pascual-Vaca, Angel; Rodriguez-Blanco, Cleofás; Heredia-Rizo, Alberto Marcos; Gogorza-Arroitaonandia, Kristobal; Almazán-Campos, Ginés

2014-08-01

Spinal Manipulation (SM) has been purported to decrease pain and improve function in subjects with non-specific neck pain. Previous research has investigated which individuals with non-specific neck pain will be more likely to benefit from SM. It has not yet been proven whether or not the effectiveness of thoracic SM depends on the specific technique being used. This double-blind randomized trial has compared the short-term effects of two thoracic SM maneuvers in subjects with chronic non-specific neck pain. Sixty participants were distributed randomly into two groups. One group received the Dog technique (n = 30), with the subject in supine position, and the other group underwent the Toggle-Recoil technique (n = 30), with the participant lying prone, T4 being the targeted area in both cases. Evaluations were made of self-reported neck pain (Visual Analogue Scale); neck mobility (Cervical Range of Motion); and pressure pain threshold at the cervical and thoracic levels (C4 and T4 spinous process) and over the site described for location of tense bands of the upper trapezius muscle. Measurements were taken before intervention, immediately afterward, and 20 min later. Both maneuvers improved neck mobility and mechanosensitivity and reduced pain in the short term. No major or clinical differences were found between the groups. In the between-groups comparison slightly better results were observed in the Toggle-Recoil group only for cervical extension (p = 0.009), right lateral flexion (p = 0.004) and left rotation (p < 0.05). Copyright © 2014 Elsevier Ltd. All rights reserved.

Loads Bias Genetic and Signaling Switches in Synthetic and Natural Systems

PubMed Central

Medford, June; Prasad, Ashok

2014-01-01

Biological protein interactions networks such as signal transduction or gene transcription networks are often treated as modular, allowing motifs to be analyzed in isolation from the rest of the network. Modularity is also a key assumption in synthetic biology, where it is similarly expected that when network motifs are combined together, they do not lose their essential characteristics. However, the interactions that a network module has with downstream elements change the dynamical equations describing the upstream module and thus may change the dynamic and static properties of the upstream circuit even without explicit feedback. In this work we analyze the behavior of a ubiquitous motif in gene transcription and signal transduction circuits: the switch. We show that adding an additional downstream component to the simple genetic toggle switch changes its dynamical properties by changing the underlying potential energy landscape, and skewing it in favor of the unloaded side, and in some situations adding loads to the genetic switch can also abrogate bistable behavior. We find that an additional positive feedback motif found in naturally occurring toggle switches could tune the potential energy landscape in a desirable manner. We also analyze autocatalytic signal transduction switches and show that a ubiquitous positive feedback switch can lose its switch-like properties when connected to a downstream load. Our analysis underscores the necessity of incorporating the effects of downstream components when understanding the physics of biochemical network motifs, and raises the question as to how these effects are managed in real biological systems. This analysis is particularly important when scaling synthetic networks to more complex organisms. PMID:24676102

High pressure induced crossover between metal and insulator conductivity type in low dimensionality electron systems

NASA Astrophysics Data System (ADS)

Dizhur, E.; Voronovskii, A.; Kostyleva, I.; Kotel'nikov, I.; Zaitsev-Zotov, S.

2011-12-01

We report the results of our recent experimental studies concerned with electron systems of lower dimensionality the conductivity of which may be toggled between metallic and insulating regime appliing high pressure. The objects under present study include: a) tunneling through Shottky barrier into two-dimension (2D) electron system formed in the δ-doped layer in GaAs under hydrostatic pressure up to 3 GPa in a cylinder-piston cell; b) quasi-one-dimension (1D) `insulator' crystals NbS3 which obtain metallic conductivity type at pressures above 5.5 GPa in `toroid' anvils.

Real-space mapping of Fano interference in plasmonic metamolecules.

PubMed

Alonso-Gonzalez, Pablo; Schnell, Martin; Sarriugarte, Paulo; Sobhani, Heidar; Wu, Chihhui; Arju, Nihal; Khanikaev, Alexander; Golmar, Federico; Albella, Pablo; Arzubiaga, Libe; Casanova, Felix; Hueso, Luis E; Nordlander, Peter; Shvets, Gennady; Hillenbrand, Rainer

2011-09-14

An unprecedented control of the spectral response of plasmonic nanoantennas has recently been achieved by designing structures that exhibit Fano resonances. This new insight is paving the way for a variety of applications, such as biochemical sensing and surface-enhanced Raman spectroscopy. Here we use scattering-type near-field optical microscopy to map the spatial field distribution of Fano modes in infrared plasmonic systems. We observe in real space the interference of narrow (dark) and broad (bright) plasmonic resonances, yielding intensity and phase toggling between different portions of the plasmonic metamolecules when either their geometric sizes or the illumination wavelength is varied.

Synthetic metabolic bypass for a metabolic toggle switch enhances acetyl-CoA supply for isopropanol production by Escherichia coli.

PubMed

Soma, Yuki; Yamaji, Taiki; Matsuda, Fumio; Hanai, Taizo

2017-05-01

Almost all synthetic pathways for biofuel production are designed to require endogenous metabolites in glycolysis, such as phosphoenolpyruvate, pyruvate, and acetyl-CoA. However, such metabolites are also required for bacterial cell growth. To reduce the metabolic imbalance between cell growth and target chemical production, we previously constructed a metabolic toggle switch (MTS) as a conditional flux redirection tool controlling metabolic flux of TCA cycle toward isopropanol production. This approach succeeded to improve the isopropanol production titer and yield while ensuring sufficient cell growth. However, excess accumulation of pyruvate, the precursor for acetyl-CoA synthesis, was also observed. In this study, for efficient conversation of pyruvate to acetyl-CoA (pyruvate oxidation), we designed a synthetic metabolic bypass composed of poxB and acs with the MTS for acetyl-CoA supply from the excess pyruvate. When this designed bypass was expressed at the appropriate expression level associated with the conditional metabolic flux redirection, pyruvate accumulation was prevented, and the isopropanol production titer and yield were improved. Final isopropanol production titer of strain harboring MTS with the synthetic metabolic bypass improved 4.4-fold compared with strain without metabolic flux regulation, and it was 1.3-fold higher than that of strain harboring the conventional MTS alone. Additionally, glucose consumption was also improved 1.7-fold compared with strain without metabolic flux regulation. On the other hand, introduction of the synthetic metabolic bypass alone showed no improvement in isopropanol production and glucose consumption. These results showed that the improvement in bio-production process caused by synergy between the MTS and the synthetic metabolic bypass. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

LabVIEW Task Manager v. 1.10.0

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

Vargo, Timothy D.

LabVIEW Task Manager is a debugging tool for use during code development in the National Instruments (NI) LabVIEW® IDE. While providing a dynamic & big-picture view of running code, an expandable/collapsible tree diagram displays detailed information (both static and dynamic) on all VIs in memory, belonging to a selected project/target. It allows for interacting with single or multiple selected VIs at a time, providing significant benefits while troubleshooting, and has the following features: Look & Feel similar to Windows® Task Manager; Selection of project/target; Lists all VIs in memory, grouped by class/library; Searches for and enumerates clones in memory; DropInmore » VI for including dynamically referenced clones (Clone Beacon); 'Refresh Now' (F5) re-reads all VIs in memory and adds new ones to the tree; Displays VI name, owning class/library, state, path, data size & code size; Displays VI FP Behavior, Reentrant?, Reentrancy Type, Paused? & Highlight?; Sort by any column, including by library name; Filter by item types vi, ctl, and vit/ctt; Filter out vi.lib and global VIs; Tracking of, and ability to toggle, execution highlighting on multiple selected VIs; Tracking of paused VIs with ability to Pause/Resume/TogglePause multiple selected VIs; DropIn VI for pausing on a condition; If a clone initiates a pause, a different pause symbol is used for all clones of that same reentrant original VI; Select multiple VIs and open or close their FPs or BDs; Double Click a VI from the tree to bring the BD (first choice) or FP to front, if already open; and Select multiple top-level VIs and Abort them.« less

Breath-hold device for laboratory rodents undergoing imaging procedures.

PubMed

Rivera, Belinda; Bushman, Mark J; Beaver, Richard G; Cody, Dianna D; Price, Roger E

2006-07-01

The increased use in noninvasive imaging of laboratory rodents has prompted innovative techniques in animal handling. Lung imaging of rodents can be a difficult task because of tissue motion caused by breathing, which affects image quality. The use of a prototype flat-panel computed tomography unit allows the acquisition of images in as little as 2, 4, or 8 s. This short acquisition time has allowed us to improve the image quality of this instrument by performing a breath-hold during image acquisition. We designed an inexpensive and safe method for performing a constant-pressure breath-hold in intubated rodents. Initially a prototypic manual 3-way valve system, consisting of a 3-way valve, an air pressure regulator, and a manometer, was used to manually toggle between the ventilator and the constant-pressure breath-hold equipment. The success of the manual 3-way valve system prompted the design of an electronically actuated valve system. In the electronic system, the manual 3-way valve was replaced with a custom designed 3-way valve operated by an electrical solenoid. The electrical solenoid is triggered by using a hand-held push button or a foot pedal that is several feet away from the gantry of the scanner. This system has provided improved image quality and is safe for the animals, easy to use, and reliable.

Toggle switch from optical bistability to multistability via an elliptically polarized field

NASA Astrophysics Data System (ADS)

Yan, Xiang-An; Ren, Bo-Quan; Wang, Li-Qiang; Liu, Yao-Wu; Yu, Hua-Wa

2017-06-01

In this paper, we propose a scheme for manipulating the behavior of optical bistability (OB) and optical multistability (OM) in an N-type four-level atomic system. In the scheme, quantum interference is optimized by the left-handed and the right-handed fields of an elliptically polarized field (EPF). The threshold and the hysteresis cycle shape of OB and OM can be controlled by modulating the intensity of the EPF. Especially, the transition from OB to OM or vice versa can also be easily realized by proper tuning the phase difference between the left-handed and right-handed polarized fields under the optimal intensity of the EPF.

CHIPSat spacecraft design: significant science on a low budget

NASA Astrophysics Data System (ADS)

Janicik, Jeffrey; Wolff, Jonathan

2003-12-01

The Cosmic Hot Interstellar Plasma Spectrometer satellite (CHIPSat) was launched on January 12, 2003 and is successfully accomplishing its mission. CHIPS is NASA"s first-ever University-Class Explorer (UNEX) project, and is performed through a grant to the University of California at Berkeley (UCB) Space Sciences Laboratory (SSL). As a small start-up aerospace company, SpaceDev was awarded responsibility for a low-cost spacecraft and mission design, build, integration and test, and mission operations. The company leveraged past small satellite mission experiences to help design a robust small spacecraft system architecture. In addition, they utilized common industry hardware and software standards to facilitate design implementation, integration, and test of the bus, including the use of TCP/IP protocols and the Internet for end-to-end satellite communications. The approach called for a single-string design except in critical areas, the use of COTS parts to incorporate the latest proven technologies in commercial electronics, and the establishment of a working system as quickly as possible in order to maximize test hours prior to launch. Furthermore, automated ground systems were combined with table-configured onboard software to allow for "hands-off" mission operations. During nominal operations, the CHIPSat spacecraft uses a 3-axis stabilized zero-momentum bias "Nominal" mode. The secondary mode is a "Safehold" mode where fixed "keep-alive" arrays maintain enough power to operate the essential spacecraft bus in any attitude and spin condition, and no a-priori attitude knowledge is required to recover. Due to the omnidirectional antenna design, communications are robust in "Safehold" mode, including the transmission of basic housekeeping data at a duty cycle that is adjusted based on available solar power. This design enables the entire mission to be spent in "Observation Mode" with timed pointing files mapping the sky as desired unless an anomalous event upsets the health of the bus such that the spacecraft system toggles back to "Safehold". In all conditions, spacecraft operations do not require any time-critical operator involvement. This paper will examine the results of the first six months of CHIPSat on-orbit operations and measure them against the expectations of the aforementioned design architecture. The end result will be a "lessons learned" account of a 3-axis sun-pointing small spacecraft design architecture that will be useful for future science missions.

Mammalian synthetic biology: emerging medical applications

PubMed Central

Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M.; Krams, Rob

2015-01-01

In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. PMID:25808341

Inaccessible Masturbation, Impossible Mourning: Collective Melancholia, the Prohibition on Female Sexual Subjects in India, and Masturbation Fantasy as a Zone of the Strange.

PubMed

Narayanan, A

2015-12-01

This paper explores a subjective experience-and identification-that a cohort of Indian women identifies as "home." This experience of "home" provides an attachment to a collective melancholia that keeps in place a prohibited female sexual subjectivity. The paper provides a brief historical overview of the prohibition of female sexual subjectivity and erotic agency in India. Following this, it discusses women's masturbation fantasies that illustrate the toggle between women's permitted and prohibited identifications. A clinical case example is presented to illustrate the hopelessness and mourning inherent in the psychoanalytic journey into subjectivity, a journey involving a departure from a shared cultural history.

Analysis of the Hexapod Work Space using integration of a CAD/CAE system and the LabVIEW software

NASA Astrophysics Data System (ADS)

Herbuś, K.; Ociepka, P.

2015-11-01

The paper presents the problems related to the integration of a CAD/CAE system with the LabVIEW software. The purpose of the integration is to determine the workspace of a hexapod model basing on a mathematical model describing it motion. In the first stage of the work concerning the integration task the 3D model to simulate movements of a hexapod was elaborated. This phase of the work was done in the “Motion Simulation” module of the CAD/CAE/CAM Siemens NX system. The first step was to define the components of the 3D model in the form of “links”. Individual links were defined according to the nature of the hexapod elements action. In the model prepared for movement simulation were created links corresponding to such elements as: electric actuator, top plate, bottom plate, ball-and-socket joint, toggle joint Phillips. Then were defined the constraints of the “joint” type (e.g.: revolute joint, slider joint, spherical joint) between the created component of the “link” type, so that the computer simulation corresponds to the operation of a real hexapod. The next stage of work included implementing the mathematical model describing the functioning of a hexapod in the LabVIEW software. At this stage, particular attention was paid to determining procedures for integrating the virtual 3D hexapod model with the results of calculations performed in the LabVIEW. The results relate to specific values of the jump of electric actuators depending on the position of the car on the hexapod. The use of integration made it possible to determine the safe operating space of a stationary hexapod taking into consideration the security of a person in the driving simulator designed for the disabled.

Biological Signal Processing with a Genetic Toggle Switch

PubMed Central

Hillenbrand, Patrick; Fritz, Georg; Gerland, Ulrich

2013-01-01

Complex gene regulation requires responses that depend not only on the current levels of input signals but also on signals received in the past. In digital electronics, logic circuits with this property are referred to as sequential logic, in contrast to the simpler combinatorial logic without such internal memory. In molecular biology, memory is implemented in various forms such as biochemical modification of proteins or multistable gene circuits, but the design of the regulatory interface, which processes the input signals and the memory content, is often not well understood. Here, we explore design constraints for such regulatory interfaces using coarse-grained nonlinear models and stochastic simulations of detailed biochemical reaction networks. We test different designs for biological analogs of the most versatile memory element in digital electronics, the JK-latch. Our analysis shows that simple protein-protein interactions and protein-DNA binding are sufficient, in principle, to implement genetic circuits with the capabilities of a JK-latch. However, it also exposes fundamental limitations to its reliability, due to the fact that biological signal processing is asynchronous, in contrast to most digital electronics systems that feature a central clock to orchestrate the timing of all operations. We describe a seemingly natural way to improve the reliability by invoking the master-slave concept from digital electronics design. This concept could be useful to interpret the design of natural regulatory circuits, and for the design of synthetic biological systems. PMID:23874595

SU-F-19A-10: Recalculation and Reporting Clinical HDR 192-Ir Head and Neck Dose Distributions Using Model Based Dose Calculation

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

Carlsson Tedgren, A; Persson, M; Nilsson, J

Purpose: To retrospectively re-calculate dose distributions for selected head and neck cancer patients, earlier treated with HDR 192Ir brachytherapy, using Monte Carlo (MC) simulations and compare results to distributions from the planning system derived using TG43 formalism. To study differences between dose to medium (as obtained with the MC code) and dose to water in medium as obtained through (1) ratios of stopping powers and (2) ratios of mass energy absorption coefficients between water and medium. Methods: The MC code Algebra was used to calculate dose distributions according to earlier actual treatment plans using anonymized plan data and CT imagesmore » in DICOM format. Ratios of stopping power and mass energy absorption coefficients for water with various media obtained from 192-Ir spectra were used in toggling between dose to water and dose to media. Results: Differences between initial planned TG43 dose distributions and the doses to media calculated by MC are insignificant in the target volume. Differences are moderate (within 4–5 % at distances of 3–4 cm) but increase with distance and are most notable in bone and at the patient surface. Differences between dose to water and dose to medium are within 1-2% when using mass energy absorption coefficients to toggle between the two quantities but increase to above 10% for bone using stopping power ratios. Conclusion: MC predicts target doses for head and neck cancer patients in close agreement with TG43. MC yields improved dose estimations outside the target where a larger fraction of dose is from scattered photons. It is important with awareness and a clear reporting of absorbed dose values in using model based algorithms. Differences in bone media can exceed 10% depending on how dose to water in medium is defined.« less

10 K gate I(2)L and 1 K component analog compatible bipolar VLSI technology - HIT-2

NASA Astrophysics Data System (ADS)

Washio, K.; Watanabe, T.; Okabe, T.; Horie, N.

1985-02-01

An advanced analog/digital bipolar VLSI technology that combines on the same chip 2-ns 10 K I(2)L gates with 1 K analog devices is proposed. The new technology, called high-density integration technology-2, is based on a new structure concept that consists of three major techniques: shallow grooved-isolation, I(2)L active layer etching, and I(2)L current gain increase. I(2)L circuits with 80-MHz maximum toggle frequency have developed compatibly with n-p-n transistors having a BV(CE0) of more than 10 V and an f(T) of 5 GHz, and lateral p-n-p transistors having an f(T) of 150 MHz.

Integrated circuit test-port architecture and method and apparatus of test-port generation

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

Teifel, John

A method and apparatus are provided for generating RTL code for a test-port interface of an integrated circuit. In an embodiment, a test-port table is provided as input data. A computer automatically parses the test-port table into data structures and analyzes it to determine input, output, local, and output-enable port names. The computer generates address-detect and test-enable logic constructed from combinational functions. The computer generates one-hot multiplexer logic for at least some of the output ports. The one-hot multiplexer logic for each port is generated so as to enable the port to toggle between data signals and test signals. Themore » computer then completes the generation of the RTL code.« less

Inverse Stochastic Resonance in Cerebellar Purkinje Cells

PubMed Central

Häusser, Michael; Gutkin, Boris S.; Roth, Arnd

2016-01-01

Purkinje neurons play an important role in cerebellar computation since their axons are the only projection from the cerebellar cortex to deeper cerebellar structures. They have complex internal dynamics, which allow them to fire spontaneously, display bistability, and also to be involved in network phenomena such as high frequency oscillations and travelling waves. Purkinje cells exhibit type II excitability, which can be revealed by a discontinuity in their f-I curves. We show that this excitability mechanism allows Purkinje cells to be efficiently inhibited by noise of a particular variance, a phenomenon known as inverse stochastic resonance (ISR). While ISR has been described in theoretical models of single neurons, here we provide the first experimental evidence for this effect. We find that an adaptive exponential integrate-and-fire model fitted to the basic Purkinje cell characteristics using a modified dynamic IV method displays ISR and bistability between the resting state and a repetitive activity limit cycle. ISR allows the Purkinje cell to operate in different functional regimes: the all-or-none toggle or the linear filter mode, depending on the variance of the synaptic input. We propose that synaptic noise allows Purkinje cells to quickly switch between these functional regimes. Using mutual information analysis, we demonstrate that ISR can lead to a locally optimal information transfer between the input and output spike train of the Purkinje cell. These results provide the first experimental evidence for ISR and suggest a functional role for ISR in cerebellar information processing. PMID:27541958

Using a Commercial Ethernet PHY Device in a Radiation Environment

NASA Technical Reports Server (NTRS)

Parks, Jeremy; Arani, Michael; Arroyo, Roberto

2014-01-01

This work involved placing a commercial Ethernet PHY on its own power boundary, with limited current supply, and providing detection methods to determine when the device is not operating and when it needs either a reset or power-cycle. The device must be radiation-tested and free of destructive latchup errors. The commercial Ethernet PHY's own power boundary must be supplied by a current-limited power regulator that must have an enable (for power cycling), and its maximum power output must not exceed the PHY's input requirements, thus preventing damage to the device. A regulator with configurable output limits and short-circuit protection (such as the RHFL4913, rad hard positive voltage regulator family) is ideal. This will prevent a catastrophic failure due to radiation (such as a short between the commercial device's power and ground) from taking down the board's main power. Logic provided on the board will detect errors in the PHY. An FPGA (field-programmable gate array) with embedded Ethernet MAC (Media Access Control) will work well. The error detection includes monitoring the PHY's interrupt line, and the status of the Ethernet's switched power. When the PHY is determined to be non-functional, the logic device resets the PHY, which will often clear radiation induced errors. If this doesn't work, the logic device power-cycles the FPGA by toggling the regulator's enable input. This should clear almost all radiation induced errors provided the device is not latched up.

A mower detector to judge soil sorting

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

Bramlitt, E.T.; Johnson, N.R.

1995-12-31

Thermo Nuclear Services (TNS) has developed a mower detector as an inexpensive and fast means for deciding potential value of soil sorting for cleanup. It is a shielded detector box on wheels pushed over the ground (as a person mows grass) at 30 ft/min with gamma-ray counts recorded every 0.25 sec. It mirror images detection by the TNS transportable sorter system which conveys soil at 30 ft/min and toggles a gate to send soil on separate paths based on counts. The mower detector shows if contamination is variable and suitable for sorting, and by unique calibration sources, it indicates detectionmore » sensitivity. The mower detector has been used to characterize some soil at Department of Energy sites in New Jersey and South Carolina.« less

Mammalian synthetic biology: emerging medical applications.

PubMed

Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M; Krams, Rob

2015-05-06

In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON-OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Apparatus and method of capturing an orbiting spacecraft

NASA Technical Reports Server (NTRS)

Harwell, William D. (Inventor); Gardner, Dale A. (Inventor)

1987-01-01

Apparatus and a method of capturing an orbiting spacecraft by attaching a grapple fixture are discussed. A probe is inserted into an opening, such as a rocket nozzle, in the spacecraft until a stop on the prove mechanism contacts the spacecraft. A lever is actuated releasing a spring loaded rod which moves axially along the probe removing a covering sleeve to expose spring loaded toffle fingers which pivot open engaging the side of the opening. The probe is shortened and tensioned by turning a screw thread, pressing the fingers inside of the opening to compress the spacecraft between the toggle fingers and the stop. A grapple fixture attached to the probe, which is thus secured to the spacecraft, is engaged by appropriate retrieval means such as a remote manipulator arm.

Multicolour Multilevel STED nanoscopy of Actin/Spectrin Organization at Synapses

PubMed Central

Sidenstein, Sven C.; D’Este, Elisa; Böhm, Marvin J.; Danzl, Johann G.; Belov, Vladimir N.; Hell, Stefan W.

2016-01-01

Superresolution fluorescence microscopy of multiple fluorophores still requires development. Here we present simultaneous three-colour stimulated emission depletion (STED) nanoscopy relying on a single STED beam at 620 nm. Toggling the STED beam between two or more power levels (“multilevelSTED”) optimizes resolution and contrast in all colour channels, which are intrinsically co-aligned and well separated. Three-colour recording is demonstrated by imaging the nanoscale cytoskeletal organization in cultured hippocampal neurons. The down to ~35 nm resolution identified periodic actin/betaII spectrin lattices along dendrites and spines; however, at presynaptic and postsynaptic sites, these patterns were found to be absent. Both our multicolour scheme and the 620 nm STED line should be attractive for routine STED microscopy applications. PMID:27220554

Genomes as geography: using GIS technology to build interactive genome feature maps

PubMed Central

Dolan, Mary E; Holden, Constance C; Beard, M Kate; Bult, Carol J

2006-01-01

Background Many commonly used genome browsers display sequence annotations and related attributes as horizontal data tracks that can be toggled on and off according to user preferences. Most genome browsers use only simple keyword searches and limit the display of detailed annotations to one chromosomal region of the genome at a time. We have employed concepts, methodologies, and tools that were developed for the display of geographic data to develop a Genome Spatial Information System (GenoSIS) for displaying genomes spatially, and interacting with genome annotations and related attribute data. In contrast to the paradigm of horizontally stacked data tracks used by most genome browsers, GenoSIS uses the concept of registered spatial layers composed of spatial objects for integrated display of diverse data. In addition to basic keyword searches, GenoSIS supports complex queries, including spatial queries, and dynamically generates genome maps. Our adaptation of the geographic information system (GIS) model in a genome context supports spatial representation of genome features at multiple scales with a versatile and expressive query capability beyond that supported by existing genome browsers. Results We implemented an interactive genome sequence feature map for the mouse genome in GenoSIS, an application that uses ArcGIS, a commercially available GIS software system. The genome features and their attributes are represented as spatial objects and data layers that can be toggled on and off according to user preferences or displayed selectively in response to user queries. GenoSIS supports the generation of custom genome maps in response to complex queries about genome features based on both their attributes and locations. Our example application of GenoSIS to the mouse genome demonstrates the powerful visualization and query capability of mature GIS technology applied in a novel domain. Conclusion Mapping tools developed specifically for geographic data can be exploited to display, explore and interact with genome data. The approach we describe here is organism independent and is equally useful for linear and circular chromosomes. One of the unique capabilities of GenoSIS compared to existing genome browsers is the capacity to generate genome feature maps dynamically in response to complex attribute and spatial queries. PMID:16984652

Clamping characteristics study on different types of clamping unit

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

Jiao, Zhiwei; Liu, Haichao; Xie, Pengcheng

2015-05-22

Plastic products are becoming more and more widely used in aerospace, IT, digital electronics and many other fields. With the development of technology, the requirement of product precision is getting higher and higher. However, type and working performance of clamping unit play a decisive role in product precision. Clamping characteristics of different types of clamping unit are discussed in this article, which use finite element numerical analysis method through the software ABAQUS to study the clamping uniformity, and detect the clamping force repeatability precision. The result shows that compared with toggled three-platen clamping unit, clamping characteristics of internal circulation two-platenmore » clamping unit are better, for instance, its mold cavity deformation and force that bars and mold parting surface suffered are more uniform, and its clamping uniformity and repeatability precision is also better.« less

Web-based software tool for constraint-based design specification of synthetic biological systems.

PubMed

Oberortner, Ernst; Densmore, Douglas

2015-06-19

miniEugene provides computational support for solving combinatorial design problems, enabling users to specify and enumerate designs for novel biological systems based on sets of biological constraints. This technical note presents a brief tutorial for biologists and software engineers in the field of synthetic biology on how to use miniEugene. After reading this technical note, users should know which biological constraints are available in miniEugene, understand the syntax and semantics of these constraints, and be able to follow a step-by-step guide to specify the design of a classical synthetic biological system-the genetic toggle switch.1 We also provide links and references to more information on the miniEugene web application and the integration of the miniEugene software library into sophisticated Computer-Aided Design (CAD) tools for synthetic biology ( www.eugenecad.org ).

Free energy landscape of G-protein coupled receptors, explored by accelerated molecular dynamics.

PubMed

Miao, Yinglong; Nichols, Sara E; McCammon, J Andrew

2014-04-14

G-protein coupled receptors (GPCRs) mediate cellular responses to various hormones and neurotransmitters and are important targets for treating a wide spectrum of diseases. They are known to adopt multiple conformational states (e.g., inactive, intermediate and active) during their modulation of various cell signaling pathways. Here, the free energy landscape of GPCRs is explored using accelerated molecular dynamics (aMD) simulations as demonstrated on the M2 muscarinic receptor, a key GPCR that regulates human heart rate and contractile forces of cardiomyocytes. Free energy profiles of important structural motifs that undergo conformational transitions upon GPCR activation and allosteric signaling are analyzed in detail, including the Arg(3.50)-Glu(6.30) ionic lock, the Trp(6.48) toggle switch and the hydrogen interactions between Tyr(5.58)-Tyr(7.53).

Quantum optics. All-optical routing of single photons by a one-atom switch controlled by a single photon.

PubMed

Shomroni, Itay; Rosenblum, Serge; Lovsky, Yulia; Bechler, Orel; Guendelman, Gabriel; Dayan, Barak

2014-08-22

The prospect of quantum networks, in which quantum information is carried by single photons in photonic circuits, has long been the driving force behind the effort to achieve all-optical routing of single photons. We realized a single-photon-activated switch capable of routing a photon from any of its two inputs to any of its two outputs. Our device is based on a single atom coupled to a fiber-coupled, chip-based microresonator. A single reflected control photon toggles the switch from high reflection (R ~ 65%) to high transmission (T ~ 90%), with an average of ~1.5 control photons per switching event (~3, including linear losses). No additional control fields are required. The control and target photons are both in-fiber and practically identical, making this scheme compatible with scalable architectures for quantum information processing. Copyright © 2014, American Association for the Advancement of Science.

Is the psychological refractory period effect for ideomotor compatible tasks eliminated by speed-stress instructions?

PubMed

Shin, Yun Kyoung; Cho, Yang Seok; Lien, Mei-Ching; Proctor, Robert W

2007-09-01

It has been argued that the psychological refractory period (PRP) effect is eliminated with two ideomotor compatible tasks when instructions stress fast and simultaneous responding. Three experiments were conducted to test this hypothesis. In all experiments, Task 1 required spatially compatible manual responses (left or right) to the direction of an arrow, and Task 2 required saying the name of the auditory letter A or B. In Experiments 1 and 3, the manual responses were keypresses made with the left and right hands, whereas in Experiment 2 they were left-right toggle-switch movements made with the dominant hand. Instructions that stressed response speed reduced reaction time and increased error rate compared to standard instructions to respond fast and accurately, but did not eliminate the PRP effect on Task 2 reaction time. These results imply that, even when response speed is emphasized, ideomotor compatible tasks do not bypass response selection.

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

D'Huys, Otti, E-mail: otti.dhuys@phy.duke.edu; Haynes, Nicholas D.; Lohmann, Johannes

Autonomous Boolean networks are commonly used to model the dynamics of gene regulatory networks and allow for the prediction of stable dynamical attractors. However, most models do not account for time delays along the network links and noise, which are crucial features of real biological systems. Concentrating on two paradigmatic motifs, the toggle switch and the repressilator, we develop an experimental testbed that explicitly includes both inter-node time delays and noise using digital logic elements on field-programmable gate arrays. We observe transients that last millions to billions of characteristic time scales and scale exponentially with the amount of time delaysmore » between nodes, a phenomenon known as super-transient scaling. We develop a hybrid model that includes time delays along network links and allows for stochastic variation in the delays. Using this model, we explain the observed super-transient scaling of both motifs and recreate the experimentally measured transient distributions.« less

Creating single-copy genetic circuits

PubMed Central

Lee, Jeong Wook; Gyorgy, Andras; Cameron, D. Ewen; Pyenson, Nora; Choi, Kyeong Rok; Way, Jeffrey C.; Silver, Pamela A.; Del Vecchio, Domitilla; Collins, James J.

2017-01-01

SUMMARY Synthetic biology is increasingly used to develop sophisticated living devices for basic and applied research. Many of these genetic devices are engineered using multi-copy plasmids, but as the field progresses from proof-of-principle demonstrations to practical applications, it is important to develop single-copy synthetic modules that minimize consumption of cellular resources and can be stably maintained as genomic integrants. Here we use empirical design, mathematical modeling and iterative construction and testing to build single-copy, bistable toggle switches with improved performance and reduced metabolic load that can be stably integrated into the host genome. Deterministic and stochastic models led us to focus on basal transcription to optimize circuit performance and helped to explain the resulting circuit robustness across a large range of component expression levels. The design parameters developed here provide important guidance for future efforts to convert functional multi-copy gene circuits into optimized single-copy circuits for practical, real-world use. PMID:27425413

Magneto-ionic control of interfacial magnetism

NASA Astrophysics Data System (ADS)

Bauer, Uwe; Yao, Lide; Tan, Aik Jun; Agrawal, Parnika; Emori, Satoru; Tuller, Harry L.; van Dijken, Sebastiaan; Beach, Geoffrey S. D.

2015-02-01

In metal/oxide heterostructures, rich chemical, electronic, magnetic and mechanical properties can emerge from interfacial chemistry and structure. The possibility to dynamically control interface characteristics with an electric field paves the way towards voltage control of these properties in solid-state devices. Here, we show that electrical switching of the interfacial oxidation state allows for voltage control of magnetic properties to an extent never before achieved through conventional magneto-electric coupling mechanisms. We directly observe in situ voltage-driven O2- migration in a Co/metal-oxide bilayer, which we use to toggle the interfacial magnetic anisotropy energy by >0.75 erg cm-2 at just 2 V. We exploit the thermally activated nature of ion migration to markedly increase the switching efficiency and to demonstrate reversible patterning of magnetic properties through local activation of ionic migration. These results suggest a path towards voltage-programmable materials based on solid-state switching of interface oxygen chemistry.

Magnetic vortex core reversal by excitation of spin waves.

PubMed

Kammerer, Matthias; Weigand, Markus; Curcic, Michael; Noske, Matthias; Sproll, Markus; Vansteenkiste, Arne; Van Waeyenberge, Bartel; Stoll, Hermann; Woltersdorf, Georg; Back, Christian H; Schuetz, Gisela

2011-01-01

Micron-sized magnetic platelets in the flux-closed vortex state are characterized by an in-plane curling magnetization and a nanometer-sized perpendicularly magnetized vortex core. Having the simplest non-trivial configuration, these objects are of general interest to micromagnetics and may offer new routes for spintronics applications. Essential progress in the understanding of nonlinear vortex dynamics was achieved when low-field core toggling by excitation of the gyrotropic eigenmode at sub-GHz frequencies was established. At frequencies more than an order of magnitude higher vortex state structures possess spin wave eigenmodes arising from the magneto-static interaction. Here we demonstrate experimentally that the unidirectional vortex core reversal process also occurs when such azimuthal modes are excited. These results are confirmed by micromagnetic simulations, which clearly show the selection rules for this novel reversal mechanism. Our analysis reveals that for spin-wave excitation the concept of a critical velocity as the switching condition has to be modified.

Force-dependent isomerization kinetics of a highly conserved proline switch modulates the mechanosensing region of filamin

PubMed Central

Rognoni, Lorenz; Möst, Tobias; Žoldák, Gabriel; Rief, Matthias

2014-01-01

Proline switches, controlled by cis–trans isomerization, have emerged as a particularly effective regulatory mechanism in a wide range of biological processes. In this study, we use single-molecule mechanical measurements to develop a full kinetic and energetic description of a highly conserved proline switch in the force-sensing domain 20 of human filamin and how prolyl isomerization modulates the force-sensing mechanism. Proline isomerization toggles domain 20 between two conformations. A stable cis conformation with slow unfolding, favoring the autoinhibited closed conformation of filamin’s force-sensing domain pair 20–21, and a less stable, uninhibited conformation promoted by the trans form. The data provide detailed insight into the folding mechanisms that underpin the functionality of this binary switch and elucidate its remarkable efficiency in modulating force-sensing, thus combining two previously unconnected regulatory mechanisms, proline switches and mechanosensing. PMID:24706888

An L-band multi-wavelength Brillouin-erbium fiber laser with switchable frequency spacing

NASA Astrophysics Data System (ADS)

Zhou, Xuefang; Hu, Kongwen; Wei, Yizhen; Bi, Meihua; Yang, Guowei

2017-01-01

In this paper, a novel L-band multi-wavelength Brillouin-erbium fiber laser consisting of two ring cavities is proposed and demonstrated. The frequency spacing can be switched, corresponding to the single and double Brillouin frequency shifts, by toggling the optical switch. Under a 980 nm pump power of 600 mw, and a Brillouin pump power of 4 mW and wavelength of 1599.4 nm, up to 16 Stokes signals with a frequency spacing of 0.089 nm and 5 Stokes signals with double spacing of 0.178 nm are generated. A wavelength tunability of 15 nm (1593 nm  -  1608 nm) is realized for both frequency spacings. The fluctuation of Stokes signals for both single and double Brillouin spacing regimes in the proposed setup is less than 1.5 dB throughout a 30 min time span.

Spin-transfer torque in multiferroic tunnel junctions with composite dielectric/ferroelectric barriers

NASA Astrophysics Data System (ADS)

Velev, Julian P.; Merodio, Pablo; Pollack, Cesar; Kalitsov, Alan; Chshiev, Mairbek; Kioussis, Nicholas

2017-12-01

Using model calculations, we demonstrate a very high level of control of the spin-transfer torque (STT) by electric field in multiferroic tunnel junctions with composite dielectric/ferroelectric barriers. We find that, for particular device parameters, toggling the polarization direction can switch the voltage-induced part of STT between a finite value and a value close to zero, i.e. quench and release the torque. Additionally, we demonstrate that under certain conditions the zero-voltage STT, i.e. the interlayer exchange coupling, can switch sign with polarization reversal, which is equivalent to reversing the magnetic ground state of the tunnel junction. This bias- and polarization-tunability of the STT could be exploited to engineer novel functionalities such as softening/hardening of the bit or increasing the signal-to-noise ratio in magnetic sensors, which can have important implications for magnetic random access memories or for combined memory and logic devices.

Engineering the entropy-driven free-energy landscape of a dynamic nanoporous protein assembly.

PubMed

Alberstein, Robert; Suzuki, Yuta; Paesani, Francesco; Tezcan, F Akif

2018-04-30

De novo design and construction of stimuli-responsive protein assemblies that predictably switch between discrete conformational states remains an essential but highly challenging goal in biomolecular design. We previously reported synthetic, two-dimensional protein lattices self-assembled via disulfide bonding interactions, which endows them with a unique capacity to undergo coherent conformational changes without losing crystalline order. Here, we carried out all-atom molecular dynamics simulations to map the free-energy landscape of these lattices, validated this landscape through extensive structural characterization by electron microscopy and established that it is predominantly governed by solvent reorganization entropy. Subsequent redesign of the protein surface with conditionally repulsive electrostatic interactions enabled us to predictably perturb the free-energy landscape and obtain a new protein lattice whose conformational dynamics can be chemically and mechanically toggled between three different states with varying porosities and molecular densities.

Applying Human Factors Evaluation and Design Guidance to a Nuclear Power Plant Digital Control System

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

Thomas Ulrich; Ronald Boring; William Phoenix

2012-08-01

The United States (U.S.) nuclear industry, like similar process control industries, has moved toward upgrading its control rooms. The upgraded control rooms typically feature digital control system (DCS) displays embedded in the panels. These displays gather information from the system and represent that information on a single display surface. In this manner, the DCS combines many previously separate analog indicators and controls into a single digital display, whereby the operators can toggle between multiple windows to monitor and control different aspects of the plant. The design of the DCS depends on the function of the system it monitors, but revolvesmore » around presenting the information most germane to an operator at any point in time. DCSs require a carefully designed human system interface. This report centers on redesigning existing DCS displays for an example chemical volume control system (CVCS) at a U.S. nuclear power plant. The crucial nature of the CVCS, which controls coolant levels and boration in the primary system, requires a thorough human factors evaluation of its supporting DCS. The initial digital controls being developed for the DCSs tend to directly mimic the former analog controls. There are, however, unique operator interactions with a digital vs. analog interface, and the differences have not always been carefully factored in the translation of an analog interface to a replacement DCS. To ensure safety, efficiency, and usability of the emerging DCSs, a human factors usability evaluation was conducted on a CVCS DCS currently being used and refined at an existing U.S. nuclear power plant. Subject matter experts from process control engineering, software development, and human factors evaluated the DCS displays to document potential usability issues and propose design recommendations. The evaluation yielded 167 potential usability issues with the DCS. These issues should not be considered operator performance problems but rather opportunities identified by experts to improve upon the design of the DCS. A set of nine design recommendations was developed to address these potential issues. The design principles addressed the following areas: (1) color, (2) pop-up window structure, (3) navigation, (4) alarms, (5) process control diagram, (6) gestalt grouping, (7) typography, (8) terminology, and (9) data entry. Visuals illustrating the improved DCS displays accompany the design recommendations. These nine design principles serve as the starting point to a planned general DCS style guide that can be used across the U.S. nuclear industry to aid in the future design of effective DCS interfaces.« less

Anatomic findings and complications after surgical treatment of chronic, partial distal biceps tendon tears: a case cohort comparison study.

PubMed

Ruch, David S; Watters, Tyler Steven; Wartinbee, Daniel A; Richard, Marc J; Leversedge, Fraser J; Mithani, Suhail K

2014-08-01

To describe pertinent anatomic findings during repair of chronic, partial distal biceps tendon tears and to compare the complications of surgery with a similar cohort of acute, complete tears. Group 1 included 14 patients (15 elbows) with partial tears managed operatively an average of 10 months from onset of injury or symptoms. Group 2 included a matched cohort of 16 patients (17 elbows) treated for complete, acute tears an average of 19 days from injury. A retrospective review of all 30 patients focused on demographic data, intraoperative findings, and postoperative complications. A single, anterior incision was used in all cases with multiple suture anchors or a bicortical toggling button for fixation of the repair. We evaluated 27 men and 3 women with an average age of 55 years (group 1) and 48 years (group 2). Intratendinous ganglion formation at the site of rupture of the degenerative tendon was observed in 5 cases of partial tears and none of the complete tears. Partial tears involved the lateral aspect or short head of the biceps tendon insertion in all cases. Postoperative complications included lateral antebrachial cutaneous nerve neuritis in 8 group 1 patients and 6 group 2 patients and transient posterior interosseus nerve palsy in 3 group 1 patients. Partial distal biceps tendon ruptures showed a consistent pattern of pathology involving disruption of the lateral side of the tendon insertion involving the small head of the biceps. Degenerative intratendinous ganglion formation was present in one third of cases. Repair of chronic, partial distal biceps tendon injuries may have a higher incidence of posterior interosseous and lateral antebrachial cutaneous nerve palsies. Therapeutic III. Copyright © 2014 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Interrogating the topological robustness of gene regulatory circuits by randomization

PubMed Central

Levine, Herbert; Onuchic, Jose N.

2017-01-01

One of the most important roles of cells is performing their cellular tasks properly for survival. Cells usually achieve robust functionality, for example, cell-fate decision-making and signal transduction, through multiple layers of regulation involving many genes. Despite the combinatorial complexity of gene regulation, its quantitative behavior has been typically studied on the basis of experimentally verified core gene regulatory circuitry, composed of a small set of important elements. It is still unclear how such a core circuit operates in the presence of many other regulatory molecules and in a crowded and noisy cellular environment. Here we report a new computational method, named random circuit perturbation (RACIPE), for interrogating the robust dynamical behavior of a gene regulatory circuit even without accurate measurements of circuit kinetic parameters. RACIPE generates an ensemble of random kinetic models corresponding to a fixed circuit topology, and utilizes statistical tools to identify generic properties of the circuit. By applying RACIPE to simple toggle-switch-like motifs, we observed that the stable states of all models converge to experimentally observed gene state clusters even when the parameters are strongly perturbed. RACIPE was further applied to a proposed 22-gene network of the Epithelial-to-Mesenchymal Transition (EMT), from which we identified four experimentally observed gene states, including the states that are associated with two different types of hybrid Epithelial/Mesenchymal phenotypes. Our results suggest that dynamics of a gene circuit is mainly determined by its topology, not by detailed circuit parameters. Our work provides a theoretical foundation for circuit-based systems biology modeling. We anticipate RACIPE to be a powerful tool to predict and decode circuit design principles in an unbiased manner, and to quantitatively evaluate the robustness and heterogeneity of gene expression. PMID:28362798

Cell-SELEX-Based Identification of a Human and Mouse Cross-Reactive Endothelial Cell-Internalizing Aptamer.

PubMed

Dua, Pooja; Kang, Sinae; Shin, Hye-Soo; Kim, Soyoun; Lee, Dong-Ki

2018-04-02

Increased interest and insights gained by researchers on the roles of endothelial cells in the pathophysiology of cancer, inflammatory, and cardiovascular diseases have led to the design of pharmacological interventions aimed at the endothelium lining in the diseased sites. Toward this end, we used established brain microvascular endothelial cell lines mouse (bEND3), human (hCMEC/D3), and Toggle Cell-SELEX to identify a species cross-reactive, endothelial cell-internalizing aptamer R11-3. This 2'F-modified RNA aptamer is specific for endothelial cells as no internalization was seen with cells of nonendothelial origin. R11-3 was truncated in size, and its potential in endothelial targeted therapeutics was established using VEGFR2 targeting long interfering RNA (liRNA) aptamer chimera. Due to its specificity for both mouse and human endothelial cells, we believe that this aptamer not only fits for development of endothelial targeted drug development for human diseases but is also suitable for preclinical evaluation in mice.

Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche

NASA Astrophysics Data System (ADS)

Shao, Yue; Taniguchi, Kenichiro; Gurdziel, Katherine; Townshend, Ryan F.; Xue, Xufeng; Yong, Koh Meng Aw; Sang, Jianming; Spence, Jason R.; Gumucio, Deborah L.; Fu, Jianping

2017-04-01

Amniogenesis--the development of amnion--is a critical developmental milestone for early human embryogenesis and successful pregnancy. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP-SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

Mechanistic insights of the Min oscillator via cell-free reconstitution and imaging

NASA Astrophysics Data System (ADS)

Mizuuchi, Kiyoshi; Vecchiarelli, Anthony G.

2018-05-01

The MinD and MinE proteins of Escherichia coli self-organize into a standing-wave oscillator on the membrane to help align division at mid-cell. When unleashed from cellular confines, MinD and MinE form a spectrum of patterns on artificial bilayers—static amoebas, traveling waves, traveling mushrooms, and bursts with standing-wave dynamics. We recently focused our cell-free studies on bursts because their dynamics recapitulate many features of Min oscillation observed in vivo. The data unveiled a patterning mechanism largely governed by MinE regulation of MinD interaction with membrane. We proposed that the MinD to MinE ratio on the membrane acts as a toggle switch between MinE-stimulated recruitment and release of MinD from the membrane. In this review, we summarize cell-free data on the Min system and expand upon a molecular mechanism that provides a biochemical explanation as to how these two ‘simple’ proteins can form the remarkable spectrum of patterns.

Time-dependent behavior in a transport-barrier model for the quasi-single helcity state

NASA Astrophysics Data System (ADS)

Terry, P. W.; Whelan, G. G.

2014-09-01

Time-dependent behavior that follows from a recent theory of the quasi-single-helicity (QSH) state of the reversed field pinch is considered. The theory (Kim and Terry 2012 Phys. Plasmas 19 122304) treats QSH as a core fluctuation structure tied to a tearing mode of the same helicity, and shows that strong magnetic and velocity shears in the structure suppress the nonlinear interaction with other fluctuations. By summing the multiple helicity fluctuation energies over wavenumber, we reduce the theory to a predator-prey model. The suppression of the nonlinear interaction is governed by the single helicity energy, which, for fixed radial structure, controls the magnetic and velocity shearing rates. It is also controlled by plasma current which, in the theory, sets the shearing threshold for suppression. The model shows a limit cycle oscillation in which the system toggles between QSH and multiple helicity states, with the single helicity phase becoming increasingly long-lived relative to the multiple helicity phase as plasma current increases.

Molybdenum Carbamate Nanosheets as a New Class of Potential Phase Change Materials.

PubMed

Zhukovskyi, Maksym; Plashnitsa, Vladimir; Petchsang, Nattasamon; Ruth, Anthony; Bajpai, Anshumaan; Vietmeyer, Felix; Wang, Yuanxing; Brennan, Michael; Pang, Yunsong; Werellapatha, Kalpani; Bunker, Bruce; Chattopadhyay, Soma; Luo, Tengfei; Janko, Boldizsar; Fay, Patrick; Kuno, Masaru

2017-06-14

We report for the first time the synthesis of large, free-standing, Mo 2 O 2 (μ-S) 2 (Et 2 dtc) 2 (MoDTC) nanosheets (NSs), which exhibit an electron-beam induced crystalline-to-amorphous phase transition. Both electron beam ionization and femtosecond (fs) optical excitation induce the phase transition, which is size-, morphology-, and composition-preserving. Resulting NSs are the largest, free-standing regularly shaped two-dimensional amorphous nanostructures made to date. More importantly, amorphization is accompanied by dramatic changes to the NS electrical and optical response wherein resulting amorphous species exhibit room-temperature conductivities 5 orders of magnitude larger than those of their crystalline counterparts. This enhancement likely stems from the amorphization-induced formation of sulfur vacancy-related defects and is supported by temperature-dependent transport measurements, which reveal efficient variable range hopping. MoDTC NSs represent one instance of a broader class of transition metal carbamates likely having applications because of their intriguing electrical properties as well as demonstrated ability to toggle metal oxidation states.

Statistical mechanics of tuned cell signalling: sensitive collective response by synthetic biological circuits

NASA Astrophysics Data System (ADS)

Voliotis, M.; Liverpool, T. B.

2017-03-01

Living cells sense and process environmental cues through noisy biochemical mechanisms. This apparatus limits the scope of engineering cells as viable sensors. Here, we highlight a mechanism that enables robust, population-wide responses to external stimulation based on cellular communication, known as quorum sensing. We propose a synthetic circuit consisting of two mutually repressing quorum sensing modules. At low cell densities the system behaves like a genetic toggle switch, while at higher cell densities the behaviour of nearby cells is coupled via diffusible quorum sensing molecules. We show by systematic coarse graining that at large length and timescales that the system can be described using the Ising model of a ferromagnet. Thus, in analogy with magnetic systems, the sensitivity of the population-wide response, or its ‘susceptibility’ to a change in the external signal, is highly enhanced for a narrow range of cell-cell coupling close to a critical value. We expect that our approach will be used to enhance the sensitivity of synthetic bio-sensing networks.

The impact of listening with directional microphone technology on self-perceived localization disabilities and handicaps.

PubMed

Ruscetta, Melissa N; Palmer, Catherine V; Durrant, John D; Grayhack, Judith; Ryan, Carey

2007-10-01

The chief complaint of individuals with hearing impairment is difficulty hearing in noise, with directional microphones emerging as the most capable remediation. Our purpose was to determine the impact of directional microphones on localization disability and concurrent handicap. Fifty-seven individuals participated unaided and then in groups of 19, using omni-directional microphones, directional-microphones, or toggle-switch equipped amplification. The outcome measure was a localization disabilities and handicaps questionnaire. Comparisons between the unaided group versus the aided groups, and the directional-microphone groups versus the other two aided groups revealed no significant differences. None of the microphone schemes either increased or decreased self-perceived localization disability or handicap. Objective measures of localization ability are warranted and if significance is noted, clinicians should caution patients when moving in their environment. If no significant objective differences exist, in light of the subjective findings in this investigation concern over decreases in quality of life and safety with directional microphones need not be considered.

Payload specialist station study: Volume 2, part 3: Program analysis and planning for phase C/D

NASA Technical Reports Server (NTRS)

1976-01-01

The controls and displays (C&D) required at the Orbiter aft-flight deck (AFD) and the core C&D required at the Payload Specialist Station (PSS) are identified in this document. The AFD C&D Concept consists of a multifunction display system (MFDS) and elements of multiuse mission support equipment (MMSE). The MFDS consists of two CRTs, a display electronics unit (DEU), and a keyboard. The MMSE consists of a manual pointing controller (MPC), five digit numeric displays, 10 character alphanumeric legends, event timers, analog meters, rotary and toggle switches. The MMSE may be hardwired to the experiment, or interface with a data bus at the PSS for signal processing. The MFDS has video capability, with alphanumeric and graphic overlay features, on one CRT and alphanumeric and graphic (tricolor) capability on a second CRT. The DEU will have the capability to communicate, via redundant data buses, with both the spacelab experiment and subsystem computers.

An analytical expression for ion velocities at the wall including the sheath electric field and surface biasing for erosion modeling at JET ILW

DOE PAGES

Borodkina, I.; Borodin, D.; Brezinsek, S.; ...

2017-04-12

For simulation of plasma-facing component erosion in fusion experiments, an analytical expression for the ion velocity just before the surface impact including the local electric field and an optional surface biasing effect is suggested. Energy and angular impact distributions and the resulting effective sputtering yields were produced for several experimental scenarios at JET ILW mostly involving PFCs exposed to an oblique magnetic field. The analytic solution has been applied as an improvement to earlier ERO modelling of localized, Be outer limiter, RF-enhanced erosion, modulated by toggling of a remote, however magnetically connected ICRH antenna. The effective W sputtering yields duemore » to D and Be ion impact in Type-I and Type-III ELMs and inter-ELM conditions were also estimated using the analytical approach and benchmarked by spectroscopy. The intra-ELM W sputtering flux increases almost 10 times in comparison to the inter-ELM flux.« less

Performance evaluation of a semi-active cladding connection for multi-hazard mitigation

NASA Astrophysics Data System (ADS)

Gong, Yongqiang; Cao, Liang; Micheli, Laura; Laflamme, Simon; Quiel, Spencer; Ricles, James

2018-03-01

A novel semi-active damping device termed Variable Friction Cladding Connection (VFCC) has been previously proposed to leverage cladding systems for the mitigation of natural and man-made hazards. The VFCC is a semi-active friction damper that connects cladding elements to the structural system. The friction force is generated by sliding plates and varied using an actuator through a system of adjustable toggles. The dynamics of the device has been previously characterized in a laboratory environment. In this paper, the performance of the VFCC at mitigating non-simultaneous multi-hazard excitations that includes wind and seismic loads is investigated on a simulated benchmark building. Simulations consider the robustness with respect to some uncertainties, including the wear of the friction surfaces and sensor failure. The performance of the VFCC is compared against other connection strategies including traditional stiffness, passive viscous, and passive friction elements. Results show that the VFCC is robust and capable of outperforming passive systems for the mitigation of multiple hazards.

Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis.

PubMed

Petrie, Emma J; Sandow, Jarrod J; Jacobsen, Annette V; Smith, Brian J; Griffin, Michael D W; Lucet, Isabelle S; Dai, Weiwen; Young, Samuel N; Tanzer, Maria C; Wardak, Ahmad; Liang, Lung-Yu; Cowan, Angus D; Hildebrand, Joanne M; Kersten, Wilhelmus J A; Lessene, Guillaume; Silke, John; Czabotar, Peter E; Webb, Andrew I; Murphy, James M

2018-06-21

Necroptotic cell death is mediated by the most terminal known effector of the pathway, MLKL. Precisely how phosphorylation of the MLKL pseudokinase domain activation loop by the upstream kinase, RIPK3, induces unmasking of the N-terminal executioner four-helix bundle (4HB) domain of MLKL, higher-order assemblies, and permeabilization of plasma membranes remains poorly understood. Here, we reveal the existence of a basal monomeric MLKL conformer present in human cells prior to exposure to a necroptotic stimulus. Following activation, toggling within the MLKL pseudokinase domain promotes 4HB domain disengagement from the pseudokinase domain αC helix and pseudocatalytic loop, to enable formation of a necroptosis-inducing tetramer. In contrast to mouse MLKL, substitution of RIPK3 substrate sites in the human MLKL pseudokinase domain completely abrogated necroptotic signaling. Therefore, while the pseudokinase domains of mouse and human MLKL function as molecular switches to control MLKL activation, the underlying mechanism differs between species.

Crystal Structure of Deinococcus Phytochrome in the Photoactivated State Reveals a Cascade of Structural Rearrangements during Photoconversion.

PubMed

Burgie, E Sethe; Zhang, Junrui; Vierstra, Richard D

2016-03-01

Phytochromes are photochromic photoreceptors responsible for a myriad of red/far-red light-dependent processes in plants and microorganisms. Interconversion is initially driven by photoreversible isomerization of bilin, but how this alteration directs the photostate-dependent changes within the protein to actuate signaling is poorly understood. Here, we describe the structure of the Deinococcus phytochrome photosensory module in its near complete far-red light-absorbing Pfr state. In addition to confirming the 180° rotation of the D-pyrrole ring, the dimeric structure clearly identifies downstream rearrangements that trigger large-scale conformational differences between the dark-adapted and photoactivated states. Mutational analyses verified the importance of residues surrounding the bilin in Pfr stabilization, and protease sensitivity assays corroborated photostate alterations that propagate along the dimeric interface. Collectively, these data support a cooperative "toggle" model for phytochrome photoconversion and advance our understanding of the allosteric connection between the photosensory and output modules. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Chen, Hang, E-mail: hangchen@mit.edu; Thill, Peter; Cao, Jianshu

In biochemical systems, intrinsic noise may drive the system switch from one stable state to another. We investigate how kinetic switching between stable states in a bistable network is influenced by dynamic disorder, i.e., fluctuations in the rate coefficients. Using the geometric minimum action method, we first investigate the optimal transition paths and the corresponding minimum actions based on a genetic toggle switch model in which reaction coefficients draw from a discrete probability distribution. For the continuous probability distribution of the rate coefficient, we then consider two models of dynamic disorder in which reaction coefficients undergo different stochastic processes withmore » the same stationary distribution. In one, the kinetic parameters follow a discrete Markov process and in the other they follow continuous Langevin dynamics. We find that regulation of the parameters modulating the dynamic disorder, as has been demonstrated to occur through allosteric control in bistable networks in the immune system, can be crucial in shaping the statistics of optimal transition paths, transition probabilities, and the stationary probability distribution of the network.« less

Biophysical Constraints Arising from Compositional Context in Synthetic Gene Networks.

PubMed

Yeung, Enoch; Dy, Aaron J; Martin, Kyle B; Ng, Andrew H; Del Vecchio, Domitilla; Beck, James L; Collins, James J; Murray, Richard M

2017-07-26

Synthetic gene expression is highly sensitive to intragenic compositional context (promoter structure, spacing regions between promoter and coding sequences, and ribosome binding sites). However, much less is known about the effects of intergenic compositional context (spatial arrangement and orientation of entire genes on DNA) on expression levels in synthetic gene networks. We compare expression of induced genes arranged in convergent, divergent, or tandem orientations. Induction of convergent genes yielded up to 400% higher expression, greater ultrasensitivity, and dynamic range than divergent- or tandem-oriented genes. Orientation affects gene expression whether one or both genes are induced. We postulate that transcriptional interference in divergent and tandem genes, mediated by supercoiling, can explain differences in expression and validate this hypothesis through modeling and in vitro supercoiling relaxation experiments. Treatment with gyrase abrogated intergenic context effects, bringing expression levels within 30% of each other. We rebuilt the toggle switch with convergent genes, taking advantage of supercoiling effects to improve threshold detection and switch stability. Copyright © 2017 Elsevier Inc. All rights reserved.

Quorum-Sensing Synchronization of Synthetic Toggle Switches: A Design Based on Monotone Dynamical Systems Theory

PubMed Central

Nikolaev, Evgeni V.

2016-01-01

Synthetic constructs in biotechnology, biocomputing, and modern gene therapy interventions are often based on plasmids or transfected circuits which implement some form of “on-off” switch. For example, the expression of a protein used for therapeutic purposes might be triggered by the recognition of a specific combination of inducers (e.g., antigens), and memory of this event should be maintained across a cell population until a specific stimulus commands a coordinated shut-off. The robustness of such a design is hampered by molecular (“intrinsic”) or environmental (“extrinsic”) noise, which may lead to spontaneous changes of state in a subset of the population and is reflected in the bimodality of protein expression, as measured for example using flow cytometry. In this context, a “majority-vote” correction circuit, which brings deviant cells back into the required state, is highly desirable, and quorum-sensing has been suggested as a way for cells to broadcast their states to the population as a whole so as to facilitate consensus. In this paper, we propose what we believe is the first such a design that has mathematically guaranteed properties of stability and auto-correction under certain conditions. Our approach is guided by concepts and theory from the field of “monotone” dynamical systems developed by M. Hirsch, H. Smith, and others. We benchmark our design by comparing it to an existing design which has been the subject of experimental and theoretical studies, illustrating its superiority in stability and self-correction of synchronization errors. Our stability analysis, based on dynamical systems theory, guarantees global convergence to steady states, ruling out unpredictable (“chaotic”) behaviors and even sustained oscillations in the limit of convergence. These results are valid no matter what are the values of parameters, and are based only on the wiring diagram. The theory is complemented by extensive computational bifurcation analysis, performed for a biochemically-detailed and biologically-relevant model that we developed. Another novel feature of our approach is that our theorems on exponential stability of steady states for homogeneous or mixed populations are valid independently of the number N of cells in the population, which is usually very large (N ≫ 1) and unknown. We prove that the exponential stability depends on relative proportions of each type of state only. While monotone systems theory has been used previously for systems biology analysis, the current work illustrates its power for synthetic biology design, and thus has wider significance well beyond the application to the important problem of coordination of toggle switches. PMID:27128344

How to build and teach with QuakeCaster: an earthquake demonstration and exploration tool

USGS Publications Warehouse

Linton, Kelsey; Stein, Ross S.

2015-01-01

QuakeCaster is an interactive, hands-on teaching model that simulates earthquakes and their interactions along a plate-boundary fault. QuakeCaster contains the minimum number of physical processes needed to demonstrate most observable earthquake features. A winch to steadily reel in a line simulates the steady plate tectonic motions far from the plate boundaries. A granite slider in frictional contact with a nonskid rock-like surface simulates a fault at a plate boundary. A rubber band connecting the line to the slider simulates the elastic character of the Earth’s crust. By stacking and unstacking sliders and cranking in the winch, one can see the results of changing the shear stress and the clamping stress on a fault. By placing sliders in series with rubber bands between them, one can simulate the interaction of earthquakes along a fault, such as cascading or toggling shocks. By inserting a load scale into the line, one can measure the stress acting on the fault throughout the earthquake cycle. As observed for real earthquakes, QuakeCaster events are not periodic, time-predictable, or slip-predictable. QuakeCaster produces rare but unreliable “foreshocks.” When fault gouge builds up, the friction goes to zero and fault creep is seen without large quakes. QuakeCaster events produce very small amounts of fault gouge that strongly alter its behavior, resulting in smaller, more frequent shocks as the gouge accumulates. QuakeCaster is designed so that students or audience members can operate it and record its output. With a stopwatch and ruler one can measure and plot the timing, slip distance, and force results of simulated earthquakes. People of all ages can use the QuakeCaster model to explore hypotheses about earthquake occurrence. QuakeCaster takes several days and about $500.00 in materials to build.

Thermal Control Using Liquid-Metal Bridge Switches

NASA Technical Reports Server (NTRS)

Hirsa, Amir H.; Olles, Joseph; Tilger, Christopher

2013-01-01

A short term effort (3-months) was undertaken to demonstrate the feasibility of a novel method to locally control the heat transfer rate and demonstrate the potential to achieve a turndown ratio of approximately 10:1. The technology had to be demonstrated to be at a TRL of 2-3, with a plan to advance it to a TRL 5-6. Here, we show that the concept recently developed in our laboratory, namely the pinned-contact, double droplet switch made by overfilling a hole drilled in a suitable substrate can be implemented with a low-melting temperature metal. When toggled near a second substrate, a liquid bridge can be reversibly connected or disconnected, on demand. We have shown experimentally that liquid-metal bridge switches can be made from gallium with a suitable choice of substrate materials, activation strategies, and control techniques. Individual as well as arrays of gallium bridge switches were shown to be feasible and can be robustly controlled. The very short response time of the bridge connection and disconnection (on the order of 1 millisecond) provides for utility in a wide range of applications. The liquid bridge switches may be controlled actively or passively. We have shown through computations and analysis that liquid bridge switches provide locally large turndown ratios (on the order of 103:1), so a relatively sparse packing of them would be needed to obtain the desired turndown ratio of 10:1. For the laboratory demonstrations, pressure activation was utilized. Simple designs for a passive control strategy are presented which are highly attractive for several reasons, including i) large turndown ratio, ii) no solid-moving parts, and iii) stable operation. Finally, we note that passive systems do not require any electronics for their control. This along with the relatively small molecular weight of candidate materials for the system, makes for a robust design outside of Earth?s magnetic field, where spacecraft are subject to significant radiation bombardment.

Structural heterogeneity of the μ-opioid receptor’s conformational ensemble in the apo state

NASA Astrophysics Data System (ADS)

Sena, Diniz M.; Cong, Xiaojing; Giorgetti, Alejandro; Kless, Achim; Carloni, Paolo

2017-04-01

G-protein coupled receptors (GPCRs) are the largest and most pharmaceutically relevant family of membrane proteins. Here, fully unbiased, enhanced sampling simulations of a constitutively active mutant (CAM) of a class A GPCR, the μ-opioid receptor (μOR), demonstrates repeated transitions between the inactive (IS) and active-like (AS-L) states. The interconversion features typical activation/inactivation patterns involving established conformational rearrangements of conserved residues. By contrast, wild-type μOR remains in IS during the same course of simulation, consistent with the low basal activity of the protein. The simulations point to an important role of residue W2936.48 at the “toggle switch” in the mutation-induced constitutive activation. Such role has been already observed for other CAMs of class A GPCRs. We also find a significantly populated intermediate state, rather similar to IS. Based on the remarkable accord between simulations and experiments, we suggest here that this state, which has escaped so far experimental characterization, might constitute an early step in the activation process of the apo μOR CAM.

Mechanisms of Cancer Cell Dormancy--Another Hallmark of Cancer?

PubMed

Yeh, Albert C; Ramaswamy, Sridhar

2015-12-01

Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biologic level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biologic insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately downregulate the RAS/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. ©2015 American Association for Cancer Research.

Mechanisms of Cancer Cell Dormancy – Another Hallmark of Cancer?

PubMed Central

Yeh, Albert C.; Ramaswamy, Sridhar

2015-01-01

Disease relapse in cancer patients many years after clinical remission, often referred to as cancer dormancy, is well documented but remains an incompletely understood phenomenon on the biological level. Recent reviews have summarized potential models that can explain this phenomenon, including angiogenic, immunologic, and cellular dormancy. We focus on mechanisms of cellular dormancy as newer biological insights have enabled better understanding of this process. We provide a historical context, synthesize current advances in the field, and propose a mechanistic framework that treats cancer cell dormancy as a dynamic cell state conferring a fitness advantage to an evolving malignancy under stress. Cellular dormancy appears to be an active process that can be toggled through a variety of signaling mechanisms that ultimately down-regulate the Ras/MAPK and PI(3)K/AKT pathways, an ability that is preserved even in cancers that constitutively depend on these pathways for their growth and survival. Just as unbridled proliferation is a key hallmark of cancer, the ability of cancer cells to become quiescent may be critical to evolving malignancies, with implications for understanding cancer initiation, progression, and treatment resistance. PMID:26354021

Lewis Acid Induced Toggle from Ir(II) to Ir(IV) Pathways in Photocatalytic Reactions: Synthesis of Thiomorpholines and Thiazepanes from Aldehydes and SLAP Reagents

PubMed Central

2016-01-01

Redox neutral photocatalytic transformations often require careful pairing of the substrates and photoredox catalysts in order to achieve a catalytic cycle. This can limit the range of viable transformations, as we recently observed in attempting to extend the scope of the photocatalytic synthesis of N-heterocycles using silicon amine protocol (SLAP) reagents to include starting materials that require higher oxidation potentials. We now report that the inclusion of Lewis acids in photocatalytic reactions of organosilanes allows access to a distinct reaction pathway featuring an Ir(III)*/Ir(IV) couple instead of the previously employed Ir(III)*/Ir(II) pathway, enabling the transformation of aromatic and aliphatic aldehydes to thiomorpholines and thiazepanes. The role of the Lewis acid in accepting an electron—either directly or via coordination to an imine—can be extended to other classes of photocatalysts and transformations, including oxidative cyclizations. The combination of light induced reactions and Lewis acids therefore promises access to new pathways and transformations that are not viable using the photocatalysts alone. PMID:28149955

Period doubling induced by thermal noise amplification in genetic circuits

PubMed Central

Ruocco, G.; Fratalocchi, A.

2014-01-01

Rhythms of life are dictated by oscillations, which take place in a wide rage of biological scales. In bacteria, for example, oscillations have been proven to control many fundamental processes, ranging from gene expression to cell divisions. In genetic circuits, oscillations originate from elemental block such as autorepressors and toggle switches, which produce robust and noise-free cycles with well defined frequency. In some circumstances, the oscillation period of biological functions may double, thus generating bistable behaviors whose ultimate origin is at the basis of intense investigations. Motivated by brain studies, we here study an “elemental” genetic circuit, where a simple nonlinear process interacts with a noisy environment. In the proposed system, nonlinearity naturally arises from the mechanism of cooperative stability, which regulates the concentration of a protein produced during a transcription process. In this elemental model, bistability results from the coherent amplification of environmental fluctuations due to a stochastic resonance of nonlinear origin. This suggests that the period doubling observed in many biological functions might result from the intrinsic interplay between nonlinearity and thermal noise. PMID:25404210

Progression from Chronic Atrophic Gastritis to Gastric Cancer; Tangle, Toggle, Tackle with Korea Red Ginseng

PubMed Central

Kim, Yoon Jae; Chung, Jun Won; Lee, So Jung; Choi, Ki Seok; Kim, Ju Hyun; Hahm, Ki Baik

2010-01-01

Key molecular players that link inflammation to carcinogenesis are prostaglandins, cytokines, nuclear factor-κB (NF-κB), chemokines, angiogenic growth factors, and free radicals, all of which lead to increased mutations and altered functions of important enzymes and proteins, for example, activation of oncogenic products and/or inhibition of tumor suppressor proteins, in inflamed tissues, thus contributing to multi-stage carcinogenesis process. Interpreted reversely, the identification of the molecular mechanisms by which chronic inflammation increases cancer risk or optimal intervention of targeted drugs or agents during the inflammation-associated carcinogenic process could be a necessary basis for developing new strategy of cancer prevention at many sites. In this review, we discuss the possibilities for cancer prevention by controlling inflammation process in Helicobacter pylori (H. pylori)-associated inflamed stomach with Korea red ginseng. Korea red ginseng is a good example of a natural herb that has ubiquitous properties that are conductive to stop inflammatory carcinogenesis that is un wanted outcome of H. pylori infection, rendering rejuvenation of chronic atrophic gastritis. PMID:20490314

3D Flow visualization in virtual reality

NASA Astrophysics Data System (ADS)

Pietraszewski, Noah; Dhillon, Ranbir; Green, Melissa

2017-11-01

By viewing fluid dynamic isosurfaces in virtual reality (VR), many of the issues associated with the rendering of three-dimensional objects on a two-dimensional screen can be addressed. In addition, viewing a variety of unsteady 3D data sets in VR opens up novel opportunities for education and community outreach. In this work, the vortex wake of a bio-inspired pitching panel was visualized using a three-dimensional structural model of Q-criterion isosurfaces rendered in virtual reality using the HTC Vive. Utilizing the Unity cross-platform gaming engine, a program was developed to allow the user to control and change this model's position and orientation in three-dimensional space. In addition to controlling the model's position and orientation, the user can ``scroll'' forward and backward in time to analyze the formation and shedding of vortices in the wake. Finally, the user can toggle between different quantities, while keeping the time step constant, to analyze flow parameter relationships at specific times during flow development. The information, data, or work presented herein was funded in part by an award from NYS Department of Economic Development (DED) through the Syracuse Center of Excellence.

A time- and matrix-dependent TGFBR3–JUND–KRT5 regulatory circuit in single breast epithelial cells and basal-like premalignancies

PubMed Central

Wang, Chun-Chao; Bajikar, Sameer S.; Jamal, Leen; Atkins, Kristen A.; Janes, Kevin A.

2014-01-01

Basal-like breast carcinoma is characterized by poor prognosis and high intratumor heterogeneity. In an immortalized basal-like breast epithelial cell line, we identified two anti-correlated gene-expression programs that arise among single extracellular matrix (ECM)-attached cells during organotypic 3D culture. The first contains multiple TGFβ-related genes including TGFBR3, whereas the second contains JUND and the basal-like marker, KRT5. TGFBR3 and JUND interconnect through four negative-feedback loops to form a circuit that exhibits spontaneous damped oscillations in 3D culture. The TGFBR3–JUND circuit appears conserved in some premalignant lesions that heterogeneously express KRT5. The circuit depends on ECM engagement, as detachment causes a rewiring that is triggered by RPS6 dephosphorylation and maintained by juxtacrine tenascin C, which is critical for intraductal colonization of basal-like breast cancer cells in vivo. Intratumor heterogeneity need not stem from partial differentiation and could instead reflect dynamic toggling of cells between expression states that are not cell autonomous. PMID:24658685

The neurobiology of focus and distraction: The case for incorporating mindfulness into leadership.

PubMed

Mohapel, Paul

2018-05-01

Increasingly health leaders are experiencing greater demands and pressures, which require the need for better focus while limiting unwarranted distractions. This article offers a neurobiological explanation of how the brain focuses and becomes distracted, in order to help health leaders gain insight into their own effectiveness. Two main neural circuits are contrasted: the mind-wandering default mode circuit and the attentional central executive system. These two systems act in an antagonistic pairing, where the degree of toggling between systems is associated with the degree a person can sustain focus and filter out unwarranted distractions. Excessive multitasking appears to compromise the neural switch of these two systems, thereby diminishing our focus and concentration. In contrast, mindfulness practice is shown to have the opposite effect by enhancing the neural switch, thereby enhancing leadership focus that can lead to greater flexibility, foresight, regulation, and creativity. To conclude, leaders who are excessively distracted, such as with multitasking, may be compromising cognitive brain functioning, while engaging in mindfulness may replenish the brain and thereby enhance leaders' ability to sustain focus and tap into higher cognitive functioning.

Period doubling induced by thermal noise amplification in genetic circuits.

PubMed

Ruocco, G; Fratalocchi, A

2014-11-18

Rhythms of life are dictated by oscillations, which take place in a wide rage of biological scales. In bacteria, for example, oscillations have been proven to control many fundamental processes, ranging from gene expression to cell divisions. In genetic circuits, oscillations originate from elemental block such as autorepressors and toggle switches, which produce robust and noise-free cycles with well defined frequency. In some circumstances, the oscillation period of biological functions may double, thus generating bistable behaviors whose ultimate origin is at the basis of intense investigations. Motivated by brain studies, we here study an "elemental" genetic circuit, where a simple nonlinear process interacts with a noisy environment. In the proposed system, nonlinearity naturally arises from the mechanism of cooperative stability, which regulates the concentration of a protein produced during a transcription process. In this elemental model, bistability results from the coherent amplification of environmental fluctuations due to a stochastic resonance of nonlinear origin. This suggests that the period doubling observed in many biological functions might result from the intrinsic interplay between nonlinearity and thermal noise.

Gene regulatory networks: a coarse-grained, equation-free approach to multiscale computation.

PubMed

Erban, Radek; Kevrekidis, Ioannis G; Adalsteinsson, David; Elston, Timothy C

2006-02-28

We present computer-assisted methods for analyzing stochastic models of gene regulatory networks. The main idea that underlies this equation-free analysis is the design and execution of appropriately initialized short bursts of stochastic simulations; the results of these are processed to estimate coarse-grained quantities of interest, such as mesoscopic transport coefficients. In particular, using a simple model of a genetic toggle switch, we illustrate the computation of an effective free energy Phi and of a state-dependent effective diffusion coefficient D that characterize an unavailable effective Fokker-Planck equation. Additionally we illustrate the linking of equation-free techniques with continuation methods for performing a form of stochastic "bifurcation analysis"; estimation of mean switching times in the case of a bistable switch is also implemented in this equation-free context. The accuracy of our methods is tested by direct comparison with long-time stochastic simulations. This type of equation-free analysis appears to be a promising approach to computing features of the long-time, coarse-grained behavior of certain classes of complex stochastic models of gene regulatory networks, circumventing the need for long Monte Carlo simulations.

Multi-static MIMO along track interferometry (ATI)

NASA Astrophysics Data System (ADS)

Knight, Chad; Deming, Ross; Gunther, Jake

2016-05-01

Along-track interferometry (ATI) has the ability to generate high-quality synthetic aperture radar (SAR) images and concurrently detect and estimate the positions of ground moving target indicators (GMTI) with moderate processing requirements. This paper focuses on several different ATI system configurations, with an emphasis on low-cost configurations employing no active electronic scanned array (AESA). The objective system has two transmit phase centers and four receive phase centers and supports agile adaptive radar behavior. The advantages of multistatic, multiple input multiple output (MIMO) ATI system configurations are explored. The two transmit phase centers can employ a ping-pong configuration to provide the multistatic behavior. For example, they can toggle between an up and down linear frequency modulated (LFM) waveform every other pulse. The four receive apertures are considered in simple linear spatial configurations. Simulated examples are examined to understand the trade space and verify the expected results. Finally, actual results are collected with the Space Dynamics Laboratorys (SDL) FlexSAR system in diverse configurations. The theory, as well as the simulated and actual SAR results, are presented and discussed.

Electric field controlled strain induced reversible switching of magnetization in Galfenol nanomagnets delineated on PMN-PT substrate

NASA Astrophysics Data System (ADS)

Ahmad, Hasnain; Atulasimha, Jayasimha; Bandyopadhyay, Supriyo

We report a non-volatile converse magneto-electric effect in elliptical Galfenol (FeGa) nanomagnets of ~300 nm lateral dimensions and ~10nm thickness delineated on a PMN-PT substrate. This effect can be harnessed for energy-efficient non-volatile memory. The nanomagnets are fabricated with e-beam lithography and sputtering. Their major axes are aligned parallel to the direction in which the substrate is poled and they are magnetized in this direction with a magnetic field. An electric field in the opposite direction generates compressive strain in the piezoelectric substrate which is partially transferred to the nanomagnets and rotates their magnetization away from the major axes to metastable orientations. There they remain after the field is removed, resulting in non-volatility. Reversing the electric field generates tensile strain which returns the magnetization to the original state. The two states can encode two binary bits which can be written using the correct voltage polarity, resulting in non-toggle behavior. Scaled memory fashioned on this effect can exhibit write energy dissipation of only ~2 aJ. Work is supported by NSF under ECCS-1124714 and CCF-1216614. Sputtering was carried out at NIST Gaithersburg.

Controllable 0–π Josephson junctions containing a ferromagnetic spin valve

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

Gingrich, E. C.; Niedzielski, Bethany M.; Glick, Joseph A.

Superconductivity and ferromagnetism are antagonistic forms of order, and rarely coexist. Many interesting new phenomena occur, however, in hybrid superconducting/ferromagnetic systems. For example, a Josephson junction containing a ferromagnetic material can exhibit an intrinsic phase shift of π in its ground state for certain thicknesses of the material. Such ‘π-junctions’ were first realized experimentally in 2001, and have been proposed as circuit elements for both high-speed classical superconducting computing and for quantum computing. Here we demonstrate experimentally that the phase state of a Josephson junction containing two ferromagnetic layers can be toggled between 0 and pi by changing the relativemore » orientation of the two magnetizations. These controllable 0–π junctions have immediate applications in cryogenic memory, where they serve as a necessary component to an ultralow power superconducting computer. Such a fully superconducting computer is estimated to be orders of magnitude more energy-efficient than current semiconductor-based supercomputers. Here, phase-controllable junctions also open up new possibilities for superconducting circuit elements such as superconducting ‘programmable logic’, where they could function in superconducting analogues to field-programmable gate arrays.« less

Glucose-Regulated Phosphorylation of the PUF Protein Puf3 Regulates the Translational Fate of Its Bound mRNAs and Association with RNA Granules.

PubMed

Lee, Chien-Der; Tu, Benjamin P

2015-06-16

PUF proteins are post-transcriptional regulators that bind to the 3' UTRs of mRNA transcripts. Herein, we show how a yeast PUF protein, Puf3p, responds to glucose availability to switch the fate of its bound transcripts that encode proteins required for mitochondrial biogenesis. Upon glucose depletion, Puf3p becomes heavily phosphorylated within its N-terminal region of low complexity, associates with polysomes, and promotes translation of its target mRNAs. Such nutrient-responsive phosphorylation toggles the activity of Puf3p to promote either degradation or translation of these mRNAs according to the needs of the cell. Moreover, activation of translation of pre-existing mRNAs might enable rapid adjustment to environmental changes without the need for de novo transcription. Strikingly, a Puf3p phosphomutant no longer promotes translation but becomes trapped in intracellular foci in an mRNA-dependent manner. Our findings suggest that the inability to properly resolve Puf3p-containing RNA-protein granules via a phosphorylation-based mechanism might be toxic to a cell. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Monte Carlo simulation of a simple gene network yields new evolutionary insights.

PubMed

Andrecut, M; Cloud, D; Kauffman, S A

2008-02-07

Monte Carlo simulations of a genetic toggle switch show that its behavior can be more complex than analytic models would suggest. We show here that as a result of the interplay between frequent and infrequent reaction events, such a switch can have more stable states than an analytic model would predict, and that the number and character of these states depend to a large extent on the propensity of transcription factors to bind to and dissociate from promoters. The effects of gene duplications differ even more; in analytic models, these seem to result in the disappearance of bi-stability and thus a loss of the switching function, but a Monte Carlo simulation shows that they can result in the appearance of new stable states without the loss of old ones, and thus in an increase of the complexity of the switch's behavior which may facilitate the evolution of new cellular functions. These differences are of interest with respect to the evolution of gene networks, particularly in clonal lines of cancer cells, where the duplication of active genes is an extremely common event, and often seems to result in the appearance of viable new cellular phenotypes.

Optimizing height presentation for aircraft cockpit displays

NASA Astrophysics Data System (ADS)

Jordan, Chris S.; Croft, D.; Selcon, Stephen J.; Markin, H.; Jackson, M.

1997-02-01

This paper describes an experiment conducted to investigate the type of display symbology that most effectively conveys height information to users of head-down plan-view radar displays. The experiment also investigated the use of multiple information sources (redundancy) in the design of such displays. Subjects were presented with eight different height display formats. These formats were constructed from a control, and/or one, two, or three sources of redundant information. The three formats were letter coding, analogue scaling, and toggling (spatially switching the position of the height information from above to below the aircraft symbol). Subjects were required to indicate altitude awareness via a four-key, forced-choice keyboard response. Error scores and response times were taken as performance measures. There were three main findings. First, there was a significant performance advantage when the altitude information was presented above and below the symbol to aid the representation of height information. Second, the analogue scale, a line whose length indicated altitude, proved significantly detrimental to performance. Finally, no relationship was found between the number of redundant information sources employed and performance. The implications for future aircraft and displays are discussed in relation to current aircraft tactical displays and in the context of perceptual psychological theory.

Synthetic biology and biomimetic chemistry as converging technologies fostering a new generation of smart biosensors.

PubMed

Scognamiglio, Viviana; Antonacci, Amina; Lambreva, Maya D; Litescu, Simona C; Rea, Giuseppina

2015-12-15

Biosensors are powerful tunable systems able to switch between an ON/OFF status in response to an external stimulus. This extraordinary property could be engineered by adopting synthetic biology or biomimetic chemistry to obtain tailor-made biosensors having the desired requirements of robustness, sensitivity and detection range. Recent advances in both disciplines, in fact, allow to re-design the configuration of the sensing elements - either by modifying toggle switches and gene networks, or by producing synthetic entities mimicking key properties of natural molecules. The present review considered the role of synthetic biology in sustaining biosensor technology, reporting examples from the literature and reflecting on the features that make it a useful tool for designing and constructing engineered biological systems for sensing application. Besides, a section dedicated to bioinspired synthetic molecules as powerful tools to enhance biosensor potential is reported, and treated as an extension of the concept of biomimetic chemistry, where organic synthesis is used to generate artificial molecules that mimic natural molecules. Thus, the design of synthetic molecules, such as aptamers, biomimetics, molecular imprinting polymers, peptide nucleic acids, and ribozymes were encompassed as "products" of biomimetic chemistry. Copyright © 2015 Elsevier B.V. All rights reserved.

PRODIGEN: visualizing the probability landscape of stochastic gene regulatory networks in state and time space.

PubMed

Ma, Chihua; Luciani, Timothy; Terebus, Anna; Liang, Jie; Marai, G Elisabeta

2017-02-15

Visualizing the complex probability landscape of stochastic gene regulatory networks can further biologists' understanding of phenotypic behavior associated with specific genes. We present PRODIGEN (PRObability DIstribution of GEne Networks), a web-based visual analysis tool for the systematic exploration of probability distributions over simulation time and state space in such networks. PRODIGEN was designed in collaboration with bioinformaticians who research stochastic gene networks. The analysis tool combines in a novel way existing, expanded, and new visual encodings to capture the time-varying characteristics of probability distributions: spaghetti plots over one dimensional projection, heatmaps of distributions over 2D projections, enhanced with overlaid time curves to display temporal changes, and novel individual glyphs of state information corresponding to particular peaks. We demonstrate the effectiveness of the tool through two case studies on the computed probabilistic landscape of a gene regulatory network and of a toggle-switch network. Domain expert feedback indicates that our visual approach can help biologists: 1) visualize probabilities of stable states, 2) explore the temporal probability distributions, and 3) discover small peaks in the probability landscape that have potential relation to specific diseases.

Granular self-organization by autotuning of friction.

PubMed

Kumar, Deepak; Nitsure, Nitin; Bhattacharya, S; Ghosh, Shankar

2015-09-15

A monolayer of granular spheres in a cylindrical vial, driven continuously by an orbital shaker and subjected to a symmetric confining centrifugal potential, self-organizes to form a distinctively asymmetric structure which occupies only the rear half-space. It is marked by a sharp leading edge at the potential minimum and a curved rear. The area of the structure obeys a power-law scaling with the number of spheres. Imaging shows that the regulation of motion of individual spheres occurs via toggling between two types of motion, namely, rolling and sliding. A low density of weakly frictional rollers congregates near the sharp leading edge whereas a denser rear comprises highly frictional sliders. Experiments further suggest that because the rolling and sliding friction coefficients differ substantially, the spheres acquire a local time-averaged coefficient of friction within a large range of intermediate values in the system. The various sets of spatial and temporal configurations of the rollers and sliders constitute the internal states of the system. Experiments demonstrate and simulations confirm that the global features of the structure are maintained robustly by autotuning of friction through these internal states, providing a previously unidentified route to self-organization of a many-body system.

Controllable 0–π Josephson junctions containing a ferromagnetic spin valve

DOE PAGES

Gingrich, E. C.; Niedzielski, Bethany M.; Glick, Joseph A.; ...

2016-03-14

Superconductivity and ferromagnetism are antagonistic forms of order, and rarely coexist. Many interesting new phenomena occur, however, in hybrid superconducting/ferromagnetic systems. For example, a Josephson junction containing a ferromagnetic material can exhibit an intrinsic phase shift of π in its ground state for certain thicknesses of the material. Such ‘π-junctions’ were first realized experimentally in 2001, and have been proposed as circuit elements for both high-speed classical superconducting computing and for quantum computing. Here we demonstrate experimentally that the phase state of a Josephson junction containing two ferromagnetic layers can be toggled between 0 and pi by changing the relativemore » orientation of the two magnetizations. These controllable 0–π junctions have immediate applications in cryogenic memory, where they serve as a necessary component to an ultralow power superconducting computer. Such a fully superconducting computer is estimated to be orders of magnitude more energy-efficient than current semiconductor-based supercomputers. Here, phase-controllable junctions also open up new possibilities for superconducting circuit elements such as superconducting ‘programmable logic’, where they could function in superconducting analogues to field-programmable gate arrays.« less

Humidity-controlled rectification switching in ruthenium-complex molecular junctions

NASA Astrophysics Data System (ADS)

Atesci, Huseyin; Kaliginedi, Veerabhadrarao; Celis Gil, Jose A.; Ozawa, Hiroaki; Thijssen, Joseph M.; Broekmann, Peter; Haga, Masa-aki; van der Molen, Sense Jan

2018-02-01

Although molecular rectifiers were proposed over four decades ago1,2, until recently reported rectification ratios (RR) were rather moderate2-11 (RR 101). This ceiling was convincingly broken using a eutectic GaIn top contact12 to probe molecular monolayers of coupled ferrocene groups (RR 105), as well as using scanning tunnelling microscopy-break junctions13-16 and mechanically controlled break junctions17 to probe single molecules (RR 102-103). Here, we demonstrate a device based on a molecular monolayer in which the RR can be switched by more than three orders of magnitude (between RR 100 and RR ≥ 103) in response to humidity. As the relative humidity is toggled between 5% and 60%, the current-voltage (I-V) characteristics of a monolayer of di-nuclear Ru-complex molecules reversibly change from symmetric to strongly asymmetric (diode-like). Key to this behaviour is the presence of two localized molecular orbitals in series, which are nearly degenerate in dry circumstances but become misaligned under high humidity conditions, due to the displacement of counter ions (PF6-). This asymmetric gating of the two relevant localized molecular orbital levels results in humidity-controlled diode-like behaviour.

Software for Better Documentation of Other Software

NASA Technical Reports Server (NTRS)

Pinedo, John

2003-01-01

The Literate Programming Extraction Engine is a Practical Extraction and Reporting Language- (PERL-)based computer program that facilitates and simplifies the implementation of a concept of self-documented literate programming in a fashion tailored to the typical needs of scientists. The advantage for the programmer is that documentation and source code are written side-by-side in the same file, reducing the likelihood that the documentation will be inconsistent with the code and improving the verification that the code performs its intended functions. The advantage for the user is the knowledge that the documentation matches the software because they come from the same file. This program unifies the documentation process for a variety of programming languages, including C, C++, and several versions of FORTRAN. This program can process the documentation in any markup language, and incorporates the LaTeX typesetting software. The program includes sample Makefile scripts for automating both the code-compilation (when appropriate) and documentation-generation processes into a single command-line statement. Also included are macro instructions for the Emacs display-editor software, making it easy for a programmer to toggle between editing in a code or a documentation mode.

Electric-field-driven switching of individual magnetic skyrmions

NASA Astrophysics Data System (ADS)

Hsu, Pin-Jui; Kubetzka, André; Finco, Aurore; Romming, Niklas; von Bergmann, Kirsten; Wiesendanger, Roland

2017-02-01

Controlling magnetism with electric fields is a key challenge to develop future energy-efficient devices. The present magnetic information technology is mainly based on writing processes requiring either local magnetic fields or spin torques, but it has also been demonstrated that magnetic properties can be altered on the application of electric fields. This has been ascribed to changes in magnetocrystalline anisotropy caused by spin-dependent screening and modifications of the band structure, changes in atom positions or differences in hybridization with an adjacent oxide layer. However, the switching between states related by time reversal, for example magnetization up and down as used in the present technology, is not straightforward because the electric field does not break time-reversal symmetry. Several workarounds have been applied to toggle between bistable magnetic states with electric fields, including changes of material composition as a result of electric fields. Here we demonstrate that local electric fields can be used to switch reversibly between a magnetic skyrmion and the ferromagnetic state. These two states are topologically inequivalent, and we find that the direction of the electric field directly determines the final state. This observation establishes the possibility to combine electric-field writing with the recently envisaged skyrmion racetrack-type memories.

A load balancing bufferless deflection router for network-on-chip

NASA Astrophysics Data System (ADS)

Xiaofeng, Zhou; Zhangming, Zhu; Duan, Zhou

2016-07-01

The bufferless router emerges as an interesting option for cost-efficient in network-on-chip (NoC) design. However, the bufferless router only works well under low network load because deflection more easily occurs as the injection rate increases. In this paper, we propose a load balancing bufferless deflection router (LBBDR) for NoC that relieves the effect of deflection in bufferless NoC. The proposed LBBDR employs a balance toggle identifier in the source router to control the initial routing direction of X or Y for a flit in the network. Based on this mechanism, the flit is routed according to XY or YX routing in the network afterward. When two or more flits contend the same one desired output port a priority policy called nearer-first is used to address output ports allocation contention. Simulation results show that the proposed LBBDR yields an improvement of routing performance over the reported bufferless routing in the flit deflection rate, average packet latency and throughput by up to 13%, 10% and 6% respectively. The layout area and power consumption compared with the reported schemes are 12% and 7% less respectively. Project supported by the National Natural Science Foundation of China (Nos. 61474087, 61322405, 61376039).

Efficient Analysis of Systems Biology Markup Language Models of Cellular Populations Using Arrays.

PubMed

Watanabe, Leandro; Myers, Chris J

2016-08-19

The Systems Biology Markup Language (SBML) has been widely used for modeling biological systems. Although SBML has been successful in representing a wide variety of biochemical models, the core standard lacks the structure for representing large complex regular systems in a standard way, such as whole-cell and cellular population models. These models require a large number of variables to represent certain aspects of these types of models, such as the chromosome in the whole-cell model and the many identical cell models in a cellular population. While SBML core is not designed to handle these types of models efficiently, the proposed SBML arrays package can represent such regular structures more easily. However, in order to take full advantage of the package, analysis needs to be aware of the arrays structure. When expanding the array constructs within a model, some of the advantages of using arrays are lost. This paper describes a more efficient way to simulate arrayed models. To illustrate the proposed method, this paper uses a population of repressilator and genetic toggle switch circuits as examples. Results show that there are memory benefits using this approach with a modest cost in runtime.

Cancer stem cells: a systems biology view of their role in prognosis and therapy.

PubMed

Mertins, Susan D

2014-04-01

Evidence has accumulated that characterizes highly tumorigenic cancer cells residing in heterogeneous populations. The accepted term for such a subpopulation is cancer stem cells (CSCs). While many questions still remain about their precise role in the origin, progression, and drug resistance of tumors, it is clear they exist. In this review, a current understanding of the nature of CSC, their potential usefulness in prognosis, and the need to target them will be discussed. In particular, separate studies now suggest that the CSC is plastic in its phenotype, toggling between tumorigenic and nontumorigenic states depending on both intrinsic and extrinsic conditions. Because of this, a static view of gene and protein levels defined by correlations may not be sufficient to either predict disease progression or aid in the discovery and development of drugs to molecular targets leading to cures. Quantitative dynamic modeling, a bottom up systems biology approach whereby signal transduction pathways are described by differential equations, may offer a novel means to overcome the challenges of oncology today. In conclusion, the complexity of CSCs can be captured in mathematical models that may be useful for selecting molecular targets, defining drug action, and predicting sensitivity or resistance pathways for improved patient outcomes.

Real-time stereographic display of volumetric datasets in radiology

NASA Astrophysics Data System (ADS)

Wang, Xiao Hui; Maitz, Glenn S.; Leader, J. K.; Good, Walter F.

2006-02-01

A workstation for testing the efficacy of stereographic displays for applications in radiology has been developed, and is currently being tested on lung CT exams acquired for lung cancer screening. The system exploits pre-staged rendering to achieve real-time dynamic display of slabs, where slab thickness, axial position, rendering method, brightness and contrast are interactively controlled by viewers. Stereo presentation is achieved by use of either frame-swapping images or cross-polarizing images. The system enables viewers to toggle between alternative renderings such as one using distance-weighted ray casting by maximum-intensity-projection, which is optimal for detection of small features in many cases, and ray casting by distance-weighted averaging, for characterizing features once detected. A reporting mechanism is provided which allows viewers to use a stereo cursor to measure and mark the 3D locations of specific features of interest, after which a pop-up dialog box appears for entering findings. The system's impact on performance is being tested on chest CT exams for lung cancer screening. Radiologists' subjective assessments have been solicited for other kinds of 3D exams (e.g., breast MRI) and their responses have been positive. Objective estimates of changes in performance and efficiency, however, must await the conclusion of our study.

Pain empathy in schizophrenia: an fMRI study

PubMed Central

Jimenez, Amy M.; Lee, Junghee; Wynn, Jonathan K.; Eisenberger, Naomi I.; Green, Michael F.

2016-01-01

Abstract Although it has been proposed that schizophrenia is characterized by impaired empathy, several recent studies found intact neural responses on tasks measuring the affective subdomain of empathy. This study further examined affective empathy in 21 schizophrenia outpatients and 21 healthy controls using a validated pain empathy paradigm with two components: (i) observing videos of people described as medical patients who were receiving a painful sound stimulation treatment; (ii) listening to the painful sounds (to create regions of interest). The observing videos component incorporated experimental manipulations of perspective taking (instructions to imagine ‘Self’ vs ‘Other’ experiencing pain) and cognitive appraisal (information about whether treatment was ‘Effective’ vs ‘Not Effective’). When considering activation across experimental conditions, both groups showed similar dorsal anterior cingulate cortex (dACC) and anterior insula (AI) activation while merely observing others in pain. However, there were group differences associated with perspective taking: controls showed relatively greater dACC and AI activation for the Self vs Other contrast whereas patients showed relatively greater activation in these and additional regions for the Other vs Self contrast. Although patients demonstrated grossly intact neural activity while observing others in pain, they showed more subtle abnormalities when required to toggle between imagining themselves vs others experiencing pain. PMID:26746181

Pain empathy in schizophrenia: an fMRI study.

PubMed

Horan, William P; Jimenez, Amy M; Lee, Junghee; Wynn, Jonathan K; Eisenberger, Naomi I; Green, Michael F

2016-05-01

Although it has been proposed that schizophrenia is characterized by impaired empathy, several recent studies found intact neural responses on tasks measuring the affective subdomain of empathy. This study further examined affective empathy in 21 schizophrenia outpatients and 21 healthy controls using a validated pain empathy paradigm with two components: (i) observing videos of people described as medical patients who were receiving a painful sound stimulation treatment; (ii) listening to the painful sounds (to create regions of interest). The observing videos component incorporated experimental manipulations of perspective taking (instructions to imagine 'Self' vs 'Other' experiencing pain) and cognitive appraisal (information about whether treatment was 'Effective' vs 'Not Effective'). When considering activation across experimental conditions, both groups showed similar dorsal anterior cingulate cortex (dACC) and anterior insula (AI) activation while merely observing others in pain. However, there were group differences associated with perspective taking: controls showed relatively greater dACC and AI activation for the Self vs Other contrast whereas patients showed relatively greater activation in these and additional regions for the Other vs Self contrast. Although patients demonstrated grossly intact neural activity while observing others in pain, they showed more subtle abnormalities when required to toggle between imagining themselves vs others experiencing pain. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

User Guide for the Anvil Threat Cooridor Forecast Tool V2.4 for AWIPS

NASA Technical Reports Server (NTRS)

Barett, Joe H., III; Bauman, William H., III

2008-01-01

The Anvil Tool GUI allows users to select a Data Type, toggle the map refresh on/off, place labels, and choose the Profiler Type (source of the KSC 50 MHz profiler data), the Date- Time of the data, the Center of Plot, and the Station (location of the RAOB or 50 MHz profiler). If the Data Type is Models, the user selects a Fcst Hour (forecast hour) instead of Station. There are menus for User Profiles, Circle Label Options, and Frame Label Options. Labels can be placed near the center circle of the plot and/or at a specified distance and direction from the center of the circle (Center of Plot). The default selection for the map refresh is "ON". When the user creates a new Anvil Tool map with Refresh Map "ON, the plot is automatically displayed in the AWIPS frame. If another Anvil Tool map is already displayed and the user does not change the existing map number shown at the bottom of the GUI, the new Anvil Tool map will overwrite the old one. If the user turns the Refresh Map "OFF", the new Anvil Tool map is created but not automatically displayed. The user can still display the Anvil Tool map through the Maps dropdown menu* as shown in Figure 4.

Dynamical sensitivity control of a single-spin quantum sensor.

PubMed

Lazariev, Andrii; Arroyo-Camejo, Silvia; Rahane, Ganesh; Kavatamane, Vinaya Kumar; Balasubramanian, Gopalakrishnan

2017-07-26

The Nitrogen-Vacancy (NV) defect in diamond is a unique quantum system that offers precision sensing of nanoscale physical quantities at room temperature beyond the current state-of-the-art. The benchmark parameters for nanoscale magnetometry applications are sensitivity, spectral resolution, and dynamic range. Under realistic conditions the NV sensors controlled by conventional sensing schemes suffer from limitations of these parameters. Here we experimentally show a new method called dynamical sensitivity control (DYSCO) that boost the benchmark parameters and thus extends the practical applicability of the NV spin for nanoscale sensing. In contrast to conventional dynamical decoupling schemes, where π pulse trains toggle the spin precession abruptly, the DYSCO method allows for a smooth, analog modulation of the quantum probe's sensitivity. Our method decouples frequency selectivity and spectral resolution unconstrained over the bandwidth (1.85 MHz-392 Hz in our experiments). Using DYSCO we demonstrate high-accuracy NV magnetometry without |2π| ambiguities, an enhancement of the dynamic range by a factor of 4 · 10 3 , and interrogation times exceeding 2 ms in off-the-shelf diamond. In a broader perspective the DYSCO method provides a handle on the inherent dynamics of quantum systems offering decisive advantages for NV centre based applications notably in quantum information and single molecule NMR/MRI.

LA-iMageS: a software for elemental distribution bioimaging using LA-ICP-MS data.

PubMed

López-Fernández, Hugo; de S Pessôa, Gustavo; Arruda, Marco A Z; Capelo-Martínez, José L; Fdez-Riverola, Florentino; Glez-Peña, Daniel; Reboiro-Jato, Miguel

2016-01-01

The spatial distribution of chemical elements in different types of samples is an important field in several research areas such as biology, paleontology or biomedicine, among others. Elemental distribution imaging by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is an effective technique for qualitative and quantitative imaging due to its high spatial resolution and sensitivity. By applying this technique, vast amounts of raw data are generated to obtain high-quality images, essentially making the use of specific LA-ICP-MS imaging software that can process such data absolutely mandatory. Since existing solutions are usually commercial or hard-to-use for average users, this work introduces LA-iMageS, an open-source, free-to-use multiplatform application for fast and automatic generation of high-quality elemental distribution bioimages from LA-ICP-MS data in the PerkinElmer Elan XL format, whose results can be directly exported to external applications for further analysis. A key strength of LA-iMageS is its substantial added value for users, with particular regard to the customization of the elemental distribution bioimages, which allows, among other features, the ability to change color maps, increase image resolution or toggle between 2D and 3D visualizations.

Leadership training for postdoctoral dental students.

PubMed

Skoulas, Angelique; Kalenderian, Elsbeth

2012-09-01

Harvard School of Dental Medicine launched a course on leadership for its postdoctoral dental students in 2010 in order to introduce them to the art of leadership and the latest theories and principles regarding becoming a leader. Nine four-hour modules over a period of six months took the students on a journey of leadership self-exploration by building awareness of their capacity in core leadership skills; providing them with tools and frameworks for developing effective leadership skills; encouraging the immediate practice of core skills; creating space for honest reflection; and providing inspiration with guest lectures. A constant toggle between the present and their future as leaders was built into the course. In the student evaluations, the course received an overall rating of 4.71 (5=excellent), and the students reported an enhanced interest in all topic areas. They reported that the ability to build trust with others was the most beneficial skill for a dentist, while viewing advocacy skills as the least beneficial. All the students indicated an intention to continue developing their leadership skills. Through the course, the students developed an understanding of their leadership strengths and limitations through case studies, role-play, and self-reflection, as well as gaining an understanding of team dynamics and cultural perceptions in the context of dentistry.

Correction of respiratory motion for IMRT using aperture adaptive technique and visual guidance: A feasibility study

NASA Astrophysics Data System (ADS)

Chen, Ho-Hsing; Wu, Jay; Chuang, Keh-Shih; Kuo, Hsiang-Chi

2007-07-01

Intensity-modulated radiation therapy (IMRT) utilizes nonuniform beam profile to deliver precise radiation doses to a tumor while minimizing radiation exposure to surrounding normal tissues. However, the problem of intrafraction organ motion distorts the dose distribution and leads to significant dosimetric errors. In this research, we applied an aperture adaptive technique with a visual guiding system to toggle the problem of respiratory motion. A homemade computer program showing a cyclic moving pattern was projected onto the ceiling to visually help patients adjust their respiratory patterns. Once the respiratory motion becomes regular, the leaf sequence can be synchronized with the target motion. An oscillator was employed to simulate the patient's breathing pattern. Two simple fields and one IMRT field were measured to verify the accuracy. Preliminary results showed that after appropriate training, the amplitude and duration of volunteer's breathing can be well controlled by the visual guiding system. The sharp dose gradient at the edge of the radiation fields was successfully restored. The maximum dosimetric error in the IMRT field was significantly decreased from 63% to 3%. We conclude that the aperture adaptive technique with the visual guiding system can be an inexpensive and feasible alternative without compromising delivery efficiency in clinical practice.

The SI-Gap: How British Units Are Impeding Advances in STEM

NASA Astrophysics Data System (ADS)

Jones, M. P.; Cook, Courtney J.

2017-11-01

The United States is one of only three countries in the world that remain uncommitted to the metric system. Perhaps to policymakers the decision to hang on to miles, pounds, and gallons is one of tradition. However, as a physics teacher I have seen firsthand how growing up with U.S. Customary Units (commonly called by the pseudonym "British Units") has negatively impacted my students. Sure, they can convert between "British" and SI units; and they can effectively toggle between SI prefixes. However, they typically lack intuition regarding the values they express in SI. This is a major problem, but is by no means a criticism against them. Their disadvantage is the result of a unique learning gap that exists in the United States. I call it the SI(sī)-gap. The SI-gap not only impedes our ability as teachers to inspire students when it comes to science, technology, engineering, and mathematics (STEM); it also prevents our students from properly assessing the validity of their own results. As we shall soon see, the SI-gap carries consequences beyond the classroom. If we are to solve the problems that relate to the SI-gap, we need to reform the way we introduce SI units to the current generation of students.

GPU-Based Simulation of Ultrasound Imaging Artifacts for Cryosurgery Training.

PubMed

Keelan, Robert; Shimada, Kenji; Rabin, Yoed

2017-02-01

This study presents an efficient computational technique for the simulation of ultrasound imaging artifacts associated with cryosurgery based on nonlinear ray tracing. This study is part of an ongoing effort to develop computerized training tools for cryosurgery, with prostate cryosurgery as a development model. The capability of performing virtual cryosurgical procedures on a variety of test cases is essential for effective surgical training. Simulated ultrasound imaging artifacts include reverberation and reflection of the cryoprobes in the unfrozen tissue, reflections caused by the freezing front, shadowing caused by the frozen region, and tissue property changes in repeated freeze-thaw cycles procedures. The simulated artifacts appear to preserve the key features observed in a clinical setting. This study displays an example of how training may benefit from toggling between the undisturbed ultrasound image, the simulated temperature field, the simulated imaging artifacts, and an augmented hybrid presentation of the temperature field superimposed on the ultrasound image. The proposed method is demonstrated on a graphic processing unit at 100 frames per second, on a mid-range personal workstation, at two orders of magnitude faster than a typical cryoprocedure. This performance is based on computation with C++ accelerated massive parallelism and its interoperability with the DirectX-rendering application programming interface.

Crystal structures and atomic model of NADPH oxidase.

PubMed

Magnani, Francesca; Nenci, Simone; Millana Fananas, Elisa; Ceccon, Marta; Romero, Elvira; Fraaije, Marco W; Mattevi, Andrea

2017-06-27

NADPH oxidases (NOXs) are the only enzymes exclusively dedicated to reactive oxygen species (ROS) generation. Dysregulation of these polytopic membrane proteins impacts the redox signaling cascades that control cell proliferation and death. We describe the atomic crystal structures of the catalytic flavin adenine dinucleotide (FAD)- and heme-binding domains of Cylindrospermum stagnale NOX5. The two domains form the core subunit that is common to all seven members of the NOX family. The domain structures were then docked in silico to provide a generic model for the NOX family. A linear arrangement of cofactors (NADPH, FAD, and two membrane-embedded heme moieties) injects electrons from the intracellular side across the membrane to a specific oxygen-binding cavity on the extracytoplasmic side. The overall spatial organization of critical interactions is revealed between the intracellular loops on the transmembrane domain and the NADPH-oxidizing dehydrogenase domain. In particular, the C terminus functions as a toggle switch, which affects access of the NADPH substrate to the enzyme. The essence of this mechanistic model is that the regulatory cues conformationally gate NADPH-binding, implicitly providing a handle for activating/deactivating the very first step in the redox chain. Such insight provides a framework to the discovery of much needed drugs that selectively target the distinct members of the NOX family and interfere with ROS signaling.

On the origin of resistive switching volatility in Ni/TiO{sub 2}/Ni stacks

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

Cortese, Simone, E-mail: simone.cortese@soton.ac.uk; Trapatseli, Maria; Khiat, Ali

2016-08-14

Resistive switching and resistive random access memories have attracted huge interest for next generation nonvolatile memory applications, also thought to be able to overcome flash memories limitations when arranged in crossbar arrays. A cornerstone of their potential success is that the toggling between two distinct resistance states, usually a High Resistive State (HRS) and a Low Resistive State (LRS), is an intrinsic non-volatile phenomenon with the two states being thermodynamically stable. TiO{sub 2} is one of the most common materials known to support non-volatile RS. In this paper, we report a volatile resistive switching in a titanium dioxide thin filmmore » sandwiched by two nickel electrodes. The aim of this work is to understand the underlying physical mechanism that triggers the volatile effect, which is ascribed to the presence of a NiO layer at the bottom interface. The NiO layer alters the equilibrium between electric field driven filament formation and thermal enhanced ion diffusion, resulting in the volatile behaviour. Although the volatility is not ideal for non-volatile memory applications, it shows merit for access devices in crossbar arrays due to its high LRS/HRS ratio, which are also briefly discussed.« less

Regulated assembly and disassembly of the yeast telomerase quaternary complex

PubMed Central

Tucey, Timothy M.

2014-01-01

The enzyme telomerase, which elongates chromosome termini, is a critical factor in determining long-term cellular proliferation and tissue renewal. Hence, even small differences in telomerase levels can have substantial consequences for human health. In budding yeast, telomerase consists of the catalytic Est2 protein and two regulatory subunits (Est1 and Est3) in association with the TLC1 RNA, with each of the four subunits essential for in vivo telomerase function. We show here that a hierarchy of assembly and disassembly results in limiting amounts of the quaternary complex late in the cell cycle, following completion of DNA replication. The assembly pathway, which is driven by interaction of the Est3 telomerase subunit with a previously formed Est1–TLC1–Est2 preassembly complex, is highly regulated, involving Est3-binding sites on both Est2 and Est1 as well as an interface on Est3 itself that functions as a toggle switch. Telomerase subsequently disassembles by a mechanistically distinct pathway due to dissociation of the catalytic subunit from the complex in every cell cycle. The balance between the assembly and disassembly pathways, which dictate the levels of the active holoenzyme in the cell, reveals a novel mechanism by which telomerase (and hence telomere homeostasis) is regulated. PMID:25240060

From the Island of the Blue Dolphins: A unique 19th century cache feature from San Nicolas Island, California

USGS Publications Warehouse

Erlandson, Jon M.; Thomas-Barnett, Lisa; Vellanoweth, René L.; Schwartz, Steven J.; Muhs, Daniel R.

2013-01-01

A cache feature salvaged from an eroding sea cliff on San Nicolas Island produced two redwood boxes containing more than 200 artifacts of Nicoleño, Native Alaskan, and Euro-American origin. Outside the boxes were four asphaltum-coated baskets, abalone shells, a sandstone dish, and a hafted stone knife. The boxes, made from split redwood planks, contained a variety of artifacts and numerous unmodified bones and teeth from marine mammals, fish, birds, and large land mammals. Nicoleño-style artifacts include 11 knives with redwood handles and stone blades, stone projectile points, steatite ornaments and effigies, a carved stone pipe, abraders and burnishing stones, bird bone whistles, bone and shell pendants, abalone shell dishes, and two unusual barbed shell fishhooks. Artifacts of Native Alaskan style include four bone toggling harpoons, two unilaterally barbed bone harpoon heads, bone harpoon fore-shafts, a ground slate blade, and an adze blade. Objects of Euro-American origin or materials include a brass button, metal harpoon blades, and ten flaked glass bifaces. The contents of the cache feature, dating to the early-to-mid nineteenth century, provide an extraordinary window on a time of European expansion and global economic development that created unique cultural interactions and social transformations.

GPU-Based Simulation of Ultrasound Imaging Artifacts for Cryosurgery Training

PubMed Central

Keelan, Robert; Shimada, Kenji

2016-01-01

This study presents an efficient computational technique for the simulation of ultrasound imaging artifacts associated with cryosurgery based on nonlinear ray tracing. This study is part of an ongoing effort to develop computerized training tools for cryosurgery, with prostate cryosurgery as a development model. The capability of performing virtual cryosurgical procedures on a variety of test cases is essential for effective surgical training. Simulated ultrasound imaging artifacts include reverberation and reflection of the cryoprobes in the unfrozen tissue, reflections caused by the freezing front, shadowing caused by the frozen region, and tissue property changes in repeated freeze–thaw cycles procedures. The simulated artifacts appear to preserve the key features observed in a clinical setting. This study displays an example of how training may benefit from toggling between the undisturbed ultrasound image, the simulated temperature field, the simulated imaging artifacts, and an augmented hybrid presentation of the temperature field superimposed on the ultrasound image. The proposed method is demonstrated on a graphic processing unit at 100 frames per second, on a mid-range personal workstation, at two orders of magnitude faster than a typical cryoprocedure. This performance is based on computation with C++ accelerated massive parallelism and its interoperability with the DirectX-rendering application programming interface. PMID:26818026

Peripheral infrastructure vectors and an extended set of plant parts for the Modular Cloning system

PubMed Central

Kretschmer, Carola; Gruetzner, Ramona; Löfke, Christian; Dagdas, Yasin; Bürstenbinder, Katharina; Marillonnet, Sylvestre

2018-01-01

Standardized DNA assembly strategies facilitate the generation of multigene constructs from collections of building blocks in plant synthetic biology. A common syntax for hierarchical DNA assembly following the Golden Gate principle employing Type IIs restriction endonucleases was recently developed, and underlies the Modular Cloning and GoldenBraid systems. In these systems, transcriptional units and/or multigene constructs are assembled from libraries of standardized building blocks, also referred to as phytobricks, in several hierarchical levels and by iterative Golden Gate reactions. Here, a toolkit containing further modules for the novel DNA assembly standards was developed. Intended for use with Modular Cloning, most modules are also compatible with GoldenBraid. Firstly, a collection of approximately 80 additional phytobricks is provided, comprising e.g. modules for inducible expression systems, promoters or epitope tags. Furthermore, DNA modules were developed for connecting Modular Cloning and Gateway cloning, either for toggling between systems or for standardized Gateway destination vector assembly. Finally, first instances of a “peripheral infrastructure” around Modular Cloning are presented: While available toolkits are designed for the assembly of plant transformation constructs, vectors were created to also use coding sequence-containing phytobricks directly in yeast two hybrid interaction or bacterial infection assays. The presented material will further enhance versatility of hierarchical DNA assembly strategies. PMID:29847550

Automatic design of synthetic gene circuits through mixed integer non-linear programming.

PubMed

Huynh, Linh; Kececioglu, John; Köppe, Matthias; Tagkopoulos, Ilias

2012-01-01

Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits.

Method for improving the angular resolution of a neutron scatter camera

DOEpatents

Mascarenhas, Nicholas; Marleau, Peter; Gerling, Mark; Cooper, Robert Lee; Mrowka, Stanley; Brennan, James S.

2012-12-25

An instrument that will directly image the fast fission neutrons from a special nuclear material source wherein the neutron detection efficiency is increased has been described. Instead of the previous technique that uses a time-of-flight (TOF) between 2 widely spaced fixed planes of neutron detectors to measure scatter neutron kinetic energy, we now use the recoil proton energy deposited in the second of the 2 scatter planes which can now be repositioned either much closer together or further apart. However, by doubling the separation distance between the 2 planes from 20 cm to a distance of 40 cm we improved the angular resolution of the detector from about 12.degree. to about 10.degree.. A further doubling of the separation distance to 80 cm provided an addition improvement in angular resolution of the detector to about 6.degree. without adding additional detectors or ancillary electronics. The distance between planes also may be dynamically changed using a suitable common technique such as a gear- or motor-drive to toggle between the various positions. The angular resolution of this new configuration, therefore, is increased at the expanse of detection sensitivity. However, the diminished sensitivity may be acceptable for those applications where the detector is able to interrogate a particular site for an extended period.

Alternative Effector-Function Profiling Identifies Broad HIV-Specific T-Cell Responses in Highly HIV-Exposed Individuals Who Remain Uninfected

PubMed Central

Ruiz-Riol, Marta; Llano, Anuska; Ibarrondo, Javier; Zamarreño, Jennifer; Yusim, Karina; Bach, Vanessa; Mothe, Beatriz; Perez-Alvarez, Susana; Fernandez, Marco A.; Requena, Gerard; Meulbroek, Michael; Pujol, Ferran; Leon, Agathe; Cobarsi, Patricia; Korber, Bette T.; Clotet, Bonaventura; Ganoza, Carmela; Sanchez, Jorge; Coll, Josep; Brander, Christian

2015-01-01

The characterization of host immune responses to human immunodeficiency virus (HIV) in HIV controllers and individuals with high exposure but seronegativity to HIV (HESN) is needed to guide the development of effective preventive and therapeutic vaccine candidates. However, several technical hurdles severely limit the definition of an effective virus-specific T-cell response. By using a toggle-peptide approach, which takes HIV sequence diversity into account, and a novel, boosted cytokine staining/flow cytometry strategy, we here describe new patterns of T-cell responses to HIV that would be missed by standard assays. Importantly, this approach also allows detection of broad and strong virus-specific T-cell responses in HESN individuals that are characterized by a T-helper type 1 cytokine–like effector profile and produce cytokines that have been associated with potential control of HIV infection, including interleukin 10, interleukin 13, and interleukin 22. These results establish a novel approach to improve the current understanding of HIV-specific T-cell immunity and identify cellular immune responses and individual cytokines as potential markers of relative HIV resistance. As such, the findings also help develop similar strategies for more-comprehensive assessments of host immune responses to other human infections and immune-mediated disorders. PMID:25249264

Stretching and Controlled Motion of Single-Stranded DNA in Locally-Heated Solid-State Nanopores

PubMed Central

Belkin, Maxim; Maffeo, Christopher; Wells, David B.

2013-01-01

Practical applications of solid-state nanopores for DNA detection and sequencing require the electrophoretic motion of DNA through the nanopores to be precisely controlled. Controlling the motion of single-stranded DNA presents a particular challenge, in part because of the multitude of conformations that a DNA strand can adopt in a nanopore. Through continuum, coarse-grained and atomistic modeling, we demonstrate that local heating of the nanopore volume can be used to alter the electrophoretic mobility and conformation of single-stranded DNA. In the nanopore systems considered, the temperature near the nanopore is modulated via a nanometer-size heater element that can be radiatively switched on and off. The local enhancement of temperature produces considerable stretching of the DNA fragment confined within the nanopore. Such stretching is reversible, so that the conformation of DNA can be toggled between compact (local heating is off) and extended (local heating is on) states. The effective thermophoretic force acting on single-stranded DNA in the vicinity of the nanopore is found to be sufficiently large (4–8 pN) to affect such changes in the DNA conformation. The local heating of the nanopore volume is observed to promote single-file translocation of DNA strands at transmembrane biases as low as 10 mV, which opens new avenues for using solid-state nanopores for detection and sequencing of DNA. PMID:23876013

Performance Evaluation of a Mobile Touchscreen Interface for Assistive Robotic Manipulators: A Pilot Study.

PubMed

Chung, Cheng-Shiu; Ka, Hyun W; Wang, Hongu; Ding, Dan; Kelleher, Annmarie; Cooper, Rory A

2017-01-01

Background: Assistive robotic manipulators (ARMs) have been developed to provide enhanced assistance and independence in performance of daily activities among people with spinal cord injury when a caregiver is not on site. However, the current commercial ARM user interfaces (UIs) may be difficult to learn and control. A touchscreen mobile UI was developed to overcome these challenges. Objective: The object of this study was to evaluate the performance between 2 ARM UIs, touchscreen and the original joystick, using an ARM evaluation tool (ARMET). Methods: This is a pilot study of people with upper extremity impairments ( N = 8). Participants were trained on 2 UIs, and then they chose one to use when performing 3 tasks on the ARMET: flipping a toggle switch, pushing down a door handle, and turning a knob. Task completion time, mean velocity, and open interviews were the main outcome measurements. Results: Among 8 novice participants, 7 chose the touchscreen UI and 1 chose the joystick UI. All participants could complete the ARMET tasks independently. Use of the touchscreen UI resulted in enhanced ARMET performance (higher mean moving speed and faster task completion). Conclusions: Mobile ARM UIs demonstrated easier learning experience, less physical effort, and better ARMET performance. The improved performance, the accessibility, and lower physical effort suggested that the touchscreen UI might be an efficient tool for the ARM users.

Synthesis, Pharmacological Evaluation, and Docking Studies of Novel Pyridazinone-Based Cannabinoid Receptor Type 2 Ligands.

PubMed

Ragusa, Giulio; Bencivenni, Serena; Morales, Paula; Callaway, Tyra; Hurst, Dow P; Asproni, Battistina; Merighi, Stefania; Loriga, Giovanni; Pinna, Gerard A; Reggio, Patricia H; Gessi, Stefania; Murineddu, Gabriele

2018-03-25

In recent years, cannabinoid type 2 receptors (CB 2 R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB 2 R are devoid of the psychoactive effects typically observed for CB 1 R ligands. Based on our recent studies on a class of pyridazinone 4-carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure-activity relationships for this promising scaffold with the aim to develop potent CB 2 R ligands. In binding assays, two of the new synthesized compounds [6-(3,4-dichlorophenyl)-2-(4-fluorobenzyl)-cis-N-(4-methylcyclohexyl)-3-oxo-2,3-dihydropyridazine-4-carboxamide (2) and 6-(4-chloro-3-methylphenyl)-cis-N-(4-methylcyclohexyl)-3-oxo-2-pentyl-2,3-dihydropyridazine-4-carboxamide (22)] showed high CB 2 R affinity, with K i values of 2.1 and 1.6 nm, respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB 2 R inverse agonists. Compound 22 displayed the highest CB 2 R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle-switch residue, W6.48. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The brain on silent: mind wandering, mindful awareness, and states of mental tranquility

PubMed Central

Vago, David R.; Zeidan, Fadel

2018-01-01

Mind wandering and mindfulness are often described as divergent mental states with opposing effects on cognitive performance and mental health. Spontaneous mind wandering is typically associated with self-reflective states that contribute to negative processing of the past, worrying/fantasizing about the future, and disruption of primary task performance. On the other hand, mindful awareness is frequently described as a focus on present sensory input without cognitive elaboration or emotional reactivity, and is associated with improved task performance and decreased stress-related symptomology. Unfortunately, such distinctions fail to acknowledge similarities and interactions between the two states. Instead of an inverse relationship between mindfulness and mind wandering, a more nuanced characterization of mindfulness may involve skillful toggling back and forth between conceptual and nonconceptual processes and networks supporting each state, to meet the contextually specified demands of the situation. In this article, we present a theoretical analysis and plausible neurocognitive framework of the restful mind, in which we attempt to clarify potentially adaptive contributions of both mind wandering and mindful awareness through the lens of the extant neurocognitive literature on intrinsic network activity, meditation, and emerging descriptions of stillness and nonduality. A neurophenomenological approach to probing modality-specific forms of concentration and nonconceptual awareness is presented that may improve our understanding of the resting state. Implications for future research are discussed. PMID:27398642

Damage Patterns at the Head-Stem Taper Junction Helps Understand the Mechanisms of Material Loss.

PubMed

Hothi, Harry S; Panagiotopoulos, Andreas C; Whittaker, Robert K; Bills, Paul J; McMillan, Rebecca A; Skinner, John A; Hart, Alister J

2017-01-01

Material loss at the taper junction of metal-on-metal total hip arthroplasties has been implicated in their early failure. The mechanisms of material loss are not fully understood; analysis of the patterns of damage at the taper can help us better understand why material loss occurs at this junction. We mapped the patterns of material loss in a series of 155 metal-on-metal total hip arthroplasties received at our center by scanning the taper surface using a roundness-measuring machine. We examined these material loss maps to develop a 5-tier classification system based on visual differences between different patterns. We correlated these patterns to surgical, implant, and patient factors known to be important for head-stem taper damage. We found that 63 implants had "minimal damage" at the taper (material loss <1 mm 3 ), and the remaining 92 implants could be categorized by 4 distinct patterns of taper material loss. We found that (1) head diameter and (2) time to revision were key significant variables separating the groups. These material loss maps allow us to suggest different mechanisms that dominate the cause of the material loss in each pattern: (1) corrosion, (2) mechanically assisted corrosion, or (3) intraoperative damage or poor size tolerances leading to toggling of trunnion in taper. Copyright © 2016 Elsevier Inc. All rights reserved.

Automatic Design of Synthetic Gene Circuits through Mixed Integer Non-linear Programming

PubMed Central

Huynh, Linh; Kececioglu, John; Köppe, Matthias; Tagkopoulos, Ilias

2012-01-01

Automatic design of synthetic gene circuits poses a significant challenge to synthetic biology, primarily due to the complexity of biological systems, and the lack of rigorous optimization methods that can cope with the combinatorial explosion as the number of biological parts increases. Current optimization methods for synthetic gene design rely on heuristic algorithms that are usually not deterministic, deliver sub-optimal solutions, and provide no guaranties on convergence or error bounds. Here, we introduce an optimization framework for the problem of part selection in synthetic gene circuits that is based on mixed integer non-linear programming (MINLP), which is a deterministic method that finds the globally optimal solution and guarantees convergence in finite time. Given a synthetic gene circuit, a library of characterized parts, and user-defined constraints, our method can find the optimal selection of parts that satisfy the constraints and best approximates the objective function given by the user. We evaluated the proposed method in the design of three synthetic circuits (a toggle switch, a transcriptional cascade, and a band detector), with both experimentally constructed and synthetic promoter libraries. Scalability and robustness analysis shows that the proposed framework scales well with the library size and the solution space. The work described here is a step towards a unifying, realistic framework for the automated design of biological circuits. PMID:22536398

The Histone Acetyltransferase Gcn5 Regulates ncRNA-ICR1 and FLO11 Expression during Pseudohyphal Development in Saccharomyces cerevisiae

PubMed Central

Wang, Long-Chi; Montalvo-Munoz, Fernando; Tsai, Yuan-Chan; Liang, Chung-Yi; Chang, Chun-Chuan; Lo, Wan-Sheng

2015-01-01

Filamentous growth is one of the key features of pathogenic fungi during the early infectious phase. The pseudohyphal development of yeast Saccharomyces cerevisiae shares similar characteristics with hyphae elongation in pathogenic fungi. The expression of FLO11 is essential for adhesive growth and filament formation in yeast and is governed by a multilayered transcriptional network. Here we discovered a role for the histone acetyltransferase general control nonderepressible 5 (Gcn5) in regulating FLO11-mediated pseudohyphal growth. The expression patterns of FLO11 were distinct in haploid and diploid yeast under amino acid starvation induced by 3-amino-1,2,4-triazole (3AT). In diploids, FLO11 expression was substantially induced at a very early stage of pseudohyphal development and decreased quickly, but in haploids, it was gradually induced. Furthermore, the transcription factor Gcn4 was recruited to the Sfl1-Flo8 toggle sites at the FLO11 promoter under 3AT treatment. Moreover, the histone acetylase activity of Gcn5 was required for FLO11 induction. Finally, Gcn5 functioned as a negative regulator of the noncoding RNA ICR1, which is known to suppress FLO11 expression. Gcn5 plays an important role in the regulatory network of FLO11 expression via Gcn4 by downregulating ICR1 expression, which derepresses FLO11 for promoting pseudohyphal development. PMID:25922832

Spin-valve Josephson junctions for cryogenic memory

NASA Astrophysics Data System (ADS)

Niedzielski, Bethany M.; Bertus, T. J.; Glick, Joseph A.; Loloee, R.; Pratt, W. P.; Birge, Norman O.

2018-01-01

Josephson junctions containing two ferromagnetic layers are being considered for use in cryogenic memory. Our group recently demonstrated that the ground-state phase difference across such a junction with carefully chosen layer thicknesses could be controllably toggled between zero and π by switching the relative magnetization directions of the two layers between the antiparallel and parallel configurations. However, several technological issues must be addressed before those junctions can be used in a large-scale memory. Many of these issues can be more easily studied in single junctions, rather than in the superconducting quantum interference device (SQUID) used for phase-sensitive measurements. In this work, we report a comprehensive study of spin-valve junctions containing a Ni layer with a fixed thickness of 2.0 nm and a NiFe layer of thickness varying between 1.1 and 1.8 nm in steps of 0.1 nm. We extract the field shift of the Fraunhofer patterns and the critical currents of the junctions in the parallel and antiparallel magnetic states, as well as the switching fields of both magnetic layers. We also report a partial study of similar junctions containing a slightly thinner Ni layer of 1.6 nm and the same range of NiFe thicknesses. These results represent the first step toward mapping out a "phase diagram" for phase-controllable spin-valve Josephson junctions as a function of the two magnetic layer thicknesses.

Reversible modulation of SIRT1 activity in a mouse strain

PubMed Central

Clark-Knowles, Katherine V.; He, Xiaohong; Jardine, Karen; Coulombe, Josée; Dewar-Darch, Danielle; Caron, Annabelle Z.

2017-01-01

The SIRT1 protein deacetylase is reported to have a remarkably wide spectrum of biological functions affecting such varied processes as aging, cancer, metabolism, neurodegeneration and immunity. However, the SIRT1 literature is also full of contradictions. To help establish the role(s) of SIRT1 in these and other biological processes, we set out to create a mouse in which the SIRT1 activity could be toggled between on and off states by fusing the estrogen receptor ligand-binding domain (ER) to the C terminus of the SIRT1 protein. We found that the catalytic activity of the SIRT1-ER fusion protein increased 4–5 fold in cells treated with its ligand, 4-hydroxy-tamoxifen (4OHT). The 4OHT-induced activation of SIRT1-ER was due in large part to a 2 to 4-fold increase in abundance of the SIRT1-ER protein in cells in culture and in tissues in vivo. This increase is reversible and is a consequence of 4OHT-induced stabilization of the SIRT1-ER protein. Since changes in SIRT1 level or activity of 2–4 fold are frequently reported to be sufficient to affect its biological functions, this mouse should be helpful in establishing the causal relationships between SIRT1 and the diseases and processes it affects. PMID:28273169

The brain on silent: mind wandering, mindful awareness, and states of mental tranquility.

PubMed

Vago, David R; Zeidan, Fadel

2016-06-01

Mind wandering and mindfulness are often described as divergent mental states with opposing effects on cognitive performance and mental health. Spontaneous mind wandering is typically associated with self-reflective states that contribute to negative processing of the past, worrying/fantasizing about the future, and disruption of primary task performance. On the other hand, mindful awareness is frequently described as a focus on present sensory input without cognitive elaboration or emotional reactivity, and is associated with improved task performance and decreased stress-related symptomology. Unfortunately, such distinctions fail to acknowledge similarities and interactions between the two states. Instead of an inverse relationship between mindfulness and mind wandering, a more nuanced characterization of mindfulness may involve skillful toggling back and forth between conceptual and nonconceptual processes and networks supporting each state, to meet the contextually specified demands of the situation. In this article, we present a theoretical analysis and plausible neurocognitive framework of the restful mind, in which we attempt to clarify potentially adaptive contributions of both mind wandering and mindful awareness through the lens of the extant neurocognitive literature on intrinsic network activity, meditation, and emerging descriptions of stillness and nonduality. A neurophenomenological approach to probing modality-specific forms of concentration and nonconceptual awareness is presented that may improve our understanding of the resting state. Implications for future research are discussed. © 2016 New York Academy of Sciences.

Crystallization of bi-functional ligand protein complexes.

PubMed

Antoni, Claudia; Vera, Laura; Devel, Laurent; Catalani, Maria Pia; Czarny, Bertrand; Cassar-Lajeunesse, Evelyn; Nuti, Elisa; Rossello, Armando; Dive, Vincent; Stura, Enrico Adriano

2013-06-01

Homodimerization is important in signal transduction and can play a crucial role in many other biological systems. To obtaining structural information for the design of molecules able to control the signalization pathways, the proteins involved will have to be crystallized in complex with ligands that induce dimerization. Bi-functional drugs have been generated by linking two ligands together chemically and the relative crystallizability of complexes with mono-functional and bi-functional ligands has been evaluated. There are problems associated with crystallization with such ligands, but overall, the advantages appear to be greater than the drawbacks. The study involves two matrix metalloproteinases, MMP-12 and MMP-9. Using flexible and rigid linkers we show that it is possible to control the crystal packing and that by changing the ligand-enzyme stoichiometric ratio, one can toggle between having one bi-functional ligand binding to two enzymes and having the same ligand bound to each enzyme. The nature of linker and its point of attachment on the ligand can be varied to aid crystallization, and such variations can also provide valuable structural information about the interactions made by the linker with the protein. We report here the crystallization and structure determination of seven ligand-dimerized complexes. These results suggest that the use of bi-functional drugs can be extended beyond the realm of protein dimerization to include all drug design projects. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Strait, R.S.; Pearson, P.K.; Sengupta, S.K.

A password system comprises a set of codewords spaced apart from one another by a Hamming distance (HD) that exceeds twice the variability that can be projected for a series of biometric measurements for a particular individual and that is less than the HD that can be encountered between two individuals. To enroll an individual, a biometric measurement is taken and exclusive-ORed with a random codeword to produce a reference value. To verify the individual later, a biometric measurement is taken and exclusive-ORed with the reference value to reproduce the original random codeword or its approximation. If the reproduced valuemore » is not a codeword, the nearest codeword to it is found, and the bits that were corrected to produce the codeword to it is found, and the bits that were corrected to produce the codeword are also toggled in the biometric measurement taken and the codeword generated during enrollment. The correction scheme can be implemented by any conventional error correction code such as Reed-Muller code R(m,n). In the implementation using a hand geometry device an R(2,5) code has been used in this invention. Such codeword and biometric measurement can then be used to see if the individual is an authorized user. Conventional Diffie-Hellman public key encryption schemes and hashing procedures can then be used to secure the communications lines carrying the biometric information and to secure the database of authorized users.« less

Ultralightweight Space Deployable Primary Reflector Demonstrator

NASA Technical Reports Server (NTRS)

Montgomery, Edward E., IV; Zeiders, Glenn W.; Smith, W. Scott (Technical Monitor)

2002-01-01

A concept has been developed and analyzed and several generational prototypes built for a gossamer-class deployable truss for a mirror or reflector with many smaller precisely-figured solid elements attached will, for at least the next several decades, minimize the mass of a large primary mirror assembly while still providing the high image quality essential for planet-finding and cosmological astronomical missions. Primary mirror segments are mounted in turn on ultralightweight thermally-formed plastic panels that hold clusters of mirror segments in rigid arrays whose tip/tilt and piston would be corrected over the scale of the plastic panels by the control segments. Prototype panels developed under this program are 45 cm wide and fabricated from commercially available Kaplan sheets. A three-strut octahedral tensegrity is the basis for the overall support structure. Each fundamental is composed of two such octahedrons, rotated oppositely about a common triangular face. Adjacent modules are joined at the nodes of the upper and lower triangles to form a deployable structure that could be made arbitrarily large. A seven-module dowel-and-wire prototype has been constructed. Deployment techniques based on the use of collapsing toggled struts with diagonal tensional elements allows an assembly of tensegrities to be fully collapsed and redeployed. The prototype designs will be described and results of a test program for measuring strength and deformation will be presented.

CRANS - CONFIGURABLE REAL-TIME ANALYSIS SYSTEM

NASA Technical Reports Server (NTRS)

Mccluney, K.

1994-01-01

In a real-time environment, the results of changes or failures in a complex, interconnected system need evaluation quickly. Tabulations showing the effects of changes and/or failures of a given item in the system are generally only useful for a single input, and only with regard to that item. Subsequent changes become harder to evaluate as combinations of failures produce a cascade effect. When confronted by multiple indicated failures in the system, it becomes necessary to determine a single cause. In this case, failure tables are not very helpful. CRANS, the Configurable Real-time ANalysis System, can interpret a logic tree, constructed by the user, describing a complex system and determine the effects of changes and failures in it. Items in the tree are related to each other by Boolean operators. The user is then able to change the state of these items (ON/OFF FAILED/UNFAILED). The program then evaluates the logic tree based on these changes and determines any resultant changes to other items in the tree. CRANS can also search for a common cause for multiple item failures, and allow the user to explore the logic tree from within the program. A "help" mode and a reference check provide the user with a means of exploring an item's underlying logic from within the program. A commonality check determines single point failures for an item or group of items. Output is in the form of a user-defined matrix or matrices of colored boxes, each box representing an item or set of items from the logic tree. Input is via mouse selection of the matrix boxes, using the mouse buttons to toggle the state of the item. CRANS is written in C-language and requires the MIT X Window System, Version 11 Revision 4 or Revision 5. It requires 78K of RAM for execution and a three button mouse. It has been successfully implemented on Sun4 workstations running SunOS, HP9000 workstations running HP-UX, and DECstations running ULTRIX. No executable is provided on the distribution medium; however, a sample makefile is included. Sample input files are also included. The standard distribution medium is a .25 inch streaming magnetic tape cartridge (Sun QIC-24) in UNIX tar format. Alternate distribution media and formats are available upon request. This program was developed in 1992.

Clinical evaluation and treatment accuracy in diabetic macular edema using navigated laser photocoagulator NAVILAS.

PubMed

Kozak, Igor; Oster, Stephen F; Cortes, Marco A; Dowell, Dennis; Hartmann, Kathrin; Kim, Jae Suk; Freeman, William R

2011-06-01

To evaluate the clinical use and accuracy of a new retinal navigating laser technology that integrates a scanning slit fundus camera system with fluorescein angiography (FA), color, red-free, and infrared imaging capabilities with a computer steerable therapeutic 532-nm laser. Interventional case series. Eighty-six eyes of 61 patients with diabetic retinopathy and macular edema treated by NAVILAS. The imaging included digital color fundus photographs and FA. The planning included graphically marking future treatment sites (microaneurysms for single-spot focal treatment and areas of diffuse leakage for grid pattern photocoagulation) on the acquired images. The preplanned treatment was visible and overlaid on the live fundus image during the actual photocoagulation. The NAVILAS automatically advances the aiming beam location from one planned treatment site to the next after each photocoagulation spot until all sites are treated. Aiming beam stabilization compensated for patient's eye movements. The pretreatment FA with the treatment plan was overlaid on top of the posttreatment color fundus images with the actual laser burns. This allowed treatment accuracy to be calculated. Independent observers evaluated the images to determine if the retinal opacification after treatment overlapped the targeted microaneurysm. Safety and accuracy of laser photocoagulation. The images were of very good quality compared with standard fundus cameras, allowing careful delineation of target areas on FA. Toggling from infrared, to monochromatic, to color view allowed evaluation and adjustment of burn intensity during treatment. There were no complications during or after photocoagulation treatment. An analysis of accuracy of 400 random focal targeted spots found that the NAVILAS achieved a microaneurysm hit rate of 92% when the placement of the treatment circle was centered by the operating surgeon on the microaneurysm. The accuracy for the control group analyzing 100 focal spots was significantly lower at 72% (P<0.01). Laser photocoagulation using the NAVILAS system is safe and achieves a higher rate of accuracy in photocoagulation treatments of diabetic retinopathy lesions than standard manual-technique laser treatment. Precise manual preplanning and positioning of the treatment sites by the surgeon is possible, allowing accurate and predictable photocoagulation of these lesions. Proprietary or commercial disclosure may be found after the references. Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Effect of augmentation techniques on the failure of pedicle screws under cranio-caudal cyclic loading.

PubMed

Bostelmann, Richard; Keiler, Alexander; Steiger, Hans Jakob; Scholz, Armin; Cornelius, Jan Frederick; Schmoelz, Werner

2017-01-01

Augmentation of pedicle screws is recommended in selected indications (for instance: osteoporosis). Generally, there are two techniques for pedicle screw augmentation: inserting the screw in the non cured cement and in situ-augmentation with cannulated fenestrated screws, which can be applied percutaneously. Most of the published studies used an axial pull out test for evaluation of the pedicle screw anchorage. However, the loading and the failure mode of pullout tests do not simulate the cranio-caudal in vivo loading and failure mechanism of pedicle screws. The purpose of the present study was to assess the fixation effects of different augmentation techniques (including percutaneous cement application) and to investigate pedicle screw loosening under physiological cyclic cranio-caudal loading. Each of the two test groups consisted of 15 vertebral bodies (L1-L5, three of each level per group). Mean age was 84.3 years (SD 7.8) for group 1 and 77.0 years (SD 7.00) for group 2. Mean bone mineral density was 53.3 mg/cm 3 (SD 14.1) for group 1 and 53.2 mg/cm 3 (SD 4.3) for group 2. 1.5 ml high viscosity PMMA bone cement was used for all augmentation techniques. For test group 1, pedicles on the right side of the vertebrae were instrumented with solid pedicle screws in standard fashion without augmentation and served as control group. Left pedicles were instrumented with cannulated screws (Viper cannulated, DePuy Spine) and augmented. For test group 2 pedicles on the left side of the vertebrae were instrumented with cannulated fenestrated screws and in situ augmented. On the right side solid pedicle screws were augmented with cement first technique. Each screw was subjected to a cranio-caudal cyclic load starting at 20-50 N with increasing upper load magnitude of 0.1 N per cycle (1 Hz) for a maximum of 5000 cycles or until total failure. Stress X-rays were taken after cyclic loading to evaluate screw loosening. Test group 1 showed a significant higher number of load cycles until failure for augmented screws compared to the control (4030 cycles, SD 827.8 vs. 1893.3 cycles, SD 1032.1; p < 0.001). Stress X-rays revealed significant less screw toggling for the augmented screws (5.2°, SD 5.4 vs. 16.1°, SD 5.9; p < 0.001). Test group 2 showed 3653.3 (SD 934) and 3723.3 (SD 560.6) load cycles until failure for in situ and cement first augmentation. Stress X-rays revealed a screw toggling of 5.1 (SD 1.9) and 6.6 (SD 4.6) degrees for in situ and cement first augmentation techniques (p > 0.05). Augmentation of pedicle screws in general significantly increased the number of load cycles and failure load comparing to the nonaugmented control group. For the augmentation technique (cement first, in situ augmented, percutaneously application) no effect could be exhibited on the failure of the pedicle screws. By the cranio-caudal cyclic loading failure of the pedicle screws occurred by screw cut through the superior endplate and the characteristic "windshield-wiper effect", typically observed in clinical practice, could be reproduced.

Intralaryngeal thyroarytaenoid lateralisation using the Fast-Fix 360 system: a canine cadaveric study.

PubMed

Stegen, Ludo; Kitshoff, Adriaan M; Van Goethem, Bart; Vandekerckhove, Peter; de Rooster, Hilde

2015-01-01

Laryngeal paralysis is a condition in which failure of arytaenoid abduction results in a reduced rima glottidis cross-sectional area. The most commonly performed surgical techniques rely on unilateral abduction of the arytaenoid, requiring a lateral or ventral surgical approach to the larynx. The aim of the study was to investigate a novel minimally invasive intralaryngeal thyroarytaenoid lateralisation technique, using the Fast-Fix 360 meniscal repair system. Larynges were harvested from large breed canine cadavers. With the aid of Kirschner wires placed between the centre of the vocal process and the centre of an imaginary line between the cranial thyroid fissure and the cricothyroid articulation, the mean insertion angle was calculated. The Fast-Fix 360 delivery needle inserted intralaryngeally (n=10), according to a simplified insertion angle (70°), resulted in thyroid penetration (>2.5 mm from margin) in all patients. The Fast-Fix was applied unilaterally at 70° with the first toggle fired on the lateral aspect of the thyroid cartilage and inside the laryngeal cavity on retraction. The suture was tightened. Preprocedural (61.06±9.21 mm2) and postprocedural (138.37±26.12 mm2) rima glottidis cross-sectional area was significantly different (P<0.0001). The mean percentage increase in rima glottidis cross-sectional area was 125.96 per cent (±16.54 per cent). Intralaryngeal thyroarytaenoid laterlisation using the Fast-Fix 360 meniscal repair system ex vivo increased the rima glottidis cross-sectional area significantly.

DNA-Binding Kinetics Determines the Mechanism of Noise-Induced Switching in Gene Networks

PubMed Central

Tse, Margaret J.; Chu, Brian K.; Roy, Mahua; Read, Elizabeth L.

2015-01-01

Gene regulatory networks are multistable dynamical systems in which attractor states represent cell phenotypes. Spontaneous, noise-induced transitions between these states are thought to underlie critical cellular processes, including cell developmental fate decisions, phenotypic plasticity in fluctuating environments, and carcinogenesis. As such, there is increasing interest in the development of theoretical and computational approaches that can shed light on the dynamics of these stochastic state transitions in multistable gene networks. We applied a numerical rare-event sampling algorithm to study transition paths of spontaneous noise-induced switching for a ubiquitous gene regulatory network motif, the bistable toggle switch, in which two mutually repressive genes compete for dominant expression. We find that the method can efficiently uncover detailed switching mechanisms that involve fluctuations both in occupancies of DNA regulatory sites and copy numbers of protein products. In addition, we show that the rate parameters governing binding and unbinding of regulatory proteins to DNA strongly influence the switching mechanism. In a regime of slow DNA-binding/unbinding kinetics, spontaneous switching occurs relatively frequently and is driven primarily by fluctuations in DNA-site occupancies. In contrast, in a regime of fast DNA-binding/unbinding kinetics, switching occurs rarely and is driven by fluctuations in levels of expressed protein. Our results demonstrate how spontaneous cell phenotype transitions involve collective behavior of both regulatory proteins and DNA. Computational approaches capable of simulating dynamics over many system variables are thus well suited to exploring dynamic mechanisms in gene networks. PMID:26488666

A single amino-acid substitution toggles chloride dependence of the alpha-amylase paralog amyrel in Drosophila melanogaster and Drosophila virilis species.

PubMed

Claisse, Gaëlle; Feller, Georges; Bonneau, Magalie; Da Lage, Jean-Luc

2016-08-01

In animals, most α-amylases are chloride-dependent enzymes. A chloride ion is required for allosteric activation and is coordinated by one asparagine and two arginine side chains. Whereas the asparagine and one arginine are strictly conserved, the main chloride binding arginine is replaced by a glutamine in some rare instances, resulting in the loss of chloride binding and activation. Amyrel is a distant paralogue of α-amylase in Diptera, which was not characterized biochemically to date. Amyrel shows both substitutions depending on the species. In Drosophila melanogaster, an arginine is present in the sequence but in Drosophila virilis, a glutamine occurs at this position. We have investigated basic enzymological parameters and the dependence to chloride of Amyrel of both species, produced in yeast, and in mutants substituting arginine to glutamine or glutamine to arginine. We found that the amylolytic activity of Amyrel is about thirty times weaker than the classical Drosophila α-amylase, and that the substitution of the arginine by a glutamine in D. melanogaster suppressed the chloride-dependence but was detrimental to activity. In contrast, changing the glutamine into an arginine rendered D. virilis Amyrel chloride-dependent, and interestingly, significantly increased its catalytic efficiency. These results show that the chloride ion is not mandatory for Amyrel but stimulates the reaction rate. The possible phylogenetic origin of the arginine/glutamine substitution is also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

BRIC-100VC Biological Research in Canisters (BRIC)-100VC

NASA Technical Reports Server (NTRS)

Richards, Stephanie E.; Levine, Howard G. (Compiler); Romero, Vergel

2016-01-01

The Biological Research in Canisters (BRIC) is an anodized-aluminum cylinder used to provide passive stowage for investigations of the effects of space flight on small specimens. The BRIC 100 mm petri dish vacuum containment unit (BRIC-100VC) has supported Dugesia japonica (flatworm) within spring under normal atmospheric conditions for 29 days in space and Hemerocallis lilioasphodelus L. (daylily) somatic embryo development within a 5% CO2 gaseous environment for 4.5 months in space. BRIC-100VC is a completely sealed, anodized-aluminum cylinder (Fig. 1) providing containment and structural support of the experimental specimens. The top and bottom lids of the canister include rapid disconnect valves for filling the canister with selected gases. These specialized valves allow for specific atmospheric containment within the canister, providing a gaseous environment defined by the investigator. Additionally, the top lid has been designed with a toggle latch and O-ring assembly allowing for prompt sealing and removal of the lid. The outside dimensions of the BRIC-100VC canisters are 16.0 cm (height) x 11.4 cm (outside diameter). The lower portion of the canister has been equipped with sufficient storage space for passive temperature and relative humidity data loggers. The BRIC- 100VC canister has been optimized to accommodate standard 100 mm laboratory petri dishes or 50 mL conical tubes. Depending on storage orientation, up to 6 or 9 canisters have been flown within an International Space Station (ISS) stowage locker.

Introducing glycomics data into the Semantic Web

PubMed Central

2013-01-01

Background Glycoscience is a research field focusing on complex carbohydrates (otherwise known as glycans)a, which can, for example, serve as “switches” that toggle between different functions of a glycoprotein or glycolipid. Due to the advancement of glycomics technologies that are used to characterize glycan structures, many glycomics databases are now publicly available and provide useful information for glycoscience research. However, these databases have almost no link to other life science databases. Results In order to implement support for the Semantic Web most efficiently for glycomics research, the developers of major glycomics databases agreed on a minimal standard for representing glycan structure and annotation information using RDF (Resource Description Framework). Moreover, all of the participants implemented this standard prototype and generated preliminary RDF versions of their data. To test the utility of the converted data, all of the data sets were uploaded into a Virtuoso triple store, and several SPARQL queries were tested as “proofs-of-concept” to illustrate the utility of the Semantic Web in querying across databases which were originally difficult to implement. Conclusions We were able to successfully retrieve information by linking UniCarbKB, GlycomeDB and JCGGDB in a single SPARQL query to obtain our target information. We also tested queries linking UniProt with GlycoEpitope as well as lectin data with GlycomeDB through PDB. As a result, we have been able to link proteomics data with glycomics data through the implementation of Semantic Web technologies, allowing for more flexible queries across these domains. PMID:24280648

Introducing glycomics data into the Semantic Web.

PubMed

Aoki-Kinoshita, Kiyoko F; Bolleman, Jerven; Campbell, Matthew P; Kawano, Shin; Kim, Jin-Dong; Lütteke, Thomas; Matsubara, Masaaki; Okuda, Shujiro; Ranzinger, Rene; Sawaki, Hiromichi; Shikanai, Toshihide; Shinmachi, Daisuke; Suzuki, Yoshinori; Toukach, Philip; Yamada, Issaku; Packer, Nicolle H; Narimatsu, Hisashi

2013-11-26

Glycoscience is a research field focusing on complex carbohydrates (otherwise known as glycans)a, which can, for example, serve as "switches" that toggle between different functions of a glycoprotein or glycolipid. Due to the advancement of glycomics technologies that are used to characterize glycan structures, many glycomics databases are now publicly available and provide useful information for glycoscience research. However, these databases have almost no link to other life science databases. In order to implement support for the Semantic Web most efficiently for glycomics research, the developers of major glycomics databases agreed on a minimal standard for representing glycan structure and annotation information using RDF (Resource Description Framework). Moreover, all of the participants implemented this standard prototype and generated preliminary RDF versions of their data. To test the utility of the converted data, all of the data sets were uploaded into a Virtuoso triple store, and several SPARQL queries were tested as "proofs-of-concept" to illustrate the utility of the Semantic Web in querying across databases which were originally difficult to implement. We were able to successfully retrieve information by linking UniCarbKB, GlycomeDB and JCGGDB in a single SPARQL query to obtain our target information. We also tested queries linking UniProt with GlycoEpitope as well as lectin data with GlycomeDB through PDB. As a result, we have been able to link proteomics data with glycomics data through the implementation of Semantic Web technologies, allowing for more flexible queries across these domains.

The interplay of intrinsic and extrinsic bounded noises in biomolecular networks.

PubMed

Caravagna, Giulio; Mauri, Giancarlo; d'Onofrio, Alberto

2013-01-01

After being considered as a nuisance to be filtered out, it became recently clear that biochemical noise plays a complex role, often fully functional, for a biomolecular network. The influence of intrinsic and extrinsic noises on biomolecular networks has intensively been investigated in last ten years, though contributions on the co-presence of both are sparse. Extrinsic noise is usually modeled as an unbounded white or colored gaussian stochastic process, even though realistic stochastic perturbations are clearly bounded. In this paper we consider Gillespie-like stochastic models of nonlinear networks, i.e. the intrinsic noise, where the model jump rates are affected by colored bounded extrinsic noises synthesized by a suitable biochemical state-dependent Langevin system. These systems are described by a master equation, and a simulation algorithm to analyze them is derived. This new modeling paradigm should enlarge the class of systems amenable at modeling. We investigated the influence of both amplitude and autocorrelation time of a extrinsic Sine-Wiener noise on: (i) the Michaelis-Menten approximation of noisy enzymatic reactions, which we show to be applicable also in co-presence of both intrinsic and extrinsic noise, (ii) a model of enzymatic futile cycle and (iii) a genetic toggle switch. In (ii) and (iii) we show that the presence of a bounded extrinsic noise induces qualitative modifications in the probability densities of the involved chemicals, where new modes emerge, thus suggesting the possible functional role of bounded noises.

Real-time fusion of coronary CT angiography with x-ray fluoroscopy during chronic total occlusion PCI.

PubMed

Ghoshhajra, Brian B; Takx, Richard A P; Stone, Luke L; Girard, Erin E; Brilakis, Emmanouil S; Lombardi, William L; Yeh, Robert W; Jaffer, Farouc A

2017-06-01

The purpose of this study was to demonstrate the feasibility of real-time fusion of coronary computed tomography angiography (CTA) centreline and arterial wall calcification with x-ray fluoroscopy during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Patients undergoing CTO PCI were prospectively enrolled. Pre-procedural CT scans were integrated with conventional coronary fluoroscopy using prototype software. We enrolled 24 patients who underwent CTO PCI using the prototype CT fusion software, and 24 consecutive CTO PCI patients without CT guidance served as a control group. Mean age was 66 ± 11 years, and 43/48 patients were men. Real-time CTA fusion during CTO PCI provided additional information regarding coronary arterial calcification and tortuosity that generated new insights into antegrade wiring, antegrade dissection/reentry, and retrograde wiring during CTO PCI. Overall CTO success rates and procedural outcomes remained similar between the two groups, despite a trend toward higher complexity in the fusion CTA group. This study demonstrates that real-time automated co-registration of coronary CTA centreline and calcification onto live fluoroscopic images is feasible and provides new insights into CTO PCI, and in particular, antegrade dissection reentry-based CTO PCI. • Real-time semi-automated fusion of CTA/fluoroscopy is feasible during CTO PCI. • CTA fusion data can be toggled on/off as desired during CTO PCI • Real-time CT calcium and centreline overlay could benefit antegrade dissection/reentry-based CTO PCI.

Regulating Set-β's Subcellular Localization Toggles Its Function between Inhibiting and Promoting Axon Growth and Regeneration

PubMed Central

Wang, Yan; Morkin, Melina I.; Fernandez, Stephanie G.; Mlacker, Gregory M.; Shechter, Jesse M.; Liu, Xiongfei; Patel, Karan H.; Lapins, Allison; Yang, Steven; Dombrowski, Susan M.

2014-01-01

The failure of the CNS neurons to regenerate axons after injury or stroke is a major clinical problem. Transcriptional regulators like Set-β are well positioned to regulate intrinsic axon regeneration capacity, which declines developmentally in maturing CNS neurons. Set-β also functions at cellular membranes and its subcellular localization is disrupted in Alzheimer's disease, but many of its biological mechanisms have not been explored in neurons. We found that Set-β was upregulated postnatally in CNS neurons, and was primarily localized to the nucleus but was also detected in the cytoplasm and adjacent to the plasma membrane. Remarkably, nuclear Set-β suppressed, whereas Set-β localized to cytoplasmic membranes promoted neurite growth in rodent retinal ganglion cells and hippocampal neurons. Mimicking serine 9 phosphorylation, as found in Alzheimer's disease brains, delayed nuclear import and furthermore blocked the ability of nuclear Set-β to suppress neurite growth. We also present data on gene regulation and protein binding partner recruitment by Set-β in primary neurons, raising the hypothesis that nuclear Set-β may preferentially regulate gene expression whereas Set-β at cytoplasmic membranes may regulate unique cofactors, including PP2A, which we show also regulates axon growth in vitro. Finally, increasing recruitment of Set-β to cellular membranes promoted adult rat optic nerve axon regeneration after injury in vivo. Thus, Set-β differentially regulates axon growth and regeneration depending on subcellular localization and phosphorylation. PMID:24849368

Method and system for normalizing biometric variations to authenticate users from a public database and that ensures individual biometric data privacy

DOEpatents

Strait, Robert S.; Pearson, Peter K.; Sengupta, Sailes K.

2000-01-01

A password system comprises a set of codewords spaced apart from one another by a Hamming distance (HD) that exceeds twice the variability that can be projected for a series of biometric measurements for a particular individual and that is less than the HD that can be encountered between two individuals. To enroll an individual, a biometric measurement is taken and exclusive-ORed with a random codeword to produce a "reference value." To verify the individual later, a biometric measurement is taken and exclusive-ORed with the reference value to reproduce the original random codeword or its approximation. If the reproduced value is not a codeword, the nearest codeword to it is found, and the bits that were corrected to produce the codeword to it is found, and the bits that were corrected to produce the codeword are also toggled in the biometric measurement taken and the codeword generated during enrollment. The correction scheme can be implemented by any conventional error correction code such as Reed-Muller code R(m,n). In the implementation using a hand geometry device an R(2,5) code has been used in this invention. Such codeword and biometric measurement can then be used to see if the individual is an authorized user. Conventional Diffie-Hellman public key encryption schemes and hashing procedures can then be used to secure the communications lines carrying the biometric information and to secure the database of authorized users.

Aging and the Mammalian Regulatory Triumvirate

PubMed Central

Rollo, C. David

2010-01-01

A temporal framework linking circadian rhythms and clocks to aging rates identifies a specific window of target of rapamycin (TOR) signaling associated with growth hormone (GH) and insulin-like growth factor (IGF-1) (largely exclusive of insulin) in early sleep. IGF-1 signaling is released by growth hormone secretory peaks and downregulation of IGF-1 binding protein-1 resulting in activation of the mitogen activated protein kinase/extracellular signal response kinase (MAPK/ERK) and phosphoinositide 3-kinase-protein kinase B (PI3K-PKB/Akt) signaling pathways. Phosphorylation of Akt activates TOR which mediates the protein synthesis and growth functions of the GH axis. TOR activity is also associated with downregulated stress resistance, faster aging and reduced lifespan. IGF-1 signaling is terminated by falling GH and upregulation of IGF-1 binding proteins mediated by somatostatin and rising corticosteroids in later sleep. This suppresses PI3K-Akt signaling, thus activating the forkhead transcription factors (FOXOs) and stress-resistance pathways involved in promoting longevity. Thus, sleep appears to encompass both pathways currently identified as most relevant to aging and they toggle successively on the phosphorylation status of Akt. I propose a modified version of Pearl’s rate of living theory emphasizing the hard-wired antagonism of growth (TOR) and stress resistance (FOXO). The sleep association of TOR and FOXO in temporally separated windows and their sequential temporal deployment may change much of the way we think about aging and how to manipulate it. PMID:22396860

Spiraling into History: A Molecular Phylogeny and Investigation of Biogeographic Origins and Floral Evolution for the Genus Costus

PubMed Central

Salzman, Shayla; Driscoll, Heather E.; Renner, Tanya; André, Thiago; Shen, Stacy; Specht, Chelsea D.

2015-01-01

Rapid radiations are notoriously difficult to resolve, yet understanding phylogenetic patterns in such lineages can be useful for investigating evolutionary processes associated with bursts of speciation and morphological diversification. Here we present an expansive molecular phylogeny of Costus L. (Costaceae Nakai) with a focus on the Neotropical species within the clade, sampling 47 of the known 51 Neotropical species and including five molecular markers for phylogenetic analysis (ITS, ETS, rps16, trnL-F, and CaM). We use the phylogenetic results to investigate shifts in pollination syndrome, with the intention of addressing potential mechanisms leading to the rapid radiation documented for this clade. Our ancestral reconstruction of pollination syndrome presents the first evidence in this genus of an evolutionary toggle in pollination morphologies, demonstrating both the multiple independent evolutions of ornithophily (bird pollination) as well as reversals to melittophily (bee pollination). We show that the ornithophilous morphology has evolved at least eight times independently with four potential reversals to melittophilous morphology, and confirm prior work showing that neither pollination syndrome defines a monophyletic lineage. Based on the current distribution for the Neotropical and African species, we reconstruct the ancestral distribution of the Neotropical clade as the Pacific Coast of Mexico and Central America. Our results indicate an historic dispersal of a bee-pollinated taxon from Africa to the Pacific Coast of Mexico/Central America, with subsequent diversification leading to the evolution of a bird-pollinated floral morphology in multiple derived lineages. PMID:26146450

Direct numerical simulation of sheared turbulent flow

NASA Technical Reports Server (NTRS)

Harris, Vascar G.

1994-01-01

The summer assignment to study sheared turbulent flow was divided into three phases which were: (1) literature survey, (2) computational familiarization, and (3) pilot computational studies. The governing equations of fluid dynamics or Navier-Stokes equations describe the velocity, pressure, and density as functions of position and time. In principle, when combined with conservation equations for mass, energy, and thermodynamic state of the fluid a determinate system could be obtained. In practice the Navier-Stokes equations have not been solved due to the nonlinear nature and complexity of these equations. Consequently, the importance of experiments in gaining insight for understanding the physics of the problem has been an ongoing process. Reasonable computer simulations of the problem have occured as the computational speed and storage of computers has evolved. The importance of the microstructure of the turbulence dictates the need for high resolution grids in extracting solutions which contain the physical mechanisms which are essential to a successful simulation. The recognized breakthrough occurred as a result of the pioneering work of Orzag and Patterson in which the Navier-Stokes equations were solved numerically utilizing a time saving toggling technique between physical and wave space, known as a spectral method. An equally analytically unsolvable problem, containing the same quasi-chaotic nature as turbulence, is known as the three body problem which was studied computationally as a first step this summer. This study was followed by computations of a two dimensional (2D) free shear layer.

Acylation of Superoxide Dismutase 1 (SOD1) at K122 Governs SOD1-Mediated Inhibition of Mitochondrial Respiration

PubMed Central

Banks, Courtney J.; Rodriguez, Nathan W.; Gashler, Kyle R.; Pandya, Rushika R.; Mortenson, Jeffrey B.; Whited, Matthew D.; Soderblom, Erik J.; Thompson, J. Will; Moseley, M. Arthur; Reddi, Amit R.; Tessem, Jeffery S.; Torres, Matthew P.; Bikman, Benjamin T.

2017-01-01

ABSTRACT In this study, we employed proteomics to identify mechanisms of posttranslational regulation on cell survival signaling proteins. We focused on Cu-Zn superoxide dismutase (SOD1), which protects cells from oxidative stress. We found that acylation of K122 on SOD1, while not impacting SOD1 catalytic activity, suppressed the ability of SOD1 to inhibit mitochondrial metabolism at respiratory complex I. We found that deacylase depletion increased K122 acylation on SOD1, which blocked the suppression of respiration in a K122-dependent manner. In addition, we found that acyl-mimicking mutations at K122 decreased SOD1 accumulation in mitochondria, initially hinting that SOD1 may inhibit respiration directly within the intermembrane space (IMS). However, surprisingly, we found that forcing the K122 acyl mutants into the mitochondria with an IMS-targeting tag did not recover their ability to suppress respiration. Moreover, we found that suppressing or boosting respiration levels toggled SOD1 in or out of the mitochondria, respectively. These findings place SOD1-mediated inhibition of respiration upstream of its mitochondrial localization. Lastly, deletion-rescue experiments show that a respiration-defective mutant of SOD1 is also impaired in its ability to rescue cells from toxicity caused by SOD1 deletion. Together, these data suggest a previously unknown interplay between SOD1 acylation, metabolic regulation, and SOD1-mediated cell survival. PMID:28739857

High spatial resolution upgrade of the electron cyclotron emission radiometer for the DIII-D tokamak.

PubMed

Truong, D D; Austin, M E

2014-11-01

The 40-channel DIII-D electron cyclotron emission (ECE) radiometer provides measurements of Te(r,t) at the tokamak midplane from optically thick, second harmonic X-mode emission over a frequency range of 83-130 GHz. The frequency spacing of the radiometer's channels results in a spatial resolution of ∼1-3 cm, depending on local magnetic field and electron temperature. A new high resolution subsystem has been added to the DIII-D ECE radiometer to make sub-centimeter (0.6-0.8 cm) resolution Te measurements. The high resolution subsystem branches off from the regular channels' IF bands and consists of a microwave switch to toggle between IF bands, a switched filter bank for frequency selectivity, an adjustable local oscillator and mixer for further frequency down-conversion, and a set of eight microwave filters in the 2-4 GHz range. Higher spatial resolution is achieved through the use of a narrower (200 MHz) filter bandwidth and closer spacing between the filters' center frequencies (250 MHz). This configuration allows for full coverage of the 83-130 GHz frequency range in 2 GHz bands. Depending on the local magnetic field, this translates into a "zoomed-in" analysis of a ∼2-4 cm radial region. Expected uses of these channels include mapping the spatial dependence of Alfven eigenmodes, geodesic acoustic modes, and externally applied magnetic perturbations. Initial Te measurements, which demonstrate that the desired resolution is achieved, are presented.

Modulation of Starch Digestion for Slow Glucose Release through “Toggling” of Activities of Mucosal α-Glucosidases*

PubMed Central

Lee, Byung-Hoo; Eskandari, Razieh; Jones, Kyra; Reddy, Kongara Ravinder; Quezada-Calvillo, Roberto; Nichols, Buford L.; Rose, David R.; Hamaker, Bruce R.; Pinto, B. Mario

2012-01-01

Starch digestion involves the breakdown by α-amylase to small linear and branched malto-oligosaccharides, which are in turn hydrolyzed to glucose by the mucosal α-glucosidases, maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI). MGAM and SI are anchored to the small intestinal brush-border epithelial cells, and each contains a catalytic N- and C-terminal subunit. All four subunits have α-1,4-exohydrolytic glucosidase activity, and the SI N-terminal subunit has an additional exo-debranching activity on the α-1,6-linkage. Inhibition of α-amylase and/or α-glucosidases is a strategy for treatment of type 2 diabetes. We illustrate here the concept of “toggling”: differential inhibition of subunits to examine more refined control of glucogenesis of the α-amylolyzed starch malto-oligosaccharides with the aim of slow glucose delivery. Recombinant MGAM and SI subunits were individually assayed with α-amylolyzed waxy corn starch, consisting mainly of maltose, maltotriose, and branched α-limit dextrins, as substrate in the presence of four different inhibitors: acarbose and three sulfonium ion compounds. The IC50 values show that the four α-glucosidase subunits could be differentially inhibited. The results support the prospect of controlling starch digestion rates to induce slow glucose release through the toggling of activities of the mucosal α-glucosidases by selective enzyme inhibition. This approach could also be used to probe associated metabolic diseases. PMID:22851177

High resolution x-ray diffraction of high quality 2 micron quaternary indium gallium arsenide antimonide digital alloy heterostructures grown by modulated molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Mourad, Carole Issa

2000-10-01

Growth of high quality mixed anion alloys such as InGaAsSb and AlGaAsSb are critical to laser heterostructures designed for 2--4 micron emission. However, run-to-run reproducibility as well as the ability to reproducibly change alloy compositions within a heterostructure tend to be poor. This is because the competition for incorporation between the two anions (As and Sb) is extremely sensitive to a large number of growth parameters such as temperature, incident fluxes, and growth rate, which may drift during the course of deposition, or are difficult to reset during growth. With the intent of improving reproducibility, we have grown and characterized InGaAsSb and AlGaAsSb "digital alloys" deposited using modulated incident As2 and Sb2 incident fluxes. In0.1Ga 0.9AsySb1-y alloy layers were grown by alternately exposing the film surface to As2 and Sb2 fluxes with a periodicity ranging from ˜9 to ˜22 A. Average alloy composition is determined by the duty-cycle of the anion-oven shutters. Structural characterization using high-resolution x-ray diffraction (HRXRD) shows clear satellite peaks indicating that the digital alloys retain the compositional modulation. Optical characterization using photoluminescence indicate that the digital alloys can successfully replace the conventionally grown quaternary alloys with the same average composition. In addition we have characterized digitally grown InGaAsSb layers using HRXRD and measured the sensitivity of the resulting average composition to the growth temperature. We find that the composition of In0.1Ga0.9AsySb1-y alloy layers grown digitally on GaSb substrates is nearly three times less sensitive to the growth temperature as conventional growth. Digital growth of InGaAsSb and AlGaAsSb layers has enabled the growth of heterostructures containing multiple alloy compositions by toggling between shutter duty-cycles during growth, without necessitating changes to the oven temperatures throughout deposition. We have grown and characterized optically pumped ˜2mum laser structures with InGaAsSb quantum wells and AlGaAsSb barriers both grown using the digital alloy technique. Room temperature operation, a low threshold current density of 104 W/cm2 (at 80K with 808nm pump), and a characteristic temperature (To) of 104 K show the feasibility of applying digital alloying techniques to mid-infrared optical devices.

Reversible online control of habitual behavior by optogenetic perturbation of medial prefrontal cortex

PubMed Central

Smith, Kyle S.; Virkud, Arti; Deisseroth, Karl; Graybiel, Ann M.

2012-01-01

Habits tend to form slowly but, once formed, can have great stability. We probed these temporal characteristics of habitual behaviors by intervening optogenetically in forebrain habit circuits as rats performed well-ingrained habitual runs in a T-maze. We trained rats to perform a maze habit, confirmed the habitual behavior by devaluation tests, and then, during the maze runs (ca. 3 s), we disrupted population activity in a small region in the medial prefrontal cortex, the infralimbic cortex. In accordance with evidence that this region is necessary for the expression of habits, we found that this cortical disruption blocked habitual behavior. Notably, however, this blockade of habitual performance occurred on line, within an average of three trials (ca. 9 s of inhibition), and as soon as during the first trial (<3 s). During subsequent weeks of training, the rats acquired a new behavioral pattern. When we again imposed the same cortical perturbation, the rats regained the suppressed maze-running that typified the original habit, and, simultaneously, the more recently acquired habit was blocked. These online changes occurred within an average of two trials (ca. 6 s of infralimbic inhibition). Measured changes in generalized performance ability and motivation to consume reward were unaffected. This immediate toggling between breaking old habits and returning to them demonstrates that even semiautomatic behaviors are under cortical control and that this control occurs online, second by second. These temporal characteristics define a framework for uncovering cellular transitions between fixed and flexible behaviors, and corresponding disturbances in pathologies. PMID:23112197

High-speed photoacoustic imaging using an LED-based photoacoustic imaging system

NASA Astrophysics Data System (ADS)

Sato, Naoto; Kuniyil Ajith Singh, Mithun; Shigeta, Yusuke; Hanaoka, Takamitsu; Agano, Toshitaka

2018-02-01

Recently we developed a multispectral LED-based photoacoustic/ultrasound imaging system (AcousticX) and have been continuously working on its technical/functional improvements. AcousticX is a linear array ultrasound transducer (128 elements, 10 MHz)-based system in which LED arrays (selectable wavelengths, pulse repetition frequency: 4 kHz, pulse width: tunable from 40 - 100 ns) are fixed on both sides of the transducer to illuminate the tissue for photoacoustic imaging. The ultrasound/photoacoustic data from all 128 elements can be simultaneously acquired, processed and displayed. We already demonstrated our system's capability to perform photoacoustic/ultrasound imaging for dynamic imaging of the tissue at a frame rate of 10 Hz (for example to visualize the pulsation of arteries in vivo in human subjects). In this work, we present the development of a new high-speed imaging mode in AcousticX. In this mode, instead of toggling between ultrasound and photoacoustic measurements, it is possible to continuously acquire only photoacoustic data for 1.5 seconds with a time interval of 1 ms. With this improvement, we can record photoacoustic signals from the whole aperture (38 mm) at fast rate and can be reviewed later at different speeds for analyzing dynamic changes in the photoacoustic signals. We believe that AcousticX with this new high-speed mode opens up a feasible technical path for multiple dynamic studies, for example one which focus on imaging the response of voltage sensitive dyes. We envisage to improve the acquisition speed further in future for exploring ultra-high-speed applications.

A fast, robust and tunable synthetic gene oscillator.

PubMed

Stricker, Jesse; Cookson, Scott; Bennett, Matthew R; Mather, William H; Tsimring, Lev S; Hasty, Jeff

2008-11-27

One defining goal of synthetic biology is the development of engineering-based approaches that enable the construction of gene-regulatory networks according to 'design specifications' generated from computational modelling. This approach provides a systematic framework for exploring how a given regulatory network generates a particular phenotypic behaviour. Several fundamental gene circuits have been developed using this approach, including toggle switches and oscillators, and these have been applied in new contexts such as triggered biofilm development and cellular population control. Here we describe an engineered genetic oscillator in Escherichia coli that is fast, robust and persistent, with tunable oscillatory periods as fast as 13 min. The oscillator was designed using a previously modelled network architecture comprising linked positive and negative feedback loops. Using a microfluidic platform tailored for single-cell microscopy, we precisely control environmental conditions and monitor oscillations in individual cells through multiple cycles. Experiments reveal remarkable robustness and persistence of oscillations in the designed circuit; almost every cell exhibited large-amplitude fluorescence oscillations throughout observation runs. The oscillatory period can be tuned by altering inducer levels, temperature and the media source. Computational modelling demonstrates that the key design principle for constructing a robust oscillator is a time delay in the negative feedback loop, which can mechanistically arise from the cascade of cellular processes involved in forming a functional transcription factor. The positive feedback loop increases the robustness of the oscillations and allows for greater tunability. Examination of our refined model suggested the existence of a simplified oscillator design without positive feedback, and we construct an oscillator strain confirming this computational prediction.

Intralaryngeal thyroarytaenoid lateralisation using the Fast-Fix 360 system: a canine cadaveric study

PubMed Central

Stegen, Ludo; Kitshoff, Adriaan M.; Van Goethem, Bart; Vandekerckhove, Peter; de Rooster, Hilde

2015-01-01

Introduction Laryngeal paralysis is a condition in which failure of arytaenoid abduction results in a reduced rima glottidis cross-sectional area. The most commonly performed surgical techniques rely on unilateral abduction of the arytaenoid, requiring a lateral or ventral surgical approach to the larynx. Aims and objectives The aim of the study was to investigate a novel minimally invasive intralaryngeal thyroarytaenoid lateralisation technique, using the Fast-Fix 360 meniscal repair system. Materials and methods Larynges were harvested from large breed canine cadavers. With the aid of Kirschner wires placed between the centre of the vocal process and the centre of an imaginary line between the cranial thyroid fissure and the cricothyroid articulation, the mean insertion angle was calculated. Results The Fast-Fix 360 delivery needle inserted intralaryngeally (n=10), according to a simplified insertion angle (70°), resulted in thyroid penetration (>2.5 mm from margin) in all patients. The Fast-Fix was applied unilaterally at 70° with the first toggle fired on the lateral aspect of the thyroid cartilage and inside the laryngeal cavity on retraction. The suture was tightened. Preprocedural (61.06±9.21 mm2) and postprocedural (138.37±26.12 mm2) rima glottidis cross-sectional area was significantly different (P<0.0001). The mean percentage increase in rima glottidis cross-sectional area was 125.96 per cent (±16.54 per cent). Conclusion Intralaryngeal thyroarytaenoid laterlisation using the Fast-Fix 360 meniscal repair system ex vivo increased the rima glottidis cross-sectional area significantly. PMID:26392907

ACCURATE CHEMICAL MASTER EQUATION SOLUTION USING MULTI-FINITE BUFFERS

PubMed Central

Cao, Youfang; Terebus, Anna; Liang, Jie

2016-01-01

The discrete chemical master equation (dCME) provides a fundamental framework for studying stochasticity in mesoscopic networks. Because of the multi-scale nature of many networks where reaction rates have large disparity, directly solving dCMEs is intractable due to the exploding size of the state space. It is important to truncate the state space effectively with quantified errors, so accurate solutions can be computed. It is also important to know if all major probabilistic peaks have been computed. Here we introduce the Accurate CME (ACME) algorithm for obtaining direct solutions to dCMEs. With multi-finite buffers for reducing the state space by O(n!), exact steady-state and time-evolving network probability landscapes can be computed. We further describe a theoretical framework of aggregating microstates into a smaller number of macrostates by decomposing a network into independent aggregated birth and death processes, and give an a priori method for rapidly determining steady-state truncation errors. The maximal sizes of the finite buffers for a given error tolerance can also be pre-computed without costly trial solutions of dCMEs. We show exactly computed probability landscapes of three multi-scale networks, namely, a 6-node toggle switch, 11-node phage-lambda epigenetic circuit, and 16-node MAPK cascade network, the latter two with no known solutions. We also show how probabilities of rare events can be computed from first-passage times, another class of unsolved problems challenging for simulation-based techniques due to large separations in time scales. Overall, the ACME method enables accurate and efficient solutions of the dCME for a large class of networks. PMID:27761104

Structural basis of rifampin inactivation by rifampin phosphotransferase

PubMed Central

Qi, Xiaofeng; Lin, Wei; Ma, Miaolian; Wang, Chengyuan; He, Yang; He, Nisha; Gao, Jing; Zhou, Hu; Xiao, Youli; Wang, Yong

2016-01-01

Rifampin (RIF) is a first-line drug used for the treatment of tuberculosis and other bacterial infections. Various RIF resistance mechanisms have been reported, and recently an RIF-inactivation enzyme, RIF phosphotransferase (RPH), was reported to phosphorylate RIF at its C21 hydroxyl at the cost of ATP. However, the underlying molecular mechanism remained unknown. Here, we solve the structures of RPH from Listeria monocytogenes (LmRPH) in different conformations. LmRPH comprises three domains: an ATP-binding domain (AD), an RIF-binding domain (RD), and a catalytic His-containing domain (HD). Structural analyses reveal that the C-terminal HD can swing between the AD and RD, like a toggle switch, to transfer phosphate. In addition to its catalytic role, the HD can bind to the AD and induce conformational changes that stabilize ATP binding, and the binding of the HD to the RD is required for the formation of the RIF-binding pocket. A line of hydrophobic residues forms the RIF-binding pocket and interacts with the 1-amino, 2-naphthol, 4-sulfonic acid and naphthol moieties of RIF. The R group of RIF points toward the outside of the pocket, explaining the low substrate selectivity of RPH. Four residues near the C21 hydroxyl of RIF, His825, Arg666, Lys670, and Gln337, were found to play essential roles in the phosphorylation of RIF; among these the His825 residue may function as the phosphate acceptor and donor. Our study reveals the molecular mechanism of RIF phosphorylation catalyzed by RPH and will guide the development of a new generation of rifamycins. PMID:27001859

Structural Dynamics as a Contributor to Error-prone Replication by an RNA-dependent RNA Polymerase*

PubMed Central

Moustafa, Ibrahim M.; Korboukh, Victoria K.; Arnold, Jamie J.; Smidansky, Eric D.; Marcotte, Laura L.; Gohara, David W.; Yang, Xiaorong; Sánchez-Farrán, María Antonieta; Filman, David; Maranas, Janna K.; Boehr, David D.; Hogle, James M.; Colina, Coray M.; Cameron, Craig E.

2014-01-01

RNA viruses encoding high- or low-fidelity RNA-dependent RNA polymerases (RdRp) are attenuated. The ability to predict residues of the RdRp required for faithful incorporation of nucleotides represents an essential step in any pipeline intended to exploit perturbed fidelity as the basis for rational design of vaccine candidates. We used x-ray crystallography, molecular dynamics simulations, NMR spectroscopy, and pre-steady-state kinetics to compare a mutator (H273R) RdRp from poliovirus to the wild-type (WT) enzyme. We show that the nucleotide-binding site toggles between the nucleotide binding-occluded and nucleotide binding-competent states. The conformational dynamics between these states were enhanced by binding to primed template RNA. For the WT, the occluded conformation was favored; for H273R, the competent conformation was favored. The resonance for Met-187 in our NMR spectra reported on the ability of the enzyme to check the correctness of the bound nucleotide. Kinetic experiments were consistent with the conformational dynamics contributing to the established pre-incorporation conformational change and fidelity checkpoint. For H273R, residues comprising the active site spent more time in the catalytically competent conformation and were more positively correlated than the WT. We propose that by linking the equilibrium between the binding-occluded and binding-competent conformations of the nucleotide-binding pocket and other active-site dynamics to the correctness of the bound nucleotide, faithful nucleotide incorporation is achieved. These studies underscore the need to apply multiple biophysical and biochemical approaches to the elucidation of the physical basis for polymerase fidelity. PMID:25378410

Evolutionary Dynamics of Floral Homeotic Transcription Factor Protein–Protein Interactions

PubMed Central

Bartlett, Madelaine; Thompson, Beth; Brabazon, Holly; Del Gizzi, Robert; Zhang, Thompson; Whipple, Clinton

2016-01-01

Protein–protein interactions (PPIs) have widely acknowledged roles in the regulation of development, but few studies have addressed the timing and mechanism of shifting PPIs over evolutionary history. The B-class MADS-box transcription factors, PISTILLATA (PI) and APETALA3 (AP3) are key regulators of floral development. PI-like (PIL) and AP3-like (AP3L) proteins from a number of plants, including Arabidopsis thaliana (Arabidopsis) and the grass Zea mays (maize), bind DNA as obligate heterodimers. However, a PIL protein from the grass relative Joinvillea can bind DNA as a homodimer. To ascertain whether Joinvillea PIL homodimerization is an anomaly or indicative of broader trends, we characterized PIL dimerization across the Poales and uncovered unexpected evolutionary lability. Both obligate B-class heterodimerization and PIL homodimerization have evolved multiple times in the order, by distinct molecular mechanisms. For example, obligate B-class heterodimerization in maize evolved very recently from PIL homodimerization. A single amino acid change, fixed during domestication, is sufficient to toggle one maize PIL protein between homodimerization and obligate heterodimerization. We detected a signature of positive selection acting on residues preferentially clustered in predicted sites of contact between MADS-box monomers and dimers, and in motifs that mediate MADS PPI specificity in Arabidopsis. Changing one positively selected residue can alter PIL dimerization activity. Furthermore, ectopic expression of a Joinvillea PIL homodimer in Arabidopsis can homeotically transform sepals into petals. Our results provide a window into the evolutionary remodeling of PPIs, and show that novel interactions have the potential to alter plant form in a context-dependent manner. PMID:26908583

Jagged–Delta asymmetry in Notch signaling can give rise to a Sender/Receiver hybrid phenotype

PubMed Central

Boareto, Marcelo; Jolly, Mohit Kumar; Lu, Mingyang; Onuchic, José N.; Clementi, Cecilia; Ben-Jacob, Eshel

2015-01-01

Notch signaling pathway mediates cell-fate determination during embryonic development, wound healing, and tumorigenesis. This pathway is activated when the ligand Delta or the ligand Jagged of one cell interacts with the Notch receptor of its neighboring cell, releasing the Notch Intracellular Domain (NICD) that activates many downstream target genes. NICD affects ligand production asymmetrically––it represses Delta, but activates Jagged. Although the dynamical role of Notch–Jagged signaling remains elusive, it is widely recognized that Notch–Delta signaling behaves as an intercellular toggle switch, giving rise to two distinct fates that neighboring cells adopt––Sender (high ligand, low receptor) and Receiver (low ligand, high receptor). Here, we devise a specific theoretical framework that incorporates both Delta and Jagged in Notch signaling circuit to explore the functional role of Jagged in cell-fate determination. We find that the asymmetric effect of NICD renders the circuit to behave as a three-way switch, giving rise to an additional state––a hybrid Sender/Receiver (medium ligand, medium receptor). This phenotype allows neighboring cells to both send and receive signals, thereby attaining similar fates. We also show that due to the asymmetric effect of the glycosyltransferase Fringe, different outcomes are generated depending on which ligand is dominant: Delta-mediated signaling drives neighboring cells to have an opposite fate; Jagged-mediated signaling drives the cell to maintain a similar fate to that of its neighbor. We elucidate the role of Jagged in cell-fate determination and discuss its possible implications in understanding tumor–stroma cross-talk, which frequently entails Notch–Jagged communication. PMID:25605936

Efficient conceptual design for LED-based pixel light vehicle headlamps

NASA Astrophysics Data System (ADS)

Held, Marcel Philipp; Lachmayer, Roland

2017-12-01

High-resolution vehicle headlamps represent a future-oriented technology that can be used to increase traffic safety and driving comfort. As a further development to the current Matrix Beam headlamps, LED-based pixel light systems enable ideal lighting functions (e.g. projection of navigation information onto the road) to be activated in any given driving scenario. Moreover, compared to other light-modulating elements such as DMDs and LCDs, instantaneous LED on-off toggling provides a decisive advantage in efficiency. To generate highly individualized light distributions for automotive applications, a number of approaches using an LED array may be pursued. One approach is to vary the LED density in the array so as to output the desired light distribution. Another notable approach makes use of an equidistant arrangement of the individual LEDs together with distortion optics to formulate the desired light distribution. The optical system adjusts the light distribution in a manner that improves resolution and increases luminous intensity of the desired area. An efficient setup for pixel generation calls for one lens per LED. Taking into consideration the limited space requirements of the system, this implies that the luminous flux, efficiency and resolution image parameters are primarily controlled by the lens dimensions. In this paper a concept for an equidistant LED array arrangement utilizing distortion optics is presented. The paper is divided into two parts. The first part discusses the influence of lens geometry on the system efficiency whereas the second part investigates the correlation between resolution and luminous flux based on the lens dimensions.

Active Solvent Modulation: A Valve-Based Approach To Improve Separation Compatibility in Two-Dimensional Liquid Chromatography.

PubMed

Stoll, Dwight R; Shoykhet, Konstantin; Petersson, Patrik; Buckenmaier, Stephan

2017-09-05

Two-dimensional liquid chromatography (2D-LC) is increasingly being viewed as a viable tool for solving difficult separation problems, ranging from targeted separations of structurally similar molecules to untargeted separations of highly complex mixtures. In spite of this performance potential, though, many users find method development challenging and most frequently cite the "incompatibility" between the solvent systems used in the first and second dimensions as a major obstacle. This solvent strength related incompatibility can lead to severe peak distortion and loss of resolution and sensitivity in the second dimension. In this paper, we describe a novel approach to address the incompatibility problem, which we refer to as Active Solvent Modulation (ASM). This valve-based approach enables dilution of 1 D effluent with weak solvent prior to transfer to the 2 D column but without the need for additional instrument hardware. ASM is related to the concept we refer to as Fixed Solvent Modulation (FSM), with the important difference being that ASM allows toggling of the diluent stream during each 2 D separation cycle. In this work, we show that ASM eliminates the major drawbacks of FSM including complex elution solvent profiles, baseline disturbances, and slow 2 D re-equilibration and demonstrate improvements in 2 D separation quality using both simple small molecule probes and degradants of heat-treated bovine insulin as case studies. We believe that ASM will significantly ease method development for 2D-LC, providing a path to practical methods that involve both highly complementary 1 D and 2 D separations and sensitive detection.

Diagnostic report acquisition unit for the Mayo/IBM PACS project

NASA Astrophysics Data System (ADS)

Brooks, Everett G.; Rothman, Melvyn L.

1991-07-01

The Mayo Clinic and IBM Rochester have jointly developed a picture archive and control system (PACS) for use with Mayo's MRI and Neuro-CT imaging modalities. One of the challenges of developing a useful PACS involves integrating the diagnostic reports with the electronic images so they can be displayed simultaneously. By the time a diagnostic report is generated for a particular case, its images have already been captured and archived by the PACS. To integrate the report with the images, the authors have developed an IBM Personal System/2 computer (PS/2) based diagnostic report acquisition unit (RAU). A typed copy of the report is transmitted via facsimile to the RAU where it is stacked electronically with other reports that have been sent previously but not yet processed. By processing these reports at the RAU, the information they contain is integrated with the image database and a copy of the report is archived electronically on an IBM Application System/400 computer (AS/400). When a user requests a set of images for viewing, the report is automatically integrated with the image data. By using a hot key, the user can toggle on/off the report on the display screen. This report describes process, hardware, and software employed to integrate the diagnostic report information into the PACS, including how the report images are captured, transmitted, and entered into the AS/400 database. Also described is how the archived reports and their associated medical images are located and merged for retrieval and display. The methods used to detect and process error conditions are also discussed.

DNA Translator and Aligner: HyperCard utilities to aid phylogenetic analysis of molecules.

PubMed

Eernisse, D J

1992-04-01

DNA Translator and Aligner are molecular phylogenetics HyperCard stacks for Macintosh computers. They manipulate sequence data to provide graphical gene mapping, conversions, translations and manual multiple-sequence alignment editing. DNA Translator is able to convert documented GenBank or EMBL documented sequences into linearized, rescalable gene maps whose gene sequences are extractable by clicking on the corresponding map button or by selection from a scrolling list. Provided gene maps, complete with extractable sequences, consist of nine metazoan, one yeast, and one ciliate mitochondrial DNAs and three green plant chloroplast DNAs. Single or multiple sequences can be manipulated to aid in phylogenetic analysis. Sequences can be translated between nucleic acids and proteins in either direction with flexible support of alternate genetic codes and ambiguous nucleotide symbols. Multiple aligned sequence output from diverse sources can be converted to Nexus, Hennig86 or PHYLIP format for subsequent phylogenetic analysis. Input or output alignments can be examined with Aligner, a convenient accessory stack included in the DNA Translator package. Aligner is an editor for the manual alignment of up to 100 sequences that toggles between display of matched characters and normal unmatched sequences. DNA Translator also generates graphic displays of amino acid coding and codon usage frequency relative to all other, or only synonymous, codons for approximately 70 select organism-organelle combinations. Codon usage data is compatible with spreadsheet or UWGCG formats for incorporation of additional molecules of interest. The complete package is available via anonymous ftp and is free for non-commercial uses.

Neural circuit mechanisms of short-term memory

NASA Astrophysics Data System (ADS)

Goldman, Mark

Memory over time scales of seconds to tens of seconds is thought to be maintained by neural activity that is triggered by a memorized stimulus and persists long after the stimulus is turned off. This presents a challenge to current models of memory-storing mechanisms, because the typical time scales associated with cellular and synaptic dynamics are two orders of magnitude smaller than this. While such long time scales can easily be achieved by bistable processes that toggle like a flip-flop between a baseline and elevated-activity state, many neuronal systems have been observed experimentally to be capable of maintaining a continuum of stable states. For example, in neural integrator networks involved in the accumulation of evidence for decision making and in motor control, individual neurons have been recorded whose activity reflects the mathematical integral of their inputs; in the absence of input, these neurons sustain activity at a level proportional to the running total of their inputs. This represents an analog form of memory whose dynamics can be conceptualized through an energy landscape with a continuum of lowest-energy states. Such continuous attractor landscapes are structurally non-robust, in seeming violation of the relative robustness of biological memory systems. In this talk, I will present and compare different biologically motivated circuit motifs for the accumulation and storage of signals in short-term memory. Challenges to generating robust memory maintenance will be highlighted and potential mechanisms for ameliorating the sensitivity of memory networks to perturbations will be discussed. Funding for this work was provided by NIH R01 MH065034, NSF IIS-1208218, Simons Foundation 324260, and a UC Davis Ophthalmology Research to Prevent Blindness Grant.

Will New Metal Heads Restore Mechanical Integrity of Corroded Trunnions?

PubMed

Derasari, Aditya; Gold, Jonathan E; Ismaily, Sabir; Noble, Philip C; Incavo, Stephen J

2017-04-01

Metal wear and corrosion from modular junctions in total hip arthroplasty can lead to further unwanted surgery. Trunnion tribocorrosion is recognized as an important contributor to failure. This study was performed to determine if new metal heads restore mechanical integrity of the original modular junction after impaction on corroded trunnions, and assess which variables affect stability of the new interface created at revision total hip arthroplasty. Twenty-two trunnions, cobalt-chromium (CoCr) and titanium alloy (TiAIV), (CoCr, n = 12; TiAIV, n = 10) and new metal heads were used, 10 trunnions in pristine condition and 12 with corrosion damage. Test states were performed using an MTS Machine and included the following: 1, Assembly; 2, Disassembly; 3, Assembly; 4, Toggling; and 5, Disassembly. During loading, three-dimensional motion of the head-trunnion junction was measured using a custom jig. There were no statistical differences in the tested mechanical properties between corroded and pristine trunnions implanted with a new metal femoral head. Average micromotion of the head versus trunnion interface was greatest at the start of loading, stabilizing after approximately 50 loading cycles at an average of 30.6 ± 3.2 μm. Corrosion at the trunnion does not disrupt mechanical integrity of the junction when a CoCr head is replaced with a CoCr trunnion. However, increased interface motion of a new metal head on a corroded titanium trunnion requires additional study. The evaluation of ball head size on mechanical integrity of trunnions would also be a potential subject of future investigation, as increasing the ball head size at the time of revision is not uncommon in revisions today. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship between Ni(II) and Zn(II) Coordination and Nucleotide Binding by the Helicobacter pylori [NiFe]-Hydrogenase and Urease Maturation Factor HypB*

PubMed Central

Sydor, Andrew M.; Lebrette, Hugo; Ariyakumaran, Rishikesh; Cavazza, Christine; Zamble, Deborah B.

2014-01-01

The pathogen Helicobacter pylori requires two nickel-containing enzymes, urease and [NiFe]-hydrogenase, for efficient colonization of the human gastric mucosa. These enzymes possess complex metallocenters that are assembled by teams of proteins in multistep pathways. One essential accessory protein is the GTPase HypB, which is required for Ni(II) delivery to [NiFe]-hydrogenase and participates in urease maturation. Ni(II) or Zn(II) binding to a site embedded in the GTPase domain of HypB modulates the enzymatic activity, suggesting a mechanism of regulation. In this study, biochemical and structural analyses of H. pylori HypB (HpHypB) revealed an intricate link between nucleotide and metal binding. HpHypB nickel coordination, stoichiometry, and affinity were modulated by GTP and GDP, an effect not observed for zinc, and biochemical evidence suggests that His-107 coordination to nickel toggles on and off in a nucleotide-dependent manner. These results are consistent with the crystal structure of HpHypB loaded with Ni(II), GDP, and Pi, which reveals a nickel site distinct from that of zinc-loaded Methanocaldococcus jannaschii HypB as well as subtle changes to the protein structure. Furthermore, Cys-142, a metal ligand from the Switch II GTPase motif, was identified as a key component of the signal transduction between metal binding and the enzymatic activity. Finally, potassium accelerated the enzymatic activity of HpHypB but had no effect on the other biochemical properties of the protein. Altogether, this molecular level information about HpHypB provides insight into its cellular function and illuminates a possible mechanism of metal ion discrimination. PMID:24338018

Performance assessment of multi-frequency processing of ICU chest images for enhanced visualization of tubes and catheters

NASA Astrophysics Data System (ADS)

Wang, Xiaohui; Couwenhoven, Mary E.; Foos, David H.; Doran, James; Yankelevitz, David F.; Henschke, Claudia I.

2008-03-01

An image-processing method has been developed to improve the visibility of tube and catheter features in portable chest x-ray (CXR) images captured in the intensive care unit (ICU). The image-processing method is based on a multi-frequency approach, wherein the input image is decomposed into different spatial frequency bands, and those bands that contain the tube and catheter signals are individually enhanced by nonlinear boosting functions. Using a random sampling strategy, 50 cases were retrospectively selected for the study from a large database of portable CXR images that had been collected from multiple institutions over a two-year period. All images used in the study were captured using photo-stimulable, storage phosphor computed radiography (CR) systems. Each image was processed two ways. The images were processed with default image processing parameters such as those used in clinical settings (control). The 50 images were then separately processed using the new tube and catheter enhancement algorithm (test). Three board-certified radiologists participated in a reader study to assess differences in both detection-confidence performance and diagnostic efficiency between the control and test images. Images were evaluated on a diagnostic-quality, 3-megapixel monochrome monitor. Two scenarios were studied: the baseline scenario, representative of today's workflow (a single-control image presented with the window/level adjustments enabled) vs. the test scenario (a control/test image pair presented with a toggle enabled and the window/level settings disabled). The radiologists were asked to read the images in each scenario as they normally would for clinical diagnosis. Trend analysis indicates that the test scenario offers improved reading efficiency while providing as good or better detection capability compared to the baseline scenario.

Structural Basis for Parathyroid Hormone-related Protein Binding to the Parathyroid Hormone Receptor and Design of Conformation-selective Peptides

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

Pioszak, Augen A.; Parker, Naomi R.; Gardella, Thomas J.

2009-12-01

Parathyroid hormone (PTH) and PTH-related protein (PTHrP) are two related peptides that control calcium/phosphate homeostasis and bone development, respectively, through activation of the PTH/PTHrP receptor (PTH1R), a class B G protein-coupled receptor. Both peptides hold clinical interest for their capacities to stimulate bone formation. PTH and PTHrP display different selectivity for two distinct PTH1R conformations, but how their binding to the receptor differs is unclear. The high resolution crystal structure of PTHrP bound to the extracellular domain (ECD) of PTH1R reveals that PTHrP binds as an amphipathic {alpha}-helix to the same hydrophobic groove in the ECD as occupied by PTH,more » but in contrast to a straight, continuous PTH helix, the PTHrP helix is gently curved and C-terminally 'unwound.' The receptor accommodates the altered binding modes by shifting the side chain conformations of two residues within the binding groove: Leu-41 and Ile-115, the former acting as a rotamer toggle switch to accommodate PTH/PTHrP sequence divergence, and the latter adapting to the PTHrP curvature. Binding studies performed with PTH/PTHrP hybrid ligands having reciprocal exchanges of residues involved in different contacts confirmed functional consequences for the altered interactions and enabled the design of altered PTH and PTHrP peptides that adopt the ECD-binding mode of the opposite peptide. Hybrid peptides that bound the ECD poorly were selective for the G protein-coupled PTH1R conformation. These results establish a molecular model for better understanding of how two biologically distinct ligands can act through a single receptor and provide a template for designing better PTH/PTHrP therapeutics.« less

Bifocal liquid lens zoom objective for mobile phone applications

NASA Astrophysics Data System (ADS)

Wippermann, F. C.; Schreiber, P.; Bräuer, A.; Craen, P.

2007-02-01

Miniaturized camera systems are an integral part of today's mobile phones which recently possess auto focus functionality. Commercially available solutions without moving parts have been developed using the electrowetting technology. Here, the contact angle of a drop of a conductive or polar liquid placed on an insulating substrate can be influenced by an electric field. Besides the compensation of the axial image shift due to different object distances, mobile phones with zoom functionality are desired as a next evolutionary step. In classical mechanically compensated zoom lenses two independently driven actuators combined with precision guides are needed leading to a delicate, space consuming and expansive opto-mechanical setup. Liquid lens technology based on the electrowetting effect gives the opportunity to built adaptive lenses without moving parts thus simplifying the mechanical setup. However, with the recent commercially available liquid lens products a completely motionless and continuously adaptive zoom system with market relevant optical performance is not feasible. This is due to the limited change in optical power the liquid lenses can provide and the dispersion of the used materials. As an intermediate step towards a continuously adjustable and motionless zoom lens we propose a bifocal system sufficient for toggling between two effective focal lengths without any moving parts. The system has its mechanical counterpart in a bifocal zoom lens where only one lens group has to be moved. In a liquid lens bifocal zoom two groups of adaptable liquid lenses are required for adjusting the effective focal length and keeping the image location constant. In order to overcome the difficulties in achromatizing the lens we propose a sequential image acquisition algorithm. Here, the full color image is obtained from a sequence of monochrome images (red, green, blue) leading to a simplified optical setup.

A computer program for the simulation of folds of different sizes under the influence of gravity

NASA Astrophysics Data System (ADS)

Vacas Peña, José M.; Martínez Catalán, José R.

2004-02-01

Folding&g is a computer program, based on the finite element method, developed to simulate the process of natural folding from small to large scales in two dimensions. Written in Pascal code and compiled with Borland Delphi 3.0, the program has a friendly interactive user interface and can be used for research as well as educational purposes. Four main menu options allow the user to import or to build and to save a model data file, select the type of graphic output, introduce and modify several physical parameters and enter the calculation routines. The program employs isoparametric, initially rectangular elements with eight nodes, which can sustain large deformations. The mathematical procedure is based on the elasticity equations, but has been modified to simulate a viscous rheology, either linear or of power-law type. The parameters to be introduced include either the linear viscosity, or, when the viscosity is non-linear, the material constant, activation energy, temperature and power of the differential stress. All the parameters can be set by rows, which simulate layers. A toggle permits gravity to be introduced into the calculations. In this case, the density of the different rows must be specified, and the sizes of the finite elements and of the whole model become meaningful. Viscosity values can also be assigned to blocks of several rows and columns, which permits the modelling of heterogeneities such as rectangular areas of high strength, which can be used to simulate shearing components interfering with the buckling process. The program is applied to several cases of folding, including a single competent bed and multilayers, and its results compared with analytical and experimental results. The influence of gravity is illustrated by the modelling of diapiric structures and of a large recumbent fold.

Relationship between Ni(II) and Zn(II) coordination and nucleotide binding by the Helicobacter pylori [NiFe]-hydrogenase and urease maturation factor HypB.

PubMed

Sydor, Andrew M; Lebrette, Hugo; Ariyakumaran, Rishikesh; Cavazza, Christine; Zamble, Deborah B

2014-02-14

The pathogen Helicobacter pylori requires two nickel-containing enzymes, urease and [NiFe]-hydrogenase, for efficient colonization of the human gastric mucosa. These enzymes possess complex metallocenters that are assembled by teams of proteins in multistep pathways. One essential accessory protein is the GTPase HypB, which is required for Ni(II) delivery to [NiFe]-hydrogenase and participates in urease maturation. Ni(II) or Zn(II) binding to a site embedded in the GTPase domain of HypB modulates the enzymatic activity, suggesting a mechanism of regulation. In this study, biochemical and structural analyses of H. pylori HypB (HpHypB) revealed an intricate link between nucleotide and metal binding. HpHypB nickel coordination, stoichiometry, and affinity were modulated by GTP and GDP, an effect not observed for zinc, and biochemical evidence suggests that His-107 coordination to nickel toggles on and off in a nucleotide-dependent manner. These results are consistent with the crystal structure of HpHypB loaded with Ni(II), GDP, and Pi, which reveals a nickel site distinct from that of zinc-loaded Methanocaldococcus jannaschii HypB as well as subtle changes to the protein structure. Furthermore, Cys-142, a metal ligand from the Switch II GTPase motif, was identified as a key component of the signal transduction between metal binding and the enzymatic activity. Finally, potassium accelerated the enzymatic activity of HpHypB but had no effect on the other biochemical properties of the protein. Altogether, this molecular level information about HpHypB provides insight into its cellular function and illuminates a possible mechanism of metal ion discrimination.

A multicenter observer performance study of 3D JPEG2000 compression of thin-slice CT.

PubMed

Erickson, Bradley J; Krupinski, Elizabeth; Andriole, Katherine P

2010-10-01

The goal of this study was to determine the compression level at which 3D JPEG2000 compression of thin-slice CTs of the chest and abdomen-pelvis becomes visually perceptible. A secondary goal was to determine if residents in training and non-physicians are substantially different from experienced radiologists in their perception of compression-related changes. This study used multidetector computed tomography 3D datasets with 0.625-1-mm thickness slices of standard chest, abdomen, or pelvis, clipped to 12 bits. The Kakadu v5.2 JPEG2000 compression algorithm was used to compress and decompress the 80 examinations creating four sets of images: lossless, 1.5 bpp (8:1), 1 bpp (12:1), and 0.75 bpp (16:1). Two randomly selected slices from each examination were shown to observers using a flicker mode paradigm in which observers rapidly toggled between two images, the original and a compressed version, with the task of deciding whether differences between them could be detected. Six staff radiologists, four residents, and six PhDs experienced in medical imaging (from three institutions) served as observers. Overall, 77.46% of observers detected differences at 8:1, 94.75% at 12:1, and 98.59% at 16:1 compression levels. Across all compression levels, the staff radiologists noted differences 64.70% of the time, the resident's detected differences 71.91% of the time, and the PhDs detected differences 69.95% of the time. Even mild compression is perceptible with current technology. The ability to detect differences does not equate to diagnostic differences, although perception of compression artifacts could affect diagnostic decision making and diagnostic workflow.

Accurate chemical master equation solution using multi-finite buffers

DOE PAGES

Cao, Youfang; Terebus, Anna; Liang, Jie

2016-06-29

Here, the discrete chemical master equation (dCME) provides a fundamental framework for studying stochasticity in mesoscopic networks. Because of the multiscale nature of many networks where reaction rates have a large disparity, directly solving dCMEs is intractable due to the exploding size of the state space. It is important to truncate the state space effectively with quantified errors, so accurate solutions can be computed. It is also important to know if all major probabilistic peaks have been computed. Here we introduce the accurate CME (ACME) algorithm for obtaining direct solutions to dCMEs. With multifinite buffers for reducing the state spacemore » by $O(n!)$, exact steady-state and time-evolving network probability landscapes can be computed. We further describe a theoretical framework of aggregating microstates into a smaller number of macrostates by decomposing a network into independent aggregated birth and death processes and give an a priori method for rapidly determining steady-state truncation errors. The maximal sizes of the finite buffers for a given error tolerance can also be precomputed without costly trial solutions of dCMEs. We show exactly computed probability landscapes of three multiscale networks, namely, a 6-node toggle switch, 11-node phage-lambda epigenetic circuit, and 16-node MAPK cascade network, the latter two with no known solutions. We also show how probabilities of rare events can be computed from first-passage times, another class of unsolved problems challenging for simulation-based techniques due to large separations in time scales. Overall, the ACME method enables accurate and efficient solutions of the dCME for a large class of networks.« less

High spatial resolution upgrade of the electron cyclotron emission radiometer for the DIII-D tokamak

DOE PAGES

Truong, D. D.; Austin, M. E.

2014-11-01

The 40-channel DIII-D electron cyclotron emission (ECE) radiometer provides measurements of Te(r,t) at the tokamak midplane from optically thick, second harmonic X-mode emission over a frequency range of 83-130 GHz. Heterodyning divides this frequency range into three 2-18 GHz intermediate frequency (IF) bands. The frequency spacing of the radiometer’s channels results in a spatial resolution of ~1-3 cm, depending on local magnetic field and electron temperature. A new high resolution subsystem has been added to the DIII-D ECE radiometer to make sub-centimeter (0.6-0.8 cm) resolution Te measurements. The high resolution subsystem branches off from the regular channels’ IF bands andmore » consists of a microwave switch to toggle between IF bands, a switched filter bank for frequency selectivity, an adjustable local oscillator and mixer for further frequency down-conversion, and a set of eight microwave filters in the 2-4 GHz range. We achieved a higher spatial resolution through the use of a narrower (200 MHz) filter bandwidth and closer spacing between the filters’ center frequencies (250 MHz). This configuration allows for full coverage of the 83-130 GHz frequency range in 2 GHz bands. Depending on the local magnetic field, this translates into a “zoomed-in” analysis of a ~2-4 cm radial region. These high resolution channels will be most useful in the low-field side edge region where modest Te values (1-2 keV) result in a minimum of relativistic broadening. Some expected uses of these channels include mapping the spatial dependence of Alfven eigenmodes, geodesic acoustic modes, and externally applied magnetic perturbations. Initial Te measurements, which demonstrate that the desired resolution is achieved, is presented.« less

Electrostatic control of DNA intersegmental translocation by the ETS transcription factor ETV6.

PubMed

Vo, Tam; Wang, Shuo; Poon, Gregory M K; Wilson, W David

2017-08-11

To find their DNA target sites in complex solution environments containing excess heterogeneous DNA, sequence-specific DNA-binding proteins execute various translocation mechanisms known collectively as facilitated diffusion. For proteins harboring a single DNA contact surface, long-range translocation occurs by jumping between widely spaced DNA segments. We have configured biosensor-based surface plasmon resonance to directly measure the affinity and kinetics of this intersegmental jumping by the ETS-family transcription factor ETS variant 6 (ETV6). To isolate intersegmental target binding in a functionally defined manner, we pre-equilibrated ETV6 with excess salmon sperm DNA, a heterogeneous polymer, before exposing the nonspecifically bound protein to immobilized oligomeric DNA harboring a high-affinity ETV6 site. In this way, the mechanism of ETV6-target association could be toggled electrostatically through varying NaCl concentration in the bulk solution. Direct measurements of association and dissociation kinetics of the site-specific complex indicated that 1) freely diffusive binding by ETV6 proceeds through a nonspecific-like intermediate, 2) intersegmental jumping is rate-limited by dissociation from the nonspecific polymer, and 3) dissociation of the specific complex is independent of the history of complex formation. These results show that target searches by proteins with an ETS domain, such as ETV6, whose single DNA-binding domain cannot contact both source and destination sites simultaneously, are nonetheless strongly modulated by intersegmental jumping in heterogeneous site environments. Our findings establish biosensors as a general technique for directly and specifically measuring target site search by DNA-binding proteins via intersegmental translocation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Low Z target switching to increase tumor endothelial cell dose enhancement during gold nanoparticle-aided radiation therapy

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

Berbeco, Ross I., E-mail: rberbeco@partners.org; Detappe, Alexandre; Tsiamas, Panogiotis

2016-01-15

Purpose: Previous studies have introduced gold nanoparticles as vascular-disrupting agents during radiation therapy. Crucial to this concept is the low energy photon content of the therapy radiation beam. The authors introduce a new mode of delivery including a linear accelerator target that can toggle between low Z and high Z targets during beam delivery. In this study, the authors examine the potential increase in tumor blood vessel endothelial cell radiation dose enhancement with the low Z target. Methods: The authors use Monte Carlo methods to simulate delivery of three different clinical photon beams: (1) a 6 MV standard (Cu/W) beam,more » (2) a 6 MV flattening filter free (Cu/W), and (3) a 6 MV (carbon) beam. The photon energy spectra for each scenario are generated for depths in tissue-equivalent material: 2, 10, and 20 cm. The endothelial dose enhancement for each target and depth is calculated using a previously published analytic method. Results: It is found that the carbon target increases the proportion of low energy (<150 keV) photons at 10 cm depth to 28% from 8% for the 6 MV standard (Cu/W) beam. This nearly quadrupling of the low energy photon content incident on a gold nanoparticle results in 7.7 times the endothelial dose enhancement as a 6 MV standard (Cu/W) beam at this depth. Increased surface dose from the low Z target can be mitigated by well-spaced beam arrangements. Conclusions: By using the fast-switching target, one can modulate the photon beam during delivery, producing a customized photon energy spectrum for each specific situation.« less

TJC: HCOs need to be on alert for HIT problems related to sociotechnical factors, take steps to improve safety culture, process, and leadership.

PubMed

2015-06-01

Noting that too many errors related to health information technology (HIT) are resulting in adverse consequences, The Joint Commission (TJC) has issued a Sentinel Event Alert, urging health care providers to take steps to improve their safety culture, approach to process improvement, and leadership in this area. In this latest alert, the accrediting agency is taking particular aim at risks posed by sociotechnical factors--or the ways in which HIT is implemented and used. Experts say that many of these risks are, in fact, exemplified at a higher level in the emergency setting, where providers are under constant pressure to see more patients and move them though the system faster. In an analysis of 3,375 sentinel events that resulted in permanent patient harm or death between January 1, 2010, and June 20, 2013, The Joint Commission (TJC) found that 120 events included HIT-related contributing factors. Many of the problems cited by TJC relate to orders or medicines being prescribed for the wrong patients. These can result from toggling errors or pop-up screens where providers are asked to click on the appropriate patient or medicine, and they mistakenly click on the wrong selection. In the ED, experts recommend the creation of a multidisciplinary performance improvement group to continuously monitor the ED information system (EDIS), recognize problems, and work with the vendor to resolve them. Also important is a quick and easy way for providers to report HIT-related problems. Experts add that emergency providers need to be fully engaged in the process of selecting HIT that they will be using, and that health care organizations should arrange for usability assessments before purchasing HIT.

A DNA-Encapsulated and Fluorescent Ag 10 6+ Cluster with a Distinct Metal-Like Core

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

Petty, Jeffrey T.; Ganguly, Mainak; Rankine, Ian J.

Silver cluster–DNA complexes are optical chromophores, and pairs of these conjugates can be toggled from fluorescently dim to bright states using DNA hybridization. This paper highlights spectral and structural differences for a specific cluster pair. We have previously characterized a cluster with low emission and violet absorption that forms a compact structure with single-stranded oligonucleotides. We now consider its counterpart with blue absorption and strong green emission. This cluster develops with a single-stranded/duplex DNA construct and is favored by low silver concentrations with ≲8 Ag+:DNA, an oxygen atmosphere, and neutral pH. The resulting cluster displays key signatures of a molecularmore » metal with well-defined absorption/emission bands at 490/550 nm, and with a fluorescence quantum yield of 15% and lifetime of 2.4 ns. The molecular cluster conjugates with the larger DNA host because it chromatographically elutes with the DNA and it exhibits circular dichroism. The silver cluster is identified as Ag106+ using two modes of mass spectrometry and elemental analysis. Our key finding is that it adopts a low-dimensional shape, as determined from a Ag K-edge extended X-ray absorption fine structure analysis. The Ag0 in this oxidized cluster segregates from the Ag+ via a sparse number of metal-like bonds and a denser network of silver–DNA bonds. This structure contrasts with the compact, octahedral-like shape of the violet counterpart to the blue cluster, which is also a Ag106+ species. We consider that the blue- and violet-absorbing clusters may be isomers with shapes that are controlled by the secondary structures of their DNA templates.« less

User-centered design of quality of life reports for clinical care of patients with prostate cancer

PubMed Central

Izard, Jason; Hartzler, Andrea; Avery, Daniel I.; Shih, Cheryl; Dalkin, Bruce L.; Gore, John L.

2014-01-01

Background Primary treatment of localized prostate cancer can result in bothersome urinary, sexual, and bowel symptoms. Yet clinical application of health-related quality-of-life (HRQOL) questionnaires is rare. We employed user-centered design to develop graphic dashboards of questionnaire responses from patients with prostate cancer to facilitate clinical integration of HRQOL measurement. Methods We interviewed 50 prostate cancer patients and 50 providers, assessed literacy with validated instruments (Rapid Estimate of Adult Literacy in Medicine short form, Subjective Numeracy Scale, Graphical Literacy Scale), and presented participants with prototype dashboards that display prostate cancer-specific HRQOL with graphic elements derived from patient focus groups. We assessed dashboard comprehension and preferences in table, bar, line, and pictograph formats with patient scores contextualized with HRQOL scores of similar patients serving as a comparison group. Results Health literacy (mean score, 6.8/7) and numeracy (mean score, 4.5/6) of patient participants was high. Patients favored the bar chart (mean rank, 1.8 [P = .12] vs line graph [P <.01] vs table and pictograph); providers demonstrated similar preference for table, bar, and line formats (ranked first by 30%, 34%, and 34% of providers, respectively). Providers expressed unsolicited concerns over presentation of comparison group scores (n = 19; 38%) and impact on clinic efficiency (n = 16; 32%). Conclusion Based on preferences of prostate cancer patients and providers, we developed the design concept of a dynamic HRQOL dashboard that permits a base patient-centered report in bar chart format that can be toggled to other formats and include error bars that frame comparison group scores. Inclusion of lower literacy patients may yield different preferences. PMID:24787105

Domain alternation and active site remodeling are conserved structural features of ubiquitin E1.

PubMed

Lv, Zongyang; Yuan, Lingmin; Atkison, James H; Aldana-Masangkay, Grace; Chen, Yuan; Olsen, Shaun K

2017-07-21

E1 enzymes for ubiquitin (Ub) and Ub-like modifiers (Ubls) harbor two catalytic activities that are required for Ub/Ubl activation: adenylation and thioester bond formation. Structural studies of the E1 for the Ubl s mall u biquitin-like mo difier (SUMO) revealed a single active site that is transformed by a conformational switch that toggles its competency for catalysis of these two distinct chemical reactions. Although the mechanisms of adenylation and thioester bond formation revealed by SUMO E1 structures are thought to be conserved in Ub E1, there is currently a lack of structural data supporting this hypothesis. Here, we present a structure of Schizosaccharomyces pombe Uba1 in which the second catalytic cysteine half-domain (SCCH domain) harboring the catalytic cysteine has undergone a 106° rotation that results in a completely different network of intramolecular interactions between the SCCH and adenylation domains and translocation of the catalytic cysteine 12 Å closer to the Ub C terminus compared with previous Uba1 structures. SCCH domain alternation is accompanied by conformational changes within the Uba1 adenylation domains that effectively disassemble the adenylation active site. Importantly, the structural and biochemical data suggest that domain alternation and remodeling of the adenylation active site are interconnected and are intrinsic structural features of Uba1 and that the overall structural basis for adenylation and thioester bond formation exhibited by SUMO E1 is indeed conserved in Ub E1. Finally, the mechanistic insights provided by the novel conformational snapshot of Uba1 presented in this study may guide efforts to develop small molecule inhibitors of this critically important enzyme that is an active target for anticancer therapeutics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Accurate chemical master equation solution using multi-finite buffers

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

Cao, Youfang; Terebus, Anna; Liang, Jie

Here, the discrete chemical master equation (dCME) provides a fundamental framework for studying stochasticity in mesoscopic networks. Because of the multiscale nature of many networks where reaction rates have a large disparity, directly solving dCMEs is intractable due to the exploding size of the state space. It is important to truncate the state space effectively with quantified errors, so accurate solutions can be computed. It is also important to know if all major probabilistic peaks have been computed. Here we introduce the accurate CME (ACME) algorithm for obtaining direct solutions to dCMEs. With multifinite buffers for reducing the state spacemore » by $O(n!)$, exact steady-state and time-evolving network probability landscapes can be computed. We further describe a theoretical framework of aggregating microstates into a smaller number of macrostates by decomposing a network into independent aggregated birth and death processes and give an a priori method for rapidly determining steady-state truncation errors. The maximal sizes of the finite buffers for a given error tolerance can also be precomputed without costly trial solutions of dCMEs. We show exactly computed probability landscapes of three multiscale networks, namely, a 6-node toggle switch, 11-node phage-lambda epigenetic circuit, and 16-node MAPK cascade network, the latter two with no known solutions. We also show how probabilities of rare events can be computed from first-passage times, another class of unsolved problems challenging for simulation-based techniques due to large separations in time scales. Overall, the ACME method enables accurate and efficient solutions of the dCME for a large class of networks.« less

User-centered design of quality of life reports for clinical care of patients with prostate cancer.

PubMed

Izard, Jason; Hartzler, Andrea; Avery, Daniel I; Shih, Cheryl; Dalkin, Bruce L; Gore, John L

2014-05-01

Primary treatment of localized prostate cancer can result in bothersome urinary, sexual, and bowel symptoms. Yet clinical application of health-related quality-of-life (HRQOL) questionnaires is rare. We employed user-centered design to develop graphic dashboards of questionnaire responses from patients with prostate cancer to facilitate clinical integration of HRQOL measurement. We interviewed 50 prostate cancer patients and 50 providers, assessed literacy with validated instruments (Rapid Estimate of Adult Literacy in Medicine short form, Subjective Numeracy Scale, Graphical Literacy Scale), and presented participants with prototype dashboards that display prostate cancer-specific HRQOL with graphic elements derived from patient focus groups. We assessed dashboard comprehension and preferences in table, bar, line, and pictograph formats with patient scores contextualized with HRQOL scores of similar patients serving as a comparison group. Health literacy (mean score, 6.8/7) and numeracy (mean score, 4.5/6) of patient participants was high. Patients favored the bar chart (mean rank, 1.8 [P = .12] vs line graph [P < .01] vs table and pictograph); providers demonstrated similar preference for table, bar, and line formats (ranked first by 30%, 34%, and 34% of providers, respectively). Providers expressed unsolicited concerns over presentation of comparison group scores (n = 19; 38%) and impact on clinic efficiency (n = 16; 32%). Based on preferences of prostate cancer patients and providers, we developed the design concept of a dynamic HRQOL dashboard that permits a base patient-centered report in bar chart format that can be toggled to other formats and include error bars that frame comparison group scores. Inclusion of lower literacy patients may yield different preferences. Copyright © 2014 Mosby, Inc. All rights reserved.

Ribosomal frameshifting and dual-target antiactivation restrict quorum-sensing-activated transfer of a mobile genetic element.

PubMed

Ramsay, Joshua P; Tester, Laura G L; Major, Anthony S; Sullivan, John T; Edgar, Christina D; Kleffmann, Torsten; Patterson-House, Jackson R; Hall, Drew A; Tate, Warren P; Hynes, Michael F; Ronson, Clive W

2015-03-31

Symbiosis islands are integrative and conjugative mobile genetic elements that convert nonsymbiotic rhizobia into nitrogen-fixing symbionts of leguminous plants. Excision of the Mesorhizobium loti symbiosis island ICEMlSym(R7A) is indirectly activated by quorum sensing through TraR-dependent activation of the excisionase gene rdfS. Here we show that a +1 programmed ribosomal frameshift (PRF) fuses the coding sequences of two TraR-activated genes, msi172 and msi171, producing an activator of rdfS expression named Frameshifted excision activator (FseA). Mass-spectrometry and mutational analyses indicated that the PRF occurred through +1 slippage of the tRNA(phe) from UUU to UUC within a conserved msi172-encoded motif. FseA activated rdfS expression in the absence of ICEMlSym(R7A), suggesting that it directly activated rdfS transcription, despite being unrelated to any characterized DNA-binding proteins. Bacterial two-hybrid and gene-reporter assays demonstrated that FseA was also bound and inhibited by the ICEMlSym(R7A)-encoded quorum-sensing antiactivator QseM. Thus, activation of ICEMlSym(R7A) excision is counteracted by TraR antiactivation, ribosomal frameshifting, and FseA antiactivation. This robust suppression likely dampens the inherent biological noise present in the quorum-sensing autoinduction circuit and ensures that ICEMlSym(R7A) transfer only occurs in a subpopulation of cells in which both qseM expression is repressed and FseA is translated. The architecture of the ICEMlSym(R7A) transfer regulatory system provides an example of how a set of modular components have assembled through evolution to form a robust genetic toggle that regulates gene transcription and translation at both single-cell and cell-population levels.

Ribosomal frameshifting and dual-target antiactivation restrict quorum-sensing–activated transfer of a mobile genetic element

PubMed Central

Ramsay, Joshua P.; Tester, Laura G. L.; Major, Anthony S.; Sullivan, John T.; Edgar, Christina D.; Kleffmann, Torsten; Patterson-House, Jackson R.; Hall, Drew A.; Tate, Warren P.; Hynes, Michael F.; Ronson, Clive W.

2015-01-01

Symbiosis islands are integrative and conjugative mobile genetic elements that convert nonsymbiotic rhizobia into nitrogen-fixing symbionts of leguminous plants. Excision of the Mesorhizobium loti symbiosis island ICEMlSymR7A is indirectly activated by quorum sensing through TraR-dependent activation of the excisionase gene rdfS. Here we show that a +1 programmed ribosomal frameshift (PRF) fuses the coding sequences of two TraR-activated genes, msi172 and msi171, producing an activator of rdfS expression named Frameshifted excision activator (FseA). Mass-spectrometry and mutational analyses indicated that the PRF occurred through +1 slippage of the tRNAphe from UUU to UUC within a conserved msi172-encoded motif. FseA activated rdfS expression in the absence of ICEMlSymR7A, suggesting that it directly activated rdfS transcription, despite being unrelated to any characterized DNA-binding proteins. Bacterial two-hybrid and gene-reporter assays demonstrated that FseA was also bound and inhibited by the ICEMlSymR7A-encoded quorum-sensing antiactivator QseM. Thus, activation of ICEMlSymR7A excision is counteracted by TraR antiactivation, ribosomal frameshifting, and FseA antiactivation. This robust suppression likely dampens the inherent biological noise present in the quorum-sensing autoinduction circuit and ensures that ICEMlSymR7A transfer only occurs in a subpopulation of cells in which both qseM expression is repressed and FseA is translated. The architecture of the ICEMlSymR7A transfer regulatory system provides an example of how a set of modular components have assembled through evolution to form a robust genetic toggle that regulates gene transcription and translation at both single-cell and cell-population levels. PMID:25787256

Micro-Ball-Lens Optical Switch Driven by SMA Actuator

NASA Technical Reports Server (NTRS)

Yang, Eui-Hyeok

2003-01-01

The figure is a simplified cross section of a microscopic optical switch that was partially developed at the time of reporting the information for this article. In a fully developed version, light would be coupled from an input optical fiber to one of two side-by-side output optical fibers. The optical connection between the input and the selected output fiber would be made via a microscopic ball lens. Switching of the optical connection from one output fiber to another would be effected by using a pair of thin-film shape-memory-alloy (SMA) actuators to toggle the lens between two resting switch positions. There are many optical switches some made of macroscopic parts by conventional fabrication techniques and some that are microfabricated and, hence, belong to the class of microelectromechanical systems (MEMS). Conventionally fabricated optical switches tend to be expensive. MEMS switches can be mass-produced at relatively low cost, but their attractiveness has been diminished by the fact that, heretofore, MEMS switches have usually been found to exhibit high insertion losses. The present switch is intended to serve as a prototype of low-loss MEMS switches. In addition, this is the first reported SMA-based optical switch. The optical fibers would be held in V grooves in a silicon frame. The lens would have a diameter of 1 m; it would be held by, and positioned between, the SMA actuators, which would be made of thin films of TiNi alloy. Although the SMA actuators are depicted here as having simple shapes for the sake of clarity of illustration, the real actuators would have complex, partly net-like shapes. With the exception of the lens and the optical fibers, the SMA actuators and other components of the switch would be made by microfabrication techniques. The components would be assembled into a sandwich structure to complete the fabrication of the switch. To effect switching, an electric current would be passed through one of the SMA actuators to heat it above its transition temperature, thereby causing it to deform to a different "remembered" shape. The two SMA actuators would be stiff enough that once switching had taken place and the electrical current was turned off, the lens would remain latched in the most recently selected position. In a test, the partially developed switch exhibited an insertion loss of only -1.9 dB and a switching contrast of 70 dB. One the basis of prior research on SMA actuators and assuming a lens displacement of 125 m between extreme positions, it has been estimated that the fully developed switch would be capable of operating at a frequency as high as 10 Hz.

Operation and Management of Thermostatically Controlled Loads for Providing Regulation Services to Power Grids

NASA Astrophysics Data System (ADS)

Vanouni, Maziar

The notion of demand-side participation in power systems operation and control is on the verge of realization because of the advancement in the required technologies an tools like communications, smart meters, sensor networks, large data management techniques, large scale optimization method, etc. Therefore, demand-response (DR) programs can be one of the prosperous solutions to accommodate part of the increasing demand for load balancing services which is brought about by the high penetration of intermittent renewable energies in power systems. This dissertation studies different aspects of the DR programs that utilized the thermostatically controlled loads (TCLs) to provide load balancing services. The importance of TCLs among the other loads lie on their flexibility in power consumption pattern while the customer/end-user comfort is not (or minimally) impacted. Chapter 2 discussed a previously presented direct load control (DLC) to control the power consumption of aggregated TCLs. The DLC method performs a power tracking control and based on central approach where a central controller broadcasts the control command to the dispersed TCLs to toggle them on/off. The central controller receives measurement feedback from the TCLs once per couple of minutes to run a successful forecast process. The performance evaluation criteria to evaluate the load balancing service provided by the TCLs are presented. The results are discussed under different scenarios and situation. The numerical results show the proper performance of the DLC method. This DLC method is used as the control method in all the studies in this dissertation. Chapter 3 presents performance improvements for the original method in Chapter 2 by communicating two more pieces of information called forecast parameters (FPs). Communicating improves the forecast process in the DLC and hence, both performance accuracy and the amount of tear-and-wear imposed on the TCLs. Chapter 4 formulates a stochastic optimization model for a load aggregator (LA) to participate in the performance-based regulation markets (PBRM). PBRMs are the recently developed and practiced regulation market structure recommended by Federal Energy Regulatory Commission (FERC) in 2011. In PBRMs, regulation resources are paid based on both regulation capacity bids and the regulation performance including the provided mileage and the performance accuracy. In order to develop the income from the PBRM, the convention of California Independent System Operator (CAISO) is used. In the presented optimization model, the amount of tear-and-wear imposed on the TCLs are confined to prevent abrupt switching of TCLs. In Chapter 5, a two-stage reward allocation mechanism is developed for a LA recruiting TCLs for regulation service provision. The mechanism helps the LA to distribute the total reward (earned from regulation service provision) among the TCLs according to their contribution in the whole provided service. In the first stage, TCLs are prioritized based on their service provision capability. In order to do so, an index called SPCI is presented to quantify TCLs capability/flexibility and therefore, prioritize them. After prioritization TCLs a priority list is constructed in the first stage. In the second stage, a reward curve is constructed representing the functionality of the possible total reward with respect to the number top TCLs in the priority list. Then, the allocated reward to individual TCLs is calculated by applying the incremental method on the constructed reward curve. This presented reward allocation mechanism is based on the definition of maximum service capacity (MSC) for a control group including TCLs. MSC is defined and its calculation method is presented before discussing the two stages of the reward allocation mechanism. The numerical results proves the suitability of the proposed prioritization method as it is observed the TCLs with higher rankings can contribute more to the total reward in comparison to the TCLs with lower rankings in the priority list.

Estimates of RF-Induced Erosion at Antenna-Connected Beryllium Plasma-Facing Components in JET

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

Borodin, D.; Groth, M.; Airila, M.

2016-01-01

During high-power, ion cyclotron resonance heating (ICRH), RF sheath rectification and RF induced plasma-wall interactions (RF-PWI) can potentially limit long-pulse operation. With toroidally-spaced ICRH antennas, in an ITER-like wall (ILW) environment, JET provides an ideal environment for ITER-relevant, RF-PWI studies. JET pulses combining sequential toggling of the antennas with q95 (edge safety factor) sweeping were recently used to localize RF-enhanced Be I and Be II spectral line emission at outboard poloidal (beryllium) limiters. These measurements were carried out in the early stages of JET-ILW and in ICRF-only, L-mode discharges. The appearance of enhanced emission spots was explained by their magneticmore » connection to regions of ICRH antennas associated with higher RF-sheath rectification [1]. The measured emission lines were the same as those already qualified in ERO modelling of inboard limiter beryllium erosion in JET limiter plasmas [2]. In the present work, we revisit this spectroscopic study with the focus on obtaining estimates of the impact of these RF-PWI on sputtering and on net erosion of the affected limiter regions. To do this, the ERO erosion and re-deposition code [2] is deployed with the detailed geometry of a JET outboard limiter. The effect of RF-PWI on sputtering is represented by varying the surface negative biasing, which affects the incidence energy and the resulting sputtering yield. The observed variations in line emission, from [1], for JET pulse 81173 of about factor 3 can be reproduced with ~ 100 200 V bias. ERO simulations show that the influence of the respective E-field on the local Be transport is localized near the surface and relatively small. Still, the distribution of the 3D plasma parameters, shadowing and other geometrical effects are quite important. The plasma parameter simulated by Edge2D-EIRENE [3] are extrapolated towards the surface and mapped in 3D. These initial modelling results are consistent with the range of potentials anticipated through RF sheath rectification (see, e.g., [4]). Shortcomings from both the modelling and experimental side will be discussed, as will be plans for improvements in both areas method for the upcoming 2015 - 2016 JET campaign. [1] C.C. Klepper et al., J. Nucl. Mater. 438 (2013) S594 S598 [2] D. Borodin et al., Phys. Scr. T159 (2014) 014057 [3] M. Groth et al., Nucl. Fusion 53 (2013) 093016 [4] Jonathan Jacquot et al., Phys. Plasmas 21 (2014) 061509 *Corresponding author: presently at CCFE (UK) tel.: +44 1235 46 4304, e-mail: kleppercc@ornl.gov **See the Appendix of F. Romanelli et al., Proc. of the 25th IAEA Fusion Energy Conference 2014, Saint Petersburg, Russia Work supported, in part, by US DOE under Contract DE-AC05-00OR22725 with UT-Battelle, LLC.« less

MapApp: A Java(TM) Applet for Accessing Geographic Databases

NASA Astrophysics Data System (ADS)

Haxby, W.; Carbotte, S.; Ryan, W. B.; OHara, S.

2001-12-01

MapApp (http://coast.ldeo.columbia.edu/help/MapApp.html) is a prototype Java(TM) applet that is intended to give easy and versatile access to geographic data sets through a web browser. It was developed initially to interface with the RIDGE Multibeam Synthesis. Subsequently, interfaces with other geophysical databases were added. At present, multibeam bathymetry grids, underway geophysics along ship tracks, and the LDEO Borehole Research Group's ODP well logging database are accessible through MapApp. We plan to add an interface with the Ridge Petrology Database in the near future. The central component of MapApp is a world physiographic map. Users may navigate around the map (zoom/pan) without waiting for HTTP requests to a remote server to be processed. A focus request loads image tiles from the server to compose a new map at the current viewing resolution. Areas in which multibeam grids are available may be focused to a pixel resolution of about 200 m. These areas may be identified by toggling a mask. Databases may be accessed through menus, and selected data objects may be loaded into MapApp by selecting items from tables. Once loaded, a bathymetry grid may be contoured or used to create bathymetric profiles; ship tracks and ODP sites may be overlain on the map and their geophysical data plotted in X-Y graphs. The advantage of applets over traditional web pages is that they permit dynamic interaction with data sets, while limiting time consuming interaction with a remote server. Users may customize the graphics display by modifying the scale, or the symbol or line characteristics of rendered data, contour interval, etc. The ease with which users can select areas, view the physiography of areas, and preview data sets and evaluate them for quality and applicability, makes MapApp a valuable tool for education and research.

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

Yewondwossen, M; Robar, J; Parsons, D

Purpose: During radiotherapy treatment, lung tumors can display substantial respiratory motion. This motion usually necessitates enlarged treatment margins to provide full tumour coverage. Unfortunately, these margins limit the dose that can be prescribed for tumour control and cause complications to normal tissue. Options for real-time methods of direct detection of tumour position, and particularly those that obviate the need for inserted fiducial markers, are limited. We propose a method of tumor tracking without implanted fiducial markers using a novel fast switching-target that toggles between a FFF copper/tungsten therapy mode and a FFF low-Z target mode for imaging. In this workmore » we demonstrate proof-of-concept of this new technology. Methods: The prototype includes two targets: i) a FFF copper/tungsten target equivalent to that in the Varian 2100 EX 6 MV, and ii) a low-Z (carbon) target with a thickness of 110% of continuous slowing down approximation range (CSDA) at 7 MeV. The two targets can be exchanged with a custom made linear slide and motor-driven actuator. The usefulness of the switching-target concept is demonstrated through experimental BEV Planar images acquired with continual treatment and imaging at a user-defined period. Results: The prototype switching-target demonstrates that two recent advances in linac technology (FFF target for therapy and low-Z target) can be combined with synergy. The switching-target approach offers the capacity for rapid switching between treatment and high-contrast imaging modes, allowing intrafractional tracking, as demonstrated in this work with dynamic breathing phantom. By using a single beam-line, the design is streamlined and may obviate the need for an auxiliary imaging system (e.g., kV OBI.) Conclusion: This switching-target approach is a feasible combination of two current advances in linac technology (FFF target for therapy and a FFF low-Z target) allowing new options in on-line IGRT.« less

A Lipid Pathway for Ligand Binding Is Necessary for a Cannabinoid G Protein-coupled Receptor*

PubMed Central

Hurst, Dow P.; Grossfield, Alan; Lynch, Diane L.; Feller, Scott; Romo, Tod D.; Gawrisch, Klaus; Pitman, Michael C.; Reggio, Patricia H.

2010-01-01

Recent isothiocyanate covalent labeling studies have suggested that a classical cannabinoid, (−)-7′-isothiocyanato-11-hydroxy-1′,1′dimethylheptyl-hexahydrocannabinol (AM841), enters the cannabinoid CB2 receptor via the lipid bilayer (Pei, Y., Mercier, R. W., Anday, J. K., Thakur, G. A., Zvonok, A. M., Hurst, D., Reggio, P. H., Janero, D. R., and Makriyannis, A. (2008) Chem. Biol. 15, 1207–1219). However, the sequence of steps involved in such a lipid pathway entry has not yet been elucidated. Here, we test the hypothesis that the endogenous cannabinoid sn-2-arachidonoylglycerol (2-AG) attains access to the CB2 receptor via the lipid bilayer. To this end, we have employed microsecond time scale all-atom molecular dynamics (MD) simulations of the interaction of 2-AG with CB2 via a palmitoyl-oleoyl-phosphatidylcholine lipid bilayer. Results suggest the following: 1) 2-AG first partitions out of bulk lipid at the transmembrane α-helix (TMH) 6/7 interface; 2) 2-AG then enters the CB2 receptor binding pocket by passing between TMH6 and TMH7; 3) the entrance of the 2-AG headgroup into the CB2 binding pocket is sufficient to trigger breaking of the intracellular TMH3/6 ionic lock and the movement of the TMH6 intracellular end away from TMH3; and 4) subsequent to protonation at D3.49/D6.30, further 2-AG entry into the ligand binding pocket results in both a W6.48 toggle switch change and a large influx of water. To our knowledge, this is the first demonstration via unbiased molecular dynamics that a ligand can access the binding pocket of a class A G protein-coupled receptor via the lipid bilayer and the first demonstration via molecular dynamics of G protein-coupled receptor activation triggered by a ligand binding event. PMID:20220143

Using a preclinical mouse model of high-grade astrocytoma to optimize p53 restoration therapy.

PubMed

Shchors, Ksenya; Persson, Anders I; Rostker, Fanya; Tihan, Tarik; Lyubynska, Natalya; Li, Nan; Swigart, Lamorna Brown; Berger, Mitchel S; Hanahan, Douglas; Weiss, William A; Evan, Gerard I

2013-04-16

Based on clinical presentation, glioblastoma (GBM) is stratified into primary and secondary types. The protein 53 (p53) pathway is functionally incapacitated in most GBMs by distinctive type-specific mechanisms. To model human gliomagenesis, we used a GFAP-HRas(V12) mouse model crossed into the p53ER(TAM) background, such that either one or both copies of endogenous p53 is replaced by a conditional p53ER(TAM) allele. The p53ER(TAM) protein can be toggled reversibly in vivo between wild-type and inactive conformations by administration or withdrawal of 4-hydroxytamoxifen (4-OHT), respectively. Surprisingly, gliomas that develop in GFAP-HRas(V12);p53(+/KI) mice abrogate the p53 pathway by mutating p19(ARF)/MDM2 while retaining wild-type p53 allele. Consequently, such tumors are unaffected by restoration of their p53ER(TAM) allele. By contrast, gliomas arising in GFAP-HRas(V12);p53(KI/KI) mice develop in the absence of functional p53. Such tumors retain a functional p19(ARF)/MDM2-signaling pathway, and restoration of p53ER(TAM) allele triggers p53-tumor-suppressor activity. Congruently, growth inhibition upon normalization of mutant p53 by a small molecule, Prima-1, in human GBM cultures also requires p14(ARF)/MDM2 functionality. Notably, the antitumoral efficacy of p53 restoration in tumor-bearing GFAP-HRas(V12);p53(KI/KI) animals depends on the duration and frequency of p53 restoration. Thus, intermittent exposure to p53ER(TAM) activity mitigated the selective pressure to inactivate the p19(ARF)/MDM2/p53 pathway as a means of resistance, extending progression-free survival. Our results suggest that intermittent dosing regimes of drugs that restore wild-type tumor-suppressor function onto mutant, inactive p53 proteins will prove to be more efficacious than traditional chronic dosing by similarly reducing adaptive resistance.

Influence of mechanical rock properties and fracture healing rate on crustal fluid flow dynamics

NASA Astrophysics Data System (ADS)

Sachau, Till; Bons, Paul; Gomez-Rivas, Enrique; Koehn, Daniel; de Riese, Tamara

2016-04-01

Fluid flow in the Earth's crust is very slow over extended periods of time, during which it occurs within the connected pore space of rocks. If the fluid production rate exceeds a certain threshold, matrix permeability alone is insufficient to drain the fluid volume and fluid pressure builds up, thereby reducing the effective stress supported by the rock matrix. Hydraulic fractures form once the effective pressure exceeds the tensile strength of the rock matrix and act subsequently as highly effective fluid conduits. Once local fluid pressure is sufficiently low again, flow ceases and fractures begin to heal. Since fluid flow is controlled by the alternation of fracture permeability and matrix permeability, the flow rate in the system is strongly discontinuous and occurs in intermittent pulses. Resulting hydraulic fracture networks are largely self-organized: opening and subsequent healing of hydraulic fractures depends on the local fluid pressure and on the time-span between fluid pulses. We simulate this process with a computer model and describe the resulting dynamics statistically. Special interest is given to a) the spatially and temporally discontinuous formation and closure of fractures and fracture networks and b) the total flow rate over time. The computer model consists of a crustal-scale dual-porosity setup. Control parameters are the pressure- and time-dependent fracture healing rate, and the strength and the permeability of the intact rock. Statistical analysis involves determination of the multifractal properties and of the power spectral density of the temporal development of the total drainage rate and hydraulic fractures. References Bons, P. D. (2001). The formation of large quartz veins by rapid ascent of fluids in mobile hydrofractures. Tectonophysics, 336, 1-17. Miller, S. a., & Nur, A. (2000). Permeability as a toggle switch in fluid-controlled crustal processes. Earth and Planetary Science Letters, 183(1-2), 133-146. Sachau, T., Bons, P. D., & Gomez-Rivas, E. (2015). Transport efficiency and dynamics of hydraulic fracture networks. Frontiers in Physics, 3.

Biomechanical validation of finite element models for two silicone metacarpophalangeal joint implants.

PubMed

Hussein, A I; Stranart, J C; Meguid, S A; Bogoch, E R

2011-02-01

Silicone implants are used for prosthetic arthroplasty of metacarpophalangeal (MCP) joints severely damaged by rheumatoid arthritis. Different silicone elastomer MCP implant designs have been developed, including the Swanson and the NeuFlex implants. The goal of this study was to compare the in vitro mechanical behavior of Swanson and NeuFlex MCP joint implants. Three-dimensional (3D) finite element (FE) models of the silicone implants were modeled using the commercial software ANSYS and subjected to angular displacement from 0 deg to 90 deg. FE models were validated using mechanical tests of implants incrementally bent from 0 deg to 90 deg in a joint simulator. Swanson size 2 and 4 implants were compared with NeuFlex size 10 and 30 implants, respectively. Good agreement was observed throughout the range of motion for the flexion bending moment derived from 3D FE models and mechanical tests. From 30 deg to 90 deg, the Swanson 2 demonstrated a greater resistance to deformation than the NeuFlex 10 and required a greater bending moment for joint flexion. For larger implant sizes, the NeuFlex 30 had a steeper moment-displacement curve, but required a lower moment than the Swanson 4, due to implant preflexion. On average, the stress generated at the implant hinge from 30 deg to 90 deg was lower in the NeuFlex than in the Swanson. On average, starting from the neutral position of 30 deg for the preflexed NeuFlex implant, higher moments were required to extend the NeuFlex implants to 0 deg compared with the Swanson implants, which returned spontaneously to resting position. Implant toggling within the medullary canals was less in the NeuFlex than in the Swanson. The differential performance of these implants may be useful in implant selection based on the preoperative condition(s) of the joint and specific patient functional needs.

Using a preclinical mouse model of high-grade astrocytoma to optimize p53 restoration therapy

PubMed Central

Shchors, Ksenya; Persson, Anders I.; Rostker, Fanya; Tihan, Tarik; Lyubynska, Natalya; Li, Nan; Swigart, Lamorna Brown; Berger, Mitchel S.; Hanahan, Douglas; Weiss, William A.; Evan, Gerard I.

2013-01-01

Based on clinical presentation, glioblastoma (GBM) is stratified into primary and secondary types. The protein 53 (p53) pathway is functionally incapacitated in most GBMs by distinctive type-specific mechanisms. To model human gliomagenesis, we used a GFAP-HRasV12 mouse model crossed into the p53ERTAM background, such that either one or both copies of endogenous p53 is replaced by a conditional p53ERTAM allele. The p53ERTAM protein can be toggled reversibly in vivo between wild-type and inactive conformations by administration or withdrawal of 4-hydroxytamoxifen (4-OHT), respectively. Surprisingly, gliomas that develop in GFAP-HRasV12;p53+/KI mice abrogate the p53 pathway by mutating p19ARF/MDM2 while retaining wild-type p53 allele. Consequently, such tumors are unaffected by restoration of their p53ERTAM allele. By contrast, gliomas arising in GFAP-HRasV12;p53KI/KI mice develop in the absence of functional p53. Such tumors retain a functional p19ARF/MDM2-signaling pathway, and restoration of p53ERTAM allele triggers p53-tumor–suppressor activity. Congruently, growth inhibition upon normalization of mutant p53 by a small molecule, Prima-1, in human GBM cultures also requires p14ARF/MDM2 functionality. Notably, the antitumoral efficacy of p53 restoration in tumor-bearing GFAP-HRasV12;p53KI/KI animals depends on the duration and frequency of p53 restoration. Thus, intermittent exposure to p53ERTAM activity mitigated the selective pressure to inactivate the p19ARF/MDM2/p53 pathway as a means of resistance, extending progression-free survival. Our results suggest that intermittent dosing regimes of drugs that restore wild-type tumor-suppressor function onto mutant, inactive p53 proteins will prove to be more efficacious than traditional chronic dosing by similarly reducing adaptive resistance. PMID:23542378

Polarization and propagation characteristics of switchable first-order azimuthally asymmetric beam generated in dual-mode fiber.

PubMed

Khan, Saba N; Chatterjee, Sudip K; Chaudhuri, Partha Roy

2015-02-20

We report here the controlled generation of a linearly polarized first-order azimuthally asymmetric beam (F-AAB) in a dual-mode fiber (DMF) by appropriate superposition of selectively excited zeroth-order vector modes that are doughnut-shaped azimuthally symmetric beams (D-ASBs). We first demonstrate continually switching polarization mode structures having an identical two-lobe intensity profile (i.e., intra-F-AAB conversion). Then, under a distinct launching state, we generate mode structures progressively toggling between the doughnut-shaped profile and two-lobe pattern having dissimilar polarization orientations (i.e., F-AAB to D-ASB conversion). Interestingly, a decentralized elliptical Gaussian beam possessing homogenous spatial polarization is obtained by enhancing the contribution of the fundamental mode (HE₁₁/LP₀₁) in selectively excited F-AAB. A smoothly varying azimuth of the input beam in this situation resulted in redistribution of transverse energy procuring a unique and exciting unconventional two-grain T-polarized beam having mutually orthogonal state of polarization (SOP). All of the above three were achieved under a given set of launching conditions (tilt/offset) of a Gaussian mode (TEM₀₀) devised with changing SOP of the input beam. A strong modulation in the output beam characteristics was also observed with the variation in propagation distance (for a fixed input SOP) owing to the large difference in propagation constants of the participating modes (LP₀₁ and one of the F-AABs). Finally, this particular study led to a design for a low-cost highly sensitive strain measuring device based on tracking the centroid movement of the output intensity pattern. Each of our experimentally observed intensity/polarization distributions is theoretically mapped on a one-to-one basis considering a linear superposition of appropriately excited LP basis modes of the waveguide toward a complete understanding of the polarization and mode propagation in the dual-mode structure.

Design and synthesis of vanadium hydrazide gels for Kubas-type hydrogen adsorption: a new class of hydrogen storage materials.

PubMed

Hoang, Tuan K A; Webb, Michael I; Mai, Hung V; Hamaed, Ahmad; Walsby, Charles J; Trudeau, Michel; Antonelli, David M

2010-08-25

In this paper we demonstrate that the Kubas interaction, a nondissociative form of weak hydrogen chemisorption with binding enthalpies in the ideal 20-30 kJ/mol range for room-temperature hydrogen storage, can be exploited in the design of a new class of hydrogen storage materials which avoid the shortcomings of hydrides and physisorpion materials. This was accomplished through the synthesis of novel vanadium hydrazide gels that use low-coordinate V centers as the principal Kubas H(2) binding sites with only a negligible contribution from physisorption. Materials were synthesized at vanadium-to-hydrazine ratios of 4:3, 1:1, 1:1.5, and 1:2 and characterized by X-ray powder diffraction, X-ray photoelectron spectroscopy, nitrogen adsorption, elemental analysis, infrared spectroscopy, and electron paramagnetic resonance spectroscopy. The material with the highest capacity possesses an excess reversible storage of 4.04 wt % at 77 K and 85 bar, corresponding to a true volumetric adsorption of 80 kg H(2)/m(3) and an excess volumetric adsorption of 60.01 kg/m(3). These values are in the range of the ultimate U.S. Department of Energy goal for volumetric density (70 kg/m(3)) as well as the best physisorption material studied to date (49 kg H(2)/m(3) for MOF-177). This material also displays a surprisingly high volumetric density of 23.2 kg H(2)/m(3) at room temperature and 85 bar--roughly 3 times higher than that of compressed gas and approaching the DOE 2010 goal of 28 kg H(2)/m(3). These materials possess linear isotherms and enthalpies that rise on coverage and have little or no kinetic barrier to adsorption or desorption. In a practical system these materials would use pressure instead of temperature as a toggle and can thus be used in compressed gas tanks, currently employed in many hydrogen test vehicles, to dramatically increase the amount of hydrogen stored and therefore the range of any vehicle.

SU-F-T-301: Planar Dose Pass Rate Inflation Due to the MapCHECK Measurement Uncertainty Function

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

Bailey, D; Spaans, J; Kumaraswamy, L

Purpose: To quantify the effect of the Measurement Uncertainty function on planar dosimetry pass rates, as analyzed with Sun Nuclear Corporation analytic software (“MapCHECK” or “SNC Patient”). This optional function is toggled on by default upon software installation, and automatically increases the user-defined dose percent difference (%Diff) tolerance for each planar dose comparison. Methods: Dose planes from 109 IMRT fields and 40 VMAT arcs were measured with the MapCHECK 2 diode array, and compared to calculated planes from a commercial treatment planning system. Pass rates were calculated within the SNC analytic software using varying calculation parameters, including Measurement Uncertainty onmore » and off. By varying the %Diff criterion for each dose comparison performed with Measurement Uncertainty turned off, an effective %Diff criterion was defined for each field/arc corresponding to the pass rate achieved with MapCHECK Uncertainty turned on. Results: For 3%/3mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.8–1.1% average, depending on plan type and calculation technique, for an average pass rate increase of 1.0–3.5% (maximum +8.7%). For 2%, 2 mm analysis, the Measurement Uncertainty function increases the user-defined %Diff by 0.7–1.2% average, for an average pass rate increase of 3.5–8.1% (maximum +14.2%). The largest increases in pass rate are generally seen with poorly-matched planar dose comparisons; the MapCHECK Uncertainty effect is markedly smaller as pass rates approach 100%. Conclusion: The Measurement Uncertainty function may substantially inflate planar dose comparison pass rates for typical IMRT and VMAT planes. The types of uncertainties incorporated into the function (and their associated quantitative estimates) as described in the software user’s manual may not accurately estimate realistic measurement uncertainty for the user’s measurement conditions. Pass rates listed in published reports or otherwise compared to the results of other users or vendors should clearly indicate whether the Measurement Uncertainty function is used.« less

State space truncation with quantified errors for accurate solutions to discrete Chemical Master Equation

PubMed Central

Cao, Youfang; Terebus, Anna; Liang, Jie

2016-01-01

The discrete chemical master equation (dCME) provides a general framework for studying stochasticity in mesoscopic reaction networks. Since its direct solution rapidly becomes intractable due to the increasing size of the state space, truncation of the state space is necessary for solving most dCMEs. It is therefore important to assess the consequences of state space truncations so errors can be quantified and minimized. Here we describe a novel method for state space truncation. By partitioning a reaction network into multiple molecular equivalence groups (MEG), we truncate the state space by limiting the total molecular copy numbers in each MEG. We further describe a theoretical framework for analysis of the truncation error in the steady state probability landscape using reflecting boundaries. By aggregating the state space based on the usage of a MEG and constructing an aggregated Markov process, we show that the truncation error of a MEG can be asymptotically bounded by the probability of states on the reflecting boundary of the MEG. Furthermore, truncating states of an arbitrary MEG will not undermine the estimated error of truncating any other MEGs. We then provide an overall error estimate for networks with multiple MEGs. To rapidly determine the appropriate size of an arbitrary MEG, we also introduce an a priori method to estimate the upper bound of its truncation error. This a priori estimate can be rapidly computed from reaction rates of the network, without the need of costly trial solutions of the dCME. As examples, we show results of applying our methods to the four stochastic networks of 1) the birth and death model, 2) the single gene expression model, 3) the genetic toggle switch model, and 4) the phage lambda bistable epigenetic switch model. We demonstrate how truncation errors and steady state probability landscapes can be computed using different sizes of the MEG(s) and how the results validate out theories. Overall, the novel state space truncation and error analysis methods developed here can be used to ensure accurate direct solutions to the dCME for a large number of stochastic networks. PMID:27105653

SU-F-J-219: Predicting Ventilation Change Due to Radiation Therapy: Dependency On Pre-RT Ventilation and Effort Correction

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

Patton, T; Du, K; Bayouth, J

Purpose: Ventilation change caused by radiation therapy (RT) can be predicted using four-dimensional computed tomography (4DCT) and image registration. This study tested the dependency of predicted post-RT ventilation on effort correction and pre-RT lung function. Methods: Pre-RT and 3 month post-RT 4DCT images were obtained for 13 patients. The 4DCT images were used to create ventilation maps using a deformable image registration based Jacobian expansion calculation. The post-RT ventilation maps were predicted in four different ways using the dose delivered, pre-RT ventilation, and effort correction. The pre-RT ventilation and effort correction were toggled to determine dependency. The four different predictedmore » ventilation maps were compared to the post-RT ventilation map calculated from image registration to establish the best prediction method. Gamma pass rates were used to compare the different maps with the criteria of 2mm distance-to-agreement and 6% ventilation difference. Paired t-tests of gamma pass rates were used to determine significant differences between the maps. Additional gamma pass rates were calculated using only voxels receiving over 20 Gy. Results: The predicted post-RT ventilation maps were in agreement with the actual post-RT maps in the following percentage of voxels averaged over all subjects: 71% with pre-RT ventilation and effort correction, 69% with no pre-RT ventilation and effort correction, 60% with pre-RT ventilation and no effort correction, and 58% with no pre-RT ventilation and no effort correction. When analyzing only voxels receiving over 20 Gy, the gamma pass rates were respectively 74%, 69%, 65%, and 55%. The prediction including both pre- RT ventilation and effort correction was the only prediction with significant improvement over using no prediction (p<0.02). Conclusion: Post-RT ventilation is best predicted using both pre-RT ventilation and effort correction. This is the only prediction that provided a significant improvement on agreement. Research support from NIH grants CA166119 and CA166703, a gift from Roger Koch, and a Pilot Grant from University of Iowa Carver College of Medicine.« less

State Space Truncation with Quantified Errors for Accurate Solutions to Discrete Chemical Master Equation

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

Cao, Youfang; Terebus, Anna; Liang, Jie

The discrete chemical master equation (dCME) provides a general framework for studying stochasticity in mesoscopic reaction networks. Since its direct solution rapidly becomes intractable due to the increasing size of the state space, truncation of the state space is necessary for solving most dCMEs. It is therefore important to assess the consequences of state space truncations so errors can be quantified and minimized. Here we describe a novel method for state space truncation. By partitioning a reaction network into multiple molecular equivalence groups (MEGs), we truncate the state space by limiting the total molecular copy numbers in each MEG. Wemore » further describe a theoretical framework for analysis of the truncation error in the steady-state probability landscape using reflecting boundaries. By aggregating the state space based on the usage of a MEG and constructing an aggregated Markov process, we show that the truncation error of a MEG can be asymptotically bounded by the probability of states on the reflecting boundary of the MEG. Furthermore, truncating states of an arbitrary MEG will not undermine the estimated error of truncating any other MEGs. We then provide an overall error estimate for networks with multiple MEGs. To rapidly determine the appropriate size of an arbitrary MEG, we also introduce an a priori method to estimate the upper bound of its truncation error. This a priori estimate can be rapidly computed from reaction rates of the network, without the need of costly trial solutions of the dCME. As examples, we show results of applying our methods to the four stochastic networks of (1) the birth and death model, (2) the single gene expression model, (3) the genetic toggle switch model, and (4) the phage lambda bistable epigenetic switch model. We demonstrate how truncation errors and steady-state probability landscapes can be computed using different sizes of the MEG(s) and how the results validate our theories. Overall, the novel state space truncation and error analysis methods developed here can be used to ensure accurate direct solutions to the dCME for a large number of stochastic networks.« less

State Space Truncation with Quantified Errors for Accurate Solutions to Discrete Chemical Master Equation

DOE PAGES

Cao, Youfang; Terebus, Anna; Liang, Jie

2016-04-22

The discrete chemical master equation (dCME) provides a general framework for studying stochasticity in mesoscopic reaction networks. Since its direct solution rapidly becomes intractable due to the increasing size of the state space, truncation of the state space is necessary for solving most dCMEs. It is therefore important to assess the consequences of state space truncations so errors can be quantified and minimized. Here we describe a novel method for state space truncation. By partitioning a reaction network into multiple molecular equivalence groups (MEGs), we truncate the state space by limiting the total molecular copy numbers in each MEG. Wemore » further describe a theoretical framework for analysis of the truncation error in the steady-state probability landscape using reflecting boundaries. By aggregating the state space based on the usage of a MEG and constructing an aggregated Markov process, we show that the truncation error of a MEG can be asymptotically bounded by the probability of states on the reflecting boundary of the MEG. Furthermore, truncating states of an arbitrary MEG will not undermine the estimated error of truncating any other MEGs. We then provide an overall error estimate for networks with multiple MEGs. To rapidly determine the appropriate size of an arbitrary MEG, we also introduce an a priori method to estimate the upper bound of its truncation error. This a priori estimate can be rapidly computed from reaction rates of the network, without the need of costly trial solutions of the dCME. As examples, we show results of applying our methods to the four stochastic networks of (1) the birth and death model, (2) the single gene expression model, (3) the genetic toggle switch model, and (4) the phage lambda bistable epigenetic switch model. We demonstrate how truncation errors and steady-state probability landscapes can be computed using different sizes of the MEG(s) and how the results validate our theories. Overall, the novel state space truncation and error analysis methods developed here can be used to ensure accurate direct solutions to the dCME for a large number of stochastic networks.« less

Multi-channel seismic reflection database for the northern Gulf of California, a highly-sedimented oblique rift

NASA Astrophysics Data System (ADS)

Steckler, M. S.; Haxby, W.; Persaud, P.; Stock, J.; Martín-Barajas, A.; Diebold, J.; Gonzalez-Fernandez, A.; Mountain, G. S.

2003-04-01

A multi-channel seismic reflection database has been developed to give access to high-resolution MCS data collected in the northern Gulf of California in May-June 1999. This data set consists of 3500 km of high-resolution MCS data acquired by the LDEO portable 48-channel MCS system using a 600-m streamer, a 1-ms sampling interval, and CDP spacing of 6.25/12.5 m on board the B/O Ulloa, the 28-m research vessel of CICESE. The resulting images have vertical resolution on the scale of meters to depths of up to 2 km below the seafloor. In addition, 48 sonobuoys recorded to 7 sec TWTT provided refraction velocities to greater depths. The northern Gulf of California is a transitional region between the oceanic ridge transform system of the central and southern Gulf and the continental San Andreas fault system of southern California. This data images the active deformation associated with the plate boundary zone in the northern Gulf of California. Multiple parallel rifts are simultaneously active in this wide complex zone of regional extension overprinted by shearing and a high sediment influx. The public-access database makes the cruise results, which is in a US MARGINS Program focus area, available to the broader geoscience community. The database includes navigation, final stacks and images for 80 seismic lines and 48 sonobuoys. The database may be accessed with MapApp, a downloadable Java application. Java applets offer many advantages over static or scripted web pages; they permit dynamic local interaction with data sets and limit time-consuming interaction with a remote server. MapApp displays the seismic lines on a map, and provides a viewer for inspecting images of the lines. Users may select a line from a list, or by clicking on the map. Once a line is selected, a user may load the image into the viewer, or download navigation, image or SEG-Y files. The viewer includes capability to zoom in and out, scroll, stretch or shrink horizontally, reverse direction, and toggle between black-on-white and white-on-black display. The section of the line in the viewer is indicated on the map, as is the current cursor location.

Full-view 3D imaging system for functional and anatomical screening of the breast

NASA Astrophysics Data System (ADS)

Oraevsky, Alexander; Su, Richard; Nguyen, Ha; Moore, James; Lou, Yang; Bhadra, Sayantan; Forte, Luca; Anastasio, Mark; Yang, Wei

2018-04-01

Laser Optoacoustic Ultrasonic Imaging System Assembly (LOUISA-3D) was developed in response to demand of diagnostic radiologists for an advanced screening system for the breast to improve on low sensitivity of x-ray based modalities of mammography and tomosynthesis in the dense and heterogeneous breast and low specificity magnetic resonance imaging. It is our working hypothesis that co-registration of quantitatively accurate functional images of the breast vasculature and microvasculature, and anatomical images of breast morphological structures will provide a clinically viable solution for the breast cancer care. Functional imaging is LOUISA-3D is enabled by the full view 3D optoacoustic images acquired at two rapidly toggling laser wavelengths in the near-infrared spectral range. 3D images of the breast anatomical background is enabled in LOUISA-3D by a sequence of B-mode ultrasound slices acquired with a transducer array rotating around the breast. This creates the possibility to visualize distributions of the total hemoglobin and blood oxygen saturation within specific morphological structures such as tumor angiogenesis microvasculature and larger vasculature in proximity of the tumor. The system has four major components: (i) a pulsed dual wavelength laser with fiberoptic light delivery system, (ii) an imaging module with two arc shaped probes (optoacoustic and ultrasonic) placed in a transparent bowl that rotates around the breast, (iii) a multichannel electronic system with analog preamplifiers and digital data acquisition boards, and (iv) computer for the system control, data processing and image reconstruction. The most important advancement of this latest system design compared with previously reported systems is the full breast illumination accomplished for each rotational step of the optoacoustic transducer array using fiberoptic illuminator rotating around the breast independently from rotation of the detector probe. We report here a pilot case studies on one healthy volunteer and on patient with a suspicious small lesion in the breast. LOUISA3D visualized deoxygenated veins and oxygenated arteries of a healthy volunteer, indicative of its capability to visualize hypoxic microvasculature in cancerous tumors. A small lesion detected on optoacoustic image of a patient was not visible on ultrasound, potentially indicating high system sensitivity of the optoacoustic subsystem to small but aggressively growing cancerous lesions with high density angiogenesis microvasculature. The main breast vasculature (0.5-1 mm) was visible at depth of up to 40-mm with 0.3-mm resolution. The results of LOUISA-3D pilot clinical validation demonstrated the system readiness for statistically significant clinical feasibility study.

Timing of PMMA cement application for pedicle screw augmentation affects screw anchorage.

PubMed

Schmoelz, Werner; Heinrichs, Christian Heinz; Schmidt, Sven; Piñera, Angel R; Tome-Bermejo, Felix; Duart, Javier M; Bauer, Marlies; Galovich, Luis Álvarez

2017-11-01

Cement augmentation is an established method to increase the pedicle screw (PS) anchorage in osteoporotic vertebral bodies. The ideal timing for augmentation when a reposition maneuver is necessary is controversial. While augmentation of the PS before reposition maneuver may increase the force applied it on the vertebrae, it bears the risk to impair PS anchorage, whereas augmenting the PS after the maneuver may restore this anchorage and prevent early screw loosening. The purpose of the present study was to evaluate the effect of cement application timing on PS anchorage in the osteoporotic vertebral body. Ten lumbar vertebrae (L1-L5) were used for testing. The left and right pedicles of each vertebra were instrumented with the same PS size and used for pairwise comparison of the two timing points for augmentation. For the reposition maneuver, the left PS was loaded axially under displacement control (2 × ±2 mm, 3 × ±6 mm, 3 × ±10 mm) to simulate a reposition maneuver. Subsequently, both PS were augmented with 2 ml PMMA cement. The same force as measured during the left PS maneuver was applied to the previously augmented right hand side PS [2 × F (±2 mm), 3 × F (±6 mm), 3 × F (±10 mm)]. Both PS were cyclically loaded with initial forces of +50 and -50 N, while the lower force was increased by 5 N every 100 cycles until total failure of the PS. The PS motion was measured with a 3D motion analysis system. After cyclic loading stress, X-rays were taken to identify the PS loosening mechanism. In comparison with PS augmented prior to the reposition maneuver, PS augmented after the reposition maneuver showed a significant higher number of load cycles until failure (5930 ± 1899 vs 3830 ± 1706, p = 0.015). The predominant loosening mechanism for PS augmented after the reposition maneuver was PS toggling with the attached cement cloud within the trabecular bone. While PS augmented prior to the reposition, maneuver showed a motion of the screw within the cement cloud. The time of cement application has an effect on PS anchorage in the osteoporotic vertebral body if a reposition maneuver of the instrumented vertebrae is carried out. PS augmented after the reposition maneuver showed a significant higher number of load cycles until screw loosening.

Visualization of Uncertainty

NASA Astrophysics Data System (ADS)

Jones, P. W.; Strelitz, R. A.

2012-12-01

The output of a simulation is best comprehended through the agency and methods of visualization, but a vital component of good science is knowledge of uncertainty. While great strides have been made in the quantification of uncertainty, especially in simulation, there is still a notable gap: there is no widely accepted means of simultaneously viewing the data and the associated uncertainty in one pane. Visualization saturates the screen, using the full range of color, shadow, opacity and tricks of perspective to display even a single variable. There is no room in the visualization expert's repertoire left for uncertainty. We present a method of visualizing uncertainty without sacrificing the clarity and power of the underlying visualization that works as well in 3-D and time-varying visualizations as it does in 2-D. At its heart, it relies on a principal tenet of continuum mechanics, replacing the notion of value at a point with a more diffuse notion of density as a measure of content in a region. First, the uncertainties calculated or tabulated at each point are transformed into a piecewise continuous field of uncertainty density . We next compute a weighted Voronoi tessellation of a user specified N convex polygonal/polyhedral cells such that each cell contains the same amount of uncertainty as defined by . The problem thus devolves into minimizing . Computation of such a spatial decomposition is O(N*N ), and can be computed iteratively making it possible to update easily over time as well as faster. The polygonal mesh does not interfere with the visualization of the data and can be easily toggled on or off. In this representation, a small cell implies a great concentration of uncertainty, and conversely. The content weighted polygons are identical to the cartogram familiar to the information visualization community in the depiction of things voting results per stat. Furthermore, one can dispense with the mesh or edges entirely to be replaced by symbols or glyphs at the generating points (effectively the center of the polygon). This methodology readily admits to rigorous statistical analysis using standard components found in R and thus entirely compatible with the visualization package we use (Visit and/or ParaView), the language we use (Python) and the UVCDAT environment that provides the programmer and analyst workbench. We will demonstrate the power and effectiveness of this methodology in climate studies. We will further argue that our method of defining (or predicting) values in a region has many advantages over the traditional visualization notion of value at a point.

Dibenzo[b,f][1,4]oxazepines and dibenzo[b,e]oxepines: Influence of the chlorine substitution pattern on the pharmacology at the H1R, H4R, 5-HT2AR and other selected GPCRs.

PubMed

Naporra, Franziska; Gobleder, Susanne; Wittmann, Hans-Joachim; Spindler, Julia; Bodensteiner, Michael; Bernhardt, Günther; Hübner, Harald; Gmeiner, Peter; Elz, Sigurd; Strasser, Andrea

2016-11-01

Inspired by VUF6884 (7-Chloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine), reported as a dual H 1 /H 4 receptor ligand (pK i : 8.11 (human H 1 R (hH 1 R)), 7.55 (human H 4 R (hH 4 R))), four known and 28 new oxazepine and related oxepine derivatives were synthesised and pharmacologically characterized at histamine receptors and selected aminergic GPCRs. In contrast to the oxazepine series, within the oxepine series, the new compounds showed high affinity to the hH 1 R (pK i : 6.8-8.7), but no or moderate affinity to the hH 4 R (pK i :≤5.3). For one oxepine derivative (1-(2-Chloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine), the enantiomers were separated and the R-enantiomer was identified as the eutomer at the hH 1 R (pK i : 8.83 (R), 7.63 (S)) and the guinea-pig H 1 R (gpH 1 R) (pK i : 8.82 (R), 7.41 (S)). Molecular dynamic studies suggest that the tricyclic core of the compounds is bound in a similar mode into the binding pocket, as described for doxepine in the hH 1 R crystal structure. Moreover, docking studies of all oxepine derivatives at the hH 1 R indicate that the oxygen and the position of the chlorine in the tricyclic core determines, if the R- or the S-enantiomer is the eutomer. For some of the oxazepines and oxepines the affinity to other aminergic GPCRs is in the same range as to hH 1 R or hH 4 R, thus, those compounds have to be classified as dirty drugs. However, one oxazepine derivative (3,7-Dichloro-11-(4-methylpiperazin-1-yl)dibenzo[b,f][1,4]oxazepine was identified as dual hH 1 /h5-HT 2A receptor ligand (pK i : 9.23 (hH 1 R), 8.74 (h5-HT 2A R), ≤7 at other analysed GPCRs), whereas one oxepine derivative (1-(3,8-Dichloro-6,11-dihydrodibenzo[b,e]oxepin-11-yl)-4-methylpiperazine) was identified as selective hH 1 R antagonist (pK i : 8.44 (hH 1 R), ≤6.7 at other analyzed GPCRs). Thus, the pharmacological results suggest that the oxazepine/oxepine moiety and additionally the chlorine substitution pattern toggles receptor selectivity and specificity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pedicle screw anchorage of carbon fiber-reinforced PEEK screws under cyclic loading.

PubMed

Lindtner, Richard A; Schmid, Rene; Nydegger, Thomas; Konschake, Marko; Schmoelz, Werner

2018-03-01

Pedicle screw loosening is a common and significant complication after posterior spinal instrumentation, particularly in osteoporosis. Radiolucent carbon fiber-reinforced polyetheretherketone (CF/PEEK) pedicle screws have been developed recently to overcome drawbacks of conventional metallic screws, such as metal-induced imaging artifacts and interference with postoperative radiotherapy. Beyond radiolucency, CF/PEEK may also be advantageous over standard titanium in terms of pedicle screw loosening due to its unique material properties. However, screw anchorage and loosening of CF/PEEK pedicle screws have not been evaluated yet. The aim of this biomechanical study therefore was to evaluate whether the use of this alternative nonmetallic pedicle screw material affects screw loosening. The hypotheses tested were that (1) nonmetallic CF/PEEK pedicle screws resist an equal or higher number of load cycles until loosening than standard titanium screws and that (2) PMMA cement augmentation further increases the number of load cycles until loosening of CF/PEEK screws. In the first part of the study, left and right pedicles of ten cadaveric lumbar vertebrae (BMD 70.8 mg/cm 3  ± 14.5) were randomly instrumented with either CF/PEEK or standard titanium pedicle screws. In the second part, left and right pedicles of ten vertebrae (BMD 56.3 mg/cm 3  ± 15.8) were randomly instrumented with either PMMA-augmented or nonaugmented CF/PEEK pedicle screws. Each pedicle screw was subjected to cyclic cranio-caudal loading (initial load ranging from - 50 N to + 50 N) with stepwise increasing compressive loads (5 N every 100 cycles) until loosening or a maximum of 10,000 cycles. Angular screw motion ("screw toggling") within the vertebra was measured with a 3D motion analysis system every 100 cycles and by stress fluoroscopy every 500 cycles. The nonmetallic CF/PEEK pedicle screws resisted a similar number of load cycles until loosening as the contralateral standard titanium screws (3701 ± 1228 vs. 3751 ± 1614 load cycles, p = 0.89). PMMA cement augmentation of CF/PEEK pedicle screws furthermore significantly increased the mean number of load cycles until loosening by 1.63-fold (5100 ± 1933 in augmented vs. 3130 ± 2132 in nonaugmented CF/PEEK screws, p = 0.015). In addition, angular screw motion assessed by stress fluoroscopy was significantly smaller in augmented than in nonaugmented CF/PEEK screws before as well as after failure. Using nonmetallic CF/PEEK instead of standard titanium as pedicle screw material did not affect screw loosening in the chosen test setup, whereas cement augmentation enhanced screw anchorage of CF/PEEK screws. While comparable to titanium screws in terms of screw loosening, radiolucent CF/PEEK pedicle screws offer the significant advantage of not interfering with postoperative imaging and radiotherapy. These slides can be retrieved under Electronic Supplementary Material.

Usability Testing of a Complex Clinical Decision Support Tool in the Emergency Department: Lessons Learned.

PubMed

Press, Anne; McCullagh, Lauren; Khan, Sundas; Schachter, Andy; Pardo, Salvatore; McGinn, Thomas

2015-09-10

As the electronic health record (EHR) becomes the preferred documentation tool across medical practices, health care organizations are pushing for clinical decision support systems (CDSS) to help bring clinical decision support (CDS) tools to the forefront of patient-physician interactions. A CDSS is integrated into the EHR and allows physicians to easily utilize CDS tools. However, often CDSS are integrated into the EHR without an initial phase of usability testing, resulting in poor adoption rates. Usability testing is important because it evaluates a CDSS by testing it on actual users. This paper outlines the usability phase of a study, which will test the impact of integration of the Wells CDSS for pulmonary embolism (PE) diagnosis into a large urban emergency department, where workflow is often chaotic and high stakes decisions are frequently made. We hypothesize that conducting usability testing prior to integration of the Wells score into an emergency room EHR will result in increased adoption rates by physicians. The objective of the study was to conduct usability testing for the integration of the Wells clinical prediction rule into a tertiary care center's emergency department EHR. We conducted usability testing of a CDS tool in the emergency department EHR. The CDS tool consisted of the Wells rule for PE in the form of a calculator and was triggered off computed tomography (CT) orders or patients' chief complaint. The study was conducted at a tertiary hospital in Queens, New York. There were seven residents that were recruited and participated in two phases of usability testing. The usability testing employed a "think aloud" method and "near-live" clinical simulation, where care providers interacted with standardized patients enacting a clinical scenario. Both phases were audiotaped, video-taped, and had screen-capture software activated for onscreen recordings. Phase I: Data from the "think-aloud" phase of the study showed an overall positive outlook on the Wells tool in assessing a patient for a PE diagnosis. Subjects described the tool as "well-organized" and "better than clinical judgment". Changes were made to improve tool placement into the EHR to make it optimal for decision-making, auto-populating boxes, and minimizing click fatigue. Phase II: After incorporating the changes noted in Phase 1, the participants noted tool improvements. There was less toggling between screens, they had all the clinical information required to complete the tool, and were able to complete the patient visit efficiently. However, an optimal location for triggering the tool remained controversial. This study successfully combined "think-aloud" protocol analysis with "near-live" clinical simulations in a usability evaluation of a CDS tool that will be implemented into the emergency room environment. Both methods proved useful in the assessment of the CDS tool and allowed us to refine tool usability and workflow.

Technical aspects of real time positron emission tracking for gated radiotherapy

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

Chamberland, Marc; Xu, Tong, E-mail: txu@physics.carleton.ca; McEwen, Malcolm R.

2016-02-15

Purpose: Respiratory motion can lead to treatment errors in the delivery of radiotherapy treatments. Respiratory gating can assist in better conforming the beam delivery to the target volume. We present a study of the technical aspects of a real time positron emission tracking system for potential use in gated radiotherapy. Methods: The tracking system, called PeTrack, uses implanted positron emission markers and position sensitive gamma ray detectors to track breathing motion in real time. PeTrack uses an expectation–maximization algorithm to track the motion of fiducial markers. A normalized least mean squares adaptive filter predicts the location of the markers amore » short time ahead to account for system response latency. The precision and data collection efficiency of a prototype PeTrack system were measured under conditions simulating gated radiotherapy. The lung insert of a thorax phantom was translated in the inferior–superior direction with regular sinusoidal motion and simulated patient breathing motion (maximum amplitude of motion ±10 mm, period 4 s). The system tracked the motion of a {sup 22}Na fiducial marker (0.34 MBq) embedded in the lung insert every 0.2 s. The position of the was marker was predicted 0.2 s ahead. For sinusoidal motion, the equation used to model the motion was fitted to the data. The precision of the tracking was estimated as the standard deviation of the residuals. Software was also developed to communicate with a Linac and toggle beam delivery. In a separate experiment involving a Linac, 500 monitor units of radiation were delivered to the phantom with a 3 × 3 cm photon beam and with 6 and 10 MV accelerating potential. Radiochromic films were inserted in the phantom to measure spatial dose distribution. In this experiment, the period of motion was set to 60 s to account for beam turn-on latency. The beam was turned off when the marker moved outside of a 5-mm gating window. Results: The precision of the tracking in the IS direction was 0.53 mm for a sinusoidally moving target, with an average count rate ∼250 cps. The average prediction error was 1.1 ± 0.6 mm when the marker moved according to irregular patient breathing motion. Across all beam deliveries during the radiochromic film measurements, the average prediction error was 0.8 ± 0.5 mm. The maximum error was 2.5 mm and the 95th percentile error was 1.5 mm. Clear improvement of the dose distribution was observed between gated and nongated deliveries. The full-width at halfmaximum of the dose profiles of gated deliveries differed by 3 mm or less than the static reference dose distribution. Monitoring of the beam on/off times showed synchronization with the location of the marker within the latency of the system. Conclusions: PeTrack can track the motion of internal fiducial positron emission markers with submillimeter precision. The system can be used to gate the delivery of a Linac beam based on the position of a moving fiducial marker. This highlights the potential of the system for use in respiratory-gated radiotherapy.« less

14 CFR 121.434 - Operating experience, operating cycles, and consolidation of knowledge and skills.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Operating experience, operating cycles, and... Qualifications § 121.434 Operating experience, operating cycles, and consolidation of knowledge and skills. (a... position, the operating experience, operating cycles, and the line operating flight time for consolidation...

47 CFR 13.9 - Eligibility and application for new license or endorsement.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Operator License, Marine Radio Operator Permit, Radiotelegraph Operator License, Ship Radar Endorsement, Six Months Service Endorsement, GMDSS Radio Operator's License, Restricted GMDSS Radio Operator's... Radiotelephone Operator License, Marine Radio Operator Permit, Radiotelegraph Operator License, Ship Radar...

47 CFR 13.9 - Eligibility and application for new license or endorsement.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Operator License, Marine Radio Operator Permit, Radiotelegraph Operator License, Ship Radar Endorsement, Six Months Service Endorsement, GMDSS Radio Operator's License, Restricted GMDSS Radio Operator's... Radiotelephone Operator License, Marine Radio Operator Permit, Radiotelegraph Operator License, Ship Radar...

76 FR 58565 - Proposed Information Collection (Operation Enduring Freedom/Operation Iraqi Freedom Seriously...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-21

... (Operation Enduring Freedom/ Operation Iraqi Freedom Seriously Injured/Ill Service Member Veteran Worksheet... solicits comments on information provided to Operation Enduring Freedom/Operation Iraqi Freedom veterans... information technology. Title: Operation Enduring Freedom/Operation Iraqi Freedom Seriously Injured/Ill...

Field Artillery And Fire Support At The Operational Level: An Analysis Of Operation Desert Storm and Operation Iraqi Freedom

DTIC Science & Technology

2017-05-25

Field Artillery and Fire Support at the Operational Level: An Analysis of Operation Desert Storm and Operation Iraqi Freedom A Monograph...Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204...AND SUBTITLE Field Artillery and Fire Support at the Operational Level: An Analysis of Operation Desert Storm and Operation Iraqi Freedom 5a

Influence of System Operation Method on CO2 Emissions of PV/Solar Heat/Cogeneration System

NASA Astrophysics Data System (ADS)

Oke, Shinichiro; Kemmoku, Yoshishige; Takikawa, Hirofumi; Sakakibara, Tateki

A PV/solar heat/cogeneration system is assumed to be installed in a hotel. The system is operated with various operation methods: CO2 minimum operation, fees minimum operation, seasonal operation, daytime operation and heat demand following operation. Of these five operations, the former two are virtual operations that are operated with the dynamic programming method, and the latter three are actual operations. Computer simulation is implemented using hourly data of solar radiation intensity, atmospheric temperature, electric, cooling, heating and hot water supply demands for one year, and the life-cycle CO2 emission and the total cost are calculated for every operations. The calculation results show that the virtual two and the actual three operations reduce the life-cycle CO2 emission by 21% and 13% compared with the conventional system, respectively. In regard to both the CO2 emission and the cost, there is no significant difference between the virtual two operation methods or among actual three operation methods.

Space Station overall management approach for operations

NASA Technical Reports Server (NTRS)

Paules, G.

1986-01-01

An Operations Management Concept developed by NASA for its Space Station Program is discussed. The operational goals, themes, and design principles established during program development are summarized. The major operations functions are described, including: space systems operations, user support operations, prelaunch/postlanding operations, logistics support operations, market research, and cost/financial management. Strategic, tactical, and execution levels of operational decision-making are defined.

76 FR 73022 - Agency Information Collection (Operation Enduring Freedom/Operation Iraqi Freedom Seriously...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-28

... (Operation Enduring Freedom/ Operation Iraqi Freedom Seriously Injured/Ill Service Member Veteran Worksheet... No. 2900-0720.'' SUPPLEMENTARY INFORMATION: Title: Operation Enduring Freedom/Operation Iraqi Freedom... used VA Form 21-0773 as a checklist to ensure they provided Operation Enduring Freedom or Operation...

An assessment of the quality indicators of operative and non-operative times in a public university hospital.

PubMed

Costa, Altair da Silva; Leão, Luiz Eduardo Villaça; Novais, Maykon Anderson Pires de; Zucchi, Paola

2015-01-01

To assess the operative time indicators in a public university hospital. A descriptive cross-sectional study was conducted using data from operating room database. The sample was obtained from January 2011 to January 2012. The operations performed in sequence in the same operating room, between 7:00 am and 5:00 pm, elective or emergency, were included. The procedures with incomplete data in the system were excluded, as well as the operations performed after 5:00 pm or on weekends or holidays. We measured the operative and non-operative time of 8,420 operations. The operative time (mean and standard deviation) of anesthesias and operations were 177.6 ± 110 and 129.8 ± 97.1 minutes, respectively. The total time of the patient in operative room (mean and standard deviation) was 196.8 ± 113.2. The non-operative time, e.g., between the arrival of the patient and the onset of anesthesia was 14.3 ± 17.3 minutes. The time to set the next patient in operating room was 119.8 ± 79.6 minutes. Our total non-operative time was 155 minutes. Delays frequently occurred in our operating room and had a major effect on patient flow and resource utilization. The non-operative time was longer than the operative time. It is possible to increase the operating room capacity by management and training of the professionals involved. The indicators provided a tool to improve operating room efficiency.

47 CFR 13.7 - Classification of operator licenses and endorsements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... are twelve types of commercial radio operator licenses, certificates and permits (licenses). The... Radiotelephone Operator License (radiotelephone operator's general certificate). (6) Marine Radio Operator Permit (radiotelephone operator's restricted certificate). (7) Restricted Radiotelephone Operator Permit (radiotelephone...

47 CFR 13.7 - Classification of operator licenses and endorsements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... are twelve types of commercial radio operator licenses, certificates and permits (licenses). The... Radiotelephone Operator License (radiotelephone operator's general certificate). (6) Marine Radio Operator Permit (radiotelephone operator's restricted certificate). (7) Restricted Radiotelephone Operator Permit (radiotelephone...

40 CFR 63.4292 - What operating limits must I meet?

Code of Federal Regulations, 2010 CFR

2010-07-01

... systems on the web coating/printing operation(s) and dyeing/finishing operations for which you use this... Limitations § 63.4292 What operating limits must I meet? (a) For any web coating/printing operation, slashing operation, or dyeing/finishing operation on which you use the compliant material option; web coating...

76 FR 49650 - Private Security Contractors (PSCs) Operating in Contingency Operations, Combat Operations or...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-11

...] Private Security Contractors (PSCs) Operating in Contingency Operations, Combat Operations or Other..., ``Contractor Personnel Authorized to Accompany the U.S. Armed Forces,'' which provides guidance for all DoD contractors operating in contingency operations. This Rule was published as an Interim Final Rule on July 17...

An assessment of the quality indicators of operative and non-operative times in a public university hospital

PubMed Central

Costa, Altair da Silva; Leão, Luiz Eduardo Villaça; de Novais, Maykon Anderson Pires; Zucchi, Paola

2015-01-01

ABSTRACT Objective To assess the operative time indicators in a public university hospital. Methods A descriptive cross-sectional study was conducted using data from operating room database. The sample was obtained from January 2011 to January 2012. The operations performed in sequence in the same operating room, between 7:00 am and 5:00 pm, elective or emergency, were included. The procedures with incomplete data in the system were excluded, as well as the operations performed after 5:00 pm or on weekends or holidays. Results We measured the operative and non-operative time of 8,420 operations. The operative time (mean and standard deviation) of anesthesias and operations were 177.6±110 and 129.8±97.1 minutes, respectively. The total time of the patient in operative room (mean and standard deviation) was 196.8±113.2. The non-operative time, e.g., between the arrival of the patient and the onset of anesthesia was 14.3±17.3 minutes. The time to set the next patient in operating room was 119.8±79.6 minutes. Our total non-operative time was 155 minutes. Conclusion Delays frequently occurred in our operating room and had a major effect on patient flow and resource utilization. The non-operative time was longer than the operative time. It is possible to increase the operating room capacity by management and training of the professionals involved. The indicators provided a tool to improve operating room efficiency. PMID:26761557

14 CFR 121.713 - Retention of contracts and amendments: Commercial operators who conduct intrastate operations for...

Code of Federal Regulations, 2010 CFR

2010-01-01

...: Commercial operators who conduct intrastate operations for compensation or hire. 121.713 Section 121.713...: Commercial operators who conduct intrastate operations for compensation or hire. (a) Each commercial operator... under which it provides services as a commercial operator for a period of at least 1 year after the date...

14 CFR 121.533 - Responsibility for operational control: Domestic operations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations... aircraft dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in compliance with this chapter and operations specifications. (c) The aircraft dispatcher is...

14 CFR 121.533 - Responsibility for operational control: Domestic operations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations... aircraft dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in compliance with this chapter and operations specifications. (c) The aircraft dispatcher is...

14 CFR 121.533 - Responsibility for operational control: Domestic operations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations... aircraft dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in compliance with this chapter and operations specifications. (c) The aircraft dispatcher is...

14 CFR 121.533 - Responsibility for operational control: Domestic operations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations... aircraft dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in compliance with this chapter and operations specifications. (c) The aircraft dispatcher is...

14 CFR 121.533 - Responsibility for operational control: Domestic operations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations... aircraft dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in compliance with this chapter and operations specifications. (c) The aircraft dispatcher is...

Determinants of re-operation for bleeding in head and neck cancer surgery.

PubMed

Haapio, E; Kinnunen, I; Airaksinen, J K E; Irjala, H; Kiviniemi, T

2018-04-01

Post-operative bleeding in the head and neck area is potentially fatal. This 'real world' study sought to assess factors that increase the risk of re-operation for post-operative bleeding in head and neck cancer surgery. A total of 456 patients underwent surgery for head and neck cancer (591 operations). The primary endpoint was re-operation for bleeding. The rate of re-operation for bleeding was 5 per cent of all operations. Re-operation for bleeding was an independent risk factor for 30-day mortality (odds ratio = 5.27, p = 0.014). Risk factors for re-operation because of bleeding included excessive (more than 4000 ml) fluid administration (over 24 hours) (p < 0.001), heavy alcohol consumption (p = 0.014), pre-operative oncological treatment (p = 0.017), advanced disease stage (p = 0.020) and higher tumour (T) classification (p = 0.034). Operations with more excessive bleeding (700 ml or more) were associated with an increased risk (p = 0.001) of re-operation for post-operative bleeding. Moreover, the risk of re-operation was significantly higher in patients undergoing microvascular surgery compared to those who had no oncological treatment pre-operatively (18 vs 6 per cent, p = 0.001). The 30-day mortality risk increased over 5-fold in patients undergoing re-operation for bleeding.

Air Force Special Operations Command > Home > POTFF

Science.gov Websites

Air Force Special Operations Command Air Force Special Operations Command Join the Air Force Home Sheets AFSOC Senior Leaders AFSOC Heritage Units 1st Special Operations Wing 24th Special Operations Wing 27th Special Operations Wing 352nd Special Operations Wing 353rd Special Operations Group 492nd Special

Operator Support System Design forthe Operation of RSG-GAS Research Reactor

NASA Astrophysics Data System (ADS)

Santoso, S.; Situmorang, J.; Bakhri, S.; Subekti, M.; Sunaryo, G. R.

2018-02-01

The components of RSG-GAS main control room are facing the problem of material ageing and technology obsolescence as well, and therefore the need for modernization and refurbishment are essential. The modernization in control room can be applied on the operator support system which bears the function in providing information for assisting the operator in conducting diagnosis and actions. The research purpose is to design an operator support system for RSG-GAS control room. The design was developed based on the operator requirement in conducting task operation scenarios and the reactor operation characteristics. These scenarios include power operation, low power operation and shutdown/scram reactor. The operator support system design is presented in a single computer display which contains structure and support system elements e.g. operation procedure, status of safety related components and operational requirements, operation limit condition of parameters, alarm information, and prognosis function. The prototype was developed using LabView software and consisted of components structure and features of the operator support system. Information of each component in the operator support system need to be completed before it can be applied and integrated in the RSG-GAS main control room.

10 CFR 55.45 - Operating tests.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Operating tests. 55.45 Section 55.45 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) OPERATORS' LICENSES Written Examinations and Operating Tests § 55.45 Operating tests. (a) Content. The operating tests administered to applicants for operator and senior...

Integrating International Space Station payload operations

NASA Technical Reports Server (NTRS)

Noneman, Steven R.

1996-01-01

The payload operations support for the International Space Station (ISS) payload is reported on, describing payload activity planning, payload operations control, payload data management and overall operations integration. The operations concept employed is based on the distribution of the payload operations responsibility between the researchers and ISS partners. The long duration nature of the ISS mission dictates the geographical distribution of the payload operations activities between the different national centers. The coordination and integration of these operations will be assured by NASA's Payload Operations Integration Center (POIC). The prime objective of the POIC is the achievement of unified operations through communication and collaboration.

14 CFR 121.537 - Responsibility for operational control: Supplemental operations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations..., and termination of a flight in compliance with this chapter and the operations specifications. The... termination of a flight but he may not delegate the responsibility for those functions. (c) The director of...

14 CFR 121.537 - Responsibility for operational control: Supplemental operations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations..., and termination of a flight in compliance with this chapter and the operations specifications. The... termination of a flight but he may not delegate the responsibility for those functions. (c) The director of...

14 CFR 121.537 - Responsibility for operational control: Supplemental operations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations..., and termination of a flight in compliance with this chapter and the operations specifications. The... termination of a flight but he may not delegate the responsibility for those functions. (c) The director of...

14 CFR 121.537 - Responsibility for operational control: Supplemental operations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations..., and termination of a flight in compliance with this chapter and the operations specifications. The... termination of a flight but he may not delegate the responsibility for those functions. (c) The director of...

14 CFR 121.537 - Responsibility for operational control: Supplemental operations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations..., and termination of a flight in compliance with this chapter and the operations specifications. The... termination of a flight but he may not delegate the responsibility for those functions. (c) The director of...

14 CFR 91.1011 - Operational control responsibilities and delegation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Operational control responsibilities and... Ownership Operations Operational Control § 91.1011 Operational control responsibilities and delegation. (a) Each owner in operational control of a program flight is ultimately responsible for safe operations and...

Kennedy Space Center Orion Processing Team Planning for Ground Operations

NASA Technical Reports Server (NTRS)

Letchworth, Gary; Schlierf, Roland

2011-01-01

Topics in this presentation are: Constellation Ares I/Orion/Ground Ops Elements Orion Ground Operations Flow Orion Operations Planning Process and Toolset Overview, including: 1 Orion Concept of Operations by Phase 2 Ops Analysis Capabilities Overview 3 Operations Planning Evolution 4 Functional Flow Block Diagrams 5 Operations Timeline Development 6 Discrete Event Simulation (DES) Modeling 7 Ground Operations Planning Document Database (GOPDb) Using Operations Planning Tools for Operability Improvements includes: 1 Kaizen/Lean Events 2 Mockups 3 Human Factors Analysis

Differences Between S/X and VLBI2010 Operation

NASA Technical Reports Server (NTRS)

Hase, Hayo; Himwich, Ed; Neidhardt, Alexander

2010-01-01

The intended VLBI2010 operation has some significant differences to the current S/X operation. The presentation focuses on the problem of extending the operation of a global VLBI network to continuous operation within the frame of the same given amount of human resources. Remote control operation is a suitable solution to minimize operational expenses. The implementation of remote control operation requires more site specific information. A concept of a distributed-centralized remote control of the operation and its implications is presented.

10 CFR 50.74 - Notification of change in operator or senior operator status.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Notification of change in operator or senior operator... or senior operator status. Each licensee shall notify the appropriate Regional Administrator as... operator or senior operator: (a) Permanent reassignment from the position for which the licensee has...

49 CFR 195.406 - Maximum operating pressure.

Code of Federal Regulations, 2010 CFR

2010-10-01

... HAZARDOUS LIQUIDS BY PIPELINE Operation and Maintenance § 195.406 Maximum operating pressure. (a) Except for surge pressures and other variations from normal operations, no operator may operate a pipeline at a... 49 Transportation 3 2010-10-01 2010-10-01 false Maximum operating pressure. 195.406 Section 195...

49 CFR 195.406 - Maximum operating pressure.

Code of Federal Regulations, 2012 CFR

2012-10-01

... HAZARDOUS LIQUIDS BY PIPELINE Operation and Maintenance § 195.406 Maximum operating pressure. (a) Except for surge pressures and other variations from normal operations, no operator may operate a pipeline at a... 49 Transportation 3 2012-10-01 2012-10-01 false Maximum operating pressure. 195.406 Section 195...

49 CFR 195.406 - Maximum operating pressure.

Code of Federal Regulations, 2014 CFR

2014-10-01

... HAZARDOUS LIQUIDS BY PIPELINE Operation and Maintenance § 195.406 Maximum operating pressure. (a) Except for surge pressures and other variations from normal operations, no operator may operate a pipeline at a... 49 Transportation 3 2014-10-01 2014-10-01 false Maximum operating pressure. 195.406 Section 195...

49 CFR 195.406 - Maximum operating pressure.

Code of Federal Regulations, 2011 CFR

2011-10-01

... HAZARDOUS LIQUIDS BY PIPELINE Operation and Maintenance § 195.406 Maximum operating pressure. (a) Except for surge pressures and other variations from normal operations, no operator may operate a pipeline at a... 49 Transportation 3 2011-10-01 2011-10-01 false Maximum operating pressure. 195.406 Section 195...

49 CFR 195.406 - Maximum operating pressure.

Code of Federal Regulations, 2013 CFR

2013-10-01

... HAZARDOUS LIQUIDS BY PIPELINE Operation and Maintenance § 195.406 Maximum operating pressure. (a) Except for surge pressures and other variations from normal operations, no operator may operate a pipeline at a... 49 Transportation 3 2013-10-01 2013-10-01 false Maximum operating pressure. 195.406 Section 195...

78 FR 22576 - Application and Amendment to Facility Operating License Involving Proposed No Significant Hazards...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

... Facility Operating License Involving Proposed No Significant Hazards Consideration Determination; San... Operating License No. NPF-10, issued to Southern California Edison (SCE, the licensee), for operation of the... operating conditions'' and ``normal steady state full power operation'' and restricts operation to 70...

Automatic control of oscillatory penetration apparatus

DOEpatents

Lucon, Peter A

2015-01-06

A system and method for controlling an oscillatory penetration apparatus. An embodiment is a system and method for controlling a sonic drill having a displacement and an operating range and operating at a phase difference, said sonic drill comprising a push-pull piston and eccentrics, said method comprising: operating the push-pull piston at an initial push-pull force while the eccentrics are operated at a plurality of different operating frequencies within the operating range of the sonic drill and measuring the displacement at each operating frequency; determining an efficient operating frequency for the material being drilled and operating the eccentrics at said efficient operating frequency; determining the phase difference at which the sonic drill is operating; and if the phase difference is not substantially equal to minus ninety degrees, operating the push-pull piston at another push-pull force.

Solar power satellite system definition study. Volume 3: Operations and systems synthesis, phase 2

NASA Technical Reports Server (NTRS)

1979-01-01

The results of the operations analyses are reported. Some of these analyses examined operations aspects of space vehicle in-space maintenance. Many of the analyses explored in great depth operations concerned the LEO Base cargo handling operations. Personnel transportation operations and cargo packaging were also analyzed. These operations analyses were performed to define the operational requirements for all of the SPS system elements so that equipment and facilities could be synthesized, and to make estimates of the manpower requirements. An overall, integrated, end-to-end description of the SPS operations is presented. The detailed operations analyses, upon which this integrated description was based, are included.

Space station operations management

NASA Technical Reports Server (NTRS)

Cannon, Kathleen V.

1989-01-01

Space Station Freedom operations management concepts must be responsive to the unique challenges presented by the permanently manned international laboratory. Space Station Freedom will be assembled over a three year period where the operational environment will change as significant capability plateaus are reached. First Element Launch, Man-Tended Capability, and Permanent Manned Capability, represent milestones in operational capability that is increasing toward mature operations capability. Operations management concepts are being developed to accomodate the varying operational capabilities during assembly, as well as the mature operational environment. This paper describes operations management concepts designed to accomodate the uniqueness of Space Station Freedoom, utilizing tools and processes that seek to control operations costs.

43 CFR 3162.3-2 - Subsequent well operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Subsequent well operations. 3162.3-2... for Operating Rights Owners and Operators § 3162.3-2 Subsequent well operations. (a) A proposal for further well operations shall be submitted by the operator on Form 3160-5 for approval by the authorized...

43 CFR 3162.3-2 - Subsequent well operations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Subsequent well operations. 3162.3-2... for Operating Rights Owners and Operators § 3162.3-2 Subsequent well operations. (a) A proposal for further well operations shall be submitted by the operator on Form 3160-5 for approval by the authorized...

43 CFR 3162.3-2 - Subsequent well operations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Subsequent well operations. 3162.3-2... for Operating Rights Owners and Operators § 3162.3-2 Subsequent well operations. (a) A proposal for further well operations shall be submitted by the operator on Form 3160-5 for approval by the authorized...

30 CFR 75.1716-1 - Operations under water; notification by operator.

Code of Federal Regulations, 2010 CFR

2010-07-01

... § 75.1716-1 Operations under water; notification by operator. An operator planning to mine coal from... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Operations under water; notification by..., and in such manner that mining operations will be conducted, or tunnels constructed, under any river...

33 CFR 154.1120 - Operating restrictions and interim operating authorization.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) Facility Operating in Prince William Sound, Alaska § 154.1120 Operating restrictions and interim operating authorization. (a) The owner or operator of a TAPAA facility may not operate in Prince William Sound, Alaska... practicable, a worst case discharge or a discharge of 200,000 barrels of oil, whichever is grater, in Prince...

On the Far Bank: The Effects of Gap Crossing on Operational Reach

DTIC Science & Technology

2015-05-25

operations. 15. SUBJECT TERMS United States Army; Gap crossing; River crossing; Operational reach; Operation Market -Garden; Operation Plunder...3 Case Study: Operation Market Garden...successful gap crossing. The Allied failure in Operation Market -Garden during World War II showed that successfully crossing a river such as the Waal does

40 CFR 63.4492 - What operating limits must I meet?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Standards for Hazardous Air Pollutants for Surface Coating of Plastic Parts and Products Emission Limitations § 63.4492 What operating limits must I meet? (a) For any coating operation(s) on which you use the... any operating limits. (b) For any controlled coating operation(s) on which you use the emission rate...

Bacterial strain changes during chronic otitis media surgery.

PubMed

Kim, G J; Yoo, S; Han, S; Bu, J; Hong, Y; Kim, D-K

2017-09-01

Cultures obtained from pre-operative middle-ear swabs from patients with chronic otitis media have traditionally been used to guide antibiotic selection. This study investigated changes in the bacterial strains of the middle ear during chronic otitis media surgery. Pre-operative bacterial cultures of otorrhoea, and peri-operative cultures of the granulation tissue in either the middle ear or mastoid cavity, were obtained. Post-operative cultures were selectively obtained when otorrhoea developed after surgery. Bacterial growth was observed in 45.5 per cent of pre-operative cultures, 13.5 per cent of peri-operative cultures and 4.5 per cent of post-operative cultures. Methicillin-resistant Staphylococcus aureus was identified as the most common bacteria in all pre-operative (32.4 per cent), peri-operative (52.4 per cent) and post-operative (71.4 per cent) tests, and the percentage of Methicillin-resistant S aureus increased from the pre- to the post-operative period. The bacterial culture results for post-operative otorrhoea showed low agreement with those for pre-operative or peri-operative culture, and strain re-identification was required.

Some induced intuitionistic fuzzy aggregation operators applied to multi-attribute group decision making

NASA Astrophysics Data System (ADS)

Su, Zhi-xin; Xia, Guo-ping; Chen, Ming-yuan

2011-11-01

In this paper, we define various induced intuitionistic fuzzy aggregation operators, including induced intuitionistic fuzzy ordered weighted averaging (OWA) operator, induced intuitionistic fuzzy hybrid averaging (I-IFHA) operator, induced interval-valued intuitionistic fuzzy OWA operator, and induced interval-valued intuitionistic fuzzy hybrid averaging (I-IIFHA) operator. We also establish various properties of these operators. And then, an approach based on I-IFHA operator and intuitionistic fuzzy weighted averaging (WA) operator is developed to solve multi-attribute group decision-making (MAGDM) problems. In such problems, attribute weights and the decision makers' (DMs') weights are real numbers and attribute values provided by the DMs are intuitionistic fuzzy numbers (IFNs), and an approach based on I-IIFHA operator and interval-valued intuitionistic fuzzy WA operator is developed to solve MAGDM problems where the attribute values provided by the DMs are interval-valued IFNs. Furthermore, induced intuitionistic fuzzy hybrid geometric operator and induced interval-valued intuitionistic fuzzy hybrid geometric operator are proposed. Finally, a numerical example is presented to illustrate the developed approaches.

Using mean duration and variation of procedure times to plan a list of surgical operations to fit into the scheduled list time.

PubMed

Pandit, Jaideep J; Tavare, Aniket

2011-07-01

It is important that a surgical list is planned to utilise as much of the scheduled time as possible while not over-running, because this can lead to cancellation of operations. We wished to assess whether, theoretically, the known duration of individual operations could be used quantitatively to predict the likely duration of the operating list. In a university hospital setting, we first assessed the extent to which the current ad-hoc method of operating list planning was able to match the scheduled operating list times for 153 consecutive historical lists. Using receiver operating curve analysis, we assessed the ability of an alternative method to predict operating list duration for the same operating lists. This method uses a simple formula: the sum of individual operation times and a pooled standard deviation of these times. We used the operating list duration estimated from this formula to generate a probability that the operating list would finish within its scheduled time. Finally, we applied the simple formula prospectively to 150 operating lists, 'shadowing' the current ad-hoc method, to confirm the predictive ability of the formula. The ad-hoc method was very poor at planning: 50% of historical operating lists were under-booked and 37% over-booked. In contrast, the simple formula predicted the correct outcome (under-run or over-run) for 76% of these operating lists. The calculated probability that a planned series of operations will over-run or under-run was found useful in developing an algorithm to adjust the planned cases optimally. In the prospective series, 65% of operating lists were over-booked and 10% were under-booked. The formula predicted the correct outcome for 84% of operating lists. A simple quantitative method of estimating operating list duration for a series of operations leads to an algorithm (readily created on an Excel spreadsheet, http://links.lww.com/EJA/A19) that can potentially improve operating list planning.

Military Police Brigade, Operational Art, and the Army Operating Concept 2016-2028

DTIC Science & Technology

2011-05-19

The Military Police Brigade, Operational Art , and the Army Operating Concept 2016-2028 A Monograph by Major Jon P. Myers United States...Brigade, Operational Art , and the Army Operating Concept 2016-2028 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS MAJ Jon P. Myers 6. AUTHOR(S...to, operational art by military police brigades and demonstrate their viability as a bridging mechanism to the operating concepts of wide area

IUS/TUG orbital operations and mission support study. Volume 3: Space tug operations

NASA Technical Reports Server (NTRS)

1975-01-01

A study was conducted to develop space tug operational concepts and baseline operations plan, and to provide cost estimates for space tug operations. Background data and study results are presented along with a transition phase analysis (the transition from interim upper state to tug operations). A summary is given of the tug operational and interface requirements with emphasis on the on-orbit checkout requirements, external interface operational requirements, safety requirements, and system operational interface requirements. Other topics discussed include reference missions baselined for the tug and details for the mission functional flows and timelines derived for the tug mission, tug subsystems, tug on-orbit operations prior to the tug first burn, spacecraft deployment and retrieval by the tug, operations centers, mission planning, potential problem areas, and cost data.

Runtime optimization of an application executing on a parallel computer

DOEpatents

None

2014-11-25

Identifying a collective operation within an application executing on a parallel computer; identifying a call site of the collective operation; determining whether the collective operation is root-based; if the collective operation is not root-based: establishing a tuning session and executing the collective operation in the tuning session; if the collective operation is root-based, determining whether all compute nodes executing the application identified the collective operation at the same call site; if all compute nodes identified the collective operation at the same call site, establishing a tuning session and executing the collective operation in the tuning session; and if all compute nodes executing the application did not identify the collective operation at the same call site, executing the collective operation without establishing a tuning session.

Runtime optimization of an application executing on a parallel computer

DOEpatents

Faraj, Daniel A; Smith, Brian E

2014-11-18

Identifying a collective operation within an application executing on a parallel computer; identifying a call site of the collective operation; determining whether the collective operation is root-based; if the collective operation is not root-based: establishing a tuning session and executing the collective operation in the tuning session; if the collective operation is root-based, determining whether all compute nodes executing the application identified the collective operation at the same call site; if all compute nodes identified the collective operation at the same call site, establishing a tuning session and executing the collective operation in the tuning session; and if all compute nodes executing the application did not identify the collective operation at the same call site, executing the collective operation without establishing a tuning session.

Runtime optimization of an application executing on a parallel computer

DOEpatents

Faraj, Daniel A.; Smith, Brian E.

2013-01-29

Identifying a collective operation within an application executing on a parallel computer; identifying a call site of the collective operation; determining whether the collective operation is root-based; if the collective operation is not root-based: establishing a tuning session and executing the collective operation in the tuning session; if the collective operation is root-based, determining whether all compute nodes executing the application identified the collective operation at the same call site; if all compute nodes identified the collective operation at the same call site, establishing a tuning session and executing the collective operation in the tuning session; and if all compute nodes executing the application did not identify the collective operation at the same call site, executing the collective operation without establishing a tuning session.

Operator function modeling: Cognitive task analysis, modeling and intelligent aiding in supervisory control systems

NASA Technical Reports Server (NTRS)

Mitchell, Christine M.

1990-01-01

The design, implementation, and empirical evaluation of task-analytic models and intelligent aids for operators in the control of complex dynamic systems, specifically aerospace systems, are studied. Three related activities are included: (1) the models of operator decision making in complex and predominantly automated space systems were used and developed; (2) the Operator Function Model (OFM) was used to represent operator activities; and (3) Operator Function Model Expert System (OFMspert), a stand-alone knowledge-based system was developed, that interacts with a human operator in a manner similar to a human assistant in the control of aerospace systems. OFMspert is an architecture for an operator's assistant that uses the OFM as its system and operator knowledge base and a blackboard paradigm of problem solving to dynamically generate expectations about upcoming operator activities and interpreting actual operator actions. An experiment validated the OFMspert's intent inferencing capability and showed that it inferred the intentions of operators in ways comparable to both a human expert and operators themselves. OFMspert was also augmented with control capabilities. An interface allowed the operator to interact with OFMspert, delegating as much or as little control responsibility as the operator chose. With its design based on the OFM, OFMspert's control capabilities were available at multiple levels of abstraction and allowed the operator a great deal of discretion over the amount and level of delegated control. An experiment showed that overall system performance was comparable for teams consisting of two human operators versus a human operator and OFMspert team.

Orthogonality preserving infinite dimensional quadratic stochastic operators

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

Akın, Hasan; Mukhamedov, Farrukh

In the present paper, we consider a notion of orthogonal preserving nonlinear operators. We introduce π-Volterra quadratic operators finite and infinite dimensional settings. It is proved that any orthogonal preserving quadratic operator on finite dimensional simplex is π-Volterra quadratic operator. In infinite dimensional setting, we describe all π-Volterra operators in terms orthogonal preserving operators.

26 CFR 1.812-4 - Operations loss carrybacks and operations loss carryovers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Gain and Loss from Operations § 1.812-4 Operations loss carrybacks and operations loss carryovers. (a) In general—(1) Years to which loss may be carried. In order to... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Operations loss carrybacks and operations loss...

Recent Human Factors Contributions to Improve Military Operations (Human Factors and Ergonomics Society Bulletin. Volume 46, Number 12, December 2003)

DTIC Science & Technology

2003-12-01

operations run the full gamut from large-scale, theater-wide combat, as witnessed in Operation Iraqi Freedom, to small-scale operations against terrorists, to... gamut from large-scale, theater-wide combat, as witnessed in Operation Iraqi Freedom, to small-scale operations against terror- ists, to operations

14 CFR 121.207 - Provisionally certificated airplanes: Operating limitations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Provisionally certificated airplanes... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Airplane Performance Operating Limitations § 121.207 Provisionally certificated airplanes: Operating limitations. In...

14 CFR 121.207 - Provisionally certificated airplanes: Operating limitations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Provisionally certificated airplanes... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Airplane Performance Operating Limitations § 121.207 Provisionally certificated airplanes: Operating limitations. In...

14 CFR 121.207 - Provisionally certificated airplanes: Operating limitations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Provisionally certificated airplanes... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Airplane Performance Operating Limitations § 121.207 Provisionally certificated airplanes: Operating limitations. In...

14 CFR 121.207 - Provisionally certificated airplanes: Operating limitations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Provisionally certificated airplanes... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Airplane Performance Operating Limitations § 121.207 Provisionally certificated airplanes: Operating limitations. In...

14 CFR 121.207 - Provisionally certificated airplanes: Operating limitations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Provisionally certificated airplanes... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Airplane Performance Operating Limitations § 121.207 Provisionally certificated airplanes: Operating limitations. In...

47 CFR 87.89 - Minimum operator requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

....89 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AVIATION SERVICES Operating Requirements and Procedures Radio Operator Requirements § 87.89 Minimum operator requirements. (a) A station operator must hold a commercial radio operator license or permit...

47 CFR 87.89 - Minimum operator requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

....89 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AVIATION SERVICES Operating Requirements and Procedures Radio Operator Requirements § 87.89 Minimum operator requirements. (a) A station operator must hold a commercial radio operator license or permit...

47 CFR 87.89 - Minimum operator requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

....89 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AVIATION SERVICES Operating Requirements and Procedures Radio Operator Requirements § 87.89 Minimum operator requirements. (a) A station operator must hold a commercial radio operator license or permit...

47 CFR 87.89 - Minimum operator requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

....89 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AVIATION SERVICES Operating Requirements and Procedures Radio Operator Requirements § 87.89 Minimum operator requirements. (a) A station operator must hold a commercial radio operator license or permit...

47 CFR 87.89 - Minimum operator requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

....89 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AVIATION SERVICES Operating Requirements and Procedures Radio Operator Requirements § 87.89 Minimum operator requirements. (a) A station operator must hold a commercial radio operator license or permit...

Operationally Efficient Propulsion System Study (OEPSS) data book. Volume 3: Operations technology

NASA Technical Reports Server (NTRS)

Vilja, John O.

1990-01-01

The study was initiated to identify operational problems and cost drivers for current propulsion systems and to identify technology and design approaches to increase the operational efficiency and reduce operations costs for future propulsion systems. To provide readily usable data for the Advanced Launch System (ALS) program, the results of the OEPSS study were organized into a series of OEPSS Data Books. This volume describes operations technologies that will enhance operational efficiency of propulsion systems. A total of 15 operations technologies were identified that will eliminate or mitigate operations problems described in Volume 2. A recommended development plan is presented for eight promising technologies that will simplify the propulsion system and reduce operational requirements.

Tele-Manipulation with Two Asymmetric Slaves: Two Operators Perform Better Than One.

PubMed

van Oosterhout, Jeroen; Heemskerk, Cock J M; de Baar, Marco R; van der Helm, Frans C T; Abbink, David A

2018-01-01

Certain tele-manipulation tasks require manipulation by two asymmetric slaves, for example, a crane for hoisting and a dexterous robotic arm for fine manipulation. It is unclear how to best design human-in-the-loop control over two asymmetric slaves. The goal of this paper is to quantitatively compare the standard approach of two co-operating operators that each control a single subtask, to a single operator performing bi-manual control over the two subtasks, and a uni-manual control approach. In a human factors experiment, participants performed a heavy load maneuvering and mounting task using a vertical crane and a robotic arm. We hypothesize that bi-manual control yields worse task performance and control activity compared to co-operation, because of conflicting spatial and temporal constraints. Literature suggests that uni-manual operators should perform better than co-operation, as co-operators critically depend on each other's actions. However, other literature provides evidence that individual operators have limited capabilities in controlling asymmetric axes of two dynamic systems. The results show that the two co-operators perform the maneuvering and mounting task faster than either bi- or uni-manual operators. Compared to co-operators, uni-manual operators required more control activity for the vertical crane and less for the robotic arm. In conclusion, this study suggests that when controlling two asymmetric slaves, a co-operating pair of operators performs better than a single operator.

Prevalence of operator fatigue in winter maintenance operations.

PubMed

Camden, Matthew C; Medina-Flintsch, Alejandra; Hickman, Jeffrey S; Bryce, James; Flintsch, Gerardo; Hanowski, Richard J

2018-02-02

Similar to commercial motor vehicle drivers, winter maintenance operators are likely to be at an increased risk of becoming fatigued while driving due to long, inconsistent shifts, environmental stressors, and limited opportunities for sleep. Despite this risk, there is little research concerning the prevalence of winter maintenance operator fatigue during winter emergencies. The purpose of this research was to investigate the prevalence, sources, and countermeasures of fatigue in winter maintenance operations. Questionnaires from 1043 winter maintenance operators and 453 managers were received from 29 Clear Road member states. Results confirmed that fatigue was prevalent in winter maintenance operations. Over 70% of the operators and managers believed that fatigue has a moderate to significant impact on winter maintenance operations. Approximately 75% of winter maintenance operators reported to at least sometimes drive while fatigued, and 96% of managers believed their winter maintenance operators drove while fatigued at least some of the time. Furthermore, winter maintenance operators and managers identified fatigue countermeasures and sources of fatigue related to winter maintenance equipment. However, the countermeasures believed to be the most effective at reducing fatigue during winter emergencies (i.e., naps) were underutilized. For example, winter maintenance operators reported to never use naps to eliminate fatigue. These results indicated winter maintenance operations are impacted by operator fatigue. These results support the increased need for research and effective countermeasures targeting winter maintenance operator fatigue. Copyright © 2018 Elsevier Ltd. All rights reserved.

40 CFR 445.1 - General applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... landfill wastewater from landfills operated in conjunction with other industrial or commercial operations... landfills operated in conjunction with other industrial or commercial operations when the landfill receives... operation. (g) This part does not apply to landfills operated in conjunction with Centralized Waste...

STS upper stage operations

NASA Technical Reports Server (NTRS)

Kitchens, M. D.; Schnyer, A. D.

1977-01-01

Several design/development and operational approaches for STS upper stages are being pursued to realize maximum operational and economic benefits upon the introduction of the STS in the 1980s. The paper focuses special attention on safety operations, launch site operations and on-orbit operations.

47 CFR 80.151 - Classification of operator licenses and endorsements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Operator Requirements § 80.151 Classification of... certificate). (5) MP. Marine Radio Operator Permit (radiotelephone operator's restricted certificate). (6) RP. Restricted Radiotelephone Operator Permit (radiotelephone operator's restricted certificate). (7) GOL. GMDSS...

47 CFR 80.151 - Classification of operator licenses and endorsements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Operator Requirements § 80.151 Classification of.... Restricted Radiotelephone Operator Permit (radiotelephone operator's restricted certificate). (2) RL. Restricted Radiotelephone Operator Permit-Limited Use. (3) MP. Marine Radio Operator Permit (radiotelephone...

47 CFR 80.151 - Classification of operator licenses and endorsements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Operator Requirements § 80.151 Classification of.... Restricted Radiotelephone Operator Permit (radiotelephone operator's restricted certificate). (2) RL. Restricted Radiotelephone Operator Permit-Limited Use. (3) MP. Marine Radio Operator Permit (radiotelephone...

47 CFR 80.151 - Classification of operator licenses and endorsements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Operator Requirements § 80.151 Classification of.... Restricted Radiotelephone Operator Permit (radiotelephone operator's restricted certificate). (2) RL. Restricted Radiotelephone Operator Permit-Limited Use. (3) MP. Marine Radio Operator Permit (radiotelephone...

Operator Variability in Scan Positioning is a Major Component of HR-pQCT Precision Error and is Reduced by Standardized Training

PubMed Central

Bonaretti, Serena; Vilayphiou, Nicolas; Chan, Caroline Mai; Yu, Andrew; Nishiyama, Kyle; Liu, Danmei; Boutroy, Stephanie; Ghasem-Zadeh, Ali; Boyd, Steven K.; Chapurlat, Roland; McKay, Heather; Shane, Elizabeth; Bouxsein, Mary L.; Black, Dennis M.; Majumdar, Sharmila; Orwoll, Eric S.; Lang, Thomas F.; Khosla, Sundeep; Burghardt, Andrew J.

2017-01-01

Introduction HR-pQCT is increasingly used to assess bone quality, fracture risk and anti-fracture interventions. The contribution of the operator has not been adequately accounted in measurement precision. Operators acquire a 2D projection (“scout view image”) and define the region to be scanned by positioning a “reference line” on a standard anatomical landmark. In this study, we (i) evaluated the contribution of positioning variability to in vivo measurement precision, (ii) measured intra- and inter-operator positioning variability, and (iii) tested if custom training software led to superior reproducibility in new operators compared to experienced operators. Methods To evaluate the operator in vivo measurement precision we compared precision errors calculated in 64 co-registered and non-co-registered scan-rescan images. To quantify operator variability, we developed software that simulates the positioning process of the scanner’s software. Eight experienced operators positioned reference lines on scout view images designed to test intra- and inter-operator reproducibility. Finally, we developed modules for training and evaluation of reference line positioning. We enrolled 6 new operators to participate in a common training, followed by the same reproducibility experiments performed by the experienced group. Results In vivo precision errors were up to three-fold greater (Tt.BMD and Ct.Th) when variability in scan positioning was included. Inter-operator precision errors were significantly greater than short-term intra-operator precision (p<0.001). New trained operators achieved comparable intra-operator reproducibility to experienced operators, and lower inter-operator reproducibility (p<0.001). Precision errors were significantly greater for the radius than for the tibia. Conclusion Operator reference line positioning contributes significantly to in vivo measurement precision and is significantly greater for multi-operator datasets. Inter-operator variability can be significantly reduced using a systematic training platform, now available online (http://webapps.radiology.ucsf.edu/refline/). PMID:27475931

Special Forces Capabilities of the European Union Military Forces

DTIC Science & Technology

2004-05-26

16 A Review of the History of Special Operations and Special Operations Forces ..... 16 Special Operations Defined...Herzegovina.15 Chapter Two - The Theory Connection - Special Operations and Special Operation Forces This chapter reviews the history and defines...18 Ibid, 87. 19 Ibid, 88. 20 Ibid, 114. 16 Special Operations and Special Operation Forces Theory A Review of the History of Special

Optimized scalar promotion with load and splat SIMD instructions

DOEpatents

Eichenberger, Alexander E; Gschwind, Michael K; Gunnels, John A

2013-10-29

Mechanisms for optimizing scalar code executed on a single instruction multiple data (SIMD) engine are provided. Placement of vector operation-splat operations may be determined based on an identification of scalar and SIMD operations in an original code representation. The original code representation may be modified to insert the vector operation-splat operations based on the determined placement of vector operation-splat operations to generate a first modified code representation. Placement of separate splat operations may be determined based on identification of scalar and SIMD operations in the first modified code representation. The first modified code representation may be modified to insert or delete separate splat operations based on the determined placement of the separate splat operations to generate a second modified code representation. SIMD code may be output based on the second modified code representation for execution by the SIMD engine.

Optimized scalar promotion with load and splat SIMD instructions

DOEpatents

Eichenberger, Alexandre E [Chappaqua, NY; Gschwind, Michael K [Chappaqua, NY; Gunnels, John A [Yorktown Heights, NY

2012-08-28

Mechanisms for optimizing scalar code executed on a single instruction multiple data (SIMD) engine are provided. Placement of vector operation-splat operations may be determined based on an identification of scalar and SIMD operations in an original code representation. The original code representation may be modified to insert the vector operation-splat operations based on the determined placement of vector operation-splat operations to generate a first modified code representation. Placement of separate splat operations may be determined based on identification of scalar and SIMD operations in the first modified code representation. The first modified code representation may be modified to insert or delete separate splat operations based on the determined placement of the separate splat operations to generate a second modified code representation. SIMD code may be output based on the second modified code representation for execution by the SIMD engine.

47 CFR 13.9 - Eligibility and application for new license or endorsement.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Radar Endorsement, Six Months Service Endorsement, GMDSS Radio Operator's License, Restricted GMDSS... Operator License, Marine Radio Operator Permit, First Class Radiotelegraph Operator's Certificate, Second... Restricted Radiotelephone Operator Permit or a Restricted Radiotelephone Operator Permit-Limited Use must be...

Reducing power consumption while performing collective operations on a plurality of compute nodes

DOEpatents

Archer, Charles J [Rochester, MN; Blocksome, Michael A [Rochester, MN; Peters, Amanda E [Rochester, MN; Ratterman, Joseph D [Rochester, MN; Smith, Brian E [Rochester, MN

2011-10-18

Methods, apparatus, and products are disclosed for reducing power consumption while performing collective operations on a plurality of compute nodes that include: receiving, by each compute node, instructions to perform a type of collective operation; selecting, by each compute node from a plurality of collective operations for the collective operation type, a particular collective operation in dependence upon power consumption characteristics for each of the plurality of collective operations; and executing, by each compute node, the selected collective operation.

Maclaurin symmetric mean operators of linguistic intuitionistic fuzzy numbers and their application to multiple-attribute decision-making

NASA Astrophysics Data System (ADS)

Liu, Peide; Qin, Xiyou

2017-11-01

Linguistic intuitionistic fuzzy number (LIFN) is a special intuitionistic fuzzy number which can more easily describe the vagueness existing in the real decision-making. Maclaurin symmetric mean (MSM) operator has the characteristic of considering the interrelationships among any number of input parameters. In this paper, we extended the MSM operator to the LIFNs and some extended MSM operators for LIFNs were proposed, some new decision-making methods were developed. Firstly, we introduced the definition, score function, properties and operational rules of the LIFNs. Then, we proposed some linguistic intuitionistic fuzzy MSM operators, such as linguistic intuitionistic fuzzy Maclaurin symmetric mean operator, weighted linguistic intuitionistic fuzzy Maclaurin symmetric mean (WLIFMSM) operator, linguistic intuitionistic fuzzy dual Maclaurin symmetric mean operator, weighted linguistic intuitionistic fuzzy dual Maclaurin symmetric mean (WLIFDMSM) operator. In the meantime, we studied some important properties of these operators, and developed some methods based on WLIFMSM operator and WLIFDMSM operator for multi-attribute decision-making. Finally, we use an example to demonstrate the effectiveness of the proposed methods.

An expert system for benzole recovery plant

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

Ishiguro, H.; Matsumura, S.; Kawashima, A.

1993-01-01

In the By-Product Plant of NKK's Keihin Works, systematization efforts were made in 1988, including integration of the control rooms, introduction of computers and installation of automatic analyzers. This has however increased the burden on operators with a huge volume of data, and a delay in coping with an operational abnormality might expand risk and extent of damages. There is, on the other hand, a pressing need to take measures to accommodate sophisticated operations resulting from the pursuit of high productivity operation. For the purpose of avoiding these possible inconveniences, development of a real-time operation system has been tried inmore » an attempt to improve safety and operating techniques and productivity in the benzole recovery plant. An offline system based on manual entry of operating data for diagnosis of operation and abnormality was developed in 1990, and an online real-time system operating by incorporating real-time operating data was developed in 1991, which is now smoothly operating in commercial operations. This report presents an outline of the benzole recovery operation diagnosis control expert system.« less

Representing operations procedures using temporal dependency networks

NASA Technical Reports Server (NTRS)

Fayyad, Kristina E.; Cooper, Lynne P.

1993-01-01

DSN Link Monitor & Control (LMC) operations consist primarily of executing procedures to configure, calibrate, test, and operate a communications link between an interplanetary spacecraft and its mission control center. Currently the LMC operators are responsible for integrating procedures into an end-to-end series of steps. The research presented in this paper is investigating new ways of specifying operations procedures that incorporate the insight of operations, engineering, and science personnel to improve mission operations. The paper describes the rationale for using Temporal Dependency Networks (TDN's) to represent the procedures, a description of how the data is acquired, and the knowledge engineering effort required to represent operations procedures. Results of operational tests of this concept, as implemented in the LMC Operator Assistant Prototype (LMCOA), are also presented.

Interactive digital signal processor

NASA Technical Reports Server (NTRS)

Mish, W. H.; Wenger, R. M.; Behannon, K. W.; Byrnes, J. B.

1982-01-01

The Interactive Digital Signal Processor (IDSP) is examined. It consists of a set of time series analysis Operators each of which operates on an input file to produce an output file. The operators can be executed in any order that makes sense and recursively, if desired. The operators are the various algorithms used in digital time series analysis work. User written operators can be easily interfaced to the sysatem. The system can be operated both interactively and in batch mode. In IDSP a file can consist of up to n (currently n=8) simultaneous time series. IDSP currently includes over thirty standard operators that range from Fourier transform operations, design and application of digital filters, eigenvalue analysis, to operators that provide graphical output, allow batch operation, editing and display information.

Tug fleet and ground operations schedules and controls. Volume 2: part 1

NASA Technical Reports Server (NTRS)

1975-01-01

This Tug Fleet and Ground Operations Schedules and Controls Study addresses both ground operational data and technical requirements that span the Tug planning phase and operations phase. A similar study covering mission operations (by others) provides the complimentary flight operations details. The two studies provide the planning data requirements, resource allocation, and control milestones for supporting the requirements of the STS program. This Tug Fleet and Ground Operations Schedules and Controls Study incorporates the basic ground operations requirements and concepts provided by previous studies with the interrelationships of the planning, IUS transition, and Tug fleet operations phases. The interrelationships of these phases were studied as a system to optimize overall program benefits and minimize operational risk factors.

14 CFR 121.535 - Responsibility for operational control: Flag operations.

Code of Federal Regulations, 2013 CFR

2013-01-01

... dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations...— (1) Monitoring the progress of each flight; (2) Issuing necessary instructions and information for...

14 CFR 121.535 - Responsibility for operational control: Flag operations.

Code of Federal Regulations, 2011 CFR

2011-01-01

... dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations...— (1) Monitoring the progress of each flight; (2) Issuing necessary instructions and information for...

14 CFR 121.535 - Responsibility for operational control: Flag operations.

Code of Federal Regulations, 2010 CFR

2010-01-01

... dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations...— (1) Monitoring the progress of each flight; (2) Issuing necessary instructions and information for...

14 CFR 121.535 - Responsibility for operational control: Flag operations.

Code of Federal Regulations, 2012 CFR

2012-01-01

... dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations...— (1) Monitoring the progress of each flight; (2) Issuing necessary instructions and information for...

14 CFR 121.535 - Responsibility for operational control: Flag operations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... dispatcher are jointly responsible for the preflight planning, delay, and dispatch release of a flight in... AND OPERATIONS OPERATING REQUIREMENTS: DOMESTIC, FLAG, AND SUPPLEMENTAL OPERATIONS Flight Operations...— (1) Monitoring the progress of each flight; (2) Issuing necessary instructions and information for...

40 CFR 60.546 - Reporting requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... cementing operation, each sidewall cementing operation, each green tire spraying operation where organic solvent-based sprays are used, each Michelin-A operation, each Michelin-B operation, and each Michelin-C...) is applicable) to be employed. (b) Each owner or operator subject to the provisions of this subpart...

49 CFR 1562.3 - Operating requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

... minimum, must: (1) Identify and provide contact information for the airport's airport security coordinator... and non-operational hours; and (ii) Alert the aircraft owner(s) and operator(s), the airport operator...) U.S. Armed forces, law enforcement, and aeromedical services aircraft. An individual may operate a U...

49 CFR 1562.3 - Operating requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... minimum, must: (1) Identify and provide contact information for the airport's airport security coordinator... and non-operational hours; and (ii) Alert the aircraft owner(s) and operator(s), the airport operator...) U.S. Armed forces, law enforcement, and aeromedical services aircraft. An individual may operate a U...

49 CFR 1562.3 - Operating requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... minimum, must: (1) Identify and provide contact information for the airport's airport security coordinator... and non-operational hours; and (ii) Alert the aircraft owner(s) and operator(s), the airport operator...) U.S. Armed forces, law enforcement, and aeromedical services aircraft. An individual may operate a U...

49 CFR 1562.3 - Operating requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

... minimum, must: (1) Identify and provide contact information for the airport's airport security coordinator... and non-operational hours; and (ii) Alert the aircraft owner(s) and operator(s), the airport operator...) U.S. Armed forces, law enforcement, and aeromedical services aircraft. An individual may operate a U...

49 CFR 1562.3 - Operating requirements.

Code of Federal Regulations, 2012 CFR

2012-10-01

... minimum, must: (1) Identify and provide contact information for the airport's airport security coordinator... and non-operational hours; and (ii) Alert the aircraft owner(s) and operator(s), the airport operator...) U.S. Armed forces, law enforcement, and aeromedical services aircraft. An individual may operate a U...

25 CFR 142.8 - Is economy of operation a requirement for the Alaska Resupply Operation?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Is economy of operation a requirement for the Alaska Resupply Operation? 142.8 Section 142.8 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES ALASKA RESUPPLY OPERATION § 142.8 Is economy of operation a requirement for the Alaska Resupply Operation? Yes. The Manager must...

ALMA Array Operations Group process overview

NASA Astrophysics Data System (ADS)

Barrios, Emilio; Alarcon, Hector

2016-07-01

ALMA Science operations activities in Chile are responsibility of the Department of Science Operations, which consists of three groups, the Array Operations Group (AOG), the Program Management Group (PMG) and the Data Management Group (DMG). The AOG includes the Array Operators and have the mission to provide support for science observations, operating safely and efficiently the array. The poster describes the AOG process, management and operational tools.

Automatic Combination of Operators in a Genetic Algorithm to Solve the Traveling Salesman Problem.

PubMed

Contreras-Bolton, Carlos; Parada, Victor

2015-01-01

Genetic algorithms are powerful search methods inspired by Darwinian evolution. To date, they have been applied to the solution of many optimization problems because of the easy use of their properties and their robustness in finding good solutions to difficult problems. The good operation of genetic algorithms is due in part to its two main variation operators, namely, crossover and mutation operators. Typically, in the literature, we find the use of a single crossover and mutation operator. However, there are studies that have shown that using multi-operators produces synergy and that the operators are mutually complementary. Using multi-operators is not a simple task because which operators to use and how to combine them must be determined, which in itself is an optimization problem. In this paper, it is proposed that the task of exploring the different combinations of the crossover and mutation operators can be carried out by evolutionary computing. The crossover and mutation operators used are those typically used for solving the traveling salesman problem. The process of searching for good combinations was effective, yielding appropriate and synergic combinations of the crossover and mutation operators. The numerical results show that the use of the combination of operators obtained by evolutionary computing is better than the use of a single operator and the use of multi-operators combined in the standard way. The results were also better than those of the last operators reported in the literature.

Automatic Combination of Operators in a Genetic Algorithm to Solve the Traveling Salesman Problem

PubMed Central

2015-01-01

Genetic algorithms are powerful search methods inspired by Darwinian evolution. To date, they have been applied to the solution of many optimization problems because of the easy use of their properties and their robustness in finding good solutions to difficult problems. The good operation of genetic algorithms is due in part to its two main variation operators, namely, crossover and mutation operators. Typically, in the literature, we find the use of a single crossover and mutation operator. However, there are studies that have shown that using multi-operators produces synergy and that the operators are mutually complementary. Using multi-operators is not a simple task because which operators to use and how to combine them must be determined, which in itself is an optimization problem. In this paper, it is proposed that the task of exploring the different combinations of the crossover and mutation operators can be carried out by evolutionary computing. The crossover and mutation operators used are those typically used for solving the traveling salesman problem. The process of searching for good combinations was effective, yielding appropriate and synergic combinations of the crossover and mutation operators. The numerical results show that the use of the combination of operators obtained by evolutionary computing is better than the use of a single operator and the use of multi-operators combined in the standard way. The results were also better than those of the last operators reported in the literature. PMID:26367182

Improved NSGA model for multi objective operation scheduling and its evaluation

NASA Astrophysics Data System (ADS)

Li, Weining; Wang, Fuyu

2017-09-01

Reasonable operation can increase the income of the hospital and improve the patient’s satisfactory level. In this paper, by using multi object operation scheduling method with improved NSGA algorithm, it shortens the operation time, reduces the operation costand lowers the operation risk, the multi-objective optimization model is established for flexible operation scheduling, through the MATLAB simulation method, the Pareto solution is obtained, the standardization of data processing. The optimal scheduling scheme is selected by using entropy weight -Topsis combination method. The results show that the algorithm is feasible to solve the multi-objective operation scheduling problem, and provide a reference for hospital operation scheduling.

International Space Station Payload Operations Integration

NASA Technical Reports Server (NTRS)

Fanske, Elizabeth Anne

2011-01-01

The Payload Operations Integrator (POINT) plays an integral part in the Certification of Flight Readiness process for the Mission Operations Laboratory and the Payload Operations Integration Function that supports International Space Station Payload operations. The POINTs operate in support of the POIF Payload Operations Manager to bring together and integrate the Certification of Flight Readiness inputs from various MOL teams through maintaining an open work tracking log. The POINTs create monthly metrics for current and future payloads that the Payload Operations Integration Function supports. With these tools, the POINTs assemble the Certification of Flight Readiness package before a given flight, stating that the Mission Operations Laboratory is prepared to support it. I have prepared metrics for Increment 29/30, maintained the Open Work Tracking Logs for Flights ULF6 (STS-134) and ULF7 (STS-135), and submitted the Mission Operations Laboratory Certification of Flight Readiness package for Flight 44P to the Mission Operations Directorate (MOD/OZ).

Path planning during combustion mode switch

DOEpatents

Jiang, Li; Ravi, Nikhil

2015-12-29

Systems and methods are provided for transitioning between a first combustion mode and a second combustion mode in an internal combustion engine. A current operating point of the engine is identified and a target operating point for the internal combustion engine in the second combustion mode is also determined. A predefined optimized transition operating point is selected from memory. While operating in the first combustion mode, one or more engine actuator settings are adjusted to cause the operating point of the internal combustion engine to approach the selected optimized transition operating point. When the engine is operating at the selected optimized transition operating point, the combustion mode is switched from the first combustion mode to the second combustion mode. While operating in the second combustion mode, one or more engine actuator settings are adjusted to cause the operating point of the internal combustion to approach the target operating point.

Control system for, and a method of, heating an operator station of a work machine

DOEpatents

Baker, Thomas M.; Hoff, Brian D.; Akasam, Sivaprasad

2005-04-05

There are situations in which an operator remains in an operator station of a work machine when an engine of the work machine is inactive. The present invention includes a control system for, and a method of, heating the operator station when the engine is inactive. A heating system of the work machine includes an electrically-powered coolant pump, a power source, and at least one piece of warmed machinery. An operator heat controller is moveable between a first and a second position, and is operable to connect the electrically-powered coolant pump to the power source when the engine is inactive and the operator heat controller is in the first position. Thus, by deactivating the engine and then moving the operator heat controller to the first position, the operator may supply electrical energy to the electrically-powered coolant pump, which is operably coupled to heat the operator station.

49 CFR 192.605 - Procedural manual for operations, maintenance, and emergencies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... operations and maintenance activities are conducted. (b) Maintenance and normal operations. The manual... personnel to determine the effectiveness, and adequacy of the procedures used in normal operation and... or flow rate outside normal operating limits; (iii) Loss of communications; (iv) Operation of any...

23 CFR 450.314 - Metropolitan planning agreements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Metropolitan planning agreements. (a) The MPO, the State(s), and the public transportation operator(s) shall...(s), and the public transportation operator(s) serving the MPA. To the extent possible, a single... agreement among the MPOs, the State(s), and the public transportation operator(s) describing how the...

43 CFR 420.12 - Requirements-operators.

Code of Federal Regulations, 2012 CFR

2012-10-01

... THE INTERIOR OFF-ROAD VEHICLE USE Operating Criteria § 420.12 Requirements—operators. (a) In addition... off-road vehicles; if State laws are lacking or less stringent than the regulations established in... operator of an off-road vehicle operated on Reclamation lands shall possess a valid motor vehicle operator...

43 CFR 420.12 - Requirements-operators.

Code of Federal Regulations, 2013 CFR

2013-10-01

... THE INTERIOR OFF-ROAD VEHICLE USE Operating Criteria § 420.12 Requirements—operators. (a) In addition... off-road vehicles; if State laws are lacking or less stringent than the regulations established in... operator of an off-road vehicle operated on Reclamation lands shall possess a valid motor vehicle operator...

43 CFR 420.12 - Requirements-operators.

Code of Federal Regulations, 2014 CFR

2014-10-01

... THE INTERIOR OFF-ROAD VEHICLE USE Operating Criteria § 420.12 Requirements—operators. (a) In addition... off-road vehicles; if State laws are lacking or less stringent than the regulations established in... operator of an off-road vehicle operated on Reclamation lands shall possess a valid motor vehicle operator...

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2011 CFR

2011-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

49 CFR 218.107 - Additional operational requirements for hand-operated crossover switches.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-operated crossover switches. 218.107 Section 218.107 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.107 Additional operational requirements for hand-operated crossover switches. (a) Each railroad shall adopt and comply with an operating rule which...

76 FR 80261 - National Emission Standards for Hazardous Air Pollutants: Area Source Standards for Prepared...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-23

... specifications and operating instructions, if available, or standard operating procedures must be developed by... manufacturer's specifications and operating instructions, if available, or standard operating procedures must... operating specifications or standard operating procedures developed by the prepared feeds manufacturer be...

49 CFR 193.2503 - Operating procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

...: FEDERAL SAFETY STANDARDS Operations § 193.2503 Operating procedures. Each operator shall follow one or more manuals of written procedures to provide safety in normal operation and in responding to an... 49 Transportation 3 2013-10-01 2013-10-01 false Operating procedures. 193.2503 Section 193.2503...

49 CFR 193.2503 - Operating procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

...: FEDERAL SAFETY STANDARDS Operations § 193.2503 Operating procedures. Each operator shall follow one or more manuals of written procedures to provide safety in normal operation and in responding to an... 49 Transportation 3 2011-10-01 2011-10-01 false Operating procedures. 193.2503 Section 193.2503...

49 CFR 193.2503 - Operating procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

...: FEDERAL SAFETY STANDARDS Operations § 193.2503 Operating procedures. Each operator shall follow one or more manuals of written procedures to provide safety in normal operation and in responding to an... 49 Transportation 3 2014-10-01 2014-10-01 false Operating procedures. 193.2503 Section 193.2503...

49 CFR 193.2503 - Operating procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

...: FEDERAL SAFETY STANDARDS Operations § 193.2503 Operating procedures. Each operator shall follow one or more manuals of written procedures to provide safety in normal operation and in responding to an... 49 Transportation 3 2012-10-01 2012-10-01 false Operating procedures. 193.2503 Section 193.2503...

Regional concept for transportation operations fosters planning for operations in the Tucson metropolitan area : operation-focused planning for operations

DOT National Transportation Integrated Search

2009-04-01

The Tucson metropolitan region embarked on developing a regional concept for transportation operations (RCTO) in 2005 as part of a Federal Highway Administration demonstration initiative to advance regional collaboration for operations. The RCTO is a...

25 CFR 573.6 - Order of temporary closure.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 514. (3) A gaming operation operates for business without a tribal ordinance or resolution that the Chairman has approved under part 522 or 523 of this chapter. (4) A gaming operation operates for business... operation operates for business without either background investigations having been completed for, or...

14 CFR 91.1013 - Operational control briefing and acknowledgment.

Code of Federal Regulations, 2010 CFR

2010-01-01

... management services contract, the program manager must brief the fractional owner on the owner's operational... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Operational control briefing and... Ownership Operations Operational Control § 91.1013 Operational control briefing and acknowledgment. (a) Upon...

Ultra-High Capacity Silicon Photonic Interconnects through Spatial Multiplexing

NASA Astrophysics Data System (ADS)

Chen, Christine P.

The market for higher data rate communication is driving the semiconductor industry to develop new techniques of writing at smaller scales, while continuing to scale bandwidth at low power consumption. Silicon photonic (SiPh) devices offer a potential solution to the electronic interconnect bandwidth bottleneck. SiPh leverages the technology commensurate of decades of fabrication development with the unique functionality of next-generation optical interconnects. Finer fabrication techniques have allowed for manufacturing physical characteristics of waveguide structures that can support multiple modes in a single waveguide. By refining modal characteristics in photonic waveguide structures, through mode multiplexing with the asymmetric y-junction and microring resonator, higher aggregate data bandwidth is demonstrated via various combinations of spatial multiplexing, broadening applications supported by the integrated platform. The main contributions of this dissertation are summarized as follows. Experimental demonstrations of new forms of spatial multiplexing combined together exhibit feasibility of data transmission through mode-division multiplexing (MDM), mode-division and wavelength-division multiplexing (MDM-WDM), and mode-division and polarization-division multiplexing (MDM-PDM) through a C-band, Si photonic platform. Error-free operation through mode multiplexers and demultiplexers show how data can be viably scaled on multiple modes and with existing spatial domains simultaneously. Furthermore, we explore expanding device channel support from two to three arms. Finding that a slight mismatch in the third arm can increase crosstalk contributions considerably, especially when increasing data rate, we explore a methodical way to design the asymmetric y-junction device by considering its angles and multiplexer/demultiplexer arm width. By taking into consideration device fabrication variations, we turn towards optimizing device performance post-fabrication. Through ModePROP simulations, optimizing device performance dynamically post-fabrication is analyzed, through either electro-optical or thermo-optical means. By biasing the arm introducing the slight spectral offset, we can quantifiably improve device performance. Scaling bandwidth is experimentally demonstrated through the device at 3 modes, 2 wavelengths, and 40 Gb/s data rate for 240 Gb/s aggregate bandwidth, with the potential to reduce power penalty per the device optimization process we described. A main motivation for this on-chip spatial multiplexing is the need to reduce costs. As the laser source serves as the greatest power consumer in an optical system, mode-division multiplexing and other forms of spatial multiplexing can be implemented to push its potentially prohibitive cost metrics down. In order to demonstrate an intelligent platform capable of dynamically multicasting data and reallocating power as needed by the system, we must first initialize the switch fabric to control with an electronic interface. A dithering mechanism, whereby exact cross, bar, and sub-percentage states are enforced through the device, is described here. Such a method could be employed for actuating the device table of bias values to states automatically. We then employ a dynamic power reallocation algorithm through a data acquisition unit, showing real-time channel recovery for channels experiencing power loss by diverting power from paths that could tolerate it. The data that is being multicast through the system is experimentally shown to be error-free at 40 Gb/s data rate, when transmitting from one to three clients and going from automatic bar/cross states to equalized power distribution. For the last portion of this topic, the switch fabric was inserted into a high-performance computing system. In order to run benchmarks at 10 Gb/s data ontop of the switch fabric, a newer model of the control plane was implemented to toggle states according to the command issued by the server. Such a programmable mechanism will prove necessary in future implementations of optical subsystems embedded inside larger systems, like data centers. Beyond the specific control plane demonstrated, the idea of an intelligent photonic layer can be applied to alleviate many kinds of optical channel abnormalities or accommodate for switching based on different patterns in data transmission. Finally, the experimental demonstration of a coherent perfect absorption Si modulator is exhibited, showing a viable extinction ratio of 24.5 dB. Using this coherent perfect absorption mechanism to demodulate signals, there is the added benefit of differential reception. Currently, an automated process for data collection is employed at a faster time scale than instabilities present in fibers in the setup with future implementations eliminating the off-chip phase modulator for greater signal stability. The field of SiPh has developed to a stage where specific application domains can take off and compete according to industrial-level standards. The work in this dissertation contributes to experimental demonstration of a newly developing area of mode-division multiplexing for substantially increasing bandwidth on-chip. While implementing the discussed photonic devices in dynamic systems, various attributes of integrated photonics are leveraged with existing electronic technologies. Future generations of computing systems should then be designed by implementing both system and device level considerations. (Abstract shortened by ProQuest.).

Erratic Black Hole Regulates Itself

NASA Astrophysics Data System (ADS)

2009-03-01

New results from NASA's Chandra X-ray Observatory have made a major advance in explaining how a special class of black holes may shut off the high-speed jets they produce. These results suggest that these black holes have a mechanism for regulating the rate at which they grow. Black holes come in many sizes: the supermassive ones, including those in quasars, which weigh in at millions to billions of times the mass of the Sun, and the much smaller stellar-mass black holes which have measured masses in the range of about 7 to 25 times the Sun's mass. Some stellar-mass black holes launch powerful jets of particles and radiation, like seen in quasars, and are called "micro-quasars". The new study looks at a famous micro-quasar in our own Galaxy, and regions close to its event horizon, or point of no return. This system, GRS 1915+105 (GRS 1915 for short), contains a black hole about 14 times the mass of the Sun that is feeding off material from a nearby companion star. As the material swirls toward the black hole, an accretion disk forms. This system shows remarkably unpredictable and complicated variability ranging from timescales of seconds to months, including 14 different patterns of variation. These variations are caused by a poorly understood connection between the disk and the radio jet seen in GRS 1915. Chandra, with its spectrograph, has observed GRS 1915 eleven times since its launch in 1999. These studies reveal that the jet in GRS 1915 may be periodically choked off when a hot wind, seen in X-rays, is driven off the accretion disk around the black hole. The wind is believed to shut down the jet by depriving it of matter that would have otherwise fueled it. Conversely, once the wind dies down, the jet can re-emerge. "We think the jet and wind around this black hole are in a sort of tug of war," said Joseph Neilsen, Harvard graduate student and lead author of the paper appearing in the journal Nature. "Sometimes one is winning and then, for reasons we don't entirely understand, the other one gets the upper hand." GRS 1915+105 Chandra X-ray Image of GRS 1915+105 The latest Chandra results also show that the wind and the jet carry about the same amount of matter away from the black hole. This is evidence that the black hole is somehow regulating its accretion rate, which may be related to the toggling between mass expulsion via either a jet or a wind from the accretion disk. Self-regulation is a common topic when discussing supermassive black holes, but this is the first clear evidence for it in stellar-mass black holes. "It is exciting that we may be on the track of explaining two mysteries at the same time: how black hole jets can be shut down and also how black holes regulate their growth," said co-author Julia Lee, assistant professor in the Astronomy department at the Harvard-Smithsonian Center for Astrophysics. "Maybe black holes can regulate themselves better than the financial markets!" Although micro-quasars and quasars differ in mass by factors of millions, they should show a similarity in behavior when their very different physical scales are taken into account. People Who Read This Also Read... Chandra Data Reveal Rapidly Whirling Black Holes Jet Power and Black Hole Assortment Revealed in New Chandra Image Celebrate the International Year of Astronomy Ghost Remains After Black Hole Eruption "If quasars and micro-quasars behave very differently, then we have a big problem to figure out why, because gravity treats them the same," said Neilsen. "So, our result is actually very reassuring, because it's one more link between these different types of black holes." The timescale for changes in behavior of a black hole should vary in proportion to the mass. For example, an hour-long timescale for changes in GRS 1915 would correspond to about 10,000 years for a supermassive black hole that weighs a billion times the mass of the Sun. "We cannot hope to explore at this level of detail in any single supermassive black hole system," said Lee. "So, we can learn a tremendous amount about black holes by just studying stellar-mass black holes like this one." It is not known what causes the jet to turn on again once the wind dies down, and this remains one of the major unsolved mysteries in astronomy. "Every major observatory, ground and space, has been used to study this black hole for the past two decades," said Neilsen. "Although we still don't have all the answers, we think our work is a step in the right direction." This was work made using Chandra's High Energy Transmission Gratings Spectrometer. These results appear in the March 26th issue of Nature. NASA's Marshall Space Flight Center in Huntsville, Ala., manages the Chandra program for NASA's Science Mission Directorate in Washington. The Smithsonian Astrophysical Observatory controls Chandra's science and flight operations from Cambridge, Mass.

Can the pre-operative Western Ontario and McMaster score predict patient satisfaction following total hip arthroplasty?

PubMed

Rogers, B A; Alolabi, B; Carrothers, A D; Kreder, H J; Jenkinson, R J

2015-02-01

In this study we evaluated whether pre-operative Western Ontario and McMaster Universities (WOMAC) osteoarthritis scores can predict satisfaction following total hip arthroplasty (THA). Prospective data for a cohort of patients undergoing THA from two large academic centres were collected, and pre-operative and one-year post-operative WOMAC scores and a 25-point satisfaction questionnaire were obtained for 446 patients. Satisfaction scores were dichotomised into either improvement or deterioration. Scatter plots and Spearman's rank correlation coefficient were used to describe the association between pre-operative WOMAC and one-year post-operative WOMAC scores and patient satisfaction. Satisfaction was compared using receiver operating characteristic (ROC) analysis against pre-operative, post-operative and δ WOMAC scores. We found no relationship between pre-operative WOMAC scores and one-year post-operative WOMAC or satisfaction scores, with Spearman's rank correlation coefficients of 0.16 and -0.05, respectively. The ROC analysis showed areas under the curve (AUC) of 0.54 (pre-operative WOMAC), 0.67 (post-operative WOMAC) and 0.43 (δ WOMAC), respectively, for an improvement in satisfaction. We conclude that the pre-operative WOMAC score does not predict the post-operative WOMAC score or patient satisfaction after THA, and that WOMAC scores can therefore not be used to prioritise patient care. ©2015 The British Editorial Society of Bone & Joint Surgery.

Cost of enlarged operating zone for an existing Francis runner

NASA Astrophysics Data System (ADS)

Monette, Christine; Marmont, Hugues; Chamberland-Lauzon, Joël; Skagerstrand, Anders; Coutu, André; Carlevi, Jens

2016-11-01

Traditionally, hydro power plants have been operated close to best efficiency point, the more stable operating condition for which they have been designed. However, because of changes in the electricity market, many hydro power plants operators wish to operate their machines differently to fulfil those new market needs. New operating conditions can include whole range operation, many start/stops, extensive low load operation, synchronous condenser mode and power/frequency regulation. Many of these new operating conditions may impose more severe fatigue damage than the traditional base load operation close to best efficiency point. Under these conditions, the fatigue life of the runner may be significantly reduced and reparation or replacement cost might occur sooner than expected. In order to design reliable Francis runners for those new challenging operating scenarios, Andritz Hydro has developed various proprietary tools and design rules. These are used within Andritz Hydro to design mechanically robust Francis runners for the operating scenarios fulfilling customer's specifications. To estimate residual life under different operating scenarios of an existing runner designed years ago for best efficiency base load operation, Andritz Hydro's design rules and tools would necessarily lead to conservative results. While the geometry of a new runner can be modified to fulfil all conservative mechanical design rules, the predicted fatigue life of an existing runner under off-design operating conditions may appear rather short because of the conservative safety factor included in the calculations. The most precise and reliable way to calculate residual life of an existing runner under different operating scenarios is to perform a strain gauge measurement campaign on the runner. This paper presents the runner strain gage measurement campaign of a mid-head Francis turbine over all the operating conditions available during the test, the analysis of the measurement signals and the runner residual life assessment under different operating scenarios. With these results, the maintenance cost of the change in operating mode can then be calculated and foreseen by the power plant owner.

21 CFR 111.110 - What quality control operations are required for laboratory operations associated with the...

Code of Federal Regulations, 2010 CFR

2010-04-01

... laboratory operations associated with the production and process control system? 111.110 Section 111.110 Food... OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control System: Requirements for Quality Control... production and process control system? Quality control operations for laboratory operations associated with...

14 CFR 380.34 - Security and depository agreements.

Code of Federal Regulations, 2010 CFR

2010-01-01

... charter operator for that charter. (2) The direct air carrier and charter operator or foreign charter... operator or foreign charter operator shall furnish a security agreement in an amount for not less than the... charter operator with respect to the charter. (b) The direct air carrier and the charter operator or...

23 CFR 450.330 - Project selection from the TIP.

Code of Federal Regulations, 2010 CFR

2010-04-01

... projects shall be jointly developed by the MPO, the State, and the public transportation operator(s) if requested by the MPO, the State, or the public transportation operator(s). If the State or public... the MPO, the State, and the public transportation operator(s) jointly develop expedited project...

25 CFR 502.10 - Gaming operation.

Code of Federal Regulations, 2010 CFR

2010-04-01

....10 Gaming operation. Gaming operation means each economic entity that is licensed by a tribe, operates the games, receives the revenues, issues the prizes, and pays the expenses. A gaming operation may... 25 Indians 2 2010-04-01 2010-04-01 false Gaming operation. 502.10 Section 502.10 Indians NATIONAL...

14 CFR 91.189 - Category II and III operations: General operating rules.

Code of Federal Regulations, 2013 CFR

2013-01-01

... pilot who is controlling the aircraft has appropriate instrumentation for the type of flight control... TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES GENERAL OPERATING AND FLIGHT RULES Flight Rules Instrument Flight Rules § 91.189 Category II and III operations: General operating rules. (a) No...

14 CFR 91.189 - Category II and III operations: General operating rules.

Code of Federal Regulations, 2012 CFR

2012-01-01

... pilot who is controlling the aircraft has appropriate instrumentation for the type of flight control... TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES GENERAL OPERATING AND FLIGHT RULES Flight Rules Instrument Flight Rules § 91.189 Category II and III operations: General operating rules. (a) No...

14 CFR 91.189 - Category II and III operations: General operating rules.

Code of Federal Regulations, 2014 CFR

2014-01-01

... pilot who is controlling the aircraft has appropriate instrumentation for the type of flight control... TRANSPORTATION (CONTINUED) AIR TRAFFIC AND GENERAL OPERATING RULES GENERAL OPERATING AND FLIGHT RULES Flight Rules Instrument Flight Rules § 91.189 Category II and III operations: General operating rules. (a) No...

30 CFR 250.1623 - Well-control fluids, equipment, and operations.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Well-control fluids, equipment, and operations... OFFSHORE OIL AND GAS AND SULPHUR OPERATIONS IN THE OUTER CONTINENTAL SHELF Sulphur Operations § 250.1623 Well-control fluids, equipment, and operations. (a) Well-control fluids, equipment, and operations...

49 CFR 218.105 - Additional operational requirements for hand-operated main track switches.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-operated main track switches. 218.105 Section 218.105 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.105 Additional operational requirements for hand-operated main track switches. (a) Each railroad shall adopt and comply with an operating rule...

49 CFR 218.105 - Additional operational requirements for hand-operated main track switches.

Code of Federal Regulations, 2011 CFR

2011-10-01

...-operated main track switches. 218.105 Section 218.105 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.105 Additional operational requirements for hand-operated main track switches. (a) Each railroad shall adopt and comply with an operating rule...

49 CFR 218.105 - Additional operational requirements for hand-operated main track switches.

Code of Federal Regulations, 2014 CFR

2014-10-01

...-operated main track switches. 218.105 Section 218.105 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.105 Additional operational requirements for hand-operated main track switches. (a) Each railroad shall adopt and comply with an operating rule...

49 CFR 218.105 - Additional operational requirements for hand-operated main track switches.

Code of Federal Regulations, 2012 CFR

2012-10-01

...-operated main track switches. 218.105 Section 218.105 Transportation Other Regulations Relating to... PRACTICES Handling Equipment, Switches, and Fixed Derails § 218.105 Additional operational requirements for hand-operated main track switches. (a) Each railroad shall adopt and comply with an operating rule...