48 CFR 16.403-2 - Fixed-price incentive (successive targets) contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (successive targets) contracts. 16.403-2 Section 16.403-2 Federal Acquisition Regulations System FEDERAL... Fixed-price incentive (successive targets) contracts. (a) Description. (1) A fixed-price incentive (successive targets) contract specifies the following elements, all of which are negotiated at the outset: (i...

Exhausting Attentional Tracking Resources with a Single Fast-Moving Object

ERIC Educational Resources Information Center

Holcombe, Alex O.; Chen, Wei-Ying

2012-01-01

Driving on a busy road, eluding a group of predators, or playing a team sport involves keeping track of multiple moving objects. In typical laboratory tasks, the number of visual targets that humans can track is about four. Three types of theories have been advanced to explain this limit. The fixed-limit theory posits a set number of attentional…

Reimagining Gender through Policy Development: The Case of a "Single-Sex" Educational Organisation

ERIC Educational Resources Information Center

Douthirt Cohen, Beth

2012-01-01

In 2005, a feminist educational organisation in the USA for young women, ages 14-21, adopted a policy in order to clarify their target constituency of girls and young women. The policy defined "girls and young women" not as a designation associated with fixed biological sex, but instead as a self-determined identity label creating an explicit…

48 CFR 216.403-2 - Fixed-price incentive (successive targets) contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (successive targets) contracts. 216.403-2 Section 216.403-2 Federal Acquisition Regulations System DEFENSE... CONTRACTS Incentive Contracts 216.403-2 Fixed-price incentive (successive targets) contracts. See PGI 216.403-2 for guidance on the use of fixed-price incentive (successive targets) contracts. [71 FR 39007...

48 CFR 216.403-2 - Fixed-price incentive (successive targets) contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (successive targets) contracts. 216.403-2 Section 216.403-2 Federal Acquisition Regulations System DEFENSE... CONTRACTS Incentive Contracts 216.403-2 Fixed-price incentive (successive targets) contracts. See PGI 216.403-2 for guidance on the use of fixed-price incentive (successive targets) contracts. [71 FR 39007...

Solid phase sequencing of double-stranded nucleic acids

DOEpatents

Fu, Dong-Jing; Cantor, Charles R.; Koster, Hubert; Smith, Cassandra L.

2002-01-01

This invention relates to methods for detecting and sequencing of target double-stranded nucleic acid sequences, to nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probe comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include nucleic acids in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated determination of molecular weights and identification of the target sequence.

Age effects on discrimination of timing in auditory sequences

NASA Astrophysics Data System (ADS)

Fitzgibbons, Peter J.; Gordon-Salant, Sandra

2004-08-01

The experiments examined age-related changes in temporal sensitivity to increments in the interonset intervals (IOI) of components in tonal sequences. Discrimination was examined using reference sequences consisting of five 50-ms tones separated by silent intervals; tone frequencies were either fixed at 4 kHz or varied within a 2-4-kHz range to produce spectrally complex patterns. The tonal IOIs within the reference sequences were either equal (200 or 600 ms) or varied individually with an average value of 200 or 600 ms to produce temporally complex patterns. The difference limen (DL) for increments of IOI was measured. Comparison sequences featured either equal increments in all tonal IOIs or increments in a single target IOI, with the sequential location of the target changing randomly across trials. Four groups of younger and older adults with and without sensorineural hearing loss participated. Results indicated that DLs for uniform changes of sequence rate were smaller than DLs for single target intervals, with the largest DLs observed for single targets embedded within temporally complex sequences. Older listeners performed more poorly than younger listeners in all conditions, but the largest age-related differences were observed for temporally complex stimulus conditions. No systematic effects of hearing loss were observed.

Combined analgesics in (headache) pain therapy: shotgun approach or precise multi-target therapeutics?

PubMed Central

2011-01-01

Background Pain in general and headache in particular are characterized by a change in activity in brain areas involved in pain processing. The therapeutic challenge is to identify drugs with molecular targets that restore the healthy state, resulting in meaningful pain relief or even freedom from pain. Different aspects of pain perception, i.e. sensory and affective components, also explain why there is not just one single target structure for therapeutic approaches to pain. A network of brain areas ("pain matrix") are involved in pain perception and pain control. This diversification of the pain system explains why a wide range of molecularly different substances can be used in the treatment of different pain states and why in recent years more and more studies have described a superior efficacy of a precise multi-target combination therapy compared to therapy with monotherapeutics. Discussion In this article, we discuss the available literature on the effects of several fixed-dose combinations in the treatment of headaches and discuss the evidence in support of the role of combination therapy in the pharmacotherapy of pain, particularly of headaches. The scientific rationale behind multi-target combinations is the therapeutic benefit that could not be achieved by the individual constituents and that the single substances of the combinations act together additively or even multiplicatively and cooperate to achieve a completeness of the desired therapeutic effect. As an example the fixesd-dose combination of acetylsalicylic acid (ASA), paracetamol (acetaminophen) and caffeine is reviewed in detail. The major advantage of using such a fixed combination is that the active ingredients act on different but distinct molecular targets and thus are able to act on more signalling cascades involved in pain than most single analgesics without adding more side effects to the therapy. Summary Multitarget therapeutics like combined analgesics broaden the array of therapeutic options, enable the completeness of the therapeutic effect, and allow doctors (and, in self-medication with OTC medications, the patients themselves) to customize treatment to the patient's specific needs. There is substantial clinical evidence that such a multi-component therapy is more effective than mono-component therapies. PMID:21453539

Renaissance of the ~1 TeV Fixed-Target Program

NASA Astrophysics Data System (ADS)

Adams, T.; Appel, J. A.; Arms, K. E.; Balantekin, A. B.; Conrad, J. M.; Cooper, P. S.; Djurcic, Z.; Dunwoodie, W.; Engelfried, J.; Fisher, P. H.; Gottschalk, E.; de Gouvea, A.; Heller, K.; Ignarra, C. M.; Karagiorgi, G.; Kwan, S.; Loinaz, W. A.; Meadows, B.; Moore, R.; Morfín, J. G.; Naples, D.; Nienaber, P.; Pate, S. F.; Papavassiliou, V.; Petrov, A. A.; Purohit, M. V.; Ray, H.; Russ, J.; Schwartz, A. J.; Seligman, W. G.; Shaevitz, M. H.; Schellman, H.; Spitz, J.; Syphers, M. J.; Tait, T. M. P.; Vannucci, F.

This document describes the physics potential of a new fixed-target program based on a ~1 TeV proton source. Two proton sources are potentially available in the future: the existing Tevatron at Fermilab, which can provide 800 GeV protons for fixed-target physics, and a possible upgrade to the SPS at CERN, called SPS+, which would produce 1 TeV protons on target. In this paper we use an example Tevatron fixed-target program to illustrate the high discovery potential possible in the charm and neutrino sectors. We highlight examples which are either unique to the program or difficult to accomplish at other venues.

Renaissance of the ~ 1-TeV Fixed-Target Program

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

Adams, T.; /Florida State U.; Appel, J.A.

2011-12-02

This document describes the physics potential of a new fixed-target program based on a {approx}1 TeV proton source. Two proton sources are potentially available in the future: the existing Tevatron at Fermilab, which can provide 800 GeV protons for fixed-target physics, and a possible upgrade to the SPS at CERN, called SPS+, which would produce 1 TeV protons on target. In this paper we use an example Tevatron fixed-target program to illustrate the high discovery potential possible in the charm and neutrino sectors. We highlight examples which are either unique to the program or difficult to accomplish at other venues.

A Spaceborne Synthetic Aperture Radar Partial Fixed-Point Imaging System Using a Field- Programmable Gate Array—Application-Specific Integrated Circuit Hybrid Heterogeneous Parallel Acceleration Technique

PubMed Central

Li, Bingyi; Chen, Liang; Wei, Chunpeng; Xie, Yizhuang; Chen, He; Yu, Wenyue

2017-01-01

With the development of satellite load technology and very large scale integrated (VLSI) circuit technology, onboard real-time synthetic aperture radar (SAR) imaging systems have become a solution for allowing rapid response to disasters. A key goal of the onboard SAR imaging system design is to achieve high real-time processing performance with severe size, weight, and power consumption constraints. In this paper, we analyse the computational burden of the commonly used chirp scaling (CS) SAR imaging algorithm. To reduce the system hardware cost, we propose a partial fixed-point processing scheme. The fast Fourier transform (FFT), which is the most computation-sensitive operation in the CS algorithm, is processed with fixed-point, while other operations are processed with single precision floating-point. With the proposed fixed-point processing error propagation model, the fixed-point processing word length is determined. The fidelity and accuracy relative to conventional ground-based software processors is verified by evaluating both the point target imaging quality and the actual scene imaging quality. As a proof of concept, a field- programmable gate array—application-specific integrated circuit (FPGA-ASIC) hybrid heterogeneous parallel accelerating architecture is designed and realized. The customized fixed-point FFT is implemented using the 130 nm complementary metal oxide semiconductor (CMOS) technology as a co-processor of the Xilinx xc6vlx760t FPGA. A single processing board requires 12 s and consumes 21 W to focus a 50-km swath width, 5-m resolution stripmap SAR raw data with a granularity of 16,384 × 16,384. PMID:28672813

A Spaceborne Synthetic Aperture Radar Partial Fixed-Point Imaging System Using a Field- Programmable Gate Array-Application-Specific Integrated Circuit Hybrid Heterogeneous Parallel Acceleration Technique.

PubMed

Yang, Chen; Li, Bingyi; Chen, Liang; Wei, Chunpeng; Xie, Yizhuang; Chen, He; Yu, Wenyue

2017-06-24

With the development of satellite load technology and very large scale integrated (VLSI) circuit technology, onboard real-time synthetic aperture radar (SAR) imaging systems have become a solution for allowing rapid response to disasters. A key goal of the onboard SAR imaging system design is to achieve high real-time processing performance with severe size, weight, and power consumption constraints. In this paper, we analyse the computational burden of the commonly used chirp scaling (CS) SAR imaging algorithm. To reduce the system hardware cost, we propose a partial fixed-point processing scheme. The fast Fourier transform (FFT), which is the most computation-sensitive operation in the CS algorithm, is processed with fixed-point, while other operations are processed with single precision floating-point. With the proposed fixed-point processing error propagation model, the fixed-point processing word length is determined. The fidelity and accuracy relative to conventional ground-based software processors is verified by evaluating both the point target imaging quality and the actual scene imaging quality. As a proof of concept, a field- programmable gate array-application-specific integrated circuit (FPGA-ASIC) hybrid heterogeneous parallel accelerating architecture is designed and realized. The customized fixed-point FFT is implemented using the 130 nm complementary metal oxide semiconductor (CMOS) technology as a co-processor of the Xilinx xc6vlx760t FPGA. A single processing board requires 12 s and consumes 21 W to focus a 50-km swath width, 5-m resolution stripmap SAR raw data with a granularity of 16,384 × 16,384.

48 CFR 16.403 - Fixed-price incentive contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... relationship of total final negotiated cost to total target cost. The final price is subject to a price ceiling, negotiated at the outset. The two forms of fixed-price incentive contracts, firm target and successive targets, are further described in 16.403-1 and 16.403-2 below. (b) Application. A fixed-price incentive...

48 CFR 16.403 - Fixed-price incentive contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... relationship of total final negotiated cost to total target cost. The final price is subject to a price ceiling, negotiated at the outset. The two forms of fixed-price incentive contracts, firm target and successive targets, are further described in 16.403-1 and 16.403-2 below. (b) Application. A fixed-price incentive...

SU-E-T-187: Collimation Methods in Spot Scanning Proton Therapy: A Treatment Plan Comparison Between a Fixed Aperture and a Dynamic Collimation System

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

Smith, B; Gelover, E; Wang, D

2015-06-15

Purpose: Low-energy treatments during spot scanning proton therapy (SSPT) suffer from poor conformity due to increased spot size. Collimation devices can reduce the lateral penumbra of a proton therapy dose distribution and improve the overall plan quality. The purpose of this work was to study the advantages of individual energy-layer collimation, which is unique to a recently proposed Dynamic Collimation System (DCS), in comparison to a standard, fixed aperture that allows only a single shape for all energy layers. Methods: Three brain patients previously planned and treated with SSPT were re-planned using an in-house treatment planning system capable of modelingmore » collimated and un-collimated proton beamlets. The un-collimated plans, which served as a baseline for comparison, reproduced the target coverage of the clinically delivered plans. The collimator opening for the aperture based plans included a 0.6 cm expansion of the largest cross section of the target in the Beam’s Eye View, while the DCS based plans were created by optimizing the collimator position for beam spots near the periphery of the target in each energy layer. Results: The reduction of mean dose to normal tissue adjacent to the target, as defined by a 10 mm ring, averaged 9.13% and 3.48% for the DCS and aperture plans, respectively. The conformity index, as defined by the ratio of the volume of the 50% isodose line to the target volume, yielded an average improvement of 16.42% and 8.16% for the DCS and aperture plans, respectively. Conclusion: Collimation reduces the dose to normal tissue adjacent to the target and increases dose conformity to the target region for low-energy SSPT. The ability of the DCS to provide collimation to each energy layer yields better conformity in comparison to fixed aperture plans. This work was partially funded by IBA (Ion Beam Applications S.A.)« less

Joint detection and tracking of size-varying infrared targets based on block-wise sparse decomposition

NASA Astrophysics Data System (ADS)

Li, Miao; Lin, Zaiping; Long, Yunli; An, Wei; Zhou, Yiyu

2016-05-01

The high variability of target size makes small target detection in Infrared Search and Track (IRST) a challenging task. A joint detection and tracking method based on block-wise sparse decomposition is proposed to address this problem. For detection, the infrared image is divided into overlapped blocks, and each block is weighted on the local image complexity and target existence probabilities. Target-background decomposition is solved by block-wise inexact augmented Lagrange multipliers. For tracking, label multi-Bernoulli (LMB) tracker tracks multiple targets taking the result of single-frame detection as input, and provides corresponding target existence probabilities for detection. Unlike fixed-size methods, the proposed method can accommodate size-varying targets, due to no special assumption for the size and shape of small targets. Because of exact decomposition, classical target measurements are extended and additional direction information is provided to improve tracking performance. The experimental results show that the proposed method can effectively suppress background clutters, detect and track size-varying targets in infrared images.

A single-molecule view of gene regulation in cancer

NASA Astrophysics Data System (ADS)

Larson, Daniel

2013-03-01

Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated gene activation. Steroid receptors coordinate a diverse range of responses in higher eukaryotes and are involved in a wide range of human diseases, including cancer. Steroid receptor response elements are present throughout the human genome and modulate chromatin remodeling and transcription in both a local and long-range fashion. As such, steroid receptor-mediated transcription is a paradigm of genetic control in the metazoan nucleus. Moreover, the ligand-dependent nature of these transcription factors makes them appealing targets for therapeutic intervention, necessitating a quantitative understanding of how receptors control output from target genes. We determine that steroids drive mRNA synthesis by frequency modulation of transcription. This digital behavior in single cells gives rise to the well-known analog dose response across the population. To test this model, we developed a light-activation technology to turn on a single gene and follow dynamic synthesis of RNA from the activated locus. The response delay is a measure of time required for chromatin remodeling at a single gene.

Beauty and charm production at fixed-target experiments

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

Erik E. Gottschalk

Fixed-target experiments continue to provide insights into the physics of particle production in strong interactions. The experiments are performed with different types of beam particles of varying energies, and many different target materials. Studies of beauty and charm production are of particular interest, since experimental results can be compared to perturbative QCD calculations. It is in this context that recent results from fixed-target experiments on beauty and charm production will be reviewed.

Hypertension management: rationale for triple therapy based on mechanisms of action.

PubMed

Neutel, Joel M; Smith, David H G

2013-10-01

An estimated 25% of patients will require 3 antihypertensive agents to achieve blood pressure (BP) control; combination therapy is thus an important strategy in hypertension treatment. This review discusses the triple-therapy combination of an angiotensin receptor blocker (ARB) or direct renin antagonist (DRI) with a calcium channel blocker (CCB) and a diuretic, with a focus on mechanisms of action. Multiple physiologic pathways contribute to hypertension. Combining antihypertensive agents not only better targets the underlying pathways, but also helps blunt compensatory responses that may be triggered by single-agent therapy. DRIs and ARBs target the renin-angiotensin-aldosterone system (RAAS) at the initial and final steps, respectively, and both classes lower BP by reducing the effects of angiotensin-2; however, ARBs may trigger a compensatory increase in renin activity. Dihydropyridine CCBs target L-type calcium channels and lower BP through potent vasodilation, but can trigger compensatory activation of the sympathetic nervous system (SNS) and RAAS. Thiazide diuretics lower BP initially through sodium depletion and plasma volume reduction, followed by total peripheral resistance reduction, but can also trigger compensatory activation of the SNS and RAAS. The combination of an agent targeting the RAAS with a CCB and diuretic is rational, and triple combinations of valsartan/amlodipine/hydrochlorothiazide, olmesartan/amlodipine/hydrochlorothiazide, and aliskiren/amlodipine/hydrochlorothiazide have demonstrated greater effectiveness compared with their respective dual-component combinations. In addition, single-pill, fixed-dose combinations can address barriers to BP control including clinical inertia and poor adherence. Fixed-dose antihypertensive combination products capitalize on complementary mechanisms of action and have been shown to result in improved BP control. © 2012 John Wiley & Sons Ltd.

Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response.

PubMed

Manno, Catherine S; Pierce, Glenn F; Arruda, Valder R; Glader, Bertil; Ragni, Margaret; Rasko, John J; Rasko, John; Ozelo, Margareth C; Hoots, Keith; Blatt, Philip; Konkle, Barbara; Dake, Michael; Kaye, Robin; Razavi, Mahmood; Zajko, Albert; Zehnder, James; Rustagi, Pradip K; Nakai, Hiroyuki; Chew, Amy; Leonard, Debra; Wright, J Fraser; Lessard, Ruth R; Sommer, Jürg M; Tigges, Michael; Sabatino, Denise; Luk, Alvin; Jiang, Haiyan; Mingozzi, Federico; Couto, Linda; Ertl, Hildegund C; High, Katherine A; Kay, Mark A

2006-03-01

We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B. We carried out a phase 1/2 dose-escalation clinical study to extend this approach to humans with severe hemophilia B. rAAV-2 vector expressing human F.IX was infused through the hepatic artery into seven subjects. The data show that: (i) vector infusion at doses up to 2 x 10(12) vg/kg was not associated with acute or long-lasting toxicity; (ii) therapeutic levels of F.IX were achieved at the highest dose tested; (iii) duration of expression at therapeutic levels was limited to a period of approximately 8 weeks; (iv) a gradual decline in F.IX was accompanied by a transient asymptomatic elevation of liver transaminases that resolved without treatment. Further studies suggested that destruction of transduced hepatocytes by cell-mediated immunity targeting antigens of the AAV capsid caused both the decline in F.IX and the transient transaminitis. We conclude that rAAV-2 vectors can transduce human hepatocytes in vivo to result in therapeutically relevant levels of F.IX, but that future studies in humans may require immunomodulation to achieve long-term expression.

When do anterior external or internal fixators provide additional stability in an unstable (Tile C) pelvic fracture? A biomechanical study.

PubMed

Mcdonald, E; Theologis, A A; Horst, P; Kandemir, U; Pekmezci, M

2015-12-01

This study aimed at evaluating the additional stability that is provided by anterior external and internal fixators in an unstable pelvic fracture model (OTA 61-C). An unstable pelvic fracture (OTA 61-C) was created in 27 synthetic pelves by making a 5-mm gap through the sacral foramina (posterior injury) and an ipsilateral pubic rami fracture (anterior injury). The posterior injury was fixed with either a single iliosacral (IS) screw, a single trans-iliac, trans-sacral (TS) screw, or two iliosacral screws (S1S2). Two anterior fixation techniques were utilized: external fixation (Ex-Fix) and supra-acetabular external fixation and internal fixation (In-Fix); supra-acetabular pedicle screws connected with a single subcutaneous spinal rod. The specimens were tested using a nondestructive single-leg stance model. Peak-to-peak (P2P) displacement and rotation and conditioning displacement (CD) were calculated. The Ex-Fix group failed in 83.3 % of specimens with concomitant single-level posterior fixation (Total: 15/18-7 of 9 IS fixation, 8 of 9 TS fixation), and 0 % (0/9) of specimens with concomitant two-level (S1S2) posterior fixation. All specimens with the In-Fix survived testing except for two specimens treated with In-Fix combined with IS fixation. Trans-sacral fixation had higher pubic rotation and greater sacral and pubic displacement than S1S2 (p < 0.05). Rotation of the pubis and sacrum was not different between In-Fix constructs combined with single-level IS and TS fixation. In this model of an unstable pelvic fracture (OTA 61-C), anterior fixation with an In-Fix was biomechanically superior to an anterior Ex-Fix in the setting of single-level posterior fixation. There was no biomechanical difference between the In-Fix and Ex-Fix when each was combined with two levels of posterior sacral fixation.

Paralyzed subject controls telepresence mobile robot using novel sEMG brain-computer interface: case study.

PubMed

Lyons, Kenneth R; Joshi, Sanjay S

2013-06-01

Here we demonstrate the use of a new singlesignal surface electromyography (sEMG) brain-computer interface (BCI) to control a mobile robot in a remote location. Previous work on this BCI has shown that users are able to perform cursor-to-target tasks in two-dimensional space using only a single sEMG signal by continuously modulating the signal power in two frequency bands. Using the cursor-to-target paradigm, targets are shown on the screen of a tablet computer so that the user can select them, commanding the robot to move in different directions for a fixed distance/angle. A Wifi-enabled camera transmits video from the robot's perspective, giving the user feedback about robot motion. Current results show a case study with a C3-C4 spinal cord injury (SCI) subject using a single auricularis posterior muscle site to navigate a simple obstacle course. Performance metrics for operation of the BCI as well as completion of the telerobotic command task are developed. It is anticipated that this noninvasive and mobile system will open communication opportunities for the severely paralyzed, possibly using only a single sensor.

Method for continuous control of composition and doping of pulsed laser deposited films

DOEpatents

Lowndes, Douglas H.; McCamy, James W.

1995-01-01

A method for growing a deposit upon a substrate of semiconductor material involves the utilization of pulsed laser deposition techniques within a low-pressure gas environment. The substrate and a target of a first material are positioned within a deposition chamber and a low-pressure gas atmosphere is developed within the chamber. The substrate is then heated, and the target is irradiated, so that atoms of the target material are ablated from the remainder of the target, while atoms of the gas simultaneously are adsorbed on the substrate/film surface. The ablated atoms build up upon the substrate, together with the adsorbed gas atoms to form the thin-film deposit on the substrate. By controlling the pressure of the gas of the chamber atmosphere, the composition of the formed deposit can be controlled, and films of continuously variable composition or doping can be grown from a single target of fixed composition.

Method for continuous control of composition and doping of pulsed laser deposited films by pressure control

DOEpatents

Lowndes, Douglas H.; McCamy, James W.

1996-01-01

A method for growing a deposit upon a substrate of semiconductor material involves the utilization of pulsed laser deposition techniques within a low-pressure gas environment. The substrate and a target of a first material are positioned within a deposition chamber and a low-pressure gas atmosphere is developed within the chamber. The substrate is then heated, and the target is irradiated, so that atoms of the target material are ablated from the remainder of the target, while atoms of the gas simultaneously are adsorbed on the substrate/film surface. The ablated atoms build up upon the substrate, together with the adsorbed gas atoms to form the thin-film deposit on the substrate. By controlling the pressure of the gas of the chamber atmosphere, the composition of the formed deposit can be controlled, and films of continuously variable composition or doping can be grown from a single target of fixed composition.

48 CFR 216.403-1 - Fixed-price incentive (firm target) contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (firm target) contracts. 216.403-1 Section 216.403-1 Federal Acquisition Regulations System DEFENSE... CONTRACTS Incentive Contracts 216.403-1 Fixed-price incentive (firm target) contracts. (b) Application. (1... target) contracts, especially for acquisitions moving from development to production. (2) The contracting...

Electron- and positron-molecule scattering: development of the molecular convergent close-coupling method

NASA Astrophysics Data System (ADS)

Zammit, Mark C.; Fursa, Dmitry V.; Savage, Jeremy S.; Bray, Igor

2017-06-01

Starting from first principles, this tutorial describes the development of the adiabatic-nuclei convergent close-coupling (CCC) method and its application to electron and (single-centre) positron scattering from diatomic molecules. We give full details of the single-centre expansion CCC method, namely the formulation of the molecular target structure; solving the momentum-space coupled-channel Lippmann-Schwinger equation; deriving adiabatic-nuclei cross sections and calculating V-matrix elements. Selected results are presented for electron and positron scattering from molecular hydrogen H2 and electron scattering from the vibrationally excited molecular hydrogen ion {{{H}}}2+ and its isotopologues (D2 +, {{{T}}}2+, HD+, HT+ and TD+). Convergence in both the close-coupling (target state) and projectile partial-wave expansions of fixed-nuclei electron- and positron-molecule scattering calculations is demonstrated over a broad energy-range and discussed in detail. In general, the CCC results are in good agreement with experiments.

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

Zammit, Mark C.; Fursa, Dmitry V.; Savage, Jeremy S.

Starting from first principles, this tutorial describes the development of the adiabatic-nuclei convergent close-coupling (CCC) method and its application to electron and (single-centre) positron scattering from diatomic molecules. In this paper, we give full details of the single-centre expansion CCC method, namely the formulation of the molecular target structure; solving the momentum-space coupled-channel Lippmann-Schwinger equation; deriving adiabatic-nuclei cross sections and calculatingmore » $V$-matrix elements. Selected results are presented for electron and positron scattering from molecular hydrogen H$$_2$$ and electron scattering from the vibrationally excited molecular hydrogen ion H$$_2^+$$ and its isotopologues (D$$_2^+$$, T$$_2^+$$, HD$^+$, HT$^+$ and TD$^+$). Finally, convergence in both the close-coupling (target state) and projectile partial-wave expansions of fixed-nuclei electron- and positron-molecule scattering calculations is demonstrated over a broad energy-range and discussed in detail. In general the CCC results are in good agreement with experiments.« less

The Speed of Serial Attention Shifts in Visual Search: Evidence from the N2pc Component.

PubMed

Grubert, Anna; Eimer, Martin

2016-02-01

Finding target objects among distractors in visual search display is often assumed to be based on sequential movements of attention between different objects. However, the speed of such serial attention shifts is still under dispute. We employed a search task that encouraged the successive allocation of attention to two target objects in the same search display and measured N2pc components to determine how fast attention moved between these objects. Each display contained one digit in a known color (fixed-color target) and another digit whose color changed unpredictably across trials (variable-color target) together with two gray distractor digits. Participants' task was to find the fixed-color digit and compare its numerical value with that of the variable-color digit. N2pc components to fixed-color targets preceded N2pc components to variable-color digits, demonstrating that these two targets were indeed selected in a fixed serial order. The N2pc to variable-color digits emerged approximately 60 msec after the N2pc to fixed-color digits, which shows that attention can be reallocated very rapidly between different target objects in the visual field. When search display durations were increased, thereby relaxing the temporal demands on serial selection, the two N2pc components to fixed-color and variable-color targets were elicited within 90 msec of each other. Results demonstrate that sequential shifts of attention between different target locations can operate very rapidly at speeds that are in line with the assumptions of serial selection models of visual search.

A review of the Fermilab fixed-target program

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

Rameika, R.

1994-12-01

All eyes are now on the Fermilab collider program as the intense search for the top quark continues. Nevertheless, Fermilab`s long tradition of operating a strong, diverse physics program depends not only on collider physics but also on effective use of the facilities the Laboratory was founded on, the fixed-target beamlines. In this talk the author presents highlights of the Fermilab fixed-target program from its (not too distant) past, (soon to be) present, and (hopefully, not too distant) future program. The author concentrates on those experiments which are unique to the fixed-target program, in particular hadron structure measurements which usemore » the varied beams and targets available in this mode and the physics results from kaon, hyperon and high statistics charm experiments which are not easily accessible in high p{sub T} hadron collider detectors.« less

Effects of Resolution, Range, and Image Contrast on Target Acquisition Performance.

PubMed

Hollands, Justin G; Terhaar, Phil; Pavlovic, Nada J

2018-05-01

We sought to determine the joint influence of resolution, target range, and image contrast on the detection and identification of targets in simulated naturalistic scenes. Resolution requirements for target acquisition have been developed based on threshold values obtained using imaging systems, when target range was fixed, and image characteristics were determined by the system. Subsequent work has examined the influence of factors like target range and image contrast on target acquisition. We varied the resolution and contrast of static images in two experiments. Participants (soldiers) decided whether a human target was located in the scene (detection task) or whether a target was friendly or hostile (identification task). Target range was also varied (50-400 m). In Experiment 1, 30 participants saw color images with a single target exemplar. In Experiment 2, another 30 participants saw monochrome images containing different target exemplars. The effects of target range and image contrast were qualitatively different above and below 6 pixels per meter of target for both tasks in both experiments. Target detection and identification performance were a joint function of image resolution, range, and contrast for both color and monochrome images. The beneficial effects of increasing resolution for target acquisition performance are greater for closer (larger) targets.

Planning multiple movements within a fixed time limit: The cost of constrained time allocation in a visuo-motor task

PubMed Central

Zhang, Hang; Wu, Shih-Wei; Maloney, Laurence T.

2010-01-01

S.-W. Wu, M. F. Dal Martello, and L. T. Maloney (2009) evaluated subjects' performance in a visuo-motor task where subjects were asked to hit two targets in sequence within a fixed time limit. Hitting targets earned rewards and Wu et al. varied rewards associated with targets. They found that subjects failed to maximize expected gain; they failed to invest more time in the movement to the more valuable target. What could explain this lack of response to reward? We first considered the possibility that subjects require training in allocating time between two movements. In Experiment 1, we found that, after extensive training, subjects still failed: They did not vary time allocation with changes in payoff. However, their actual gains equaled or exceeded the expected gain of an ideal time allocator, indicating that constraining time itself has a cost for motor accuracy. In a second experiment, we found that movements made under externally imposed time limits were less accurate than movements made with the same timing freely selected by the mover. Constrained time allocation cost about 17% in expected gain. These results suggest that there is no single speed–accuracy tradeoff for movement in our task and that subjects pursued different motor strategies with distinct speed–accuracy tradeoffs in different conditions. PMID:20884550

On the nature of phase attraction in sensorimotor synchronization with interleaved auditory sequences.

PubMed

Repp, Bruno H

2004-10-01

In a task that requires in-phase synchronization of finger taps with an isochronous sequence of target tones that is interleaved with a sequence of distractor tones at various fixed phase relationships, the taps tend to be attracted to the distractor tones, especially when the distractor tones closely precede the target tones [Repp, B. H. (2003a). Phase attraction in sensorimotor synchronization with auditory sequences: Effects of single and periodic distractors on synchronization accuracy. Journal of Experimental Psychology: Human Perception and Performance, 29, 290-309]. The present research addressed two related questions about this distractor effect: (1) Is it a function of the absolute temporal separation or of the relative phase of the two stimulus sequences? (2) Is it the result of perceptual grouping (integration) of target and distractor tones or of simultaneous attraction to two independent sequences? In three experiments, distractor effects were compared across two different sequence rates. The results suggest that absolute temporal separation, not relative phase, is the critical variable. Experiment 3 also included an anti-phase tapping task that addressed the second question directly. The results suggest that the attraction of taps to distractor tones is caused mainly by temporal integration of target and distractor tones within a fixed window of 100-150 ms duration, with the earlier-occurring tone being weighted more strongly than the later-occurring one.

The Benefit of a Visually Guided Beamformer in a Dynamic Speech Task

PubMed Central

Roverud, Elin; Streeter, Timothy; Mason, Christine R.; Kidd, Gerald

2017-01-01

The aim of this study was to evaluate the performance of a visually guided hearing aid (VGHA) under conditions designed to capture some aspects of “real-world” communication settings. The VGHA uses eye gaze to steer the acoustic look direction of a highly directional beamforming microphone array. Although the VGHA has been shown to enhance speech intelligibility for fixed-location, frontal targets, it is currently not known whether these benefits persist in the face of frequent changes in location of the target talker that are typical of conversational turn-taking. Participants were 14 young adults, 7 with normal hearing and 7 with bilateral sensorineural hearing impairment. Target stimuli were sequences of 12 question–answer pairs that were embedded in a mixture of competing conversations. The participant’s task was to respond via a key press after each answer indicating whether it was correct or not. Spatialization of the stimuli and microphone array processing were done offline using recorded impulse responses, before presentation over headphones. The look direction of the array was steered according to the eye movements of the participant as they followed a visual cue presented on a widescreen monitor. Performance was compared for a “dynamic” condition in which the target stimulus moved between three locations, and a “fixed” condition with a single target location. The benefits of the VGHA over natural binaural listening observed in the fixed condition were reduced in the dynamic condition, largely because visual fixation was less accurate. PMID:28758567

Low- Z polymer sample supports for fixed-target serial femtosecond X-ray crystallography

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

Feld, Geoffrey K.; Heymann, Michael; Benner, W. Henry

X-ray free-electron lasers (XFELs) offer a new avenue to the structural probing of complex materials, including biomolecules. Delivery of precious sample to the XFEL beam is a key consideration, as the sample of interest must be serially replaced after each destructive pulse. The fixed-target approach to sample delivery involves depositing samples on a thin-film support and subsequent serial introduction via a translating stage. Some classes of biological materials, including two-dimensional protein crystals, must be introduced on fixed-target supports, as they require a flat surface to prevent sample wrinkling. A series of wafer and transmission electron microscopy (TEM)-style grid supports constructedmore » of low- Z plastic have been custom-designed and produced. Aluminium TEM grid holders were engineered, capable of delivering up to 20 different conventional or plastic TEM grids using fixed-target stages available at the Linac Coherent Light Source (LCLS). As proof-of-principle, X-ray diffraction has been demonstrated from two-dimensional crystals of bacteriorhodopsin and three-dimensional crystals of anthrax toxin protective antigen mounted on these supports at the LCLS. In conclusion, the benefits and limitations of these low- Z fixed-target supports are discussed; it is the authors' belief that they represent a viable and efficient alternative to previously reported fixed-target supports for conducting diffraction studies with XFELs.« less

Visual accommodation trainer-tester

NASA Technical Reports Server (NTRS)

Randle, Robert J. (Inventor)

1988-01-01

An apparatus for training the human visual accommodation system is described. Specifically, the apparatus is useful for training personnel to volitionally control focus to the far point (normally infinity) from a position of myopia due to functional causes. The functional causes could be due, for example, to a behavioral accommodative spasm or the effects of an empty field. The device may also be used to measure accommodation, the accommodation resting position and the near and far points of vision. The device comprises a number of optical elements arranged on a single optical axis. Several of the elements are arranged in order on a movable stage in fixed relationship to each other: a light source, a lens, a target, an aperture and/or a second lens. On a base and in fixed relationship to each other are eyepiece and third lens. A stage generates an image of the target and the stage is movable with respect to the base by means of a knob. The device is utilized for the various training and test functions by following a series of procedural steps, and interchanging the apertures as necessary for the selected procedure.

Two-photon imaging of neuronal activity in motor cortex of marmosets during upper-limb movement tasks.

PubMed

Ebina, Teppei; Masamizu, Yoshito; Tanaka, Yasuhiro R; Watakabe, Akiya; Hirakawa, Reiko; Hirayama, Yuka; Hira, Riichiro; Terada, Shin-Ichiro; Koketsu, Daisuke; Hikosaka, Kazuo; Mizukami, Hiroaki; Nambu, Atsushi; Sasaki, Erika; Yamamori, Tetsuo; Matsuzaki, Masanori

2018-05-14

Two-photon imaging in behaving animals has revealed neuronal activities related to behavioral and cognitive function at single-cell resolution. However, marmosets have posed a challenge due to limited success in training on motor tasks. Here we report the development of protocols to train head-fixed common marmosets to perform upper-limb movement tasks and simultaneously perform two-photon imaging. After 2-5 months of training sessions, head-fixed marmosets can control a manipulandum to move a cursor to a target on a screen. We conduct two-photon calcium imaging of layer 2/3 neurons in the motor cortex during this motor task performance, and detect task-relevant activity from multiple neurons at cellular and subcellular resolutions. In a two-target reaching task, some neurons show direction-selective activity over the training days. In a short-term force-field adaptation task, some neurons change their activity when the force field is on. Two-photon calcium imaging in behaving marmosets may become a fundamental technique for determining the spatial organization of the cortical dynamics underlying action and cognition.

Video sensor with range measurement capability

NASA Technical Reports Server (NTRS)

Howard, Richard T. (Inventor); Briscoe, Jeri M. (Inventor); Corder, Eric L. (Inventor); Broderick, David J. (Inventor)

2008-01-01

A video sensor device is provided which incorporates a rangefinder function. The device includes a single video camera and a fixed laser spaced a predetermined distance from the camera for, when activated, producing a laser beam. A diffractive optic element divides the beam so that multiple light spots are produced on a target object. A processor calculates the range to the object based on the known spacing and angles determined from the light spots on the video images produced by the camera.

Monoclonal antibody specific for IDH1 R132H mutation.

PubMed

Capper, David; Zentgraf, Hanswalter; Balss, Jörg; Hartmann, Christian; von Deimling, Andreas

2009-11-01

IDH1 R132H mutations occur in approximately 70% of astrocytomas and oligodendroglial tumors. We developed a mouse monoclonal antibody targeting the IDH1 R132H mutation. Here, we show the high specificity and sensitivity of this antibody on Western blots and tissue sections from formalin fixed paraffin embedded tumor specimens. This antibody is highly useful for tumor classification, in detecting single infiltrating tumor cells and for the characterization of the cellular role of mutant IDH1 protein.

Accounting for uncertainty in the historical response rate of the standard treatment in single-arm two-stage designs based on Bayesian power functions.

PubMed

Matano, Francesca; Sambucini, Valeria

2016-11-01

In phase II single-arm studies, the response rate of the experimental treatment is typically compared with a fixed target value that should ideally represent the true response rate for the standard of care therapy. Generally, this target value is estimated through previous data, but the inherent variability in the historical response rate is not taken into account. In this paper, we present a Bayesian procedure to construct single-arm two-stage designs that allows to incorporate uncertainty in the response rate of the standard treatment. In both stages, the sample size determination criterion is based on the concepts of conditional and predictive Bayesian power functions. Different kinds of prior distributions, which play different roles in the designs, are introduced, and some guidelines for their elicitation are described. Finally, some numerical results about the performance of the designs are provided and a real data example is illustrated. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Beauty and charm production in fixed target experiments

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

Kidonakis, Nikolaos; Vogt, Ramona

We present calculations of NNLO threshold corrections for beauty and charm production in {pi}{sup -} p and pp interactions at fixed-target experiments. Recent calculations for heavy quark hadroproduction have included next-to-next-to-leading-order (NNLO) soft-gluon corrections [1] to the double differential cross section from threshold resummation techniques [2]. These corrections are important for near-threshold beauty and charm production at fixed-target experiments, including HERA-B and some of the current and future heavy ion experiments.

Low-dose fixed-target serial synchrotron crystallography.

PubMed

Owen, Robin L; Axford, Danny; Sherrell, Darren A; Kuo, Anling; Ernst, Oliver P; Schulz, Eike C; Miller, R J Dwayne; Mueller-Werkmeister, Henrike M

2017-04-01

The development of serial crystallography has been driven by the sample requirements imposed by X-ray free-electron lasers. Serial techniques are now being exploited at synchrotrons. Using a fixed-target approach to high-throughput serial sampling, it is demonstrated that high-quality data can be collected from myoglobin crystals, allowing room-temperature, low-dose structure determination. The combination of fixed-target arrays and a fast, accurate translation system allows high-throughput serial data collection at high hit rates and with low sample consumption.

Drivers' detection of roadside targets when driving vehicles with three headlight systems during high beam activation.

PubMed

Reagan, Ian J; Brumbelow, Matthew L

2017-02-01

A previous open-road experiment indicated that curve-adaptive HID headlights driven with low beams improved drivers' detection of low conspicuity targets compared with fixed halogen and fixed HID low beam systems. The current study used the same test environment and targets to assess whether drivers' detection of targets was affected by the same three headlight systems when using high beams. Twenty drivers search and responded for 60 8×12inch targets of high or low reflectance that were distributed evenly across straight and curved road sections as they drove at 30 mph on an unlit two-lane rural road. The results indicate that target detection performance was generally similar across the three systems. However, one interaction indicated that drivers saw low reflectance targets on straight road sections from further away when driving with the fixed halogen high beam condition compared with curve-adaptive HID high beam headlights and also indicated a possible benefit for the curve-adaptive HID high beams for high reflectance targets placed on the inside of curves. The results of this study conflict with the previous study of low beams, which showed a consistent benefit for the curve-adaptive HID low beams for targets placed on curves compared with fixed HID and fixed halogen low beam conditions. However, a comparison of mean detection distances from the two studies indicated uniformly longer mean target detection distances for participants driving with high beams and implicates the potential visibility benefits for systems that optimize proper high beam use. Copyright © 2016 Elsevier Ltd. All rights reserved.

Robust Control Design via Linear Programming

NASA Technical Reports Server (NTRS)

Keel, L. H.; Bhattacharyya, S. P.

1998-01-01

This paper deals with the problem of synthesizing or designing a feedback controller of fixed dynamic order. The closed loop specifications considered here are given in terms of a target performance vector representing a desired set of closed loop transfer functions connecting various signals. In general these point targets are unattainable with a fixed order controller. By enlarging the target from a fixed point set to an interval set the solvability conditions with a fixed order controller are relaxed and a solution is more easily enabled. Results from the parametric robust control literature can be used to design the interval target family so that the performance deterioration is acceptable, even when plant uncertainty is present. It is shown that it is possible to devise a computationally simple linear programming approach that attempts to meet the desired closed loop specifications.

SU-E-J-146: A Research of PET-CT SUV Range for the Online Dose Verification in Carbon Ion Radiation Therapy

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

Sun, L; Hu, W; Moyers, M

2015-06-15

Purpose: Positron-emitting isotope distributions can be used for the image fusion of the carbon ion planning CT and online target verification PETCT, after radiation in the same decay period,the relationship between the same target volume and the SUV value of different every single fraction dose can be found,then the range of SUV for the radiation target could be decided.So this online range also can provide reference for the correlation and consistency in planning target dose verification and evaluation for the clinical trial. Methods: The Rando head phantom can be used as real body,the 10cc cube volume target contouring is done,beammore » ISO Center depth is 7.6cm and the 90 degree fixed carbon ion beams should be delivered in single fraction effective dose of 2.5GyE,5GyE and 8GyE.After irradiation,390 seconds later the 30 minutes PET-CT scanning is performed,parameters are set to 50Kg virtual weight,0.05mCi activity.MIM Maestro is used for the image processing and fusion,five 16mm diameter SUV spheres have been chosen in the different direction in the target.The average SUV in target for different fraction dose can be found by software. Results: For 10cc volume target,390 seconds decay period,the Single fraction effective dose equal to 2.5Gy,Ethe SUV mean value is 3.42,the relative range is 1.72 to 6.83;Equal to 5GyE,SUV mean value is 9.946,the relative range is 7.016 to 12.54;Equal or above to 8GyE,SUV mean value is 20.496,the relative range is 11.16 to 34.73. Conclusion: Making an evaluation for accuracy of the dose distribution using the SUV range which is from the planning CT with after treatment online PET-CT fusion for the normal single fraction carbon ion treatment is available.Even to the plan which single fraction dose is above 2GyE,in the condition of other parameters all the same,the SUV range is linearly dependent with single fraction dose,so this method also can be used in the hyper-fraction treatment plan.« less

Efficacy and Safety of a Single-Pill Fixed-Dose Combination of Azilsartan and Amlodipine.

PubMed

Motozato, Kota; Miura, Shin-Ichiro; Shiga, Yuhei; Kusumoto, Takaaki; Saku, Keijiro

2016-12-01

Guidelines for the management of hypertension recommend the use of drugs with different mechanisms of action in antihypertensive regimens that include single-pill fixed-dose combinations of medications. There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP). Forty hypertensive patients who were receiving a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day were enrolled. They were randomly divided into two treatment groups, a group that changed to a single-pill fixed-dose combination of azilsartan 20 mg/day and amlodipine 5 mg/day (changeover group) and a group that continued to receive valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day (control group), and treated for 16 weeks. There were no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP) or pulse rate (PR) at 16 weeks between the control and changeover groups. In addition, there were no significant changes in biochemical parameters throughout the study period in both groups. The ability of a single-pill fixed-dose combination of azilsartan and amlodipine to reduce BP may be comparable to that of a combination of valsartan and amlodipine or irbesartan and amlodipine.

Context matters: the structure of task goals affects accuracy in multiple-target visual search.

PubMed

Clark, Kait; Cain, Matthew S; Adcock, R Alison; Mitroff, Stephen R

2014-05-01

Career visual searchers such as radiologists and airport security screeners strive to conduct accurate visual searches, but despite extensive training, errors still occur. A key difference between searches in radiology and airport security is the structure of the search task: Radiologists typically scan a certain number of medical images (fixed objective), and airport security screeners typically search X-rays for a specified time period (fixed duration). Might these structural differences affect accuracy? We compared performance on a search task administered either under constraints that approximated radiology or airport security. Some displays contained more than one target because the presence of multiple targets is an established source of errors for career searchers, and accuracy for additional targets tends to be especially sensitive to contextual conditions. Results indicate that participants searching within the fixed objective framework produced more multiple-target search errors; thus, adopting a fixed duration framework could improve accuracy for career searchers. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Vestibular and Non-vestibular Contributions to Eye Movements that Compensate for Head Rotations during Viewing of Near Targets

NASA Technical Reports Server (NTRS)

Han, Yanning H.

2006-01-01

We studied horizontal eye movements induced by en-bloc yaw rotation, over a frequency range 0.2 - 2.8 Hz, in 10 normal human subjects as they monocularly viewed a target located at their near point of focus. We measured gain and phase relationships between eye-in-head velocity and head velocity when the near target was either earth-fixed or head-fixed. During viewing of the earth-fixed near target, median gain was 1.49 (range 1.24 - 1.87) at 0.2 Hz for the group of subjects, but declined at higher frequencies, so that at 2.8 Hz median gain was 1.08 (range 0.68 - 1.67). During viewing of the head-fixed near target , median gain was 0.03 (range 0.01 - 0.10) at 0.2 Hz for the group of subjects, but increased at higher frequencies, so that at 2.8 Hz median gain was 0.71 (range 0.28 - 0.94). We estimated the vestibular contribution to these responses vestibulo-ocular reflex gain (Gvor) by applying transient head perturbations (peak acceleration> 1,000 deg/s(exp 2)) during sinusoidal rotation under the two viewing conditions. Median Gvor, estimated < 70ms after the onset of head perturbation, was 0.98 (range 0.39 - 1.42) while viewing the earth-fixed near target, and 0.97 (range 0.37 - 1.33) while viewing the head-fixed near target. For the group of subjects, 9 out of 10 subjects showed no significant difference of Gvor between the two viewing conditions ( p > 0.053 ) at all test frequencies. Since Gvor accounted for only -73% of the overall response gain during viewing of the earth-fixed target, we investigated the relative contributions of non-vestibular factors. When subjects viewed the earth-fixed target under strobe illumination, to eliminate retinal image slip information, the gain of compensatory eye movements declined compared with viewing in ambient room light. During sum-of-sine head rotations, while viewing the earth-fixed target, to Han et al./VOR during near-viewing minimize contributions from predictive mechanisms, gain also declined Nonetheless, simple superposition of smooth-pursuit tracking of sinusoidal target motion could not fully account for the overall response at higher frequencies, suggesting other nonvestibular contributions. During binocular viewing conditions when vergence angle was significantly greater than monocular viewing (p < 0.00l), the gain of compensatory eye movements did not show proportional change; indeed, gain could not be correlated with vergence angle during monocular or binocular viewing. We conclude that several separate factors contribute to generate eye rotations during sinusoidal yaw head rotations while viewing a near target; these include the VOR, visual-tracking eye movements that utilize retinal image motion, predictive eye movements and, possibly, other unidentified non-vestibular factors. For these experiments, vergence was not an important determinant of response gam.

Vestibular and Non-vestibular Contributions to Eye Movements that Compensate for Head Rotations during Viewing of Near Targets

NASA Technical Reports Server (NTRS)

Han, Yanning H.; Kumar, Arun N.; Reschke, Millard F.; Somers, Jeffrey T.; Dell'Osso, Louis F.; Leigh, R. John

2004-01-01

We studied horizontal eye movements induced by en-bloc yaw rotation, over a frequency range 0.2 - 2.8 Hz, in 10 normal human subjects as th ey monocularly viewed a target located at their near point of focus. We measured gain and phase relationships between eye-in-head velocity and head velocity when the near target was either earth-fixed or head-fixed. During viewing of the earth-fixed near target,median gain was 1.49 (range 1.24 - 1.87) at 0.2 Hz for the group of subjects, but decl ined at higher frequencies, so that at 2.8 Hz median gain was 1.08 (r ange 0.68 - 1.67). During viewing of the head-fixed near target, median gain was 0.03 (range 0.01 - 0.10) at 0.2 Hz for the group of subjec ts, but increased at higher frequencies, so that at 2.8 Hz median gai n was 0.71 (range 0.28 - 0.94). We estimated the vestibular contribution to these responses (vestibulo-ocular reflex gain, Gvor) by applyin g transient head perturbations (peak acceleration> 1,000 deg's(exp 2) ) during sinusoidal rotation under the two viewing conditions. Median Gvor, estimated < 70m after the onset of head perturbation, was 0.98 (range 0.39 - 1.42) while viewing the earth-fixed near target, and 0. 97 (range 0.37 - 1.33) while viewing the head-fixed near target. For the group of subjects, 9 out of 10 subjects showed no sigificant diff erence of Gvor between the two viewing conditions ( p > 0.053 ) at all test frequencies. Since Gvor accounted for only approximately 73% of the overall response gain during viewing of the earth-fixed target, we investigated the relative contributions of non-vestibular factors. When subjects viewed the earth-fixed target under strobe illumination , to eliminate retinal image slip information, the gain of compensato ry eye movements declined compared with viewing in ambient room light . During sum-of-sine head rotations, while viewing the earth-fixed target, to minimize contributions from predictive mechanisms, gain also declined Nonetheless, simple superposition of smooth-pursuit tracking of sinusoidal target motion could not fully account for the overall r esponse at higher frequencies, suggesting other non-vestibular contributions. During binocular viewing conditions when vergence angle was s ignificantly greater than monocular viewing (p < 0.001), this gain of compensatory eye movements did not show proportional change; indeed, gain could not be correlated with vergence angle during monocular or binocular viewing. We conclude that several separate factors contribute to generate eye rotations during sinusoidal yaw head rotations whi le viewing a near target; these include the VOR, visual-tracking eye movements that utilize retinal image motion, predictive eye movements and, possibly, other unidentified nonvestibular factors. For these experiments, vergence was not an important determinant of response gain .

Role of Alpha-Band Oscillations in Spatial Updating across Whole Body Motion

PubMed Central

Gutteling, Tjerk P.; Medendorp, W. P.

2016-01-01

When moving around in the world, we have to keep track of important locations in our surroundings. In this process, called spatial updating, we must estimate our body motion and correct representations of memorized spatial locations in accordance with this motion. While the behavioral characteristics of spatial updating across whole body motion have been studied in detail, its neural implementation lacks detailed study. Here we use electroencephalography (EEG) to distinguish various spectral components of this process. Subjects gazed at a central body-fixed point in otherwise complete darkness, while a target was briefly flashed, either left or right from this point. Subjects had to remember the location of this target as either moving along with the body or remaining fixed in the world while being translated sideways on a passive motion platform. After the motion, subjects had to indicate the remembered target location in the instructed reference frame using a mouse response. While the body motion, as detected by the vestibular system, should not affect the representation of body-fixed targets, it should interact with the representation of a world-centered target to update its location relative to the body. We show that the initial presentation of the visual target induced a reduction of alpha band power in contralateral parieto-occipital areas, which evolved to a sustained increase during the subsequent memory period. Motion of the body led to a reduction of alpha band power in central parietal areas extending to lateral parieto-temporal areas, irrespective of whether the targets had to be memorized relative to world or body. When updating a world-fixed target, its internal representation shifts hemispheres, only when subjects’ behavioral responses suggested an update across the body midline. Our results suggest that parietal cortex is involved in both self-motion estimation and the selective application of this motion information to maintaining target locations as fixed in the world or fixed to the body. PMID:27199882

Further studies to extend and test the area-time-integral technique applied to satellite data

NASA Technical Reports Server (NTRS)

Smith, Paul L.; Vonderhaar, Thomas H.

1993-01-01

The principal goal of this project is to establish relationships that would allow application of area-time integral (ATI) calculations based upon satellite data to estimate rainfall volumes. The research has been pursued using two different approaches, which for convenience can be designated as the 'fixed-threshold approach' and the 'variable-threshold approach'. In the former approach, an attempt is made to determine a single temperature threshold in the satellite infrared data that would yield ATI values for identifiable cloud clusters which are most closely related to the corresponding rainfall amounts. Results thus far have indicated that a strong correlation exists between the rain volumes and the satellite ATI values, but the optimum threshold for this relationship seems to differ from one geographic location to another. The difference is probably related to differences in the basic precipitation mechanisms that dominate in the different regions. The average rainfall rate associated with each cloudy pixel is also found to vary across the spectrum of ATI values. Work on the second, or 'variable-threshold', approach for determining the satellite ATI values was essentially suspended during this period due to exhaustion of project funds. Most of the ATI work thus far has dealt with cloud clusters from the Lagrangian or 'floating-target' point of view. For many purposes, however, the Eulerian or 'fixed-target' perspective is more appropriate. For a very large target area encompassing entire cluster life histories, the rain volume-ATI relationship would obviously be the same in either case. The important question for the Eulerian perspective is how small the fixed area can be made while maintaining consistency in that relationship.

Physics perspectives with AFTER@LHC (A Fixed Target ExpeRiment at LHC)

NASA Astrophysics Data System (ADS)

Massacrier, L.; Anselmino, M.; Arnaldi, R.; Brodsky, S. J.; Chambert, V.; Da Silva, C.; Didelez, J. P.; Echevarria, M. G.; Ferreiro, E. G.; Fleuret, F.; Gao, Y.; Genolini, B.; Hadjidakis, C.; Hřivnáčová, I.; Kikola, D.; Klein, A.; Kurepin, A.; Kusina, A.; Lansberg, J. P.; Lorcé, C.; Lyonnet, F.; Martinez, G.; Nass, A.; Pisano, C.; Robbe, P.; Schienbein, I.; Schlegel, M.; Scomparin, E.; Seixas, J.; Shao, H. S.; Signori, A.; Steffens, E.; Szymanowski, L.; Topilskaya, N.; Trzeciak, B.; Uggerhøj, U. I.; Uras, A.; Ulrich, R.; Wagner, J.; Yamanaka, N.; Yang, Z.

2018-02-01

AFTER@LHC is an ambitious fixed-target project in order to address open questions in the domain of proton and neutron spins, Quark Gluon Plasma and high-x physics, at the highest energy ever reached in the fixed-target mode. Indeed, thanks to the highly energetic 7 TeV proton and 2.76 A.TeV lead LHC beams, center-of-mass energies as large as = 115 GeV in pp/pA and = 72 GeV in AA can be reached, corresponding to an uncharted energy domain between SPS and RHIC. We report two main ways of performing fixed-target collisions at the LHC, both allowing for the usage of one of the existing LHC experiments. In these proceedings, after discussing the projected luminosities considered for one year of data taking at the LHC, we will present a selection of projections for light and heavy-flavour production.

Evidence-Based Design of Fixed-Dose Combinations: Principles and Application to Pediatric Anti-Tuberculosis Therapy.

PubMed

Svensson, Elin M; Yngman, Gunnar; Denti, Paolo; McIlleron, Helen; Kjellsson, Maria C; Karlsson, Mats O

2018-05-01

Fixed-dose combination formulations where several drugs are included in one tablet are important for the implementation of many long-term multidrug therapies. The selection of optimal dose ratios and tablet content of a fixed-dose combination and the design of individualized dosing regimens is a complex task, requiring multiple simultaneous considerations. In this work, a methodology for the rational design of a fixed-dose combination was developed and applied to the case of a three-drug pediatric anti-tuberculosis formulation individualized on body weight. The optimization methodology synthesizes information about the intended use population, the pharmacokinetic properties of the drugs, therapeutic targets, and practical constraints. A utility function is included to penalize deviations from the targets; a sequential estimation procedure was developed for stable estimation of break-points for individualized dosing. The suggested optimized pediatric anti-tuberculosis fixed-dose combination was compared with the recently launched World Health Organization-endorsed formulation. The optimized fixed-dose combination included 15, 36, and 16% higher amounts of rifampicin, isoniazid, and pyrazinamide, respectively. The optimized fixed-dose combination is expected to result in overall less deviation from the therapeutic targets based on adult exposure and substantially fewer children with underexposure (below half the target). The development of this design tool can aid the implementation of evidence-based formulations, integrating available knowledge and practical considerations, to optimize drug exposures and thereby treatment outcomes.

Feasibility Studies for Single Transverse-Spin Asymmetry Measurements at a Fixed-Target Experiment Using the LHC Proton and Lead Beams (AFTER@LHC)

DOE PAGES

Kikoła, Daniel; Echevarria, Miguel García; Hadjidakis, Cynthia; ...

2017-05-17

Measurement of Single Transverse-Spin Asymmetrymore » $$A_N$$ for various quarkonia states and Drell-Yan lepton pairs can shed light on the orbital angular momentum of quarks and gluons, a fundamental ingredient of the spin puzzle of the proton. The AFTER@LHC experiment combines a unique kinematic coverage and large luminosities of the Large Hadron Collider beams to deliver precise measurements, complementary to the knowledge provided by collider experiments such as RHIC. Here, we report on sensitivity studies for $$J/\\Psi$$, $$\\Upsilon$$ and Drell-Yan $$A_N$$ done using the performance of a LHCb-like and ALICE-like detectors, combined with a polarised hydrogen and $^3$He target. Particularly, such research will provide new insights and knowledge about transverse-momentum-dependent parton distribution functions for quarks and gluons and on twist-3 collinear matrix elements in a proton and a neutron.« less

Electron– and positron–molecule scattering: development of the molecular convergent close-coupling method

DOE PAGES

Zammit, Mark C.; Fursa, Dmitry V.; Savage, Jeremy S.; ...

2017-05-22

Starting from first principles, this tutorial describes the development of the adiabatic-nuclei convergent close-coupling (CCC) method and its application to electron and (single-centre) positron scattering from diatomic molecules. In this paper, we give full details of the single-centre expansion CCC method, namely the formulation of the molecular target structure; solving the momentum-space coupled-channel Lippmann-Schwinger equation; deriving adiabatic-nuclei cross sections and calculatingmore » $V$-matrix elements. Selected results are presented for electron and positron scattering from molecular hydrogen H$$_2$$ and electron scattering from the vibrationally excited molecular hydrogen ion H$$_2^+$$ and its isotopologues (D$$_2^+$$, T$$_2^+$$, HD$^+$, HT$^+$ and TD$^+$). Finally, convergence in both the close-coupling (target state) and projectile partial-wave expansions of fixed-nuclei electron- and positron-molecule scattering calculations is demonstrated over a broad energy-range and discussed in detail. In general the CCC results are in good agreement with experiments.« less

GE781: a Monte Carlo package for fixed target experiments

NASA Astrophysics Data System (ADS)

Davidenko, G.; Funk, M. A.; Kim, V.; Kuropatkin, N.; Kurshetsov, V.; Molchanov, V.; Rud, S.; Stutte, L.; Verebryusov, V.; Zukanovich Funchal, R.

The Monte Carlo package for the fixed target experiment B781 at Fermilab, a third generation charmed baryon experiment, is described. This package is based on GEANT 3.21, ADAMO database and DAFT input/output routines.

Videogrammetric Model Deformation Measurement System User's Manual

NASA Technical Reports Server (NTRS)

Dismond, Harriett R.

2002-01-01

The purpose of this manual is to provide the user of the NASA VMD system, running the MDef software, Version 1.10, all information required to operate the system. The NASA Videogrammetric Model Deformation system consists of an automated videogrammetric technique used to measure the change in wing twist and bending under aerodynamic load in a wind tunnel. The basic instrumentation consists of a single CCD video camera and a frame grabber interfaced to a computer. The technique is based upon a single view photogrammetric determination of two-dimensional coordinates of wing targets with fixed (and known) third dimensional coordinate, namely the span-wise location. The major consideration in the development of the measurement system was that productivity must not be appreciably reduced.

Comparison of experimental and theoretical triple differential cross sections for the single ionization of C O2 (1 πg ) by electron impact

NASA Astrophysics Data System (ADS)

Ozer, Zehra N.; Ali, Esam; Dogan, Mevlut; Yavuz, Murat; Alwan, Osman; Naja, Adnan; Chuluunbaatar, Ochbadrakh; Joulakian, Boghos B.; Ning, Chuan-Gang; Colgan, James; Madison, Don

2016-06-01

Experimental and theoretical triple differential cross sections for intermediate-energy (250 eV) electron-impact single ionization of the CO2 are presented for three fixed projectile scattering angles. Results are presented for ionization of the outermost 1 πg molecular orbital of C O2 in a coplanar asymmetric geometry. The experimental data are compared to predictions from the three-center Coulomb continuum approximation for triatomic targets, and the molecular three-body distorted wave (M3DW) model. It is observed that while both theories are in reasonable qualitative agreement with experiment, the M3DW is in the best overall agreement with experiment.

Efficacy and Safety of a Single-Pill Fixed-Dose Combination of Azilsartan and Amlodipine

PubMed Central

Motozato, Kota; Miura, Shin-ichiro; Shiga, Yuhei; Kusumoto, Takaaki; Saku, Keijiro

2016-01-01

Background Guidelines for the management of hypertension recommend the use of drugs with different mechanisms of action in antihypertensive regimens that include single-pill fixed-dose combinations of medications. There is some controversy regarding which single-pill fixed-dose combinations of angiotensin II type 1 receptor blockers (ARBs) and calcium channel blockers (CCBs) are effective at reducing blood pressure (BP). Methods Forty hypertensive patients who were receiving a single-pill fixed-dose combination of valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day were enrolled. They were randomly divided into two treatment groups, a group that changed to a single-pill fixed-dose combination of azilsartan 20 mg/day and amlodipine 5 mg/day (changeover group) and a group that continued to receive valsartan 80 mg/day and amlodipine 5 mg/day or irbesartan 100 mg/day and amlodipine 5 mg/day (control group), and treated for 16 weeks. Results There were no significant differences in systolic blood pressure (SBP), diastolic blood pressure (DBP) or pulse rate (PR) at 16 weeks between the control and changeover groups. In addition, there were no significant changes in biochemical parameters throughout the study period in both groups. Conclusion The ability of a single-pill fixed-dose combination of azilsartan and amlodipine to reduce BP may be comparable to that of a combination of valsartan and amlodipine or irbesartan and amlodipine. PMID:27829955

A four-dimensional virtual hand brain-machine interface using active dimension selection.

PubMed

Rouse, Adam G

2016-06-01

Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. ADS utilizes a two stage decoder by using neural signals to both (i) select an active dimension being controlled and (ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits s(-1) for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand.

Identification and genetic analysis of cancer cells with PCR-activated cell sorting

PubMed Central

Eastburn, Dennis J.; Sciambi, Adam; Abate, Adam R.

2014-01-01

Cell sorting is a central tool in life science research for analyzing cellular heterogeneity or enriching rare cells out of large populations. Although methods like FACS and FISH-FC can characterize and isolate cells from heterogeneous populations, they are limited by their reliance on antibodies, or the requirement to chemically fix cells. We introduce a new cell sorting technology that robustly sorts based on sequence-specific analysis of cellular nucleic acids. Our approach, PCR-activated cell sorting (PACS), uses TaqMan PCR to detect nucleic acids within single cells and trigger their sorting. With this method, we identified and sorted prostate cancer cells from a heterogeneous population by performing >132 000 simultaneous single-cell TaqMan RT-PCR reactions targeting vimentin mRNA. Following vimentin-positive droplet sorting and downstream analysis of recovered nucleic acids, we found that cancer-specific genomes and transcripts were significantly enriched. Additionally, we demonstrate that PACS can be used to sort and enrich cells via TaqMan PCR reactions targeting single-copy genomic DNA. PACS provides a general new technical capability that expands the application space of cell sorting by enabling sorting based on cellular information not amenable to existing approaches. PMID:25030902

Rabbit genome analysis reveals a polygenic basis for phenotypic change during domestication.

PubMed

Carneiro, Miguel; Rubin, Carl-Johan; Di Palma, Federica; Albert, Frank W; Alföldi, Jessica; Martinez Barrio, Alvaro; Pielberg, Gerli; Rafati, Nima; Sayyab, Shumaila; Turner-Maier, Jason; Younis, Shady; Afonso, Sandra; Aken, Bronwen; Alves, Joel M; Barrell, Daniel; Bolet, Gerard; Boucher, Samuel; Burbano, Hernán A; Campos, Rita; Chang, Jean L; Duranthon, Veronique; Fontanesi, Luca; Garreau, Hervé; Heiman, David; Johnson, Jeremy; Mage, Rose G; Peng, Ze; Queney, Guillaume; Rogel-Gaillard, Claire; Ruffier, Magali; Searle, Steve; Villafuerte, Rafael; Xiong, Anqi; Young, Sarah; Forsberg-Nilsson, Karin; Good, Jeffrey M; Lander, Eric S; Ferrand, Nuno; Lindblad-Toh, Kerstin; Andersson, Leif

2014-08-29

The genetic changes underlying the initial steps of animal domestication are still poorly understood. We generated a high-quality reference genome for the rabbit and compared it to resequencing data from populations of wild and domestic rabbits. We identified more than 100 selective sweeps specific to domestic rabbits but only a relatively small number of fixed (or nearly fixed) single-nucleotide polymorphisms (SNPs) for derived alleles. SNPs with marked allele frequency differences between wild and domestic rabbits were enriched for conserved noncoding sites. Enrichment analyses suggest that genes affecting brain and neuronal development have often been targeted during domestication. We propose that because of a truly complex genetic background, tame behavior in rabbits and other domestic animals evolved by shifts in allele frequencies at many loci, rather than by critical changes at only a few domestication loci. Copyright © 2014, American Association for the Advancement of Science.

Technical Note: A treatment plan comparison between dynamic collimation and a fixed aperture during spot scanning proton therapy for brain treatment

PubMed Central

Smith, Blake; Gelover, Edgar; Moignier, Alexandra; Wang, Dongxu; Flynn, Ryan T.; Lin, Liyong; Kirk, Maura; Solberg, Tim; Hyer, Daniel E.

2016-01-01

Purpose: To quantitatively assess the advantages of energy-layer specific dynamic collimation system (DCS) versus a per-field fixed aperture for spot scanning proton therapy (SSPT). Methods: Five brain cancer patients previously planned and treated with SSPT were replanned using an in-house treatment planning system capable of modeling collimated and uncollimated proton beamlets. The uncollimated plans, which served as a baseline for comparison, reproduced the target coverage and organ-at-risk sparing of the clinically delivered plans. The collimator opening for the fixed aperture-based plans was determined from the combined cross sections of the target in the beam’s eye view over all energy layers which included an additional margin equivalent to the maximum beamlet displacement for the respective energy of that energy layer. The DCS-based plans were created by selecting appropriate collimator positions for each row of beam spots during a Raster-style scanning pattern which were optimized to maximize the dose contributions to the target and limited the dose delivered to adjacent normal tissue. Results: The reduction of mean dose to normal tissue adjacent to the target, as defined by a 10 mm ring surrounding the target, averaged 13.65% (range: 11.8%–16.9%) and 5.18% (2.9%–7.1%) for the DCS and fixed aperture plans, respectively. The conformity index, as defined by the ratio of the volume of the 50% isodose line to the target volume, yielded an average improvement of 21.35% (19.4%–22.6%) and 8.38% (4.7%–12.0%) for the DCS and fixed aperture plans, respectively. Conclusions: The ability of the DCS to provide collimation to each energy layer yielded better conformity in comparison to fixed aperture plans. PMID:27487886

Signal transduction and phosphoryl transfer by a FixL hybrid kinase with low oxygen affinity: importance of the vicinal PAS domain and receiver aspartate.

PubMed

Sousa, Eduardo H S; Tuckerman, Jason R; Gondim, Ana C S; Gonzalez, Gonzalo; Gilles-Gonzalez, Marie-Alda

2013-01-22

FixL is a prototype for heme-based sensors, multidomain proteins that typically couple a histidine protein kinase activity to a heme-binding domain for sensing of diatomic gases such as oxygen, carbon monoxide, and nitric oxide. Despite the relatively well-developed understanding of FixL, the importance of some of its domains has been unclear. To explore the impact of domain-domain interactions on oxygen sensing and signal transduction, we characterized and investigated Rhizobium etli hybrid sensor ReFixL. In ReFixL, the core heme-containing PAS domain and kinase region is preceded by an N-terminal PAS domain of unknown function and followed by a C-terminal receiver domain. The latter resembles a target substrate domain that usually occurs independently of the kinase and contains a phosphorylatable aspartate residue. We isolated the full-length ReFixL as a soluble holoprotein with a single heme b cofactor. Despite a low affinity for oxygen (K(d) for O₂ of 738 μM), the kinase activity was completely switched off by O₂ at concentrations well below the K(d). A deletion of the first PAS domain strongly increased the oxygen affinity but essentially prohibited autophosphorylation, although the truncated protein was competent to accept phosphoryl groups in trans. These studies provide new insights into histidyl-aspartyl phosphoryl transfers in two-component systems and suggest that the control of ligand affinity and signal transduction by PAS domains can be direct or indirect.

Transforming graph states using single-qubit operations.

PubMed

Dahlberg, Axel; Wehner, Stephanie

2018-07-13

Stabilizer states form an important class of states in quantum information, and are of central importance in quantum error correction. Here, we provide an algorithm for deciding whether one stabilizer (target) state can be obtained from another stabilizer (source) state by single-qubit Clifford operations (LC), single-qubit Pauli measurements (LPM) and classical communication (CC) between sites holding the individual qubits. What is more, we provide a recipe to obtain the sequence of LC+LPM+CC operations which prepare the desired target state from the source state, and show how these operations can be applied in parallel to reach the target state in constant time. Our algorithm has applications in quantum networks, quantum computing, and can also serve as a design tool-for example, to find transformations between quantum error correcting codes. We provide a software implementation of our algorithm that makes this tool easier to apply. A key insight leading to our algorithm is to show that the problem is equivalent to one in graph theory, which is to decide whether some graph G ' is a vertex-minor of another graph G The vertex-minor problem is, in general, [Formula: see text]-Complete, but can be solved efficiently on graphs which are not too complex. A measure of the complexity of a graph is the rank-width which equals the Schmidt-rank width of a subclass of stabilizer states called graph states, and thus intuitively is a measure of entanglement. Here, we show that the vertex-minor problem can be solved in time O (| G | 3 ), where | G | is the size of the graph G , whenever the rank-width of G and the size of G ' are bounded. Our algorithm is based on techniques by Courcelle for solving fixed parameter tractable problems, where here the relevant fixed parameter is the rank width. The second half of this paper serves as an accessible but far from exhausting introduction to these concepts, that could be useful for many other problems in quantum information.This article is part of a discussion meeting issue 'Foundations of quantum mechanics and their impact on contemporary society'. © 2018 The Author(s).

Splitting attention reduces temporal resolution from 7 Hz for tracking one object to <3 Hz when tracking three.

PubMed

Holcombe, Alex O; Chen, Wei-Ying

2013-01-09

Overall performance when tracking moving targets is known to be poorer for larger numbers of targets, but the specific effect on tracking's temporal resolution has never been investigated. We document a broad range of display parameters for which visual tracking is limited by temporal frequency (the interval between when a target is at each location and a distracter moves in and replaces it) rather than by object speed. We tested tracking of one, two, and three moving targets while the eyes remained fixed. Variation of the number of distracters and their speed revealed both speed limits and temporal frequency limits on tracking. The temporal frequency limit fell from 7 Hz with one target to 4 Hz with two targets and 2.6 Hz with three targets. The large size of this performance decrease implies that in the two-target condition participants would have done better by tracking only one of the two targets and ignoring the other. These effects are predicted by serial models involving a single tracking focus that must switch among the targets, sampling the position of only one target at a time. If parallel processing theories are to explain why dividing the tracking resource reduces temporal resolution so markedly, supplemental assumptions will be required.

Assessment of the efficacy of a novel tailored vitamin K dosing regimen in lowering the International Normalised Ratio in over-anticoagulated patients: a randomised clinical trial.

PubMed

Kampouraki, Emmanouela; Avery, Peter J; Wynne, Hilary; Biss, Tina; Hanley, John; Talks, Kate; Kamali, Farhad

2017-09-01

Current guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism. We compared the performance of a novel tailored vitamin K dosing regimen to that of a fixed-dose regimen with the primary measure being the proportion of over-anticoagulated patients returning to their target INR within 24 h. One hundred and eighty-one patients with an index INR > 6·0 (asymptomatic or with minor bleeding) were randomly allocated to receive oral administration of either a tailored dose (based upon index INR and body surface area) or a fixed-dose (1 or 2 mg) of vitamin K. A greater proportion of patients treated with the tailored dose returned to within target INR range compared to the fixed-dose regimen (68·9% vs. 52·8%; P = 0·026), whilst a smaller proportion of patients remained above target INR range (12·2% vs. 34·0%; P < 0·001). Individualised vitamin K dosing is more accurate than fixed-dose regimen in lowering INR to within target range in excessively anticoagulated patients. © 2017 John Wiley & Sons Ltd.

Encoding of Target Detection during Visual Search by Single Neurons in the Human Brain.

PubMed

Wang, Shuo; Mamelak, Adam N; Adolphs, Ralph; Rutishauser, Ueli

2018-06-08

Neurons in the primate medial temporal lobe (MTL) respond selectively to visual categories such as faces, contributing to how the brain represents stimulus meaning. However, it remains unknown whether MTL neurons continue to encode stimulus meaning when it changes flexibly as a function of variable task demands imposed by goal-directed behavior. While classically associated with long-term memory, recent lesion and neuroimaging studies show that the MTL also contributes critically to the online guidance of goal-directed behaviors such as visual search. Do such tasks modulate responses of neurons in the MTL, and if so, do their responses mirror bottom-up input from visual cortices or do they reflect more abstract goal-directed properties? To answer these questions, we performed concurrent recordings of eye movements and single neurons in the MTL and medial frontal cortex (MFC) in human neurosurgical patients performing a memory-guided visual search task. We identified a distinct population of target-selective neurons in both the MTL and MFC whose response signaled whether the currently fixated stimulus was a target or distractor. This target-selective response was invariant to visual category and predicted whether a target was detected or missed behaviorally during a given fixation. The response latencies, relative to fixation onset, of MFC target-selective neurons preceded those in the MTL by ∼200 ms, suggesting a frontal origin for the target signal. The human MTL thus represents not only fixed stimulus identity, but also task-specified stimulus relevance due to top-down goal relevance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Neighborhood-targeted and case-triggered use of a single dose of oral cholera vaccine in an urban setting: Feasibility and vaccine coverage.

PubMed

Parker, Lucy A; Rumunu, John; Jamet, Christine; Kenyi, Yona; Lino, Richard Laku; Wamala, Joseph F; Mpairwe, Allan M; Muller, Vincent; Llosa, Augusto E; Uzzeni, Florent; Luquero, Francisco J; Ciglenecki, Iza; Azman, Andrew S

2017-06-01

In June 2015, a cholera outbreak was declared in Juba, South Sudan. In addition to standard outbreak control measures, oral cholera vaccine (OCV) was proposed. As sufficient doses to cover the at-risk population were unavailable, a campaign using half the standard dosing regimen (one-dose) targeted high-risk neighborhoods and groups including neighbors of suspected cases. Here we report the operational details of this first public health use of a single-dose regimen of OCV and illustrate the feasibility of conducting highly targeted vaccination campaigns in an urban area. Neighborhoods of the city were prioritized for vaccination based on cumulative attack rates, active transmission and local knowledge of known cholera risk factors. OCV was offered to all persons older than 12 months at 20 fixed sites and to select groups, including neighbors of cholera cases after the main campaign ('case-triggered' interventions), through mobile teams. Vaccination coverage was estimated by multi-stage surveys using spatial sampling techniques. 162,377 individuals received a single-dose of OCV in the targeted neighborhoods. In these neighborhoods vaccine coverage was 68.8% (95% Confidence Interval (CI), 64.0-73.7) and was highest among children ages 5-14 years (90.0%, 95% CI 85.7-94.3), with adult men being less likely to be vaccinated than adult women (Relative Risk 0.81, 95% CI: 0.68-0.96). In the case-triggered interventions, each lasting 1-2 days, coverage varied (range: 30-87%) with an average of 51.0% (95% CI 41.7-60.3). Vaccine supply constraints and the complex realities where cholera outbreaks occur may warrant the use of flexible alternative vaccination strategies, including highly-targeted vaccination campaigns and single-dose regimens. We showed that such campaigns are feasible. Additional work is needed to understand how and when to use different strategies to best protect populations against epidemic cholera.

Direction information in multiple object tracking is limited by a graded resource.

PubMed

Horowitz, Todd S; Cohen, Michael A

2010-10-01

Is multiple object tracking (MOT) limited by a fixed set of structures (slots), a limited but divisible resource, or both? Here, we answer this question by measuring the precision of the direction representation for tracked targets. The signature of a limited resource is a decrease in precision as the square root of the tracking load. The signature of fixed slots is a fixed precision. Hybrid models predict a rapid decrease to asymptotic precision. In two experiments, observers tracked moving disks and reported target motion direction by adjusting a probe arrow. We derived the precision of representation of correctly tracked targets using a mixture distribution analysis. Precision declined with target load according to the square-root law up to six targets. This finding is inconsistent with both pure and hybrid slot models. Instead, directional information in MOT appears to be limited by a continuously divisible resource.

Physics opportunities with a fixed target experiment at the LHC (AFTER@LHC)

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

Hadjidakis, Cynthia; Anselmino, Mauro; Arnaldi, R.

By extracting the beam with a bent crystal or by using an internal gas target, the multi-TeV proton and lead LHC beams allow one to perform the most energetic fixed-target experiments (AFTER@LHC) and to study p+p and p+A collisions at \\sqrt{s_NN}=115 GeV and Pb+p and Pb+A collisions at \\sqrt{s_NN}=72 GeV. Such studies would address open questions in the domain of the nucleon and nucleus partonic structure at high-x, quark-gluon plasma and, by using longitudinally or transversally polarised targets, spin physics. In this paper, we discuss the physics opportunities of a fixed-target experiment at the LHC and we report on themore » possible technical implementations of a high-luminosity experiment. We finally present feasibility studies for Drell-Yan, open heavy-flavour and quarkonium production, with an emphasis on high-x and spin physics.« less

Laboratory Measurements of Single-Particle Polarimetric Spectrum

NASA Astrophysics Data System (ADS)

Gritsevich, M.; Penttila, A.; Maconi, G.; Kassamakov, I.; Helander, P.; Puranen, T.; Salmi, A.; Hæggström, E.; Muinonen, K.

2017-12-01

Measuring scattering properties of different targets is important for material characterization, remote sensing applications, and for verifying theoretical results. Furthermore, there are usually simplifications made when we model targets and compute the scattering properties, e.g., ideal shape or constant optical parameters throughout the target material. Experimental studies help in understanding the link between the observed properties and computed results. Experimentally derived Mueller matrices of studied particles can be used as input for larger-scale scattering simulations, e.g., radiative transfer computations. This method allows to bypass the problem of using an idealized model for single-particle optical properties. While existing approaches offer ensemble- and orientation-averaged particle properties, our aim is to measure individual particles with controlled or known orientation. With the newly developed scatterometer, we aim to offer novel possibility to measure single, small (down to μm-scale) targets and their polarimetric spectra. This work presents an experimental setup that measures light scattered by a fixed small particle with dimensions ranging between micrometer and millimeter sizes. The goal of our setup is nondestructive characterization of such particles by measuring light of multiple wavelengths scattered in 360° in a horizontal plane by an ultrasonically levitating sample, whilst simultaneously controlling its 3D position and orientation. We describe the principles and design of our instrument and its calibration. We also present example measurements of real samples. This study was conducted under the support from the European Research Council, in the frame of the Advanced Grant project No. 320773 `Scattering and Absorption of Electromagnetic Waves in Particulate Media' (SAEMPL).

Triangulation methods for automated docking

NASA Technical Reports Server (NTRS)

Bales, John W.

1996-01-01

An automated docking system must have a reliable method for determining range and orientation of the passive (target) vehicle with respect to the active vehicle. This method must also provide accurate information on the rates of change of range to and orientation of the passive vehicle. The method must be accurate within required tolerances and capable of operating in real time. The method being developed at Marshall Space Flight Center employs a single TV camera, a laser illumination system and a target consisting, in its minimal configuration, of three retro-reflectors. Two of the retro-reflectors are mounted flush to the same surface, with the third retro-reflector mounted to a post fixed midway between the other two and jutting at a right angle from the surface. For redundancy, two additional retroreflectors are mounted on the surface on a line at right angles to the line containing the first two retro-reflectors, and equally spaced on either side of the post. The target vehicle will contain a large target for initial acquisition and several smaller targets for close range.

Perspective: A Dynamics-Based Classification of Ventricular Arrhythmias

PubMed Central

Weiss, James N.; Garfinkel, Alan; Karagueuzian, Hrayr S.; Nguyen, Thao P.; Olcese, Riccardo; Chen, Peng-Sheng; Qu, Zhilin

2015-01-01

Despite key advances in the clinical management of life-threatening ventricular arrhythmias, culminating with the development of implantable cardioverter-defibrillators and catheter ablation techniques, pharmacologic/biologic therapeutics have lagged behind. The fundamental issue is that biological targets are molecular factors. Diseases, however, represent emergent properties at the scale of the organism that result from dynamic interactions between multiple constantly changing molecular factors. For a pharmacologic/biologic therapy to be effective, it must target the dynamic processes that underlie the disease. Here we propose a classification of ventricular arrhythmias that is based on our current understanding of the dynamics occurring at the subcellular, cellular, tissue and organism scales, which cause arrhythmias by simultaneously generating arrhythmia triggers and exacerbating tissue vulnerability. The goal is to create a framework that systematically links these key dynamic factors together with fixed factors (structural and electrophysiological heterogeneity) synergistically promoting electrical dispersion and increased arrhythmia risk to molecular factors that can serve as biological targets. We classify ventricular arrhythmias into three primary dynamic categories related generally to unstable Ca cycling, reduced repolarization, and excess repolarization, respectively. The clinical syndromes, arrhythmia mechanisms, dynamic factors and what is known about their molecular counterparts are discussed. Based on this framework, we propose a computational-experimental strategy for exploring the links between molecular factors, fixed factors and dynamic factors that underlie life-threatening ventricular arrhythmias. The ultimate objective is to facilitate drug development by creating an in silico platform to evaluate and predict comprehensively how molecular interventions affect not only a single targeted arrhythmia, but all primary arrhythmia dynamics categories as well as normal cardiac excitation-contraction coupling. PMID:25769672

Compact and cost effective instrument for detecting drug precursors in different environments based on fluorescence polarization

NASA Astrophysics Data System (ADS)

Antolín-Urbaneja, J. C.; Eguizabal, I.; Briz, N.; Dominguez, A.; Estensoro, P.; Secchi, A.; Varriale, A.; Di Giovanni, S.; D'Auria, S.

2013-05-01

Several techniques for detecting chemical drug precursors have been developed in the last decade. Most of them are able to identify molecules at very low concentration under lab conditions. Other commercial devices are able to detect a fixed number and type of target substances based on a single detection technique providing an absence of flexibility with respect to target compounds. The construction of compact and easy to use detection systems providing screening for a large number of compounds being able to discriminate them with low false alarm rate and high probability of detection is still an open concern. Under CUSTOM project, funded by the European Commission within the FP7, a stand-alone portable sensing device based on multiple techniques is being developed. One of these techniques is based on the LED induced fluorescence polarization to detect Ephedrine and Benzyl Methyl Keton (BMK) as a first approach. This technique is highly selective with respect to the target compounds due to the generation of properly engineered fluorescent proteins which are able to bind the target analytes, as it happens in an "immune-type reaction". This paper deals with the advances in the design, construction and validation of the LED induced fluorescence sensor to detect BMK analytes. This sensor includes an analysis module based on high performance LED and PMT detector, a fluidic system to dose suitable quantities of reagents and some printed circuit boards, all of them fixed in a small structure (167mm × 193mm × 228mm) with the capability of working as a stand-alone application.

Fiber-reinforced composite fixed dental prostheses: two clinical reports.

PubMed

Zarow, Maciej; Paisley, Carl Stuart; Krupinski, Jerzy; Brunton, Paul Anthony

2010-06-01

Various options are available in clinical practice for the replacement of a single missing tooth, ranging from conventional fixed and removable dental prostheses to a single implant-supported crown. There are situations in which a semipermanent fixed dental prosthesis may be desirable, particularly for patients who have completed orthodontic treatment but are too young to embark on implant therapy. Following advances in fiber-reinforcement technology, fiber-reinforced composite resin (FRC) now represents a lower-cost alternative to traditional metal-ceramic for the construction of resin-bonded prostheses. Two case reports illustrate the use of FRC prostheses as fixed semipermanent_restorations.

Electromagnetic Interference in Implantable Defibrillators in Single-Engine Fixed-Wing Aircraft.

PubMed

de Rotte, Alexandra A J; van der Kemp, Peter; Mundy, Peter A; Rienks, Rienk; de Rotte, August A

2017-01-01

Little is known about the possible electromagnetic interferences (EMI) in the single-engine fixed-wing aircraft environment with implantable cardio-defibrillators (ICDs). Our hypothesis is that EMI in the cockpit of a single-engine fixed-wing aircraft does not result in erroneous detection of arrhythmias and the subsequent delivery of an inappropriate device therapy. ICD devices of four different manufacturers, incorporated in a thorax phantom, were transported in a Piper Dakota Aircraft with ICAO type designator P28B during several flights. The devices under test were programmed to the most sensitive settings for detection of electromagnetic signals from their environment. After the final flight the devices under test were interrogated with the dedicated programmers in order to analyze the number of tachycardias detected. Cumulative registration time of the devices under test was 11,392 min, with a mean of 2848 min per device. The registration from each one of the devices did not show any detectable "tachycardia" or subsequent inappropriate device therapy. This indicates that no external signals, which could be originating from electromagnetic fields from the aircraft's avionics, were detected by the devices under test. During transport in the cockpit of a single-engine fixed-wing aircraft, the tested ICDs did not show any signs of being affected by electromagnetic fields originating from the avionics of the aircraft. This current study indicates that EMI is not a potential safety issue for transportation of passengers with an ICD implanted in a single-engine fixed-wing aircraft.de Rotte AAJ, van der Kemp P, Mundy PA, Rienks R, de Rotte AA. Electromagnetic interference in implantable defibrillators in single-engine fixed-wing aircraft. Aerosp Med Hum Perform. 2017; 88(1):52-55.

Determining inter-system bias of GNSS signals with narrowly spaced frequencies for GNSS positioning

NASA Astrophysics Data System (ADS)

Tian, Yumiao; Liu, Zhizhao; Ge, Maorong; Neitzel, Frank

2017-12-01

Relative positioning using multi-GNSS (global navigation satellite systems) can improve accuracy, reliability, and availability compared to the use of a single constellation system. Intra-system double-difference (DD) ambiguities (ISDDAs) refer to the DD ambiguities between satellites of a single constellation system and can be fixed to an integer to derive the precise fixed solution. Inter-system ambiguities, which denote the DD ambiguities between different constellation systems, can also be fixed to integers on overlapping frequencies, once the inter-system bias (ISB) is removed. Compared with fixing ISDDAs, fixing both integer intra- and inter-system DD ambiguities (IIDDAs) means an increase of positioning precision through an integration of multiple GNSS constellations. Previously, researchers have studied IIDDA fixing with systems of the same frequencies, but not with systems of different frequencies. Integer IIDDAs can be determined from single-difference (SD) ambiguities, even if the frequencies of multi-GNSS signals used in the positioning are different. In this study, we investigated IIDDA fixing for multi-GNSS signals of narrowly spaced frequencies. First, the inter-system DD models of multi-GNSS signals of different frequencies are introduced, and the strategy for compensating for ISB is presented. The ISB is decomposed into three parts: 1) a float approximate ISB number that can be considered equal to the ISB of code pseudorange observations and thus can be estimated through single point positioning (SPP); 2) a number that is a multiple of the GNSS signal wavelength; and 3) a fractional ISB part, with a magnitude smaller than a single wavelength. Then, the relationship between intra- and inter-system DD ambiguity RATIO values and ISB was investigated by integrating GPS L1 and GLONASS L1 signals. In our numerical analyses with short baselines, the ISB parameter and IIDDA were successfully fixed, even if the number of observed satellites in each system was small.

Sputter deposition for multi-component thin films

DOEpatents

Krauss, A.R.; Auciello, O.

1990-05-08

Ion beam sputter-induced deposition using a single ion beam and a multicomponent target is capable of reproducibly producing thin films of arbitrary composition, including those which are close to stoichiometry. Using a quartz crystal deposition monitor and a computer controlled, well-focused ion beam, this sputter-deposition approach is capable of producing metal oxide superconductors and semiconductors of the superlattice type such as GaAs-AlGaAs as well as layered metal/oxide/semiconductor/superconductor structures. By programming the dwell time for each target according to the known sputtering yield and desired layer thickness for each material, it is possible to deposit composite films from a well-controlled sub-monolayer up to thicknesses determined only by the available deposition time. In one embodiment, an ion beam is sequentially directed via a set of X-Y electrostatic deflection plates onto three or more different element or compound targets which are constituents of the desired film. In another embodiment, the ion beam is directed through an aperture in the deposition plate and is displaced under computer control to provide a high degree of control over the deposited layer. In yet another embodiment, a single fixed ion beam is directed onto a plurality of sputter targets in a sequential manner where the targets are each moved in alignment with the beam under computer control in forming a multilayer thin film. This controlled sputter-deposition approach may also be used with laser and electron beams. 10 figs.

Sputter deposition for multi-component thin films

DOEpatents

Krauss, Alan R.; Auciello, Orlando

1990-01-01

Ion beam sputter-induced deposition using a single ion beam and a multicomponent target is capable of reproducibly producing thin films of arbitrary composition, including those which are close to stoichiometry. Using a quartz crystal deposition monitor and a computer controlled, well-focused ion beam, this sputter-deposition approach is capable of producing metal oxide superconductors and semiconductors of the superlattice type such as GaAs-AlGaAs as well as layered metal/oxide/semiconductor/superconductor structures. By programming the dwell time for each target according to the known sputtering yield and desired layer thickness for each material, it is possible to deposit composite films from a well-controlled sub-monolayer up to thicknesses determined only by the available deposition time. In one embodiment, an ion beam is sequentially directed via a set of X-Y electrostatic deflection plates onto three or more different element or compound targets which are constituents of the desired film. In another embodiment, the ion beam is directed through an aperture in the deposition plate and is displaced under computer control to provide a high degree of control over the deposited layer. In yet another embodiment, a single fixed ion beam is directed onto a plurality of sputter targets in a sequential manner where the targets are each moved in alignment with the beam under computer control in forming a multilayer thin film. This controlled sputter-deposition approach may also be used with laser and electron beams.

Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNA genes

PubMed Central

Taylor, Benjamin JM; Wu, Yee Ling; Rada, Cristina

2014-01-01

Cytidine deaminases are single stranded DNA mutators diversifying antibodies and restricting viral infection. Improper access to the genome leads to translocations and mutations in B cells and contributes to the mutation landscape in cancer, such as kataegis. It remains unclear how deaminases access double stranded genomes and whether off-target mutations favor certain loci, although transcription and opportunistic access during DNA repair are thought to play a role. In yeast, AID and the catalytic domain of APOBEC3G preferentially mutate transcriptionally active genes within narrow regions, 110 base pairs in width, fixed at RNA polymerase initiation sites. Unlike APOBEC3G, AID shows enhanced mutational preference for small RNA genes (tRNAs, snoRNAs and snRNAs) suggesting a putative role for RNA in its recruitment. We uncover the high affinity of the deaminases for the single stranded DNA exposed by initiating RNA polymerases (a DNA configuration reproduced at stalled polymerases) without a requirement for specific cofactors. DOI: http://dx.doi.org/10.7554/eLife.03553.001 PMID:25237741

Crowding in central vision in normally sighted and visually impaired [corrected] children aged 4 to 8 years: the influence of age and test design.

PubMed

Huurneman, Bianca; Boonstra, F Nienke; Cillessen, Antonius H N; van Rens, Ger; Cox, Ralf F A

2012-06-01

To investigate crowding ratios in children with a visual impairment due to ocular disease (n = 58) and normally sighted children (n = 75) aged 4 to 8 years using several variants of two clinically available tests with different optotype spacing (fixed or proportional to the optotype size). Crowding ratios, calculated by dividing the single acuity by the linear acuity, were measured binocularly with the C-test and the LH line chart. Ratios >1.00 indicate crowding. The charts with fixed spacing revealed significantly higher crowding ratios for visually impaired children than normally sighted children (both for measurements at 40 cm and 5 m). The age-related reduction of the crowding ratios seen in normally sighted children when tested with near-vision charts with fixed spacing was not present in the visually impaired group. Visually impaired children with nystagmus showed higher crowding ratios than visually impaired children without nystagmus. The chart with proportional intersymbol spacing (ISS) did not reveal differences between the normally sighted and visually impaired children; nor did it show group, age, or nystagmus effects. Visually impaired children showed higher crowding ratios than normally sighted children when measured with charts with fixed ISS. This study illustrates that test design and target/flanker interference as a manifestation of crowding are critical issues to bear in mind when assessing crowding ratios in children.

Technical Note: A treatment plan comparison between dynamic collimation and a fixed aperture during spot scanning proton therapy for brain treatment

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

Smith, Blake, E-mail: bsmith34@wisc.edu; Gelover,

Purpose: To quantitatively assess the advantages of energy-layer specific dynamic collimation system (DCS) versus a per-field fixed aperture for spot scanning proton therapy (SSPT). Methods: Five brain cancer patients previously planned and treated with SSPT were replanned using an in-house treatment planning system capable of modeling collimated and uncollimated proton beamlets. The uncollimated plans, which served as a baseline for comparison, reproduced the target coverage and organ-at-risk sparing of the clinically delivered plans. The collimator opening for the fixed aperture-based plans was determined from the combined cross sections of the target in the beam’s eye view over all energy layersmore » which included an additional margin equivalent to the maximum beamlet displacement for the respective energy of that energy layer. The DCS-based plans were created by selecting appropriate collimator positions for each row of beam spots during a Raster-style scanning pattern which were optimized to maximize the dose contributions to the target and limited the dose delivered to adjacent normal tissue. Results: The reduction of mean dose to normal tissue adjacent to the target, as defined by a 10 mm ring surrounding the target, averaged 13.65% (range: 11.8%–16.9%) and 5.18% (2.9%–7.1%) for the DCS and fixed aperture plans, respectively. The conformity index, as defined by the ratio of the volume of the 50% isodose line to the target volume, yielded an average improvement of 21.35% (19.4%–22.6%) and 8.38% (4.7%–12.0%) for the DCS and fixed aperture plans, respectively. Conclusions: The ability of the DCS to provide collimation to each energy layer yielded better conformity in comparison to fixed aperture plans.« less

47 CFR 25.277 - Temporary fixed earth station operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Temporary fixed earth station operations. 25... SERVICES SATELLITE COMMUNICATIONS Technical Operations § 25.277 Temporary fixed earth station operations. (a) When an earth station in the Fixed-Satellite Service is to remain at a single location for fewer...

47 CFR 25.277 - Temporary fixed earth station operations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Temporary fixed earth station operations. 25... SERVICES SATELLITE COMMUNICATIONS Technical Operations § 25.277 Temporary fixed earth station operations. (a) When an earth station in the Fixed-Satellite Service is to remain at a single location for fewer...

47 CFR 25.277 - Temporary fixed earth station operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Temporary fixed earth station operations. 25... SERVICES SATELLITE COMMUNICATIONS Technical Operations § 25.277 Temporary fixed earth station operations. (a) When an earth station in the Fixed-Satellite Service is to remain at a single location for fewer...

47 CFR 25.277 - Temporary fixed earth station operations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Temporary fixed earth station operations. 25... SERVICES SATELLITE COMMUNICATIONS Technical Operations § 25.277 Temporary fixed earth station operations. (a) When an earth station in the Fixed-Satellite Service is to remain at a single location for fewer...

47 CFR 25.277 - Temporary fixed earth station operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Temporary fixed earth station operations. 25... SERVICES SATELLITE COMMUNICATIONS Technical Operations § 25.277 Temporary fixed earth station operations. (a) When an earth station in the Fixed-Satellite Service is to remain at a single location for fewer...

Ultrasensitive electrochemical detection of avian influenza A (H7N9) virus DNA based on isothermal exponential amplification coupled with hybridization chain reaction of DNAzyme nanowires.

PubMed

Yu, Yanyan; Chen, Zuanguang; Jian, Wensi; Sun, Duanping; Zhang, Beibei; Li, Xinchun; Yao, Meicun

2015-02-15

In this work, a simple and label-free electrochemical biosensor with duel amplification strategy was developed for DNA detection based on isothermal exponential amplification (EXPAR) coupled with hybridization chain reaction (HCR) of DNAzymes nanowires. Through rational design, neither the primer nor the DNAzymes containing molecular beacons (MBs) could react with the duplex probe which were fixed on the electrode surface. Once challenged with target, the duplex probe cleaved and triggered the EXPAR mediated target recycle and regeneration circles as well as the HCR process. As a result, a greater amount of targets were generated to cleave the duplex probes. Subsequently, the nanowires consisting of the G-quadruplex units were self-assembled through hybridization with the strand fixed on the electrode surface. In the presence of hemin, the resulting catalytic G-quadruplex-hemin HRP-mimicking DNAzymes were formed. Electrochemical signals can be obtained by measuring the increase in reduction current of oxidized 3.3',5.5'-tetramethylbenzidine sulfate (TMB), which was generated by DNAzyme in the presence of H2O2. This method exhibited ultrahigh sensitivity towards avian influenza A (H7N9) virus DNA sequence with detection limits of 9.4 fM and a detection range of 4 orders of magnitude. The biosensor was also capable of discriminating single-nucleotide difference among concomitant DNA sequences and performed well in spiked cell lysates. Copyright © 2014 Elsevier B.V. All rights reserved.

[Antihypertensive Efficacy of Fixed Combination Azilsartan Medoxomil / Chlorthalidone in Patients With Uncontrolled Arterial Hypertension].

PubMed

Kobalava, Z D; Villevalde, S V; Kulakov, V V

2017-11-01

To study effects of a fixed azilsartan medoxomil/chlorthalidone combination (Edarbi Clo) on clinical, ambulatory and central blood pressure (BP) in patients with uncontrolled arterial hypertension (AH)). Patients (n=25) with uncontrolled AH were given fixed azilsartan medoxomil/chlorthalidone combination (40 / 12.5 mg / day) for 4 weeks. After 4 weeks, in patients who did not achieve target BP levels the dose was increased up to 40 / 25 mg / day. Duration of the study was 12 weeks. After 12 weeks of treatment 88 % of patients achieved target clinical BP (.

Visual–Motor Transformations Within Frontal Eye Fields During Head-Unrestrained Gaze Shifts in the Monkey

PubMed Central

Sajad, Amirsaman; Sadeh, Morteza; Keith, Gerald P.; Yan, Xiaogang; Wang, Hongying; Crawford, John Douglas

2015-01-01

A fundamental question in sensorimotor control concerns the transformation of spatial signals from the retina into eye and head motor commands required for accurate gaze shifts. Here, we investigated these transformations by identifying the spatial codes embedded in visually evoked and movement-related responses in the frontal eye fields (FEFs) during head-unrestrained gaze shifts. Monkeys made delayed gaze shifts to the remembered location of briefly presented visual stimuli, with delay serving to dissociate visual and movement responses. A statistical analysis of nonparametric model fits to response field data from 57 neurons (38 with visual and 49 with movement activities) eliminated most effector-specific, head-fixed, and space-fixed models, but confirmed the dominance of eye-centered codes observed in head-restrained studies. More importantly, the visual response encoded target location, whereas the movement response mainly encoded the final position of the imminent gaze shift (including gaze errors). This spatiotemporal distinction between target and gaze coding was present not only at the population level, but even at the single-cell level. We propose that an imperfect visual–motor transformation occurs during the brief memory interval between perception and action, and further transformations from the FEF's eye-centered gaze motor code to effector-specific codes in motor frames occur downstream in the subcortical areas. PMID:25491118

A four-dimensional virtual hand brain-machine interface using active dimension selection

NASA Astrophysics Data System (ADS)

Rouse, Adam G.

2016-06-01

Objective. Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. Approach. ADS utilizes a two stage decoder by using neural signals to both (i) select an active dimension being controlled and (ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Main results. Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits s-1 for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. Significance. ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand.

A four-dimensional virtual hand brain-machine interface using active dimension selection

PubMed Central

Rouse, Adam G.

2018-01-01

Objective Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. Approach ADS utilizes a two stage decoder by using neural signals to both i) select an active dimension being controlled and ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Main Results Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits/s for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. Significance ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand. PMID:27171896

Genome-Wide Association Studies with a Genomic Relationship Matrix: A Case Study with Wheat and Arabidopsis

PubMed Central

Gianola, Daniel; Fariello, Maria I.; Naya, Hugo; Schön, Chris-Carolin

2016-01-01

Standard genome-wide association studies (GWAS) scan for relationships between each of p molecular markers and a continuously distributed target trait. Typically, a marker-based matrix of genomic similarities among individuals (G) is constructed, to account more properly for the covariance structure in the linear regression model used. We show that the generalized least-squares estimator of the regression of phenotype on one or on m markers is invariant with respect to whether or not the marker(s) tested is(are) used for building G, provided variance components are unaffected by exclusion of such marker(s) from G. The result is arrived at by using a matrix expression such that one can find many inverses of genomic relationship, or of phenotypic covariance matrices, stemming from removing markers tested as fixed, but carrying out a single inversion. When eigenvectors of the genomic relationship matrix are used as regressors with fixed regression coefficients, e.g., to account for population stratification, their removal from G does matter. Removal of eigenvectors from G can have a noticeable effect on estimates of genomic and residual variances, so caution is needed. Concepts were illustrated using genomic data on 599 wheat inbred lines, with grain yield as target trait, and on close to 200 Arabidopsis thaliana accessions. PMID:27520956

Accuracy of six elastic impression materials used for complete-arch fixed partial dentures.

PubMed

Stauffer, J P; Meyer, J M; Nally, J N

1976-04-01

1. The accuracy of four types of impression materials used to make a complete-arch fixed partial denture was evaluated by visual comparison and indirect measurement methods. 2. None of the tested materials allows safe finishing of a complete-arch fixed partial denture on a cast poured from one single master impression. 3. All of the tested materials can be used for impressions for a complete-arch fixed partial denture provided it is not finished on one single cast. Errors can be avoided by making a new impression with the fitted castings in place. Assembly and soldering should be done on the second cast. 4. In making the master fixed partial denture for this study, inaccurate soldering was a problem that was overcome with the use of epoxy glue. Hence, soldering seems to be a major source of inaccuracy for every fixed partial denture.

TumorNext: A comprehensive tumor profiling assay that incorporates high resolution copy number analysis and germline status to improve testing accuracy

PubMed Central

Gray, Phillip N.; Vuong, Huy; Tsai, Pei; Lu, Hsaio-Mei; Mu, Wenbo; Hsuan, Vickie; Hoo, Jayne; Shah, Swati; Uyeda, Lisa; Fox, Susanne; Patel, Harshil; Janicek, Mike; Brown, Sandra; Dobrea, Lavinia; Wagman, Lawrence; Plimack, Elizabeth; Mehra, Ranee; Golemis, Erica A.; Bilusic, Marijo; Zibelman, Matthew; Elliott, Aaron

2016-01-01

The development of targeted therapies for both germline and somatic DNA mutations has increased the need for molecular profiling assays to determine the mutational status of specific genes. Moreover, the potential of off-label prescription of targeted therapies favors classifying tumors based on DNA alterations rather than traditional tissue pathology. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext, which can detect single nucleotide variants, small insertions and deletions in 142 genes that are frequently mutated in somatic and/or germline cancers. TumorNext also detects gene fusions and structural variants, such as tandem duplications and inversions, in 15 frequently disrupted oncogenes and tumor suppressors. The assay uses a matched control and custom bioinformatics pipeline to differentiate between somatic and germline mutations, allowing precise variant classification. We tested 170 previously characterized samples, of which > 95% were formalin-fixed paraffin embedded tissue from 8 different cancer types, and highlight examples where lack of germline status may have led to the inappropriate prescription of therapy. We also describe the validation of the Affymetrix OncoScan platform, an array technology for high resolution copy number variant detection for use in parallel with the NGS panel that can detect single copy amplifications and hemizygous deletions. We analyzed 80 previously characterized formalin-fixed paraffin-embedded specimens and provide examples of hemizygous deletion detection in samples with known pathogenic germline mutations. Thus, the TumorNext combined approach of NGS and OncoScan potentially allows for the identification of the “second hit” in hereditary cancer patients. PMID:27626691

Dosimetric comparison between cone/Iris-based and InCise MLC-based CyberKnife plans for single and multiple brain metastases.

PubMed

Jang, Si Young; Lalonde, Ron; Ozhasoglu, Cihat; Burton, Steven; Heron, Dwight; Huq, M Saiful

2016-09-08

We performed an evaluation of the CyberKnife InCise MLC by comparing plan qualities for single and multiple brain lesions generated using the first version of InCise MLC, fixed cone, and Iris collimators. We also investigated differences in delivery efficiency among the three collimators. Twenty-four patients with single or multiple brain mets treated previously in our clinic on a CyberKnife M6 using cone/Iris collimators were selected for this study. Treatment plans were generated for all lesions using the InCise MLC. Number of monitor units, delivery time, target coverage, conformity index, and dose falloff were compared between MLC- and clinical cone/Iris-based plans. Statistical analysis was performed using the non-parametric Wilcoxon-Mann-Whitney signed-rank test. The planning accuracy of the MLC-based plans was validated using chamber and film measurements. The InCise MLC-based plans achieved mean dose and target coverage comparable to the cone/Iris-based plans. Although the conformity indices of the MLC-based plans were slightly higher than those of the cone/Iris-based plans, beam delivery time for the MLC-based plans was shorter by 30% ~ 40%. For smaller targets or cases with OARs located close to or abutting target volumes, MLC-based plans provided inferior dose conformity compared to cone/Iris-based plans. The QA results of MLC-based plans were within 5% absolute dose difference with over 90% gamma passing rate using 2%/2 mm gamma criteria. The first version of InCise MLC could be a useful delivery modality, especially for clinical situations for which delivery time is a limiting factor or for multitarget cases. © 2016 The Authors.

Finite-horizon differential games for missile-target interception system using adaptive dynamic programming with input constraints

NASA Astrophysics Data System (ADS)

Sun, Jingliang; Liu, Chunsheng

2018-01-01

In this paper, the problem of intercepting a manoeuvring target within a fixed final time is posed in a non-linear constrained zero-sum differential game framework. The Nash equilibrium solution is found by solving the finite-horizon constrained differential game problem via adaptive dynamic programming technique. Besides, a suitable non-quadratic functional is utilised to encode the control constraints into a differential game problem. The single critic network with constant weights and time-varying activation functions is constructed to approximate the solution of associated time-varying Hamilton-Jacobi-Isaacs equation online. To properly satisfy the terminal constraint, an additional error term is incorporated in a novel weight-updating law such that the terminal constraint error is also minimised over time. By utilising Lyapunov's direct method, the closed-loop differential game system and the estimation weight error of the critic network are proved to be uniformly ultimately bounded. Finally, the effectiveness of the proposed method is demonstrated by using a simple non-linear system and a non-linear missile-target interception system, assuming first-order dynamics for the interceptor and target.

A Bayesian predictive two-stage design for phase II clinical trials.

PubMed

Sambucini, Valeria

2008-04-15

In this paper, we propose a Bayesian two-stage design for phase II clinical trials, which represents a predictive version of the single threshold design (STD) recently introduced by Tan and Machin. The STD two-stage sample sizes are determined specifying a minimum threshold for the posterior probability that the true response rate exceeds a pre-specified target value and assuming that the observed response rate is slightly higher than the target. Unlike the STD, we do not refer to a fixed experimental outcome, but take into account the uncertainty about future data. In both stages, the design aims to control the probability of getting a large posterior probability that the true response rate exceeds the target value. Such a probability is expressed in terms of prior predictive distributions of the data. The performance of the design is based on the distinction between analysis and design priors, recently introduced in the literature. The properties of the method are studied when all the design parameters vary.

The four fixed points of scale invariant single field cosmological models

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

Xue, BingKan, E-mail: bxue@princeton.edu

2012-10-01

We introduce a new set of flow parameters to describe the time dependence of the equation of state and the speed of sound in single field cosmological models. A scale invariant power spectrum is produced if these flow parameters satisfy specific dynamical equations. We analyze the flow of these parameters and find four types of fixed points that encompass all known single field models. Moreover, near each fixed point we uncover new models where the scale invariance of the power spectrum relies on having simultaneously time varying speed of sound and equation of state. We describe several distinctive new modelsmore » and discuss constraints from strong coupling and superluminality.« less

[Considerations about the efficiency of treatment regimens with fixed Rifampicin-Isoniazid combinations in pulmonary tuberculosis].

PubMed

Munteanu, Ioana; Husar, Iulia; Didilescu, C; Stoicescu, I P

2004-01-01

Here are presented the results of a prospective, randomized study regarding the efficiency of regimens with fixed drug combination Rifampicin-Isoniazide manufactured by Antibiotics S.A. of Iasi in comparison with single drugs routinely used in treatment of patients with pulmonary tuberculosis. Newly diagnosed (confirmed by smear and culture) pulmonary tuberculosis patients were selected, and those who accepted to be included in the study, were admitted to the National Institute of Pneumology "Marius Nasta" between August 2001 and September 2002. At the time of admission, they were randomized into two groups: 20 patients received fixed drug combination RMP300 HIN150, and 18 patients received RMP and HIN in single drug tablets (2 patients were excluded). The follow-up of the patients was for one year from the date of enclosure. The smear conversion rate was 83,3% for the patients using single drug tablets, and 70% for those using fixed drug combination, motivated with some more severe TB patterns. The success rate was 100% for all TB patients. Although the present study was done for few patients, we can say that it demonstrated the same efficiency of fixed drug combination produced in Romania, with the single drug tablets, and it suggests a better compliance to treatment with a lower price.

Nanomedicine: nanoparticles, molecular biosensors, and targeted gene/drug delivery for combined single-cell diagnostics and therapeutics

NASA Astrophysics Data System (ADS)

Prow, Tarl W.; Salazar, Jose H.; Rose, William A.; Smith, Jacob N.; Reece, Lisa; Fontenot, Andrea A.; Wang, Nan A.; Lloyd, R. Stephen; Leary, James F.

2004-07-01

Next generation nanomedicine technologies are being developed to provide for continuous and linked molecular diagnostics and therapeutics. Research is being performed to develop "sentinel nanoparticles" which will seek out diseased (e.g. cancerous) cells, enter those living cells, and either perform repairs or induce those cells to die through apoptosis. These nanoparticles are envisioned as multifunctional "smart drug delivery systems". The nanosystems are being developed as multilayered nanoparticles (nanocrystals, nanocapsules) containing cell targeting molecules, intracellular re-targeting molecules, molecular biosensor molecules, and drugs/enzymes/gene therapy. These "nanomedicine systems" are being constructed to be autonomous, much like present-day vaccines, but will have sophisticated targeting, sensing, and feedback control systems-much more sophisticated than conventional antibody-based therapies. The fundamental concept of nanomedicine is to not to just kill all aberrant cells by surgery, radiation therapy, or chemotherapy. Rather it is to fix cells, when appropriate, one cell-at-a-time, to preserve and re-build organ systems. When cells should not be fixed, such as in cases where an improperly repaired cell might give rise to cancer cells, the nanomedical therapy would be to induce apoptosis in those cells to eliminate them without the damagin bystander effects of the inflammatory immune response system reacting to necrotic cells or those which have died from trauma or injury. The ultimate aim of nanomedicine is to combine diagnostics and therapeutics into "real-time medicine", using where possible in-vivo cytometry techniques for diagnostics and therapeutics. A number of individual components of these multi-component nanoparticles are already working in in-vitro and ex-vivo cell and tissue systems. Work has begun on construction of integrated nanomedical systems.

Exact Green's functions for a Brownian particle reversibly binding to a fixed target in a finite, two-dimensional, circular domain

NASA Astrophysics Data System (ADS)

Kalay, Ziya

2012-06-01

Despite the apparent need to study reversible reactions between molecules confined to a two-dimensional space such as the cell membrane, exact Green’s functions for this case have not been reported. Here we present exact analytical Green’s functions for a Brownian particle reversibly reacting with a fixed reaction center in a finite two-dimensional circular region with reflecting or absorbing boundaries, considering either a spherically symmetric initial distribution or a particle that is initially bound. We show that Green’s function can be used to predict the effect of measurement uncertainties on the outcome of single-particle/molecule-tracking experiments in which molecular interactions are investigated. Hence, we bridge the gap between previously known solutions in one dimension (Agmon 1984 J. Chem. Phys. 81 2811) and three dimensions (Kim and Shin 1999 Phys. Rev. Lett. 82 1578), and provide an example of how the knowledge of Green’s function can be used to predict experimentally accessible quantities.

The Fixed Target Experiment for Studies of Baryonic Matter at the Nuclotron (BM@N)

NASA Astrophysics Data System (ADS)

Kapishin, M. N.

2017-12-01

BM@N (Baryonic Matter at Nuclotron) is the first experiment to be realized at the NICA-Nuclotron accelerator complex. The aim of the BM@N experiment is to study relativistic heavy ion beam interactions with fixed targets. The BM@N setup, results of Monte Carlo simulations, and the BM@N experimental program are presented.

Choice between Single and Multiple Reinforcers in Concurrent-Chains Schedules

ERIC Educational Resources Information Center

Mazur, James E.

2006-01-01

Pigeons responded on concurrent-chains schedules with equal variable-interval schedules as initial links. One terminal link delivered a single reinforcer after a fixed delay, and the other terminal link delivered either three or five reinforcers, each preceded by a fixed delay. Some conditions included a postreinforcer delay after the single…

The effects of context and musical training on auditory temporal-interval discrimination.

PubMed

Banai, Karen; Fisher, Shirley; Ganot, Ron

2012-02-01

Non sensory factors such as stimulus context and musical experience are known to influence auditory frequency discrimination, but whether the context effect extends to auditory temporal processing remains unknown. Whether individual experiences such as musical training alter the context effect is also unknown. The goal of the present study was therefore to investigate the effects of stimulus context and musical experience on auditory temporal-interval discrimination. In experiment 1, temporal-interval discrimination was compared between fixed context conditions in which a single base temporal interval was presented repeatedly across all trials and variable context conditions in which one of two base intervals was randomly presented on each trial. Discrimination was significantly better in the fixed than in the variable context conditions. In experiment 2 temporal discrimination thresholds of musicians and non-musicians were compared across 3 conditions: a fixed context condition in which the target interval was presented repeatedly across trials, and two variable context conditions differing in the frequencies used for the tones marking the temporal intervals. Musicians outperformed non-musicians on all 3 conditions, but the effects of context were similar for the two groups. Overall, it appears that, like frequency discrimination, temporal-interval discrimination benefits from having a fixed reference. Musical experience, while improving performance, did not alter the context effect, suggesting that improved discrimination skills among musicians are probably not an outcome of more sensitive contextual facilitation or predictive coding mechanisms. Copyright © 2011 Elsevier B.V. All rights reserved.

General Quantum Meet-in-the-Middle Search Algorithm Based on Target Solution of Fixed Weight

NASA Astrophysics Data System (ADS)

Fu, Xiang-Qun; Bao, Wan-Su; Wang, Xiang; Shi, Jian-Hong

2016-10-01

Similar to the classical meet-in-the-middle algorithm, the storage and computation complexity are the key factors that decide the efficiency of the quantum meet-in-the-middle algorithm. Aiming at the target vector of fixed weight, based on the quantum meet-in-the-middle algorithm, the algorithm for searching all n-product vectors with the same weight is presented, whose complexity is better than the exhaustive search algorithm. And the algorithm can reduce the storage complexity of the quantum meet-in-the-middle search algorithm. Then based on the algorithm and the knapsack vector of the Chor-Rivest public-key crypto of fixed weight d, we present a general quantum meet-in-the-middle search algorithm based on the target solution of fixed weight, whose computational complexity is \\sumj = 0d {(O(\\sqrt {Cn - k + 1d - j }) + O(C_kj log C_k^j))} with Σd i =0 Ck i memory cost. And the optimal value of k is given. Compared to the quantum meet-in-the-middle search algorithm for knapsack problem and the quantum algorithm for searching a target solution of fixed weight, the computational complexity of the algorithm is lower. And its storage complexity is smaller than the quantum meet-in-the-middle-algorithm. Supported by the National Basic Research Program of China under Grant No. 2013CB338002 and the National Natural Science Foundation of China under Grant No. 61502526

PEST reduces bias in forced choice psychophysics.

PubMed

Taylor, M M; Forbes, S M; Creelman, C D

1983-11-01

Observers performed several different detection tasks using both the PEST adaptive psychophysical procedure and a fixed-level (method of constant stimuli) psychophysical procedure. In two experiments, PEST runs targeted at P (C) = 0.80 were immediately followed by fixed-level detection runs presented at the difficulty level resulting from the PEST run. The fixed-level runs yielded P (C) about 0.75. During the fixed-level runs, the probability of a correct response was greater when the preceding response was correct than when it was wrong. Observers, even highly trained ones, perform in a nonstationary manner. The sequential dependency data can be used to determine a lower bound for the observer's "true" capability when performing optimally; this lower bound is close to the PEST target, and well above the forced choice P (C). The observer's "true" capability is the measure used by most theories of detection performance. A further experiment compared psychometric functions obtained from a set of PEST runs using different targets with those obtained from blocks of fixed-level trials at different levels. PEST results were more stable across observers, performance at all but the highest signal levels was better with PEST, and the PEST psychometric functions had shallower slopes. We hypothesize that PEST permits the observer to keep track of what he is trying to detect, whereas in the fixed-level method performance is disrupted by memory failure. Some recently suggested "more virulent" versions of PEST may be subject to biases similar to those of the fixed-level procedures.(ABSTRACT TRUNCATED AT 250 WORDS)

Migration and clinical outcome of mobile-bearing versus fixed-bearing single-radius total knee arthroplasty.

PubMed

Van Hamersveld, Koen T; Marang-Van De Mheen, Perla J; Van Der Heide, Huub J L; Van Der Linden-Van Der Zwaag, Henrica M J; Valstar, Edward R; Nelissen, Rob G H H

2018-04-01

Background and purpose - Mobile-bearing total knee prostheses (TKPs) were developed in the 1970s in an attempt to increase function and improve implant longevity. However, modern fixed-bearing designs like the single-radius TKP may provide similar advantages. We compared tibial component migration measured with radiostereometric analysis (RSA) and clinical outcome of otherwise similarly designed cemented fixed-bearing and mobile-bearing single-radius TKPs. Patients and methods - RSA measurements and clinical scores were assessed in 46 randomized patients at baseline, 6 months, 1 year, and annually thereafter up to 6 years postoperatively. A linear mixed-effects model was used to analyze the repeated measurements. Results - Both groups showed comparable migration (p = 0.3), with a mean migration at 6-year follow-up of 0.90 mm (95% CI 0.49-1.41) for the fixed-bearing group compared with 1.22 mm (95% CI 0.75-1.80) for the mobile-bearing group. Clinical outcomes were similar between groups. 1 fixed-bearing knee was revised for aseptic loosening after 6 years and 2 knees (1 in each group) were revised for late infection. 2 knees (1 in each group) were suspected for loosening due to excessive migration. Another mobile-bearing knee was revised after an insert dislocation due to failure of the locking mechanism 6 weeks postoperatively, after which study inclusion was preliminary terminated. Interpretation - Fixed-bearing and mobile-bearing single-radius TKPs showed similar migration. The latter may, however, expose patients to more complex surgical techniques and risks such as insert dislocations inherent to this rotating-platform design.

Candidate adaptive genes associated with lineage divergence: identifying SNPs via next-generation targeted resequencing in mule deer (Odocoileus hemionus).

PubMed

Powell, John H; Amish, Stephen J; Haynes, Gwilym D; Luikart, Gordon; Latch, Emily K

2016-09-01

Mule deer (Odocoileus hemionus) are an excellent nonmodel species for empirically testing hypotheses in landscape and population genomics due to their large population sizes (low genetic drift), relatively continuous distribution, diversity of occupied habitats and phenotypic variation. Because few genomic resources are currently available for this species, we used exon data from a cattle (Bos taurus) reference genome to direct targeted resequencing of 5935 genes in mule deer. We sequenced approximately 3.75 Mbp at minimum 20X coverage in each of the seven mule deer, identifying 23 204 single nucleotide polymorphisms (SNPs) within, or adjacent to, 6886 exons in 3559 genes. We found 91 SNP loci (from 69 genes) with putatively fixed allele frequency differences between the two major lineages of mule deer (mule deer and black-tailed deer), and our estimate of mean genetic divergence (genome-wide FST  = 0.123) between these lineages was consistent with previous findings using microsatellite loci. We detected an over-representation of gamete generation and amino acid transport genes among the genes with SNPs exhibiting potentially fixed allele frequency differences between lineages. This targeted resequencing approach using exon capture techniques has identified a suite of loci that can be used in future research to investigate the genomic basis of adaptation and differentiation between black-tailed deer and mule deer. This study also highlights techniques (and an exon capture array) that will facilitate population genomic research in other cervids and nonmodel organisms. © 2016 John Wiley & Sons Ltd.

Fixed-dose combination therapy of nebivolol and valsartan for the treatment of hypertension.

PubMed

Sander, Gary E; Fernandez, Camilo; Giles, Thomas D

2016-01-01

Recent large clinical trials have refuted earlier suggestions from the Joint National Committee 8 committee that less aggressive targets for blood pressure control were all that could be justified in most hypertensive patients. It now does appear that in fact "lower is better," with blood pressure targets < 120/80 mm Hg appropriate for many hypertensive patients. Two drug combinations are often indicated as initial therapy if a 20/10 mm Hg or greater blood pressure reduction is necessary to reach target. Combinations consisting of β-blockers and renin-angiotensin-aldosterone system inhibitors have previously been deemed "less effective," based on partially overlapping mechanisms of action and limited clinical trial evidence. Nebivolol is a vasodilating β1-selective blocker and β3- adrenoceptor agonist; β3-adrenoceptor activation increases nitric oxide concentrations and thus explains the vasodilatory effect. A recent 8-week randomized trial (N=4,161) in individuals with stage 1-2 hypertension demonstrated that single-pill fixed dose combinations (FDC) of nebivolol and valsartan, an angiotensin II subtype 1 receptor blocker, were more effective in reducing blood pressure than the corresponding monotherapies, with comparable tolerability. In addition, an ABPM-biomarkers substudy from that trial (n=805) demonstrated that the FDC prevented a valsartan-induced increase in plasma renin activity, and that the nebivolol/valsartan 20/320 mg/day dose reduced plasma aldosterone concentration significantly more than valsartan 320 mg/day. This article will describe the properties of nebivolol that make it unique and separate it from other β-blockers, and will further support the pharmacological advantages of this particular combination.

Functional Single-Cell Approach to Probing Nitrogen-Fixing Bacteria in Soil Communities by Resonance Raman Spectroscopy with 15N2 Labeling.

PubMed

Cui, Li; Yang, Kai; Li, Hong-Zhe; Zhang, Han; Su, Jian-Qiang; Paraskevaidi, Maria; Martin, Francis L; Ren, Bin; Zhu, Yong-Guan

2018-04-17

Nitrogen (N) fixation is the conversion of inert nitrogen gas (N 2 ) to bioavailable N essential for all forms of life. N 2 -fixing microorganisms (diazotrophs), which play a key role in global N cycling, remain largely obscure because a large majority are uncultured. Direct probing of active diazotrophs in the environment is still a major challenge. Herein, a novel culture-independent single-cell approach combining resonance Raman (RR) spectroscopy with 15 N 2 stable isotope probing (SIP) was developed to discern N 2 -fixing bacteria in a complex soil community. Strong RR signals of cytochrome c (Cyt c, frequently present in diverse N 2 -fixing bacteria), along with a marked 15 N 2 -induced Cyt c band shift, generated a highly distinguishable biomarker for N 2 fixation. 15 N 2 -induced shift was consistent well with 15 N abundance in cell determined by isotope ratio mass spectroscopy. By applying this biomarker and Raman imaging, N 2 -fixing bacteria in both artificial and complex soil communities were discerned and imaged at the single-cell level. The linear band shift of Cyt c versus 15 N 2 percentage allowed quantification of N 2 fixation extent of diverse soil bacteria. This single-cell approach will advance the exploration of hitherto uncultured diazotrophs in diverse ecosystems.

48 CFR 1852.216-83 - Fixed price incentive.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Price Incentive (OCT 1996) The target cost of this contract is $___. The Target profit of this contract is $___. The target price (target cost plus target profit) of this contract is $___. [The ceiling price is $___.] The cost sharing for target cost underruns is: Government ___percent; Contractor...

48 CFR 1852.216-83 - Fixed price incentive.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Price Incentive (OCT 1996) The target cost of this contract is $___. The Target profit of this contract is $___. The target price (target cost plus target profit) of this contract is $___. [The ceiling price is $___.] The cost sharing for target cost underruns is: Government ___percent; Contractor...

Mean first passage time of active Brownian particle in one dimension

NASA Astrophysics Data System (ADS)

Scacchi, A.; Sharma, A.

2018-02-01

We investigate the mean first passage time of an active Brownian particle in one dimension using numerical simulations. The activity in one dimension is modelled as a two state model; the particle moves with a constant propulsion strength but its orientation switches from one state to other as in a random telegraphic process. We study the influence of a finite resetting rate r on the mean first passage time to a fixed target of a single free active Brownian particle and map this result using an effective diffusion process. As in the case of a passive Brownian particle, we can find an optimal resetting rate r* for an active Brownian particle for which the target is found with the minimum average time. In the case of the presence of an external potential, we find good agreement between the theory and numerical simulations using an effective potential approach.

Strength of fixation constructs for basilar osteotomies of the first metatarsal.

PubMed

Lian, G J; Markolf, K; Cracchiolo, A

1992-01-01

Twenty-four pairs of fresh-frozen human feet had a proximal osteotomy of the first metatarsal that was fixed using either screws, staples, or K wires. Each metatarsal was excised and the specimen was loaded to failure in a cantilever beam configuration by applying a superiorly directed force to the metatarsal head using an MTS servohydraulic test machine. Specimens with a crescentic osteotomy that were fixed using a single screw demonstrated higher mean failure moments than pairs that were fixed with four staples or two K wires; staples were the weakest construct. All specimens fixed with staples failed by bending of the staples without bony fracture; all K wire constructs but one failed by wire bending. Chevron and crescentic osteotomies fixed with a single screw demonstrated equal bending strengths; the bending strength of an oblique osteotomy fixed with two screws was 82% greater than for a crescentic osteotomy fixed with a single screw. Basilar osteotomies of the first metatarsal are useful in correcting metatarsus primus varus often associated with hallux valgus pathology. Fixation strength is an important consideration since weightbearing forces on the head of the first metatarsal acting at a distance from the osteotomy site subject the construct to a dorsiflexion bending moment, as simulated in our tests. Our results show that screw fixation is the strongest method for stabilizing a basilar osteotomy. Based upon the relatively low bending strengths of the staple and K wire constructs, we would not recommend these forms of fixation.(ABSTRACT TRUNCATED AT 250 WORDS)

Global calibration of multi-cameras with non-overlapping fields of view based on photogrammetry and reconfigurable target

NASA Astrophysics Data System (ADS)

Xia, Renbo; Hu, Maobang; Zhao, Jibin; Chen, Songlin; Chen, Yueling

2018-06-01

Multi-camera vision systems are often needed to achieve large-scale and high-precision measurement because these systems have larger fields of view (FOV) than a single camera. Multiple cameras may have no or narrow overlapping FOVs in many applications, which pose a huge challenge to global calibration. This paper presents a global calibration method for multi-cameras without overlapping FOVs based on photogrammetry technology and a reconfigurable target. Firstly, two planar targets are fixed together and made into a long target according to the distance between the two cameras to be calibrated. The relative positions of the two planar targets can be obtained by photogrammetric methods and used as invariant constraints in global calibration. Then, the reprojection errors of target feature points in the two cameras’ coordinate systems are calculated at the same time and optimized by the Levenberg–Marquardt algorithm to find the optimal solution of the transformation matrix between the two cameras. Finally, all the camera coordinate systems are converted to the reference coordinate system in order to achieve global calibration. Experiments show that the proposed method has the advantages of high accuracy (the RMS error is 0.04 mm) and low cost and is especially suitable for on-site calibration.

A new pulsed laser deposition technique: scanning multi-component pulsed laser deposition method.

PubMed

Fischer, D; de la Fuente, G F; Jansen, M

2012-04-01

The scanning multi-component pulsed laser deposition (PLD) method realizes uniform depositions of desired coatings by a modified pulsed laser deposition process, preferably with a femto-second laser-system. Multi-component coatings (single or multilayered) are thus deposited onto substrates via laser induced ablation of segmented targets. This is achieved via horizontal line-scanning of a focused laser beam over a uniformly moving target's surface. This process allows to deposit the desired composition of the coating simultaneously, starting from the different segments of the target and adjusting the scan line as a function of target geometry. The sequence and thickness of multilayers can easily be adjusted by target architecture and motion, enabling inter/intra layer concentration gradients and thus functional gradient coatings. This new, simple PLD method enables the achievement of uniform, large-area coatings. Case studies were performed with segmented targets containing aluminum, titanium, and niobium. Under the laser irradiation conditions applied, all three metals were uniformly ablated. The elemental composition within the rough coatings obtained was fixed by the scanned area to Ti-Al-Nb = 1:1:1. Crystalline aluminum, titanium, and niobium were found to coexist side by side at room temperature within the substrate, without alloy formation up to 600 °C. © 2012 American Institute of Physics

Application of real-time single camera SLAM technology for image-guided targeting in neurosurgery

NASA Astrophysics Data System (ADS)

Chang, Yau-Zen; Hou, Jung-Fu; Tsao, Yi Hsiang; Lee, Shih-Tseng

2012-10-01

In this paper, we propose an application of augmented reality technology for targeting tumors or anatomical structures inside the skull. The application is a combination of the technologies of MonoSLAM (Single Camera Simultaneous Localization and Mapping) and computer graphics. A stereo vision system is developed to construct geometric data of human face for registration with CT images. Reliability and accuracy of the application is enhanced by the use of fiduciary markers fixed to the skull. The MonoSLAM keeps track of the current location of the camera with respect to an augmented reality (AR) marker using the extended Kalman filter. The fiduciary markers provide reference when the AR marker is invisible to the camera. Relationship between the markers on the face and the augmented reality marker is obtained by a registration procedure by the stereo vision system and is updated on-line. A commercially available Android based tablet PC equipped with a 320×240 front-facing camera was used for implementation. The system is able to provide a live view of the patient overlaid by the solid models of tumors or anatomical structures, as well as the missing part of the tool inside the skull.

A Novel Fixed-Target Task to Determine Articulatory Speed Constraints in Persons with Amyotrophic Lateral Sclerosis

ERIC Educational Resources Information Center

Mefferd, Antje S.; Green, Jordan R.; Pattee, Gary

2012-01-01

Purpose: The goal of this study was to determine if talkers with ALS are limited in their ability to increase lower lip and jaw speed at an early stage of the disease when their speaking rate and intelligibility are only minimally or not affected. Method: A novel metronome paced fixed-target task was used to assess movement speed capacities during…

Studies of the vestibulo-ocular reflex on STS 4, 5 and 6

NASA Technical Reports Server (NTRS)

Thornton, William E.; Pool, Sam L.; Moore, Thomas P.; Uri, John J.

1988-01-01

The vestibulo-ocular reflex (VOR) may be altered by weightlessness. Since this reflex plays a large role in visual stabilization, it was important to document any changes caused by space flight. This is a report on findings on STS-4 through 6 and is part of a larger study of neurosensory adaptation done on STS-4 through 8. Voluntary horizontal head oscillations at 1/3 Hz with amplitude of 30 deg right and left of center were recorded by a potentiometer and compared to eye position recorded by electroculography under the following conditions: eyes open, head fixed, tracking horizontal targets switched 0, 15, and 30 degrees right and left (optokinetic reflex - OKR - and calibration); eyes open and fixed on static external target with oscillation, (vestibulo ocular reflex, eyes closed - VOR EC); eyes open and wearing opaque goggles with target fixed in imagination (vestibulo-ocular reflex, eyes shaded - VOR ES); and eyes open and fixed on a head synchronized target with head oscillation (VOR suppression). No significant changes were found in voluntary head oscillation frequency or amplitude in those with (n=5), and without (n=3), space motion sickness (SMS), with phase of flight or test condition. Variations in head oscillation were too small to have produced detectable changes in test results.

Observing a light dark matter beam with neutrino experiments

NASA Astrophysics Data System (ADS)

Deniverville, Patrick; Pospelov, Maxim; Ritz, Adam

2011-10-01

We consider the sensitivity of fixed-target neutrino experiments at the luminosity frontier to light stable states, such as those present in models of MeV-scale dark matter. To ensure the correct thermal relic abundance, such states must annihilate via light mediators, which in turn provide an access portal for direct production in colliders or fixed targets. Indeed, this framework endows the neutrino beams produced at fixed-target facilities with a companion “dark matter beam,” which may be detected via an excess of elastic scattering events off electrons or nuclei in the (near-)detector. We study the high-luminosity proton fixed-target experiments at LSND and MiniBooNE, and determine that the ensuing sensitivity to light dark matter generally surpasses that of other direct probes. For scenarios with a kinetically-mixed U(1)' vector mediator of mass mV, we find that a large volume of parameter space is excluded for mDM˜1-5MeV, covering vector masses 2mDM≲mV≲mη and a range of kinetic mixing parameters reaching as low as κ˜10-5. The corresponding MeV-scale dark matter scenarios motivated by an explanation of the galactic 511 keV line are thus strongly constrained.

An Evaluation of the Value of Choice-Making Opportunities in Single-Operant Arrangements: Simple Fixed- and Progressive-Ratio Schedules

ERIC Educational Resources Information Center

Tiger, Jeffrey H.; Toussaint, Karen A.; Roath, Christopher T.

2010-01-01

The current study compared the effects of choice and no-choice reinforcement conditions on the task responding of 3 children with autism across 2 single-operant paradigm reinforcer assessments. The first assessment employed simple fixed-ratio (FR) schedules; the second used progressive-ratio (PR) schedules. The latter assessment identified the…

Application of mapped plots for single-owner forest surveys

Treesearch

Paul C. Van Deusen; Francis Roesch

2009-01-01

Mapped plots are used for the nation forest inventory conducted by the U.S. Forest Service. Mapped plots are also useful foro single ownership inventoires. Mapped plots can handle boundary overlap and can aprovide less variable estimates for specified forest conditions. Mapping is a good fit for fixed plot inventories where the fixed area plot is used for both mapping...

Visual-Motor Transformations Within Frontal Eye Fields During Head-Unrestrained Gaze Shifts in the Monkey.

PubMed

Sajad, Amirsaman; Sadeh, Morteza; Keith, Gerald P; Yan, Xiaogang; Wang, Hongying; Crawford, John Douglas

2015-10-01

A fundamental question in sensorimotor control concerns the transformation of spatial signals from the retina into eye and head motor commands required for accurate gaze shifts. Here, we investigated these transformations by identifying the spatial codes embedded in visually evoked and movement-related responses in the frontal eye fields (FEFs) during head-unrestrained gaze shifts. Monkeys made delayed gaze shifts to the remembered location of briefly presented visual stimuli, with delay serving to dissociate visual and movement responses. A statistical analysis of nonparametric model fits to response field data from 57 neurons (38 with visual and 49 with movement activities) eliminated most effector-specific, head-fixed, and space-fixed models, but confirmed the dominance of eye-centered codes observed in head-restrained studies. More importantly, the visual response encoded target location, whereas the movement response mainly encoded the final position of the imminent gaze shift (including gaze errors). This spatiotemporal distinction between target and gaze coding was present not only at the population level, but even at the single-cell level. We propose that an imperfect visual-motor transformation occurs during the brief memory interval between perception and action, and further transformations from the FEF's eye-centered gaze motor code to effector-specific codes in motor frames occur downstream in the subcortical areas. © The Author 2014. Published by Oxford University Press.

Genome-Wide Association Studies with a Genomic Relationship Matrix: A Case Study with Wheat and Arabidopsis.

PubMed

Gianola, Daniel; Fariello, Maria I; Naya, Hugo; Schön, Chris-Carolin

2016-10-13

Standard genome-wide association studies (GWAS) scan for relationships between each of p molecular markers and a continuously distributed target trait. Typically, a marker-based matrix of genomic similarities among individuals ( G: ) is constructed, to account more properly for the covariance structure in the linear regression model used. We show that the generalized least-squares estimator of the regression of phenotype on one or on m markers is invariant with respect to whether or not the marker(s) tested is(are) used for building G,: provided variance components are unaffected by exclusion of such marker(s) from G: The result is arrived at by using a matrix expression such that one can find many inverses of genomic relationship, or of phenotypic covariance matrices, stemming from removing markers tested as fixed, but carrying out a single inversion. When eigenvectors of the genomic relationship matrix are used as regressors with fixed regression coefficients, e.g., to account for population stratification, their removal from G: does matter. Removal of eigenvectors from G: can have a noticeable effect on estimates of genomic and residual variances, so caution is needed. Concepts were illustrated using genomic data on 599 wheat inbred lines, with grain yield as target trait, and on close to 200 Arabidopsis thaliana accessions. Copyright © 2016 Gianola et al.

Testing light dark matter coannihilation with fixed-target experiments

DOE PAGES

Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan; ...

2017-09-01

In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and downscattering as well as decaymore » of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.« less

Testing light dark matter coannihilation with fixed-target experiments

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

Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan

In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and downscattering as well as decaymore » of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.« less

Testing light dark matter coannihilation with fixed-target experiments

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

Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan

In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and down-scattering as well as decaymore » of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.« less

Migration and clinical outcome of mobile-bearing versus fixed-bearing single-radius total knee arthroplasty

PubMed Central

Van Hamersveld, Koen T; Marang-Van De Mheen, Perla J; Van Der Heide, Huub J L; Van Der Linden-Van Der Zwaag, Henrica M J; Valstar, Edward R; Nelissen, Rob G H H

2018-01-01

Background and purpose Mobile-bearing total knee prostheses (TKPs) were developed in the 1970s in an attempt to increase function and improve implant longevity. However, modern fixed-bearing designs like the single-radius TKP may provide similar advantages. We compared tibial component migration measured with radiostereometric analysis (RSA) and clinical outcome of otherwise similarly designed cemented fixed-bearing and mobile-bearing single-radius TKPs. Patients and methods RSA measurements and clinical scores were assessed in 46 randomized patients at baseline, 6 months, 1 year, and annually thereafter up to 6 years postoperatively. A linear mixed-effects model was used to analyze the repeated measurements. Results Both groups showed comparable migration (p = 0.3), with a mean migration at 6-year follow-up of 0.90 mm (95% CI 0.49–1.41) for the fixed-bearing group compared with 1.22 mm (95% CI 0.75–1.80) for the mobile-bearing group. Clinical outcomes were similar between groups. 1 fixed-bearing knee was revised for aseptic loosening after 6 years and 2 knees (1 in each group) were revised for late infection. 2 knees (1 in each group) were suspected for loosening due to excessive migration. Another mobile-bearing knee was revised after an insert dislocation due to failure of the locking mechanism 6 weeks postoperatively, after which study inclusion was preliminary terminated. Interpretation Fixed-bearing and mobile-bearing single-radius TKPs showed similar migration. The latter may, however, expose patients to more complex surgical techniques and risks such as insert dislocations inherent to this rotating-platform design. PMID:29448880

A mathematical analysis of multiple-target SELEX.

PubMed

Seo, Yeon-Jung; Chen, Shiliang; Nilsen-Hamilton, Marit; Levine, Howard A

2010-10-01

SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be fractionated with the goal of identifying those with specific biochemical activities. One combines the mixture with a specific target molecule and then separates the target-NA complex from the resulting reactions. The target-NA complex is separated from the unbound NA by mechanical means (such as by filtration), the NA is eluted from the complex, amplified by PCR (polymerase chain reaction), and the process repeated. After several rounds, one should be left with the nucleic acids that best bind to the target. The problem was first formulated mathematically in Irvine et al. (J. Mol. Biol. 222:739-761, 1991). In Levine and Nilsen-Hamilton (Comput. Biol. Chem. 31:11-25, 2007), a mathematical analysis of the process was given. In Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998), multiple target SELEX was considered. It was assumed that each target has a single nucleic acid binding site that permits occupation by no more than one nucleic acid. Here, we revisit Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998) using the same assumptions. The iteration scheme is shown to be convergent and a simplified algorithm is given. Our interest here is in the behavior of the multiple target SELEX process as a discrete "time" dynamical system. Our goal is to characterize the limiting states and their dependence on the initial distribution of nucleic acid and target fraction components. (In multiple target SELEX, we vary the target component fractions, but not their concentrations, as fixed and the initial pool of nucleic acids as a variable starting condition). Given N nucleic acids and a target consisting of M subtarget component species, there is an M × N matrix of affinities, the (i,j) entry corresponding to the affinity of the jth nucleic acid for the ith subtarget. We give a structure condition on this matrix that is equivalent to the following statement: For any initial pool of nucleic acids such that all N species are represented, the dynamical system defined by the multiple target SELEX process will converge to a unique subset of nucleic acids, each of whose concentrations depend only upon the total nucleic acid concentration, the initial fractional target distribution (both of which are assumed to be the same from round to round), and the overall limiting association constant. (The overall association constant is the equilibrium constant for the system of MN reactions when viewed as a composite single reaction). This condition is equivalent to the statement that every member of a certain family of chemical potentials at infinite target dilution can have at most one critical point. (The condition replaces the statement for single target SELEX that the dynamical system generated via the process always converges to a pool that contains only the nucleic acid that binds best to the target). This suggests that the effectiveness of multiple target SELEX as a separation procedure may not be as useful as single target SELEX unless the thermodynamic properties of these chemical potentials are well understood.

Flexible Fusion Structure-Based Performance Optimization Learning for Multisensor Target Tracking

PubMed Central

Ge, Quanbo; Wei, Zhongliang; Cheng, Tianfa; Chen, Shaodong; Wang, Xiangfeng

2017-01-01

Compared with the fixed fusion structure, the flexible fusion structure with mixed fusion methods has better adjustment performance for the complex air task network systems, and it can effectively help the system to achieve the goal under the given constraints. Because of the time-varying situation of the task network system induced by moving nodes and non-cooperative target, and limitations such as communication bandwidth and measurement distance, it is necessary to dynamically adjust the system fusion structure including sensors and fusion methods in a given adjustment period. Aiming at this, this paper studies the design of a flexible fusion algorithm by using an optimization learning technology. The purpose is to dynamically determine the sensors’ numbers and the associated sensors to take part in the centralized and distributed fusion processes, respectively, herein termed sensor subsets selection. Firstly, two system performance indexes are introduced. Especially, the survivability index is presented and defined. Secondly, based on the two indexes and considering other conditions such as communication bandwidth and measurement distance, optimization models for both single target tracking and multi-target tracking are established. Correspondingly, solution steps are given for the two optimization models in detail. Simulation examples are demonstrated to validate the proposed algorithms. PMID:28481243

SapTrap, a Toolkit for High-Throughput CRISPR/Cas9 Gene Modification in Caenorhabditis elegans.

PubMed

Schwartz, Matthew L; Jorgensen, Erik M

2016-04-01

In principle, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 allows genetic tags to be inserted at any locus. However, throughput is limited by the laborious construction of repair templates and guide RNA constructs and by the identification of modified strains. We have developed a reagent toolkit and plasmid assembly pipeline, called "SapTrap," that streamlines the production of targeting vectors for tag insertion, as well as the selection of modified Caenorhabditis elegans strains. SapTrap is a high-efficiency modular plasmid assembly pipeline that produces single plasmid targeting vectors, each of which encodes both a guide RNA transcript and a repair template for a particular tagging event. The plasmid is generated in a single tube by cutting modular components with the restriction enzyme SapI, which are then "trapped" in a fixed order by ligation to generate the targeting vector. A library of donor plasmids supplies a variety of protein tags, a selectable marker, and regulatory sequences that allow cell-specific tagging at either the N or the C termini. All site-specific sequences, such as guide RNA targeting sequences and homology arms, are supplied as annealed synthetic oligonucleotides, eliminating the need for PCR or molecular cloning during plasmid assembly. Each tag includes an embedded Cbr-unc-119 selectable marker that is positioned to allow concurrent expression of both the tag and the marker. We demonstrate that SapTrap targeting vectors direct insertion of 3- to 4-kb tags at six different loci in 10-37% of injected animals. Thus SapTrap vectors introduce the possibility for high-throughput generation of CRISPR/Cas9 genome modifications. Copyright © 2016 by the Genetics Society of America.

[Treatment of a single-tooth space in the occlusal system].

PubMed

Meijer, H J A; Cune, M S

2012-12-01

The space created by the absence of 1 not-free-ending tooth in an occlusal system can be indicated as a single-tooth space. For treating a single-tooth space, several options are available to restore the functions of the occlusal system. Feasible options are a resin-bonded fixed prosthesis, a conventional fixed prosthesis, and an implant-supported restoration. Implant-supported restorations have a good prognosis, high patient satisfaction, and the advantage that adjacent teeth are not involved in the treatment. Anxiety about surgical treatment, the width of the single-tooth space, and financial aspects may be reasons not to consider an implant-supported restoration as first-choice treatment.

Averting group failures in collective-risk social dilemmas

NASA Astrophysics Data System (ADS)

Chen, Xiaojie; Szolnoki, Attila; Perc, Matjaž

2012-09-01

Free-riding on a joint venture bears the risk of losing personal endowment as the group may fail to reach the collective target due to insufficient contributions. A collective-risk social dilemma emerges, which we here study in the realm of the spatial public goods game with group-performance-dependent risk levels. Instead of using an overall fixed value, we update the risk level in each group based on the difference between the actual contributions and the declared target. A single parameter interpolates between a step-like risk function and virtual irrelevance of the group's performance in averting the failure, thus bridging the two extremes constituting maximal and minimal feedback. We show that stronger feedback between group performance and risk level is in general more favorable for the successful evolution of public cooperation, yet only if the collective target to be reached is moderate. Paradoxically, if the goals are overambitious, intermediate feedback strengths yield optimal conditions for cooperation. This can be explained by the propagation of players that employ identical strategies but experience different individual success while trying to cope with the collective-risk social dilemma.

Effects of variability of practice in music: a pilot study on fast goal-directed movements in pianists

PubMed Central

Bangert, Marc; Wiedemann, Anna; Jabusch, Hans-Christian

2014-01-01

Variability of Practice (VOP) refers to the acquisition of a particular target movement by practicing a range of varying targets rather than by focusing on fixed repetitions of the target only. VOP has been demonstrated to have beneficial effects on transfer to a novel task and on skill consolidation. This study extends the line of research to musical practice. In a task resembling a barrier-knockdown paradigm, 36 music students trained to perform a wide left-hand interval leap on the piano. Performance at the target distance was tested before and after a 30-min standardized training session. The high-variability group (VAR) practiced four different intervals including the target. Another group (FIX) practiced the target interval only. A third group (SPA) performed spaced practice on the target only, interweaving with periods of not playing. Transfer was tested by introducing an interval novel to either group. After a 24-h period with no further exposure to the instrument, performance was retested. All groups performed at comparable error levels before training, after training, and after the retention (RET) interval. At transfer, however, the FIX group, unlike the other groups, committed significantly more errors than in the target task. After the RET period, the effect was washed out for the FIX group but then was present for VAR. Thus, the results provide only partial support for the VOP hypothesis for the given setting. Additional exploratory observations suggest tentative benefits of VOP regarding execution speed, loudness, and performance confidence. We derive specific hypotheses and specific recommendations regarding sample selection and intervention duration for future investigations. Furthermore, the proposed leap task measurement is shown to be (a) robust enough to serve as a standard framework for studies in the music domain, yet (b) versatile enough to allow for a wide range of designs not previously investigated for music on a standardized basis. PMID:25157223

A MATHEMATICAL ANALYSIS OF SELEX

PubMed Central

Levine, Howard A.; Nilsen-Hamilton, Marit

2007-01-01

SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be separated into pure components with the goal of isolating those with specific biochemical activities. The basic idea is to combine the mixture with a specific target molecule and then separate the target-NA complex from the resulting reaction. The target-NA complex is then separated by mechanical means (for example by nitrocellulose filtration), the NA is then eluted from the complex, amplified by PCR (polymerase chain reaction) and the process repeated. After several rounds, one should be left with a pool of [NA]that consists mostly of the species in the original pool that best binds to the target. In Irvine et al. (1991) a mathematical analysis of this process was given. In this paper we revisit Irvine et al. (1991). By rewriting the equations for the SELEX process, we considerably reduce the labor of computing the round to round distribution of nucleic acid fractions. We also establish necessary and sufficient conditions for the SELEX process to converge to a pool consisting solely of the best binding nucleic acid to a fixed target in a manner that maximizes the percentage of bound target. The assumption is that there is a single nucleic acid binding site on the target that permits occupation by no more than one nucleic acid. We analyze the case for which there is no background loss, (no support losses and no free [NA] left on the support.) We then examine the case in which such there are such losses. The significance of the analysis is that it suggests an experimental approach for the SELEX process as defined in Irvine et al. (1991) to converge to a pool consisting of a single best binding nucleic acid without recourse to any a-priori information about the nature of the binding constants or the distribution of the individual nucleic acid fragments. PMID:17218151

Evaluation of a Dual ALK/ROS1 Fluorescent In Situ Hybridization Test in Non-Small-cell Lung Cancer.

PubMed

Ginestet, Florent; Lambros, Laetitia; Le Flahec, Glen; Marcorelles, Pascale; Uguen, Arnaud

2018-05-05

Several therapeutics targets have emerged to treat patients with non-small-cell lung carcinoma (NSCLC), with numerous biomarkers available to test for treatment choices. Minimum tumor wastage is necessary to permit the analysis of every potentially relevant target. Searching for targetable ALK and ROS1 rearrangements is now mandatory in NSCLC. In the present study, we evaluated the performance of a dual ALK/ROS1 fluorescent in situ hybridization (FISH) probe that concurrently analyzed the 2 oncogenes on a same FISH slide. We used the FlexISH ALK/ROS1 DistinguISH Probe (Zytovision, Bremerhaven, Germany) to analyze a set of 28 formalin-fixed paraffin-embedded NSCLC tumor samples enriched in tumors with ALK- and ROS1-rearranged status. The dual ALK/ROS1 FISH probe test results were fully concordant with the results of previous single ALK and ROS1 FISH tests (15 ALK and 3 ROS1 rearrangements) without any false-positive results. Dual- and single-probe FISH test results were also concordant regarding the unusual ALK FISH patterns. These included 1 sample that had negative FISH results with diffuse single 5'-ALK signals and positive ALK immunohistochemistry findings in a patient with a response to crizotinib, 2 paired samples with high percentages of ALK FISH-rearranged nuclei despite negative ALK immunohistochemistry findings, and ALK FISH-positive samples from 2 patients lacking a response to crizotinib therapy despite concordant ALK FISH and immunohistochemistry-positive results. The dual ALK/ROS1 FISH probe test is a valuable tool to search concurrently for both ALK and ROS1 rearrangements on a same FISH slide and could help to spare tumor tissue for other biomarkers tests. Copyright © 2018 Elsevier Inc. All rights reserved.

Double versus single stenting for coronary bifurcation lesions: a meta-analysis.

PubMed

Katritsis, Demosthenes G; Siontis, George C M; Ioannidis, John P A

2009-10-01

Several trials have addressed whether bifurcation lesions require stenting of both the main vessel and side branch, but uncertainty remains on the benefits of such double versus single stenting of the main vessel only. We have conducted a meta-analysis of randomized trials including patients with coronary bifurcation lesions who were randomly selected to undergo percutaneous coronary intervention by either double or single stenting. Six studies (n=1642 patients) were eligible. There was increased risk of myocardial infarction with double stenting (risk ratio, 1.78; P=0.001 by fixed effects; risk ratio, 1.49 with Bayesian meta-analysis). The summary point estimate suggested also an increased risk of stent thrombosis with double stenting, but the difference was not nominally significant given the sparse data (risk ratio, 1.85; P=0.19). No obvious difference was seen for death (risk ratio, 0.81; P=0.66) and target lesion revascularization (risk ratio, 1.09; P=0.67). Stenting of both the main vessel and side branch in bifurcation lesions may increase myocardial infarction and stent thrombosis risk compared with stenting of the main vessel only.

SU-E-T-539: Fixed Versus Variable Optimization Points in Combined-Mode Modulated Arc Therapy Planning

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

Kainz, K; Prah, D; Ahunbay, E

2014-06-01

Purpose: A novel modulated arc therapy technique, mARC, enables superposition of step-and-shoot IMRT segments upon a subset of the optimization points (OPs) of a continuous-arc delivery. We compare two approaches to mARC planning: one with the number of OPs fixed throughout optimization, and another where the planning system determines the number of OPs in the final plan, subject to an upper limit defined at the outset. Methods: Fixed-OP mARC planning was performed for representative cases using Panther v. 5.01 (Prowess, Inc.), while variable-OP mARC planning used Monaco v. 5.00 (Elekta, Inc.). All Monaco planning used an upper limit of 91more » OPs; those OPs with minimal MU were removed during optimization. Plans were delivered, and delivery times recorded, on a Siemens Artiste accelerator using a flat 6MV beam with 300 MU/min rate. Dose distributions measured using ArcCheck (Sun Nuclear Corporation, Inc.) were compared with the plan calculation; the two were deemed consistent if they agreed to within 3.5% in absolute dose and 3.5 mm in distance-to-agreement among > 95% of the diodes within the direct beam. Results: Example cases included a prostate and a head-and-neck planned with a single arc and fraction doses of 1.8 and 2.0 Gy, respectively. Aside from slightly more uniform target dose for the variable-OP plans, the DVHs for the two techniques were similar. For the fixed-OP technique, the number of OPs was 38 and 39, and the delivery time was 228 and 259 seconds, respectively, for the prostate and head-and-neck cases. For the final variable-OP plans, there were 91 and 85 OPs, and the delivery time was 296 and 440 seconds, correspondingly longer than for fixed-OP. Conclusion: For mARC, both the fixed-OP and variable-OP approaches produced comparable-quality plans whose delivery was successfully verified. To keep delivery time per fraction short, a fixed-OP planning approach is preferred.« less

[Application of single-retainer all-ceramic resin-bonded fixed partial denture in replacing single anterior tooth].

PubMed

Lili, Yang; Debiao, Du; Ruoyu, Ning; Deying, Chen; Junling, Wu

2017-08-01

Objective In this study, we aimed to evaluate the clinical effect of single-retainer all-ceramic resin-bonded fixed partial denture (RBFPD) on the single anterior tooth loss patients. Methods A total of 20 single-retainer all-ceramic RBFPD
were fabricated and evaluated in a two-year follow-up observation. The restorations were examined on the basis of the American Public Health Association (APHA) criteria. Results A total of 20 single-retainer all-ceramic RBFPD achieved class A evaluation after a six-month follow-up observation. One single-retainer all-ceramic RBFPD was classified as class B for secondary caries after a one-year follow-up observation. After a two-year follow-up observation, one single-retainer all-ceramic RBFPD was classified as class B because of secondary caries, and one single-retainer all-ceramic RBFPD was classified as class B because of fracture. Conclusion Single-retainer all-ceramic RBFPD is a promising and optional method in replacing single anterior tooth.

The course of visual searching to a target in a fixed location: electrophysiological evidence from an emotional flanker task.

PubMed

Dong, Guangheng; Yang, Lizhu; Shen, Yue

2009-08-21

The present study investigated the course of visual searching to a target in a fixed location, using an emotional flanker task. Event-related potentials (ERPs) were recorded while participants performed the task. Emotional facial expressions were used as emotion-eliciting triggers. The course of visual searching was analyzed through the emotional effects arising from these emotion-eliciting stimuli. The flanker stimuli showed effects at about 150-250 ms following the stimulus onset, while the effect of target stimuli showed effects at about 300-400 ms. The visual search sequence in an emotional flanker task moved from a whole overview to a specific target, even if the target always appeared at a known location. The processing sequence was "parallel" in this task. The results supported the feature integration theory of visual search.

Centrifugal multiplexing fixed-volume dispenser on a plastic lab-on-a-disk for parallel biochemical single-end-point assays

PubMed Central

La, Moonwoo; Park, Sang Min; Kim, Dong Sung

2015-01-01

In this study, a multiple sample dispenser for precisely metered fixed volumes was successfully designed, fabricated, and fully characterized on a plastic centrifugal lab-on-a-disk (LOD) for parallel biochemical single-end-point assays. The dispenser, namely, a centrifugal multiplexing fixed-volume dispenser (C-MUFID) was designed with microfluidic structures based on the theoretical modeling about a centrifugal circumferential filling flow. The designed LODs were fabricated with a polystyrene substrate through micromachining and they were thermally bonded with a flat substrate. Furthermore, six parallel metering and dispensing assays were conducted at the same fixed-volume (1.27 μl) with a relative variation of ±0.02 μl. Moreover, the samples were metered and dispensed at different sub-volumes. To visualize the metering and dispensing performances, the C-MUFID was integrated with a serpentine micromixer during parallel centrifugal mixing tests. Parallel biochemical single-end-point assays were successfully conducted on the developed LOD using a standard serum with albumin, glucose, and total protein reagents. The developed LOD could be widely applied to various biochemical single-end-point assays which require different volume ratios of the sample and reagent by controlling the design of the C-MUFID. The proposed LOD is feasible for point-of-care diagnostics because of its mass-producible structures, reliable metering/dispensing performance, and parallel biochemical single-end-point assays, which can identify numerous biochemical. PMID:25610516

Clinical and Radiographic Assessment of Reasons for Replacement of Metal- Ceramic Fixed Dental Prostheses in Patients Referring to Dental School.

PubMed

Al Refai, Roa'a; Saker, Samah

2018-01-01

The expected length of service and reasons for fixed dental prostheses (FDPs) replacement are a frequent inquiry by patients while the answers were mainly based on studies reports that was conducted outside the middle east region. This clinical and radiographic survey was constructed to assess and survey clinically and radiographically the reasons of replacement of metal-ceramic fixed dental prostheses, amongst patients reporting at dental school in Taibah University. Between January and May 2016, 151 patients were recruited for this study. Interview (include questions pertained to the length of service of the prosthesis, the nature of complaint as told by patient in her own words), clinical examination, intra-oral photographs, and periapical radiographs, were done by the researchers. The parameters assessed were secondary caries, open margins, loss of retention, failure of endodontic treatment of the abutment and periodontal diseases. A total number of 249 failed fixed dental prostheses were evaluated. Of which 180 (39.7%) were single crowns, 159 (35.0%) were retainers and 117 (25.8%) were pontics in 69 fixed partial denture. The most common reason for replacement of fixed restorations was periodontal diseases affecting 92.8% of all types' restorations, followed by defective margin in 90.4% of examined restoration, poor aesthetic in 88% of restorations, while periapical involvement was found in 85.5% of fixed dental prosthesis. The survival rates of fixed prostheses were not predictable, and no association was found between number of years in service and the number of restorations. The most common reasons for replacing single unit fixed dental prostheses are periodontal diseases and periapical involvement, while defective margins and poor aesthetic mainly associated with multi-unit fixed dental prostheses. Key words: Failure, Fixed dental prosthesis, Survival, Replacement.

UAVs Task and Motion Planning in the Presence of Obstacles and Prioritized Targets

PubMed Central

Gottlieb, Yoav; Shima, Tal

2015-01-01

The intertwined task assignment and motion planning problem of assigning a team of fixed-winged unmanned aerial vehicles to a set of prioritized targets in an environment with obstacles is addressed. It is assumed that the targets’ locations and initial priorities are determined using a network of unattended ground sensors used to detect potential threats at restricted zones. The targets are characterized by a time-varying level of importance, and timing constraints must be fulfilled before a vehicle is allowed to visit a specific target. It is assumed that the vehicles are carrying body-fixed sensors and, thus, are required to approach a designated target while flying straight and level. The fixed-winged aerial vehicles are modeled as Dubins vehicles, i.e., having a constant speed and a minimum turning radius constraint. The investigated integrated problem of task assignment and motion planning is posed in the form of a decision tree, and two search algorithms are proposed: an exhaustive algorithm that improves over run time and provides the minimum cost solution, encoded in the tree, and a greedy algorithm that provides a quick feasible solution. To satisfy the target’s visitation timing constraint, a path elongation motion planning algorithm amidst obstacles is provided. Using simulations, the performance of the algorithms is compared, evaluated and exemplified. PMID:26610522

Measuring mRNA copy-number in individual Escherichia coli cells using single-molecule fluorescent in situ hybridization (smFISH)

PubMed Central

Skinner, Samuel O.; Sepúlveda, Leonardo A.; Xu, Heng; Golding, Ido

2014-01-01

We present a method for measuring the absolute number of mRNA molecules from a gene of interest in individual, chemically fixed Escherichia coli cells. A set of fluorescently-labeled oligonucleotide probes are hybridized to the target mRNA, so that each mRNA molecule is decorated by a known number of fluorescent dyes. Cells are then imaged using fluorescence microscopy. The number of target mRNA is estimated from the total intensity of fluorescent foci in the cell, rather than from counting discrete “spots” as in other currently available protocols. Image analysis is performed using an automated algorithm. The measured mRNA copy-number distribution obtained from many individual cells can be used to extract the parameters of stochastic gene activity, namely the frequency and size of transcription bursts from the gene of interest. The experimental procedure takes 2 days, with another 2-3 days typically required for image and data analysis. PMID:23680982

Scalable and responsive event processing in the cloud

PubMed Central

Suresh, Visalakshmi; Ezhilchelvan, Paul; Watson, Paul

2013-01-01

Event processing involves continuous evaluation of queries over streams of events. Response-time optimization is traditionally done over a fixed set of nodes and/or by using metrics measured at query-operator levels. Cloud computing makes it easy to acquire and release computing nodes as required. Leveraging this flexibility, we propose a novel, queueing-theory-based approach for meeting specified response-time targets against fluctuating event arrival rates by drawing only the necessary amount of computing resources from a cloud platform. In the proposed approach, the entire processing engine of a distinct query is modelled as an atomic unit for predicting response times. Several such units hosted on a single node are modelled as a multiple class M/G/1 system. These aspects eliminate intrusive, low-level performance measurements at run-time, and also offer portability and scalability. Using model-based predictions, cloud resources are efficiently used to meet response-time targets. The efficacy of the approach is demonstrated through cloud-based experiments. PMID:23230164

Low-energy electron scattering from water molecules: A study of angular distributions

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

Gianturco, F.A.; Scialla, S.

1987-12-01

We report quantal calculations of elastic differential and momentum transfercross sections for the scattering of electrons by H/sub 2/O at low and intermediatecollision energies, i.e., from 2 to 20 eV. The fixed-nuclei approximation (FNA) was employed and a single-center expanded (SCE) wave function was used to represent the molecular target. The well-known divergence in the forward direction was corrected via Born closure formulas (see the text) and a parameter-free model, previously tested for methane targets, was used to describe exchange and polarization effects. The present results can be used to adequately describe angular distributions even at very small angles andmore » can be extended beyond the largest angles that have been experimentally measured. The behavior of momentum-transfer cross sections as a function of energy, and the comparison of our results with other static-exchange (SE) calculations, which use an entirely different approach, are presented and discussed.« less

Transforaminal Anterior Release for the Treatment of Fixed Sagittal Imbalance and Segmental Kyphosis, Minimum 2-Year Follow-Up Study.

PubMed

Sweet, Fred A; Sweet, Andrea

2015-09-01

Retrospective review of prospectively accrued patient cohort. To report minimum 2 years' follow-up after a single-surgeon series of 47 consecutive patients in whom fixed sagittal imbalance or segmental kyphosis was treated with a novel unilateral transforaminal annular release. Fixed sagittal imbalance has been treated most recently with pedicle subtraction osteotomy with great success but is associated with significant blood loss and neurologic risk. Forty-seven consecutive patients with fixed sagittal imbalance (n = 29) or segmental kyphosis (n = 18) were treated by a single surgeon with a single-level transforaminal anterior release (TFAR) to effect an opening wedge correction. Sagittal and coronal correction was performed with in situ rod contouring. An interbody cage was captured in the disc space with rod compression. Radiographic and clinical outcome analysis was performed with a minimum 2-year follow-up (range 2-7.8 years). The average increase in lordosis was 36° (range 24°-56°) in the fixed sagittal deformity group. Coronal corrections averaged 34° (range 18°-48°). The average improvement in plumb line was 13.6 cm. There were four pseudarthroses, one at the TFAR. Average blood loss was 578 mL (range 200-1,200). One patient had a transient grade 4/5 anterior tibialis weakness. There were no vascular injuries or permanent neurologic deficits. There were significant improvements in the Oswestry Disability Index (p < .001) and Scoliosis Research Society Questionnaire scores (p = .003). Eighty-four percent of patients reported improvement in pain, self-image, and satisfaction with the procedure. TFAR is a useful procedure for correcting segmental kyphosis and fixed sagittal imbalance with relatively low blood loss and was found to be neurologically safe in this single-surgeon series. Therapeutic study, Level IV (case series, no control group). Copyright © 2015 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Applicator-guided volumetric-modulated arc therapy for low-risk endometrial cancer

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

Cilla, Savino, E-mail: savinocilla@gmail.com; Macchia, Gabriella; Sabatino, Domenico

2013-04-01

The aim of this study was to report the feasibility of volumetric-modulated arc therapy (VMAT) in the postoperative irradiation of the vaginal vault. Moreover, the VMAT technique was compared with 3D conformal radiotherapy (3D-CRT) and fixed-field intensity-modulated radiotherapy (IMRT), in terms of target coverage and organs at risk sparing. The number of monitor units and the delivery time were analyzed to score the treatment efficiency. All plans were verified in a dedicated solid water phantom using a 2D array of ionization chambers. Twelve patients with endometrial carcinoma who underwent radical hystero-adenexectomy and fixed-field IMRT treatments were retrospectively included in thismore » analysis; for each patient, plans were compared in terms of dose-volume histograms, homogeneity index, and conformity indexes. All techniques met the prescription goal for planning target volume coverage, with VMAT showing the highest level of conformity at all dose levels. VMAT resulted in significant reduction of rectal and bladder volumes irradiated at all dose levels compared with 3D-CRT. No significant differences were found with respect to IMRT. Moreover, a significant improvement of the dose conformity was reached by VMAT technique not only at the 95% dose level (0.74 vs. 0.67 and 0.62) but also at 50% and 75% levels of dose prescription. In addition, VMAT plans showed a significant reduction of monitor units by nearly 28% with respect to IMRT, and reduced treatment time from 11 to <3 minutes for a single 6-Gy fraction. In conclusion, VMAT plans can be planned and carried out with high quality and efficiency for the irradiation of vaginal vault alone, providing similar or better sparing of organs at risk to fixed-field IMRT and resulting in the most efficient treatment option. VMAT is currently our standard approach for radiotherapy of low-risk endometrial cancer.« less

Fixed target experiments at the Fermilab Tevatron

DOE PAGES

Gutierrez, Gaston; Reyes, Marco A.

2014-11-10

This paper presents a review of the study of Exclusive Central Production at a Center of Mass energy of √s = 40 GeV at the Fermilab Fixed Target program. In all reactions reviewed in this paper, protons with an energy of 800 GeV were extracted from the Tevatron accelerator at Fermilab and directed to a Liquid Hydrogen target. The states reviewed include π⁺π⁻, K⁰ s K⁰ s, K⁰ s K ±π ∓, φφ and D *±. Partial Wave Analysis results will be presented on the light states but only the cross-section will be reviewed in the diffractive production of Dmore » *±.« less

Applications of mass spectrometry for quantitative protein analysis in formalin-fixed paraffin-embedded tissues

PubMed Central

Steiner, Carine; Ducret, Axel; Tille, Jean-Christophe; Thomas, Marlene; McKee, Thomas A; Rubbia-Brandt, Laura A; Scherl, Alexander; Lescuyer, Pierre; Cutler, Paul

2014-01-01

Proteomic analysis of tissues has advanced in recent years as instruments and methodologies have evolved. The ability to retrieve peptides from formalin-fixed paraffin-embedded tissues followed by shotgun or targeted proteomic analysis is offering new opportunities in biomedical research. In particular, access to large collections of clinically annotated samples should enable the detailed analysis of pathologically relevant tissues in a manner previously considered unfeasible. In this paper, we review the current status of proteomic analysis of formalin-fixed paraffin-embedded tissues with a particular focus on targeted approaches and the potential for this technique to be used in clinical research and clinical diagnosis. We also discuss the limitations and perspectives of the technique, particularly with regard to application in clinical diagnosis and drug discovery. PMID:24339433

Single-Center Experience with a Targeted Next Generation Sequencing Assay for Assessment of Relevant Somatic Alterations in Solid Tumors.

PubMed

Paasinen-Sohns, Aino; Koelzer, Viktor H; Frank, Angela; Schafroth, Julian; Gisler, Aline; Sachs, Melanie; Graber, Anne; Rothschild, Sacha I; Wicki, Andreas; Cathomas, Gieri; Mertz, Kirsten D

2017-03-01

Companion diagnostics rely on genomic testing of molecular alterations to enable effective cancer treatment. Here we report the clinical application and validation of the Oncomine Focus Assay (OFA), an integrated, commercially available next-generation sequencing (NGS) assay for the rapid and simultaneous detection of single nucleotide variants, short insertions and deletions, copy number variations, and gene rearrangements in 52 cancer genes with therapeutic relevance. Two independent patient cohorts were investigated to define the workflow, turnaround times, feasibility, and reliability of OFA targeted sequencing in clinical application and using archival material. Cohort I consisted of 59 diagnostic clinical samples from the daily routine submitted for molecular testing over a 4-month time period. Cohort II consisted of 39 archival melanoma samples that were up to 15years old. Libraries were prepared from isolated nucleic acids and sequenced on the Ion Torrent PGM sequencer. Sequencing datasets were analyzed using the Ion Reporter software. Genomic alterations were identified and validated by orthogonal conventional assays including pyrosequencing and immunohistochemistry. Sequencing results of both cohorts, including archival formalin-fixed, paraffin-embedded material stored up to 15years, were consistent with published variant frequencies. A concordance of 100% between established assays and OFA targeted NGS was observed. The OFA workflow enabled a turnaround of 3½ days. Taken together, OFA was found to be a convenient tool for fast, reliable, broadly applicable and cost-effective targeted NGS of tumor samples in routine diagnostics. Thus, OFA has strong potential to become an important asset for precision oncology. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

A prospective 10-year study of metal ceramic single crowns and fixed dental prosthesis retainers in private practice settings.

PubMed

Reitemeier, Bernd; Hänsel, Kristina; Kastner, Christian; Weber, Anke; Walter, Michael H

2013-03-01

Metal ceramic restorations are widely used in prosthodontics, but long-term data on their clinical performance in private practice settings based on prospective trials are sparse. This clinical trial was designed to provide realistic long-term survival rates for different outcomes related to tooth loss, crown loss, and metal ceramic defect. Ninety-five participants were provided with 190 noble metal ceramic single crowns and 138 participants with 276 fixed dental prosthesis retainer crowns on vital posterior teeth. Follow-up examinations were scheduled 2 weeks after insertion, annually up to 8 years, and after 10 years. Kaplan-Meier survival analyses, Mantel-Cox logrank tests, and Cox regression analyses were conducted. Because of variations in the time of the last examinations, the maximum observation period was 12.1 years. For the primary outcome 'loss of crown or tooth', the Kaplan-Meier survival rate was 94.3% ±1.8% (standard error) at 8.0 years (last outcome event) for single crowns and 94.4% ±1.5% at 11.0 years for fixed dental prosthesis retainer crowns. The difference between the survival functions was not significant (P>.05). For the secondary outcome 'metal ceramic defect', the survival rate was 88.8% ±3.2% at 11.0 years for single crowns and 81.7% ±3.5% at 11.0 years for fixed dental prosthesis retainer crowns. In Cox regression models, the only significant covariates for the outcome event 'metal ceramic defect' were bruxism in the medical history (single crowns) and signs and symptoms of bruxism (fixed dental prosthesis retainer crowns) with hazard ratios of 3.065 (95% CI 1.063 - 8.832) and 2.554 (95% CI 1.307 - 4.992). Metal ceramic crowns provided in private practice settings show good longevity. Bruxism appears to indicate a risk for metal ceramic defects. Copyright © 2013 The Editorial Council of the Journal of Prosthetic Dentistry. Published by Mosby, Inc. All rights reserved.

Evaluation of integration methods for hybrid simulation of complex structural systems through collapse

NASA Astrophysics Data System (ADS)

Del Carpio R., Maikol; Hashemi, M. Javad; Mosqueda, Gilberto

2017-10-01

This study examines the performance of integration methods for hybrid simulation of large and complex structural systems in the context of structural collapse due to seismic excitations. The target application is not necessarily for real-time testing, but rather for models that involve large-scale physical sub-structures and highly nonlinear numerical models. Four case studies are presented and discussed. In the first case study, the accuracy of integration schemes including two widely used methods, namely, modified version of the implicit Newmark with fixed-number of iteration (iterative) and the operator-splitting (non-iterative) is examined through pure numerical simulations. The second case study presents the results of 10 hybrid simulations repeated with the two aforementioned integration methods considering various time steps and fixed-number of iterations for the iterative integration method. The physical sub-structure in these tests consists of a single-degree-of-freedom (SDOF) cantilever column with replaceable steel coupons that provides repeatable highlynonlinear behavior including fracture-type strength and stiffness degradations. In case study three, the implicit Newmark with fixed-number of iterations is applied for hybrid simulations of a 1:2 scale steel moment frame that includes a relatively complex nonlinear numerical substructure. Lastly, a more complex numerical substructure is considered by constructing a nonlinear computational model of a moment frame coupled to a hybrid model of a 1:2 scale steel gravity frame. The last two case studies are conducted on the same porotype structure and the selection of time steps and fixed number of iterations are closely examined in pre-test simulations. The generated unbalance forces is used as an index to track the equilibrium error and predict the accuracy and stability of the simulations.

Evaluation of large-truck fixed-object crashes at bridge structures in Kansas.

DOT National Transportation Integrated Search

2012-12-01

The aim of this study was to investigate any possible relationships between roadway geometry, pavement conditions, and : large-truck, fixed object crashes at bridge sites. Data on single-vehicle and multiple-vehicle large-truck crashes were : extract...

Precise orbit determination of the Sentinel-3A altimetry satellite using ambiguity-fixed GPS carrier phase observations

NASA Astrophysics Data System (ADS)

Montenbruck, Oliver; Hackel, Stefan; Jäggi, Adrian

2017-11-01

The Sentinel-3 mission takes routine measurements of sea surface heights and depends crucially on accurate and precise knowledge of the spacecraft. Orbit determination with a targeted uncertainty of less than 2 cm in radial direction is supported through an onboard Global Positioning System (GPS) receiver, a Doppler Orbitography and Radiopositioning Integrated by Satellite instrument, and a complementary laser retroreflector for satellite laser ranging. Within this study, the potential of ambiguity fixing for GPS-only precise orbit determination (POD) of the Sentinel-3 spacecraft is assessed. A refined strategy for carrier phase generation out of low-level measurements is employed to cope with half-cycle ambiguities in the tracking of the Sentinel-3 GPS receiver that have so far inhibited ambiguity-fixed POD solutions. Rather than explicitly fixing double-difference phase ambiguities with respect to a network of terrestrial reference stations, a single-receiver ambiguity resolution concept is employed that builds on dedicated GPS orbit, clock, and wide-lane bias products provided by the CNES/CLS (Centre National d'Études Spatiales/Collecte Localisation Satellites) analysis center of the International GNSS Service. Compared to float ambiguity solutions, a notably improved precision can be inferred from laser ranging residuals. These decrease from roughly 9 mm down to 5 mm standard deviation for high-grade stations on average over low and high elevations. Furthermore, the ambiguity-fixed orbits offer a substantially improved cross-track accuracy and help to identify lateral offsets in the GPS antenna or center-of-mass (CoM) location. With respect to altimetry, the improved orbit precision also benefits the global consistency of sea surface measurements. However, modeling of the absolute height continues to rely on proper dynamical models for the spacecraft motion as well as ground calibrations for the relative position of the altimeter reference point and the CoM.

The use of combination therapies in the acute management of migraine.

PubMed

Krymchantowski, Abouch Valenty

2006-09-01

Migraine is a highly prevalent neurological disorder with multiple peripheral and central mechanisms. Targeting a single mechanism for treating individual attacks as well as for performing the prophylaxis has been shown to be only partially effective. Recently, the role of combining agents for acute migraine treatment has gained attention and the combination of a triptan plus a non-steroidal anti-inflammatory drug (NSAID) has demonstrated better efficacy. This review focuses on the fundamentals of treating migraine attacks with two or more agents, and emphasizes the characteristics of the recently approved fixed combination sumatriptan-naproxen. A PubMed search using the terms "migraine", "treatment", "acute", "triptans", "non-steroidal anti-inflammatory drugs", "sumatriptan", "naproxen", and "combination" was used. In addition, abstracts presented in the major meetings of the American Headache and the International Headache Societies along with the American Academy of Neurology were also evaluated. Although most of the few studies encountered were not controlled, there is a clear trend for better efficacy in combining triptans with NSAID. Additionally, the results of two recent large and controlled studies using fixed combinations of sumatriptan (50 mg and 85 mg) with 500 mg naproxen sodium confirm the initial observations of the clear superiority of this combination over the use of each agent alone. The differences in the endpoints 24-hour pain-relief response as well as pain-free and pain-relief parameters at 2-hour time-point are the most noticeable efficacy measures. Tolerability was not different between studied drugs. Combining triptans with NSAID and other agents for the acute treatment of migraine suggests better outcome efficacy measures than the use of single agents. The fixed combination of sumatriptan and naproxen sodium offers improved 2-hour and 24-hour benefits over monotherapy with each one these options. Recently issued FDA approval for marketing the combination (sumatriptan 50 mg-naproxen 500 mg) emphasizes the usefulness and safety of this new treatment for migraine attacks.

Determining the use of prophylactic antibiotics in breast cancer surgeries: a survey of practice

PubMed Central

2012-01-01

Background Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. Methods An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. Results The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). Conclusion Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery. PMID:22937833

Determining the use of prophylactic antibiotics in breast cancer surgeries: a survey of practice.

PubMed

Acuna, Sergio A; Angarita, Fernando A; Escallon, Jaime; Tawil, Mauricio; Torregrosa, Lilian

2012-08-31

Prophylactic antibiotics (PAs) are beneficial to breast cancer patients undergoing surgery because they prevent surgical site infection (SSI), but limited information regarding their use has been published. This study aims to determine the use of PAs prior to breast cancer surgery amongst breast surgeons in Colombia. An online survey was distributed amongst the breast surgeon members of the Colombian Association of Mastology, the only breast surgery society of Colombia. The scope of the questions included demographics, clinical practice characteristics, PA prescription characteristics, and the use of PAs in common breast surgical procedures. The survey was distributed amongst eighty-eight breast surgeons of whom forty-seven responded (response rate: 53.4%). Forty surgeons (85.1%) reported using PAs prior to surgery of which >60% used PAs during mastectomy, axillary lymph node dissection, and/or breast reconstruction. Surgeons reported they targeted the use of PAs in cases in which patients had any of the following SSI risk factors: diabetes mellitus, drains in situ, obesity, and neoadjuvant therapy. The distribution of the self-reported PA dosing regimens was as follows: single pre-operative fixed-dose (27.7%), single preoperative dose followed by a second dose if the surgery was prolonged (44.7%), single preoperative dose followed by one or more postoperative doses for >24 hours (10.6%), and single preoperative weight-adjusted dose (2.1%). Although this group of breast surgeons is aware of the importance of PAs in breast cancer surgery there is a discrepancy in how they use it, specifically with regards to prescription and timeliness of drug administration. Our findings call for targeted quality-improvement initiatives, such as standardized national guidelines, which can provide sufficient evidence for all stakeholders and therefore facilitate best practice medicine for breast cancer surgery.

Roles of gravitational cues and efference copy signals in the rotational updating of memory saccades.

PubMed

Klier, Eliana M; Angelaki, Dora E; Hess, Bernhard J M

2005-07-01

Primates are able to localize a briefly flashed target despite intervening movements of the eyes, head, or body. This ability, often referred to as updating, requires extraretinal signals related to the intervening movement. With active roll rotations of the head from an upright position it has been shown that the updating mechanism is 3-dimensional, robust, and geometrically sophisticated. Here we examine whether such a rotational updating mechanism operates during passive motion both with and without inertial cues about head/body position in space. Subjects were rotated from either an upright or supine position, about a nasal-occipital axis, briefly shown a world-fixed target, rotated back to their original position, and then asked to saccade to the remembered target location. Using this paradigm, we tested subjects' abilities to update from various tilt angles (0, +/-30, +/-45, +/-90 degrees), to 8 target directions and 2 target eccentricities. In the upright condition, subjects accurately updated the remembered locations from all tilt angles independent of target direction or eccentricity. Slopes of directional errors versus tilt angle ranged from -0.011 to 0.15, and were significantly different from a slope of 1 (no compensation for head-in-space roll) and a slope of 0.9 (no compensation for eye-in-space roll). Because the eyes, head, and body were fixed throughout these passive movements, subjects could not use efference copies or neck proprioceptive cues to assess the amount of tilt, suggesting that vestibular signals and/or body proprioceptive cues suffice for updating. In the supine condition, where gravitational signals could not contribute, slopes ranged from 0.60 to 0.82, indicating poor updating performance. Thus information specifying the body's orientation relative to gravity is critical for maintaining spatial constancy and for distinguishing body-fixed versus world-fixed reference frames.

'Where' and 'what' in visual search.

PubMed

Atkinson, J; Braddick, O J

1989-01-01

A line segment target can be detected among distractors of a different orientation by a fast 'preattentive' process. One view is that this depends on detection of a 'feature gradient', which enables subjects to locate where the target is without necessarily identifying what it is. An alternative view is that a target can be identified as distinctive in a particular 'feature map' without subjects knowing where it is in that map. Experiments are reported in which briefly exposed arrays of line segments were followed by a pattern mask, and the threshold stimulus-mask interval determined for three tasks: 'what'--subjects reported whether the target was vertical or horizontal among oblique distractors; 'coarse where'--subjects reported whether the target was in the upper or lower half of the array; 'fine where'--subjects reported whether or not the target was in a set of four particular array positions. The threshold interval was significantly lower for the 'coarse where' than for the 'what' task, indicating that, even though localization in this task depends on the target's orientation difference, this localization is possible without absolute identification of target orientation. However, for the 'fine where' task, intervals as long as or longer than those for the 'what' task were required. It appears either that different localization processes work at different levels of resolution, or that a single localization process, independent of identification, can increase its resolution at the expense of processing speed. These possibilities are discussed in terms of distinct neural representations of the visual field and fixed or variable localization processes acting upon them.

76 FR 78591 - Corporate Reorganizations; Guidance on the Measurement of Continuity of Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

... determining whether the target shareholders are fully subject to market appreciation and depreciation, certain... circumstances under which the consideration to be exchanged for the proprietary interests in the target... binding contract provides for fixed consideration, the target corporation shareholders can generally be...

The effects of age-in-block on RNA-seq analysis of archival formalin-fixed paraffin-embedded (FFPE) samples

EPA Science Inventory

Archival samples represent a vast resource for identification of chemical and pharmaceutical targets. Previous use of formalin-fixed paraffin-embedded (FFPE) samples has been limited due to changes in RNA introduced by fixation and embedding procedures. Recent advances in RNA-seq...

Single-Receiver GPS Phase Bias Resolution

NASA Technical Reports Server (NTRS)

Bertiger, William I.; Haines, Bruce J.; Weiss, Jan P.; Harvey, Nathaniel E.

2010-01-01

Existing software has been modified to yield the benefits of integer fixed double-differenced GPS-phased ambiguities when processing data from a single GPS receiver with no access to any other GPS receiver data. When the double-differenced combination of phase biases can be fixed reliably, a significant improvement in solution accuracy is obtained. This innovation uses a large global set of GPS receivers (40 to 80 receivers) to solve for the GPS satellite orbits and clocks (along with any other parameters). In this process, integer ambiguities are fixed and information on the ambiguity constraints is saved. For each GPS transmitter/receiver pair, the process saves the arc start and stop times, the wide-lane average value for the arc, the standard deviation of the wide lane, and the dual-frequency phase bias after bias fixing for the arc. The second step of the process uses the orbit and clock information, the bias information from the global solution, and only data from the single receiver to resolve double-differenced phase combinations. It is called "resolved" instead of "fixed" because constraints are introduced into the problem with a finite data weight to better account for possible errors. A receiver in orbit has much shorter continuous passes of data than a receiver fixed to the Earth. The method has parameters to account for this. In particular, differences in drifting wide-lane values must be handled differently. The first step of the process is automated, using two JPL software sets, Longarc and Gipsy-Oasis. The resulting orbit/clock and bias information files are posted on anonymous ftp for use by any licensed Gipsy-Oasis user. The second step is implemented in the Gipsy-Oasis executable, gd2p.pl, which automates the entire process, including fetching the information from anonymous ftp

[Aftercare for durability and profitability of single-unit and multi-unit fixed dental prostheses].

PubMed

de Baat, C; van Loveren, C; van der Maarel-Wierink, C D; Witter, D J; Creugers, N H J

2013-01-01

An important aim ofa treatment with single-unit and multi-unit fixed dental prostheses is a durable and profitable treatment outcome. That requires aftercare, too. First, the frequency of routine oral examinations should be assessed, using an individual risk profile. The objectives of the routine oral examinations are the prevention and, when necessary, the treatment of pathological conditions and complications. With regard to prevention, attention should be paid to information and instruction, oral biofilm and calculus, non-functional activities, hard tooth tissues, periodontal and peri-implant tissues, and saliva. Subsequently, it can be determined whether the intended durability and profitability have been achieved or can still be achieved, whether or not through indicated adjustments. Special attention should be paid to endodontically treated teeth. Restorative, repair or replacement treatments may be indicated in case ofcomplications, such as loose single- or multi-unitfixed dental prosthesis, fracture of a fixed dental prosthesis unit, lost tooth pulp vitality, tooth root fracture, and implant or implant abutment problems.

Antares reference telescope system

NASA Astrophysics Data System (ADS)

Viswanathan, V. K.; Kaprelian, E.; Swann, T.; Parker, J.; Wolfe, P.; Woodfin, G.; Knight, D.

Antares is a 24 beam, 40 TW carbon dioxide laser fusion system currently nearing completion. The 24 beams will be focused onto a tiny target. It is to position the targets to within 10 (SIGMA)m of a selected nominal position, which may be anywhere within a fixed spherical region 1 cm in diameter. The Antares reference telescope system is intended to help achieve this goal for alignment and viewing of the various targets used in the laser system. The Antares reference telescope system consists of two similar electrooptical systems positioned in a near orthogonal manner in the target chamber area of the laser. Each of these consists of four subsystems: (1) a fixed 9% optical imaging subsystem which produces an image of the target at the vidicon; (2) a reticle projection subsystem which superimposes an image of the reticle pattern at the vidicon; (3) an adjustable front lighting subsystem which illuminates the target; and (4) an adjustable back lighting subsystem which also can be used to illuminate the target. The various optical, mechanical, and vidicon design considerations and tradeoffs are discussed. The final system chosen and its current status are described.

Fixed-dose combination and single active ingredient drugs: a comparative cost analysis.

PubMed

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2016-01-01

Fixed-dose combination (FDC) drugs are formulations of two or more active ingredients. To assess the pricing structure and price difference of all US FDA-approved FDCs and single drugs included in the combination. Data were collected from the FDA Orange Book and Drugs@FDA. Average Wholesale Price (AWP) unit price data were derived from The Red Book. The FDA approved 117 FDC. The average AWP difference percentage between the FDC and the sum of the single drugs in the FDC is 84.9 ± 26.2%, and varied by therapeutic class (p < 0.001). The FDC AWP averaged 83.3 ± 23.4% of the single drug AWP sum when there are no generics, and 95.1 ± 42.3% (p < 0.01) when there are two generic single active ingredients in the FDC. The price difference between FDC and single active ingredients in the combination is correlated with the therapeutic class, the year of FDC approval, and the number of single ingredients in the combination that have generics.

Enhancing the reproducibility of ocular vestibular evoked myogenic potentials by use of a visual target originating from a head-mounted laser.

PubMed

Jerin, Claudia; Bartl, Klaus; Schneider, Erich; Gürkov, Robert

2015-10-01

Ocular vestibular evoked myogenic potentials (oVEMPs) represent extraocular muscle activity in response to vestibular stimulation. oVEMP amplitudes are known to increase with increasing upward gaze angle, while the patient fixates a visual target. We investigated two different methods of presenting a visual target during oVEMP recordings. 57 healthy subjects were enrolled in this study. oVEMPs were elicited by 500 Hz air-conducted tone bursts while the subjects were looking upward at a marking which was either fixed on the wall or originated from a head-mounted laser attached to a headband, in either case corresponding to a 35° upward gaze angle. oVEMP amplitudes and latencies did not differ between the subjects looking at the fixed marking and the ones looking at the laser marking. The intra-individual standard deviation of amplitudes obtained by two separate measurements for each subject, however, as a measure of test-retest reliability, was significantly smaller for the laser headband group (0.60) in comparison to the group looking at the fixed marking (0.96; p = 0.007). The intraclass correlation coefficient revealed better test-retest reliability for oVEMP amplitudes when using the laser headband (0.957) than using the fixed marking (0.908). Hence, the use of a visual target originating from a headband enhances the reproducibility of oVEMPs. This might be due to the fact that the laser headband ensures a constant gaze angle and rules out the influence of small involuntary head movements on the gaze angle.

Inter-track interference mitigation with two-dimensional variable equalizer for bit patterned media recording

NASA Astrophysics Data System (ADS)

Wang, Yao; Vijaya Kumar, B. V. K.

2017-05-01

The increased track density in bit patterned media recording (BPMR) causes increased inter-track interference (ITI), which degrades the bit error rate (BER) performance. In order to mitigate the effect of the ITI, signals from multiple tracks can be equalized by a 2D equalizer with 1D target. Usually, the 2D fixed equalizer coefficients are obtained by using a pseudo-random bit sequence (PRBS) for training. In this study, a 2D variable equalizer is proposed, where various sets of 2D equalizer coefficients are predetermined and stored for different ITI patterns besides the usual PRBS training. For data detection, as the ITI patterns are unknown in the first global iteration, the main and adjacent tracks are equalized with the conventional 2D fixed equalizer, detected with Bahl-Cocke-Jelinek-Raviv (BCJR) detector and decoded with low-density parity-check (LDPC) decoder. Then using the estimated bit information from main and adjacent tracks, the ITI pattern for each island of the main track can be estimated and the corresponding 2D variable equalizers are used to better equalize the bits on the main track. This process is executed iteratively by feeding back the main track information. Simulation results indicate that for both single-track and two-track detection, the proposed 2D variable equalizer can achieve better BER and frame error rate (FER) compared to that with the 2D fixed equalizer.

Design of microarray experiments for genetical genomics studies.

PubMed

Bueno Filho, Júlio S S; Gilmour, Steven G; Rosa, Guilherme J M

2006-10-01

Microarray experiments have been used recently in genetical genomics studies, as an additional tool to understand the genetic mechanisms governing variation in complex traits, such as for estimating heritabilities of mRNA transcript abundances, for mapping expression quantitative trait loci, and for inferring regulatory networks controlling gene expression. Several articles on the design of microarray experiments discuss situations in which treatment effects are assumed fixed and without any structure. In the case of two-color microarray platforms, several authors have studied reference and circular designs. Here, we discuss the optimal design of microarray experiments whose goals refer to specific genetic questions. Some examples are used to illustrate the choice of a design for comparing fixed, structured treatments, such as genotypic groups. Experiments targeting single genes or chromosomic regions (such as with transgene research) or multiple epistatic loci (such as within a selective phenotyping context) are discussed. In addition, microarray experiments in which treatments refer to families or to subjects (within family structures or complex pedigrees) are presented. In these cases treatments are more appropriately considered to be random effects, with specific covariance structures, in which the genetic goals relate to the estimation of genetic variances and the heritability of transcriptional abundances.

Visual-search models for location-known detection tasks

NASA Astrophysics Data System (ADS)

Gifford, H. C.; Karbaschi, Z.; Banerjee, K.; Das, M.

2017-03-01

Lesion-detection studies that analyze a fixed target position are generally considered predictive of studies involving lesion search, but the extent of the correlation often goes untested. The purpose of this work was to develop a visual-search (VS) model observer for location-known tasks that, coupled with previous work on localization tasks, would allow efficient same-observer assessments of how search and other task variations can alter study outcomes. The model observer featured adjustable parameters to control the search radius around the fixed lesion location and the minimum separation between suspicious locations. Comparisons were made against human observers, a channelized Hotelling observer and a nonprewhitening observer with eye filter in a two-alternative forced-choice study with simulated lumpy background images containing stationary anatomical and quantum noise. These images modeled single-pinhole nuclear medicine scans with different pinhole sizes. When the VS observer's search radius was optimized with training images, close agreement was obtained with human-observer results. Some performance differences between the humans could be explained by varying the model observer's separation parameter. The range of optimal pinhole sizes identified by the VS observer was in agreement with the range determined with the channelized Hotelling observer.

48 CFR 49.115 - Settlement of terminated incentive contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Revision—Firm Target, and 52.249-2, Termination for Convenience of the Government (Fixed-Price). (1... Price Revision—Firm Target, or paragraph (1) of the clause at 52.216-17, Incentive Price Revision—Successive Targets. The contracting officer shall apply the incentive price revision provisions to completed...

48 CFR 32.503-9 - Liquidation rates-alternate method.

Code of Federal Regulations, 2011 CFR

2011-10-01

... with the successive changes to the contract price or target profit when— (i) The target profit is changed under a fixed-price incentive contract with successive targets; or (ii) A redetermined price... modification to specify the new rate in the Progress Payments clause. Adequate consideration for these contract...

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines.

PubMed

Li, Ruijie; Wang, Meng; Yao, Jiwei; Liang, Shanshan; Liao, Xiang; Yang, Mengke; Zhang, Jianxiong; Yan, Junan; Jia, Hongbo; Chen, Xiaowei; Li, Xingyi

2018-01-01

In vivo two-photon Ca 2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca 2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca 2+ indicators, we recorded the Ca 2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca 2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors.

Two-Photon Functional Imaging of the Auditory Cortex in Behaving Mice: From Neural Networks to Single Spines

PubMed Central

Li, Ruijie; Wang, Meng; Yao, Jiwei; Liang, Shanshan; Liao, Xiang; Yang, Mengke; Zhang, Jianxiong; Yan, Junan; Jia, Hongbo; Chen, Xiaowei; Li, Xingyi

2018-01-01

In vivo two-photon Ca2+ imaging is a powerful tool for recording neuronal activities during perceptual tasks and has been increasingly applied to behaving animals for acute or chronic experiments. However, the auditory cortex is not easily accessible to imaging because of the abundant temporal muscles, arteries around the ears and their lateral locations. Here, we report a protocol for two-photon Ca2+ imaging in the auditory cortex of head-fixed behaving mice. By using a custom-made head fixation apparatus and a head-rotated fixation procedure, we achieved two-photon imaging and in combination with targeted cell-attached recordings of auditory cortical neurons in behaving mice. Using synthetic Ca2+ indicators, we recorded the Ca2+ transients at multiple scales, including neuronal populations, single neurons, dendrites and single spines, in auditory cortex during behavior. Furthermore, using genetically encoded Ca2+ indicators (GECIs), we monitored the neuronal dynamics over days throughout the process of associative learning. Therefore, we achieved two-photon functional imaging at multiple scales in auditory cortex of behaving mice, which extends the tool box for investigating the neural basis of audition-related behaviors. PMID:29740289

Dynamic analysis of fixed-free single-walled carbon nanotube-based bio-sensors because of various viruses.

PubMed

Gupta, A; Joshi, A Y; Sharma, S C; Harsha, S P

2012-09-01

In the present study, the vibrations of the fixed-free single-walled carbon nanotube (SWCNT) with attached bacterium/virus on the tip have been investigated. To explore the suitability of the SWCNT as a bacterium/virus detector device, first the various types of virus have been taken for the study and then the resonant frequencies of fixed-free SWCNT with attachment of those viruses have been simulated. These resonant frequencies are compared with the published analytical data, and it is shown that the finite element method (FEM) simulation results are in good agreement with the analytical data. The results showed the sensitivity and suitability of the SWCNT having different length and different masses (attached at the tip SWCNT) to identify the bacterium or virus.

Fixation and chemical analysis of single fog and rain droplets

NASA Astrophysics Data System (ADS)

Kasahara, M.; Akashi, S.; Ma, C.-J.; Tohno, S.

Last decade, the importance of global environmental problems has been recognized worldwide. Acid rain is one of the most important global environmental problems as well as the global warming. The grasp of physical and chemical properties of fog and rain droplets is essential to make clear the physical and chemical processes of acid rain and also their effects on forests, materials and ecosystems. We examined the physical and chemical properties of single fog and raindrops by applying fixation technique. The sampling method and treatment procedure to fix the liquid droplets as a solid particle were investigated. Small liquid particles like fog droplet could be easily fixed within few minutes by exposure to cyanoacrylate vapor. The large liquid particles like raindrops were also fixed successively, but some of them were not perfect. Freezing method was applied to fix the large raindrops. Frozen liquid particles existed stably by exposure to cyanoacrylate vapor after freezing. The particle size measurement and the elemental analysis of the fixed particle were performed in individual base using microscope, and SEX-EDX, particle-induced X-ray emission (PIXE) and micro-PIXE analyses, respectively. The concentration in raindrops was dependent upon the droplet size and the elapsed time from the beginning of rainfall.

Targeted Coagulation Management in Severe Trauma: The Controversies and the Evidence.

PubMed

Winearls, James; Reade, Michael; Miles, Helen; Bulmer, Andrew; Campbell, Don; Görlinger, Klaus; Fraser, John F

2016-10-01

Hemorrhage in the setting of severe trauma is a leading cause of death worldwide. The pathophysiology of hemorrhage and coagulopathy in severe trauma is complex and remains poorly understood. Most clinicians currently treating trauma patients acknowledge the presence of a coagulopathy unique to trauma patients-trauma-induced coagulopathy (TIC)-independently associated with increased mortality. The complexity and incomplete understanding of TIC has resulted in significant controversy regarding optimum management. Although the majority of trauma centers utilize fixed-ratio massive transfusion protocols in severe traumatic hemorrhage, a widely accepted "ideal" transfusion ratio of blood to blood products remains elusive. The recent use of viscoelastic hemostatic assays (VHAs) to guide blood product replacement has further provoked debate as to the optimum transfusion strategy. The use of VHA to quantify the functional contributions of individual components of the coagulation system may permit targeted treatment of TIC but remains controversial and is unlikely to demonstrate a mortality benefit in light of the heterogeneity of the trauma population. Thus, VHA-guided algorithms as an alternative to fixed product ratios in trauma are not universally accepted, and a hybrid strategy starting with fixed-ratio transfusion and incorporating VHA data as they become available is favored by some institutions. We review the current evidence for the management of coagulopathy in trauma, the rationale behind the use of targeted and fixed-ratio approaches and explore future directions.

Why to Treat Subjects as Fixed Effects

ERIC Educational Resources Information Center

Adelman, James S.; Estes, Zachary

2015-01-01

Adelman, Marquis, Sabatos-DeVito, and Estes (2013) collected word naming latencies from 4 participants who read 2,820 words 50 times each. Their recommendation and practice was that R2 targets set for models should take into account subject idiosyncrasies as replicable patterns, equivalent to a subjects-as-fixed-effects assumption. In light of an…

Diffractively Produced Charm Final States in 800-GeV / c pp Collisions

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

Wang, M. H. L. S.; Berisso, M. C.; Christian, D. C.

We report the first observation of diffractively produced open charm in 800-GeV/c pp collisions of the type pp{yields}pD{sup *}X. We measure cross sections of {sigma}{sub diff}(D{sup *+})= (0.185{+-}0.044{+-}0.054) {mu}b and {sigma}{sub diff}(D{sup *-})= (0.174{+-}0.034{+-}0.029) {mu}b. Our measurements are based on 4.3 x 10{sup 9} events recorded by FNAL E690 in the fixed-target run of 1991. We compare our results with previous fixed-target charm experiments.

Is fixed combination therapy appropriate for initial hypertension treatment?

PubMed

Elliott, William J

2002-08-01

Recent clinical trials in hypertension prove how seldom single drug therapy achieves target blood pressure (BP) and reduces cardiovascular morbidity and mortality. A natural response is the testing and marketing of fixed-dose combination products for hypertension, of which 14 have been approved in the United States since 1993. Currently, only five products are indicated by the Food and Drug Administration for initial therapy of hypertension; all include a diuretic. To achieve such an indication, studies must show not only safety and efficacy of the combination, but also BP lowering that is at least additive compared with the two agents given separately, as well as a "synergy" not present when each agent is given alone. Some advantages to initial combination therapy include greater BP reduction, improved adherence to pill taking, fewer side effects, and lower cost. The most likely candidates for initial combination therapy are patients with initial BP higher than 160/100 mm Hg, or those with a BP goal lower than the customary 140/90 mm Hg. These include patients with target organ damage, clinical cardiovascular disease, proteinuria, renal impairment, or diabetes mellitus. In many of these circumstances, an angiotensin converting enzyme inhibitor or angiotensin II receptor antagonist is frequently recommended; adding a diuretic or calcium antagonist to it is much more likely to result in achievement of the BP goal. More research is being done to explore the combination of not only two representatives from classes of conventional agents, but also other drugs that may help address the multiple manifestations of the "metabolic syndrome" that often accompanies hypertension.

Clinical utility of an automated instrument for gram staining single slides.

PubMed

Baron, Ellen Jo; Mix, Samantha; Moradi, Wais

2010-06-01

Gram stains of 87 different clinical samples were prepared by the laboratory's conventional methods (automated or manual) and by a new single-slide-type automated staining instrument, GG&B AGS-1000. Gram stains from either heat- or methanol-fixed slides stained with the new instrument were easy to interpret, and results were essentially the same as those from the methanol-fixed slides prepared as a part of the routine workflow. This instrument is well suited to a rapid-response laboratory where Gram stain requests are commonly received on a stat basis.

Targeted traction of impacted teeth with C-tube miniplates.

PubMed

Chung, Kyu-Rhim; Kim, Yong; Ahn, Hyo-Won; Lee, Dongjoo; Yang, Dong-Min; Kim, Seong-Hun; Nelson, Gerald

2014-09-01

Orthodontic traction of impacted teeth has typically been performed using full fixed appliance as anchorage against the traction force. This conventional approach can be difficult to apply in the mixed dentition if the partial fixed appliance offers an insufficient anchor unit. In addition, full fixed appliance can induce unwanted movement of adjacent teeth. This clinical report presents 3 cases where impacted teeth were recovered in the mixed or transitional dentition with skeletal anchorage on the opposite arch without full fixed appliance. Instead, intermaxillary traction was used to bring the impacted teeth into position. With this approach, side effects on teeth and periodontal tissues adjacent to the impaction were minimized.

SIMSISH Technique Does Not Alter the Apparent Isotopic Composition of Bacterial Cells

PubMed Central

Chapleur, Olivier; Wu, Ting-Di; Guerquin-Kern, Jean-Luc; Mazéas, Laurent; Bouchez, Théodore

2013-01-01

In order to identify the function of uncultured microorganisms in their environment, the SIMSISH method, combining in situ hybridization (ISH) and nanoscale secondary ion mass spectrometry (nanoSIMS) imaging, has been proposed to determine the quantitative uptake of specific labelled substrates by uncultured microbes at the single cell level. This technique requires the hybridization of rRNA targeted halogenated DNA probes on fixed and permeabilized microorganisms. Exogenous atoms are introduced into cells and endogenous atoms removed during the experimental procedures. Consequently differences between the original and the apparent isotopic composition of cells may occur. In the present study, the influence of the experimental procedures of SIMSISH on the isotopic composition of carbon in E. coli cells was evaluated with nanoSIMS and compared to elemental analyser-isotopic ratio mass spectrometer (EA-IRMS) measurements. Our results show that fixation and hybridization have a very limited, reproducible and homogeneous influence on the isotopic composition of cells. Thereby, the SIMSISH procedure minimizes the contamination of the sample by exogenous atoms, thus providing a means to detect the phylogenetic identity and to measure precisely the carbon isotopic composition at the single cell level. This technique was successfully applied to a complex sample with double bromine – iodine labelling targeting a large group of bacteria and a specific archaea to evaluate their specific 13C uptake during labelled methanol anaerobic degradation. PMID:24204855

A stereotaxic method of recording from single neurons in the intact in vivo eye of the cat.

PubMed

Molenaar, J; Van de Grind, W A

1980-04-01

A method is described for recording stereotaxically from single retinal neurons in the optically intact in vivo eye of the cat. The method is implemented with the help of a new type of stereotaxic instrument and a specially developed stereotaxic atlas of the cat's eye and retina. The instrument is extremely stable and facilitates intracellular recording from retinal neurons. The microelectrode can be rotated about two mutually perpendicular axes, which intersect in the freely positionable pivot point of the electrode manipulation system. When the pivot point is made to coincide with a small electrode-entrance hole in the sclera of the eye, a large retinal region can be reached through this fixed hole in the immobilized eye. The stereotaxic method makes it possible to choose a target point on the presented eye atlas and predict the settings of the instrument necessary to reach this target. This method also includes the prediction of the corresponding light stimulus position on a tangent screen and the calculation of the projection of the recording electrode on this screen. The sources of error in the method were studied experimentally and a numerical perturbation analysis was carried out to study the influence of each of the sources of error on the final result. The overall accuracy of the method is of the order of 5 degrees of visual angle, which will be sufficient for most purposes.

In vitro biomechanical comparison after fixed- and mobile-core artificial cervical disc replacement versus fusion

PubMed Central

Lou, Jigang; Li, Yuanchao; Wang, Beiyu; Meng, Yang; Wu, Tingkui; Liu, Hao

2017-01-01

Abstract In vitro biomechanical analysis after cervical disc replacement (CDR) with a novel artificial disc prosthesis (mobile core) was conducted and compared with the intact model, simulated fusion, and CDR with a fixed-core prosthesis. The purpose of this experimental study was to analyze the biomechanical changes after CDR with a novel prosthesis and the differences between fixed- and mobile-core prostheses. Six human cadaveric C2–C7 specimens were biomechanically tested sequentially in 4 different spinal models: intact specimens, simulated fusion, CDR with a fixed-core prosthesis (Discover, DePuy), and CDR with a mobile-core prosthesis (Pretic-I, Trauson). Moments up to 2 Nm with a 75 N follower load were applied in flexion–extension, left and right lateral bending, and left and right axial rotation. The total range of motion (ROM), segmental ROM, and adjacent intradiscal pressure (IDP) were calculated and analyzed in 4 different spinal models, as well as the differences between 2 disc prostheses. Compared with the intact specimens, the total ROM, segmental ROM, and IDP at the adjacent segments showed no significant difference after arthroplasty. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment (C5/6) and total ROM than CDR with a fixed-core prosthesis (P > .05). Besides, the difference in IDP at C4/5 after CDR with 2 prostheses was without statistical significance in all the directions of motion. However, the IDP at C6/7 after CDR with a mobile-core prosthesis was lower than CDR with a fixed-core prosthesis in flexion, extension, and lateral bending, with significant difference (P < .05), but not under axial rotation. CDR with a novel prosthesis was effective to maintain the ROM at the target segment and did not affect the ROM and IDP at the adjacent segments. Moreover, CDR with a mobile-core prosthesis presented a little higher values of target segment and total ROM, but lower IDP at the inferior adjacent segment than CDR with a fixed-core prosthesis. PMID:29019902

FIXED-BED HYDROGENATION OF ORGANIC COMPOUNDS IN SUPERCRITICAL CARBON DIOXIDE. (R826034)

EPA Science Inventory

Abstract

The Pd/C hydrogenation of cyclohexene to cyclohexane was performed in a continuous fixed-bed reactor employing CO₂ to solubilize the reaction mixture in a single supercritical (sc) phase surrounding the solid catalyst. Employing an equimolar feed of...

Design of a multi-arm randomized clinical trial with no control arm.

PubMed

Magaret, Amalia; Angus, Derek C; Adhikari, Neill K J; Banura, Patrick; Kissoon, Niranjan; Lawler, James V; Jacob, Shevin T

2016-01-01

Clinical trial designs that include multiple treatments are currently limited to those that perform pairwise comparisons of each investigational treatment to a single control. However, there are settings, such as the recent Ebola outbreak, in which no treatment has been demonstrated to be effective; and therefore, no standard of care exists which would serve as an appropriate control. For illustrative purposes, we focused on the care of patients presenting in austere settings with critically ill 'sepsis-like' syndromes. Our approach involves a novel algorithm for comparing mortality among arms without requiring a single fixed control. The algorithm allows poorly-performing arms to be dropped during interim analyses. Consequently, the study may be completed earlier than planned. We used simulation to determine operating characteristics for the trial and to estimate the required sample size. We present a potential study design targeting a minimal effect size of a 23% relative reduction in mortality between any pair of arms. Using estimated power and spurious significance rates from the simulated scenarios, we show that such a trial would require 2550 participants. Over a range of scenarios, our study has 80 to 99% power to select the optimal treatment. Using a fixed control design, if the control arm is least efficacious, 640 subjects would be enrolled into the least efficacious arm, while our algorithm would enroll between 170 and 430. This simulation method can be easily extended to other settings or other binary outcomes. Early dropping of arms is efficient and ethical when conducting clinical trials with multiple arms. Copyright © 2015 Elsevier Inc. All rights reserved.

26 CFR 1.368-1T - Purpose and scope of exception of reorganization exchanges (temporary).

Code of Federal Regulations, 2011 CFR

2011-04-01

.... In determining whether a proprietary interest in the target corporation is preserved, the consideration to be exchanged for the proprietary interests in the target corporation pursuant to a contract to... interest in the target corporation is preserved. If the contract does not provide for fixed consideration...

26 CFR 1.368-1T - Purpose and scope of exception of reorganization exchanges (temporary).

Code of Federal Regulations, 2010 CFR

2010-04-01

.... In determining whether a proprietary interest in the target corporation is preserved, the consideration to be exchanged for the proprietary interests in the target corporation pursuant to a contract to... interest in the target corporation is preserved. If the contract does not provide for fixed consideration...

Locations of serial reach targets are coded in multiple reference frames.

PubMed

Thompson, Aidan A; Henriques, Denise Y P

2010-12-01

Previous work from our lab, and elsewhere, has demonstrated that remembered target locations are stored and updated in an eye-fixed reference frame. That is, reach errors systematically vary as a function of gaze direction relative to a remembered target location, not only when the target is viewed in the periphery (Bock, 1986, known as the retinal magnification effect), but also when the target has been foveated, and the eyes subsequently move after the target has disappeared but prior to reaching (e.g., Henriques, Klier, Smith, Lowy, & Crawford, 1998; Sorrento & Henriques, 2008; Thompson & Henriques, 2008). These gaze-dependent errors, following intervening eye movements, cannot be explained by representations whose frame is fixed to the head, body or even the world. However, it is unknown whether targets presented sequentially would all be coded relative to gaze (i.e., egocentrically/absolutely), or if they would be coded relative to the previous target (i.e., allocentrically/relatively). It might be expected that the reaching movements to two targets separated by 5° would differ by that distance. But, if gaze were to shift between the first and second reaches, would the movement amplitude between the targets differ? If the target locations are coded allocentrically (i.e., the location of the second target coded relative to the first) then the movement amplitude should be about 5°. But, if the second target is coded egocentrically (i.e., relative to current gaze direction), then the reaches to this target and the distances between the subsequent movements should vary systematically with gaze as described above. We found that requiring an intervening saccade to the opposite side of 2 briefly presented targets between reaches to them resulted in a pattern of reaching error that systematically varied as a function of the distance between current gaze and target, and led to a systematic change in the distance between the sequential reach endpoints as predicted by an egocentric frame anchored to the eye. However, the amount of change in this distance was smaller than predicted by a pure eye-fixed representation, suggesting that relative positions of the targets or allocentric coding was also used in sequential reach planning. The spatial coding and updating of sequential reach target locations seems to rely on a combined weighting of multiple reference frames, with one of them centered on the eye. Copyright © 2010 Elsevier Ltd. All rights reserved.

Exploration of mechanisms underlying the strain-rate-dependent mechanical property of single chondrocytes

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

Nguyen, Trung Dung; Gu, YuanTong, E-mail: yuantong.gu@qut.edu.au

2014-05-05

Based on the characterization by Atomic Force Microscopy, we report that the mechanical property of single chondrocytes has dependency on the strain-rates. By comparing the mechanical deformation responses and the Young's moduli of living and fixed chondrocytes at four different strain-rates, we explore the deformation mechanisms underlying this dependency property. We found that the strain-rate-dependent mechanical property of living cells is governed by both of the cellular cytoskeleton and the intracellular fluid when the fixed chondrocytes are mainly governed by their intracellular fluid, which is called the consolidation-dependent deformation behavior. Finally, we report that the porohyperelastic constitutive material model whichmore » can capture the consolidation-dependent behavior of both living and fixed chondrocytes is a potential candidature to study living cell biomechanics.« less

What top-down task sets do for us: an ERP study on the benefits of advance preparation in visual search.

PubMed

Eimer, Martin; Kiss, Monika; Nicholas, Susan

2011-12-01

When target-defining features are specified in advance, attentional target selection in visual search is controlled by preparatory top-down task sets. We used ERP measures to study voluntary target selection in the absence of such feature-specific task sets, and to compare it to selection that is guided by advance knowledge about target features. Visual search arrays contained two different color singleton digits, and participants had to select one of these as target and report its parity. Target color was either known in advance (fixed color task) or had to be selected anew on each trial (free color-choice task). ERP correlates of spatially selective attentional target selection (N2pc) and working memory processing (SPCN) demonstrated rapid target selection and efficient exclusion of color singleton distractors from focal attention and working memory in the fixed color task. In the free color-choice task, spatially selective processing also emerged rapidly, but selection efficiency was reduced, with nontarget singleton digits capturing attention and gaining access to working memory. Results demonstrate the benefits of top-down task sets: Feature-specific advance preparation accelerates target selection, rapidly resolves attentional competition, and prevents irrelevant events from attracting attention and entering working memory.

Perspective of Muon Production Target at J-PARC MLF MUSE

NASA Astrophysics Data System (ADS)

Makimura, Shunsuke; Matoba, Shiro; Kawamura, Naritoshi; Matsuzawa, Yukihiro; Tabe, Masato; Aoyagi, Hiroyuki; Kondo, Hiroto; Kobayashi, Yasuo; Fujimori, Hiroshi; Ikedo, Yutaka; Kadono, Ryosuke; Koda, Akihiro; Kojima, Kenji M.; Miyake, Yasuhiro; Nakamura, Jumpei G.; Oishi, Yu; Okabe, Hirotaka; Shimomura, Koichiro; Strasser, Patrick

A pulsed muon beam with unprecedented intensity will be generated by a 3-GeV 333-microA proton beam on a muon target made of 20-mm thick isotropic graphite at J-PARC MLF MUSE (Muon Science Establishment). The first muon beam was successfully generated on September 26th, 2008. Gradually upgrading the beam intensity, continuous 300-kW proton beam has been operated by a fixed target method without replacements till June of 2014. However, the lifetime of the fixed target was anticipated to be less than 1 year by the proton-irradiation damage of the graphite through 1-MW beam operation. To extend the lifetime, a muon rotating target, in which the radiation damage is distributed to a wider area, was installed in September of 2014, and continuous and stable operation has been successfully performed. Because the muon target becomes highly radioactive by the proton irradiation, the maintenance is conducted by remote handling in the Hot cell. In September of 2015, a scraper No. 1 to collimate the proton beam scattered by the target was replaced for further high-power beam operation. Recently, new developments on monitoring and maintenance of the muon target for higher power operation are in progress. In this article, perspective of muon production target at J-PARC MLF MUSE will be described.

Designing manufacturable filters for a 16-band plenoptic camera using differential evolution

NASA Astrophysics Data System (ADS)

Doster, Timothy; Olson, Colin C.; Fleet, Erin; Yetzbacher, Michael; Kanaev, Andrey; Lebow, Paul; Leathers, Robert

2017-05-01

A 16-band plenoptic camera allows for the rapid exchange of filter sets via a 4x4 filter array on the lens's front aperture. This ability to change out filters allows for an operator to quickly adapt to different locales or threat intelligence. Typically, such a system incorporates a default set of 16 equally spaced at-topped filters. Knowing the operating theater or the likely targets of interest it becomes advantageous to tune the filters. We propose using a modified beta distribution to parameterize the different possible filters and differential evolution (DE) to search over the space of possible filter designs. The modified beta distribution allows us to jointly optimize the width, taper and wavelength center of each single- or multi-pass filter in the set over a number of evolutionary steps. Further, by constraining the function parameters we can develop solutions which are not just theoretical but manufacturable. We examine two independent tasks: general spectral sensing and target detection. In the general spectral sensing task we utilize the theory of compressive sensing (CS) and find filters that generate codings which minimize the CS reconstruction error based on a fixed spectral dictionary of endmembers. For the target detection task and a set of known targets, we train the filters to optimize the separation of the background and target signature. We compare our results to the default 16 at-topped non-overlapping filter set which comes with the plenoptic camera and full hyperspectral resolution data which was previously acquired.

The Athena Microscopic Imager on the Mars Exploration Rovers

NASA Astrophysics Data System (ADS)

Herkenhoff, K. E.; Squyres, S. W.; Bell, J. F.; Maki, J. N.; Schwochert, M. A.

2002-12-01

The Athena science payload on the Mars Exploration Rovers (MER) includes the Microscopic Imager (MI). The MI is a fixed-focus camera mounted on the end of the Instrument Deployment Device (IDD). The MI was designed to acquire images at a spatial resolution of 30 microns/pixel over a broad spectral range (400-700 nm). Technically speaking, the ''microscopic'' imager is not a microscope: it has a fixed magnification of 0.4, and is intended to produce images that simulate a geologist's view when using a common hand lens. The MI uses the same electronics design as the other MER cameras, but has optics that yield a field of view of 31 x 31 mm. The MI will acquire images using only solar or skylight illumination of the target surface. A contact sensor will be used to place the MI slightly closer to the target surface than its best focus distance (about 66 mm), allowing concave surfaces to be imaged in good focus. Because the MI has a relatively small depth of field (+/- 3 mm), a single MI image of a rough surface will contain both focused and unfocused areas. Coarse (~2 mm precision) focusing will be achieved by moving the IDD away from a target after the contact sensor is activated. Multiple images taken at various distances will be acquired to ensure good focus on all parts of rough surfaces. By combining a set of images acquired in this way, a completely focused image will be assembled. The MI optics will be protected from the martian environment by a dust cover. The dust cover includes a polycarbonate window that is tinted yellow to restrict the spectral bandpass to 500-700 nm and allow color information to be obtained by taking images with the dust cover open and closed. The MI will be used to image the same materials measured by other Athena instruments, as well as targets of opportunity (before rover traverses). The resulting images will be used to place other instrumental data in context and to aid in the petrologic interpretation of rocks and soils on Mars.

Bar coded retroreflective target

DOEpatents

Vann, Charles S.

2000-01-01

This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

Mapping a multiplexed zoo of mRNA expression.

PubMed

Choi, Harry M T; Calvert, Colby R; Husain, Naeem; Huss, David; Barsi, Julius C; Deverman, Benjamin E; Hunter, Ryan C; Kato, Mihoko; Lee, S Melanie; Abelin, Anna C T; Rosenthal, Adam Z; Akbari, Omar S; Li, Yuwei; Hay, Bruce A; Sternberg, Paul W; Patterson, Paul H; Davidson, Eric H; Mazmanian, Sarkis K; Prober, David A; van de Rijn, Matt; Leadbetter, Jared R; Newman, Dianne K; Readhead, Carol; Bronner, Marianne E; Wold, Barbara; Lansford, Rusty; Sauka-Spengler, Tatjana; Fraser, Scott E; Pierce, Niles A

2016-10-01

In situ hybridization methods are used across the biological sciences to map mRNA expression within intact specimens. Multiplexed experiments, in which multiple target mRNAs are mapped in a single sample, are essential for studying regulatory interactions, but remain cumbersome in most model organisms. Programmable in situ amplifiers based on the mechanism of hybridization chain reaction (HCR) overcome this longstanding challenge by operating independently within a sample, enabling multiplexed experiments to be performed with an experimental timeline independent of the number of target mRNAs. To assist biologists working across a broad spectrum of organisms, we demonstrate multiplexed in situ HCR in diverse imaging settings: bacteria, whole-mount nematode larvae, whole-mount fruit fly embryos, whole-mount sea urchin embryos, whole-mount zebrafish larvae, whole-mount chicken embryos, whole-mount mouse embryos and formalin-fixed paraffin-embedded human tissue sections. In addition to straightforward multiplexing, in situ HCR enables deep sample penetration, high contrast and subcellular resolution, providing an incisive tool for the study of interlaced and overlapping expression patterns, with implications for research communities across the biological sciences. © 2016. Published by The Company of Biologists Ltd.

Mapping a multiplexed zoo of mRNA expression

PubMed Central

Choi, Harry M. T.; Calvert, Colby R.; Husain, Naeem; Huss, David; Barsi, Julius C.; Deverman, Benjamin E.; Hunter, Ryan C.; Kato, Mihoko; Lee, S. Melanie; Abelin, Anna C. T.; Rosenthal, Adam Z.; Akbari, Omar S.; Li, Yuwei; Hay, Bruce A.; Sternberg, Paul W.; Patterson, Paul H.; Davidson, Eric H.; Mazmanian, Sarkis K.; Prober, David A.; van de Rijn, Matt; Leadbetter, Jared R.; Newman, Dianne K.; Readhead, Carol; Bronner, Marianne E.; Wold, Barbara; Lansford, Rusty; Sauka-Spengler, Tatjana; Fraser, Scott E.

2016-01-01

In situ hybridization methods are used across the biological sciences to map mRNA expression within intact specimens. Multiplexed experiments, in which multiple target mRNAs are mapped in a single sample, are essential for studying regulatory interactions, but remain cumbersome in most model organisms. Programmable in situ amplifiers based on the mechanism of hybridization chain reaction (HCR) overcome this longstanding challenge by operating independently within a sample, enabling multiplexed experiments to be performed with an experimental timeline independent of the number of target mRNAs. To assist biologists working across a broad spectrum of organisms, we demonstrate multiplexed in situ HCR in diverse imaging settings: bacteria, whole-mount nematode larvae, whole-mount fruit fly embryos, whole-mount sea urchin embryos, whole-mount zebrafish larvae, whole-mount chicken embryos, whole-mount mouse embryos and formalin-fixed paraffin-embedded human tissue sections. In addition to straightforward multiplexing, in situ HCR enables deep sample penetration, high contrast and subcellular resolution, providing an incisive tool for the study of interlaced and overlapping expression patterns, with implications for research communities across the biological sciences. PMID:27702788

Fixed and equilibrium endpoint problems in uneven-aged stand management

Treesearch

Robert G. Haight; Wayne M. Getz

1987-01-01

Studies in uneven-aged management have concentrated on the determination of optimal steady-state diameter distribution harvest policies for single and mixed species stands. To find optimal transition harvests for irregular stands, either fixed endpoint or equilibrium endpoint constraints can be imposed after finite transition periods. Penalty function and gradient...

Testing for Additivity in Chemical Mixtures Using a Fixed-Ratio Ray Design and Statistical Equivalence Testing Methods

EPA Science Inventory

Fixed-ratio ray designs have been used for detecting and characterizing interactions of large numbers of chemicals in combination. Single chemical dose-response data are used to predict an “additivity curve” along an environmentally relevant ray. A “mixture curve” is estimated fr...

PCC Framework for Program-Generators

NASA Technical Reports Server (NTRS)

Kong, Soonho; Choi, Wontae; Yi, Kwangkeun

2009-01-01

In this paper, we propose a proof-carrying code framework for program-generators. The enabling technique is abstract parsing, a static string analysis technique, which is used as a component for generating and validating certificates. Our framework provides an efficient solution for certifying program-generators whose safety properties are expressed in terms of the grammar representing the generated program. The fixed-point solution of the analysis is generated and attached with the program-generator on the code producer side. The consumer receives the code with a fixed-point solution and validates that the received fixed point is indeed a fixed point of the received code. This validation can be done in a single pass.

Flight Management System Execution of Idle-Thrust Descents in Operations

NASA Technical Reports Server (NTRS)

Stell, Laurel L.

2011-01-01

To enable arriving aircraft to fly optimized descents computed by the flight management system (FMS) in congested airspace, ground automation must accurately predict descent trajectories. To support development of the trajectory predictor and its error models, commercial flights executed idle-thrust descents, and the recorded data includes the target speed profile and FMS intent trajectories. The FMS computes the intended descent path assuming idle thrust after top of descent (TOD), and any intervention by the controllers that alters the FMS execution of the descent is recorded so that such flights are discarded from the analysis. The horizontal flight path, cruise and meter fix altitudes, and actual TOD location are extracted from the radar data. Using more than 60 descents in Boeing 777 aircraft, the actual speeds are compared to the intended descent speed profile. In addition, three aspects of the accuracy of the FMS intent trajectory are analyzed: the meter fix crossing time, the TOD location, and the altitude at the meter fix. The actual TOD location is within 5 nmi of the intent location for over 95% of the descents. Roughly 90% of the time, the airspeed is within 0.01 of the target Mach number and within 10 KCAS of the target descent CAS, but the meter fix crossing time is only within 50 sec of the time computed by the FMS. Overall, the aircraft seem to be executing the descents as intended by the designers of the onboard automation.

Preparation of a primary argon beam for the CERN fixed target physics.

PubMed

Küchler, D; O'Neil, M; Scrivens, R; Thomae, R

2014-02-01

The fixed target experiment NA61 in the North Area of the Super Proton Synchrotron is studying phase transitions in strongly interacting matter. Up to now they used the primary beams available from the CERN accelerator complex (protons and lead ions) or fragmented beams created from the primary lead ion beam. To explore a wider range of energies and densities a request was made to provide primary argon and xenon beams. This paper describes the results of the setting up and 10 week test run of the Ar(11+) beam from the 14.5 GHz ECR ion source and the linear accelerator (Linac3) at CERN.

Studies of the horizontal vestibulo-ocular reflex on STS 7 and 8

NASA Technical Reports Server (NTRS)

Thornton, William E.; Uri, John J.; Moore, Thomas P.; Pool, Sam L.

1988-01-01

Unpaced voluntary horizontal head oscillation was used to study the Vestibulo-Ocular Reflex (VOR) on Shuttle flights STS 7 and 8. Ten subjects performed head oscillations at 0.33 Hz + or - 30 deg amplitude under the followng conditions: VVOR (visual VOR), eyes open and fixed on a stationary target; VOR-EC, with eyes closed and fixed on the same target in imagination; and VOR-S (VOR suppression), with eyes open and fixed on a head-synchronized target. Effects of weightlessness, flight phase, and Space Motion Sickness (SMS) on head oscillation characteristics were examined. A significant increase in head oscillation frequency was noted inflight in subjects free from SMS. In subjects susceptible to SMS, frequency was reduced during their Symptomatic period. The data also suggest that the amplitude and peak velocity of head oscillation were reduced early inflight. No significant changes were noted in reflex gain or phase in any of the test conditions; however, there was a suggestion of an increase in VVOR and VOR-ES gain early inflight in asymptomatic subjects. A significant difference in VOR-S was found between SMS susceptible and non-susceptible subjects. There is no evidence that any changes in VOR characteristics contributed to SMS.

Discussion and a new method of optical cryptosystem based on interference

NASA Astrophysics Data System (ADS)

Lu, Dajiang; He, Wenqi; Liao, Meihua; Peng, Xiang

2017-02-01

A discussion and an objective security analysis of the well-known optical image encryption based on interference are presented in this paper. A new method is also proposed to eliminate the security risk of the original cryptosystem. For a possible practical application, we expand this new method into a hierarchical authentication scheme. In this authentication system, with a pre-generated and fixed random phase lock, different target images indicating different authentication levels are analytically encoded into corresponding phase-only masks (phase keys) and amplitude-only masks (amplitude keys). For the authentication process, a legal user can obtain a specified target image at the output plane if his/her phase key, and amplitude key, which should be settled close against the fixed internal phase lock, are respectively illuminated by two coherent beams. By comparing the target image with all the standard certification images in the database, the system can thus verify the user's legality even his/her identity level. Moreover, in despite of the internal phase lock of this system being fixed, the crosstalk between different pairs of keys held by different users is low. Theoretical analysis and numerical simulation are both provided to demonstrate the validity of this method.

Survival of anterior cantilevered all-ceramic resin-bonded fixed dental prostheses made from zirconia ceramic.

PubMed

Sasse, Martin; Kern, Matthias

2014-06-01

This study evaluated the clinical outcome of all-ceramic resin-bonded fixed dental prostheses (RBFDPs) with a cantilevered single-retainer design made from zirconia ceramic. Forty-two anterior RBFDPs with a cantilevered single-retainer design were made from yttrium oxide-stabilized zirconium oxide ceramic. RBFDPs were inserted using Panavia 21 TC as luting agent after air-abrasion of the ceramic bonding surface. During a mean observation time of 61.8 months two debondings occurred. Both RBFDPs were rebonded using Panavia 21 TC and are still in function. A caries lesion was detected at one abutment tooth during recall and was treated with a composite filling. Therefore, the overall six-year failure-free rate according to Kaplan-Meier was 91.1%. If only debonding was defined as failure the survival rate increased to 95.2%. Since all RBFDPs are still in function the overall survival rate was 100% after six years. Cantilevered zirconia ceramic RBFDPs showed promising results within the observation period. Single-retainer resin-bonded fixed dental prostheses made from zirconia ceramic show very good mid-term clinical survival rates. They should therefore be considered as a viable treatment alternative for the replacement of single missing anterior teeth especially as compared to an implant therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

PubMed Central

Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

2016-01-01

Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence). When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence). We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings. Authors' conclusions Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB. PLAIN LANGUAGE SUMMARY Fixed-dose combinations for treating pulmonary tuberculosis What are fixed-dose combinations and how might they improve care of people with tuberculosis Tuberculosis (TB) is an important health problem, especially in developing countries. The treatment for pulmonary TB in new patients includes four oral medicines taken for six months, sometimes as fixed-dose combinations (FDCs) that are combined in one tablet, or taken separately as single-drug formulations. The World Health Organization recommends prescribers use fixed-dose combinations to reduce the number of tablets that people take. On the supply side, this might reduce prescribing errors and improve drug supply efficiency; on the patient's side, FDCS simplify treatment and improve adherence. We conducted a review to assess the efficacy, safety, and acceptability of FDCs compared with single-drug formulations for treating people with newly diagnosed pulmonary TB. What the research says We searched for relevant trials up to 20 November 2015, and included 13 randomized controlled trials that enrolled 5824 people. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. There is probably little or no difference in FDCs compared to single-drug formulations for treatment failure (moderate quality evidence); relapse may be more frequent (low quality evidence); and the number of deaths were similar (moderate quality evidence). There is little or no difference in sputum smear or culture conversion (high quality evidence), and no difference was shown for serious adverse events (moderate quality evidence) or adverse events that led to discontinuation of therapy (low quality evidence). Authors' conclusions We concluded that fixed-dose combinations have similar efficacy to single-drug formulations for treating people with newly diagnosed pulmonary TB. PMID:27186634

Clinical Utility of an Automated Instrument for Gram Staining Single Slides ▿

PubMed Central

Baron, Ellen Jo; Mix, Samantha; Moradi, Wais

2010-01-01

Gram stains of 87 different clinical samples were prepared by the laboratory's conventional methods (automated or manual) and by a new single-slide-type automated staining instrument, GG&B AGS-1000. Gram stains from either heat- or methanol-fixed slides stained with the new instrument were easy to interpret, and results were essentially the same as those from the methanol-fixed slides prepared as a part of the routine workflow. This instrument is well suited to a rapid-response laboratory where Gram stain requests are commonly received on a stat basis. PMID:20410348

Quantitative targeted and retrospective data analysis of relevant pesticides, antibiotics and mycotoxins in bakery products by liquid chromatography-single-stage Orbitrap mass spectrometry.

PubMed

De Dominicis, Emiliano; Commissati, Italo; Gritti, Elisa; Catellani, Dante; Suman, Michele

2015-01-01

In addition to 'traditional' multi-residue and multi-contaminant multiple reaction monitoring (MRM) mass spectrometric techniques devoted to quantifying a list of targeted compounds, the global food industry requires non-targeted methods capable of detecting other possible potentially hazardous compounds. Ultra-high-performance liquid chromatography combined with a single-stage Orbitrap high-resolution mass spectrometer (UHPLC-HRMS Exactive™-Orbitrap Technology) was successfully exploited for the complete selective and quantitative determination of 33 target compounds within three major cross categories (pesticides, antibiotics and mycotoxins) in bakery matrices (specifically milk, wheat flour and mini-cakes). Resolution was set at 50 000 full width at half maximum (FWHM) to achieve the right compromise between an adequate scan speed and selectivity, allowing for the limitations related to the necessary generic sample preparation approach. An exact mass with tolerance of 5 ppm and minimum peak threshold of 10 000 units were fixed as the main identification conditions, including retention time and isotopic pattern as additional criteria devoted to greatly reducing the risk of false-positive findings. The full validation for all the target analytes was performed: linearity, intermediate repeatability and recovery (28 analytes within 70-120%) were positively assessed; furthermore, limits of quantification between 5 and 100 µg kg(-1) (with most of the analytes having a limit of detection below 6 µg kg(-1)) indicate good performance, which is compatible with almost all the regulatory needs. Naturally contaminated and fortified mini-cakes, prepared through combined use of industrial and pilot plant production lines, were analysed at two different concentration levels, obtaining good overall quantitative results and providing preliminary indications of the potential of full-scan HRMS cluster analysis. The effectiveness of this analytical approach was also tested in terms of the formulation of hypotheses for the identification of other analytes not initially targeted which can have toxicological implications (e.g. 3-acetyl-deoxynivalenol and deoxynivalenol-3-glucoside), opening a window on retrospective investigation perspectives in food safety laboratories.

Command Wire Sensor Measurements

DTIC Science & Technology

2012-09-01

coupled with the extreme harsh terrain has meant that few of these techniques have proved robust enough when moved from the laboratory to the field...to image stationary objects and does not accurately image moving targets. Moving targets can be seriously distorted and displaced from their true...battlefield and for imaging of fixed targets. Moving targets can be detected with a SAR if they have a Doppler frequency shift greater than the

Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies.

PubMed

Harris, Katherine E; Aldred, Shelley Force; Davison, Laura M; Ogana, Heather Anne N; Boudreau, Andrew; Brüggemann, Marianne; Osborn, Michael; Ma, Biao; Buelow, Benjamin; Clarke, Starlynn C; Dang, Kevin H; Iyer, Suhasini; Jorgensen, Brett; Pham, Duy T; Pratap, Payal P; Rangaswamy, Udaya S; Schellenberger, Ute; van Schooten, Wim C; Ugamraj, Harshad S; Vafa, Omid; Buelow, Roland; Trinklein, Nathan D

2018-01-01

We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1). This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs) isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.

Miniature Laser Tracker

DOEpatents

Vann, Charles S.

2003-09-09

This small, inexpensive, non-contact laser sensor can detect the location of a retroreflective target in a relatively large volume and up to six degrees of position. The tracker's laser beam is formed into a plane of light which is swept across the space of interest. When the beam illuminates the retroreflector, some of the light returns to the tracker. The intensity, angle, and time of the return beam is measured to calculate the three dimensional location of the target. With three retroreflectors on the target, the locations of three points on the target are measured, enabling the calculation of all six degrees of target position. Until now, devices for three-dimensional tracking of objects in a large volume have been heavy, large, and very expensive. Because of the simplicity and unique characteristics of this tracker, it is capable of three-dimensional tracking of one to several objects in a large volume, yet it is compact, light-weight, and relatively inexpensive. Alternatively, a tracker produces a diverging laser beam which is directed towards a fixed position, and senses when a retroreflective target enters the fixed field of view. An optically bar coded target can be read by the tracker to provide information about the target. The target can be formed of a ball lens with a bar code on one end. As the target moves through the field, the ball lens causes the laser beam to scan across the bar code.

Improved TNT detoxification by starch addition in a nitrogen-fixing Methylophilus-dominant aerobic microbial consortium.

PubMed

Khan, Muhammad Imran; Lee, Jaejin; Yoo, Keunje; Kim, Seonghoon; Park, Joonhong

2015-12-30

In this study, a novel aerobic microbial consortium for the complete detoxification of 2,4,6-trinitrotoluene (TNT) was developed using starch as a slow-releasing carbon source under nitrogen-fixing conditions. Aerobic TNT biodegradation coupled with microbial growth was effectively stimulated by the co-addition of starch and TNT under nitrogen-fixing conditions. The addition of starch with TNT led to TNT mineralization via ring cleavage without accumulation of any toxic by-products, indicating improved TNT detoxification by the co-addition of starch and TNT. Pyrosequencing targeting the bacterial 16S rRNA gene suggested that Methylophilus and Pseudoxanthomonas population were significantly stimulated by the co-addition of starch and TNT and that the Methylophilus population became predominant in the consortium. Together with our previous study regarding starch-stimulated RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) degradation (Khan et al., J. Hazard. Mater. 287 (2015) 243-251), this work suggests that the co-addition of starch with a target explosive is an effective way to stimulate aerobic explosive degradation under nitrogen-fixing conditions for enhancing explosive detoxification. Copyright © 2015 Elsevier B.V. All rights reserved.

Analytic validation and real-time clinical application of an amplicon-based targeted gene panel for advanced cancer

PubMed Central

Wing, Michele R.; Reeser, Julie W.; Smith, Amy M.; Reeder, Matthew; Martin, Dorrelyn; Jewell, Benjamin M.; Datta, Jharna; Miya, Jharna; Monk, J. Paul; Mortazavi, Amir; Otterson, Gregory A.; Goldberg, Richard M.; VanDeusen, Jeffrey B.; Cole, Sharon; Dittmar, Kristin; Jaiswal, Sunny; Kinzie, Matthew; Waikhom, Suraj; Freud, Aharon G.; Zhou, Xiao-Ping; Chen, Wei; Bhatt, Darshna; Roychowdhury, Sameek

2017-01-01

Multiplex somatic testing has emerged as a strategy to test patients with advanced cancer. We demonstrate our analytic validation approach for a gene hotspot panel and real-time prospective clinical application for any cancer type. The TruSight Tumor 26 assay amplifies 85 somatic hotspot regions across 26 genes. Using cell line and tumor mixes, we observed that 100% of the 14,715 targeted bases had at least 1000x raw coverage. We determined the sensitivity (100%, 95% CI: 96-100%), positive predictive value (100%, 95% CI: 96-100%), reproducibility (100% concordance), and limit of detection (3% variant allele frequency at 1000x read depth) of this assay to detect single nucleotide variants and small insertions and deletions. Next, we applied the assay prospectively in a clinical tumor sequencing study to evaluate 174 patients with metastatic or advanced cancer, including frozen tumors, formalin-fixed tumors, and enriched peripheral blood mononuclear cells in hematologic cancers. We reported one or more somatic mutations in 89 (53%) of the sequenced tumors (167 passing quality filters). Forty-three of these patients (26%) had mutations that would enable eligibility for targeted therapies. This study demonstrates the validity and feasibility of applying TruSight Tumor 26 for pan-cancer testing using multiple specimen types. PMID:29100271

Volumetric-modulated arc therapy for the treatment of a large planning target volume in thoracic esophageal cancer.

PubMed

Abbas, Ahmar S; Moseley, Douglas; Kassam, Zahra; Kim, Sun Mo; Cho, Charles

2013-05-06

Recently, volumetric-modulated arc therapy (VMAT) has demonstrated the ability to deliver radiation dose precisely and accurately with a shorter delivery time compared to conventional intensity-modulated fixed-field treatment (IMRT). We applied the hypothesis of VMAT technique for the treatment of thoracic esophageal carcinoma to determine superior or equivalent conformal dose coverage for a large thoracic esophageal planning target volume (PTV) with superior or equivalent sparing of organs-at-risk (OARs) doses, and reduce delivery time and monitor units (MUs), in comparison with conventional fixed-field IMRT plans. We also analyzed and compared some other important metrics of treatment planning and treatment delivery for both IMRT and VMAT techniques. These metrics include: 1) the integral dose and the volume receiving intermediate dose levels between IMRT and VMATI plans; 2) the use of 4D CT to determine the internal motion margin; and 3) evaluating the dosimetry of every plan through patient-specific QA. These factors may impact the overall treatment plan quality and outcomes from the individual planning technique used. In this study, we also examined the significance of using two arcs vs. a single-arc VMAT technique for PTV coverage, OARs doses, monitor units and delivery time. Thirteen patients, stage T2-T3 N0-N1 (TNM AJCC 7th edn.), PTV volume median 395 cc (range 281-601 cc), median age 69 years (range 53 to 85), were treated from July 2010 to June 2011 with a four-field (n = 4) or five-field (n = 9) step-and-shoot IMRT technique using a 6 MV beam to a prescribed dose of 50 Gy in 20 to 25 F. These patients were retrospectively replanned using single arc (VMATI, 91 control points) and two arcs (VMATII, 182 control points). All treatment plans of the 13 study cases were evaluated using various dose-volume metrics. These included PTV D99, PTV D95, PTV V9547.5Gy(95%), PTV mean dose, Dmax, PTV dose conformity (Van't Riet conformation number (CN)), mean lung dose, lung V20 and V5, liver V30, and Dmax to the spinal canal prv3mm. Also examined were the total plan monitor units (MUs) and the beam delivery time. Equivalent target coverage was observed with both VMAT single and two-arc plans. The comparison of VMATI with fixed-field IMRT demonstrated equivalent target coverage; statistically no significant difference were found in PTV D99 (p = 0.47), PTV mean (p = 0.12), PTV D95 and PTV V9547.5Gy (95%) (p = 0.38). However, Dmax in VMATI plans was significantly lower compared to IMRT (p = 0.02). The Van't Riet dose conformation number (CN) was also statistically in favor of VMATI plans (p = 0.04). VMATI achieved lower lung V20 (p = 0.05), whereas lung V5 (p = 0.35) and mean lung dose (p = 0.62) were not significantly different. The other OARs, including spinal canal, liver, heart, and kidneys showed no statistically significant differences between the two techniques. Treatment time delivery for VMATI plans was reduced by up to 55% (p = 5.8E-10) and MUs reduced by up to 16% (p = 0.001). Integral dose was not statistically different between the two planning techniques (p = 0.99). There were no statistically significant differences found in dose distribution of the two VMAT techniques (VMATI vs. VMATII) Dose statistics for both VMAT techniques were: PTV D99 (p = 0.76), PTV D95 (p = 0.95), mean PTV dose (p = 0.78), conformation number (CN) (p = 0.26), and MUs (p = 0.1). However, the treatment delivery time for VMATII increased significantly by two-fold (p = 3.0E-11) compared to VMATI. VMAT-based treatment planning is safe and deliverable for patients with thoracic esophageal cancer with similar planning goals, when compared to standard IMRT. The key benefit for VMATI was the reduction in treatment delivery time and MUs, and improvement in dose conformality. In our study, we found no significant difference in VMATII over single-arc VMATI for PTV coverage or OARs doses. However, we observed significant increase in delivery time for VMATII compared to VMATI.

SU-E-J-187: Management of Optic Organ Motion in Fractionated Stereotactic Radiotherapy

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

Manning, M; Maurer, J

2015-06-15

Purpose: Fractionated stereotactic radiotherapy (FSRT) for optic nerve tumors can potentially use planning target volume (PTV) expansions as small as 1–5 mm. However, the motion of the intraorbital segment of the optic nerve has not been studied. Methods: A subject with a right optic nerve sheath meningioma underwent CT simulation in three fixed gaze positions: right, left, and fixed forward at a marker. The gross tumor volume (GTV) and the organs-at-risk (OAR) were contoured on all three scans. An IMRT plan using 10 static non-coplanar fields to 50.4 Gy in 28 fractions was designed to treat the fixed-forward gazing GTVmore » with a 1 mm PTV, then resulting coverage was evaluated for the GTV in the three positions. As an alternative, the composite structures were computed to generate the internal target volume (ITV), 1 mm expansion free-gazing PTV, and planning organat-risk volumes (PRVs) for free-gazing treatment. A comparable IMRT plan was created for the free-gazing PTV. Results: If the patient were treated using the fixed forward gaze plan looking straight, right, and left, the V100% for the GTV was 100.0%, 33.1%, and 0.1%, respectively. The volumes of the PTVs for fixed gaze and free-gazing plans were 0.79 and 2.21 cc, respectively, increasing the PTV by a factor of 2.6. The V100% for the fixed gaze and free-gazing plans were 0.85 cc and 2.8 cc, respectively increasing the treated volume by a factor of 3.3. Conclusion: Fixed gaze treatment appears to provide greater organ sparing than free-gazing. However unanticipated intrafraction right or left gaze can produce a geometric miss. Further study of optic nerve motion appears to be warranted in areas such as intrafraction optical confirmation of fixed gaze and optimized gaze directions to minimize lens and other normal organ dose in cranial radiotherapy.« less

Maintenance service contract model for heavy equipment in mining industry using principal agent theory

NASA Astrophysics Data System (ADS)

Pakpahan, Eka K. A.; Iskandar, Bermawi P.

2015-12-01

Mining industry is characterized by a high operational revenue, and hence high availability of heavy equipment used in mining industry is a critical factor to ensure the revenue target. To maintain high avaliability of the heavy equipment, the equipment's owner hires an agent to perform maintenance action. Contract is then used to control the relationship between the two parties involved. The traditional contracts such as fixed price, cost plus or penalty based contract studied is unable to push agent's performance to exceed target, and this in turn would lead to a sub-optimal result (revenue). This research deals with designing maintenance contract compensation schemes. The scheme should induce agent to select the highest possible maintenance effort level, thereby pushing agent's performance and achieve maximum utility for both parties involved. Principal agent theory is used as a modeling approach due to its ability to simultaneously modeled owner and agent decision making process. Compensation schemes considered in this research includes fixed price, cost sharing and revenue sharing. The optimal decision is obtained using a numerical method. The results show that if both parties are risk neutral, then there are infinite combination of fixed price, cost sharing and revenue sharing produced the same optimal solution. The combination of fixed price and cost sharing contract results in the optimal solution when the agent is risk averse, while the optimal combination of fixed price and revenue sharing contract is obtained when agent is risk averse. When both parties are risk averse, the optimal compensation scheme is a combination of fixed price, cost sharing and revenue sharing.

Out of the Blue: NATO SOF Air Wing

DTIC Science & Technology

2012-03-01

surveillance, targeting, and reconnaissance aircraft . This research also examines NSHQ’s training and readiness organizational structure, and proposes...mix contains rotary-wing and fixed-wing aviation platforms, as well as intelligence, surveillance, targeting, and reconnaissance aircraft . This...METHODOLOGY ..........................................................................................9  II.  AIRCRAFT CATEGORIZATION

Respiration-rate estimation of a moving target using impulse-based ultra wideband radars.

PubMed

Sharafi, Azadeh; Baboli, Mehran; Eshghi, Mohammad; Ahmadian, Alireza

2012-03-01

Recently, Ultra-wide band signals have become attractive for their particular advantage of having high spatial resolution and good penetration ability which makes them suitable in medical applications. One of these applications is wireless detection of heart rate and respiration rate. Two hypothesis of static environment and fixed patient are considered in the method presented in previous literatures which are not valid for long term monitoring of ambulant patients. In this article, a new method to detect the respiration rate of a moving target is presented. The first algorithm is applied to the simulated and experimental data for detecting respiration rate of a fixed target. Then, the second algorithm is developed to detect respiration rate of a moving target. The proposed algorithm uses correlation for body movement cancellation, and then detects the respiration rate based on energy in frequency domain. The results of algorithm prove an accuracy of 98.4 and 97% in simulated and experimental data, respectively.

Suprathreshold contrast summation over area using drifting gratings.

PubMed

McDougall, Thomas J; Dickinson, J Edwin; Badcock, David R

2018-04-01

This study investigated contrast summation over area for moving targets applied to a fixed-size contrast pedestal-a technique originally developed by Meese and Summers (2007) to demonstrate strong spatial summation of contrast for static patterns at suprathreshold contrast levels. Target contrast increments (drifting gratings) were applied to either the entire 20% contrast pedestal (a full fixed-size drifting grating), or in the configuration of a checkerboard pattern in which the target increment was applied to every alternate check region. These checked stimuli are known as "Battenberg patterns" and the sizes of the checks were varied (within a fixed overall area), across conditions, to measure summation behavior. Results showed that sensitivity to an increment covering the full pedestal was significantly higher than that for the Battenberg patterns (areal summation). Two observers showed strong summation across all check sizes (0.71°-3.33°), and for two other observers the summation ratio dropped to levels consistent with probability summation once check size reached 2.00°. Therefore, areal summation with moving targets does operate at high contrast, and is subserved by relatively large receptive fields covering a square area extending up to at least 3.33° × 3.33° for some observers. Previous studies in which the spatial structure of the pedestal and target covaried were unable to demonstrate spatial summation, potentially due to increasing amounts of suppression from gain-control mechanisms which increases as pedestal size increases. This study shows that when this is controlled, by keeping the pedestal the same across all conditions, extensive summation can be demonstrated.

Decay analysis of compound nuclei formed in reactions with exotic neutron-rich 9Li projectile and the synthesis of 217At* within the dynamical cluster-decay model

NASA Astrophysics Data System (ADS)

Kaur, Arshdeep; Kaushal, Pooja; Hemdeep; Gupta, Raj K.

2018-01-01

The decay of various compound nuclei formed via exotic neutron-rich 9Li projectile is studied within the dynamical cluster-decay model (DCM). Following the earlier work of one of us (RKG) and collaborators (M. Kaur et al. (2015) [1]), for an empirically fixed neck-length parameter ΔRemp, the only parameter in the DCM, at a given incident laboratory energy ELab, we are able to fit almost exactly the (total) fusion cross section σfus =∑x=16σxn for 9Li projectile on 208Pb and other targets, with σfus depending strongly on the target mass of the most abundant isotope and its (magic) shell structure. This result shows the predictable nature of the DCM. The neck-length parameter ΔRemp is fixed empirically for the decay of 217At* formed in 9Li + 208Pb reaction at a fixed laboratory energy ELab, and then the total fusion cross section σfus calculated for all other reactions using 9Li as a projectile on different targets. Apparently, this procedure could be used to predict σfus for 9Li-induced reactions where experimental data are not available. Furthermore, optimum choice of "cold" target-projectile combinations, forming "hot" compact configurations, are predicted for the synthesis of compound nucleus 217At* with 8Li + 209Pb as one of the target-projectile combination, or another (t , p) combination 48Ca + 169Tb, with a doubly magic 48Ca, as the best possibility.

Safety and pharmacokinetic profiles of phosphorodiamidate morpholino oligomers with activity against ebola virus and marburg virus: results of two single-ascending-dose studies.

PubMed

Heald, Alison E; Iversen, Patrick L; Saoud, Jay B; Sazani, Peter; Charleston, Jay S; Axtelle, Tim; Wong, Michael; Smith, William B; Vutikullird, Apinya; Kaye, Edward

2014-11-01

Two identical single-ascending-dose studies evaluated the safety and pharmacokinetics (PK) of AVI-6002 and AVI-6003, two experimental combinations of phosphorodiamidate morpholino oligomers with positive charges (PMOplus) that target viral mRNA encoding Ebola virus and Marburg virus proteins, respectively. Both AVI-6002 and AVI-6003 were found to suppress disease in virus-infected nonhuman primates in previous studies. AVI-6002 (a combination of AVI-7537 and AVI-7539) or AVI-6003 (a combination of AVI-7287 and AVI-7288) were administered as sequential intravenous (i.v.) infusions of a 1:1 fixed dose ratio of the two subcomponents. In each study, 30 healthy male and female subjects between 18 and 50 years of age were enrolled in six-dose escalation cohorts of five subjects each and received a single i.v. infusion of active study drug (0.005, 0.05, 0.5, 1.5, 3, and 4.5 mg/kg per component) or placebo in a 4:1 ratio. Both AVI-6002 and AVI-6003 were safe and well tolerated at the doses studied. A maximum tolerated dose was not observed in either study. The four chemically similar PMOplus components exhibited generally similar PK profiles. The mean peak plasma concentration and area under the concentration-time curve values of the four components exhibited dose-proportional PK. The estimated plasma half-life of all four components was 2 to 5 h. The safety of the two combinations and the PK of the four components were similar, regardless of the target RNA sequence. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Six Basic Plan Concepts Used for California School Housing. A Sequential Development from 1900 to Today.

ERIC Educational Resources Information Center

California State Dept. of Education, Sacramento. Bureau of School Planning.

A floor plan accompanies each of six chronologically arranged schemes for housing educational programs. Scheme A represents the in-line corridor plan whose main characteristics are--(1) double loaded corridors with fixed bearing walls, (2) single window walls providing minimal light and ventilation, and (3) small classrooms with fixed desks and…

33 CFR 118.75 - Lights on single-opening drawbridges.

Code of Federal Regulations, 2010 CFR

2010-07-01

... span. (c) Pier or abutment lights. Every swing bridge shall be lighted so that the end of each pier, abutment or fixed portion of the bridge adjacent to the navigable channel through the draw, or each end of the protection piers for such piers, abutments, or fixed portion of the bridge will be marked by a red...

Bias and Precision of Measures of Association for a Fixed-Effect Multivariate Analysis of Variance Model

ERIC Educational Resources Information Center

Kim, Soyoung; Olejnik, Stephen

2005-01-01

The sampling distributions of five popular measures of association with and without two bias adjusting methods were examined for the single factor fixed-effects multivariate analysis of variance model. The number of groups, sample sizes, number of outcomes, and the strength of association were manipulated. The results indicate that all five…

Absorbed dose estimates from a single measurement one to three days after the administration of 177Lu-DOTATATE/-TOC.

PubMed

Hänscheid, Heribert; Lapa, Constantin; Buck, Andreas K; Lassmann, Michael; Werner, Rudolf A

2017-01-01

To retrospectively analyze the accuracy of absorbed dose estimates from a single measurement of the activity concentrations in tumors and relevant organs one to three days after the administration of 177 Lu-DOTA-TATE/TOC assuming tissue specific effective half-lives. Activity kinetics in 54 kidneys, 30 neuroendocrine tumor lesions, 25 livers, and 27 spleens were deduced from series of planar images in 29 patients. After adaptation of mono- or bi-exponential fit functions to the measured data, it was analyzed for each fit function how precise the time integral can be estimated from fixed tissue-specific half-lives and a single measurement at 24, 48, or 72 h after the administration. For the kidneys, assuming a fixed tissue-specific half-life of 50 h, the deviations of the estimate from the actual integral were median (5 % percentile, 95 % percentile): -3 °% (-15 %>; +16 °%) for measurements after 24 h, +2 %> (-9 %>; +12 %>) for measurements after 48 h, and 0 % (-2 %; +12 %) for measurements after 72 h. The corresponding values for the other tissues, assuming fixed tissue-specific half-lives of 67 h for liver and spleen and 77 h for tumors, were +2 % (-25 %; +20 %) for measurements after 24 h, +2 °% (-16 %>; +17 %>) for measurements after 48 h, and +2 %> (-11 %>; +10 %>) for measurements after 72 h. Especially for the kidneys, which often represent the dose limiting organ, but also for liver, spleen, and neuroendocrine tumors, a meaningful absorbed dose estimate is possible from a single measurement after 2, more preferably 3 days after the administration of 177 Lu-DOTA-TATE/-TOC assuming fixed tissue specific effective half-lives. Schattauer GmbH.

Capturing Context-Related Change in Emotional Dynamics via Fixed Moderated Time Series Analysis.

PubMed

Adolf, Janne K; Voelkle, Manuel C; Brose, Annette; Schmiedek, Florian

2017-01-01

Much of recent affect research relies on intensive longitudinal studies to assess daily emotional experiences. The resulting data are analyzed with dynamic models to capture regulatory processes involved in emotional functioning. Daily contexts, however, are commonly ignored. This may not only result in biased parameter estimates and wrong conclusions, but also ignores the opportunity to investigate contextual effects on emotional dynamics. With fixed moderated time series analysis, we present an approach that resolves this problem by estimating context-dependent change in dynamic parameters in single-subject time series models. The approach examines parameter changes of known shape and thus addresses the problem of observed intra-individual heterogeneity (e.g., changes in emotional dynamics due to observed changes in daily stress). In comparison to existing approaches to unobserved heterogeneity, model estimation is facilitated and different forms of change can readily be accommodated. We demonstrate the approach's viability given relatively short time series by means of a simulation study. In addition, we present an empirical application, targeting the joint dynamics of affect and stress and how these co-vary with daily events. We discuss potentials and limitations of the approach and close with an outlook on the broader implications for understanding emotional adaption and development.

Noninvasive diagnosis of oral cancer by Stokes shift spectroscopy

NASA Astrophysics Data System (ADS)

Ebenezar, Jeyasingh; Ganesan, Singaravelu; Aruna, Prakasrao; Muralinaidu, Radhakrishnan

2014-03-01

The objective of this study is to evaluate the diagnostic potential of stokes shift (SS) spectroscopy (S3) for normal, precancer and cancerous oral lesions in vivo. The SS spectra were recorded in the 250 - 650 nm spectral range by simultaneously scanning both the excitation and emission wavelengths while keeping a fixed wavelength interval Δλ=20 nm between them. Characteristic, highly resolved peaks and significant spectral differences between normal and different pathological oral lesions observed around 300, 355, 395, and 420 nm which are attributed to tryptophan, collagen, and NADH respectively. Using S3 technique one can obtain the key fluorophores in a single scan and hence they can be targeted as a tumor markers in this study. In order to quantify the altered spectral differences between normal and different pathological oral lesions are verified by different ratio parameters.

Signatures of Long-Term Balancing Selection in Human Genomes

PubMed Central

de Filippo, Cesare; Teixeira, João C; Schmidt, Joshua M; Kleinert, Philip; Meyer, Diogo; Andrés, Aida M

2018-01-01

Abstract Balancing selection maintains advantageous diversity in populations through various mechanisms. Although extensively explored from a theoretical perspective, an empirical understanding of its prevalence and targets lags behind our knowledge of positive selection. Here, we describe the Non-central Deviation (NCD), a simple yet powerful statistic to detect long-term balancing selection (LTBS) that quantifies how close frequencies are to expectations under LTBS, and provides the basis for a neutrality test. NCD can be applied to a single locus or genomic data, and can be implemented considering only polymorphisms (NCD1) or also considering fixed differences with respect to an outgroup (NCD2) species. Incorporating fixed differences improves power, and NCD2 has higher power to detect LTBS in humans under different frequencies of the balanced allele(s) than other available methods. Applied to genome-wide data from African and European human populations, in both cases using chimpanzee as an outgroup, NCD2 shows that, albeit not prevalent, LTBS affects a sizable portion of the genome: ∼0.6% of analyzed genomic windows and 0.8% of analyzed positions. Significant windows (P < 0.0001) contain 1.6% of SNPs in the genome, which disproportionally fall within exons and change protein sequence, but are not enriched in putatively regulatory sites. These windows overlap ∼8% of the protein-coding genes, and these have larger number of transcripts than expected by chance even after controlling for gene length. Our catalog includes known targets of LTBS but a majority of them (90%) are novel. As expected, immune-related genes are among those with the strongest signatures, although most candidates are involved in other biological functions, suggesting that LTBS potentially influences diverse human phenotypes. PMID:29608730

Comparison of Expandable and Fixed Interbody Cages in a Human Cadaver Corpectomy Model: Fatigue Characteristics.

PubMed

Pekmezci, Murat; Tang, Jessica A; Cheng, Liu; Modak, Ashin; McClellan, Robert T; Buckley, Jenni M; Ames, Christopher P

2016-11-01

In vitro cadaver biomechanics study. The goal of this study is to compare the in situ fatigue life of expandable versus fixed interbody cage designs. Expandable cages are becoming more popular, in large part, due to their versatility; however, subsidence and catastrophic failure remain a concern. This in vitro analysis investigates the fatigue life of expandable and fixed interbody cages in a single level human cadaver corpectomy model by evaluating modes of subsidence of expandable and fixed cages as well as change in stiffness of the constructs with cyclic loading. Nineteen specimens from 10 human thoracolumbar spines (T10-L2, L3-L5) were biomechanically evaluated after a single level corpectomy that was reconstructed with an expandable or fixed cage and anterior dual rod instrumentation. All specimens underwent 98 K cycles to simulate 3 months of postoperative weight bearing. In addition, a third group with hyperlordotic cages was used to simulate catastrophic failure that is observed in clinical practice. Three fixed and 2 expandable cages withstood the cyclic loading despite perfect sagittal and coronal plane fitting of the endcaps. The majority of the constructs settled in after initial subsidence. The catastrophic failures that were observed in clinical practice could not be reproduced with hyperlordotic cages. However, all cages in this group subsided, and 60% resulted in endplate fractures during deployment of the cage. Despite greater surface contact area, expandable cages have a trend for higher subsidence rates when compared with fixed cages. When there is edge loading as in the hyperlordotic cage scenario, there is a higher risk of subsidence and intraoperative fracture during deployment of expandable cages.

One-Step Preservation of Phosphoproteins and Tissue Morphology at Room Temperature for Diagnostic and Research Specimens

PubMed Central

Mueller, Claudius; Edmiston, Kirsten H.; Carpenter, Calvin; Gaffney, Eoin; Ryan, Ciara; Ward, Ronan; White, Susan; Memeo, Lorenzo; Colarossi, Cristina; Petricoin, Emanuel F.; Liotta, Lance A.; Espina, Virginia

2011-01-01

Background There is an urgent need to measure phosphorylated cell signaling proteins in cancer tissue for the individualization of molecular targeted kinase inhibitor therapy. However, phosphoproteins fluctuate rapidly following tissue procurement. Snap-freezing preserves phosphoproteins, but is unavailable in most clinics and compromises diagnostic morphology. Formalin fixation preserves tissue histomorphology, but penetrates tissue slowly, and is unsuitable for stabilizing phosphoproteins. We originated and evaluated a novel one-step biomarker and histology preservative (BHP) chemistry that stabilizes signaling protein phosphorylation and retains formalin-like tissue histomorphology with equivalent immunohistochemistry in a single paraffin block. Results Total protein yield extracted from BHP-fixed, routine paraffin-embedded mouse liver was 100% compared to snap-frozen tissue. The abundance of 14 phosphorylated proteins was found to be stable over extended fixation times in BHP fixed paraffin embedded human colon mucosa. Compared to matched snap-frozen tissue, 8 phosphoproteins were equally preserved in mouse liver, while AMPKβ1 Ser108 was slightly elevated after BHP fixation. More than 25 tissues from mouse, cat and human specimens were evaluated for preservation of histomorphology. Selected tissues were evaluated in a multi-site, independent pathology review. Tissue fixed with BHP showed equivalent preservation of cytoplasmic and membrane cytomorphology, with significantly better nuclear chromatin preservation by BHP compared to formalin. Immunohistochemical staining of 13 non-phosphorylated proteins, including estrogen receptor alpha, progesterone receptor, Ki-67 and Her2, was equal to or stronger in BHP compared to formalin. BHP demonstrated significantly improved immunohistochemical detection of phosphorylated proteins ERK Thr202/Tyr204, GSK3-α/β Ser21/Ser9, p38-MAPK Thr180/Tyr182, eIF4G Ser1108 and Acetyl-CoA Carboxylase Ser79. Conclusion In a single paraffin block BHP preserved the phosphorylation state of several signaling proteins at a level comparable to snap-freezing, while maintaining the full diagnostic immunohistochemical and histomorphologic detail of formalin fixation. This new tissue fixative has the potential to greatly facilitate personalized medicine, biobanking, and phospho-proteomic research. PMID:21858221

NEPA, a fixed oral combination of netupitant and palonosetron, improves control of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of chemotherapy: results of a randomized, double-blind, phase 3 trial versus oral palonosetron.

PubMed

Aapro, Matti; Karthaus, Meinolf; Schwartzberg, Lee; Bondarenko, Igor; Sarosiek, Tomasz; Oprean, Cristina; Cardona-Huerta, Servando; Hansen, Vincent; Rossi, Giorgia; Rizzi, Giada; Borroni, Maria Elisa; Rugo, Hope

2017-04-01

Antiemetic guidelines recommend co-administration of targeted prophylactic medications inhibiting molecular pathways involved in emesis. NEPA is a fixed oral combination of a new NK 1 receptor antagonist (RA), netupitant (NETU 300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT 3 RA. NEPA showed superior prevention of chemotherapy-induced nausea and vomiting (CINV) compared with oral PALO in a single chemotherapy cycle; maintenance of efficacy/safety over continuing cycles is the objective of this study. This study is a multinational, double-blind study comparing a single oral dose of NEPA vs oral PALO in chemotherapy-naïve patients receiving anthracycline/cyclophosphamide-based chemotherapy along with dexamethasone 12 mg (NEPA) or 20 mg (PALO) on day 1. The primary efficacy endpoint was delayed (25-120 h) complete response (CR: no emesis, no rescue medication) in cycle 1. Sustained efficacy was evaluated during the multicycle extension by calculating the proportion of patients with overall (0-120 h) CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. Of 1455 patients randomized, 1286 (88 %) participated in the multiple-cycle extension for a total of 5969 cycles; 76 % completed ≥4 cycles. The proportion of patients with an overall CR was significantly greater for NEPA than oral PALO for cycles 1-4 (74.3 vs 66.6 %, 80.3 vs 66.7 %, 83.8 vs 70.3 %, and 83.8 vs 74.6 %, respectively; p ≤ 0.001 each cycle). The cumulative percentage of patients with a sustained CR over all 4 cycles was also greater for NEPA (p < 0.0001). NEPA was well tolerated over cycles. NEPA, a convenient, guideline-consistent, fixed antiemetic combination is effective and safe over multiple cycles of chemotherapy.

Evaluating the Performance of a Visually Guided Hearing Aid Using a Dynamic Auditory-Visual Word Congruence Task.

PubMed

Roverud, Elin; Best, Virginia; Mason, Christine R; Streeter, Timothy; Kidd, Gerald

2017-12-15

The "visually guided hearing aid" (VGHA), consisting of a beamforming microphone array steered by eye gaze, is an experimental device being tested for effectiveness in laboratory settings. Previous studies have found that beamforming without visual steering can provide significant benefits (relative to natural binaural listening) for speech identification in spatialized speech or noise maskers when sound sources are fixed in location. The aim of the present study was to evaluate the performance of the VGHA in listening conditions in which target speech could switch locations unpredictably, requiring visual steering of the beamforming. To address this aim, the present study tested an experimental simulation of the VGHA in a newly designed dynamic auditory-visual word congruence task. Ten young normal-hearing (NH) and 11 young hearing-impaired (HI) adults participated. On each trial, three simultaneous spoken words were presented from three source positions (-30, 0, and 30 azimuth). An auditory-visual word congruence task was used in which participants indicated whether there was a match between the word printed on a screen at a location corresponding to the target source and the spoken target word presented acoustically from that location. Performance was compared for a natural binaural condition (stimuli presented using impulse responses measured on KEMAR), a simulated VGHA condition (BEAM), and a hybrid condition that combined lowpass-filtered KEMAR and highpass-filtered BEAM information (BEAMAR). In some blocks, the target remained fixed at one location across trials, and in other blocks, the target could transition in location between one trial and the next with a fixed but low probability. Large individual variability in performance was observed. There were significant benefits for the hybrid BEAMAR condition relative to the KEMAR condition on average for both NH and HI groups when the targets were fixed. Although not apparent in the averaged data, some individuals showed BEAM benefits relative to KEMAR. Under dynamic conditions, BEAM and BEAMAR performance dropped significantly immediately following a target location transition. However, performance recovered by the second word in the sequence and was sustained until the next transition. When performance was assessed using an auditory-visual word congruence task, the benefits of beamforming reported previously were generally preserved under dynamic conditions in which the target source could move unpredictably from one location to another (i.e., performance recovered rapidly following source transitions) while the observer steered the beamforming via eye gaze, for both young NH and young HI groups.

Helical tomotherapy with dynamic running-start-stop delivery compared to conventional tomotherapy delivery

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

Rong, Yi, E-mail: yi.rong@osumc.edu; Chen, Yu; Lu, Weiguo

Purpose: Despite superior target dose uniformity, helical tomotherapy{sup ®} (HT) may involve a trade-off between longitudinal dose conformity and beam-on time (BOT), due to the limitation of only three available jaw sizes with the conventional HT (1.0, 2.5, and 5.0 cm). The recently introduced dynamic running-start-stop (RSS) delivery allows smaller jaw opening at the superior and inferior ends of the target when a sharp penumbra is needed. This study compared the dosimetric performance of RSS delivery with the fixed jaw HT delivery. Methods: Twenty patient cases were selected and deidentified prior to treatment planning, including 16 common clinical cases (brain,more » head and neck (HN), lung, and prostate) and four special cases of whole brain with hippocampus avoidance (WBHA) that require a high degree of dose modulation. HT plans were generated for common clinical cases using the fixed 2.5 cm jaw width (HT2.5) and WBHA cases using 1.0 cm (HT1.0). The jaw widths for RSS were preset with a larger size (RSS5.0 vs HT2.5 and RSS2.5 vs HT1.0). Both delivery techniques were planned based on identical contours, prescriptions, and planning objectives. Dose indices for targets and critical organs were compared using dose-volume histograms, BOT, and monitor units. Results: The average BOT was reduced from 4.8 min with HT2.5 to 2.5 min with RSS5.0. Target dose homogeneity with RSS5.0 was shown comparable to HT2.5 for common clinical sites. Superior normal tissue sparing was observed in RSS5.0 for optic nerves and optic chiasm in brain and HN cases. RSS5.0 demonstrated improved dose sparing for cord and esophagus in lung cases, as well as penile bulb in prostate cases. The mean body dose was comparable for both techniques. For the WBHA cases, the target homogeneity was significantly degraded in RSS2.5 without distinct dose sparing for hippocampus, compared to HT1.0. Conclusions: Compared to the fixed jaw HT delivery, RSS combined with a larger jaw width provides faster treatment delivery and improved cranial-caudal target dose conformity. The target coverage achieved by RSS with a large jaw width is comparable to the fixed jaw HT delivery for common cancer sites, but may deteriorate for cases where complex geometry is present in the middle part of the target.« less

Common mycorrhizal networks amplify competition by preferential mineral nutrient allocation to large host plants.

PubMed

Weremijewicz, Joanna; Sternberg, Leonel da Silveira Lobo O'Reilly; Janos, David P

2016-10-01

Arbuscular mycorrhizal (AM) fungi interconnect plants in common mycorrhizal networks (CMNs) which can amplify competition among neighbors. Amplified competition might result from the fungi supplying mineral nutrients preferentially to hosts that abundantly provide fixed carbon, as suggested by research with organ-cultured roots. We examined whether CMNs supplied (15) N preferentially to large, nonshaded, whole plants. We conducted an intraspecific target-neighbor pot experiment with Andropogon gerardii and several AM fungi in intact, severed or prevented CMNs. Neighbors were supplied (15) N, and half of the target plants were shaded. Intact CMNs increased target dry weight (DW), intensified competition and increased size inequality. Shading decreased target weight, but shaded plants in intact CMNs had mycorrhizal colonization similar to that of sunlit plants. AM fungi in intact CMNs acquired (15) N from the substrate of neighbors and preferentially allocated it to sunlit, large, target plants. Sunlit, intact CMN, target plants acquired as much as 27% of their nitrogen from the vicinity of their neighbors, but shaded targets did not. These results suggest that AM fungi in CMNs preferentially provide mineral nutrients to those conspecific host individuals best able to provide them with fixed carbon or representing the strongest sinks, thereby potentially amplifying asymmetric competition below ground. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Association of tooth brushing behavior with oral hygiene index among students using fixed appliance

NASA Astrophysics Data System (ADS)

Ria, N.; Eyanoer, P.

2018-03-01

Uses of fixed appliance have become popular recently. The purpose of its use is to correct malposition of teeth in order to normalize the masticatory function and to eliminate the accumulation of food remain between the teeth. These will prevent the formation of caries and any periodontal tissue disease. Fixed appliance patients must routinely maintain their oral hygiene. This study was an analytical survey with cross-sectional design to know the relationship between behavior in tooth brushing of students using thefixed appliance and oral hygiene in Poltekkes Kemenkes Medan. The average of Oral Hygiene Index – Simplified (OHI-S) value of students using fixed appliance (2.68) was still above national target which is ≤2, and there was a relationship between behavior in tooth brushing of students using the fixed appliance and oral hygiene (p<0.02). In conclusion, to get good oral hygiene and to prevent caries formation and periodontal disease patients using fixed appliances should maintain their dental health.

A single-phase multi-level D-STATCOM inverter using modular multi-level converter (MMC) topology for renewable energy sources

NASA Astrophysics Data System (ADS)

Sotoodeh, Pedram

This dissertation presents the design of a novel multi-level inverter with FACTS capability for small to mid-size (10-20kW) permanent-magnet wind installations using modular multi-level converter (MMC) topology. The aim of the work is to design a new type of inverter with D-STATCOM option to provide utilities with more control on active and reactive power transfer of distribution lines. The inverter is placed between the renewable energy source, specifically a wind turbine, and the distribution grid in order to fix the power factor of the grid at a target value, regardless of wind speed, by regulating active and reactive power required by the grid. The inverter is capable of controlling active and reactive power by controlling the phase angle and modulation index, respectively. The unique contribution of the proposed work is to combine the two concepts of inverter and D-STATCOM using a novel voltage source converter (VSC) multi-level topology in a single unit without additional cost. Simulations of the proposed inverter, with 5 and 11 levels, have been conducted in MATLAB/Simulink for two systems including 20 kW/kVAR and 250 W/VAR. To validate the simulation results, a scaled version (250 kW/kVAR) of the proposed inverter with 5 and 11 levels has been built and tested in the laboratory. Experimental results show that the reduced-scale 5- and 11-level inverter is able to fix PF of the grid as well as being compatible with IEEE standards. Furthermore, total cost of the prototype models, which is one of the major objectives of this research, is comparable with market prices.

Transverse momentum of hadrons produced in ν and overlineν interactions on an isoscalar target in BEBC

NASA Astrophysics Data System (ADS)

Deden, H.; Fritze, P.; Grässler, H.; Hasert, F. J.; Morfin, J.; Schulte, R.; Böckmann, K.; Geich-Gimbel, C.; Kokott, T. P.; Nellen, B.; Pech, R.; Saarikko, H.; Bosetti, P. C.; Cundy, D. C.; Grant, A. L.; Hulth, P. O.; Pape, L.; Scott, W. G.; Skjeggestad, O.; Mermikides, M.; Simopoulou, E.; Vayaki, A.; Barnham, K. W. J.; Butterworth, I.; Chima, J. S.; Clayton, E. F.; Miller, D. B.; Mobayyen, M.; Penfold, C.; Powell, K. J.; Batley, J. R.; Giles, R.; Grossmann, P.; Lloyd, J. L.; Myatt, G.; Perkins, D. H.; Radojicic, D.; Renton, P.; Saitta, B.; Bloch, M.; Bolognese, T.; Tallini, B.; Velasco, J.; Vignaud, D.; Aachen-Bonn-CERN-Demokritos Athens-I. C. London-Oxford-Saclay Collaboration

1981-04-01

The average transverse momentum squared, < p⊥2>, of hadrons is studied as a function of W2 and of Q2 for ν and overlineν interactions on an isoscalar target. An increase of < p⊥2> with W2 is observed for the hadrons emitted forward in the hadronic c.m.s. The p⊥ dependence of the fragmentation function is found to factorise from the structure function at fixed W, but does not factorise at fixed Q2. Unlike the case of forward-going particles, the < p⊥2> of hadrons going backward in the c.m.s. shows no strong dependence on W2.

Preparation of a primary argon beam for the CERN fixed target physics

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

Küchler, D., E-mail: detlef.kuchler@cern.ch; O’Neil, M.; Scrivens, R.

2014-02-15

The fixed target experiment NA61 in the North Area of the Super Proton Synchrotron is studying phase transitions in strongly interacting matter. Up to now they used the primary beams available from the CERN accelerator complex (protons and lead ions) or fragmented beams created from the primary lead ion beam. To explore a wider range of energies and densities a request was made to provide primary argon and xenon beams. This paper describes the results of the setting up and 10 week test run of the Ar{sup 11+} beam from the 14.5 GHz ECR ion source and the linear acceleratormore » (Linac3) at CERN.« less

Targeted delivery of lovastatin and tocotrienol to fracture site promotes fracture healing in osteoporosis model: micro-computed tomography and biomechanical evaluation.

PubMed

Ibrahim, Nurul 'Izzah; Khamis, Mohd Fadhli; Mod Yunoh, Mohd Faridz; Abdullah, Shahrum; Mohamed, Norazlina; Shuid, Ahmad Nazrun

2014-01-01

Osteoporosis is becoming a major health problem that is associated with increased fracture risk. Previous studies have shown that osteoporosis could delay fracture healing. Although there are potential agents available to promote fracture healing of osteoporotic bone such as statins and tocotrienol, studies on direct delivery of these agents to the fracture site are limited. This study was designed to investigate the effects of two potential agents, lovastatin and tocotrienol using targeted drug delivery system on fracture healing of postmenopausal osteoporosis rats. The fracture healing was evaluated using micro CT and biomechanical parameters. Forty-eight Sprague-Dawley female rats were divided into 6 groups. The first group was sham-operated (SO), while the others were ovariectomized (OVx). After two months, the right tibiae of all rats were fractured at metaphysis region using pulsed ultrasound and were fixed with plates and screws. The SO and OVxC groups were given two single injections of lovastatin and tocotrienol carriers. The estrogen group (OVx+EST) was given daily oral gavages of Premarin (64.5 µg/kg). The Lovastatin treatment group (OVx+Lov) was given a single injection of 750 µg/kg lovastatin particles. The tocotrienol group (OVx+TT) was given a single injection of 60 mg/kg tocotrienol particles. The combination treatment group (OVx+Lov+TT) was given two single injections of 750 µg/kg lovastatin particles and 60 mg/kg tocotrienol particles. After 4 weeks of treatment, the fractured tibiae were dissected out for micro-CT and biomechanical assessments. The combined treatment group (OVx+Lov+TT) showed significantly higher callus volume and callus strength than the OVxC group (p<0.05). Both the OVx+Lov and OVx+TT groups showed significantly higher callus strength than the OVxC group (p<0.05), but not for callus volume. In conclusion, combined lovastatin and tocotrienol may promote better fracture healing of osteoporotic bone.

Visual-Vestibular Conflict Detection Depends on Fixation.

PubMed

Garzorz, Isabelle T; MacNeilage, Paul R

2017-09-25

Visual and vestibular signals are the primary sources of sensory information for self-motion. Conflict among these signals can be seriously debilitating, resulting in vertigo [1], inappropriate postural responses [2], and motion, simulator, or cyber sickness [3-8]. Despite this significance, the mechanisms mediating conflict detection are poorly understood. Here we model conflict detection simply as crossmodal discrimination with benchmark performance limited by variabilities of the signals being compared. In a series of psychophysical experiments conducted in a virtual reality motion simulator, we measure these variabilities and assess conflict detection relative to this benchmark. We also examine the impact of eye movements on visual-vestibular conflict detection. In one condition, observers fixate a point that is stationary in the simulated visual environment by rotating the eyes opposite head rotation, thereby nulling retinal image motion. In another condition, eye movement is artificially minimized via fixation of a head-fixed fixation point, thereby maximizing retinal image motion. Visual-vestibular integration performance is also measured, similar to previous studies [9-12]. We observe that there is a tradeoff between integration and conflict detection that is mediated by eye movements. Minimizing eye movements by fixating a head-fixed target leads to optimal integration but highly impaired conflict detection. Minimizing retinal motion by fixating a scene-fixed target improves conflict detection at the cost of impaired integration performance. The common tendency to fixate scene-fixed targets during self-motion [13] may indicate that conflict detection is typically a higher priority than the increase in precision of self-motion estimation that is obtained through integration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Litho hotspots fixing using model based algorithm

NASA Astrophysics Data System (ADS)

Zhang, Meili; Yu, Shirui; Mao, Zhibiao; Shafee, Marwa; Madkour, Kareem; ElManhawy, Wael; Kwan, Joe; Hu, Xinyi; Wan, Qijian; Du, Chunshan

2017-04-01

As technology advances, IC designs are getting more sophisticated, thus it becomes more critical and challenging to fix printability issues in the design flow. Running lithography checks before tapeout is now mandatory for designers, which creates a need for more advanced and easy-to-use techniques for fixing hotspots found after lithographic simulation without creating a new design rule checking (DRC) violation or generating a new hotspot. This paper presents a new methodology for fixing hotspots on layouts while using the same engine currently used to detect the hotspots. The fix is achieved by applying minimum movement of edges causing the hotspot, with consideration of DRC constraints. The fix is internally simulated by the lithographic simulation engine to verify that the hotspot is eliminated and that no new hotspot is generated by the new edge locations. Hotspot fix checking is enhanced by adding DRC checks to the litho-friendly design (LFD) rule file to guarantee that any fix options that violate DRC checks are removed from the output hint file. This extra checking eliminates the need to re-run both DRC and LFD checks to ensure the change successfully fixed the hotspot, which saves time and simplifies the designer's workflow. This methodology is demonstrated on industrial designs, where the fixing rate of single and dual layer hotspots is reported.

Attentional Spreading in Object-Based Attention

ERIC Educational Resources Information Center

Richard, Ashleigh M.; Lee, Hyunkyu; Vecera, Shaun P.

2008-01-01

The authors investigated 2 effects of object-based attention: the spread of attention within an attended object and the prioritization of search across possible target locations within an attended object. Participants performed a flanker task in which the location of the task-relevant target was fixed and known to participants. A spreading…

STAR Au + Au Fixed Target Results

NASA Astrophysics Data System (ADS)

Meehan, Kathryn; STAR Collaboration

2015-10-01

The RHIC Beam Energy Scan (BES) program was proposed to look for the turn-off of signatures of the quark gluon plasma (QGP), search for a possible QCD critical point, and study the nature of the phase transition between hadronic and partonic matter. The results from the NA49 experiment at CERN have been used to claim that the onset of deconfinement occurs at a collision energy around a center-of-mass energy of 7 GeV, the low end of the BES range. Data from lower energies are needed to test if this onset occurs. The goal of the STAR Fixed-Target Program is to extend the collision energy range in BES II with the same detector to energies that are likely below the onset of deconfinement. Currently, STAR has inserted a gold target into the beam pipe and conducted test runs at center-of-mass energies 3.9 and 4.5 GeV. Tests have been done with both Au and Al beams. First physics results from a Coulomb analysis of Au + Au fixed-target collisions, which are found to be consistent with previous experiments, will be presented. These results demonstrate that STAR has good particle identification capabilities in this novel detector setup. Furthermore, the Coulomb potential, which is sensitive to the Z of the projectile and degree of baryonic stopping, will be compared with published results from the AGS. This material is based upon work supported by the National Science Foundation under Grant No. 1068833.

Molecular characterization of oral squamous cell carcinoma using targeted next-generation sequencing.

PubMed

Er, Tze-Kiong; Wang, Yen-Yun; Chen, Chih-Chieh; Herreros-Villanueva, Marta; Liu, Ta-Chih; Yuan, Shyng-Shiou F

2015-10-01

Many genetic factors play an important role in the development of oral squamous cell carcinoma. The aim of this study was to assess the mutational profile in oral squamous cell carcinoma using formalin-fixed, paraffin-embedded tumors from a Taiwanese population by performing targeted sequencing of 26 cancer-associated genes that are frequently mutated in solid tumors. Next-generation sequencing was performed in 50 formalin-fixed, paraffin-embedded tumor specimens obtained from patients with oral squamous cell carcinoma. Genetic alterations in the 26 cancer-associated genes were detected using a deep sequencing (>1000X) approach. TP53, PIK3CA, MET, APC, CDH1, and FBXW7 were most frequently mutated genes. Most remarkably, TP53 mutations and PIK3CA mutations, which accounted for 68% and 18% of tumors, respectively, were more prevalent in a Taiwanese population. Other genes including MET (4%), APC (4%), CDH1 (2%), and FBXW7 (2%) were identified in our population. In summary, our study shows the feasibility of performing targeted sequencing using formalin-fixed, paraffin-embedded samples. Additionally, this study also reports the mutational landscape of oral squamous cell carcinoma in the Taiwanese population. We believe that this study will shed new light on fundamental aspects in understanding the molecular pathogenesis of oral squamous cell carcinoma and may aid in the development of new targeted therapies. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Single-Word Recognition Need Not Depend on Single-Word Features: Narrative Coherence Counteracts Effects of Single-Word Features That Lexical Decision Emphasizes

ERIC Educational Resources Information Center

Teng, Dan W.; Wallot, Sebastian; Kelty-Stephen, Damian G.

2016-01-01

Research on reading comprehension of connected text emphasizes reliance on single-word features that organize a stable, mental lexicon of words and that speed or slow the recognition of each new word. However, the time needed to recognize a word might not actually be as fixed as previous research indicates, and the stability of the mental lexicon…

Adaptive HIFU noise cancellation for simultaneous therapy and imaging using an integrated HIFU/imaging transducer

PubMed Central

Jeong, Jong Seob; Cannata, Jonathan Matthew; Shung, K Kirk

2010-01-01

It was previously demonstrated that it is feasible to simultaneously perform ultrasound therapy and imaging of a coagulated lesion during treatment with an integrated transducer that is capable of high intensity focused ultrasound (HIFU) and B-mode ultrasound imaging. It was found that coded excitation and fixed notch filtering upon reception could significantly reduce interference caused by the therapeutic transducer. During HIFU sonication, the imaging signal generated with coded excitation and fixed notch filtering had a range side-lobe level of less than −40 dB, while traditional short-pulse excitation and fixed notch filtering produced a range side-lobe level of −20 dB. The shortcoming is, however, that relatively complicated electronics may be needed to utilize coded excitation in an array imaging system. It is for this reason that in this paper an adaptive noise canceling technique is proposed to improve image quality by minimizing not only the therapeutic interference, but also the remnant side-lobe ‘ripples’ when using the traditional short-pulse excitation. The performance of this technique was verified through simulation and experiments using a prototype integrated HIFU/imaging transducer. Although it is known that the remnant ripples are related to the notch attenuation value of the fixed notch filter, in reality, it is difficult to find the optimal notch attenuation value due to the change in targets or the media resulted from motion or different acoustic properties even during one sonication pulse. In contrast, the proposed adaptive noise canceling technique is capable of optimally minimizing both the therapeutic interference and residual ripples without such constraints. The prototype integrated HIFU/imaging transducer is composed of three rectangular elements. The 6 MHz center element is used for imaging and the outer two identical 4 MHz elements work together to transmit the HIFU beam. Two HIFU elements of 14.4 mm × 20.0 mm dimensions could increase the temperature of the soft biological tissue from 55 °C to 71 °C within 60 s. Two types of experiments for simultaneous therapy and imaging were conducted to acquire a single scan-line and B-mode image with an aluminum plate and a slice of porcine muscle, respectively. The B-mode image was obtained using the single element imaging system during HIFU beam transmission. The experimental results proved that the combination of the traditional short-pulse excitation and the adaptive noise canceling method could significantly reduce therapeutic interference and remnant ripples and thus may be a better way to implement real-time simultaneous therapy and imaging. PMID:20224162

Adaptive HIFU noise cancellation for simultaneous therapy and imaging using an integrated HIFU/imaging transducer.

PubMed

Jeong, Jong Seob; Cannata, Jonathan Matthew; Shung, K Kirk

2010-04-07

It was previously demonstrated that it is feasible to simultaneously perform ultrasound therapy and imaging of a coagulated lesion during treatment with an integrated transducer that is capable of high intensity focused ultrasound (HIFU) and B-mode ultrasound imaging. It was found that coded excitation and fixed notch filtering upon reception could significantly reduce interference caused by the therapeutic transducer. During HIFU sonication, the imaging signal generated with coded excitation and fixed notch filtering had a range side-lobe level of less than -40 dB, while traditional short-pulse excitation and fixed notch filtering produced a range side-lobe level of -20 dB. The shortcoming is, however, that relatively complicated electronics may be needed to utilize coded excitation in an array imaging system. It is for this reason that in this paper an adaptive noise canceling technique is proposed to improve image quality by minimizing not only the therapeutic interference, but also the remnant side-lobe 'ripples' when using the traditional short-pulse excitation. The performance of this technique was verified through simulation and experiments using a prototype integrated HIFU/imaging transducer. Although it is known that the remnant ripples are related to the notch attenuation value of the fixed notch filter, in reality, it is difficult to find the optimal notch attenuation value due to the change in targets or the media resulted from motion or different acoustic properties even during one sonication pulse. In contrast, the proposed adaptive noise canceling technique is capable of optimally minimizing both the therapeutic interference and residual ripples without such constraints. The prototype integrated HIFU/imaging transducer is composed of three rectangular elements. The 6 MHz center element is used for imaging and the outer two identical 4 MHz elements work together to transmit the HIFU beam. Two HIFU elements of 14.4 mm x 20.0 mm dimensions could increase the temperature of the soft biological tissue from 55 degrees C to 71 degrees C within 60 s. Two types of experiments for simultaneous therapy and imaging were conducted to acquire a single scan-line and B-mode image with an aluminum plate and a slice of porcine muscle, respectively. The B-mode image was obtained using the single element imaging system during HIFU beam transmission. The experimental results proved that the combination of the traditional short-pulse excitation and the adaptive noise canceling method could significantly reduce therapeutic interference and remnant ripples and thus may be a better way to implement real-time simultaneous therapy and imaging.

[Combination therapy in the medical treatment of glaucoma].

PubMed

Hommer, A

2013-02-01

A combination of antiglaucoma medications is indicated if monotherapy is not sufficient to achieve the predefined target pressure and/or in case of a progression of glaucomatous damage or conversion from ocular hypertension to glaucomatous optic neuropathy. Most recently many fixed combinations with two active compounds have become available for the medical treatment of glaucoma. Compared to non-fixed combinations, these drugs offer a much easier use for the patients. Fixed combinations have to be applied less frequently which may improve adherence. Furthermore, they most likely contain a lower amount of toxic preservatives compared to non-fixed combinations. And finally, fixed combinations may eliminate the risk of a "washout" of the first medication by using the second product of a non-fixed combination too soon after the first drop has been installed. This review aims to examine the most important aspects of IOP-lowering fixed and non-fixed combinations in glaucoma management with a clear focus on the results obtained with fixed combinations. In Germany, fixed combinations with the compositions dorzolamide/timolol (FCDT), brinzolamide/timolol (FCBRINT), latanoprost/timolol (FCLT), travoprost/timolol (FCTT), bimatoprost/timolol (FCBIMT), brimonidine/timolol (FCBT), pilocarpine/timolol (FCPT) and metipranolol/timolol (FCMT) are approved for the medical management of glaucoma and ocular hypertension. The results of clinical studies comparing fixed combinations with their active ingredients and with the corresponding non-fixed combinations will be discussed. Furthermore - if available - the results of direct comparisons of the efficacy and safety of different IOP-lowering fixed combinations are summarised. Georg Thieme Verlag KG Stuttgart · New York.

CASFISH: CRISPR/Cas9-mediated in situ labeling of genomic loci in fixed cells.

PubMed

Deng, Wulan; Shi, Xinghua; Tjian, Robert; Lionnet, Timothée; Singer, Robert H

2015-09-22

Direct visualization of genomic loci in the 3D nucleus is important for understanding the spatial organization of the genome and its association with gene expression. Various DNA FISH methods have been developed in the past decades, all involving denaturing dsDNA and hybridizing fluorescent nucleic acid probes. Here we report a novel approach that uses in vitro constituted nuclease-deficient clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated caspase 9 (Cas9) complexes as probes to label sequence-specific genomic loci fluorescently without global DNA denaturation (Cas9-mediated fluorescence in situ hybridization, CASFISH). Using fluorescently labeled nuclease-deficient Cas9 (dCas9) protein assembled with various single-guide RNA (sgRNA), we demonstrated rapid and robust labeling of repetitive DNA elements in pericentromere, centromere, G-rich telomere, and coding gene loci. Assembling dCas9 with an array of sgRNAs tiling arbitrary target loci, we were able to visualize nonrepetitive genomic sequences. The dCas9/sgRNA binary complex is stable and binds its target DNA with high affinity, allowing sequential or simultaneous probing of multiple targets. CASFISH assays using differently colored dCas9/sgRNA complexes allow multicolor labeling of target loci in cells. In addition, the CASFISH assay is remarkably rapid under optimal conditions and is applicable for detection in primary tissue sections. This rapid, robust, less disruptive, and cost-effective technology adds a valuable tool for basic research and genetic diagnosis.

TARDEC FIXED HEEL POINT (FHP): DRIVER CAD ACCOMMODATION MODEL VERIFICATION REPORT

DTIC Science & Technology

2017-11-09

SUPPLEMENTARY NOTES N/A 14. ABSTRACT Easy-to-use Computer-Aided Design (CAD) tools, known as accommodation models, are needed by the ground vehicle... designers when developing the interior workspace for the occupant. The TARDEC Fixed Heel Point (FHP): Driver CAD Accommodation Model described in this...is intended to provide the composite boundaries representing the body of the defined target design population, including posture prediction

SU-G-TeP4-12: Individual Beam QA for a Robotic Radiosurgery System Using a Scintillator Cone

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

McGuinness, C; Descovich, M; Sudhyadhom, A

2016-06-15

Purpose: The targeting accuracy of the Cyberknife system is measured by end-to-end tests delivering multiple isocentric beams to a point in space. While the targeting accuracy of two representative beams can be determined by a Winston-Lutz-type test, no test is available today to determine the targeting accuracy of each clinical beam. We used a scintillator cone to measure the accuracy of each individual beam. Methods: The XRV-124 from Logos Systems Int’l is a scintillator cone with an imaging system that is able to measure individual beam vectors and a resulting error between planned and measured beam coordinates. We measured themore » targeting accuracy of isocentric and non-isocentric beams for a number of test cases using the Iris and the fixed collimator. The average difference between plan and measured beam position was 0.8–1.2mm across the collimator sizes and plans considered here. The max error for a single beam was 2.5mm for the isocentric plans, and 1.67mm for the non-isocentric plans. The standard deviation of the differences was 0.5mm or less. Conclusion: The CyberKnife System is specified to have an overall targeting accuracy for static targets of less than 0.95mm. In E2E tests using the XRV124 system we measure average beam accuracy between 0.8 to 1.23mm, with maximum of 2.5mm. We plan to investigate correlations between beam position error and robot position, and to quantify the effect of beam position errors on patient specific plans. Martina Descovich has received research support and speaker honoraria from Accuray.« less

Targeted therapies in cancer - challenges and chances offered by newly developed techniques for protein analysis in clinical tissues

PubMed Central

Malinowsky, K; Wolff, C; Gündisch, S; Berg, D; Becker, KF

2011-01-01

In recent years, new anticancer therapies have accompanied the classical approaches of surgery and radio- and chemotherapy. These new forms of treatment aim to inhibit specific molecular targets namely altered or deregulated proteins, which offer the possibility of individualized therapies. The specificity and efficiency of these new approaches, however, bring about a number of challenges. First of all, it is essential to specifically identify and quantify protein targets in tumor tissues for the reasonable use of such targeted therapies. Additionally, it has become even more obvious in recent years that the presence of a target protein is not always sufficient to predict the outcome of targeted therapies. The deregulation of downstream signaling molecules might also play an important role in the success of such therapeutic approaches. For these reasons, the analysis of tumor-specific protein expression profiles prior to therapy has been suggested as the most effective way to predict possible therapeutic results. To further elucidate signaling networks underlying cancer development and to identify new targets, it is necessary to implement tools that allow the rapid, precise, inexpensive and simultaneous analysis of many network components while requiring only a small amount of clinical material. Reverse phase protein microarray (RPPA) is a promising technology that meets these requirements while enabling the quantitative measurement of proteins. Together with recently developed protocols for the extraction of proteins from formalin-fixed, paraffin-embedded (FFPE) tissues, RPPA may provide the means to quantify therapeutic targets and diagnostic markers in the near future and reliably screen for new protein targets. With the possibility to quantitatively analyze DNA, RNA and protein from a single FFPE tissue sample, the methods are available for integrated patient profiling at all levels of gene expression, thus allowing optimal patient stratification for individualized therapies. PMID:21197262

Voyager 2 Uranus and Neptune targeting

NASA Technical Reports Server (NTRS)

Gray, D. L.; Cesarone, R. J.; Van Allen, R. E.

1982-01-01

Targeting strategies are developed for the Voyager 2 flybys of Uranus and Neptune/Triton. The need to maximize science return, conserve propellant, and maintain spacecraft safety presents a challenge, given the difficulty in estimating the spacecraft orbit relative to these outer planets. Expected propellant usage, science return, and targeting complexity are presented for each targeting strategy. For the dual encounter of Neptune and its satellite Triton, split targeting conditions are proposed to fix the most important conditions at each body, and thus minimize science losses resulting from Triton ephemeris uncertainties.

Measured Visual Motion Sensitivity at Fixed Contrast in the Periphery and Far Periphery

DTIC Science & Technology

2017-08-01

group Soldier performance. Soldier performance depends on visual detection of enemy personnel and materiel. Vision modeling in IWARS is neither...a highly time-critical and order- dependent activity, these unrealistic characterizations of target detection time and order severely limit the...recognize that MVTs should depend on target contrast, so we selected a target design different from that used in the Monaco et al. (2007) study. Based

Coil planet centrifugation as a means for small particle separation

NASA Technical Reports Server (NTRS)

Herrmann, F. T.

1983-01-01

The coil planet centrifuge uses a centrifugal force field to provide separation of particles based on differences in sedimentation rates by flow through a rotating coiled tube. Three main separations are considered: (1) single phase fresh sheep and human erythrocytes, (2) single phase fixed heep and human erythrocytes, and (3) electrophoretically enhanced single phase fresh sheep and human erythrocytes.

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service.

PubMed

Hamblin, Angela; Wordsworth, Sarah; Fermont, Jilles M; Page, Suzanne; Kaur, Kulvinder; Camps, Carme; Kaisaki, Pamela; Gupta, Avinash; Talbot, Denis; Middleton, Mark; Henderson, Shirley; Cutts, Anthony; Vavoulis, Dimitrios V; Housby, Nick; Tomlinson, Ian; Taylor, Jenny C; Schuh, Anna

2017-02-01

Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing. We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of "real world" data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds. This study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers.

The Fiscal and Social Costs of Consolidating Student Loans at Fixed Interest Rates. Working Paper No. 104

ERIC Educational Resources Information Center

Hassett, Kevin A.; Shapiro, Robert J.

2004-01-01

The federal government's student loan programs have been very successful, with two-thirds of all students or their families relying on loans provided or subsidized by the federal government. One of these student loan programs allows student borrowers to consolidate their previous loans into a single loan at a subsidized fixed rate based on the…

The Particle Adventure | Glossary

Science.gov Websites

Interaction Electron Electroweak Interaction Event Fermilab Fermion Fixed-target Experiment Flavor Fundamental Interaction Fundamental Particle Generation GeV Gluon Gravitational Interaction Graviton Hadron Interaction

Acoustics Discipline Overview

NASA Technical Reports Server (NTRS)

Envia, Edmane; Thomas, Russell

2007-01-01

As part of the Fundamental Aeronautics Program Annual Review, a summary of the progress made in 2007 in acoustics research under the Subsonic Fixed Wing project is given. The presentation describes highlights from in-house and external activities including partnerships and NRA-funded research with industry and academia. Brief progress reports from all acoustics Phase 1 NRAs are also included as are outlines of the planned activities for 2008 and all Phase 2 NRAs. N+1 and N+2 technology paths outlined for Subsonic Fixed Wing noise targets. NRA Round 1 progressing with focus on prediction method advancement. NRA Round 2 initiating work focused on N+2 technology, prediction methods, and validation. Excellent partnerships in progress supporting N+1 technology targets and providing key data sets.

Parallel Fixed Point Implementation of a Radial Basis Function Network in an FPGA

PubMed Central

de Souza, Alisson C. D.; Fernandes, Marcelo A. C.

2014-01-01

This paper proposes a parallel fixed point radial basis function (RBF) artificial neural network (ANN), implemented in a field programmable gate array (FPGA) trained online with a least mean square (LMS) algorithm. The processing time and occupied area were analyzed for various fixed point formats. The problems of precision of the ANN response for nonlinear classification using the XOR gate and interpolation using the sine function were also analyzed in a hardware implementation. The entire project was developed using the System Generator platform (Xilinx), with a Virtex-6 xc6vcx240t-1ff1156 as the target FPGA. PMID:25268918

Visual performance on detection tasks with double-targets of the same and different difficulty.

PubMed

Chan, Alan H S; Courtney, Alan J; Ma, C W

2002-10-20

This paper reports a study of measurement of horizontal visual sensitivity limits for 16 subjects in single-target and double-targets detection tasks. Two phases of tests were conducted in the double-targets task; targets of the same difficulty were tested in phase one while targets of different difficulty were tested in phase two. The range of sensitivity for the double-targets test was found to be smaller than that for single-target in both the same and different target difficulty cases. The presence of another target was found to affect performance to a marked degree. Interference effect of the difficult target on detection of the easy one was greater than that of the easy one on the detection of the difficult one. Performance decrement was noted when correct percentage detection was plotted against eccentricity of target in both the single-target and double-targets tests. Nevertheless, the non-significant correlation found between the performance for the two tasks demonstrated that it was impossible to predict quantitatively ability for detection of double targets from the data for single targets. This indicated probable problems in generalizing data for single target visual lobes to those for multiple targets. Also lobe area values obtained from measurements using a single-target task cannot be applied in a mathematical model for situations with multiple occurrences of targets.

[Single-molecule detection and characterization of DNA replication based on DNA origami].

PubMed

Wang, Qi; Fan, Youjie; Li, Bin

2014-08-01

To investigate single-molecule detection and characterization of DNA replication. Single-stranded DNA (ssDNA) as the template of DNA replication was attached to DNA origami by a hybridization reaction based on the complementary base-pairing principle. DNA replication catalyzed by E.coli DNA polymerase I Klenow Fragment (KF) was detected using atomic force microscopy (AFM). The height variations between the ssDNA and the double-stranded DNA (dsDNA), the distribution of KF during DNA replication and biotin-streptavidin (BA) complexes on the DNA strand after replication were detected. Agarose gel electrophoresis was employed to analyze the changes in the DNA after replication. The designed ssDNA could be anchored on the target positions of over 50% of the DNA origami. The KF was capable of binding to the ssDNA fixed on DNA origami and performing its catalytic activities, and was finally dissociated from the DNA after replication. The height of DNA strand increased by about 0.7 nm after replication. The addition of streptavidin also resulted in an DNA height increase to about 4.9 nm due to the formation of BA complexes on the biotinylated dsDNA. The resulting dsDNA and BA complex were subsequently confirmed by agarose gel electrophoresis. The combination of AFM and DNA origami allows detection and characterization of DNA replication at the single molecule level, and this approach provides better insights into the mechanism of DNA polymerase and the factors affecting DNA replication.

Analysis of DNA methylation in FFPE tissues using the MethyLight technology.

PubMed

Dallol, Ashraf; Al-Ali, Waleed; Al-Shaibani, Amina; Al-Mulla, Fahd

2011-01-01

Novel biomarkers are sought after by mining DNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissues. Such tissues offer the great advantage of often having complete clinical data (including survival), as well as the tissues are amenable for laser microdissection targeting specific tissue areas. Downstream analysis of such DNA includes mutational screens and methylation profiling. Screening for mutations by sequencing requires a significant amount of DNA for PCR and cycle sequencing. This is self-inhibitory if the gene screened has a large number of exons. Profiling DNA methylation using the MethyLight technology circumvents this problem and allows for the mining of several biomarkers from DNA extracted from a single microscope slide of the tissue of interest. We describe in this chapter a detailed protocol for MethyLight and its use in the determination of CpG Island Methylator Phenotype status in FFPE colorectal cancer samples.

Simulator study of the effect of visual-motion time delays on pilot tracking performance with an audio side task

NASA Technical Reports Server (NTRS)

Riley, D. R.; Miller, G. K., Jr.

1978-01-01

The effect of time delay was determined in the visual and motion cues in a flight simulator on pilot performance in tracking a target aircraft that was oscillating sinusoidally in altitude only. An audio side task was used to assure the subject was fully occupied at all times. The results indicate that, within the test grid employed, about the same acceptable time delay (250 msec) was obtained for a single aircraft (fighter type) by each of two subjects for both fixed-base and motion-base conditions. Acceptable time delay is defined as the largest amount of delay that can be inserted simultaneously into the visual and motion cues before performance degradation occurs. A statistical analysis of the data was made to establish this value of time delay. Audio side task provided quantitative data that documented the subject's work level.

Between-object and within-object saccade programming in a visual search task.

PubMed

Vergilino-Perez, Dorine; Findlay, John M

2006-07-01

The role of the perceptual organization of the visual display on eye movement control was examined in two experiments using a task where a two-saccade sequence was directed toward either a single elongated object or three separate shorter objects. In the first experiment, we examined the consequences for the second saccade of a small displacement of the whole display during the first saccade. We found that between-object saccades compensated for the displacement to aim for a target position on the new object whereas within-object saccades did not show compensation but were coded as a fixed motor vector applied irrespective of wherever the preceding saccade landed. In the second experiment, we extended the paradigm to examine saccades performed in different directions. The results suggest that the within-object and between-object saccade distinction is an essential feature of saccadic planning.

Scaling earthquake ground motions for performance-based assessment of buildings

USGS Publications Warehouse

Huang, Y.-N.; Whittaker, A.S.; Luco, N.; Hamburger, R.O.

2011-01-01

The impact of alternate ground-motion scaling procedures on the distribution of displacement responses in simplified structural systems is investigated. Recommendations are provided for selecting and scaling ground motions for performance-based assessment of buildings. Four scaling methods are studied, namely, (1)geometric-mean scaling of pairs of ground motions, (2)spectrum matching of ground motions, (3)first-mode-period scaling to a target spectral acceleration, and (4)scaling of ground motions per the distribution of spectral demands. Data were developed by nonlinear response-history analysis of a large family of nonlinear single degree-of-freedom (SDOF) oscillators that could represent fixed-base and base-isolated structures. The advantages and disadvantages of each scaling method are discussed. The relationship between spectral shape and a ground-motion randomness parameter, is presented. A scaling procedure that explicitly considers spectral shape is proposed. ?? 2011 American Society of Civil Engineers.

Allosteric Modulation of Ca2+ flux in Ligand-gated Cation Channel (P2X4) by Actions on Lateral Portals*

PubMed Central

Samways, Damien S. K.; Khakh, Baljit S.; Egan, Terrance M.

2012-01-01

Human P2X receptors are a family of seven ATP-gated ion channels that transport Na+, K+, and Ca2+ across cell surface membranes. The P2X4 receptor is unique among family members in its sensitivity to the macrocyclic lactone, ivermectin, which allosterically modulates both ion conduction and channel gating. In this paper we show that removing the fixed negative charge of a single acidic amino acid (Glu51) in the lateral entrance to the transmembrane pore markedly attenuates the effect of ivermectin on Ca2+ current and channel gating. Ca2+ entry through P2X4 receptors is known to trigger downstream signaling pathways in microglia. Our experiments show that the lateral portals could present a novel target for drugs in the treatment of microglia-associated disease including neuropathic pain. PMID:22219189

Real-life helping behaviours in North America: A genome-wide association approach

PubMed Central

Fieder, Martin

2018-01-01

In humans, prosocial behaviour is essential for social functioning. Twin studies suggest this distinct human trait to be partly hardwired. In the last decade research on the genetics of prosocial behaviour focused on neurotransmitters and neuropeptides, such as oxytocin, dopamine, and their respective pathways. Recent trends towards large scale medical studies targeting the genetic basis of complex diseases such as Alzheimer’s disease and schizophrenia pave the way for new directions also in behavioural genetics. Based on data from 10,713 participants of the American Health and Retirement Study we estimated heritability of helping behaviour–its total variance explained by 1.2 million single nucleotide polymorphisms–to be 11%. Both, fixed models and mixed linear models identified rs11697300, an intergene variant on chromosome 20, as a candidate variant moderating this particular helping behaviour. We assume that this so far undescribed area is worth further investigation in association with human prosocial behaviour. PMID:29324852

Versatile design and synthesis platform for visualizing genomes with Oligopaint FISH probes

PubMed Central

Beliveau, Brian J.; Joyce, Eric F.; Apostolopoulos, Nicholas; Yilmaz, Feyza; Fonseka, Chamith Y.; McCole, Ruth B.; Chang, Yiming; Li, Jin Billy; Senaratne, Tharanga Niroshini; Williams, Benjamin R.; Rouillard, Jean-Marie; Wu, Chao-ting

2012-01-01

A host of observations demonstrating the relationship between nuclear architecture and processes such as gene expression have led to a number of new technologies for interrogating chromosome positioning. Whereas some of these technologies reconstruct intermolecular interactions, others have enhanced our ability to visualize chromosomes in situ. Here, we describe an oligonucleotide- and PCR-based strategy for fluorescence in situ hybridization (FISH) and a bioinformatic platform that enables this technology to be extended to any organism whose genome has been sequenced. The oligonucleotide probes are renewable, highly efficient, and able to robustly label chromosomes in cell culture, fixed tissues, and metaphase spreads. Our method gives researchers precise control over the sequences they target and allows for single and multicolor imaging of regions ranging from tens of kilobases to megabases with the same basic protocol. We anticipate this technology will lead to an enhanced ability to visualize interphase and metaphase chromosomes. PMID:23236188

CCC calculated integrated cross sections of electron-H2 scattering

NASA Astrophysics Data System (ADS)

Zammit, Mark; Fursa, Dmitry; Savage, Jeremy; Bray, Igor

2016-09-01

Recently we applied the molecular convergent close-coupling (CCC) method to electron scattering from molecular hydrogen H2. Convergence of the major integrated cross sections has been explicitly demonstrated in the fixed-nuclei approximation by increasing the number of H2 target states in the close-coupling expansion from 9 to 491. The calculations have been performed using a projectile partial wave expansion with maximum orbital angular momentum Lmax = 8 and total orbital angular momentum projections | M | <= 8 . Coupling to the ionization continuum is modeled via a large pseudo state expansion, which we found is required to obtain reliable elastic and excitation cross sections. Here we present benchmark elastic, single-ionization, electronic excitation and total integrated cross sections over a broad energy range (0.1 to 300 eV) and compare with available experiment and previous calculations. Los Alamos National Laboratory and Curtin University.

47 CFR 25.208 - Power flux density limits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... from all co-frequency space stations of a single non-geostationary-satellite orbit (NGSO) system... geostationary satellite orbit (GSO) by the emissions from all co-frequency earth stations in a non-geostationary... single non-geostationary-satellite orbit (NGSO) system operating in the Fixed-Satellite Service (FSS...

Antares Reference Telescopes System

NASA Astrophysics Data System (ADS)

Viswanathan, V. K.; Kaprelian, E.; Swann, T.; Parker, J.; Wolfe, P.; Woodfin, G.; Knight, D.

1983-11-01

Antares is a 24-beam, 40-TW carbon-dioxide laser fusion system currently nearing completion at the Los Alamos National Laboratory. The 24 beams will be focused onto a tiny target (typically 300-1000 pm in diameter) located approximately at the center of a 7.3-m diameter by 9.3-m long vacuum (10-6 torr) chamber. The design goal is to position the targets to within 10 μm of a selected nominal position, which may be anywhere within a fixed spherical region 1 cm in diameter. The Antares Reference Telescope System is intended to help achieve this goal for alignment and viewing of the various targets used in the laser system. The Antares Reference Telescope System consists of two similar electro-optical systems positioned in a near orthogonal manner in the target chamber area of the laser. Each of these consists of four subsystems: 1) a fixed 9X optical imaging subsystem which produces an image of the target at the vidicon; 2) a reticle projection subsystem which superimposes an image of the reticle pattern at the vidicon; 3) an adjustable front-lighting subsystem which illuminates tne target; and 4) an adjustable back-lighting subsystem which also can be used to illuminate the target. The various optical, mechanical, and vidicon design considerations and trade-offs are discussed. The final system chosen (which is being built) and its current status are described in detail.

Submillimeter Planetary Atmospheric Chemistry Exploration Sounder

NASA Technical Reports Server (NTRS)

Schlecht, Erich T.; Allen, Mark A.; Gill, John J.; Choonsup, Lee; Lin, Robert H.; Sin, Seth; Mehdi, Imran; Siegel, Peter H.; Maestrini, Alain

2013-01-01

Planetary Atmospheric Chemistry Exploration Sounder (SPACES), a high-sensitivity laboratory breadboard for a spectrometer targeted at orbital planetary atmospheric analysis. The frequency range is 520 to 590 GHz, with a target noise temperature sensitivity of 2,500 K for detecting water, sulfur compounds, carbon compounds, and other atmospheric constituents. SPACES is a prototype for a powerful tool for the exploration of the chemistry and dynamics of any planetary atmosphere. It is fundamentally a single-pixel receiver for spectral signals emitted by the relevant constituents, intended to be fed by a fixed or movable telescope/antenna. Its front-end sensor translates the received signal down to the 100-MHz range where it can be digitized and the data transferred to a spectrum analyzer for processing, spectrum generation, and accumulation. The individual microwave and submillimeter wave components (mixers, LO high-powered amplifiers, and multipliers) of SPACES were developed in cooperation with other programs, although with this type of instrument in mind. Compared to previous planetary and Earth science instruments, its broad bandwidth (approx. =.13%) and rapid tunability (approx. =.10 ms) are new developments only made possible recently by the advancement in submillimeter circuit design and processing at JPL.

Design and Processing of a Novel Chaos-Based Stepped Frequency Synthesized Wideband Radar Signal.

PubMed

Zeng, Tao; Chang, Shaoqiang; Fan, Huayu; Liu, Quanhua

2018-03-26

The linear stepped frequency and linear frequency shift keying (FSK) signal has been widely used in radar systems. However, such linear modulation signals suffer from the range-Doppler coupling that degrades radar multi-target resolution. Moreover, the fixed frequency-hopping or frequency-coded sequence can be easily predicted by the interception receiver in the electronic countermeasures (ECM) environments, which limits radar anti-jamming performance. In addition, the single FSK modulation reduces the radar low probability of intercept (LPI) performance, for it cannot achieve a large time-bandwidth product. To solve such problems, we propose a novel chaos-based stepped frequency (CSF) synthesized wideband signal in this paper. The signal introduces chaotic frequency hopping between the coherent stepped frequency pulses, and adopts a chaotic frequency shift keying (CFSK) and phase shift keying (PSK) composited coded modulation in a subpulse, called CSF-CFSK/PSK. Correspondingly, the processing method for the signal has been proposed. According to our theoretical analyses and the simulations, the proposed signal and processing method achieve better multi-target resolution and LPI performance. Furthermore, flexible modulation is able to increase the robustness against identification of the interception receiver and improve the anti-jamming performance of the radar.

The Space Operations Simulation Center (SOSC) and Closed-loop Hardware Testing for Orion Rendezvous System Design

NASA Technical Reports Server (NTRS)

D'Souza, Christopher; Milenkovich, Zoran; Wilson, Zachary; Huich, David; Bendle, John; Kibler, Angela

2011-01-01

The Space Operations Simulation Center (SOSC) at the Lockheed Martin (LM) Waterton Campus in Littleton, Colorado is a dynamic test environment focused on Autonomous Rendezvous and Docking (AR&D) development testing and risk reduction activities. The SOSC supports multiple program pursuits and accommodates testing Guidance, Navigation, and Control (GN&C) algorithms for relative navigation, hardware testing and characterization, as well as software and test process development. The SOSC consists of a high bay (60 meters long by 15.2 meters wide by 15.2 meters tall) with dual six degree-of-freedom (6DOF) motion simulators and a single fixed base 6DOF robot. The large testing area (maximum sensor-to-target effective range of 60 meters) allows for large-scale, flight-like simulations of proximity maneuvers and docking events. The facility also has two apertures for access to external extended-range outdoor target test operations. In addition, the facility contains four Mission Operations Centers (MOCs) with connectivity to dual high bay control rooms and a data/video interface room. The high bay is rated at Class 300,000 (. 0.5 m maximum particles/m3) cleanliness and includes orbital lighting simulation capabilities.

Impacts of Transitioning from Firm Fixed Price to Fixed Price Incentive Firm Target Contracts in PEO Missiles and Space

DTIC Science & Technology

2016-09-01

including suggestions for reducing this burden, to Washington headquarters Services, Directorate for Information Operations and Reports, 1215...OSD) Defense Procurement and Acquisition Policy (DPAP), they were directed by Mr. Assad, Director of Defense Pricing, to change contract type to FPIF...Review. It was the determination of the Director of Army Contracting Command, Redstone Arsenal to make this transition. Shortly following this

Auditory, Vestibular and Cognitive Effects due to Repeated Blast Exposure on the Warfighter

DTIC Science & Technology

2012-10-01

Gaze Horizontal (Left and Right) Description: The primary purpose of the Gaze Horizontal subtest was to detect nystagmus when the head is fixed and...to detect nystagmus when the head is fixed and the eyes are gazing off center from the primary (straight ahead) gaze position. This test is designed...physiological target area and examiner instructions for testing): Spontaneous Nystagmus Smooth Harmonic Acceleration (.01, .08, .32, .64, 1.75

Robust fixed-time synchronization for uncertain complex-valued neural networks with discontinuous activation functions.

PubMed

Ding, Xiaoshuai; Cao, Jinde; Alsaedi, Ahmed; Alsaadi, Fuad E; Hayat, Tasawar

2017-06-01

This paper is concerned with the fixed-time synchronization for a class of complex-valued neural networks in the presence of discontinuous activation functions and parameter uncertainties. Fixed-time synchronization not only claims that the considered master-slave system realizes synchronization within a finite time segment, but also requires a uniform upper bound for such time intervals for all initial synchronization errors. To accomplish the target of fixed-time synchronization, a novel feedback control procedure is designed for the slave neural networks. By means of the Filippov discontinuity theories and Lyapunov stability theories, some sufficient conditions are established for the selection of control parameters to guarantee synchronization within a fixed time, while an upper bound of the settling time is acquired as well, which allows to be modulated to predefined values independently on initial conditions. Additionally, criteria of modified controller for assurance of fixed-time anti-synchronization are also derived for the same system. An example is included to illustrate the proposed methodologies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Control allocation for gimballed/fixed thrusters

NASA Astrophysics Data System (ADS)

Servidia, Pablo A.

2010-02-01

Some overactuated control systems use a control distribution law between the controller and the set of actuators, usually called control allocator. Beyond the control allocator, the configuration of actuators may be designed to be able to operate after a single point of failure, for system optimization and/or decentralization objectives. For some type of actuators, a control allocation is used even without redundancy, being a good example the design and operation of thruster configurations. In fact, as the thruster mass flow direction and magnitude only can be changed under certain limits, this must be considered in the feedback implementation. In this work, the thruster configuration design is considered in the fixed (F), single-gimbal (SG) and double-gimbal (DG) thruster cases. The minimum number of thrusters for each case is obtained and for the resulting configurations a specific control allocation is proposed using a nonlinear programming algorithm, under nominal and single-point of failure conditions.

Interactions between moist heating and dynamics in atmospheric predictability

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

Straus, D.M.; Huntley, M.A.

1994-02-01

The predictability properties of a fixed heating version of a GCM in which the moist heating is specified beforehand are studied in a series of identical twin experiments. Comparison is made to an identical set of experiments using the control GCM, a five-level R30 version of the COLA GCM. The experiments each contain six ensembles, with a single ensemble consisting of six 30-day integrations starting from slightly perturbed Northern Hemisphere wintertime initial conditions. The moist heating from each integration within a single control ensemble was averaged over the ensemble. This averaged heating (a function of three spatial dimensions and time)more » was used as the prespecified heating in each member of the corresponding fixed heating ensemble. The errors grow less rapidly in the fixed heating case. The most rapidly growing scales at small times (global wavenumber 6) have doubling times of 3.2 days compared to 2.4 days for the control experiments. The predictability times for the most energetic scales (global wavenumbers 9-12) are about two weeks for the fixed heating experiments, compared to 9 days for the control. The ratio of error energy in the fixed heating to the control case falls below 0.5 by day 8, and then gradually increases as the error growth slows in the control case. The growth of errors is described in terms of budgets of error kinetic energy (EKE) and error available potential energy (EAPE) developed in terms of global wavenumber n. The diabatic generation of EAPE (G[sub APE]) is positive in the control case and is dominated by midlatitude heating errors after day 2. The fixed heating G[sub APE] is negative at all times due to longwave radiative cooling. 36 refs., 9 figs., 1 tab.« less

Imaging Determinants of Clinical Effectiveness of Lumbar Transforaminal Epidural Steroid Injections.

PubMed

Maus, Timothy P; El-Yahchouchi, Christine A; Geske, Jennifer R; Carter, Rickey E; Kaufmann, Timothy J; Wald, John T; Diehn, Felix E

2016-12-01

To examine associations between imaging characteristics of compressive lesions and patient outcomes after lumbar transforaminal epidural steroid injections (TFESIs) stratified by steroid formulation (solution versus suspension). Retrospective observational study, academic radiology practice. A 516-patient sample was selected from 2,634 consecutive patients receiving lumbar TFESI for radicular pain. The advanced imaging study(s) preceding sampled TFESI were reviewed. Compressive lesions were described by a) nature of the lesion [disc herniation, fixed stenosis, synovial cyst, epidural fibrosis, no lesion] b) degree of neural compression [4 part scale], and c) presence of a tandem lesion. Associations between 2-month categorical outcomes (responder rates for pain, functional recovery) and imaging characteristics, stratified by steroid formulation, were examined with chi-squared tests of categorical outcomes and multivariable logistic regression models. Disc herniation patients had more responders for functional recovery than patients with fixed lesions (54% versus 38%, P = 0.01). Patients with fixed lesions receiving steroid solution (dexamethasone) had more responders for pain relief, with a similar trend for functional recovery, than patients receiving suspensions (59% versus 40%, P = 0.01). Outcomes for patients with fixed lesions treated with dexamethasone were not statistically different from those for disc herniation patients. Patients with single compressive lesions had more responders than those with tandem lesions (55% versus 41%, P = 0.03). In the entire sample, outcomes for disc herniations were more favorable than for fixed lesions. However, fixed lesions treated with dexamethasone had outcomes indistinguishable from disc herniations. Single lesions had better outcomes than tandem lesions. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Psychophysical spectro-temporal receptive fields in an auditory task.

PubMed

Shub, Daniel E; Richards, Virginia M

2009-05-01

Psychophysical relative weighting functions, which provide information about the importance of different regions of a stimulus in forming decisions, are traditionally estimated using trial-based procedures, where a single stimulus is presented and a single response is recorded. Everyday listening is much more "free-running" in that we often must detect randomly occurring signals in the presence of a continuous background. Psychophysical relative weighting functions have not been measured with free-running paradigms. Here, we combine a free-running paradigm with the reverse correlation technique used to estimate physiological spectro-temporal receptive fields (STRFs) to generate psychophysical relative weighting functions that are analogous to physiological STRFs. The psychophysical task required the detection of a fixed target signal (a sequence of spectro-temporally coherent tone pips with a known frequency) in the presence of a continuously presented informational masker (spectro-temporally random tone pips). A comparison of psychophysical relative weighting functions estimated with the current free-running paradigm and trial-based paradigms, suggests that in informational-masking tasks subjects' decision strategies are similar in both free-running and trial-based paradigms. For more cognitively challenging tasks there may be differences in the decision strategies with free-running and trial-based paradigms.

Two MicroRNAs Linked to Nodule Infection and Nitrogen-Fixing Ability in the Legume Lotus japonicus1[W

PubMed Central

De Luis, Ana; Markmann, Katharina; Cognat, Valérie; Holt, Dennis B.; Charpentier, Myriam; Parniske, Martin; Stougaard, Jens; Voinnet, Olivier

2012-01-01

Legumes overcome nitrogen shortage by developing root nodules in which symbiotic bacteria fix atmospheric nitrogen in exchange for host-derived carbohydrates and mineral nutrients. Nodule development involves the distinct processes of nodule organogenesis, bacterial infection, and the onset of nitrogen fixation. These entail profound, dynamic gene expression changes, notably contributed to by microRNAs (miRNAs). Here, we used deep-sequencing, candidate-based expression studies and a selection of Lotus japonicus mutants uncoupling different symbiosis stages to identify miRNAs involved in symbiotic nitrogen fixation. Induction of a noncanonical miR171 isoform, which targets the key nodulation transcription factor Nodulation Signaling Pathway2, correlates with bacterial infection in nodules. A second candidate, miR397, is systemically induced in the presence of active, nitrogen-fixing nodules but not in that of noninfected or inactive nodule organs. It is involved in nitrogen fixation-related copper homeostasis and targets a member of the laccase copper protein family. These findings thus identify two miRNAs specifically responding to symbiotic infection and nodule function in legumes. PMID:23071252

Improved decision making for prioritizing tumor targeting antibodies in human xenografts: Utility of fluorescence imaging to verify tumor target expression, antibody binding and optimization of dosage and application schedule.

PubMed

Dobosz, Michael; Haupt, Ute; Scheuer, Werner

2017-01-01

Preclinical efficacy studies of antibodies targeting a tumor-associated antigen are only justified when the expression of the relevant antigen has been demonstrated. Conventionally, antigen expression level is examined by immunohistochemistry of formalin-fixed paraffin-embedded tumor tissue section. This method represents the diagnostic "gold standard" for tumor target evaluation, but is affected by a number of factors, such as epitope masking and insufficient antigen retrieval. As a consequence, variances and discrepancies in histological staining results can occur, which may influence decision-making and therapeutic outcome. To overcome these problems, we have used different fluorescence-labeled therapeutic antibodies targeting human epidermal growth factor receptor (HER) family members and insulin-like growth factor-1 receptor (IGF1R) in combination with fluorescence imaging modalities to determine tumor antigen expression, drug-target interaction, and biodistribution and tumor saturation kinetics in non-small cell lung cancer xenografts. For this, whole-body fluorescence intensities of labeled antibodies, applied as a single compound or antibody mixture, were measured in Calu-1 and Calu-3 tumor-bearing mice, then ex vivo multispectral tumor tissue analysis at microscopic resolution was performed. With the aid of this simple and fast imaging method, we were able to analyze the tumor cell receptor status of HER1-3 and IGF1R, monitor the antibody-target interaction and evaluate the receptor binding sites of anti-HER2-targeting antibodies. Based on this, the most suitable tumor model, best therapeutic antibody, and optimal treatment dosage and application schedule was selected. Predictions drawn from obtained imaging data were in excellent concordance with outcome of conducted preclinical efficacy studies. Our results clearly demonstrate the great potential of combined in vivo and ex vivo fluorescence imaging for the preclinical development and characterization of monoclonal antibodies.

Single passenger rail car impact test. Volume 1 : overview and selected results : rail passenger equipment collision tests

DOT National Transportation Integrated Search

2000-03-01

On November 16, 1999, at the Transportation Technology Center in Pueblo, Colorado, a test was conducted of a single rail passenger car colliding with a fixed wall at 35 mph. The car was instrumented to measure (1) the deformations of critical structu...

The effect of single engine fixed wing air transport on rate-responsive pacemakers.

PubMed

De Rotte, A A; Van Der Kemp, P

1999-09-01

Insufficient information exists about the safety of patients with accelerometer-based rate-responsive pacemakers in air transport by general aviation aircraft. The response in pacing rate of two types of accelerometer-based rate-responsive pacemakers with data logging capabilities was studied during test flights with single engine fixed wing aircraft. Results were compared with the rate-response of these pacemakers during transportation by car and were also interpreted in respect to physiological heart rate response of aircrew during flights in single engine fixed wing aircraft. In addition, a continuous accelerometer readout was recorded during a turbulent phase of flight. This recording was used for a pacemaker-simulator experiment with maximal sensitive motion-sensor settings. Only a minor increase in pacing rate due to aircraft motion could be demonstrated during all phases of flight at all altitudes with the pacemakers programmed in the normal mode. This increase was of the same magnitude as induced during transport by car and would be of negligible influence on the performance of the individual pacemaker patient equipped with such a pacemaker. Moreover, simultaneous Holter monitoring of the pilots during these flights showed a similar rate-response in natural heart rate compared with the increase in pacing rate induced by aircraft motion in accelerometer-based rate-responsive pacemakers. No sensor-mediated pacemaker tachycardia was seen during any of these recordings. However, a 15% increase in pacing rate was induced by severe air turbulence. Programming the maximal sensitivity of the motion sensor into the pacemaker could, on the other hand, induce a significant increase in pacing rate as was demonstrated by the simulation experiments. These results seem to rule out potentially dangerous or adverse effects from motional or vibrational influences during transport in single engine fixed wing aircraft on accelerometer-based rate-responsive pacemakers with normal activity sensor settings.

EAO consensus conference: economic evaluation of implant-supported prostheses.

PubMed

Beikler, Thomas; Flemmig, Thomas F

2015-09-01

There are various alternatives for the management of oral conditions that may lead to or already have lead to partial or full edentulism. Economic evaluations measure the efficiency of alternative healthcare interventions and provide useful information for decision-making and the allocation of scarce resources. The current English literature dealing with "cost-effectiveness" of dental implant therapy versus different alternative treatment modalities, that is, complete and fixed partial dentures, root canal, and periodontal treatment, has been included in this narrative review. Due to the high heterogeneity within the literature, a meta-analysis could not be conducted. The available evidence from economic evaluations indicated that for the treatment of central incisors with irreversible pulpitis and coronal lesions, root canal treatments were most cost-effective initial treatment options. When initial root canal treatments failed, orthograde retreatments were most cost-effective. When root canal retreatments failed, extractions and replacement with single implant-supported crowns were more cost-effective compared to fixed or removable partial dentures. In the treatment of periodontitis in molars with Class I furcation invasion, non-surgical periodontal therapy was more effective and costed less than implant-supported single crowns. For the replacement of single missing teeth, two evaluations indicated that implant-supported single crowns provided better outcomes in terms of greater quality-adjusted tooth years or survival rates at lower costs compared to fixed partial prostheses. Another economic evaluation found that implant-supported crowns costed more, but provided greater survival rates compared to fixed partial dentures. For the restoration of edentulous mandibles, two evaluations indicated that overdentures retained by two or four implants improved oral health-related quality of life outcomes, but costed more than complete dentures. To better assess the efficiency of implant-supported prostheses in various clinical conditions, more economic evaluations are needed that follow well-established methodologies in health economics. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Attentional Control via Parallel Target-Templates in Dual-Target Search

PubMed Central

Barrett, Doug J. K.; Zobay, Oliver

2014-01-01

Simultaneous search for two targets has been shown to be slower and less accurate than independent searches for the same two targets. Recent research suggests this ‘dual-target cost’ may be attributable to a limit in the number of target-templates than can guide search at any one time. The current study investigated this possibility by comparing behavioural responses during single- and dual-target searches for targets defined by their orientation. The results revealed an increase in reaction times for dual- compared to single-target searches that was largely independent of the number of items in the display. Response accuracy also decreased on dual- compared to single-target searches: dual-target accuracy was higher than predicted by a model restricting search guidance to a single target-template and lower than predicted by a model simulating two independent single-target searches. These results are consistent with a parallel model of dual-target search in which attentional control is exerted by more than one target-template at a time. The requirement to maintain two target-templates simultaneously, however, appears to impose a reduction in the specificity of the memory representation that guides search for each target. PMID:24489793

Fluorescent probes for nucleic Acid visualization in fixed and live cells.

PubMed

Boutorine, Alexandre S; Novopashina, Darya S; Krasheninina, Olga A; Nozeret, Karine; Venyaminova, Alya G

2013-12-11

This review analyses the literature concerning non-fluorescent and fluorescent probes for nucleic acid imaging in fixed and living cells from the point of view of their suitability for imaging intracellular native RNA and DNA. Attention is mainly paid to fluorescent probes for fluorescence microscopy imaging. Requirements for the target-binding part and the fluorophore making up the probe are formulated. In the case of native double-stranded DNA, structure-specific and sequence-specific probes are discussed. Among the latest, three classes of dsDNA-targeting molecules are described: (i) sequence-specific peptides and proteins; (ii) triplex-forming oligonucleotides and (iii) polyamide oligo(N-methylpyrrole/N-methylimidazole) minor groove binders. Polyamides seem to be the most promising targeting agents for fluorescent probe design, however, some technical problems remain to be solved, such as the relatively low sequence specificity and the high background fluorescence inside the cells. Several examples of fluorescent probe applications for DNA imaging in fixed and living cells are cited. In the case of intracellular RNA, only modified oligonucleotides can provide such sequence-specific imaging. Several approaches for designing fluorescent probes are considered: linear fluorescent probes based on modified oligonucleotide analogs, molecular beacons, binary fluorescent probes and template-directed reactions with fluorescence probe formation, FRET donor-acceptor pairs, pyrene excimers, aptamers and others. The suitability of all these methods for living cell applications is discussed.

Effectiveness of Vildagliptin in Clinical Practice: Pooled Analysis of Three Korean Observational Studies (the VICTORY Study).

PubMed

Suh, Sunghwan; Song, Sun Ok; Kim, Jae Hyeon; Cho, Hyungjin; Lee, Woo Je; Lee, Byung-Wan

2017-01-01

The present observational study aimed to evaluate the clinical effectiveness of vildagliptin with metformin in Korean patients with type 2 diabetes mellitus (T2DM). Data were pooled from the vildagliptin postmarketing survey (PMS), the vildagliptin/metformin fixed drug combination (DC) PMS, and a retrospective observational study of vildagliptin/metformin (fixed DC or free DC). The effectiveness endpoint was the proportion of patients who achieved a glycemic target (HbA1c) of ≤7.0% at 24 weeks. In total, 4303 patients were included in the analysis; of these, 2087 patients were eligible. The mean patient age was 56.99 ± 11.25 years. Overall, 58.94% patients achieved an HbA1c target of ≤7.0% at 24 weeks. The glycemic target achievement rate was significantly greater in patients with baseline HbA1c < 7.5% versus ≥7.5% (84.64% versus 43.97%), receiving care at the hospital versus clinic (67.95% versus 52.33%), and receiving vildagliptin/metformin fixed DC versus free DC (70.69% versus 55.42%). Multivariate logistic regression analysis indicated that disease duration ( P < 0.0001), baseline HbA1c ( P < 0.0001), and DC type ( P = 0.0103) had significant effects on drug effectiveness. Vildagliptin plus metformin appeared as an effective treatment option for patients with T2DM in clinical practice settings in Korea.

Low power multi-camera system and algorithms for automated threat detection

NASA Astrophysics Data System (ADS)

Huber, David J.; Khosla, Deepak; Chen, Yang; Van Buer, Darrel J.; Martin, Kevin

2013-05-01

A key to any robust automated surveillance system is continuous, wide field-of-view sensor coverage and high accuracy target detection algorithms. Newer systems typically employ an array of multiple fixed cameras that provide individual data streams, each of which is managed by its own processor. This array can continuously capture the entire field of view, but collecting all the data and back-end detection algorithm consumes additional power and increases the size, weight, and power (SWaP) of the package. This is often unacceptable, as many potential surveillance applications have strict system SWaP requirements. This paper describes a wide field-of-view video system that employs multiple fixed cameras and exhibits low SWaP without compromising the target detection rate. We cycle through the sensors, fetch a fixed number of frames, and process them through a modified target detection algorithm. During this time, the other sensors remain powered-down, which reduces the required hardware and power consumption of the system. We show that the resulting gaps in coverage and irregular frame rate do not affect the detection accuracy of the underlying algorithms. This reduces the power of an N-camera system by up to approximately N-fold compared to the baseline normal operation. This work was applied to Phase 2 of DARPA Cognitive Technology Threat Warning System (CT2WS) program and used during field testing.

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

Scorsetti, Marta; Bignardi, Mario; Clivio, Alessandro

Purpose: A planning study was performed to evaluate RapidArc (RA), a volumetric modulated arc technique, on malignant pleural mesothelioma. The benchmark was conventional fixed-field intensity-modulated radiotherapy (IMRT). Methods and materials: The computed tomography data sets of 6 patients were included. The plans for IMRT with nine fixed beams were compared against double-modulated arcs with a single isocenter. All plans were optimized for 15-MV photon beams. The dose prescription was 54 Gy to the planning target volume. The planning objectives for the planning target volume were a minimal dose of >95% and maximal dose of <107%. For the organs at risk,more » the parameters were as follows: contralateral lung, percentage of volume receiving 5 Gy (V{sub 5Gy}) <60%, V{sub 20Gy} < 10%, mean <10.0 Gy; liver, V{sub 30Gy} <33%, mean <31 Gy; heart, V{sub 45Gy} <30%, V{sub 50Gy} <20%, dose received by 1% of the volume (D{sub 1%}) <60 Gy; contralateral kidney, V{sub 15Gy} <20%; spine, D{sub 1%} <45 Gy; esophagus, V{sub 55Gy} <30%; and spleen, V{sub 40Gy} <50%. The monitor units (MUs) and delivery time were scored to measure the treatment efficiency. The pretreatment portal dosimetry scored delivery to the calculation agreement with the Gamma Agreement Index. Results: RA and IMRT provided equivalent coverage and homogeneity. Both techniques fulfilled objectives on organs at risk with a tendency of RA to improve sparing. The conformity index was 1.9 {+-} 0.1 for RA and IMRT. The number of MU/2Gy was 734 {+-} 82 for RA and 2,195 {+-} 317 for IMRT. The planning vs. delivery agreement revealed a Gamma Agreement Index for IMRT of 96.0% {+-} 2.6% and for RA of 95.7% {+-} 1.5%. The treatment time was 3.7 {+-} 0.3min for RA and 13.4 {+-} 0.1min for IMRT. Conclusion: RA demonstrated compared with conventional IMRT, similar target coverage and better dose sparing to the organs at risks. The number of MUs and the time required to deliver a 2-Gy fraction were much lower for RA, allowing the possibility to incorporate this technique in the treatment options for mesothelioma patients.« less

Application of a GPU-Assisted Maxwell Code to Electromagnetic Wave Propagation in ITER

NASA Astrophysics Data System (ADS)

Kubota, S.; Peebles, W. A.; Woodbury, D.; Johnson, I.; Zolfaghari, A.

2014-10-01

The Low Field Side Reflectometer (LSFR) on ITER is envisioned to provide capabilities for electron density profile and fluctuations measurements in both the plasma core and edge. The current design for the Equatorial Port Plug 11 (EPP11) employs seven monostatic antennas for use with both fixed-frequency and swept-frequency systems. The present work examines the characteristics of this layout using the 3-D version of the GPU-Assisted Maxwell Code (GAMC-3D). Previous studies in this area were performed with either 2-D full wave codes or 3-D ray- and beam-tracing. GAMC-3D is based on the FDTD method and can be run with either a fixed-frequency or modulated (e.g. FMCW) source, and with either a stationary or moving target (e.g. Doppler backscattering). The code is designed to run on a single NVIDIA Tesla GPU accelerator, and utilizes a technique based on the moving window method to overcome the size limitation of the onboard memory. Effects such as beam drift, linear mode conversion, and diffraction/scattering will be examined. Comparisons will be made with beam-tracing calculations using the complex eikonal method. Supported by U.S. DoE Grants DE-FG02-99ER54527 and DE-AC02-09CH11466, and the DoE SULI Program at PPPL.

Multifunctional and Context-Dependent Control of Vocal Acoustics by Individual Muscles

PubMed Central

Srivastava, Kyle H.; Elemans, Coen P.H.

2015-01-01

The relationship between muscle activity and behavioral output determines how the brain controls and modifies complex skills. In vocal control, ensembles of muscles are used to precisely tune single acoustic parameters such as fundamental frequency and sound amplitude. If individual vocal muscles were dedicated to the control of single parameters, then the brain could control each parameter independently by modulating the appropriate muscle or muscles. Alternatively, if each muscle influenced multiple parameters, a more complex control strategy would be required to selectively modulate a single parameter. Additionally, it is unknown whether the function of single muscles is fixed or varies across different vocal gestures. A fixed relationship would allow the brain to use the same changes in muscle activation to, for example, increase the fundamental frequency of different vocal gestures, whereas a context-dependent scheme would require the brain to calculate different motor modifications in each case. We tested the hypothesis that single muscles control multiple acoustic parameters and that the function of single muscles varies across gestures using three complementary approaches. First, we recorded electromyographic data from vocal muscles in singing Bengalese finches. Second, we electrically perturbed the activity of single muscles during song. Third, we developed an ex vivo technique to analyze the biomechanical and acoustic consequences of single-muscle perturbations. We found that single muscles drive changes in multiple parameters and that the function of single muscles differs across vocal gestures, suggesting that the brain uses a complex, gesture-dependent control scheme to regulate vocal output. PMID:26490859

A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research.

PubMed

Kouzani, Abbas Z; Abulseoud, Osama A; Tye, Susannah J; Hosain, M D Kamal; Berk, Michael

2013-01-01

Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.

Radial scaling in inclusive jet production at hadron colliders

NASA Astrophysics Data System (ADS)

Taylor, Frank E.

2018-03-01

Inclusive jet production in p-p and p ¯ -p collisions shows many of the same kinematic systematics as observed in single-particle inclusive production at much lower energies. In an earlier study (1974) a phenomenology, called radial scaling, was developed for the single-particle inclusive cross sections that attempted to capture the essential underlying physics of pointlike parton scattering and the fragmentation of partons into hadrons suppressed by the kinematic boundary. The phenomenology was successful in emphasizing the underlying systematics of the inclusive particle productions. Here we demonstrate that inclusive jet production at the Large Hadron Collider (LHC) in high-energy p-p collisions and at the Tevatron in p ¯ -p inelastic scattering shows similar behavior. The ATLAS inclusive jet production plotted as a function of this scaling variable is studied for √s of 2.76, 7 and 13 TeV and is compared to p ¯ -p inclusive jet production at 1.96 TeV measured at the CDF and D0 at the Tevatron and p-Pb inclusive jet production at the LHC ATLAS at √sNN=5.02 TeV . Inclusive single-particle production at Fermi National Accelerator Laboratory fixed target and Intersecting Storage Rings energies are compared to inclusive J /ψ production at the LHC measured in ATLAS, CMS and LHCb. Striking common features of the data are discussed.

Quality target negotiation in health care: evidence from the English NHS.

PubMed

Fichera, Eleonora; Gravelle, Hugh; Pezzino, Mario; Sutton, Matt

2016-09-01

We examine how public sector third-party purchasers and hospitals negotiate quality targets when a fixed proportion of hospital revenue is required to be linked to quality. We develop a bargaining model linking the number of quality targets to purchaser and hospital characteristics. Using data extracted from 153 contracts for acute hospital services in England in 2010/2011, we find that the number of quality targets is associated with the purchaser's population health and its budget, the hospital type, whether the purchaser delegated negotiation to an agency, and the quality targets imposed by the supervising regional health authority.

Review of the inverse scattering problem at fixed energy in quantum mechanics

NASA Technical Reports Server (NTRS)

Sabatier, P. C.

1972-01-01

Methods of solution of the inverse scattering problem at fixed energy in quantum mechanics are presented. Scattering experiments of a beam of particles at a nonrelativisitic energy by a target made up of particles are analyzed. The Schroedinger equation is used to develop the quantum mechanical description of the system and one of several functions depending on the relative distance of the particles. The inverse problem is the construction of the potentials from experimental measurements.

Comparison of long-term safety of fixed-dose combinations azilsartan medoxomil/chlorthalidone vs olmesartan medoxomil/hydrochlorothiazide.

PubMed

Neutel, Joel M; Cushman, William C; Lloyd, Eric; Barger, Bruce; Handley, Alison

2017-09-01

This 52-week, randomized, open-label study evaluated long-term safety/tolerability of fixed-dose combination azilsartan medoxomil/chlorthalidone (AZL-M/CLD) vs fixed-dose combination olmesartan medoxomil/hydrochlorothiazide (OLM/HCTZ) in patients with essential hypertension (stage 2; clinic systolic blood pressure 160-190 mm Hg). Initial AZL-M/CLD 40/12.5 mg/d (n=418) or OLM/HCTZ 20/12.5 mg/d (n=419) could be uptitrated during weeks 4 to 52 (AZL-M/CLD to 80/25 mg; OLM/HCTZ to 40/25 mg [United States] or 20/25 mg [Europe]) to meet blood pressure targets. Treatment-emergent adverse events/serious adverse events occurred in 78.5%/5.7% of patients taking AZL-M/CLD vs 76.4%/6.2% taking OLM/HCTZ. The most frequent adverse events were dizziness (16.3% vs 12.6%), blood creatinine increase (21.5% vs 8.6%), headache (7.4% vs 11.0%), and nasopharyngitis (12.2% vs 11.5%). Hypokalemia was uncommon (1.0% vs 0.7%). Greater blood pressure reductions with AZL-M/CLD by week 2 were maintained throughout the study, despite less uptitration (32.3% vs 48.9% with OLM/HCTZ). Fixed-dose combination AZL-M/CLD showed an encouraging benefit-risk profile when used per standard clinical practice in a titrate-to-target strategy. ©2017 Wiley Periodicals, Inc.

Method for Correcting Control Surface Angle Measurements in Single Viewpoint Photogrammetry

NASA Technical Reports Server (NTRS)

Burner, Alpheus W. (Inventor); Barrows, Danny A. (Inventor)

2006-01-01

A method of determining a corrected control surface angle for use in single viewpoint photogrammetry to correct control surface angle measurements affected by wing bending. First and second visual targets are spaced apart &om one another on a control surface of an aircraft wing. The targets are positioned at a semispan distance along the aircraft wing. A reference target separation distance is determined using single viewpoint photogrammetry for a "wind off condition. An apparent target separation distance is then computed for "wind on." The difference between the reference and apparent target separation distances is minimized by recomputing the single viewpoint photogrammetric solution for incrementally changed values of target semispan distances. A final single viewpoint photogrammetric solution is then generated that uses the corrected semispan distance that produced the minimized difference between the reference and apparent target separation distances. The final single viewpoint photogrammetric solution set is used to determine the corrected control surface angle.

Infrared dim moving target tracking via sparsity-based discriminative classifier and convolutional network

NASA Astrophysics Data System (ADS)

Qian, Kun; Zhou, Huixin; Wang, Bingjian; Song, Shangzhen; Zhao, Dong

2017-11-01

Infrared dim and small target tracking is a great challenging task. The main challenge for target tracking is to account for appearance change of an object, which submerges in the cluttered background. An efficient appearance model that exploits both the global template and local representation over infrared image sequences is constructed for dim moving target tracking. A Sparsity-based Discriminative Classifier (SDC) and a Convolutional Network-based Generative Model (CNGM) are combined with a prior model. In the SDC model, a sparse representation-based algorithm is adopted to calculate the confidence value that assigns more weights to target templates than negative background templates. In the CNGM model, simple cell feature maps are obtained by calculating the convolution between target templates and fixed filters, which are extracted from the target region at the first frame. These maps measure similarities between each filter and local intensity patterns across the target template, therefore encoding its local structural information. Then, all the maps form a representation, preserving the inner geometric layout of a candidate template. Furthermore, the fixed target template set is processed via an efficient prior model. The same operation is applied to candidate templates in the CNGM model. The online update scheme not only accounts for appearance variations but also alleviates the migration problem. At last, collaborative confidence values of particles are utilized to generate particles' importance weights. Experiments on various infrared sequences have validated the tracking capability of the presented algorithm. Experimental results show that this algorithm runs in real-time and provides a higher accuracy than state of the art algorithms.

GalaxyTBM: template-based modeling by building a reliable core and refining unreliable local regions.

PubMed

Ko, Junsu; Park, Hahnbeom; Seok, Chaok

2012-08-10

Protein structures can be reliably predicted by template-based modeling (TBM) when experimental structures of homologous proteins are available. However, it is challenging to obtain structures more accurate than the single best templates by either combining information from multiple templates or by modeling regions that vary among templates or are not covered by any templates. We introduce GalaxyTBM, a new TBM method in which the more reliable core region is modeled first from multiple templates and less reliable, variable local regions, such as loops or termini, are then detected and re-modeled by an ab initio method. This TBM method is based on "Seok-server," which was tested in CASP9 and assessed to be amongst the top TBM servers. The accuracy of the initial core modeling is enhanced by focusing on more conserved regions in the multiple-template selection and multiple sequence alignment stages. Additional improvement is achieved by ab initio modeling of up to 3 unreliable local regions in the fixed framework of the core structure. Overall, GalaxyTBM reproduced the performance of Seok-server, with GalaxyTBM and Seok-server resulting in average GDT-TS of 68.1 and 68.4, respectively, when tested on 68 single-domain CASP9 TBM targets. For application to multi-domain proteins, GalaxyTBM must be combined with domain-splitting methods. Application of GalaxyTBM to CASP9 targets demonstrates that accurate protein structure prediction is possible by use of a multiple-template-based approach, and ab initio modeling of variable regions can further enhance the model quality.

The importance of fixed costs in animal health systems.

PubMed

Tisdell, C A; Adamson, D

2017-04-01

In this paper, the authors detail the structure and optimal management of health systems as influenced by the presence and level of fixed costs. Unlike variable costs, fixed costs cannot be altered, and are thus independent of the level of veterinary activity in the short run. Their importance is illustrated by using both single-period and multi-period models. It is shown that multi-stage veterinary decision-making can often be envisaged as a sequence of fixed-cost problems. In general, it becomes clear that, the higher the fixed costs, the greater the net benefit of veterinary activity must be, if such activity is to be economic. The authors also assess the extent to which it pays to reduce fixed costs and to try to compensate for this by increasing variable costs. Fixed costs have major implications for the industrial structure of the animal health products industry and for the structure of the private veterinary services industry. In the former, they favour market concentration and specialisation in the supply of products. In the latter, they foster increased specialisation. While cooperation by individual farmers may help to reduce their individual fixed costs, the organisational difficulties and costs involved in achieving this cooperation can be formidable. In such cases, the only solution is government provision of veterinary services. Moreover, international cooperation may be called for. Fixed costs also influence the nature of the provision of veterinary education.

Performance determinants of fixed gear cycling during criteriums.

PubMed

Babault, Nicolas; Poisson, Maxime; Cimadoro, Guiseppe; Cometti, Carole; Païzis, Christos

2018-06-17

Nowadays, fixed gear competitions on outdoor circuits such as criteriums are regularly organized worldwide. To date, no study has investigated this alternative form of cycling. The purpose of the present study was to examine fixed gear performance indexes and to characterize physiological determinants of fixed gear cyclists. This study was carried out in two parts. Part 1 (n = 36) examined correlations between performance indexes obtained during a real fixed gear criterium (time trial, fastest laps, averaged lap time during races, fatigue indexes) and during a sprint track time trial. Part 2 (n = 9) examined correlations between the recorded performance indexes and some aerobic and anaerobic performance outputs (VO 2max , maximal aerobic power, knee extensor and knee flexor maximal voluntary torque, vertical jump height and performance during a modified Wingate test). Results from Part 1 indicated significant correlations between fixed gear final performance (i.e. average lap time during the finals) and single lap time (time trial, fastest lap during races and sprint track time trial). In addition, results from Part 2 revealed significant correlations between fixed gear performance and aerobic indicators (VO 2max and maximal aerobic power). However, no significant relationship was obtained between fixed gear cycling and anaerobic qualities such as strength. Similarly to traditional cycling disciplines, we concluded that fixed gear cycling is mainly limited by aerobic capacity, particularly criteriums final performance. However, specific skills including technical competency should be considered.

The unified database for the fixed target experiment BM@N

NASA Astrophysics Data System (ADS)

Gertsenberger, K. V.

2016-09-01

The article describes the developed database designed as comprehensive data storage of the fixed target experiment BM@N [1] at Joint Institute for Nuclear Research (JINR) in Dubna. The structure and purposes of the BM@N facility will be briefly presented. The scheme of the unified database and its parameters will be described in detail. The use of the BM@N database implemented on the PostgreSQL database management system (DBMS) allows one to provide user access to the actual information of the experiment. Also the interfaces developed for the access to the database will be presented. One was implemented as the set of C++ classes to access the data without SQL statements, the other-Web-interface being available on the Web page of the BM@N experiment.

Polarimetric ISAR: Simulation and image reconstruction

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

Chambers, David H.

In polarimetric ISAR the illumination platform, typically airborne, carries a pair of antennas that are directed toward a fixed point on the surface as the platform moves. During platform motion, the antennas maintain their gaze on the point, creating an effective aperture for imaging any targets near that point. The interaction between the transmitted fields and targets (e.g. ships) is complicated since the targets are typically many wavelengths in size. Calculation of the field scattered from the target typically requires solving Maxwell’s equations on a large three-dimensional numerical grid. This is prohibitive to use in any real-world imaging algorithm, somore » the scattering process is typically simplified by assuming the target consists of a cloud of independent, non-interacting, scattering points (centers). Imaging algorithms based on this scattering model perform well in many applications. Since polarimetric radar is not very common, the scattering model is often derived for a scalar field (single polarization) where the individual scatterers are assumed to be small spheres. However, when polarization is important, we must generalize the model to explicitly account for the vector nature of the electromagnetic fields and its interaction with objects. In this note, we present a scattering model that explicitly includes the vector nature of the fields but retains the assumption that the individual scatterers are small. The response of the scatterers is described by electric and magnetic dipole moments induced by the incident fields. We show that the received voltages in the antennas are linearly related to the transmitting currents through a scattering impedance matrix that depends on the overall geometry of the problem and the nature of the scatterers.« less

Spatial decoupling of targets and flashing stimuli for visual brain-computer interfaces

NASA Astrophysics Data System (ADS)

Waytowich, Nicholas R.; Krusienski, Dean J.

2015-06-01

Objective. Recently, paradigms using code-modulated visual evoked potentials (c-VEPs) have proven to achieve among the highest information transfer rates for noninvasive brain-computer interfaces (BCIs). One issue with current c-VEP paradigms, and visual-evoked paradigms in general, is that they require direct foveal fixation of the flashing stimuli. These interfaces are often visually unpleasant and can be irritating and fatiguing to the user, thus adversely impacting practical performance. In this study, a novel c-VEP BCI paradigm is presented that attempts to perform spatial decoupling of the targets and flashing stimuli using two distinct concepts: spatial separation and boundary positioning. Approach. For the paradigm, the flashing stimuli form a ring that encompasses the intended non-flashing targets, which are spatially separated from the stimuli. The user fixates on the desired target, which is classified using the changes to the EEG induced by the flashing stimuli located in the non-foveal visual field. Additionally, a subset of targets is also positioned at or near the stimulus boundaries, which decouples targets from direct association with a single stimulus. This allows a greater number of target locations for a fixed number of flashing stimuli. Main results. Results from 11 subjects showed practical classification accuracies for the non-foveal condition, with comparable performance to the direct-foveal condition for longer observation lengths. Online results from 5 subjects confirmed the offline results with an average accuracy across subjects of 95.6% for a 4-target condition. The offline analysis also indicated that targets positioned at or near the boundaries of two stimuli could be classified with the same accuracy as traditional superimposed (non-boundary) targets. Significance. The implications of this research are that c-VEPs can be detected and accurately classified to achieve comparable BCI performance without requiring potentially irritating direct foveation of flashing stimuli. Furthermore, this study shows that it is possible to increase the number of targets beyond the number of stimuli without degrading performance. Given the superior information transfer rate of c-VEP paradigms, these results can lead to the development of more practical and ergonomic BCIs.

An Analytical Assessment of NASA's N+1 Subsonic Fixed Wing Project Noise Goal

NASA Technical Reports Server (NTRS)

Berton, Jeffrey J.; Envia, Edmane; Burley, Casey L.

2009-01-01

The Subsonic Fixed Wing Project of NASA's Fundamental Aeronautics Program has adopted a noise reduction goal for new, subsonic, single-aisle, civil aircraft expected to replace current 737 and A320 airplanes. These so-called 'N+1' aircraft - designated in NASA vernacular as such since they will follow the current, in-service, 'N' airplanes - are hoped to achieve certification noise goal levels of 32 cumulative EPNdB under current Stage 4 noise regulations. A notional, N+1, single-aisle, twinjet transport with ultrahigh bypass ratio turbofan engines is analyzed in this study using NASA software and methods. Several advanced noise-reduction technologies are analytically applied to the propulsion system and airframe. Certification noise levels are predicted and compared with the NASA goal.

Operant conditioning of neural activity in freely behaving monkeys with intracranial reinforcement

PubMed Central

Eaton, Ryan W.; Libey, Tyler

2017-01-01

Operant conditioning of neural activity has typically been performed under controlled behavioral conditions using food reinforcement. This has limited the duration and behavioral context for neural conditioning. To reward cell activity in unconstrained primates, we sought sites in nucleus accumbens (NAc) whose stimulation reinforced operant responding. In three monkeys, NAc stimulation sustained performance of a manual target-tracking task, with response rates that increased monotonically with increasing NAc stimulation. We recorded activity of single motor cortex neurons and documented their modulation with wrist force. We conditioned increased firing rates with the monkey seated in the training booth and during free behavior in the cage using an autonomous head-fixed recording and stimulating system. Spikes occurring above baseline rates triggered single or multiple electrical pulses to the reinforcement site. Such rate-contingent, unit-triggered stimulation was made available for periods of 1–3 min separated by 3–10 min time-out periods. Feedback was presented as event-triggered clicks both in-cage and in-booth, and visual cues were provided in many in-booth sessions. In-booth conditioning produced increases in single neuron firing probability with intracranial reinforcement in 48 of 58 cells. Reinforced cell activity could rise more than five times that of non-reinforced activity. In-cage conditioning produced significant increases in 21 of 33 sessions. In-cage rate changes peaked later and lasted longer than in-booth changes, but were often comparatively smaller, between 13 and 18% above non-reinforced activity. Thus intracranial stimulation reinforced volitional increases in cortical firing rates during both free behavior and a controlled environment, although changes in the latter were more robust. NEW & NOTEWORTHY Closed-loop brain-computer interfaces (BCI) were used to operantly condition increases in muscle and neural activity in monkeys by delivering activity-dependent stimuli to an intracranial reinforcement site (nucleus accumbens). We conditioned increased firing rates with the monkeys seated in a training booth and also, for the first time, during free behavior in a cage using an autonomous head-fixed BCI. PMID:28031396

Operant conditioning of neural activity in freely behaving monkeys with intracranial reinforcement.

PubMed

Eaton, Ryan W; Libey, Tyler; Fetz, Eberhard E

2017-03-01

Operant conditioning of neural activity has typically been performed under controlled behavioral conditions using food reinforcement. This has limited the duration and behavioral context for neural conditioning. To reward cell activity in unconstrained primates, we sought sites in nucleus accumbens (NAc) whose stimulation reinforced operant responding. In three monkeys, NAc stimulation sustained performance of a manual target-tracking task, with response rates that increased monotonically with increasing NAc stimulation. We recorded activity of single motor cortex neurons and documented their modulation with wrist force. We conditioned increased firing rates with the monkey seated in the training booth and during free behavior in the cage using an autonomous head-fixed recording and stimulating system. Spikes occurring above baseline rates triggered single or multiple electrical pulses to the reinforcement site. Such rate-contingent, unit-triggered stimulation was made available for periods of 1-3 min separated by 3-10 min time-out periods. Feedback was presented as event-triggered clicks both in-cage and in-booth, and visual cues were provided in many in-booth sessions. In-booth conditioning produced increases in single neuron firing probability with intracranial reinforcement in 48 of 58 cells. Reinforced cell activity could rise more than five times that of non-reinforced activity. In-cage conditioning produced significant increases in 21 of 33 sessions. In-cage rate changes peaked later and lasted longer than in-booth changes, but were often comparatively smaller, between 13 and 18% above non-reinforced activity. Thus intracranial stimulation reinforced volitional increases in cortical firing rates during both free behavior and a controlled environment, although changes in the latter were more robust. NEW & NOTEWORTHY Closed-loop brain-computer interfaces (BCI) were used to operantly condition increases in muscle and neural activity in monkeys by delivering activity-dependent stimuli to an intracranial reinforcement site (nucleus accumbens). We conditioned increased firing rates with the monkeys seated in a training booth and also, for the first time, during free behavior in a cage using an autonomous head-fixed BCI. Copyright © 2017 the American Physiological Society.

Bearings Only Air-to-Air Ranging

DTIC Science & Technology

1988-07-25

directly in fiut of the observer whem first detected, more time will be needed for a good estimate. A sound uinp them is for the observer, having...altitude angle to provide an estimate of the z component. Moving targets commonly require some 60 seconds for good estimates of target location and...fixed target case, where a good strategy for the observer can be determined a priori, highly effective maneuvers for the observer in the case of a moving

Classification of underwater targets from autonomous underwater vehicle sampled bistatic acoustic scattered fields.

PubMed

Fischell, Erin M; Schmidt, Henrik

2015-12-01

One of the long term goals of autonomous underwater vehicle (AUV) minehunting is to have multiple inexpensive AUVs in a harbor autonomously classify hazards. Existing acoustic methods for target classification using AUV-based sensing, such as sidescan and synthetic aperture sonar, require an expensive payload on each outfitted vehicle and post-processing and/or image interpretation. A vehicle payload and machine learning classification methodology using bistatic angle dependence of target scattering amplitudes between a fixed acoustic source and target has been developed for onboard, fully autonomous classification with lower cost-per-vehicle. To achieve the high-quality, densely sampled three-dimensional (3D) bistatic scattering data required by this research, vehicle sampling behaviors and an acoustic payload for precision timed data acquisition with a 16 element nose array were demonstrated. 3D bistatic scattered field data were collected by an AUV around spherical and cylindrical targets insonified by a 7-9 kHz fixed source. The collected data were compared to simulated scattering models. Classification and confidence estimation were shown for the sphere versus cylinder case on the resulting real and simulated bistatic amplitude data. The final models were used for classification of simulated targets in real time in the LAMSS MOOS-IvP simulation package [M. Benjamin, H. Schmidt, P. Newman, and J. Leonard, J. Field Rob. 27, 834-875 (2010)].

Surface target-tracking guidance by self-organizing formation flight of fixed-wing UAV

NASA Astrophysics Data System (ADS)

Regina, N.; Zanzi, M.

This paper presents a new concept of ground target surveillance based on a formation flight of two Unmanned Aerial Vehicles (UAVs) of fixed-wing type. Each UAV considered in this work has its own guidance law specifically designed for two different aims. A self organizing non-symmetric collaborative surveying scheme has been developed based on pursuers with different roles: the close-up-pursuer and the distance-pursuer. The close-up-pursuer behaves according to a guidance law which takes it to continually over-fly the target, also optimizing flight endurance. On the other hand, the distancepursuer behaves so as to circle around the target by flying at a certain distance and altitude from it; moreover, its motion ensures the maximum “ seeability” of the ground based target. In addition, the guidance law designed for the distance-pursuer also implements a collision avoidance feature in order to prevent possible risks of collision with the close-up-pursuer during the tracking maneuvers. The surveying scheme is non-symmetric in the sense that the collision avoidance feature is accomplished by a guidance law implemented only on one of the two pursuers; moreover, it is collaborative because the surveying is performed by different tasks of two UAVs and is self-organizing because, due to the collision avoidance feature, target tracking does not require pre-planned collision-risk-free trajectories but trajectories are generated in real time.

Fiber alignment apparatus and method

DOEpatents

Kravitz, Stanley H.; Warren, Mial Evans; Snipes, Jr., Morris Burton; Armendariz, Marcelino Guadalupe; Word, V., James Cole

1997-01-01

A fiber alignment apparatus includes a micro-machined nickel spring that captures and locks arrays of single mode fibers into position. The design consists of a movable nickel leaf shaped spring and a fixed pocket where fibers are held. The fiber is slid between the spring and a fixed block, which tensions the spring. When the fiber reaches the pocket, it automatically falls into the pocket and is held by the pressure of the leaf spring.

Fiber alignment apparatus and method

DOEpatents

Kravitz, S.H.; Warren, M.E.; Snipes, M.B. Jr.; Armendariz, M.G.; Word, J.C. V

1997-08-19

A fiber alignment apparatus includes a micro-machined nickel spring that captures and locks arrays of single mode fibers into position. The design consists of a movable nickel leaf shaped spring and a fixed pocket where fibers are held. The fiber is slid between the spring and a fixed block, which tensions the spring. When the fiber reaches the pocket, it automatically falls into the pocket and is held by the pressure of the leaf spring. 8 figs.

Single passenger rail car impact test. Volume 2 : summary of occupant protection program : rail passenger equipment collision tests

DOT National Transportation Integrated Search

2000-03-01

A test in which a single rail passenger car was crashed into a fixed wall at 35 mph was conducted at the Transportation Technology Center on November 16, 1999. The car was instrumented to measure (1) the deformations of critical structural elements, ...

Finite-horizon control-constrained nonlinear optimal control using single network adaptive critics.

PubMed

Heydari, Ali; Balakrishnan, Sivasubramanya N

2013-01-01

To synthesize fixed-final-time control-constrained optimal controllers for discrete-time nonlinear control-affine systems, a single neural network (NN)-based controller called the Finite-horizon Single Network Adaptive Critic is developed in this paper. Inputs to the NN are the current system states and the time-to-go, and the network outputs are the costates that are used to compute optimal feedback control. Control constraints are handled through a nonquadratic cost function. Convergence proofs of: 1) the reinforcement learning-based training method to the optimal solution; 2) the training error; and 3) the network weights are provided. The resulting controller is shown to solve the associated time-varying Hamilton-Jacobi-Bellman equation and provide the fixed-final-time optimal solution. Performance of the new synthesis technique is demonstrated through different examples including an attitude control problem wherein a rigid spacecraft performs a finite-time attitude maneuver subject to control bounds. The new formulation has great potential for implementation since it consists of only one NN with single set of weights and it provides comprehensive feedback solutions online, though it is trained offline.

Selective Blockade of Human Natural Killer Cells by a Monoclonal Antibody

NASA Astrophysics Data System (ADS)

Newman, Walter

1982-06-01

A murine monoclonal antibody, 13.1, which blocks human natural killer (NK) cell-mediated lysis, has been developed. Hybridoma 13.1 was derived by fusion of NS-1 cells with spleen cells from mice immunized with an enriched population of NK cells. Supernatants of growing hybridomas were screened for their ability to block NK cell-mediated lysis of K562 targets. Antibody 13.1 is an IgG1 with a single light chain type and it does not fix complement. The 13.1 antigen is expressed on all peripheral blood mononuclear cells, with an antigen density approximately 1/30th that of HLA antigen heavy chain. Pretreatment and washing experiments revealed that inhibition of cytotoxicity occurred at the effector cell level only. Significant blocking was achieved with nanogram quantities of antibody and was not due to toxic effects on NK cells. Likewise, controls with other antibodies of the same subclass demonstrated that blocking was not a consequence of mere binding to NK cells. When a panel of 17 NK cell-susceptible targets was tested, the lysis of only 5 of these was blocked, namely K562, HL-60, KG-1, Daudi, and HEL, a human erythroleukemic cell line. The lysis of 12 human B cell and T cell line targets was not inhibited. In addition to the demonstration that the 13.1 antigen is a crucial cell surface structure involved in NK lysis, a heterogeneity of target cell recognition has been revealed that argues for the proposition that individual NK cells have multiple recognitive capabilities.

Autonomous search and surveillance with small fixed wing aircraft

NASA Astrophysics Data System (ADS)

McGee, Timothy Garland

Small unmanned aerial vehicles (UAVs) have the potential to act as low cost tools in a variety of both civilian and military applications including traffic monitoring, border patrol, and search and rescue. While most current operational UAV systems require human operators, advances in autonomy will allow these systems to reach their full potential as sensor platforms. This dissertation specifically focuses on developing advanced control, path planning, search, and image processing techniques that allow small fixed wing aircraft to autonomously collect data. The problems explored were motivated by experience with the development and experimental flight testing of a fleet of small autonomous fixed wing aircraft. These issues, which have not been fully addressed in past work done on ground vehicles or autonomous helicopters, include the influence of wind and turning rate constraints, the non-negligible velocity of ground targets relative to the aircraft velocity, and limitations on sensor size and processing power on small vehicles. Several contributions for the autonomous operation of small fixed wing aircraft are presented. Several sliding surface controllers are designed which extend previous techniques to include variable sliding surface coefficients and the use of spatial vehicle dynamics. These advances eliminate potential singularities in the control laws to follow spatially defined paths and allow smooth transition between controllers. The optimal solution for the problem of path planning through an ordered set of points for an aircraft with a bounded turning rate in the presence of a constant wind is then discussed. Path planning strategies are also explored to guarantee that a searcher will travel within sensing distance of a mobile ground target. This work assumes only a maximum velocity of the target and is designed to succeed for any possible path of the target. Closed-loop approximations of both the path planning and search techniques, using the sliding surface controllers already discussed, are also studied. Finally, a novel method is presented to detect obstacles by segmenting an image into sky and non-sky regions. The feasibility of this method is demonstrated experimentally on an aircraft test bed.

The Hardest Straight-in Pool Shot

ERIC Educational Resources Information Center

Mabry, Rick

2010-01-01

When playing pool or billiards, a player often has the opportunity to make a "straight-in" shot, that is, one in which the cue ball, the object ball, and the target (e.g., a pocket) are collinear. With the distance from the cue ball to the target assumed fixed, the relative difficulty is here explored of shots taken at varying positions of the…

Interaction of fluorescently labeled pyrrole-imidazole polyamide probes with fixed and living murine and human cells.

PubMed

Nozeret, Karine; Loll, François; Cardoso, Gildas Mouta; Escudé, Christophe; Boutorine, Alexandre S

2018-06-01

Pericentromeric heterochromatin plays important roles in controlling gene expression and cellular differentiation. Fluorescent pyrrole-imidazole polyamides targeting murine pericentromeric DNA (major satellites) can be used for the visualization of pericentromeric heterochromatin foci in live mouse cells. New derivatives targeting human repeated DNA sequences (α-satellites) were synthesized and their interaction with target DNA was characterized. The possibility to use major satellite and α -satellite binding polyamides as tools for staining pericentromeric heterochromatin was further investigated in fixed and living mouse and human cells. The staining that was previously observed using the mouse model was further characterized and optimized, but remained limited regarding the fluorophores that can be used. The promising results regarding the staining in the mouse model could not be extended to the human model. Experiments performed in human cells showed chromosomal DNA staining without selectivity. Factors limiting the use of fluorescent polyamides, in particular probe aggregation in the cytoplasm, were investigated. Results are discussed with regards to structure and affinity of probes, density of target sites and chromatin accessibility in both models. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Unexpected timely fracture union in matrix metalloproteinase 9 deficient mice.

PubMed

Yuasa, Masato; Saito, Masanori; Molina, Cesar; Moore-Lotridge, Stephanie N; Benvenuti, Michael A; Mignemi, Nicholas A; Okawa, Atsushi; Yoshii, Toshitaka; Schwartz, Herbert S; Nyman, Jeffry S; Schoenecker, Jonathan G

2018-01-01

Immediately following a fracture, a fibrin laden hematoma is formed to prevent bleeding and infection. Subsequently, the organized removal of fibrin, via the protease plasmin, is essential to permit fracture repair through angiogenesis and ossification. Yet, when plasmin activity is lost, the depletion of fibrin alone is insufficient to fully restore fracture repair, suggesting the existence of additional plasmin targets important for fracture repair. Previously, activated matrix metalloproteinase 9 (MMP-9) was demonstrated to function in fracture repair by promoting angiogenesis. Given that MMP-9 is a defined plasmin target, it was hypothesized that pro-MMP-9, following plasmin activation, promotes fracture repair. This hypothesis was tested in a fixed murine femur fracture model with serial assessment of fracture healing. Contrary to previous findings, a complete loss of MMP-9 failed to affect fracture healing and union through 28 days post injury. Therefore, these results demonstrated that MMP-9 is dispensable for timely fracture union and cartilage transition to bone in fixed femur fractures. Pro-MMP-9 is therefore not a significant target of plasmin in fracture repair and future studies assessing additional plasmin targets associated with angiogenesis are warranted.

An unbinding problem? The disintegration of visible, previously attended objects does not attract attention.

PubMed

Wolfe, Jeremy M; Oliva, Aude; Butcher, Serena J; Arsenio, Helga C

2002-01-01

In seven experiments, observers searched for a scrambled object among normal objects. The critical comparison was between repeated search in which the same set of stimuli remained present in fixed positions in the display for many (>100) trials and unrepeated conditions in which new stimuli were presented on each trial. In repeated search conditions, observers monitored an essentially stable display for the disruption of a clearly visible object. This is an extension of repeated search experiments in which subjects search a fixed set of items for different targets on each trial (Wolfe, Klempen, & Dahlen, 2000) and can be considered as a form of a "change blindness" task. The unrepeated search was very inefficient, showing that a scrambled object does not "pop-out" among intact objects (or vice versa). Interestingly, the repeated search condition was just as inefficient, as if participants had to search for the scrambled target even after extensive experience with the specific change in the specific scene. The results suggest that the attentional processes involved in searching for a target in a novel scene may be very similar to those used to confirm the presence of a target in a familiar scene.

Separability study of wheat and small grains

NASA Technical Reports Server (NTRS)

Lennington, R. K.; Marquina, N. E. (Principal Investigator)

1978-01-01

The author has identified the following significant results. Barley showed significant separability from spring wheat, both multitemporally and on a single date chosen near the turning time for barley. Oats showed occasional multitemporal separability from barley and spring wheat; however, the cause of this separability was not well understood. Oats showed no significant separability from spring wheat on any single date during the growing season. By pooling data from segments having an acquisition near the turning time for barley, a fixed unitemporal projection for aiding in the labeling of barley versus spring wheat and oats was constructed. This projection has about the same separability of barley from spring wheat and oats as the unitemporal greeness versus brightness plot. The new fixed projection has the advantage that barley occurs consistently in the same general location on the plot with respect to spring wheat and oats. Attempts to construct a fixed multitemporal or a segment-dependent multitemporal projection for aiding in the labeling of spring wheat versus other small grains were unsuccessful due to segment availability and the fact that each segment has a unique acquisition history.

Electrophoretic cell separation by means of microspheres

NASA Technical Reports Server (NTRS)

Smolka, A. J. K.; Nerren, B. H.; Margel, S.; Rembaum, A.

1979-01-01

The electrophoretic mobility of fixed human erythrocytes immunologically labeled with poly(vinylpyridine) or poly(glutaraldehyde) microspheres was reduced by approximately 40%. This observation was utilized in preparative scale electrophoretic separations of fixed human and turkey erythrocytes, the mobilities of which under normal physiological conditions do not differ sufficiently to allow their separation by continuous flow electrophoresis. We suggest that resolution in the electrophoretic separation of cell subpopulations, currently limited by finite and often overlapping mobility distributions, may be significantly enhanced by immunospecific labeling of target populations using microspheres.

Quantifying the contribution of single microbial cells to nitrogen assimilation in aquatic environments

NASA Astrophysics Data System (ADS)

Musat, N.; Kuypers, M. M. M.

2009-04-01

Nitrogen is a primary productivity-limiting nutrient in the ocean. The nitrogen limitation of productivity may be overcome by organisms capable of converting dissolved N2 into fixed nitrogen available to the ecosystem. In many oceanic regions, growth of phytoplankton is nitrogen limited because fixation of N2 cannot make up for the removal of fixed inorganic nitrogen (NH4+, NO2-, NO3-) by anaerobic microbial processes. The amount of available fixed nitrogen in the ocean can be changed by the biological processes of heterotrophic denitrification, anaerobic ammonium oxidation and nitrogen fixation. For a complete understanding of nitrogen cycling in the ocean a link between the microbial and biogeochemical processes at the single cell level and their role in global biogeochemical cycles is essential. Here we report a recently developed method, Halogen In Situ Hybridization-Secondary Ion Mass Spectroscopy (HISH-SIMS) and its potential application to study the nitrogen-cycle processes in the ocean. The method allows simultaneous phylogenetic identification and quantitation of metabolic activities of single microbial cells in the environment. It uses horseradish-peroxidase-labeled oligonucleotide probes and fluorine-containing tyramides for the identification of microorganisms in combination with stable-isotope-labeling experiments for analyzing the metabolic function of single microbial cells. HISH-SIMS was successfully used to study nitrogen assimilation and nitrogen fixation by anaerobic phototrophs in a meromictic alpine lake. The HISH-SIMS method enables studies of the ecophysiology of individual, phylogenetically identified microorganisms involved in the N-cycle and allows us to track the flow of nitrogen within microbial communities.

Comparison of radiofrequency body coils for MRI at 3 Tesla: a simulation study using parallel transmission on various anatomical targets

PubMed Central

Wu, Xiaoping; Zhang, Xiaotong; Tian, Jinfeng; Schmitter, Sebastian; Hanna, Brian; Strupp, John; Pfeuffer, Josef; Hamm, Michael; Wang, Dingxin; Nistler, Juergen; He, Bin; Vaughan, J. Thomas; Ugurbil, Kamil; Van de Moortele, Pierre-Francois

2015-01-01

The performance of multichannel transmit coil layouts and parallel transmission (pTx) radiofrequency (RF) pulse design was evaluated with respect to transmit B1 (B1+) homogeneity and Specific Absorption Rate (SAR) at 3 Tesla for a whole body coil. Five specific coils were modeled and compared: a 32-rung birdcage body coil (driven either in a fixed quadrature mode or a two-channel transmit mode), two single-ring stripline arrays (with either 8 or 16 elements), and two multi-ring stripline arrays (with 2 or 3 identical rings, stacked in the z-axis and each comprising eight azimuthally distributed elements). Three anatomical targets were considered, each defined by a 3D volume representative of a meaningful region of interest (ROI) in routine clinical applications. For a given anatomical target, global or local SAR controlled pTx pulses were designed to homogenize RF excitation within the ROI. At the B1+ homogeneity achieved by the quadrature driven birdcage design, pTx pulses with multichannel transmit coils achieved up to ~8 fold reduction in local and global SAR. When used for imaging head and cervical spine or imaging thoracic spine, the double-ring array outperformed all coils including the single-ring arrays. While the advantage of the double-ring array became much less pronounced for pelvic imaging with a substantially larger ROI, the pTx approach still provided significant gains over the quadrature birdcage coil. For all design scenarios, using the 3-ring array did not necessarily improve the RF performance. Our results suggest that pTx pulses with multichannel transmit coils can reduce local and global SAR substantially for body coils while attaining improved B1+ homogeneity, particularly for a “z-stacked” double-ring design with coil elements arranged on two transaxial rings. PMID:26332290

Multi-Maneuver Clohessy-Wiltshire Targeting

NASA Technical Reports Server (NTRS)

Dannemiller, David P.

2011-01-01

Orbital rendezvous involves execution of a sequence of maneuvers by a chaser vehicle to bring the chaser to a desired state relative to a target vehicle while meeting intermediate and final relative constraints. Intermediate and final relative constraints are necessary to meet a multitude of requirements such as to control approach direction, ensure relative position is adequate for operation of space-to-space communication systems and relative sensors, provide fail-safe trajectory features, and provide contingency hold points. The effect of maneuvers on constraints is often coupled, so the maneuvers must be solved for as a set. For example, maneuvers that affect orbital energy change both the chaser's height and downrange position relative to the target vehicle. Rendezvous designers use experience and rules-of-thumb to design a sequence of maneuvers and constraints. A non-iterative method is presented for targeting a rendezvous scenario that includes a sequence of maneuvers and relative constraints. This method is referred to as Multi-Maneuver Clohessy-Wiltshire Targeting (MM_CW_TGT). When a single maneuver is targeted to a single relative position, the classic CW targeting solution is obtained. The MM_CW_TGT method involves manipulation of the CW state transition matrix to form a linear system. As a starting point for forming the algorithm, the effects of a series of impulsive maneuvers on the state are derived. Simple and moderately complex examples are used to demonstrate the pattern of the resulting linear system. The general form of the pattern results in an algorithm for formation of the linear system. The resulting linear system relates the effect of maneuver components and initial conditions on relative constraints specified by the rendezvous designer. Solution of the linear system includes the straight-forward inverse of a square matrix. Inversion of the square matrix is assured if the designer poses a controllable scenario - a scenario where the the constraints can be met by the sequence of maneuvers. Matrices in the linear system are dependent on selection of maneuvers and constraints by the designer, but the matrices are independent of the chaser's initial conditions. For scenarios where the sequence of maneuvers and constraints are fixed, the linear system can be formed and the square matrix inverted prior to real-time operations. Example solutions are presented for several rendezvous scenarios to illustrate the utility of the method. The MM_CW_TGT method has been used during the preliminary design of rendezvous scenarios and is expected to be useful for iterative methods in the generation of an initial guess and corrections.

The 3D laser radar vision processor system

NASA Astrophysics Data System (ADS)

Sebok, T. M.

1990-10-01

Loral Defense Systems (LDS) developed a 3D Laser Radar Vision Processor system capable of detecting, classifying, and identifying small mobile targets as well as larger fixed targets using three dimensional laser radar imagery for use with a robotic type system. This processor system is designed to interface with the NASA Johnson Space Center in-house Extra Vehicular Activity (EVA) Retriever robot program and provide to it needed information so it can fetch and grasp targets in a space-type scenario.

The 3D laser radar vision processor system

NASA Technical Reports Server (NTRS)

Sebok, T. M.

1990-01-01

Loral Defense Systems (LDS) developed a 3D Laser Radar Vision Processor system capable of detecting, classifying, and identifying small mobile targets as well as larger fixed targets using three dimensional laser radar imagery for use with a robotic type system. This processor system is designed to interface with the NASA Johnson Space Center in-house Extra Vehicular Activity (EVA) Retriever robot program and provide to it needed information so it can fetch and grasp targets in a space-type scenario.

Percutaneous nephrostomy for symptomatic hypermobile kidney: a single centre experience.

PubMed

Starownik, Radosław; Golabek, Tomasz; Bar, Krzysztof; Muc, Kamil; Płaza, Paweł; Chlosta, Piotr

2014-12-01

Symptomatic hypermobile kidney is treated with nephropexy, a surgical procedure through which the floating kidney is fixed to the retroperitoneum. Although both open and endoscopic procedures have a high success rate, they can be associated with risk of complications, relatively long hospital stay and high cost. We describe our percutaneous technique for fixing a hypermobile kidney and evaluate the efficacy of the percutaneous nephrostomy insertion in management of symptomatic nephroptosis. Between January 2005 and December 2011, 11 patients diagnosed with a symptomatic right nephroptosis of at least 1 year duration were treated with a single point percutaneous nephrostomy technique. All data were retrieved from patients' medical records and then retrospectively analysed. Nephropexy through a single point percutaneous nephrostomy technique was successfully accomplished in 11 women. The mean operative time was 20 min. The intraoperative estimated blood loss was minimal in all cases. No major or minor intraoperative complications were noted. The average postoperative hospital stay was 2 days. Women returned to their usual activities 14 days following the surgery. Nine women had complete resolution of their pain, and 2 patients continued to complain of discomfort in their lumbar area. One patient was re-operated upon with satisfactory subjective and objective outcomes achieved. One patient refused re-operation. Percutaneous nephropexy is simple, inexpensive and effective for treatment of symptomatic hypermobile kidney. It remains a valuable alternative to open, laparoscopic, and robotic methods for fixing a floating kidney.

The Simple Map for a Single-null Divertor Tokamak: How to Find the Last Good Surface

NASA Astrophysics Data System (ADS)

Phan, Huong; Ali, Halima; Punjabi, Alkesh

2000-10-01

The Simple Map^1 is a representation of the magnetic field inside a single-null divertor tokamak. It is given by the equations: X_n+1=X_n kYn (1-Y_n), Y_n+1= Y_n+kX_n+1. These equations mimic the motion of the magnetic field lines in a single-null divertor tokamak. The fixed stable point is (0,0) and the unstable fixed oint is (0,1). k is fixed at 0.60. In our work, the starting values of Y in the map is kept in the interval of 0 to 1, and the starting value of X is 0. Using the successive bifurcation method, we first run these equations for 10^6 iterations to find the approximate value of Y when chaos occurs. We examine the neighborhood of this Y value to find the exact value of Y for the last good surface. We call this value Y_lgs. We find Y_lgs to be 0.997135768 for k=0.60 and X=0. This work is supported by US DOE OFES. Ms. Huong Phan is a HU CFRT Summer Fusion High School Workshop Scholar from Andrew P. Hill High School in California. She is supported by NASA SHARP Plus Program. 1. Punjabi A, Verma A and Boozer A, Phys Rev Lett 69 3322 (1992) and J Plasma Phys 52 91 (1994)

Iterative reconstruction in single source dual-energy CT pulmonary angiography: Is it sufficient to achieve a radiation dose as low as state-of-the-art single-energy CTPA?

PubMed

Ohana, M; Labani, A; Jeung, M Y; El Ghannudi, S; Gaertner, S; Roy, C

2015-11-01

Dual-energy (DE) brings numerous significant improvements in pulmonary CT angiography (CTPA), but is associated with a 15-50% increase in radiation dose that prevents its widespread use. We hypothesize that thanks to iterative reconstruction (IR), single source DE-CTPA acquired at the same radiation dose that a single-energy examination will maintain an equivalent quantitative and qualitative image quality, allowing a more extensive use of the DE technique in the clinical routine. Fifty patients (58% men, mean age 64.8yo ± 16.2, mean BMI 25.6 ± 4.5) were prospectively included and underwent single source DE-CTPA with acquisition parameters (275 mA fixed tube current, 50% IR) tweaked to target a radiation dose similar to a 100 kV single-energy CTPA (SE-CTPA), i.e., a DLP of 260 mGy cm. Thirty patients (47% men, 64.4yo ± 18.6, BMI 26.2 ± 4.6) from a previous prospective study on DE-CTPA (375 mA fixed tube current, reconstruction with filtered-back projection) were used as the reference group. Thirty-five consecutive patients (57% men, 65.8yo ± 15.5, BMI 25.7 ± 4.4) who underwent SE-CTPA on the same scanner (automated tube current modulation, 50% IR) served as a comparison. Subjective image quality was scored by two radiologists using a 5-level scale and compared with a Kruskal-Wallis nonparametric test. Density measurements on the 65 keV monochromatic reconstructions were used to calculate signal-to-noise (SNR) and contrast-to-noise (CNR) ratios that were compared using a Student's t test. Correlations between image quality, SNR, CNR and BMI were sought using a Pearson's test. p<0.05 was considered significant. All examinations were of diagnostic quality (score ≥ 3). In comparison with the reference DE-CTPA and the SE-CTPA protocols, the DE-IR group exhibited a non-inferior image quality (p=0.95 and p=0.21, respectively) and a significantly lower mean image noise (p<0.01 and p=0.01) thus slightly improving the SNR (p=0.09 and p=0.47) and the CNR (p=0.12 and p=0.51). There was a strong negative relationship between BMI and SNR/CNR (ρ=-0.59 and -0.55 respectively), but only a moderate negative relationship between BMI and image quality (ρ=-0.27). With iterative reconstruction, objective and subjective image quality of single source DE-CTPA are preserved even though the radiation dose is lowered to that of a single-energy examination, overcoming a major limitation of the DE technique and allowing a widespread use in the clinical routine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Eley, J; Mehta, M; Molitoris, J

Purpose: The purpose of this study was to propose a method to implement arc therapy that is compatible with existing particle therapy systems having gantries and pencil-beam scanning capacities. Furthermore, we sought to demonstrate expected benefits of this method for selected clival chordoma patients. Methods: We propose that a desired particle arc treatment plan can be discretized into a finite number of fixed beams and that only one (or a subset) of these beams be delivered in any single treatment fraction; the target should receive uniform dose during each fraction. For 3 clival-chordoma patients, robust-optimized, scanned proton beams were simulatedmore » to deliver 78 Gy (RBE) to clinical target volumes (CTVs), using either a single-field plan with a posterior-anterior (PA) beam or a discrete-arc plan with 16 beams that were equally spaced throughout a 360-degree axial arc. Dose-volume metrics were compared with emphasis on the brainstem, since risk of radiation necrosis there can often restrict application of tumoricidal doses for chordomas. Results: The mean volume of brainstem receiving a dose of 60 Gy (RBE) or higher (V60Gy) was 10.3±0.9 cm{sup 3} for the single-field plan and 4.7±1.8 cm{sup 3} for the discrete-arc plan, a reduction of 55% in favor of arcs. The mean dose to the brainstem was also reduced using arcs, by 18%, while the maximum dose was nearly identical for both methods. For the whole brain, V60Gy was reduced by 23%, in favor of arcs. Mean dose to the CTVs were nearly identical for both strategies, within 0.3%. Conclusion: Discrete arc treatments can be implemented using existing scanned particle-beam facilities. Aside from the physical advantages, the biological uncertainties of particle therapy, particularly high in the distal edge, can be reduced by arc therapy via rotational smearing, which may be of benefit for tumors near the brainstem.« less

Improved Tumor Penetration and Single-Cell Targeting of Antibody-Drug Conjugates Increases Anticancer Efficacy and Host Survival.

PubMed

Cilliers, Cornelius; Menezes, Bruna; Nessler, Ian; Linderman, Jennifer; Thurber, Greg M

2018-02-01

Current antibody-drug conjugates (ADC) have made advances in engineering the antibody, linker, conjugation site, small-molecule payload, and drug-to-antibody ratio (DAR). However, the relationship between heterogeneous intratumoral distribution and efficacy of ADCs is poorly understood. Here, we compared trastuzumab and ado-trastuzumab emtansine (T-DM1) to study the impact of ADC tumor distribution on efficacy. In a mouse xenograft model insensitive to trastuzumab, coadministration of trastuzumab with a fixed dose of T-DM1 at 3:1 and 8:1 ratios dramatically improved ADC tumor penetration and resulted in twice the improvement in median survival compared with T-DM1 alone. In this setting, the effective DAR was lowered, decreasing the amount of payload delivered to each targeted cell but increasing the number of cells that received payload. This result is counterintuitive because trastuzumab acts as an antagonist in vitro and has no single-agent efficacy in vivo , yet improves the effectiveness of T-DM1 in vivo Novel dual-channel fluorescence ratios quantified single-cell ADC uptake and metabolism and confirmed that the in vivo cellular dose of T-DM1 alone exceeded the minimum required for efficacy in this model. In addition, this technique characterized cellular pharmacokinetics with heterogeneous delivery after 1 day, degradation and payload release by 2 days, and in vitro cell killing and in vivo tumor shrinkage 2 to 3 days later. This work demonstrates that the intratumoral distribution of ADC, independent of payload dose or plasma clearance, plays a major role in ADC efficacy. Significance: This study shows how lowering the drug-to-antibody ratio during treatment can improve the intratumoral distribution of a antibody-drug conjugate, with implications for improving the efficacy of this class of cancer drugs. Cancer Res; 78(3); 758-68. ©2017 AACR . ©2017 American Association for Cancer Research.

Clinical applicability and cost of a 46-gene panel for genomic analysis of solid tumours: Retrospective validation and prospective audit in the UK National Health Service

PubMed Central

Kaur, Kulvinder; Camps, Carme; Kaisaki, Pamela; Gupta, Avinash; Talbot, Denis; Middleton, Mark; Henderson, Shirley; Cutts, Anthony; Vavoulis, Dimitrios V.; Housby, Nick; Taylor, Jenny C.; Schuh, Anna

2017-01-01

Background Single gene tests to predict whether cancers respond to specific targeted therapies are performed increasingly often. Advances in sequencing technology, collectively referred to as next generation sequencing (NGS), mean the entire cancer genome or parts of it can now be sequenced at speed with increased depth and sensitivity. However, translation of NGS into routine cancer care has been slow. Healthcare stakeholders are unclear about the clinical utility of NGS and are concerned it could be an expensive addition to cancer diagnostics, rather than an affordable alternative to single gene testing. Methods and findings We validated a 46-gene hotspot cancer panel assay allowing multiple gene testing from small diagnostic biopsies. From 1 January 2013 to 31 December 2013, solid tumour samples (including non-small-cell lung carcinoma [NSCLC], colorectal carcinoma, and melanoma) were sequenced in the context of the UK National Health Service from 351 consecutively submitted prospective cases for which treating clinicians thought the patient had potential to benefit from more extensive genetic analysis. Following histological assessment, tumour-rich regions of formalin-fixed paraffin-embedded (FFPE) sections underwent macrodissection, DNA extraction, NGS, and analysis using a pipeline centred on Torrent Suite software. With a median turnaround time of seven working days, an integrated clinical report was produced indicating the variants detected, including those with potential diagnostic, prognostic, therapeutic, or clinical trial entry implications. Accompanying phenotypic data were collected, and a detailed cost analysis of the panel compared with single gene testing was undertaken to assess affordability for routine patient care. Panel sequencing was successful for 97% (342/351) of tumour samples in the prospective cohort and showed 100% concordance with known mutations (detected using cobas assays). At least one mutation was identified in 87% (296/342) of tumours. A locally actionable mutation (i.e., available targeted treatment or clinical trial) was identified in 122/351 patients (35%). Forty patients received targeted treatment, in 22/40 (55%) cases solely due to use of the panel. Examination of published data on the potential efficacy of targeted therapies showed theoretically actionable mutations (i.e., mutations for which targeted treatment was potentially appropriate) in 66% (71/107) and 39% (41/105) of melanoma and NSCLC patients, respectively. At a cost of £339 (US$449) per patient, the panel was less expensive locally than performing more than two or three single gene tests. Study limitations include the use of FFPE samples, which do not always provide high-quality DNA, and the use of “real world” data: submission of cases for sequencing did not always follow clinical guidelines, meaning that when mutations were detected, patients were not always eligible for targeted treatments on clinical grounds. Conclusions This study demonstrates that more extensive tumour sequencing can identify mutations that could improve clinical decision-making in routine cancer care, potentially improving patient outcomes, at an affordable level for healthcare providers. PMID:28196074

Lagrangian Modeling of Evaporating Sprays at Diesel Engine Conditions: Effects of Multi-Hole Injector Nozzles With JP-8 Surrogates

DTIC Science & Technology

2014-05-01

solver to treat the spray process. An Adaptive Mesh Refinement (AMR) and fixed embedding technique is employed to capture the gas - liquid interface with...Adaptive Mesh Refinement (AMR) and fixed embedding technique is employed to capture the gas - liquid interface with high fidelity while keeping the cell...in single and multi-hole nozzle configurations. The models were added to the present CONVERGE liquid fuel database and validated extensively

The largest survivorship and clinical outcomes study of the fixed bearing Stryker Triathlon Partial Knee Replacement - A multi-surgeon, single centre cohort study with a minimum of two years of follow-up.

PubMed

Middleton, S W F; Schranz, P J; Mandalia, V I; Toms, A D

2018-05-03

The surgical management of isolated medial compartment degenerative disease of the knee causes debate. Unicompartmental arthroplasty options include fixed and mobile bearing implant designs with fixed bearing becoming increasingly popular. We present the largest cohort of a fixed bearing single radius design, Stryker Triathlon Partial Knee Replacement (PKR). We prospectively collected demographic data and patient reported outcome measures (PROMs) on our cohort of PKR implants since its adoption in our unit, 2009 until March 2015. A total of 129 implants in 115 patients with a mean follow-up of 5.5 years (2.5 to 8.5 years) were included. There were 11 revisions at an average of 1.7 years (0.6-4.1 years), two for infection, two for mal-alignment, five for progression of disease and two for loosening. The survivorship of the implants at five years is 90%. The PKR provides good survivorship at five years and PROM scores that are equal to the largest and most popular comparable implants. There is an associated learning curve with this implant, as there is with all systems and this is reflected in our results. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Budesonide + formoterol fumarate dihydrate for the treatment of asthma.

PubMed

Wolthers, Ole D

2016-01-01

One of the most widely used fixed combinations in asthma management is dry powder budesonide+formoterol fumarate dihydrate which is commercially available as Symbicort Turbuhaler(®) (and generic products), Easyhaler Bufomix(®) and DuoRespSpiromax(®) inhaler. The aim of this paper was to review the fixed dry powder combination of inhaled budesonide+formoterol fumarate dihydrate for asthma treatment in adolescents and adults. A literature search using relevant search terms, reference lists for reviews and meta-analyses was performed. In symptomatic adolescent and adult patients with asthma maintenance and reliever therapy with a single-inhaler fixed combination of dry powder budesonide+formoterol fumarate dihydrate is an evidenced option. The combination treatment is convenient to patients. It reduces the number of exacerbations requiring treatment with oral corticosteroids. In some patients the strategy may also reduce the total intake of inhaled corticosteroids over time. Whether important outcome measures of asthma treatment, such as hospital admission and emergency room visit rates, may be reduced is less well documented since the published studies may have been influenced by publication bias. Non-pharmaceutical company-sponsored research evaluating such measures is needed. There is no evidence for the use of single inhaler fixed combinations of inhaled corticosteroids+long-acting β(2)-agonists in children (<12 years of age), and budesonide+formoterol fumarate dihydrate should not be prescribed to the age group.

User's guide to four-body and three-body trajectory optimization programs

NASA Technical Reports Server (NTRS)

Pu, C. L.; Edelbaum, T. N.

1974-01-01

A collection of computer programs and subroutines written in FORTRAN to calculate 4-body (sun-earth-moon-space) and 3-body (earth-moon-space) optimal trajectories is presented. The programs incorporate a variable step integration technique and a quadrature formula to correct single step errors. The programs provide capability to solve initial value problem, two point boundary value problem of a transfer from a given initial position to a given final position in fixed time, optimal 2-impulse transfer from an earth parking orbit of given inclination to a given final position and velocity in fixed time and optimal 3-impulse transfer from a given position to a given final position and velocity in fixed time.

SU-E-T-130: Are Proton Gantries Needed? An Analysis of 4332 Patient Proton Gantry Treatment Plans From the Past 10 Years

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

Yan, S; Lu, H; Flanz, J

2015-06-15

Purpose: To ascertain the necessity of a proton gantry, as compared to the feasibility of using a horizontal fixed proton beam-line for treatment with advanced technology. Methods: To calculate the percentage of patients that can be treated with a horizontal fixed beam-line instead of a gantry, we analyze the distributions of beam orientations of our proton gantry patients treated over the past 10 years. We identify three horizontal fixed beam geometries (FIXED, BEND and MOVE) with the patient in lying and/or sitting positions. The FIXED geometry includes only table/chair rotations and translations. In BEND, the beam can be bent up/downmore » for up to 20 degrees. MOVE allows for patient head/body angle adjustment. Based on the analysis, we select eight patients whose plan involves beams which are still challenging to achieve with a horizontal fixed beam. These beams are removed in the pencil beam scanning (PBS) plan optimized for the fixed beam-line (PBS-fix). We generate non-coplanar PBS-gantry plans for comparison, and perform a robustness analysis. Results: The percentage of patients with head-and-neck/brain tumors that can be treated with horizontal fixed beam is 44% in FIXED, 70% in 20-degrees BEND, and 100% in 90-degrees MOVE. For torso regions, 99% of the patients can be treated in 20-degree BEND. The target coverage is more homogeneous with PBS-fix plans compared to the clinical scattering treatment plans. The PBS-fix plans reduce the mean dose to organs-at-risk by a factor of 1.1–28.5. PBS-gantry plans are as good as PBS-fix plans, sometimes marginally better. Conclusion: The majority of the beam orientations can be realized with a horizontal fixed beam-line. Challenging non-coplanar beams can be eliminated with PBS delivery. Clinical implementation of the proposed fixed beam-line requires use of robotic patient positioning, further developments in immobilization, and image guidance. However, our results suggest that fixed beam-lines can be as effective as gantries.« less

Results of a Markov model analysis to assess the cost-effectiveness of a single tablet of fixed-dose amlodipine and atorvastatin for the primary prevention of cardiovascular disease in Korea.

PubMed

Liew, Danny; Park, Hye-Jin; Ko, Su-Kyoung

2009-10-01

In Korea, the treatment of hypertension and dyslipidemia constitutes an important strategy for the prevention of cardiovascular disease (CVD). This study sought to investigate the cost-effectiveness (from the Korean health care system perspective) of prescribing a proprietary formulation single-tablet fixed-dose combination of amlodipine and atorvastatin (at weighted mean doses of 5 mg and 10.25 mg, respectively) to all eligible patients aged > or = 45 years for the primary prevention of CVD (ie, coronary heart disease and ischemic stroke) in Korea, compared with currently observed patterns of blood-pressure and lipid-lowering medication prescription and use. A Markov model was developed with 4 health states: alive without CVD, alive with CVD, dead from CVD, and dead from non-CVD causes. The model population comprised 244 Koreans aged >/=45 years from the 2005 Korean National Health and Nutrition Examination Survey (KNHNES) without a history of myocardial infarction (MI) or stroke who met current criteria for both blood-pressure and lipid-lowering treatment. From a 2008 baseline, follow-up was simulated for 40 years. Cardiovascular risk was estimated for each subject individually using a multivariate, Asian population-specific equation, and updated with ongoing cycles. Decision analysis compared the effects of prescribing the fixed-dose combination to all subjects versus currently observed patterns of treatment. Data regarding the blood-pressure and lipid-lowering efficacies of combination therapy were drawn from the Respond trial. Costs of the fixed-dose combination tablet and CVD were sourced from pharmaceutical pricing lists and Korean Health Insurance Review and Assessment Services estimates, respectively. Utility values for CVD were obtained from a large Korean utility study. In the model, of the 244 treatment-eligible subjects, 126 (51.6%) and 13 (5.3%) were taking blood-pressure and lipid-lowering therapy, respectively. Use of single-tablet fixed-dose combination amlodipine and atorvastatin by all subjects was associated with estimated incremental cost-effectiveness ratios of 7,773,063 Korean won (KRW) per quality-adjusted life-year gained and 10,378,230 KRW per overall life-year gained (1300 KRW approximately US $1). Sensitivity and uncertainty analyses indicated these results to be robust. In this model, based on data from the 2005 KNHNES, hypertension and dyslipidemia were undertreated among Koreans aged > or = 45 years without a history of MI or stroke. The administration of single-tablet fixed-dose combination amlodipine and atorvastatin to all such individuals was likely to represent a cost-effective means of preventing first-onset CVD (ie, coronary heart disease and ischemic stroke) in this subgroup, compared with current patterns of treatment.

Preclinical safety and efficacy of a new recombinant FIX drug product for treatment of hemophilia B.

PubMed

Dietrich, Barbara; Schiviz, Alexandra; Hoellriegl, Werner; Horling, Frank; Benamara, Karima; Rottensteiner, Hanspeter; Turecek, Peter L; Schwarz, Hans Peter; Scheiflinger, Friedrich; Muchitsch, Eva-Maria

2013-11-01

Baxter has developed a new recombinant factor IX (rFIX) drug product (BAX326) for treating patients with hemophilia B, or congenital FIX deficiency. An extensive preclinical program evaluated the pharmacokinetics, efficacy, and safety of BAX326 in different species. The efficacy of BAX326 was tested in three mouse models of primary pharmacodynamics: tail-tip bleeding, carotid occlusion, and thrombelastography. The pharmacokinetics was evaluated after a single intravenous bolus injection in mice, rats, and macaques. Toxicity was assessed in rats and macaques, safety pharmacology in rabbits and macaques, and immunogenicity in mice. BAX326 was shown to be efficacious in all three primary pharmacodynamic studies (P ≤ 0.0076). Hemostatic efficacy was dose related and similar for the three lots tested. Pharmacokinetic results showed that rFIX activity and rFIX antigen concentrations declined in a bi-phasic manner, similar to a previously licensed rFIX product. BAX326 was well tolerated in rabbits and macaques at all dose levels; no thrombogenic events and no adverse clinical, respiratory, or cardiovascular effects occurred. BAX326 was also shown to have a similar immunogenicity profile to the comparator rFIX product in mice. These results demonstrate that BAX326 has a favorable preclinical safety and efficacy profile, predictive of a comparable effect to that of the previously licensed rFIX in humans.

Primary Characterization of Small RNAs in Symbiotic Nitrogen-Fixing Bacteria.

PubMed

Robledo, Marta; García-Tomsig, Natalia I; Jiménez-Zurdo, José I

2018-01-01

High-throughput transcriptome profiling (RNAseq) has uncovered large and heterogeneous populations of small noncoding RNA species (sRNAs) with potential regulatory roles in bacteria. A large fraction of sRNAs are differentially regulated and rely on protein-assisted antisense interactions to trans-encoded target mRNAs to fine-tune posttranscriptional reprogramming of gene expression in response to external cues. However, annotation and function of sRNAs are still largely overlooked in nonmodel bacteria with complex lifestyles. Here, we describe experimental protocols successfully applied for the accurate annotation, expression profiling and target mRNA identification of trans-acting sRNAs in the nitrogen-fixing α-rhizobium Sinorhizobium meliloti. The protocols presented here can be similarly applied for the characterization of trans-sRNAs in genetically tractable α-proteobacteria of agronomical or clinical relevance interacting with eukaryotic hosts.

Can An Evolutionary Process Create English Text?

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

Bailey, David H.

Critics of the conventional theory of biological evolution have asserted that while natural processes might result in some limited diversity, nothing fundamentally new can arise from 'random' evolution. In response, biologists such as Richard Dawkins have demonstrated that a computer program can generate a specific short phrase via evolution-like iterations starting with random gibberish. While such demonstrations are intriguing, they are flawed in that they have a fixed, pre-specified future target, whereas in real biological evolution there is no fixed future target, but only a complicated 'fitness landscape'. In this study, a significantly more sophisticated evolutionary scheme is employed tomore » produce text segments reminiscent of a Charles Dickens novel. The aggregate size of these segments is larger than the computer program and the input Dickens text, even when comparing compressed data (as a measure of information content).« less

Fixed-target hadron production experiments

NASA Astrophysics Data System (ADS)

Popov, Boris A.

2015-08-01

Results from fixed-target hadroproduction experiments (HARP, MIPP, NA49 and NA61/SHINE) as well as their implications for cosmic ray and neutrino physics are reviewed. HARP measurements have been used for predictions of neutrino beams in K2K and MiniBooNE/SciBooNE experiments and are also being used to improve predictions of the muon yields in EAS and of the atmospheric neutrino fluxes as well as to help in the optimization of neutrino factory and super-beam designs. Recent measurements released by the NA61/SHINE experiment are of significant importance for a precise prediction of the J-PARC neutrino beam used for the T2K experiment and for interpretation of EAS data. These hadroproduction experiments provide also a large amount of input for validation and tuning of hadron production models in Monte-Carlo generators.

The LysR-type transcription factor PacR is a global regulator of photosynthetic carbon assimilation in Anabaena.

PubMed

Picossi, Silvia; Flores, Enrique; Herrero, Antonia

2015-09-01

Cyanobacteria perform water-splitting photosynthesis and are important primary producers impacting the carbon and nitrogen cycles at global scale. They fix CO2 through ribulose-bisphosphate carboxylase/oxygenase (RuBisCo) and have evolved a distinct CO2 concentrating mechanism (CCM) that builds high CO2 concentrations in the vicinity of RuBisCo favouring its carboxylase activity. Filamentous cyanobacteria such as Anabaena fix CO2 in photosynthetic vegetative cells, which donate photosynthate to heterocysts that rely on a heterotrophic metabolism to fix N2 . CCM elements are induced in response to inorganic carbon limitation, a cue that exposes the photosynthetic apparatus to photodamage by over-reduction. An Anabaena mutant lacking the LysR-type transcription factor All3953 grew poorly and dies under high light. The rbcL operon encoding RuBisCo was induced upon carbon limitation in the wild type but not in the mutant. ChIP-Seq analysis was used to globally identify All3953 targets under carbon limitation. Targets include, besides rbcL, genes encoding CCM elements, photorespiratory pathway- photosystem- and electron transport-related components, and factors, including flavodiiron proteins, with a demonstrated or putative function in photoprotection. Quantitative reverse transcription polymerase chain reaction analysis of selected All3953 targets showed regulation in the wild type but not in the mutant. All3953 (PacR) is a global regulator of carbon assimilation in an oxygenic photoautotroph. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Effectiveness of Vildagliptin in Clinical Practice: Pooled Analysis of Three Korean Observational Studies (the VICTORY Study)

PubMed Central

Suh, Sunghwan; Song, Sun Ok; Kim, Jae Hyeon; Cho, Hyungjin

2017-01-01

The present observational study aimed to evaluate the clinical effectiveness of vildagliptin with metformin in Korean patients with type 2 diabetes mellitus (T2DM). Data were pooled from the vildagliptin postmarketing survey (PMS), the vildagliptin/metformin fixed drug combination (DC) PMS, and a retrospective observational study of vildagliptin/metformin (fixed DC or free DC). The effectiveness endpoint was the proportion of patients who achieved a glycemic target (HbA1c) of ≤7.0% at 24 weeks. In total, 4303 patients were included in the analysis; of these, 2087 patients were eligible. The mean patient age was 56.99 ± 11.25 years. Overall, 58.94% patients achieved an HbA1c target of ≤7.0% at 24 weeks. The glycemic target achievement rate was significantly greater in patients with baseline HbA1c < 7.5% versus ≥7.5% (84.64% versus 43.97%), receiving care at the hospital versus clinic (67.95% versus 52.33%), and receiving vildagliptin/metformin fixed DC versus free DC (70.69% versus 55.42%). Multivariate logistic regression analysis indicated that disease duration (P < 0.0001), baseline HbA1c (P < 0.0001), and DC type (P = 0.0103) had significant effects on drug effectiveness. Vildagliptin plus metformin appeared as an effective treatment option for patients with T2DM in clinical practice settings in Korea. PMID:29057274

Adapting to variable prismatic displacement

NASA Technical Reports Server (NTRS)

Welch, Robert B.; Cohen, Malcolm M.

1989-01-01

In each of two studies, subjects were exposed to a continuously changing prismatic displacement with a mean value of 19 prism diopters (variable displacement) and to a fixed 19-diopter displacement (fixed displacement). In Experiment 1, significant adaptation (post-pre shifts in hand-eye coordination) was found for fixed, but not for variable, displacement. Experiment 2 demonstrated that adaptation was obtained for variable displacement, but it was very fragile and is lost if the measures of adaptation are preceded by even a very brief exposure of the hand to normal or near-normal vision. Contrary to the results of some previous studies, an increase in within-S dispersion was not found of target pointing responses as a result of exposure to variable displacement.

Testing the Efficacy of a Scholarship Program for Single Parent, Post-Freshmen, Full Time Undergraduates

ERIC Educational Resources Information Center

Carpenter, Dick M., II; Kaka, Sarah J.; Tygret, Jennifer A.; Cathcart, Katy

2018-01-01

This study examines the efficacy of a scholarship program designed to assist single parent, post-freshmen, full time undergraduate students and predictors of success among a sample of said students, where success is defined as progress toward completion, academic achievement, and degree completion. Results of fixed effects regression and…

47 CFR 25.146 - Licensing and operating authorization provisions for the non-geostationary satellite orbit fixed...

Code of Federal Regulations, 2012 CFR

2012-10-01

... following: (1) Single-entry validation equivalent power flux-density, in the space-to-Earth direction, (EPFD down) limits. (i) Provide a set of power flux-density (pfd) masks, on the surface of the Earth, for... section. (2) Single-entry validation equivalent power flux-density, in the Earth-to-space direction, EPFD...

47 CFR 25.146 - Licensing and operating authorization provisions for the non-geostationary satellite orbit fixed...

Code of Federal Regulations, 2010 CFR

2010-10-01

... following: (1) Single-entry validation equivalent power flux-density, in the space-to-Earth direction, (EPFD down) limits. (i) Provide a set of power flux-density (pfd) masks, on the surface of the Earth, for... section. (2) Single-entry validation equivalent power flux-density, in the Earth-to-space direction, EPFD...

47 CFR 25.146 - Licensing and operating authorization provisions for the non-geostationary satellite orbit fixed...

Code of Federal Regulations, 2011 CFR

2011-10-01

... following: (1) Single-entry validation equivalent power flux-density, in the space-to-Earth direction, (EPFD down) limits. (i) Provide a set of power flux-density (pfd) masks, on the surface of the Earth, for... section. (2) Single-entry validation equivalent power flux-density, in the Earth-to-space direction, EPFD...

Confidence intervals from single observations in forest research

Treesearch

Harry T. Valentine; George M. Furnival; Timothy G. Gregoire

1991-01-01

A procedure for constructing confidence intervals and testing hypothese from a single trial or observation is reviewed. The procedure requires a prior, fixed estimate or guess of the outcome of an experiment or sampling. Two examples of applications are described: a confidence interval is constructed for the expected outcome of a systematic sampling of a forested tract...

Inheritance and world variation in thermal requirements for egg hatch in Lymantria dispar (Lepidoptera: Erebidae)

Treesearch

M.A. Keena

2016-01-01

Mode of inheritance of hatch traits in Lymantria dispar L. was determined by crossing populations nearly fixed for the phenotypic extremes. The nondiapausing phenotype was inherited via a single recessive gene and the phenotype with reduced low temperature exposure requirements before hatch was inherited via a single dominant gene. There was no...

The feasibility assessment of radiation dose of movement 3D NIPAM gel by magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Hsieh, Chih-Ming; Leung, Joseph Hang; Ng, Yu-Bun; Cheng, Chih-Wu; Sun, Jung-Chang; Lin, Ping-Chin; Hsieh, Bor-Tsung

2015-11-01

NIPAM dosimeter is widely accepted and recommended for its 3D distribution and accuracy in dose absorption. Up to the moment, most research works on dose measurement are based on a fixed irradiation target without the consideration of the effect from physiological motion. We present a study to construct a respiratory motion simulating patient anatomical and dosimetry model for the study of dosimetic effect of organ motion. The dose on fixed and motion targets was measured by MRI after a dose adminstration of 1, 2, 5, 8, and 10 Gy from linear accelerator. Comparison of two situations is made. The average sensitivity of fixed NIPAM was 0.1356 s-1/Gy with linearity R2=0.998. The average sensitivity of movement NIPAM was 0.1366 s-1/Gy with linearity R2=0.998 both having only 0.001 of the sensitivity difference. The difference between the two based on dose rate dependency, position and depth was not significant. There was thus no apparent impact on NIPAM dosimeter from physiological motion. The high sensitivity, linearity and stability of NIPAM dosimeter proved to be an ideal apparatus in the dose measurement in these circumstances.

Hippocampus-Dependent Goal Localization by Head-Fixed Mice in Virtual Reality.

PubMed

Sato, Masaaki; Kawano, Masako; Mizuta, Kotaro; Islam, Tanvir; Lee, Min Goo; Hayashi, Yasunori

2017-01-01

The demonstration of the ability of rodents to navigate in virtual reality (VR) has made it an important behavioral paradigm for studying spatially modulated neuronal activity in these animals. However, their behavior in such simulated environments remains poorly understood. Here, we show that encoding and retrieval of goal location memory in mice head-fixed in VR depends on the postsynaptic scaffolding protein Shank2 and the dorsal hippocampus. In our newly developed virtual cued goal location task, a head-fixed mouse moves from one end of a virtual linear track to seek rewards given at a target location along the track. The mouse needs to visually recognize the target location and stay there for a short period of time to receive the reward. Transient pharmacological blockade of fast glutamatergic synaptic transmission in the dorsal hippocampus dramatically and reversibly impaired performance of this task. Encoding and updating of virtual cued goal location memory was impaired in mice deficient in the postsynaptic scaffolding protein Shank2, a mouse model of autism that exhibits impaired spatial learning in a real environment. These results highlight the crucial roles of the dorsal hippocampus and postsynaptic protein complexes in spatial learning and navigation in VR.

Hippocampus-Dependent Goal Localization by Head-Fixed Mice in Virtual Reality

PubMed Central

Kawano, Masako; Mizuta, Kotaro; Islam, Tanvir; Lee, Min Goo; Hayashi, Yasunori

2017-01-01

Abstract The demonstration of the ability of rodents to navigate in virtual reality (VR) has made it an important behavioral paradigm for studying spatially modulated neuronal activity in these animals. However, their behavior in such simulated environments remains poorly understood. Here, we show that encoding and retrieval of goal location memory in mice head-fixed in VR depends on the postsynaptic scaffolding protein Shank2 and the dorsal hippocampus. In our newly developed virtual cued goal location task, a head-fixed mouse moves from one end of a virtual linear track to seek rewards given at a target location along the track. The mouse needs to visually recognize the target location and stay there for a short period of time to receive the reward. Transient pharmacological blockade of fast glutamatergic synaptic transmission in the dorsal hippocampus dramatically and reversibly impaired performance of this task. Encoding and updating of virtual cued goal location memory was impaired in mice deficient in the postsynaptic scaffolding protein Shank2, a mouse model of autism that exhibits impaired spatial learning in a real environment. These results highlight the crucial roles of the dorsal hippocampus and postsynaptic protein complexes in spatial learning and navigation in VR. PMID:28484738

Targeted or whole genome sequencing of formalin fixed tissue samples: potential applications in cancer genomics.

PubMed

Munchel, Sarah; Hoang, Yen; Zhao, Yue; Cottrell, Joseph; Klotzle, Brandy; Godwin, Andrew K; Koestler, Devin; Beyerlein, Peter; Fan, Jian-Bing; Bibikova, Marina; Chien, Jeremy

2015-09-22

Current genomic studies are limited by the poor availability of fresh-frozen tissue samples. Although formalin-fixed diagnostic samples are in abundance, they are seldom used in current genomic studies because of the concern of formalin-fixation artifacts. Better characterization of these artifacts will allow the use of archived clinical specimens in translational and clinical research studies. To provide a systematic analysis of formalin-fixation artifacts on Illumina sequencing, we generated 26 DNA sequencing data sets from 13 pairs of matched formalin-fixed paraffin-embedded (FFPE) and fresh-frozen (FF) tissue samples. The results indicate high rate of concordant calls between matched FF/FFPE pairs at reference and variant positions in three commonly used sequencing approaches (whole genome, whole exome, and targeted exon sequencing). Global mismatch rates and C · G > T · A substitutions were comparable between matched FF/FFPE samples, and discordant rates were low (<0.26%) in all samples. Finally, low-pass whole genome sequencing produces similar pattern of copy number alterations between FF/FFPE pairs. The results from our studies suggest the potential use of diagnostic FFPE samples for cancer genomic studies to characterize and catalog variations in cancer genomes.

Performance comparison of two commercial human whole-exome capture systems on formalin-fixed paraffin-embedded lung adenocarcinoma samples.

PubMed

Bonfiglio, Silvia; Vanni, Irene; Rossella, Valeria; Truini, Anna; Lazarevic, Dejan; Dal Bello, Maria Giovanna; Alama, Angela; Mora, Marco; Rijavec, Erika; Genova, Carlo; Cittaro, Davide; Grossi, Francesco; Coco, Simona

2016-08-30

Next Generation Sequencing (NGS) has become a valuable tool for molecular landscape characterization of cancer genomes, leading to a better understanding of tumor onset and progression, and opening new avenues in translational oncology. Formalin-fixed paraffin-embedded (FFPE) tissue is the method of choice for storage of clinical samples, however low quality of FFPE genomic DNA (gDNA) can limit its use for downstream applications. To investigate the FFPE specimen suitability for NGS analysis and to establish the performance of two solution-based exome capture technologies, we compared the whole-exome sequencing (WES) data of gDNA extracted from 5 fresh frozen (FF) and 5 matched FFPE lung adenocarcinoma tissues using: SeqCap EZ Human Exome v.3.0 (Roche NimbleGen) and SureSelect XT Human All Exon v.5 (Agilent Technologies). Sequencing metrics on Illumina HiSeq were optimal for both exome systems and comparable among FFPE and FF samples, with a slight increase of PCR duplicates in FFPE, mainly in Roche NimbleGen libraries. Comparison of single nucleotide variants (SNVs) between FFPE-FF pairs reached overlapping values >90 % in both systems. Both WES showed high concordance with target re-sequencing data by Ion PGM™ in 22 lung-cancer genes, regardless the source of samples. Exon coverage of 623 cancer-related genes revealed high coverage efficiency of both kits, proposing WES as a valid alternative to target re-sequencing. High-quality and reliable data can be successfully obtained from WES of FFPE samples starting from a relatively low amount of input gDNA, suggesting the inclusion of NGS-based tests into clinical contest. In conclusion, our analysis suggests that the WES approach could be extended to a translational research context as well as to the clinic (e.g. to study rare malignancies), where the simultaneous analysis of the whole coding region of the genome may help in the detection of cancer-linked variants.

Shuttle-promoted nano-mechanical current switch

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

Song, Taegeun, E-mail: tsong@ictp.it; Kiselev, Mikhail N.; Gorelik, Leonid Y.

2015-09-21

We investigate electron shuttling in three-terminal nanoelectromechanical device built on a movable metallic rod oscillating between two drains. The device shows a double-well shaped electromechanical potential tunable by a source-drain bias voltage. Four stationary regimes controllable by the bias are found for this device: (i) single stable fixed point, (ii) two stable fixed points, (iii) two limit cycles, and (iv) single limit cycle. In the presence of perpendicular magnetic field, the Lorentz force makes possible switching from one electromechanical state to another. The mechanism of tunable transitions between various stable regimes based on the interplay between voltage controlled electromechanical instabilitymore » and magnetically controlled switching is suggested. The switching phenomenon is implemented for achieving both a reliable active current switch and sensoring of small variations of magnetic field.« less

An Analytical Assessment of NASA's N(+)1 Subsonic Fixed Wing Project Noise Goal

NASA Technical Reports Server (NTRS)

Berton, Jeffrey J.; Envia, Edmane; Burley, Casey L.

2010-01-01

The Subsonic Fixed Wing Project of NASA s Fundamental Aeronautics Program has adopted a noise reduction goal for new, subsonic, single-aisle, civil aircraft expected to replace current 737 and A320 airplanes. These so-called "N+1" aircraft--designated in NASA vernacular as such since they will follow the current, in-service, "N" airplanes--are hoped to achieve certification noise goal levels of 32 cumulative EPNdB under current Stage 4 noise regulations. A notional, N+1, single-aisle, twinjet transport with ultrahigh bypass ratio turbofan engines is analyzed in this study using NASA software and methods. Several advanced noise-reduction technologies are empirically applied to the propulsion system and airframe. Certification noise levels are predicted and compared with the NASA goal.

High-Throughput Sequencing and Copy Number Variation Detection Using Formalin Fixed Embedded Tissue in Metastatic Gastric Cancer

PubMed Central

Hong, Min Eui; Do, In-Gu; Kang, So Young; Ha, Sang Yun; Kim, Seung Tae; Park, Se Hoon; Kang, Won Ki; Choi, Min-Gew; Lee, Jun Ho; Sohn, Tae Sung; Bae, Jae Moon; Kim, Sung; Kim, Duk-Hwan; Kim, Kyoung-Mee

2014-01-01

In the era of targeted therapy, mutation profiling of cancer is a crucial aspect of making therapeutic decisions. To characterize cancer at a molecular level, the use of formalin-fixed paraffin-embedded tissue is important. We tested the Ion AmpliSeq Cancer Hotspot Panel v2 and nCounter Copy Number Variation Assay in 89 formalin-fixed paraffin-embedded gastric cancer samples to determine whether they are applicable in archival clinical samples for personalized targeted therapies. We validated the results with Sanger sequencing, real-time quantitative PCR, fluorescence in situ hybridization and immunohistochemistry. Frequently detected somatic mutations included TP53 (28.17%), APC (10.1%), PIK3CA (5.6%), KRAS (4.5%), SMO (3.4%), STK11 (3.4%), CDKN2A (3.4%) and SMAD4 (3.4%). Amplifications of HER2, CCNE1, MYC, KRAS and EGFR genes were observed in 8 (8.9%), 4 (4.5%), 2 (2.2%), 1 (1.1%) and 1 (1.1%) cases, respectively. In the cases with amplification, fluorescence in situ hybridization for HER2 verified gene amplification and immunohistochemistry for HER2, EGFR and CCNE1 verified the overexpression of proteins in tumor cells. In conclusion, we successfully performed semiconductor-based sequencing and nCounter copy number variation analyses in formalin-fixed paraffin-embedded gastric cancer samples. High-throughput screening in archival clinical samples enables faster, more accurate and cost-effective detection of hotspot mutations or amplification in genes. PMID:25372287

Land mobile satellite system requirements

NASA Astrophysics Data System (ADS)

Kiesling, J. D.

1983-05-01

A Land Mobile Satellite System (LMSS) provides voice, data and related communications services to moving vehicles and persons. Communications between the mobiles and satellite are in the 806-890 MHz band. The satellite translates these signals to a ""fixed services band'' such as 14/12 GHz band (Ku-band), and communicates in this band with fixed terminals called gateways. The gateways are located at convenient places such as telephone switches (which provide entry into the national telephone system), dispatcher headquarters, computer centers, etc. Communications are therefore principally mobile to fixed. A third communications link, also at Ku-band, is needed between the satellite and a single fixed ground station. This link provides satellite command, telemetry and ranging and also provides a network control function. The latter, through a common signalling system, receives requests and assigns channel slots, and otherwise controls, monitors and polices the network and collects billing information.

Deep-Sea Archaea Fix and Share Nitrogen in Methane-Consuming Microbial Consortia

NASA Astrophysics Data System (ADS)

Dekas, Anne E.; Poretsky, Rachel S.; Orphan, Victoria J.

2009-10-01

Nitrogen-fixing (diazotrophic) microorganisms regulate productivity in diverse ecosystems; however, the identities of diazotrophs are unknown in many oceanic environments. Using single-cell-resolution nanometer secondary ion mass spectrometry images of 15N incorporation, we showed that deep-sea anaerobic methane-oxidizing archaea fix N2, as well as structurally similar CN-, and share the products with sulfate-reducing bacterial symbionts. These archaeal/bacterial consortia are already recognized as the major sink of methane in benthic ecosystems, and we now identify them as a source of bioavailable nitrogen as well. The archaea maintain their methane oxidation rates while fixing N2 but reduce their growth, probably in compensation for the energetic burden of diazotrophy. This finding extends the demonstrated lower limits of respiratory energy capable of fueling N2 fixation and reveals a link between the global carbon, nitrogen, and sulfur cycles.

Land mobile satellite system requirements

NASA Technical Reports Server (NTRS)

Kiesling, J. D.

1983-01-01

A Land Mobile Satellite System (LMSS) provides voice, data and related communications services to moving vehicles and persons. Communications between the mobiles and satellite are in the 806-890 MHz band. The satellite translates these signals to a ""fixed services band'' such as 14/12 GHz band (Ku-band), and communicates in this band with fixed terminals called gateways. The gateways are located at convenient places such as telephone switches (which provide entry into the national telephone system), dispatcher headquarters, computer centers, etc. Communications are therefore principally mobile to fixed. A third communications link, also at Ku-band, is needed between the satellite and a single fixed ground station. This link provides satellite command, telemetry and ranging and also provides a network control function. The latter, through a common signalling system, receives requests and assigns channel slots, and otherwise controls, monitors and polices the network and collects billing information.

Speech Segregation based on Binary Classification

DTIC Science & Technology

2016-07-15

including the IBM, the target binary mask (TBM), the IRM, the short -time Fourier transform spectral magnitude (FFT-MAG) and its corresponding mask (FFT...complementary features and a fixed DNN as the discriminative learning machine. For evaluation metrics, besides SNR, we use the Short -Time Objective...target analysis is a recent successful intelligibility test conducted on both normal-hearing (NH) and hearing-impaired (HI) listeners. The speech

Advanced development of immobilized enzyme reactors

NASA Technical Reports Server (NTRS)

Jolly, Clifford D.; Schussel, Leonard J.; Carter, Layne

1991-01-01

Fixed-bed reactors have been used at NASA-Marshall to purify wastewater generated by an end-use equipment facility, on the basis of a combination of multifiltration unibeds and enzyme unibeds. The enzyme beds were found to effectively remove such targeted organics as urea, alcohols, and aldehydes, down to levels lying below detection limits. The enzyme beds were also found to remove organic contaminants not specifically targeted.

RT-PCR analysis of RNA extracted from Bouin-fixed and paraffin-embedded lymphoid tissues.

PubMed

Gloghini, Annunziata; Canal, Barbara; Klein, Ulf; Dal Maso, Luigino; Perin, Tiziana; Dalla-Favera, Riccardo; Carbone, Antonino

2004-11-01

In the present study, we have investigated whether RNA can be efficiently isolated from Bouin-fixed or formalin-fixed, paraffin-embedded lymphoid tissue specimens. To this aim, we applied a new and simple method that includes the combination of proteinase K digestion and column purification. By this method, we demonstrated that the amplification of long fragments could be accomplished after a pre-heating step before cDNA synthesis associated with the use of enzymes that work at high temperature. By means of PCR using different primers for two examined genes (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]- and CD40), we amplified segments of cDNA obtained by reverse transcription of the isolated RNA extracted from Bouin-fixed or formalin-fixed paraffin-embedded tissues. Amplified fragments of the expected sizes were obtained for both genes tested indicating that this method is suitable for the isolation of high-quality RNA. To explore the possibility for giving accurate real time quantitative RT-PCR results, cDNA obtained from matched frozen, Bouin-fixed and formalin-fixed neoplastic samples (two diffuse large cell lymphomas, one plasmacytoma) was tested for the following target genes: CD40, Aquaporin-3, BLIMP1, IRF4, Syndecan-1. Delta threshold cycle (DeltaC(T)) values for Bouin-fixed and formalin-fixed paraffin-embedded tissues and their correlation with those for frozen samples showed an extremely high correlation (r > 0.90) for all of the tested genes. These results show that the method of RNA extraction we propose is suitable for giving accurate real time quantitative RT-PCR results.

Development and validation of the JAX Cancer Treatment Profile™ for detection of clinically actionable mutations in solid tumors

PubMed Central

Ananda, Guruprasad; Mockus, Susan; Lundquist, Micaela; Spotlow, Vanessa; Simons, Al; Mitchell, Talia; Stafford, Grace; Philip, Vivek; Stearns, Timothy; Srivastava, Anuj; Barter, Mary; Rowe, Lucy; Malcolm, Joan; Bult, Carol; Karuturi, Radha Krishna Murthy; Rasmussen, Karen; Hinerfeld, Douglas

2015-01-01

Background The continued development of targeted therapeutics for cancer treatment has required the concomitant development of more expansive methods for the molecular profiling of the patient’s tumor. We describe the validation of the JAX Cancer Treatment Profile™ (JAX-CTP™), a next generation sequencing (NGS)-based molecular diagnostic assay that detects actionable mutations in solid tumors to inform the selection of targeted therapeutics for cancer treatment. Methods NGS libraries are generated from DNA extracted from formalin fixed paraffin embedded tumors. Using hybrid capture, the genes of interest are enriched and sequenced on the Illumina HiSeq 2500 or MiSeq sequencers followed by variant detection and functional and clinical annotation for the generation of a clinical report. Results The JAX-CTP™ detects actionable variants, in the form of single nucleotide variations and small insertions and deletions (≤50bp) in 190 genes in specimens with a neoplastic cell content of ≥10%. The JAX-CTP™ is also validated for the detection of clinically actionable gene amplifications. Conclusions There is a lack of consensus in the molecular diagnostics field on the best method for the validation of NGS-based assays in oncology, thus the importance of communicating methods, as contained in this report. The growing number of targeted therapeutics and the complexity of the tumor genome necessitates continued development and refinement of advanced assays for tumor profiling to enable precision cancer treatment. PMID:25562415

Rapid targeted somatic mutation analysis of solid tumors in routine clinical diagnostics.

PubMed

Magliacane, Gilda; Grassini, Greta; Bartocci, Paola; Francaviglia, Ilaria; Dal Cin, Elena; Barbieri, Gianluca; Arrigoni, Gianluigi; Pecciarini, Lorenza; Doglioni, Claudio; Cangi, Maria Giulia

2015-10-13

Tumor genotyping is an essential step in routine clinical practice and pathology laboratories face a major challenge in being able to provide rapid, sensitive and updated molecular tests. We developed a novel mass spectrometry multiplexed genotyping platform named PentaPanel to concurrently assess single nucleotide polymorphisms in 56 hotspots of the 5 most clinically relevant cancer genes, KRAS, NRAS, BRAF, EGFR and PIK3CA for a total of 221 detectable mutations. To both evaluate and validate the PentaPanel performance, we investigated 1025 tumor specimens of 6 different cancer types (carcinomas of colon, lung, breast, pancreas, and biliary tract, and melanomas), systematically addressing sensitivity, specificity, and reproducibility of our platform. Sanger sequencing was also performed for all the study samples. Our data showed that PentaPanel is a high throughput and robust tool, allowing genotyping for targeted therapy selection of 10 patients in the same run, with a practical turnaround time of 2 working days. Importantly, it was successfully used to interrogate different DNAs isolated from routinely processed specimens (formalin-fixed paraffin embedded, frozen, and cytological samples), covering all the requirements of clinical tests. In conclusion, the PentaPanel platform can provide an immediate, accurate and cost effective multiplex approach for clinically relevant gene mutation analysis in many solid tumors and its utility across many diseases can be particularly relevant in multiple clinical trials, including the new basket trial approach, aiming to identify appropriate targeted drug combination strategies.

Validation of a single-stage fixed-rate step test for the prediction of maximal oxygen uptake in healthy adults.

PubMed

Hansen, Dominique; Jacobs, Nele; Thijs, Herbert; Dendale, Paul; Claes, Neree

2016-09-01

Healthcare professionals with limited access to ergospirometry remain in need of valid and simple submaximal exercise tests to predict maximal oxygen uptake (VO2max ). Despite previous validation studies concerning fixed-rate step tests, accurate equations for the estimation of VO2max remain to be formulated from a large sample of healthy adults between age 18-75 years (n > 100). The aim of this study was to develop a valid equation to estimate VO2max from a fixed-rate step test in a larger sample of healthy adults. A maximal ergospirometry test, with assessment of cardiopulmonary parameters and VO2max , and a 5-min fixed-rate single-stage step test were executed in 112 healthy adults (age 18-75 years). During the step test and subsequent recovery, heart rate was monitored continuously. By linear regression analysis, an equation to predict VO2max from the step test was formulated. This equation was assessed for level of agreement by displaying Bland-Altman plots and calculation of intraclass correlations with measured VO2max . Validity further was assessed by employing a Jackknife procedure. The linear regression analysis generated the following equation to predict VO2max (l min(-1) ) from the step test: 0·054(BMI)+0·612(gender)+3·359(body height in m)+0·019(fitness index)-0·012(HRmax)-0·011(age)-3·475. This equation explained 78% of the variance in measured VO2max (F = 66·15, P<0·001). The level of agreement and intraclass correlation was high (ICC = 0·94, P<0·001) between measured and predicted VO2max . From this study, a valid fixed-rate single-stage step test equation has been developed to estimate VO2max in healthy adults. This tool could be employed by healthcare professionals with limited access to ergospirometry. © 2015 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Calculation of the Frequency Distribution of the Energy Deposition in DNA Volumes by Heavy Ions

NASA Technical Reports Server (NTRS)

Plante, Ianik; Cicinotta, Francis A.

2012-01-01

Radiation quality effects are largely determined by energy deposition in small volumes of characteristic sizes less than 10 nm representative of short-segments of DNA, the DNA nucleosome, or molecules initiating oxidative stress in the nucleus, mitochondria, or extra-cellular matrix. On this scale, qualitatively distinct types of molecular damage are possible for high linear energy transfer (LET) radiation such as heavy ions compared to low LET radiation. Unique types of DNA lesions or oxidative damages are the likely outcome of the energy deposition. The frequency distribution for energy imparted to 1-20 nm targets per unit dose or particle fluence is a useful descriptor and can be evaluated as a function of impact parameter from an ions track. In this work, the simulation of 1-Gy irradiation of a cubic volume of 5 micron by: 1) 450 (1)H(+) ions, 300 MeV; 2) 10 (12)C(6+) ions, 290 MeV/amu and 3) (56)Fe(26+) ions, 1000 MeV/amu was done with the Monte-Carlo simulation code RITRACKS. Cylindrical targets are generated in the irradiated volume, with random orientation. The frequency distribution curves of the energy deposited in the targets is obtained. For small targets (i.e. <25 nm size), the probability of an ion to hit a target is very small; therefore a large number of tracks and targets as well as a large number of histories are necessary to obtain statistically significant results. This simulation is very time-consuming and is difficult to perform by using the original version of RITRACKS. Consequently, the code RITRACKS was adapted to use multiple CPU on a workstation or on a computer cluster. To validate the simulation results, similar calculations were performed using targets with fixed position and orientation, for which experimental data are available [5]. Since the probability of single- and double-strand breaks in DNA as function of energy deposited is well know, the results that were obtained can be used to estimate the yield of DSB, and can be extended to include other targeted or non-target effects.

No difference in terms of radiostereometric analysis between fixed- and mobile-bearing total knee arthroplasty: a randomized, single-blind, controlled trial.

PubMed

Schotanus, M G M; Pilot, P; Kaptein, B L; Draijer, W F; Tilman, P B J; Vos, R; Kort, N P

2017-09-01

A concern that arises with any new prosthesis is whether it will achieve satisfactory long-term implant stability. The gold standard of assessing the quality of fixation in a new or relatively new implant is to undertake a randomized controlled trial using radiostereometric analysis. It was hypothesized that both mobile-bearing total knee arthroplasty and fixed-bearing total knee arthroplasty have comparable migration patterns at 2-year follow-up. This study investigated two types of cemented total knee arthroplasty, the mobile- or fixed-bearing variant from the same family with use of radiostereometric analysis. This prospective, patient-blinded, randomized, controlled trial was designed to investigate early migration of the tibia component after two years of follow-up with use of radiostereometric analysis. A total of 50 patients were randomized to receive a mobile- or fixed-bearing TKA from the same family. Patients were evaluated during 2-year follow-up, including radiostereometric analysis, physical and clinical examination and patient reported outcome measures (PROMs). At two-year follow-up, the mean (±SD) maximum total point motion (MTPM) in the fixed-bearing group was 0.82 (±1.16) versus 0.92 mm (±0.64) in the mobile-bearing group (p = n.s) with the largest migration seen during the first 6 weeks (0.45 ± 0.32 vs. 0.54 ± 0.30). The clinical outcome and PROMs significantly improved within each group, not between both groups. Measuring early micromotion is useful for predicting clinical loosening that can lead to revision. The results of this study demonstrate that early migration of the mobile-bearing is similar to that of the fixed-bearing component at two years and was mainly seen in the first weeks after implantation. Randomized, single-blind, controlled trial, Level I.

Symbiotic N2-Fixer Community Composition, but Not Diversity, Shifts in Nodules of a Single Host Legume Across a 2-Million-Year Dune Chronosequence.

PubMed

Birnbaum, Christina; Bissett, Andrew; Teste, Francois P; Laliberté, Etienne

2018-04-16

Long-term soil age gradients are useful model systems to study how changes in nutrient limitation shape communities of plant root mutualists because they represent strong natural gradients of nutrient availability, particularly of nitrogen (N) and phosphorus (P). Here, we investigated changes in the dinitrogen (N 2 )-fixing bacterial community composition and diversity in nodules of a single host legume (Acacia rostellifera) across the Jurien Bay chronosequence, a retrogressive 2 million-year-old sequence of coastal dunes representing an exceptionally strong natural soil fertility gradient. We collected nodules from plants grown in soils from five chronosequence stages ranging from very young (10s of years; associated with strong N limitation for plant growth) to very old (> 2,000,000 years; associated with strong P limitation), and sequenced the nifH gene in root nodules to determine the composition and diversity of N 2 -fixing bacterial symbionts. A total of 335 unique nifH gene operational taxonomic units (OTUs) were identified. Community composition of N 2 -fixing bacteria within nodules, but not diversity, changed with increasing soil age. These changes were attributed to pedogenesis-driven shifts in edaphic conditions, specifically pH, exchangeable manganese, resin-extractable phosphate, nitrate and nitrification rate. A large number of common N 2 -fixing bacteria genera (e.g. Bradyrhizobium, Ensifer, Mesorhizobium and Rhizobium) belonging to the Rhizobiaceae family (α-proteobacteria) comprised 70% of all raw sequences and were present in all nodules. However, the oldest soils, which show some of the lowest soil P availability ever recorded, harboured the largest proportion of unclassified OTUs, suggesting a unique set of N 2 -fixing bacteria adapted to extreme P limitation. Our results show that N 2 -fixing bacterial composition varies strongly during long-term ecosystem development, even within the same host, and therefore rhizobia show strong edaphic preferences.

Generalization of vestibular learning to earth-fixed targets is possible but limited when the polarity of afferent vestibular information is changed.

PubMed

Mackrous, I; Simoneau, M

2014-02-28

To maintain perception of the world around us during body motion, the brain must update the spatial presentation of visual stimuli, known as space updating. Previous studies have demonstrated that vestibular signals contribute to space updating. Nonetheless, when being passively rotated in the dark, the ability to keep track of a memorized earth-fixed target (EFT) involves learning mechanism(s). We tested whether such learning generalizes across different EFT eccentricities. Furthermore, we ascertained whether learning transfers to similar target eccentricities but in the opposite direction. Participants were trained to predict the position of an EFT (located at 45° to their left) while being rotated counterclockwise (i.e., they press a push button when they perceived that their body midline have cross the position of the target). Overall, the results indicated that learning transferred to other target eccentricity (30° and 60°) for identical body rotation direction. In contrast, vestibular learning partly transferred to target location's matching body rotation but in the opposite rotation direction. Generalization of learning implies that participants do not adopt cognitive strategies to improve their performance during training. We argue that the brain learned to use vestibular signals for space updating. Generalization of learning while being rotated in the opposite direction implies that some parts of the neural networks involved in space updating is shared between trained and untrained direction. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Construction and Gluing of G10 Frames and Printed Circuit Boards to be used in COMPASS Drift Chamber 5

NASA Astrophysics Data System (ADS)

Britto, Vivek

2014-09-01

COMPASS is a fixed-target nuclear physics experiment at CERN which explores the internal structure of the proton. One specific area of research is the measurement of single transverse spin asymmetries in pion beam induced Drell-Yan production of muon pairs from polarized proton targets. The spin dependence of the Drell-Yan cross section may be indicative of contributions from quark orbital angular momentum to the spin of the proton. The University of Illinois at Urbana-Champaign (UIUC), in collaboration with institutes in Taiwan, France, Italy and Germany, is designing and building a new drift chamber, DC5, to replace an aging detector in the COMPASS spectrometer. The frames supporting the anode wires and cathode planes in DC5 are constructed from G10, a fiberglass-epoxy composite. Once the individual sides of each frame have been milled, they are glued together at the corner lap joints. Additionally, printed circuit boards are glued to the anode frames, where sense and field wires will later be soldered. To maintain optimal operation of the drift chamber, the frame thickness after gluing must be within 50 μm of the design value. This presentation will explain the methods employed to achieve the required tolerances for this precision gluing process.

Numerical simulations of recent proton acceleration experiments with sub-100 TW laser systems

NASA Astrophysics Data System (ADS)

Sinigardi, Stefano

2016-09-01

Recent experiments carried out at the Italian National Research Center, National Optics Institute Department in Pisa, are showing interesting results regarding maximum proton energies achievable with sub-100 TW laser systems. While laser systems are being continuously upgraded in laboratories around the world, at the same time a new trend on stabilizing and making ion acceleration results reproducible is growing in importance. Almost all applications require a beam with fixed performance, so that the energy spectrum and the total charge exhibit moderate shot to shot variations. This result is surely far from being achieved, but many paths are being explored in order to reach it. Some of the reasons for this variability come from fluctuations in laser intensity and focusing, due to optics instability. Other variation sources come from small differences in the target structure. The target structure can vary substantially, when it is impacted by the main pulse, due to the prepulse duration and intensity, the shape of the main pulse and the total energy deposited. In order to qualitatively describe the prepulse effect, we will present a two dimensional parametric scan of its relevant parameters. A single case is also analyzed with a full three dimensional simulation, obtaining reasonable agreement between the numerical and the experimental energy spectrum.

Distractor ratio and grouping processes in visual conjunction search.

PubMed

Poisson, M E; Wilkinson, F

1992-01-01

According to feature integration theory, conjunction search is conducted via a serial self-terminating search. However, effects attributed to search processes operating on the entire display may actually reflect search restricted to elements defined by a single feature. In experiment 1 this question is addressed in a reaction-time (RT) paradigm by varying distractor ratios within an array of fixed size. For trials in which the target was present in the array, RT functions were roughly symmetric, the shortest RTs being for extreme distractor ratios, and the longest RTs being for arrays in which there were an equal number of each distractor type. This result is superficially consistent with Zohary and Hochstein's interpretation that subjects search for only one distractor type and are able to switch search strategy from trial to trial. However, negative-trial data from experiment 1 case doubt on this interpretation. In experiment 2 the possible role of 'pop out' and of distractor grouping in visual conjunction search is investigated. Results of experiment 2 suggest that grouping may play a more important role than does distractor ratio, and point to the importance of the spatial layout of the target and of the distractor elements in visual conjunction search. Results of experiment 2 also provide clear evidence that groups of spatially adjacent homogeneous elements may be processed as a unit.

Oligonucleotide gap-fill ligation for mutation detection and sequencing in situ

PubMed Central

Mignardi, Marco; Mezger, Anja; Qian, Xiaoyan; La Fleur, Linnea; Botling, Johan; Larsson, Chatarina; Nilsson, Mats

2015-01-01

In clinical diagnostics a great need exists for targeted in situ multiplex nucleic acid analysis as the mutational status can offer guidance for effective treatment. One well-established method uses padlock probes for mutation detection and multiplex expression analysis directly in cells and tissues. Here, we use oligonucleotide gap-fill ligation to further increase specificity and to capture molecular substrates for in situ sequencing. Short oligonucleotides are joined at both ends of a padlock gap probe by two ligation events and are then locally amplified by target-primed rolling circle amplification (RCA) preserving spatial information. We demonstrate the specific detection of the A3243G mutation of mitochondrial DNA and we successfully characterize a single nucleotide variant in the ACTB mRNA in cells by in situ sequencing of RCA products generated by padlock gap-fill ligation. To demonstrate the clinical applicability of our assay, we show specific detection of a point mutation in the EGFR gene in fresh frozen and formalin-fixed, paraffin-embedded (FFPE) lung cancer samples and confirm the detected mutation by in situ sequencing. This approach presents several advantages over conventional padlock probes allowing simpler assay design for multiplexed mutation detection to screen for the presence of mutations in clinically relevant mutational hotspots directly in situ. PMID:26240388

Are Age-Related Differences Uniform Across Different Inhibitory Functions?

PubMed

Vadaga, Kiran K; Blair, Mervin; Li, Karen Z H

2016-07-01

In the current experiment, we examined the relative age-sensitivity of 3 inhibitory functions: access, deletion, and restraint by taking into consideration their underlying control processes: proactive and reactive control. The 3 inhibitory functions were measured using a sequential flanker task. Young (age: 18-35, n = 24) and older adults (age: 60-75, n = 25) first memorized a series of 8 animal words in a fixed order. In the test phase, these stimuli were presented randomly either singly or with flankers and participants responded "yes" or "no" based on the prelearned sequence. In the access trials, flankers were either ahead of the current target or unrelated. In the deletion trials, flankers were previous target items. In the restraint trials, the flanker cues (XXXX) prompted the participants to withhold responses occasionally. Unflanked trials served as the baseline condition. Age-related differences in the magnitude of inhibition effects were largest in restraint, followed by deletion. No age-related differences were observed in access. Our findings suggest that the magnitude of age-related differences in inhibitory functions is contingent on the degree of proactive control recruited by a given inhibitory function. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Methods for selecting fixed-effect models for heterogeneous codon evolution, with comments on their application to gene and genome data.

PubMed

Bao, Le; Gu, Hong; Dunn, Katherine A; Bielawski, Joseph P

2007-02-08

Models of codon evolution have proven useful for investigating the strength and direction of natural selection. In some cases, a priori biological knowledge has been used successfully to model heterogeneous evolutionary dynamics among codon sites. These are called fixed-effect models, and they require that all codon sites are assigned to one of several partitions which are permitted to have independent parameters for selection pressure, evolutionary rate, transition to transversion ratio or codon frequencies. For single gene analysis, partitions might be defined according to protein tertiary structure, and for multiple gene analysis partitions might be defined according to a gene's functional category. Given a set of related fixed-effect models, the task of selecting the model that best fits the data is not trivial. In this study, we implement a set of fixed-effect codon models which allow for different levels of heterogeneity among partitions in the substitution process. We describe strategies for selecting among these models by a backward elimination procedure, Akaike information criterion (AIC) or a corrected Akaike information criterion (AICc). We evaluate the performance of these model selection methods via a simulation study, and make several recommendations for real data analysis. Our simulation study indicates that the backward elimination procedure can provide a reliable method for model selection in this setting. We also demonstrate the utility of these models by application to a single-gene dataset partitioned according to tertiary structure (abalone sperm lysin), and a multi-gene dataset partitioned according to the functional category of the gene (flagellar-related proteins of Listeria). Fixed-effect models have advantages and disadvantages. Fixed-effect models are desirable when data partitions are known to exhibit significant heterogeneity or when a statistical test of such heterogeneity is desired. They have the disadvantage of requiring a priori knowledge for partitioning sites. We recommend: (i) selection of models by using backward elimination rather than AIC or AICc, (ii) use a stringent cut-off, e.g., p = 0.0001, and (iii) conduct sensitivity analysis of results. With thoughtful application, fixed-effect codon models should provide a useful tool for large scale multi-gene analyses.

Vibrational and rotational transitions in low-energy electron-diatomic-molecule collisions. I - Close-coupling theory in the moving body-fixed frame. II - Hybrid theory and close-coupling theory: An /l subscript z-prime/-conserving close-coupling approximation

NASA Technical Reports Server (NTRS)

Choi, B. H.; Poe, R. T.

1977-01-01

A detailed vibrational-rotational (V-R) close-coupling formulation of electron-diatomic-molecule scattering is developed in which the target molecular axis is chosen to be the z-axis and the resulting coupled differential equation is solved in the moving body-fixed frame throughout the entire interaction region. The coupled differential equation and asymptotic boundary conditions in the body-fixed frame are given for each parity, and procedures are outlined for evaluating V-R transition cross sections on the basis of the body-fixed transition and reactance matrix elements. Conditions are discussed for obtaining identical results from the space-fixed and body-fixed formulations in the case where a finite truncated basis set is used. The hybrid theory of Chandra and Temkin (1976) is then reformulated, relevant expressions and formulas for the simultaneous V-R transitions of the hybrid theory are obtained in the same forms as those of the V-R close-coupling theory, and distorted-wave Born-approximation expressions for the cross sections of the hybrid theory are presented. A close-coupling approximation that conserves the internuclear axis component of the incident electronic angular momentum (l subscript z-prime) is derived from the V-R close-coupling formulation in the moving body-fixed frame.

Bioequivalence of fixed-dose combination RIN®-150 to each reference drug in loose combination.

PubMed

Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Damle, B

2015-03-01

RIN(®)-150 is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg) and isoniazid (INH, 75 mg) developed for the treatment of tuberculosis. This study was conducted at a single center: the Pfizer Clinical Research Unit in Singapore. To demonstrate bioequivalence of each drug component between RIN-150 and individual products in a loose combination. This was a randomized, open-label, single-dose, two-way crossover study. Subjects received single doses of RIN-150 or two individual reference products under fasting conditions in a crossover fashion, with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC). Of 28 subjects enrolled, 26 completed the study. The adjusted geometric mean ratios of Cmax and AUClast between the FDC and single-drug references and 90% confidence intervals were respectively 91.63% (90%CI 83.13-101.01) and 95.45% (90%CI 92.07-98.94) for RMP, and 107.58% (90%CI 96.07-120.47) and 103.45% (90%CI 99.33-107.75) for INH. Both formulations were generally well tolerated in this study. The RIN-150 FDC tablet formulation is bioequivalent to the two single-drug references for RMP and INH at equivalent doses.

DAEδALUS and dark matter detection

DOE PAGES

Kahn, Yonatan; Krnjaic, Gordan; Thaler, Jesse; ...

2015-03-05

Among laboratory probes of dark matter, fixed-target neutrino experiments are particularly well suited to search for light weakly coupled dark sectors. Here in this paper, we show that the DAEδALUS source setup$-$an 800 MeV proton beam impinging on a target of graphite and copper$-$can improve the present LSND bound on dark photon models by an order of magnitude over much of the accessible parameter space for light dark matter when paired with a suitable neutrino detector such as LENA. Interestingly, both DAEδALUS and LSND are sensitive to dark matter produced from off-shell dark photons. We show for the first timemore » that LSND can be competitive with searches for visible dark photon decays and that fixed-target experiments have sensitivity to a much larger range of heavy dark photon masses than previously thought. We review the mechanism for dark matter production and detection through a dark photon mediator, discuss the beam-off and beam-on backgrounds, and present the sensitivity in dark photon kinetic mixing for both the DAEδALUS/LENA setup and LSND in both the on- and off-shell regimes.« less

Targeted resequencing reveals ALK fusions in non-small cell lung carcinomas detected by FISH, immunohistochemistry, and real-time RT-PCR: a comparison of four methods.

PubMed

Tuononen, Katja; Sarhadi, Virinder Kaur; Wirtanen, Aino; Rönty, Mikko; Salmenkivi, Kaisa; Knuuttila, Aija; Remes, Satu; Telaranta-Keerie, Aino I; Bloor, Stuart; Ellonen, Pekka; Knuutila, Sakari

2013-01-01

Anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements occur in a subgroup of non-small cell lung carcinomas (NSCLCs). The identification of these rearrangements is important for guiding treatment decisions. The aim of our study was to screen ALK gene fusions in NSCLCs and to compare the results detected by targeted resequencing with results detected by commonly used methods, including fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcription-PCR (RT-PCR). Furthermore, we aimed to ascertain the potential of targeted resequencing in detection of ALK-rearranged lung carcinomas. We assessed ALK fusion status for 95 formalin-fixed paraffin-embedded tumor tissue specimens from 87 patients with NSCLC by FISH and real-time RT-PCR, for 57 specimens from 56 patients by targeted resequencing, and for 14 specimens from 14 patients by IHC. All methods were performed successfully on formalin-fixed paraffin-embedded tumor tissue material. We detected ALK fusion in 5.7% (5 out of 87) of patients examined. The results obtained from resequencing correlated significantly with those from FISH, real-time RT-PCR, and IHC. Targeted resequencing proved to be a promising method for ALK gene fusion detection in NSCLC. Means to reduce the material and turnaround time required for analysis are, however, needed.

Development of hydrolysis probe-based real-time PCR for identification of virulent gene targets of Burkholderia pseudomallei and B. mallei--a retrospective study on archival cases of service members with melioidosis and glanders.

PubMed

Zhang, Binxue; Wear, Douglas J; Kim, H S; Weina, Peter; Stojadinovic, Alexander; Izadjoo, Mina

2012-02-01

Burkholderia pseudomallei and B. mallei are two highly pathogenic bacteria responsible for melioidosis and glanders, respectively. Our laboratory developed hydrolysis probe-based real-time polymerase chain reaction assays targeting type three secretion system (TTS) and transposase family protein (TFP) of B. pseudomallei and B. malli, respectively. The assays were validated for target specificity, amplification sensitivity, and reproducibility. A bacterial DNA panel, composed of B. pseudomallei (13 strains), B. mallei (11 strains), Burkholderia species close neighbors (5 strains), and other bacterial species (17 strains), was prepared for specificity testing. Reference DNAs from B. pseudomallei and B. mallei bacterial cultures were used as controls for amplification, limit of detection, and reproducibility testing. The two TaqMan assays, Bp-TTS 1 and Bm-TFP, were optimized and applied in a retrospective study of archived cases from the Armed Forces Institute of Pathology. We tested 10 formalin-fixed paraffin-embedded blocks originally from autopsy specimens of patients who died of melioidosis or glanders during or after overseas tours in 1960s. Polymerase chain reaction results confirmed that DNA samples from formalin-fixed paraffin-embedded blocks of eight patients with melioidosis were positive for Bp-TTS 1 target and two patients with glanders were positive for Bm-TFP target.

Sealed One Piece Battery Having A Prism Shape Container

DOEpatents

Verhoog, Roelof; Barbotin, Jean-Loup

2000-03-28

A sealed one-piece battery having a prism-shaped container including: a tank consisting of a single plastic material, a member fixed and sealed to the tank and to partitions on the side of the tank opposite the transverse wall to seal the tank, two flanges fixed and sealed to longitudinal walls defining flow compartments for a heat-conducting fluid, and two tubes on the transverse wall of the tank forming an inlet and an outlet for fluid common to the compartments.

A data driven partial ambiguity resolution: Two step success rate criterion, and its simulation demonstration

NASA Astrophysics Data System (ADS)

Hou, Yanqing; Verhagen, Sandra; Wu, Jie

2016-12-01

Ambiguity Resolution (AR) is a key technique in GNSS precise positioning. In case of weak models (i.e., low precision of data), however, the success rate of AR may be low, which may consequently introduce large errors to the baseline solution in cases of wrong fixing. Partial Ambiguity Resolution (PAR) is therefore proposed such that the baseline precision can be improved by fixing only a subset of ambiguities with high success rate. This contribution proposes a new PAR strategy, allowing to select the subset such that the expected precision gain is maximized among a set of pre-selected subsets, while at the same time the failure rate is controlled. These pre-selected subsets are supposed to obtain the highest success rate among those with the same subset size. The strategy is called Two-step Success Rate Criterion (TSRC) as it will first try to fix a relatively large subset with the fixed failure rate ratio test (FFRT) to decide on acceptance or rejection. In case of rejection, a smaller subset will be fixed and validated by the ratio test so as to fulfill the overall failure rate criterion. It is shown how the method can be practically used, without introducing a large additional computation effort. And more importantly, how it can improve (or at least not deteriorate) the availability in terms of baseline precision comparing to classical Success Rate Criterion (SRC) PAR strategy, based on a simulation validation. In the simulation validation, significant improvements are obtained for single-GNSS on short baselines with dual-frequency observations. For dual-constellation GNSS, the improvement for single-frequency observations on short baselines is very significant, on average 68%. For the medium- to long baselines, with dual-constellation GNSS the average improvement is around 20-30%.

A Low Cost Single Chip VDL Compatible Transceiver ASIC

NASA Technical Reports Server (NTRS)

Becker, Robert

2004-01-01

Recent trends in commercial communications system components have focussed almost exclusively on cellular telephone technology. As many of the traditional sources of receiver components have discontinued non-cellular telephone products, the designers of avionics and other low volume radio applications find themselves increasingly unable to find highly integrated components. This is particularly true for low power, low cost applications which cannot afford the lavish current consumption of the software defined radio approach increasingly taken by certified device manufacturers. In this paper, we describe a low power transceiver chip targeting applications from low VHF to low UHF frequencies typical of avionics systems. The chip encompasses a selectable single or double conversion design for the receiver and a low power IF upconversion transmitter. All local oscillators are synthesized and integrated into the chip. An on-chip I-Q modulator and demodulator provide baseband modulation and demodulation capability allowing the use of low power, fixed point signal processing components for signal demodulation. The goal of this program is to demonstrate a low cost VDL mode-3 transceiver using this chip to receive text weather information sent using 4-slot TDMA with no support for voice. The data will be sent from an experimental ground station. This work is funded by NASA Glenn Research Center.

A high-sensitivity electrochemical aptasensor of carcinoembryonic antigen based on graphene quantum dots-ionic liquid-nafion nanomatrix and DNAzyme-assisted signal amplification strategy.

PubMed

Huang, Jing-Yi; Zhao, Lang; Lei, Wan; Wen, Wei; Wang, Yi-Jia; Bao, Ting; Xiong, Hua-Yu; Zhang, Xiu-Hua; Wang, Sheng-Fu

2018-01-15

In this work, we have developed an electrochemical aptasensor for high-sensitivity determination of carcinoembryonic antigen (CEA) based on lead ion (Pb 2+ )-dependent DNAzyme-assisted signal amplification and graphene quantum dot-ionic liquid-nafion (GQDs-IL-NF) composite film. We designed hairpin DNA containing CEA-specific aptamers and DNAzyme chains. In the presence of CEA, hairpin DNA recognized the target and performed a DNAzyme-assisted signal amplification reaction to yield a large number of single-stranded DNA. The GQDs-IL-NF composite film was immobilized on the glassy carbon electrode for the interaction with single-stranded DNA through noncovalent π-π stacking interaction. Therefore, the methylene blue-labeled substrate DNA (MB-substrate) was fixed on the electrode and exhibited an initial electrochemical signal. Under optimal conditions, the response current change was proportional to the concentration of CEA, demonstrating a wide linear range from 0.5fgmL -1 to 0.5ngmL -1 , with a low detection limit of 0.34fgmL -1 . Furthermore, the proposed aptasensor was successfully applied in determining CEA in serum samples, showing its superior prospects in clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

NanoString, a novel digital color-coded barcode technology: current and future applications in molecular diagnostics.

PubMed

Tsang, Hin-Fung; Xue, Vivian Weiwen; Koh, Su-Pin; Chiu, Ya-Ming; Ng, Lawrence Po-Wah; Wong, Sze-Chuen Cesar

2017-01-01

Formalin-fixed, paraffin-embedded (FFPE) tissue sample is a gold mine of resources for molecular diagnosis and retrospective clinical studies. Although molecular technologies have expanded the range of mutations identified in FFPE samples, the applications of existing technologies are limited by the low nucleic acids yield and poor extraction quality. As a result, the routine clinical applications of molecular diagnosis using FFPE samples has been associated with many practical challenges. NanoString technologies utilize a novel digital color-coded barcode technology based on direct multiplexed measurement of gene expression and offer high levels of precision and sensitivity. Each color-coded barcode is attached to a single target-specific probe corresponding to a single gene which can be individually counted without amplification. Therefore, NanoString is especially useful for measuring gene expression in degraded clinical specimens. Areas covered: This article describes the applications of NanoString technologies in molecular diagnostics and challenges associated with its applications and the future development. Expert commentary: Although NanoString technology is still in the early stages of clinical use, it is expected that NanoString-based cancer expression panels would play more important roles in the future in classifying cancer patients and in predicting the response to therapy for better personal therapeutic care.

Bio-compatible organic humidity sensor transferred to arbitrary surfaces fabricated using single-cell-thick onion membrane as both the substrate and sensing layer

NASA Astrophysics Data System (ADS)

Sajid, Memoon; Aziz, Shahid; Kim, Go Bum; Kim, Soo Wan; Jo, Jeongdai; Choi, Kyung Hyun

2016-07-01

A bio-compatible disposable organic humidity sensor has been fabricated that can be transferred to any arbitrary target surface. Single cell thick onion membrane has been used as the substrate while it also doubles as the active layer of the sensor. Two different types of sensors were fabricated. In type-1, the membrane was fixed into a plastic frame with IDT patterns on one side while the other side was also exposed to environment. In type-2, onion membrane was attached to a glass substrate with one side exposed to environment having an IDT screen-printed on top of it. The electrical output response of the sensors showed their ability to detect relative humidity between 0% RH and 80% RH with stable response and good sensitivity. The impedance of the sensors changed from 16 MΩ to 2 MΩ for type-1 and 6 MΩ to 20 KΩ for type-2. The response times of type-1 and type-2 were ~1 and 1.5 seconds respectively. The recovery times were ~10.75 seconds and ~11.25 seconds for type-1 and type-2 respectively. The device was successfully transferred to various randomly shaped surfaces without damaging the device.

Pilot validation of an individualised pharmacokinetic algorithm for protamine dosing after systemic heparinisation for cardiopulmonary bypass.

PubMed

Miles, Lachlan F; Marchiori, Paolo; Falter, Florian

2017-09-01

This manuscript represents a pilot study assessing the feasibility of a single-compartment, individualised, pharmacokinetic algorithm for protamine dosing after cardiopulmonary bypass. A pilot cohort study in a specialist NHS cardiothoracic hospital targeting patients undergoing elective cardiac surgery using cardiopulmonary bypass. Patients received protamine doses according to a pharmacokinetic algorithm (n = 30) or using an empirical, fixed-dose model (n = 30). Categorical differences between the groups were evaluated using the Chi-squared test or Fisher's exact test. Continuous data was analysed using a paired Student's t-test for parametric data and the paired samples Wilcoxon test for non-parametric data. Patients who had protamine dosing according to the algorithm demonstrated a lower protamine requirement post-bypass relative to empirical management as measured by absolute dose (243 ± 49mg vs. 305 ± 34.7mg; p<0.001) and the heparin to protamine ratio (0.79 ± 0.12 vs. 1.1 ± 0.15; p<0.001). There was no difference in the pre- to post-bypass activated clotting time (ACT) ratio (1.05 ± 0.12 vs. 1.02 ± 0.15; p=0.9). Patients who received protamine according to the algorithm had no significant difference in transfusion requirement (13.3% vs. 30.0%; p=0.21). This study showed that an individualized pharmacokinetic algorithm for the reversal of heparin after cardiopulmonary bypass is feasible in comparison with a fixed dosing strategy and may reduce the protamine requirement following on-pump cardiac surgery.

Single-mode laser studies: Design and performance of a fixed-wave length source and coupling of lasers to thin-film optical waveguides

NASA Technical Reports Server (NTRS)

Ladany, I.; Hammer, J. M.

1980-01-01

A module developed for the generation of a stable single wavelength to be used for a fiber optic multiplexing scheme is described. The laser is driven with RZ pulses, and the temperature is stabilized thermoelectrically. The unit is capable of maintaining a fixed wavelength within about 6 A as the pulse duty cycle is changed between 0 and 100 percent. This is considered the most severe case, and much tighter tolerances are obtainable for constant input power coding schemes. Using a constricted double heterostructure laser, a wavelength shift of 0.083 A mA is obtained due to laser self-heating by a dc driving current. The thermoelectric unit is capable of maintaining a constant laser heat-sink temperature within 0.02 C. In addition, miniature lenses and couplers are described which allow efficient coupling of single wavelength modes of junction lasers to thin film optical waveguides. The design of the miniature cylinder lenses and the prism coupling techniques allow 2 mW of single wavelength mode junction laser light to b coupled into thin film waveguides using compact assemblies. Selective grating couplers are also studied.

A High-Resolution Endoscope of Small Diameter Using Electromagnetically Vibration of Single Fiber

NASA Astrophysics Data System (ADS)

Matsunaga, Tadao; Hino, Ryunosuke; Makishi, Wataru; Esashi, Masayoshi; Haga, Yoichi

For high resolution visual inspection in the narrow space of the human body, small diameter endoscope has been developed which utilize electromagnetically vibration of single fiber. Thin endoscopes are effective for inspection in the narrow space of the human body, for example, in the blood vessel, lactiferous duct for detection infiltration of breast cancer, and periodontal gap between gingiva and tooth. This endoscope consists of single optical fiber and photofabricated driving coils. A collimator lens and a cylindrical permanent magnet are fixed on the optical fiber, and the tilted driving coils have been patterned on a 1.08 mm outer diameter thin tube. The fiber is positioned at the center of the tube which is patterned the coils. When an electrical alternating current at the resonance frequency is supplied to the coils, the permanent magnet which is fixed to the fiber is vibrated electromagnetically and scanned one or two dimensionally. This paper reports small diameter endoscope by using electromagnetically vibration of single fiber. Optical coherence tomography imaging has also been carried out with the fabricated endoscope and cross-section image of sub-surface skin of thumb was observed.

Electrophoretic cell separation by means of immunomicrospheres

NASA Technical Reports Server (NTRS)

Rembaum, A.; Smolka, A. J. K.

1980-01-01

The electrophoretic mobility of fixed human red blood cells immunologically labeled with polymeric (4-vinyl)pyridine or polyglutaraldehyde microspheres was altered to a considerable extent. This observation was utilized in the preparative scale electrophoretic separation of human and turkey fixed red blood cells, whose mobilities under normal physiological conditions do not differ sufficiently to allow their separation by continuous flow electrophoresis. It is suggested that resolution in the electrophoretic separation of cell subpopulations, currently limited by finite and often overlapping mobility distributions, may be significantly enhanced by immuno-specific labeling of target populations using microspheres.

[Fixed-dose combination fluticasone propionate/formoterol for the treatment of asthma: a review of its pharmacology, efficacy and tolerability].

PubMed

Quintano Jiménez, J A; Ginel Mendoza, L; Entrenas Costa, L M; Polo García, J

2016-02-01

The fixed-dose combination fluticasone propionate/formoterol (FPF) is a novel combination of a widely known and used inhaled glucocorticoid (IGC) and a long-acting β2-adrenergic agonist (LABA), available for the first time in a single device. This fixed-dose combination of FPF has a demonstrated efficacy and safety profile in clinical trials compared with its individual components and other fixed-dose combinations of IGC/LABA and is indicated for the treatment of persistent asthma in adults and adolescents. FPF is available in a wide range of doses that can adequately cover the therapeutic steps recommended by treatment guidelines, constituting a fixed-dose combination of GCI/LABA that is effective, rapid, well tolerated and with a reasonable acquisition cost. Various assessment agencies of the Spanish Autonomous Communities consider this combination to be an appropriate alternative therapy for asthma in the primary care setting. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Medicina Rural y Generalista (SEMERGEN). All rights reserved.

Exact results for the O( N ) model with quenched disorder

NASA Astrophysics Data System (ADS)

Delfino, Gesualdo; Lamsen, Noel

2018-04-01

We use scale invariant scattering theory to exactly determine the lines of renormalization group fixed points for O( N )-symmetric models with quenched disorder in two dimensions. Random fixed points are characterized by two disorder parameters: a modulus that vanishes when approaching the pure case, and a phase angle. The critical lines fall into three classes depending on the values of the disorder modulus. Besides the class corresponding to the pure case, a second class has maximal value of the disorder modulus and includes Nishimori-like multicritical points as well as zero temperature fixed points. The third class contains critical lines that interpolate, as N varies, between the first two classes. For positive N , it contains a single line of infrared fixed points spanning the values of N from √{2}-1 to 1. The symmetry sector of the energy density operator is superuniversal (i.e. N -independent) along this line. For N = 2 a line of fixed points exists only in the pure case, but accounts also for the Berezinskii-Kosterlitz-Thouless phase observed in presence of disorder.

Relationship of extinction to perceptual thresholds for single stimuli.

PubMed

Meador, K J; Ray, P G; Day, L J; Loring, D W

2001-04-24

To demonstrate the effects of target stimulus intensity on extinction to double simultaneous stimuli. Attentional deficits contribute to extinction in patients with brain lesions, but extinction (i.e., masking) can also be produced in healthy subjects. The relationship of extinction to perceptual thresholds for single stimuli remains uncertain. Brief electrical pulses were applied simultaneously to the left and right index fingers of 16 healthy volunteers (8 young and 8 elderly adults) and 4 patients with right brain stroke (RBS). The stimulus to be perceived (i.e., target stimulus) was given at the lowest perceptual threshold to perceive any single stimulus (i.e., Minimal) and at the threshold to perceive 100% of single stimuli. The mask stimulus (i.e., stimulus given to block the target) was applied to the contralateral hand at intensities just below discomfort. Extinction was less for target stimuli at 100% than Minimal threshold for healthy subjects. Extinction of left targets was greater in patients with RBS than elderly control subjects. Left targets were extinguished less than right in healthy subjects. In contrast, the majority of left targets were extinguished in patients with RBS even when right mask intensity was reduced below right 100% threshold for single stimuli. RBS patients had less extinction for right targets despite having greater left mask - threshold difference than control subjects. In patients with RBS, right "targets" at 100% threshold extinguished left "masks" (20%) almost as frequently as left masks extinguished right targets (32%). Subtle changes in target intensity affect extinction in healthy adults. Asymmetries in mask and target intensities (relative to single-stimulus perceptual thresholds) affect extinction in RBS patients less for left targets but more for right targets as compared with control subjects.

Aclidinium bromide plus formoterol for the treatment of chronic obstructive pulmonary disease.

PubMed

Lal, Chitra; Strange, Charlie

2015-02-01

Drugs that target dynamic hyperinflation such as long-acting β-2 agonists and long-acting antimuscarinic antagonists form a cornerstone of chronic obstructive pulmonary disease (COPD) management. The idea of combining these two medications in a single formulation, which may potentially improve patient compliance, is novel and attractive. The pharmacologic profiles of aclidinium bromide and formoterol fumarate are discussed. However, studies to define drug interactions and alterations in the pharmacodynamics and pharmacokinetics of the fixed dose combination (FDC) of aclidinium bromide/formoterol fumarate in large populations remain unpublished. Results of Phase II and two Phase III pivotal trials, ACLIFORM/COPD and AUGMENT COPD, evaluating the FDC are discussed. Initial data for the aclidinium/formoterol inhaler appears to be promising for impacting the lung function. To define if this benefit translates into improved long-term outcomes of decreased exacerbation frequency, improved quality of life and decreased disease-specific mortality are important. The introduction of this combination will likely have a significant impact on the prescribing habits of physicians across the world.

Microsatellites within the feline androgen receptor are suitable for X chromosome-linked clonality testing in archival material.

PubMed

Farwick, Nadine M; Klopfleisch, Robert; Gruber, Achim D; Weiss, Alexander Th A

2017-04-01

Objectives A hallmark of neoplasms is their origin from a single cell; that is, clonality. Many techniques have been developed in human medicine to utilise this feature of tumours for diagnostic purposes. One approach is X chromosome-linked clonality testing using polymorphisms of genes encoded by genes on the X chromosome. The aim of this study was to determine if the feline androgen receptor gene was suitable for X chromosome-linked clonality testing. Methods The feline androgen receptor gene was characterised and used to test clonality of feline lymphomas by PCR and polyacrylamide gel electrophoresis, using archival formalin-fixed, paraffin-embedded material. Results Clonality of the feline lymphomas under study was confirmed and the gene locus was shown to represent a suitable target in clonality testing. Conclusions and relevance Because there are some pitfalls of using X chromosome-linked clonality testing, further studies are necessary to establish this technique in the cat.

Algorithms and Complexity Results for Genome Mapping Problems.

PubMed

Rajaraman, Ashok; Zanetti, Joao Paulo Pereira; Manuch, Jan; Chauve, Cedric

2017-01-01

Genome mapping algorithms aim at computing an ordering of a set of genomic markers based on local ordering information such as adjacencies and intervals of markers. In most genome mapping models, markers are assumed to occur uniquely in the resulting map. We introduce algorithmic questions that consider repeats, i.e., markers that can have several occurrences in the resulting map. We show that, provided with an upper bound on the copy number of repeated markers and with intervals that span full repeat copies, called repeat spanning intervals, the problem of deciding if a set of adjacencies and repeat spanning intervals admits a genome representation is tractable if the target genome can contain linear and/or circular chromosomal fragments. We also show that extracting a maximum cardinality or weight subset of repeat spanning intervals given a set of adjacencies that admits a genome realization is NP-hard but fixed-parameter tractable in the maximum copy number and the number of adjacent repeats, and tractable if intervals contain a single repeated marker.

DART -- Data acquisition for the next generation of Fermilab fixed target experiments

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

Oleynik, G.; Anderson, J.; Appleton, L.

1994-02-01

DART is the name of the data acquisition effort for Fermilab experiments taking data in the '94--'95 time frame and beyond. Its charge is to provide a common system of hardware and software, which can be easily configured and extended to meet the wide range of data acquisition requirements of the experiments. Its strategy is to provide incrementally functional data acquisition systems to the experiments at frequent intervals to support the ongoing DA activities of the experiments. DART is a collaborative development effort between the experimenters and the Fermilab Computing Division. Experiments collaborating in DART cover a range of requirementsmore » from 400 Kbytes/sec event readout using a single DA processor, to 200 Mbytes/sec event readout involving 10 parallel readout streams, 10 VME event building planes and greater than 1,000 MIPs of event filter processing. The authors describe the requirements, architecture, and plans for the project and report on its current status.« less

Imaging transcription factors dynamics with advanced fluorescence microscopy methods.

PubMed

Verneri, Paula; Romero, Juan José; De Rossi, María Cecilia; Alvarez, Yanina; Oses, Camila; Guberman, Alejandra; Levi, Valeria

2018-05-10

Pluripotent stem cells (PSCs) are capable of self-renewing and producing all cell types derived from the three germ layers in response to developmental cues, constituting an important promise for regenerative medicine. Pluripotency depends on specific transcription factors (TFs) that induce genes required to preserve the undifferentiated state and repress other genes related to differentiation. The transcription machinery and regulatory components such as TFs are recruited dynamically on their target genes making it essential exploring their dynamics in living cells to understand the transcriptional output. Non-invasive and very sensitive fluorescence microscopy methods are making it possible visualizing the dynamics of TFs in living specimens, complementing the information extracted from studies in fixed specimens and bulk assays. In this work, we briefly describe the basis of these microscopy methods and review how they contributed to our knowledge of the function of TFs relevant to embryo development and cell differentiation in a variety of systems ranging from single cells to whole organisms. Copyright © 2017. Published by Elsevier B.V.

Ambiguous Capture: Collaborative Capitalism and the Meningitis Vaccine Project

PubMed Central

Graham, Janice

2016-01-01

ABSTRACT The primary health care approach advanced at Alma Ata to address social determinants of health was replaced by selective health care a year later at Bellagio. Subsequently, immunization was endorsed as a cost-effective technical intervention to combat targeted infectious diseases. Multilateral efforts to collaborate on immunization as a universal public health good ambiguously capture the interests of the world’s governments as well as private, public, and not-for-profit institutions. Global assemblages of scientists, governments, industry and nongovernmental organizations now work in public-private partnerships to develop and make essential vaccines accessible, with vaccines marketed as single fix solutions for global health. Drawing from ethnographic fieldwork in France and Burkina Faso that followed the development, regulation, and implementation of the group A meningococcal conjugate vaccine for sub-Saharan Africa, in this article I describe events during and after the development of MenAfriVac. A technological success narrative steeped in collaborative capitalist rhetoric disguises neglected health care systems. PMID:27027575

Ambiguous Capture: Collaborative Capitalism and the Meningitis Vaccine Project.

PubMed

Graham, Janice

2016-01-01

The primary health care approach advanced at Alma Ata to address social determinants of health was replaced by selective health care a year later at Bellagio. Subsequently, immunization was endorsed as a cost-effective technical intervention to combat targeted infectious diseases. Multilateral efforts to collaborate on immunization as a universal public health good ambiguously capture the interests of the world's governments as well as private, public, and not-for-profit institutions. Global assemblages of scientists, governments, industry and nongovernmental organizations now work in public-private partnerships to develop and make essential vaccines accessible, with vaccines marketed as single fix solutions for global health. Drawing from ethnographic fieldwork in France and Burkina Faso that followed the development, regulation, and implementation of the group A meningococcal conjugate vaccine for sub-Saharan Africa, in this article I describe events during and after the development of MenAfriVac. A technological success narrative steeped in collaborative capitalist rhetoric disguises neglected health care systems.

A generic model of contagious disease and its application to human-to-human transmission of avian influenza.

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

Hirsch, Gary B.

2007-03-01

Modeling contagious diseases has taken on greater importance over the past several years as diseases such as SARS and avian influenza have raised concern about worldwide pandemics. Most models developed to consider projected outbreaks have been specific to a single disease. This paper describes a generic System Dynamics contagious disease model and its application to human-to-human transmission of a mutant version of avian influenza. The model offers the option of calculating rates of new infections over time based either on a fixed ''reproductive number'' that is traditional in contagious disease models or on contact rates for different sub-populations and likelihoodmore » of transmission per contact. The paper reports on results with various types of interventions. These results suggest the potential importance of contact tracing, limited quarantine, and targeted vaccination strategies as methods for controlling outbreaks, especially when vaccine supplies may initially be limited and the efficacy of anti-viral drugs uncertain.« less

Identification of diazotrophic microorganisms in marine sediment via fluorescence in situ hybridization coupled to nanoscale secondary ion mass spectrometry (FISH-NanoSIMS).

PubMed

Dekas, Anne E; Orphan, Victoria J

2011-01-01

Growing appreciation for the biogeochemical significance of uncultured microorganisms is changing the focus of environmental microbiology. Techniques designed to investigate microbial metabolism in situ are increasingly popular, from mRNA-targeted fluorescence in situ hybridization (FISH) to the "-omics" revolution, including metagenomics, transcriptomics, and proteomics. Recently, the coupling of FISH with nanometer-scale secondary ion mass spectrometry (NanoSIMS) has taken this movement in a new direction, allowing single-cell metabolic analysis of uncultured microbial phylogenic groups. The main advantage of FISH-NanoSIMS over previous noncultivation-based techniques to probe metabolism is its ability to directly link 16S rRNA phylogenetic identity to metabolic function. In the following chapter, we describe the procedures necessary to identify nitrogen-fixing microbes within marine sediment via FISH-NanoSIMS, using our work on nitrogen fixation by uncultured deep-sea methane-consuming archaea as a case study. Copyright © 2011 Elsevier Inc. All rights reserved.

Long-term imaging in awake mice using removable cranial windows

PubMed Central

Glickfeld, Lindsey L.; Kerlin, Aaron M.; Reid, R. Clay; Bonin, Vincent; Schafer, Dorothy P.; Andermann, Mark L.

2015-01-01

Cranial window implants in head-fixed rodents are becoming a preparation of choice for stable optical access to large areas of cortex over extended periods of time. Here, we provide a highly detailed and reliable surgical protocol for a cranial window implantation procedure for chronic widefield and cellular imaging in awake, head-fixed mice, which enables subsequent window removal and replacement in the weeks and months following the initial craniotomy. This protocol has facilitated awake, chronic imaging in adolescent as well as adult mice over several months from a large number of cortical brain regions; targeted virus and tracer injections from data obtained using prior awake functional mapping; and functionally-targeted two-photon imaging across all cortical layers in awake mice using a microprism attachment to the cranial window. Collectively, these procedures extend the reach of chronic imaging of cortical function and dysfunction in behaving animals. PMID:25275789

Heavy-Ion Physics at a Fixed-Target Experiment Using the LHC Proton and Lead Beams (AFTER@LHC): Feasibility Studies for Quarkonium and Drell-Yan Production

NASA Astrophysics Data System (ADS)

Trzeciak, B.; Da Silva, C.; Ferreiro, E. G.; Hadjidakis, C.; Kikola, D.; Lansberg, J. P.; Massacrier, L.; Seixas, J.; Uras, A.; Yang, Z.

2017-09-01

We outline the case for heavy-ion-physics studies using the multi-TeV lead LHC beams in the fixed-target mode. After a brief contextual reminder, we detail the possible contributions of AFTER@LHC to heavy-ion physics with a specific emphasis on quarkonia. We then present performance simulations for a selection of observables. These show that Υ (nS), J/ψ and ψ (2S) production in heavy-ion collisions can be studied in new energy and rapidity domains with the LHCb and ALICE detectors. We also discuss the relevance to analyse the Drell-Yan pair production in asymmetric nucleus-nucleus collisions to study the factorisation of the nuclear modification of partonic densities and of further quarkonium states to restore their status of golden probes of the quark-gluon plasma formation.

Gottfried Sum Rule in QCD Nonsinglet Analysis of DIS Fixed-Target Data

NASA Astrophysics Data System (ADS)

Kotikov, A. V.; Krivokhizhin, V. G.; Shaikhatdenov, B. G.

2018-03-01

Deep-inelastic-scattering data from fixed-target experiments on the structure function F 2 were analyzed in the valence-quark approximation at the next-to-next-to-leading-order accuracy level in the strong-coupling constant. In this analysis, parton distributions were parametrized by employing information from the Gottfried sum rule. The strong-coupling constant was found to be α s ( M 2 Z) = 0.1180 ± 0.0020 (total expt. error), which is in perfect agreement with the world-averaged value from an updated Particle Data Group (PDG) report, α PDG s ( M 2 Z) = 0.1181 ± 0.0011. Also, the value of < x> u- d = 0.187 ± 0.021 found for the second moment of the difference in the u- and d-quark distributions complies very well with the most recent lattice result < x>LATTICE u- d = 0.208 ± 0.024.

Effect of radiation protraction on BED in the case of large fraction dose

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

Kuperman, V. Y.

2013-08-15

Purpose: To investigate the effect of radiation protraction on biologically effective dose (BED) in the case when dose per fraction is significantly greater than the standard dose of 2 Gy.Methods: By using the modified linear-quadratic model with monoexponential repair, the authors investigate the effect of long treatment times combined with dose escalation.Results: The dependences of the protraction factor and the corresponding BED on fraction time were determined for different doses per fraction typical for stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT). In the calculations, the authors consider changes in the BED to the normal tissue under the conditionmore » of fixed BED to the target.Conclusion: The obtained results demonstrate that simultaneous increase in fraction time and dose per fraction can be beneficial for SRS and SBRT because of the related decrease in BED to normal structures while BED to the target is fixed.« less

Computing Satellite Maneuvers For A Repeating Ground Track

NASA Technical Reports Server (NTRS)

Shapiro, Bruce

1994-01-01

TOPEX/POSEIDON Ground Track Maintenance Maneuver Targeting Program (GTARG) assists in designing maneuvers to maintain orbit of TOPEX/POSEIDON satellite. Targeting strategies used either maximize time between maneuvers or force control band exit to occur at specified intervals. Runout mode allows for ground-track propagation without targeting. GTARG incorporates analytic mean-element propagation algorithm accounting for all perturbations known to cause significant variations in ground track. Perturbations include oblateness of Earth, luni-solar gravitation, drag, thrusts associated with impulsive maneuvers, and unspecified fixed forces acting on satellite in direction along trajectory. Written in VAX-FORTRAN.

Can heterotrophic uptake of dissolved organic carbon and zooplankton mitigate carbon budget deficits in annually bleached corals?

NASA Astrophysics Data System (ADS)

Levas, Stephen; Grottoli, Andréa G.; Schoepf, Verena; Aschaffenburg, Matthew; Baumann, Justin; Bauer, James E.; Warner, Mark E.

2016-06-01

Annual coral bleaching events due to increasing sea surface temperatures are predicted to occur globally by the mid-century and as early as 2025 in the Caribbean, and severely impact coral reefs. We hypothesize that heterotrophic carbon (C) in the form of zooplankton and dissolved organic carbon (DOC) is a significant source of C to bleached corals. Thus, the ability to utilize multiple pools of fixed carbon and/or increase the amount of fixed carbon acquired from one or more pools of fixed carbon (defined here as heterotrophic plasticity) could underlie coral acclimatization and persistence under future ocean-warming scenarios. Here, three species of Caribbean coral— Porites divaricata, P. astreoides, and Orbicella faveolata—were experimentally bleached for 2.5 weeks in two successive years and allowed to recover in the field. Zooplankton feeding was assessed after single and repeat bleaching, while DOC fluxes and the contribution of DOC to the total C budget were determined after single bleaching, 11 months on the reef, and repeat bleaching. Zooplankton was a large C source for P. astreoides, but only following single bleaching. DOC was a source of C for single-bleached corals and accounted for 11-36 % of daily metabolic demand (CHARDOC), but represented a net loss of C in repeat-bleached corals. In repeat-bleached corals, DOC loss exacerbated the negative C budgets in all three species. Thus, the capacity for heterotrophic plasticity in corals is compromised under annual bleaching, and heterotrophic uptake of DOC and zooplankton does not mitigate C budget deficits in annually bleached corals. Overall, these findings suggest that some Caribbean corals may be more susceptible to repeat bleaching than to single bleaching due to a lack of heterotrophic plasticity, and coral persistence under increasing bleaching frequency may ultimately depend on other factors such as energy reserves and symbiont shuffling.

Effect of contact time and force on monocyte adhesion to vascular endothelium.

PubMed Central

Rinker, K D; Prabhakar, V; Truskey, G A

2001-01-01

In this study we examined whether monocytic cell attachment to vascular endothelium was affected by elevating shear stress at a constant shear rate. Contact time, which is inversely related to the shear rate, was fixed and viscosity elevated with dextran to increase the shear stress (and hence the net force on the cell) independently of shear rate. At a fixed contact time, tethering frequencies increased, rolling velocities decreased, and median arrest durations increased with increasing shear stress. Rolling and short arrests (< 0.2 s) were well fit by a single exponential consistent with adhesion via the formation of a single additional bond. The cell dissociation constant, k(off), increased when the shear stress was elevated at constant shear rate. Firmly adherent cells arresting for at least 0.2 s were well fit by a stochastic model involving dissociation from multiple bonds. Therefore, at a fixed contact time and increasing shear stress, bonds formed more frequently for rolling cells resulting in more short arrests, and more bonds formed for firmly arresting cells resulting in longer arrest durations. Possible mechanisms for this increased adhesion include greater monocyte deformation and/or more frequent penetration of microvilli through steric and charge barriers. PMID:11259286

Optimization of Self-Directed Target Coverage in Wireless Multimedia Sensor Network

PubMed Central

Yang, Yang; Wang, Yufei; Pi, Dechang; Wang, Ruchuan

2014-01-01

Video and image sensors in wireless multimedia sensor networks (WMSNs) have directed view and limited sensing angle. So the methods to solve target coverage problem for traditional sensor networks, which use circle sensing model, are not suitable for WMSNs. Based on the FoV (field of view) sensing model and FoV disk model proposed, how expected multimedia sensor covers the target is defined by the deflection angle between target and the sensor's current orientation and the distance between target and the sensor. Then target coverage optimization algorithms based on expected coverage value are presented for single-sensor single-target, multisensor single-target, and single-sensor multitargets problems distinguishingly. Selecting the orientation that sensor rotated to cover every target falling in the FoV disk of that sensor for candidate orientations and using genetic algorithm to multisensor multitargets problem, which has NP-complete complexity, then result in the approximated minimum subset of sensors which covers all the targets in networks. Simulation results show the algorithm's performance and the effect of number of targets on the resulting subset. PMID:25136667

Implant dentistry curriculum in undergraduate education: part 2-program at the Albert-Ludwigs University, Freiburg, Germany.

PubMed

Kroeplin, Birgit S; Strub, Joerg R

2011-01-01

The aim of this study was to describe the didactic and clinical undergraduate implant dentistry program of the Albert-Ludwigs University, Freiburg, Germany, with emphasis on the clinical implant experience. A detailed description of the implant curriculum at Albert-Ludwigs University is given with documented exemplary cases and additional flow charts. All students participate in 28 hours of lectures and approximately 64 hours of seminars with hands-on courses and gain clinical experience. All undergraduate students are eligible to place and restore oral implants. Emphasis is placed on prosthetic-driven planning of implant positions, three-dimensional imaging, and computer-guided implant placement. Implant restorations performed by undergraduate students comprise single crowns and small multiunit fixed dental prostheses in partially edentulous posterior maxillae and anterior or posterior mandibles, implant-retained overdentures (snap attachment) in edentulous patients, and telescopic fixed-removable dental prostheses on remaining teeth and strategically placed additional implants. Over the past 2.5 years, 51 patients were treated with 97 dental implants placed by students in the undergraduate program. Seventy-one restorations were inserted: 60.6% single crowns, 7% fixed dental protheses, 21.1% overdentures, and 11.3% telescopic fixed-removable dental prostheses. The implant survival rate was 98.9%. Because survival rates for dental implants placed and restored by students are comparable to those of experienced dentists, oral implant dentistry should be implemented as part of the undergraduate dental curriculum.

Fragmentation of organic ions bearing fixed multiple charges observed in MALDI MS.

PubMed

Lou, Xianwen; Li, Bao; de Waal, Bas F M; Schill, Jurgen; Baker, Matthew B; Bovee, Ralf A A; van Dongen, Joost L J; Milroy, Lech-Gustav; Meijer, E W

2018-01-01

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI TOF MS) was used to analyze a series of synthetic organic ions bearing fixed multiple charges. Despite the multiple intrinsic charges, only singly charged ions were recorded in each case. In addition to the pseudo-molecular ions formed by counterion adduction, deprotonation and electron capture, a number of fragment ions were also observed. Charge splitting by fragmentation was found to be a viable route for charge reduction leading to the formation of the observed singly charged fragment ions. Unlike multivalent metal ions, organic ions can rearrange and/or fragment during charge reduction. This fragmentation process will evidently complicate the interpretation of the MALDI MS spectrum. Because MALDI MS is usually considered as a soft ionization technique, the fragment ion peaks can easily be erroneously interpreted as impurities. Therefore, the awareness and understanding of the underlying MALDI-induced fragmentation pathways is essential for a proper interpretation of the corresponding mass spectra. Due to the fragment ions generated during charge reduction, special care should be taken in the MALDI MS analysis of multiply charged ions. In this work, the possible mechanisms by which the organic ions bearing fixed multiple charges fragment are investigated. With an improved understanding of the fragmentation mechanisms, MALDI TOF MS should still be a useful technique for the characterization of organic ions with fixed multiple charges. Copyright © 2017 John Wiley & Sons, Ltd.

IMRT treatment of anal cancer with a scrotal shield

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

Hood, Rodney C., E-mail: Rodney.Hood@duke.edu; Wu, Q. Jackie; McMahon, Ryan

The risk of sterility in males undergoing radiotherapy in the pelvic region indicates the use of a shielding device, which offers protection to the testes for patients wishing to maintain fertility. The use of such devices in the realm of intensity-modulated radiotherapy (IMRT) in the pelvic region can pose many obstacles during simulation, treatment planning, and delivery of radiotherapy. This work focuses on the development and execution of an IMRT plan for the treatment of anal cancer using a scrotal shielding device on a clinical patient. An IMRT plan was developed using Eclipse treatment planning system (Varian Medical Systems, Palomore » Alto, CA), using a wide array of gantry angles as well as fixed jaw and fluence editing techniques. When possible, the entire target volume was encompassed by the treatment field. When the beam was incident on the scrotal shield, the jaw was fixed to avoid the device and the collimator rotation optimized to irradiate as much of the target as possible. This technique maximizes genital sparing and allows minimal irradiation of the gonads. When this fixed-jaw technique was found to compromise adequate coverage of the target, manual fluence editing techniques were used to avoid the shielding device. Special procedures for simulation, imaging, and treatment verification were also developed. In vivo dosimetry was used to verify and ensure acceptable dose to the gonads. The combination of these techniques resulted in a highly conformal plan that spares organs and risk and avoids the genitals as well as entrance of primary radiation onto the shielding device.« less

Optimization of the strength of the efavirenz/lamivudine/abacavir fixed-dose combination for paediatric patients.

PubMed

Bouazza, Naïm; Cressey, Tim R; Foissac, Frantz; Bienczak, Andrzej; Denti, Paolo; McIlleron, Helen; Burger, David; Penazzato, Martina; Lallemant, Marc; Capparelli, Edmund V; Treluyer, Jean-Marc; Urien, Saïk

2017-02-01

Child-friendly, low-cost, solid, oral fixed-dose combinations (FDCs) of efavirenz with lamivudine and abacavir are urgently needed to improve clinical management and drug adherence for children. Data were pooled from several clinical trials and therapeutic drug monitoring datasets from different countries. The number of children/observations was 505/3667 for efavirenz. Population pharmacokinetic analyses were performed using a non-linear mixed-effects approach. For abacavir and lamivudine, data from 187 and 920 subjects were available (population pharmacokinetic models previously published). Efavirenz/lamivudine/abacavir FDC strength options assessed were (I) 150/75/150, (II) 120/60/120 and (III) 200/100/200 mg. Monte Carlo simulations of the different FDC strengths were performed to determine the optimal dose within each of the WHO weight bands based on drug efficacy/safety targets. The probability of being within the target efavirenz concentration range 12 h post-dose (1-4 mg/L) varied between 56% and 60%, regardless of FDC option. Option I provided a best possible balance between efavirenz treatment failure and toxicity risks. For abacavir and lamivudine, simulations showed that for option I >75% of subjects were above the efficacy target. According to simulations, a paediatric efavirenz/lamivudine/abacavir fixed-dose formulation of 150 mg efavirenz, 75 mg lamivudine and 150 mg abacavir provided the most effective and safe concentrations across WHO weight bands, with the flexibility of dosage required across the paediatric population. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Retrospective analysis of porcelain failures of metal ceramic crowns and fixed partial dentures supported by 729 implants in 152 patients: patient-specific and implant-specific predictors of ceramic failure.

PubMed

Kinsel, Richard P; Lin, Dongming

2009-06-01

Porcelain fracture associated with an implant-supported, metal ceramic crown or fixed partial denture occurs at a higher rate than in tooth-supported restorations, according to the literature. Implant-specific and patient-specific causes of ceramic failure have not been fully evaluated. The purpose of this retrospective study was to evaluate the potential statistical predictors for porcelain fracture of implant-supported, metal ceramic restorations. Over a 6-month period, a consecutive series of patients having previously received implant-supported, metal ceramic fixed restorations were examined during periodic recall appointments. The number of supporting implants, number of dental units, type of restoration, date of prosthesis insertion, location in the dental arch, opposing dentition, type of occlusion, presence of parafunctional habits, use of an occlusal protective device, presence or absence of ceramic fractures, gender, and age were recorded for each patient. The generalized estimating equation (GEE) approach was used for the intrasubject correlated measurements analysis of categorical outcomes (presence or absence of ceramic fractures) to determine which patient- and implant-specific factors would predict porcelain fracture (alpha=.05). Data were collected from 152 patients representing 998 dental units (390 single crowns and 94 fixed partial dentures) supported by 729 implants. Porcelain fractures of 94 dental units occurred in 35 patients. The fractures were significantly (P<.05) associated with opposing implant-supported metal ceramic restorations, bruxism, and not wearing a protective occlusal device. Metal ceramic prostheses (single crown or fixed partial dentures) had approximately 7 times higher odds of porcelain fracture (odds ratio (OR)=7.06; 95% confidence interval (CI): 2.57 to 19.37) and 13 times greater odds of a fracture requiring either repair or replacement (OR=13.95; 95% CI: 2.25 to 86.41) when in occlusion with another implant-supported restoration, as compared to opposing a natural tooth. In addition, patients exhibiting bruxism or not wearing an occlusal device had approximately 7 times higher odds (OR=7.23; 95% CI: 3.86 to 13.54), and 2 times higher odds (OR=1.92; 95% CI: 1.01 to 3.67) of porcelain fracture when compared to patients without bruxism and patients not wearing an occlusal device. Implant-supported metal ceramic single crowns and fixed partial dentures were found to have a significantly higher risk of porcelain fracture in patients with bruxism habits, when a protective occlusal device was not used, and when the restoration opposed another implant-supported metal ceramic restoration.

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

Yokosawa, A.

We summarize activities concerning the Fermilab polarized beams. They include a description of the polarized-beam facility, measurements of beam polarization by polarimeters, asymmetry measurements in the production at large x, and experiments with polarized beams during the next fixed-target period. 8 refs., 9 figs.

Sedation-analgesia with propofol and remifentanil: concentrations required to avoid gag reflex in upper gastrointestinal endoscopy.

PubMed

Borrat, Xavier; Valencia, José Fernando; Magrans, Rudys; Gimenez-Mila, Marc; Mellado, Ricard; Sendino, Oriol; Perez, Maria; Nunez, Matilde; Jospin, Mathieu; Jensen, Erik Weber; Troconiz, Inaki; Gambus, Pedro L

2015-07-01

The purpose of this study was to identify optimal target propofol and remifentanil concentrations to avoid a gag reflex in response to insertion of an upper gastrointestinal endoscope. Patients presenting for endoscopy received target-controlled infusions (TCI) of both propofol and remifentanil for sedation-analgesia. Patients were randomized to 4 groups of fixed target effect-site concentrations: remifentanil 1 ng•mL (REMI 1) or 2 ng•mL (REMI 2) and propofol 2 μg•mL (PROP 2) or 3 μg•mL (PROP 3). For each group, the other drug (propofol for the REMI groups and vice versa) was increased or decreased using the "up-down" method based on the presence or absence of a gag response in the previous patient. A modified isotonic regression method was used to estimate the median effective Ce,50 from the up-down method in each group. A concentration-effect (sigmoid Emax) model was built to estimate the corresponding Ce,90 for each group. These data were used to estimate propofol bolus doses and remifentanil infusion rates that would achieve effect-site concentrations between Ce,50 and Ce,90 when a TCI system is not available for use. One hundred twenty-four patients were analyzed. To achieve between a 50% and 90% probability of no gag response, propofol TCIs were between 2.40 and 4.23 μg•mL (that could be achieved with a bolus of 1 mg•kg) when remifentanil TCI was fixed at 1 ng•mL, and target propofol TCIs were between 2.15 and 2.88 μg•mL (that could be achieved with a bolus of 0.75 mg•kg) when remifentanil TCI was fixed at 2 ng•mL. Remifentanil ranges were 1.00 to 4.79 ng•mL and 0.72 to 3.19 ng•mL when propofol was fixed at 2 and 3 μg•mL, respectively. We identified a set of propofol and remifentanil TCIs that blocked the gag response to endoscope insertion in patients undergoing endoscopy. Propofol bolus doses and remifentanil infusion rates designed to achieve similar effect-site concentrations can be used to prevent gag response when TCI is not available.

New force replica exchange method and protein folding pathways probed by force-clamp technique.

PubMed

Kouza, Maksim; Hu, Chin-Kun; Li, Mai Suan

2008-01-28

We have developed a new extended replica exchange method to study thermodynamics of a system in the presence of external force. Our idea is based on the exchange between different force replicas to accelerate the equilibrium process. This new approach was applied to obtain the force-temperature phase diagram and other thermodynamical quantities of the three-domain ubiquitin. Using the C(alpha)-Go model and the Langevin dynamics, we have shown that the refolding pathways of single ubiquitin depend on which terminus is fixed. If the N end is fixed then the folding pathways are different compared to the case when both termini are free, but fixing the C terminal does not change them. Surprisingly, we have found that the anchoring terminal does not affect the pathways of individual secondary structures of three-domain ubiquitin, indicating the important role of the multidomain construction. Therefore, force-clamp experiments, in which one end of a protein is kept fixed, can probe the refolding pathways of a single free-end ubiquitin if one uses either the polyubiquitin or a single domain with the C terminus anchored. However, it is shown that anchoring one end does not affect refolding pathways of the titin domain I27, and the force-clamp spectroscopy is always capable to predict folding sequencing of this protein. We have obtained the reasonable estimate for unfolding barrier of ubiquitin, using the microscopic theory for the dependence of unfolding time on the external force. The linkage between residue Lys48 and the C terminal of ubiquitin is found to have the dramatic effect on the location of the transition state along the end-to-end distance reaction coordinate, but the multidomain construction leaves the transition state almost unchanged. We have found that the maximum force in the force-extension profile from constant velocity force pulling simulations depends on temperature nonlinearly. However, for some narrow temperature interval this dependence becomes linear, as have been observed in recent experiments.

Clinical and Analytical Evaluation of a Single-Vial Stool Collection Device with Formalin-Free Fixative for Improved Processing and Comprehensive Detection of Gastrointestinal Parasites

PubMed Central

Couturier, Brianne A.; Jensen, Ryan; Arias, Nora; Heffron, Michael; Gubler, Elyse; Case, Kristin; Gowans, Jason

2015-01-01

Microscopic examination of feces is a standard laboratory method for diagnosing gastrointestinal parasite infections. In North America, the ovum and parasite (O&P) examination is typically performed using stool that is chemically fixed in polyvinyl alcohol (PVA) and formalin, after which the stool is concentrated by filtration to enhance sensitivity. Mini Parasep solvent-free (SF) tubes allow collection and concentration within a single collection vial. The goal of the study was to determine whether consolidated processing and concentration with the Parasep tubes using an alcohol-based fixative (Alcorfix) provide O&P examinations equivalent to or better than those done by processing of PVA-formalin-fixed stool using a SpinCon concentration device. Parasep tubes revealed filtration performance equivalent to that of the SpinCon concentration device using PVA-formalin-fixed stool containing protozoa. Specimens cocollected in Parasep tubes containing PVA-formalin and Alcorfix revealed comparable morphology and staining for various protozoa. Alcorfix effectively fixed live Cryptosporidium and microsporidia such that morphology and staining were conserved for modified acid-fast and modified trichrome stains. A work flow analysis revealed significant time savings for batches of 10 or 30 O&P specimens in tubes with Alcorfix compared to the amount of time that it took to analyze the same number of specimens in tubes with PVA-formalin. The direct hands-on time savings with Mini Parasep tubes were 17 min and 41 s and 32 min and 1 s for batches of 10 and 30 specimens, respectively. Parasep tubes containing Alcorfix provide significant work flow advantages to laboratories that process medium to high volumes of O&P specimens by streamlining processing and converting to a single tube. These improvements in work flow, reduction of the amount of formalin used in the laboratory, and equivalent microscopy results are attractive advancements in O&P testing for North American diagnostic parasitology laboratories. PMID:26019199

Bone anchors or interference screws? A biomechanical evaluation for autograft ankle stabilization.

PubMed

Jeys, Lee; Korrosis, Sotiris; Stewart, Todd; Harris, Nicholas J

2004-01-01

Autograft stabilization uses free semitendinosus tendon grafts to anatomically reconstruct the anterior talofibular ligament. Study aims were to evaluate the biomechanical properties of Mitek GII anchors compared with the Arthrex Bio-Tenodesis Screw for free tendon reconstruction of the anterior talofibular ligament. There are no differences in load to failure and percentage specimen elongation at failure between the 2 methods. Controlled laboratory study using porcine models. Sixty porcine tendon constructs were failure tested. Re-creating the pull of the anterior talofibular ligament, loads were applied at 70 degrees to the bones. Thirty-six tendons were fixed to porcine tali and tested using a single pull to failure; 10 were secured with anchors and No. 2 Ethibond, 10 with anchors and FiberWire, 10 with screws and Fiberwire, and 6 with partially gripped screws. Cyclic preloading was conducted on 6 tendons fixed by anchors and on 6 tendons fixed by screws before failure testing. Two groups of 6 components fixed to the fibula were also tested. The talus single-pull anchor group produced a mean load of 114 N and elongation of 37% at failure. The talus single-pull screw group produced a mean load of 227 N and elongation of 22% at failure (P <.05). Cyclic preloading at 65% failure load before failure testing produced increases in load and decreases in elongation at failure. Partially gripped screws produced a load of 133 N and elongation of 30% at failure. The fibula model produced significant increases in load to failure for both. The human anterior talofibular ligament has loads of 139 N at failure with instability occurring at 20% elongation. Interference screw fixation produced significantly greater failure strength and less elongation at failure than bone anchors. The improved biomechanics of interference screws suggests that these may be more suited to in vivo reconstruction of the anterior talofibular ligament than are bone anchors.

Clinical and Analytical Evaluation of a Single-Vial Stool Collection Device with Formalin-Free Fixative for Improved Processing and Comprehensive Detection of Gastrointestinal Parasites.

PubMed

Couturier, Brianne A; Jensen, Ryan; Arias, Nora; Heffron, Michael; Gubler, Elyse; Case, Kristin; Gowans, Jason; Couturier, Marc Roger

2015-08-01

Microscopic examination of feces is a standard laboratory method for diagnosing gastrointestinal parasite infections. In North America, the ovum and parasite (O&P) examination is typically performed using stool that is chemically fixed in polyvinyl alcohol (PVA) and formalin, after which the stool is concentrated by filtration to enhance sensitivity. Mini Parasep solvent-free (SF) tubes allow collection and concentration within a single collection vial. The goal of the study was to determine whether consolidated processing and concentration with the Parasep tubes using an alcohol-based fixative (Alcorfix) provide O&P examinations equivalent to or better than those done by processing of PVA-formalin-fixed stool using a SpinCon concentration device. Parasep tubes revealed filtration performance equivalent to that of the SpinCon concentration device using PVA-formalin-fixed stool containing protozoa. Specimens cocollected in Parasep tubes containing PVA-formalin and Alcorfix revealed comparable morphology and staining for various protozoa. Alcorfix effectively fixed live Cryptosporidium and microsporidia such that morphology and staining were conserved for modified acid-fast and modified trichrome stains. A work flow analysis revealed significant time savings for batches of 10 or 30 O&P specimens in tubes with Alcorfix compared to the amount of time that it took to analyze the same number of specimens in tubes with PVA-formalin. The direct hands-on time savings with Mini Parasep tubes were 17 min and 41 s and 32 min and 1 s for batches of 10 and 30 specimens, respectively. Parasep tubes containing Alcorfix provide significant work flow advantages to laboratories that process medium to high volumes of O&P specimens by streamlining processing and converting to a single tube. These improvements in work flow, reduction of the amount of formalin used in the laboratory, and equivalent microscopy results are attractive advancements in O&P testing for North American diagnostic parasitology laboratories. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Improved Time-Lapsed Angular Scattering Microscopy of Single Cells

NASA Astrophysics Data System (ADS)

Cannaday, Ashley E.

By measuring angular scattering patterns from biological samples and fitting them with a Mie theory model, one can estimate the organelle size distribution within many cells. Quantitative organelle sizing of ensembles of cells using this method has been well established. Our goal is to develop the methodology to extend this approach to the single cell level, measuring the angular scattering at multiple time points and estimating the non-nuclear organelle size distribution parameters. The diameters of individual organelle-size beads were successfully extracted using scattering measurements with a minimum deflection angle of 20 degrees. However, the accuracy of size estimates can be limited by the angular range detected. In particular, simulations by our group suggest that, for cell organelle populations with a broader size distribution, the accuracy of size prediction improves substantially if the minimum angle of detection angle is 15 degrees or less. The system was therefore modified to collect scattering angles down to 10 degrees. To confirm experimentally that size predictions will become more stable when lower scattering angles are detected, initial validations were performed on individual polystyrene beads ranging in diameter from 1 to 5 microns. We found that the lower minimum angle enabled the width of this delta-function size distribution to be predicted more accurately. Scattering patterns were then acquired and analyzed from single mouse squamous cell carcinoma cells at multiple time points. The scattering patterns exhibit angular dependencies that look unlike those of any single sphere size, but are well-fit by a broad distribution of sizes, as expected. To determine the fluctuation level in the estimated size distribution due to measurement imperfections alone, formaldehyde-fixed cells were measured. Subsequent measurements on live (non-fixed) cells revealed an order of magnitude greater fluctuation in the estimated sizes compared to fixed cells. With our improved and better-understood approach to single cell angular scattering, we are now capable of reliably detecting changes in organelle size predictions due to biological causes above our measurement error of 20 nm, which enables us to apply our system to future studies of the investigation of various single cell biological processes.

Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma.

PubMed

Konstas, Anastasios G P; Holló, Gabor

2016-06-01

Medical therapy of glaucoma aims to maintain the patient's visual function and quality of life. This generally commences with monotherapy, but it is often difficult to reach the predetermined target pressure with this approach. Fixed combinations (FCs) are therefore selected as the next step of the medical therapy algorithm. By employing a prostaglandin/timolol fixed combination (PTFC) the desired target 24-hour intraocular pressure can be reached in many glaucoma patients with the convenience of once-a-day administration and the associated high rate of adherence. The current role and value of FCs in the medical therapy of glaucoma is critically appraised. Special attention is paid to the PTFCs and the emerging role of preservative-free PTFCs. This review summarizes existing information on the efficacy and tolerability of the new preservative-free tafluprost/timolol FC (Taptiqom®). The preservative-free tafluprost/timolol FC represents a promising stepwise treatment option for those patients whose intraocular pressure is insufficiently controlled with available monotherapy options. This novel FC has the potential to substantially improve glaucoma management and through evolution of the current glaucoma treatment paradigm, to become a core therapeutic option in the future. Nonetheless, future research is needed to better delineate the therapeutic role of current and future preservative-free FCs in glaucoma therapy.

Prediction of the body rotation-induced torques on the arm during reaching movements: evidence from a proprioceptively deafferented subject.

PubMed

Guillaud, Etienne; Simoneau, Martin; Blouin, Jean

2011-06-01

Reaching for a target while rotating the trunk generates substantial Coriolis and centrifugal torques that push the arm in the opposite direction of the rotations. These torques rarely perturb movement accuracy, suggesting that they are compensated for during the movement. Here we tested whether signals generated during body motion (e.g., vestibular) can be used to predict the torques induced by the body rotation and to modify the motor commands accordingly. We asked a deafferented subject to reach for a memorized visual target in darkness. At the onset of the reaching, the patient was rotated 25° or 40° in the clockwise or the counterclockwise directions. During the rotation, the patient's head remained either fixed in space (Head-Fixed condition) or fixed on the trunk (Head Rotation condition). At the rotation onset, the deafferented patient's hand largely deviated from the mid-sagittal plane in both conditions. The hand deviations were compensated for in the Head Rotation condition only. These results highlight the computational faculty of the brain and show that body rotation-related information can be processed for predicting the consequence of the rotation dynamics on the reaching arm movements. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fixed-Rate Compressed Floating-Point Arrays.

PubMed

Lindstrom, Peter

2014-12-01

Current compression schemes for floating-point data commonly take fixed-precision values and compress them to a variable-length bit stream, complicating memory management and random access. We present a fixed-rate, near-lossless compression scheme that maps small blocks of 4(d) values in d dimensions to a fixed, user-specified number of bits per block, thereby allowing read and write random access to compressed floating-point data at block granularity. Our approach is inspired by fixed-rate texture compression methods widely adopted in graphics hardware, but has been tailored to the high dynamic range and precision demands of scientific applications. Our compressor is based on a new, lifted, orthogonal block transform and embedded coding, allowing each per-block bit stream to be truncated at any point if desired, thus facilitating bit rate selection using a single compression scheme. To avoid compression or decompression upon every data access, we employ a software write-back cache of uncompressed blocks. Our compressor has been designed with computational simplicity and speed in mind to allow for the possibility of a hardware implementation, and uses only a small number of fixed-point arithmetic operations per compressed value. We demonstrate the viability and benefits of lossy compression in several applications, including visualization, quantitative data analysis, and numerical simulation.

FixO3 project results, legacy and module migration to EMSO

NASA Astrophysics Data System (ADS)

Lampitt, Richard

2017-04-01

The fixed point open ocean observatory network (FixO3) project is an international project aimed at integrating in a single network all fixed point open ocean observatories operated by European organisations and to harmonise and coordinate technological, procedural and data management across the stations. The project is running for four years since September 2013 with 29 partners across Europe and a budget of 7M Euros and is now coming to its final phase. In contrast to several past programmes, the opportunity has arisen to ensure that many of the project achievements can migrate into the newly formed European Multidisciplinary Seafloor and water column Observatory (EMSO) research infrastructure. The final phase of the project will focus on developing a strategy to transfer the results in an efficient way to maintain their relevance and maximise their use. In this presentation, we will highlight the significant achievements of FixO3 over the past three years focussing on the modules which will be transferred to EMSO in the coming 9 months. These include: 1. Handbook of best practices for operating fixed point observatories 2. Metadata catalogue 3. Earth Virtual Observatory (EarthVO) for data visualisation and comparison 4. Open Ocean Observatory Yellow Pages (O3YP) 5. Training material for hardware, data and data products used

Matrix-assisted laser-desorption/ionization mass spectrometric imaging of olanzapine in a single hair using esculetin as a matrix.

PubMed

Wang, Hang; Wang, Ying; Wang, Ge; Hong, Lizhi

2017-07-15

Matrix-assisted laser desorption/ionization-mass spectrometric imaging (MALDI-MSI) for the analysis of intact hair is a powerful tool for monitoring changes in drug consumption. The embedding of a low drug concentration in the hydrophobic hair matrix makes it difficult to extract and detect, and requires an improved method to increase detection sensitivity. In this study, an MSI method using MALDI-Fourier transform ion cyclotron resonance was developed for direct identification and imaging of olanzapine in hair samples using the positive ion mode. Following decontamination, scalp hair samples from an olanzapine user were scraped from the proximal to the distal end three times, and 5mm hair sections were fixed onto an Indium-Tin-Oxide (ITO)-coated microscopic glass slide. Esculetin (6,7-dihydroxy-2H-chromen-2-one) was used as a new hydrophobic matrix to increase the affinity, extraction and ionization efficiency of olanzapine in the hair samples. The spatial distribution of olanzapine was observed using five single hairs from the same drug user. This matrix improves the affinity of olanzapine in hair for molecular imaging with mass spectrometry. This method may provide a detection power for olanzapine to the nanogram level per 5mm hair. Time course changes in the MSI results were also compared with quantitative HPLC-MS/MS for each 5mm segment of single hair shafts selected from the MALDI target. MALDI imaging intensities in single hairs showed good semi-quantitative correlation with the results from conventional HPLC-MS/MS. MALDI-MSI is suitable for monitoring drug intake with a high time resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Research on key technologies of LADAR echo signal simulator

NASA Astrophysics Data System (ADS)

Xu, Rui; Shi, Rui; Ye, Jiansen; Wang, Xin; Li, Zhuo

2015-10-01

LADAR echo signal simulator is one of the most significant components of hardware-in-the-loop (HWIL) simulation systems for LADAR, which is designed to simulate the LADAR return signal in laboratory conditions. The device can provide the laser echo signal of target and background for imaging LADAR systems to test whether it is of good performance. Some key technologies are investigated in this paper. Firstly, the 3D model of typical target is built, and transformed to the data of the target echo signal based on ranging equation and targets reflection characteristics. Then, system model and time series model of LADAR echo signal simulator are established. Some influential factors which could induce fixed delay error and random delay error on the simulated return signals are analyzed. In the simulation system, the signal propagating delay of circuits and the response time of pulsed lasers are belong to fixed delay error. The counting error of digital delay generator, the jitter of system clock and the desynchronized between trigger signal and clock signal are a part of random delay error. Furthermore, these system insertion delays are analyzed quantitatively, and the noisy data are obtained. The target echo signals are got by superimposing of the noisy data and the pure target echo signal. In order to overcome these disadvantageous factors, a method of adjusting the timing diagram of the simulation system is proposed. Finally, the simulated echo signals are processed by using a detection algorithm to complete the 3D model reconstruction of object. The simulation results reveal that the range resolution can be better than 8 cm.

Quantification of cell surface receptor expression in live tissue culture media using a dual-tracer stain and rinse approach

NASA Astrophysics Data System (ADS)

Xu, Xiaochun; Sinha, Lagnojita; Singh, Aparna; Yang, Cynthia; Xiang, Jialing; Tichauer, Kenneth M.

2015-03-01

Immunofluorescence staining is a robust way to visualize the distribution of targeted biomolecules invasively in in fixed tissues and tissue culture. Despite the fact that these methods has been a well-established method in fixed tissue imaging for over 70 years, quantification of receptor concentration still simply assumes that the signal from the targeted fluorescent marker after incubation and sufficient rinsing is directly proportional to the concentration of targeted biomolecules, thus neglecting the experimental inconsistencies in incubation and rinsing procedures and assuming no, nonspecific binding of the fluorescent markers. This work presents the first imaging approach capable of quantifying the concentration of cell surface receptor on cancer cells grown in vitro based on compartment modeling in a nondestructive way. The approach utilizes a dual-tracer protocol where any non-specific retention or variability in incubation and rinsing of a receptor-targeted imaging agent is corrected by simultaneously imaging the retention of a chemically similar, "untargeted" imaging agent. Various different compartment models were used to analyze the data in order to find the optimal procedure for extracting estimates of epidermal growth factor receptor (EGFR) concentration (a receptor overexpressed in many cancers and a key target for emerging molecular therapies) in tissue cultures with varying concentrations of human glioma cells (U251). Preliminary results demonstrated a need to model nonspecific binding of both the targeted and untargeted imaging agents used. The approach could be used to carry out the first repeated measures of cell surface receptor dynamics during 3D tumor mass development, in addition to the receptor response to therapies.

Direct observation of frequency modulated transcription in single cells using light activation

PubMed Central

Larson, Daniel R; Fritzsch, Christoph; Sun, Liang; Meng, Xiuhau; Lawrence, David S; Singer, Robert H

2013-01-01

Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated gene activation. We determine that steroids drive mRNA synthesis by frequency modulation of transcription. This digital behavior in single cells gives rise to the well-known analog dose response across the population. To test this model, we developed a light-activation technology to turn on a single steroid-responsive gene and follow dynamic synthesis of RNA from the activated locus. DOI: http://dx.doi.org/10.7554/eLife.00750.001 PMID:24069527

Human Visuospatial Updating After Passive Translations In Three-Dimensional Space

PubMed Central

Klier, Eliana M.; Hess, Bernhard J. M.; Angelaki, Dora E.

2013-01-01

To maintain a stable representation of the visual environment as we move, the brain must update the locations of targets in space using extra-retinal signals. Humans can accurately update after intervening active whole-body translations. But can they also update for passive translations (i.e., without efference copy signals of an outgoing motor command)? We asked six head-fixed subjects to remember the location of a briefly flashed target (five possible targets were located at depths of 23, 33, 43, 63 and 150cm in front of the cyclopean eye) as they moved 10cm left, right, up, down, forward or backward, while fixating a head-fixed target at 53cm. After the movement, the subjects made a saccade to the remembered location of the flash with a combination of version and vergence eye movements. We computed an updating ratio where 0 indicates no updating and 1 indicates perfect updating. For lateral and vertical whole-body motion, where updating performance is judged by the size of the version movement, the updating ratios were similar for leftward and rightward translations, averaging 0.84±0.28 (mean±SD), as compared to 0.51±0.33 for downward and 1.05±0.50 for upward translations. For forward/backward movements, where updating performance is judged by the size of the vergence movement, the average updating ratio was 1.12±0.45. Updating ratios tended to be larger for far targets than near targets, although both intra- and inter-subject variabilities were smallest for near targets. Thus, in addition to self-generated movements, extra-retinal signals involving otolith and proprioceptive cues can also be used for spatial constancy. PMID:18256164

The MTA UXO Survey and Target Recovery on Lake Erie at the Former Erie Army Depot

DTIC Science & Technology

2009-12-01

MTA Demonstration Front Matter ii FIGURES 1. Firing fans and target locations for Erie Army Depot in 1965...triangles at the base of the image show the locations of the 15 fixed firing positions that were used for proof firing projectiles...the marshland adjacent to the firing ranges, and along beaches fronting the former Depot, (Reference 2, Appendices B and J).3-5 The impact areas

Air-to-Ground Target Acquisition Source Book: A Review of the Literature

DTIC Science & Technology

1974-09-30

Verbal Countdown and No- Countdown Conditions . . . ’ 5-50 S-27 The Effects on Target Recognitio Proficiency ofVarying ’ Scn’ Time and of Display Aids...Dad(D)d4Wat4ao~tt Inter’ J194 ttre’tlo vsvisbleo (1) tsit.n logo proaraiti to olulsto fixed IOv thrl"i.,l. cloture ’A tarpato at 4C1slre4 rtes (I

Multi-Objective Optimization of a Turbofan for an Advanced, Single-Aisle Transport

NASA Technical Reports Server (NTRS)

Berton, Jeffrey J.; Guynn, Mark D.

2012-01-01

Considerable interest surrounds the design of the next generation of single-aisle commercial transports in the Boeing 737 and Airbus A320 class. Aircraft designers will depend on advanced, next-generation turbofan engines to power these airplanes. The focus of this study is to apply single- and multi-objective optimization algorithms to the conceptual design of ultrahigh bypass turbofan engines for this class of aircraft, using NASA s Subsonic Fixed Wing Project metrics as multidisciplinary objectives for optimization. The independent design variables investigated include three continuous variables: sea level static thrust, wing reference area, and aerodynamic design point fan pressure ratio, and four discrete variables: overall pressure ratio, fan drive system architecture (i.e., direct- or gear-driven), bypass nozzle architecture (i.e., fixed- or variable geometry), and the high- and low-pressure compressor work split. Ramp weight, fuel burn, noise, and emissions are the parameters treated as dependent objective functions. These optimized solutions provide insight to the ultrahigh bypass engine design process and provide information to NASA program management to help guide its technology development efforts.

Mixture genotoxicity of 2,4-dichlorophenoxyacetic acid, acrylamide, and maleic hydrazide on human Caco-2 cells assessed with comet assay.

PubMed

Syberg, Kristian; Binderup, Mona-Lise; Cedergreen, Nina; Rank, Jette

2015-01-01

Assessment of genotoxic properties of chemicals is mainly conducted only for single chemicals, without taking mixture genotoxic effects into consideration. The current study assessed mixture effects of the three known genotoxic chemicals, 2,4-dichlorophenoxyacetic acid (2,4-D), acrylamide (AA), and maleic hydrazide (MH), in an experiment with a fixed ratio design setup. The genotoxic effects were assessed with the single-cell gel electrophoresis assay (comet assay) for both single chemicals and the ternary mixture. The concentration ranges used were 0-1.4, 0-20, and 0-37.7 mM for 2,4-D, AA, and MH, respectively. Mixture toxicity was tested with a fixed ratio design at a 10:23:77% ratio for 2.4-D:AA:MH. Results indicated that the three chemicals yielded a synergistic mixture effect. It is not clear which mechanisms are responsible for this interaction. A few possible interactions are discussed, but further investigations including in vivo studies are needed to clarify how important these more-than-additive effects are for risk assessment.

An alternative technique in the treatment of anterior cross bite in a case of Nickel allergy: a case report.

PubMed

Giancotti, A; Mozzicato, P; Mampieri, G

2011-03-01

The objective of this paper is to show an alternative use of an Essix based appliance in the treatment of anterior single-tooth crossbite malocclusion in a patient with Nickel allergy. Anterior crossbite malocclusion of one or more teeth, without posterior crossbite association, is a relatively frequent condition both in the mixed and the permanent dentition. This kind of malocclusion is usually treated with either fixed or removable appliances. The use of preformed Essix appliances could be an alternative to traditional removable and fixed orthodontic devices in patients with Nickel allergy as well as in every patient. The treatment was successfully completed in 12 weeks, the anterior single tooth crossbite was corrected using three full arch Essix-based appliances planned on the set-up casting, providing a gradual vestibular movement. Patient compliance was requested in order to provide the planned dental movement. The Essix appliance can be successfully used to correct a single-tooth crossbite even in allergic subjects in a short time with patient cooperation.

Optical Tweezers for Sample Fixing in Micro-Diffraction Experiments

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

Amenitsch, H.; Rappolt, M.; Sartori, B.

2007-01-19

In order to manipulate, characterize and measure the micro-diffraction of individual structural elements down to single phospholipid liposomes we have been using optical tweezers (OT) combined with an imaging microscope. We were able to install the OT system at the microfocus beamline ID13 at the ESRF and trap clusters of about 50 multi-lamellar liposomes (< 10 {mu}m large cluster). Further we have performed a scanning diffraction experiment with a 1 micrometer beam to demonstrate the fixing capabilities and to confirm the size of the liposome cluster by X-ray diffraction.

Experimental and theoretical analysis for improved microscope design of optical projection tomographic microscopy.

PubMed

Coe, Ryan L; Seibel, Eric J

2013-09-01

We present theoretical and experimental results of axial displacement of objects relative to a fixed condenser focal plane (FP) in optical projection tomographic microscopy (OPTM). OPTM produces three-dimensional, reconstructed images of single cells from two-dimensional projections. The cell rotates in a microcapillary to acquire projections from different perspectives where the objective FP is scanned through the cell while the condenser FP remains fixed at the center of the microcapillary. This work uses a combination of experimental and theoretical methods to improve the OPTM instrument design.

Is there scale-dependent bias in single-field inflation?

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

De Putter, Roland; Doré, Olivier; Green, Daniel, E-mail: rdputter@caltech.edu, E-mail: Olivier.P.Dore@jpl.nasa.gov, E-mail: drgreen@cita.utoronto.ca

2015-10-01

Scale-dependent halo bias due to local primordial non-Gaussianity provides a strong test of single-field inflation. While it is universally understood that single-field inflation predicts negligible scale-dependent bias compared to current observational uncertainties, there is still disagreement on the exact level of scale-dependent bias at a level that could strongly impact inferences made from future surveys. In this paper, we clarify this confusion and derive in various ways that there is exactly zero scale-dependent bias in single-field inflation. Much of the current confusion follows from the fact that single-field inflation does predict a mode coupling of matter perturbations at the levelmore » of f{sub NL}{sup local}; ≈ −5/3, which naively would lead to scale-dependent bias. However, we show explicitly that this mode coupling cancels out when perturbations are evaluated at a fixed physical scale rather than fixed coordinate scale. Furthermore, we show how the absence of scale-dependent bias can be derived easily in any gauge. This result can then be incorporated into a complete description of the observed galaxy clustering, including the previously studied general relativistic terms, which are important at the same level as scale-dependent bias of order f{sub NL}{sup local} ∼ 1. This description will allow us to draw unbiased conclusions about inflation from future galaxy clustering data.« less

Simultaneous generation of aptamers to multiple gamma-carboxyglutamic acid proteins from a focused aptamer library using DeSELEX and convergent selection.

PubMed

Layzer, Juliana M; Sullenger, Bruce A

2007-01-01

By using the in vitro selection method SELEX against the complex mixture of GLA proteins and utilizing methods to deconvolute the resulting ligands, we were able to successfully generate 2'-ribo purine, 2'-fluoro pyrimidine aptamers to various individual targets in the GLA protein proteome that ranged in concentration from 10 nM to 1.4 microM in plasma. Perhaps not unexpectedly, the majority of the aptamers isolated following SELEX bind the most abundant protein in the mixture, prothrombin (FII), with high affinity. We show that by deselecting the dominant prothrombin aptamer the selection can be redirected. By using this DeSELEX approach, we were able to shift the selection toward other sequences and to less abundant protein targets and obtained an aptamer to Factor IX (FIX). We also demonstrate that by using an RNA library that is focused around a proteome, purified protein targets can then be used to rapidly generate aptamers to the protein targets that are rare in the initial mixture such as Factor VII (FVII) and Factor X (FX). Moreover, for all four proteins targeted (FII, FVII, FIX, and FX), aptamers were identified that could inhibit the individual protein's activitity in coagulation assays. Thus, by applying the concepts of DeSELEX and focused library selection, aptamers specific for any protein in a particular proteome can theoretically be generated, even when the proteins in the mixture are present at very different concentrations.

Learning Probabilities From Random Observables in High Dimensions: The Maximum Entropy Distribution and Others

NASA Astrophysics Data System (ADS)

Obuchi, Tomoyuki; Cocco, Simona; Monasson, Rémi

2015-11-01

We consider the problem of learning a target probability distribution over a set of N binary variables from the knowledge of the expectation values (with this target distribution) of M observables, drawn uniformly at random. The space of all probability distributions compatible with these M expectation values within some fixed accuracy, called version space, is studied. We introduce a biased measure over the version space, which gives a boost increasing exponentially with the entropy of the distributions and with an arbitrary inverse `temperature' Γ . The choice of Γ allows us to interpolate smoothly between the unbiased measure over all distributions in the version space (Γ =0) and the pointwise measure concentrated at the maximum entropy distribution (Γ → ∞ ). Using the replica method we compute the volume of the version space and other quantities of interest, such as the distance R between the target distribution and the center-of-mass distribution over the version space, as functions of α =(log M)/N and Γ for large N. Phase transitions at critical values of α are found, corresponding to qualitative improvements in the learning of the target distribution and to the decrease of the distance R. However, for fixed α the distance R does not vary with Γ which means that the maximum entropy distribution is not closer to the target distribution than any other distribution compatible with the observable values. Our results are confirmed by Monte Carlo sampling of the version space for small system sizes (N≤ 10).

Assessment of knowledge, attitude, and practices on fixed dose combinations among postgraduate dental students.

PubMed

Vinnakota, Narayana R; Krishna, V; Viswanath, V; Ahmed, Zaheer; Shaik, Kamal S; Boppana, Naveen K

2016-12-01

To assess the knowledge, attitude, and practices of fixed dose combination drugs among postgraduate dental students. A cross-sectional study was carried out among postgraduate dental students of dental colleges in coastal Andhra Pradesh. Three colleges were randomly selected and students of all the three years were included. Data was collected from the specialities of oral medicine and radiology, oral surgery, endodontics, pedodontics, periodontics, and public health dentistry. The total sample was 90 postgraduate students; informed consent was obtained from the participants, and a pretested questionnaire was distributed to them. Data was analyzed using the Statistical Package for the Social Sciences version 20 software. Out of 90 postgraduates, 33 were males and 57 were females. Thirty-five percent were aware of the essential medical list (EML), among them 11% were from oral medicine and radiology and 6.7% were from pedodontics. However, most of them were unaware of the number of fixed dose combination drugs present in the World Health Organization EML. None of them were able to name at least a single banned fixed dose combination drug. Most of them were unaware of the advantages and disadvantages of using fixed dose combination drugs. Amoxicillin with clavulanic acid was the most common drug prescribed by students (73.3%) followed by ofloxacin with ornidazole (54.4%), ibuprofen with paracetamol (53.3%), and sulfamethoxazole with trimethoprim (6%). Most of them were unaware of the rationality in using fixed dose combination drugs. Common sources of information were medical representatives 43 (47.8%), internet 39 (43.3%), and 12 (13.3%) reported using WHO EML. There is an urgent need to improve knowledge on the rationality for using fixed dose combination, EML, and banned fixed dose combination in India to the promote rational use of fixed dose combination.

Risk based management of invading plant disease

USDA-ARS?s Scientific Manuscript database

Effective control of new and emerging plant disease remains a key challenge. Attempts to eradicate pathogens often involve removal of all plants within a fixed distance of detected infected hosts, targeting asymptomatic infection. Here we develop and test potentially more efficient, epidemiologicall...

Comparative Genomic Analysis of N2-Fixing and Non-N2-Fixing Paenibacillus spp.: Organization, Evolution and Expression of the Nitrogen Fixation Genes

PubMed Central

Xie, Jian-Bo; Du, Zhenglin; Bai, Lanqing; Tian, Changfu; Zhang, Yunzhi; Xie, Jiu-Yan; Wang, Tianshu; Liu, Xiaomeng; Chen, Xi; Cheng, Qi; Chen, Sanfeng; Li, Jilun

2014-01-01

We provide here a comparative genome analysis of 31 strains within the genus Paenibacillus including 11 new genomic sequences of N2-fixing strains. The heterogeneity of the 31 genomes (15 N2-fixing and 16 non-N2-fixing Paenibacillus strains) was reflected in the large size of the shell genome, which makes up approximately 65.2% of the genes in pan genome. Large numbers of transposable elements might be related to the heterogeneity. We discovered that a minimal and compact nif cluster comprising nine genes nifB, nifH, nifD, nifK, nifE, nifN, nifX, hesA and nifV encoding Mo-nitrogenase is conserved in the 15 N2-fixing strains. The nif cluster is under control of a σ70-depedent promoter and possesses a GlnR/TnrA-binding site in the promoter. Suf system encoding [Fe–S] cluster is highly conserved in N2-fixing and non-N2-fixing strains. Furthermore, we demonstrate that the nif cluster enabled Escherichia coli JM109 to fix nitrogen. Phylogeny of the concatenated NifHDK sequences indicates that Paenibacillus and Frankia are sister groups. Phylogeny of the concatenated 275 single-copy core genes suggests that the ancestral Paenibacillus did not fix nitrogen. The N2-fixing Paenibacillus strains were generated by acquiring the nif cluster via horizontal gene transfer (HGT) from a source related to Frankia. During the history of evolution, the nif cluster was lost, producing some non-N2-fixing strains, and vnf encoding V-nitrogenase or anf encoding Fe-nitrogenase was acquired, causing further diversification of some strains. In addition, some N2-fixing strains have additional nif and nif-like genes which may result from gene duplications. The evolution of nitrogen fixation in Paenibacillus involves a mix of gain, loss, HGT and duplication of nif/anf/vnf genes. This study not only reveals the organization and distribution of nitrogen fixation genes in Paenibacillus, but also provides insight into the complex evolutionary history of nitrogen fixation. PMID:24651173

[All-ceramic resin bonded fixed partial denture made of IPS hot-pressed casting porcelain restore anterior missing teeth: a three years clinical observation].

PubMed

Zhou, Tuan feng; Wang, Xin zhi; Zhang, Gui rong

2011-02-18

To clinic observation of IPS Empress2 and IPS e.max all ceramic resin bonded fixed partial dentures used in one anterior teeth lost in upper jaw or less than two anterior tooth lost in lower jaw. 22 patients, 26 restorations had been made, which included 16 single-retainer all ceramic resin bonded fixed partial dentures and 10 two-retainers all ceramic resin bonded fixed partial dentures. Secondary caries of the abutments, shade in the margin of the retainers and the integrity of the restorations had been observed at 3 months, 6 months, 1 year, 2 years and 3 years after all ceramic resin bonded fixed partial dentures having been bonded. In the 3 years of clinic observation of the anterior all ceramic resin bonded fixed partial dentures, 1 two-retainers restoration lost bond after it had been made for 3 months, a retainer of one two-retainers restoration was broken after 6 months, but they are still used after modified as one-retainer all ceramic resin bonded fixed partial dentures, 1 two-retainers restoration lost bond two year later, It was integrity and re-bonded again that was still stable. No secondary carries and no shade in margin of the retainers had been found. Their color matches with the nature teeth excellently. The success rate was 88.5%. IPS Empress 2 and IPS e.max all ceramic resin bonded fixed partial dentures should be a good selection in one or two teeth lose in anterior jaws.

Radar Interferometer for Topographic Mapping of Glaciers and Ice Sheets

NASA Technical Reports Server (NTRS)

Moller, Delwyn K.; Sadowy, Gregory A.; Rignot, Eric J.; Madsen, Soren N.

2007-01-01

A report discusses Ka-band (35-GHz) radar for mapping the surface topography of glaciers and ice sheets at high spatial resolution and high vertical accuracy, independent of cloud cover, with a swath-width of 70 km. The system is a single- pass, single-platform interferometric synthetic aperture radar (InSAR) with an 8-mm wavelength, which minimizes snow penetration while remaining relatively impervious to atmospheric attenuation. As exhibited by the lower frequency SRTM (Shuttle Radar Topography Mission) AirSAR and GeoSAR systems, an InSAR measures topography using two antennas separated by a baseline in the cross-track direction, to view the same region on the ground. The interferometric combination of data received allows the system to resolve the pathlength difference from the illuminated area to the antennas to a fraction of a wavelength. From the interferometric phase, the height of the target area can be estimated. This means an InSAR system is capable of providing not only the position of each image point in along-track and slant range as with a traditional SAR but also the height of that point through interferometry. Although the evolution of InSAR to a millimeter-wave center frequency maximizes the interferometric accuracy from a given baseline length, the high frequency also creates a fundamental problem of swath coverage versus signal-to-noise ratio. While the length of SAR antennas is typically fixed by mass and stowage or deployment constraints, the width is constrained by the desired illuminated swath width. As the across-track beam width which sets the swath size is proportional to the wavelength, a fixed swath size equates to a smaller antenna as the frequency is increased. This loss of antenna size reduces the two-way antenna gain to the second power, drastically reducing the signal-to-noise ratio of the SAR system. This fundamental constraint of high-frequency SAR systems is addressed by applying digital beam-forming (DBF) techniques to synthesize multiple simultaneous receive beams in elevation while maintaining a broad transmit illumination. Through this technique, a high antenna gain on receive is preserved, thereby reducing the required transmit power and thus enabling high-frequency SARs and high-precision InSAR from a single spacecraft.

Engineering calculations for communications satellite systems planning

NASA Technical Reports Server (NTRS)

Levis, C. A.; Martin, C. H.; Reilly, C. H.; Gonsalvez, D. J.; Yamaura, Y.

1985-01-01

An extended gradient search code for broadcasting satellite service (BSS) spectrum/orbit assignment synthesis is discussed. Progress is also reported on both single-entry and full synthesis computational aids for fixed satellite service (FSS) spectrum/orbit assignment purposes.

Analysis of bulk arrival queueing system with batch size dependent service and working vacation

NASA Astrophysics Data System (ADS)

Niranjan, S. P.; Indhira, K.; Chandrasekaran, V. M.

2018-04-01

This paper concentrates on single server bulk arrival queue system with batch size dependent service and working vacation. The server provides service in two service modes depending upon the queue length. The server provides single service if the queue length is at least `a'. On the other hand the server provides fixed batch service if the queue length is at least `k' (k > a). Batch service is provided with some fixed batch size `k'. After completion of service if the queue length is less than `a' then the server leaves for working vacation. During working vacation customers are served with lower service rate than the regular service rate. Service during working vacation also contains two service modes. For the proposed model probability generating function of the queue length at an arbitrary time will be obtained by using supplementary variable technique. Some performance measures will also be presented with suitable numerical illustrations.

Finite-dimensional approximation for optimal fixed-order compensation of distributed parameter systems

NASA Technical Reports Server (NTRS)

Bernstein, Dennis S.; Rosen, I. G.

1988-01-01

In controlling distributed parameter systems it is often desirable to obtain low-order, finite-dimensional controllers in order to minimize real-time computational requirements. Standard approaches to this problem employ model/controller reduction techniques in conjunction with LQG theory. In this paper we consider the finite-dimensional approximation of the infinite-dimensional Bernstein/Hyland optimal projection theory. This approach yields fixed-finite-order controllers which are optimal with respect to high-order, approximating, finite-dimensional plant models. The technique is illustrated by computing a sequence of first-order controllers for one-dimensional, single-input/single-output, parabolic (heat/diffusion) and hereditary systems using spline-based, Ritz-Galerkin, finite element approximation. Numerical studies indicate convergence of the feedback gains with less than 2 percent performance degradation over full-order LQG controllers for the parabolic system and 10 percent degradation for the hereditary system.

Decentralised fixed modes of networked MIMO systems

NASA Astrophysics Data System (ADS)

Hao, Yuqing; Duan, Zhisheng; Chen, Guanrong

2018-04-01

In this paper, decentralised fixed modes (DFMs) of a networked system are studied. The network topology is directed and weighted and the nodes are higher-dimensional linear time-invariant (LTI) dynamical systems. The effects of the network topology, the node-system dynamics, the external control inputs, and the inner interactions on the existence of DFMs for the whole networked system are investigated. A necessary and sufficient condition for networked multi-input/multi-output (MIMO) systems in a general topology to possess no DFMs is derived. For networked single-input/single-output (SISO) LTI systems in general as well as some typical topologies, some specific conditions for having no DFMs are established. It is shown that the existence of DFMs is an integrated result of the aforementioned relevant factors which cannot be decoupled into individual DFMs of the node-systems and the properties solely determined by the network topology.

Bacterial fatty acid metabolism in modern antibiotic discovery.

PubMed

Yao, Jiangwei; Rock, Charles O

2017-11-01

Bacterial fatty acid synthesis is essential for many pathogens and different from the mammalian counterpart. These features make bacterial fatty acid synthesis a desirable target for antibiotic discovery. The structural divergence of the conserved enzymes and the presence of different isozymes catalyzing the same reactions in the pathway make bacterial fatty acid synthesis a narrow spectrum target rather than the traditional broad spectrum target. Furthermore, bacterial fatty acid synthesis inhibitors are single-targeting, rather than multi-targeting like traditional monotherapeutic, broad-spectrum antibiotics. The single-targeting nature of bacterial fatty acid synthesis inhibitors makes overcoming fast-developing, target-based resistance a necessary consideration for antibiotic development. Target-based resistance can be overcome through multi-targeting inhibitors, a cocktail of single-targeting inhibitors, or by making the single targeting inhibitor sufficiently high affinity through a pathogen selective approach such that target-based mutants are still susceptible to therapeutic concentrations of drug. Many of the pathogens requiring new antibiotic treatment options encode for essential bacterial fatty acid synthesis enzymes. This review will evaluate the most promising targets in bacterial fatty acid metabolism for antibiotic therapeutics development and review the potential and challenges in advancing each of these targets to the clinic and circumventing target-based resistance. This article is part of a Special Issue entitled: Bacterial Lipids edited by Russell E. Bishop. Copyright © 2016 Elsevier B.V. All rights reserved.

Integrated optimization of unmanned aerial vehicle task allocation and path planning under steady wind.

PubMed

Luo, He; Liang, Zhengzheng; Zhu, Moning; Hu, Xiaoxuan; Wang, Guoqiang

2018-01-01

Wind has a significant effect on the control of fixed-wing unmanned aerial vehicles (UAVs), resulting in changes in their ground speed and direction, which has an important influence on the results of integrated optimization of UAV task allocation and path planning. The objective of this integrated optimization problem changes from minimizing flight distance to minimizing flight time. In this study, the Euclidean distance between any two targets is expanded to the Dubins path length, considering the minimum turning radius of fixed-wing UAVs. According to the vector relationship between wind speed, UAV airspeed, and UAV ground speed, a method is proposed to calculate the flight time of UAV between targets. On this basis, a variable-speed Dubins path vehicle routing problem (VS-DP-VRP) model is established with the purpose of minimizing the time required for UAVs to visit all the targets and return to the starting point. By designing a crossover operator and mutation operator, the genetic algorithm is used to solve the model, the results of which show that an effective UAV task allocation and path planning solution under steady wind can be provided.

Integrated optimization of unmanned aerial vehicle task allocation and path planning under steady wind

PubMed Central

Liang, Zhengzheng; Zhu, Moning; Hu, Xiaoxuan; Wang, Guoqiang

2018-01-01

Wind has a significant effect on the control of fixed-wing unmanned aerial vehicles (UAVs), resulting in changes in their ground speed and direction, which has an important influence on the results of integrated optimization of UAV task allocation and path planning. The objective of this integrated optimization problem changes from minimizing flight distance to minimizing flight time. In this study, the Euclidean distance between any two targets is expanded to the Dubins path length, considering the minimum turning radius of fixed-wing UAVs. According to the vector relationship between wind speed, UAV airspeed, and UAV ground speed, a method is proposed to calculate the flight time of UAV between targets. On this basis, a variable-speed Dubins path vehicle routing problem (VS-DP-VRP) model is established with the purpose of minimizing the time required for UAVs to visit all the targets and return to the starting point. By designing a crossover operator and mutation operator, the genetic algorithm is used to solve the model, the results of which show that an effective UAV task allocation and path planning solution under steady wind can be provided. PMID:29561888

Performance of a visuomotor walking task in an augmented reality training setting.

PubMed

Haarman, Juliet A M; Choi, Julia T; Buurke, Jaap H; Rietman, Johan S; Reenalda, Jasper

2017-12-01

Visual cues can be used to train walking patterns. Here, we studied the performance and learning capacities of healthy subjects executing a high-precision visuomotor walking task, in an augmented reality training set-up. A beamer was used to project visual stepping targets on the walking surface of an instrumented treadmill. Two speeds were used to manipulate task difficulty. All participants (n = 20) had to change their step length to hit visual stepping targets with a specific part of their foot, while walking on a treadmill over seven consecutive training blocks, each block composed of 100 stepping targets. Distance between stepping targets was varied between short, medium and long steps. Training blocks could either be composed of random stepping targets (no fixed sequence was present in the distance between the stepping targets) or sequenced stepping targets (repeating fixed sequence was present). Random training blocks were used to measure non-specific learning and sequenced training blocks were used to measure sequence-specific learning. Primary outcome measures were performance (% of correct hits), and learning effects (increase in performance over the training blocks: both sequence-specific and non-specific). Secondary outcome measures were the performance and stepping-error in relation to the step length (distance between stepping target). Subjects were able to score 76% and 54% at first try for lower speed (2.3 km/h) and higher speed (3.3 km/h) trials, respectively. Performance scores did not increase over the course of the trials, nor did the subjects show the ability to learn a sequenced walking task. Subjects were better able to hit targets while increasing their step length, compared to shortening it. In conclusion, augmented reality training by use of the current set-up was intuitive for the user. Suboptimal feedback presentation might have limited the learning effects of the subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

Implementation of Amplicon Parallel Sequencing Leads to Improvement of Diagnosis and Therapy of Lung Cancer Patients.

PubMed

König, Katharina; Peifer, Martin; Fassunke, Jana; Ihle, Michaela A; Künstlinger, Helen; Heydt, Carina; Stamm, Katrin; Ueckeroth, Frank; Vollbrecht, Claudia; Bos, Marc; Gardizi, Masyar; Scheffler, Matthias; Nogova, Lucia; Leenders, Frauke; Albus, Kerstin; Meder, Lydia; Becker, Kerstin; Florin, Alexandra; Rommerscheidt-Fuss, Ursula; Altmüller, Janine; Kloth, Michael; Nürnberg, Peter; Henkel, Thomas; Bikár, Sven-Ernö; Sos, Martin L; Geese, William J; Strauss, Lewis; Ko, Yon-Dschun; Gerigk, Ulrich; Odenthal, Margarete; Zander, Thomas; Wolf, Jürgen; Merkelbach-Bruse, Sabine; Buettner, Reinhard; Heukamp, Lukas C

2015-07-01

The Network Genomic Medicine Lung Cancer was set up to rapidly translate scientific advances into early clinical trials of targeted therapies in lung cancer performing molecular analyses of more than 3500 patients annually. Because sequential analysis of the relevant driver mutations on fixated samples is challenging in terms of workload, tissue availability, and cost, we established multiplex parallel sequencing in routine diagnostics. The aim was to analyze all therapeutically relevant mutations in lung cancer samples in a high-throughput fashion while significantly reducing turnaround time and amount of input DNA compared with conventional dideoxy sequencing of single polymerase chain reaction amplicons. In this study, we demonstrate the feasibility of a 102 amplicon multiplex polymerase chain reaction followed by sequencing on an Illumina sequencer on formalin-fixed paraffin-embedded tissue in routine diagnostics. Analysis of a validation cohort of 180 samples showed this approach to require significantly less input material and to be more reliable, robust, and cost-effective than conventional dideoxy sequencing. Subsequently, 2657 lung cancer patients were analyzed. We observed that comprehensive biomarker testing provided novel information in addition to histological diagnosis and clinical staging. In 2657 consecutively analyzed lung cancer samples, we identified driver mutations at the expected prevalence. Furthermore we found potentially targetable DDR2 mutations at a frequency of 3% in both adenocarcinomas and squamous cell carcinomas. Overall, our data demonstrate the utility of systematic sequencing analysis in a clinical routine setting and highlight the dramatic impact of such an approach on the availability of therapeutic strategies for the targeted treatment of individual cancer patients.

Clinical Validation and Implementation of a Targeted Next-Generation Sequencing Assay to Detect Somatic Variants in Non-Small Cell Lung, Melanoma, and Gastrointestinal Malignancies

PubMed Central

Fisher, Kevin E.; Zhang, Linsheng; Wang, Jason; Smith, Geoffrey H.; Newman, Scott; Schneider, Thomas M.; Pillai, Rathi N.; Kudchadkar, Ragini R.; Owonikoko, Taofeek K.; Ramalingam, Suresh S.; Lawson, David H.; Delman, Keith A.; El-Rayes, Bassel F.; Wilson, Malania M.; Sullivan, H. Clifford; Morrison, Annie S.; Balci, Serdar; Adsay, N. Volkan; Gal, Anthony A.; Sica, Gabriel L.; Saxe, Debra F.; Mann, Karen P.; Hill, Charles E.; Khuri, Fadlo R.; Rossi, Michael R.

2017-01-01

We tested and clinically validated a targeted next-generation sequencing (NGS) mutation panel using 80 formalin-fixed, paraffin-embedded (FFPE) tumor samples. Forty non-small cell lung carcinoma (NSCLC), 30 melanoma, and 30 gastrointestinal (12 colonic, 10 gastric, and 8 pancreatic adenocarcinoma) FFPE samples were selected from laboratory archives. After appropriate specimen and nucleic acid quality control, 80 NGS libraries were prepared using the Illumina TruSight tumor (TST) kit and sequenced on the Illumina MiSeq. Sequence alignment, variant calling, and sequencing quality control were performed using vendor software and laboratory-developed analysis workflows. TST generated ≥500× coverage for 98.4% of the 13,952 targeted bases. Reproducible and accurate variant calling was achieved at ≥5% variant allele frequency with 8 to 12 multiplexed samples per MiSeq flow cell. TST detected 112 variants overall, and confirmed all known single-nucleotide variants (n = 27), deletions (n = 5), insertions (n = 3), and multinucleotide variants (n = 3). TST detected at least one variant in 85.0% (68/80), and two or more variants in 36.2% (29/80), of samples. TP53 was the most frequently mutated gene in NSCLC (13 variants; 13/32 samples), gastrointestinal malignancies (15 variants; 13/25 samples), and overall (30 variants; 28/80 samples). BRAF mutations were most common in melanoma (nine variants; 9/23 samples). Clinically relevant NGS data can be obtained from routine clinical FFPE solid tumor specimens using TST, benchtop instruments, and vendor-supplied bioinformatics pipelines. PMID:26801070

A human scFv antibody that targets and neutralizes high molecular weight pathogenic amyloid-β oligomers.

PubMed

Sebollela, Adriano; Cline, Erika N; Popova, Izolda; Luo, Kevin; Sun, Xiaoxia; Ahn, Jay; Barcelos, Milena A; Bezerra, Vanessa N; Lyra E Silva, Natalia M; Patel, Jason; Pinheiro, Nathalia R; Qin, Lei A; Kamel, Josette M; Weng, Anthea; DiNunno, Nadia; Bebenek, Adrian M; Velasco, Pauline T; Viola, Kirsten L; Lacor, Pascale N; Ferreira, Sergio T; Klein, William L

2017-07-03

Brain accumulation of soluble oligomers of the amyloid-β peptide (AβOs) is increasingly considered a key early event in the pathogenesis of Alzheimer's disease (AD). A variety of AβO species have been identified, both in vitro and in vivo, ranging from dimers to 24mers and higher order oligomers. However, there is no consensus in the literature regarding which AβO species are most germane to AD pathogenesis. Antibodies capable of specifically recognizing defined subpopulations of AβOs would be a valuable asset in the identification, isolation, and characterization of AD-relevant AβO species. Here, we report the characterization of a human single chain antibody fragment (scFv) denoted NUsc1, one of a number of scFvs we have identified that stringently distinguish AβOs from both monomeric and fibrillar Aβ. NUsc1 readily detected AβOs previously bound to dendrites in cultured hippocampal neurons. In addition, NUsc1 blocked AβO binding and reduced AβO-induced neuronal oxidative stress and tau hyperphosphorylation in cultured neurons. NUsc1 further distinguished brain extracts from AD-transgenic mice from wild type (WT) mice, and detected endogenous AβOs in fixed AD brain tissue and AD brain extracts. Biochemical analyses indicated that NUsc1 targets a subpopulation of AβOs with apparent molecular mass greater than 50 kDa. Results indicate that NUsc1 targets a particular AβO species relevant to AD pathogenesis, and suggest that NUsc1 may constitute an effective tool for AD diagnostics and therapeutics. © 2017 International Society for Neurochemistry.

Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

PubMed

Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

2015-01-01

Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

Economic evaluation of single-tooth replacement: dental implant versus fixed partial denture.

PubMed

Kim, Younhee; Park, Joo-Yeon; Park, Sun-Young; Oh, Sung-Hee; Jung, YeaJi; Kim, Ji-Min; Yoo, Soo-Yeon; Kim, Seong-Kyun

2014-01-01

This study assessed the cost-effectiveness from a societal perspective of a dental implant compared with a three-unit tooth-supported fixed partial denture (FPD) for the replacement of a single tooth in 2010. A decision tree was developed to estimate cost-effectiveness over a 10-year period. The survival rates of single-tooth implants and FPDs were extracted from a meta-analysis of single-arm studies. Medical costs included initial treatment costs, maintenance costs, and costs to treat complications. Patient surveys were used to obtain the costs of the initial single-tooth implant or FPD. Maintenance costs and costs to treat complications were based on surveys of seven clinical experts at dental clinics or hospitals. Transportation costs were calculated based on the number of visits for implant or FPD treatment. Patient time costs were estimated using the number of visits and time required, hourly wage, and employment rate. Future costs were discounted by 5% to convert to present values. The results of a 10-year period model showed that a single dental implant cost US $261 (clinic) to $342 (hospital) more than an FPD and had an average survival rate that was 10.4% higher. The incremental cost-effectiveness ratio was $2,514 in a clinic and $3,290 in a hospital for a prosthesis in situ for 10 years. The sensitivity analysis showed that initial treatment costs and survival rate influenced the cost-effectiveness. If the cost of an implant were reduced to 80% of the current cost, the implant would become the dominant intervention. Although the level of evidence for effectiveness is low, and some aspects of single-tooth implants or FPDs, such as satisfaction, were not considered, this study will help patients requiring single-tooth replacement to choose the best treatment option.

Optimization of brain metabolism using metabolic-targeted therapeutic hypothermia can reduce mortality from traumatic brain injury.

PubMed

Feng, Jin-Zhou; Wang, Wen-Yuan; Zeng, Jun; Zhou, Zhi-Yuan; Peng, Jin; Yang, Hao; Deng, Peng-Chi; Li, Shi-Jun; Lu, Charles D; Jiang, Hua

2017-08-01

Therapeutic hypothermia is widely used to treat traumatic brain injuries (TBIs). However, determining the best hypothermia therapy strategy remains a challenge. We hypothesized that reducing the metabolic rate, rather than reaching a fixed body temperature, would be an appropriate target because optimizing metabolic conditions especially the brain metabolic environment may enhance neurologic protection. A pilot single-blind randomized controlled trial was designed to test this hypothesis, and a nested metabolomics study was conducted to explore the mechanics thereof. Severe TBI patients (Glasgow Coma Scale score, 3-8) were randomly divided into the metabolic-targeted hypothermia treatment (MTHT) group, 50% to 60% rest metabolic ratio as the hypothermia therapy target, and the body temperature-targeted hypothermia treatment (BTHT) control group, hypothermia therapy target of 32°C to 35°C body temperature. Brain and circulatory metabolic pool blood samples were collected at baseline and on days 1, 3, and 7 during the hypothermia treatment, which were selected randomly from a subgroup of MTHT and BTHT groups. The primary outcome was mortality. Using H nuclear magnetic resonance technology, we tracked and located the disturbances of metabolic networks. Eighty-eight severe TBI patients were recruited and analyzed from December 2013 to December 2014, 44 each were assigned in the MTHT and BTHT groups (median age, 42 years; 69.32% men; mean Glasgow Coma Scale score, 6.17 ± 1.02). The mortality was significantly lower in the MTHT than the BTHT group (15.91% vs. 34.09%; p = 0.049). From these, eight cases of MTHT and six cases from BTHT group were enrolled for metabolomics analysis, which showed a significant difference between the brain and circulatory metabolic patterns in MTHT group on day 7 based on the model parameters and scores plots. Finally, metabolites representing potential neuroprotective monitoring parameters for hypothermia treatment were identified through H nuclear magnetic resonance metabolomics. MTHT can significantly reduce the mortality of severe TBI patients. Metabolomics research showed that this strategy could effectively improve brain metabolism, suggesting that reducing the metabolic rate to 50% to 60% should be set as the hypothermia therapy target. Therapeutic study, Level I.

[Pathophysiology of muscular atrophy due to disuse--with special reference to a single muscle fiber and its ultrastructure].

PubMed

Sukegawa, T

1983-08-01

Immobilization muscule atrophy was experimentally induced by fixing one ankle joint with a K-wire in an extended position in rats. The animals were sacrificed at designated intervals to obtain the soleus muscle from the fixed (or disused) side and the free side; the muscles were weighed wet, evaluated (musculo) physiologically using a single-skinned muscle fiber method, and further examined histochemically and electron-microscopically. The wet weight of the disused soleus muscle was reduced to 54% of that of the healthy (used) muscle. According to classification by types of muscle fibers stained for ATPase, conversion of muscle fiber type, i.e., conversions of type 1 (red muscle) into type 2 (white muscle) was noted on the disused side, and similar findings were also observed by examination using a single skinned muscle fiber method. The maximal tension developed by the disused single muscle fiber was lower. This may be attributable to structural changes in the myofilament arrangement observed under an electron microscope. No abnormalities were found in calcium ion uptake by the sarcoplasmic reticulum. Under the present experimental conditions, it was clarified that the disuse atrophy of skeletal muscle induces not only reduction of muscle fibers in diameter but also their dedifferentiation and redifferentiation.

Evaluation of safety and efficacy of a fixed olmesartan/amlodipine combination therapy compared to single monotherapies.

PubMed

Derosa, Giuseppe; Cicero, Arrigo Francesco Giuseppe; Carbone, Anna; Querci, Fabrizio; Fogari, Elena; D'Angelo, Angela; Maffioli, Pamela

2013-09-01

Hypertension is known to be one of the main risk factors for cardiovascular disease. To evaluate the safety and efficacy of a fixed olmesartan/amlodipine (Olme/Amlo) combination in improving blood pressure control, lipid profile, insulin sensitivity and some inflammatory and insulin resistance markers. Two hundred and seventy-six hypertensive patients were randomly assigned to olmesartan 20 mg, amlodipine 10 mg or a single pill containing an Olme/Amlo combination 20/5 mg for 12 months. We evaluated after 6 and 12 months: body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP and DBP, respectively), fasting plasma glucose (FPG), fasting plasma insulin (FPI), lipid profile, vaspin, visfatin, interleukins 8 and 10 (IL-8 and IL-10, respectively). Patients also underwent an euglycemic, hyperinsulinemic clamp. Olme/Amlo combination was more effective in decreasing SBP, and DPB compared to single monotherapies after 12 months. Olme/Amlo combination, but not amlodipine, decreased FPG after 12 months. FPI and HOMA index were decreased, and M value increased by Olme/Amlo combination compared to olmesartan monotherapy, and to amlodipine monotherapy. Olme/Amlo significantly decreased IL-8 and IL-10 better than each monotherapy. Olme/Amlo single pill combination can be a safe and effective option to reduce blood pressure, improve insulin sensitivity and decrease inflammatory markers.

Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination.

PubMed

Wang, H F; Wang, R; O'Gorman, M; Crownover, P; Naqvi, A; Jafri, I

2013-12-01

Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB). This study was conducted at a single centre--the Pfizer Clinical Research Unit in Singapore. To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination. In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (C(max)) and the area under plasma concentration-time curve (AUC). Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for C(max) and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study. The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.

Effect of viewing distance on the generation of vertical eye movements during locomotion

NASA Technical Reports Server (NTRS)

Moore, S. T.; Hirasaki, E.; Cohen, B.; Raphan, T.

1999-01-01

Vertical head and eye coordination was studied as a function of viewing distance during locomotion. Vertical head translation and pitch movements were measured using a video motion analysis system (Optotrak 3020). Vertical eye movements were recorded using a video-based pupil tracker (Iscan). Subjects (five) walked on a linear treadmill at a speed of 1.67 m/s (6 km/h) while viewing a target screen placed at distances ranging from 0.25 to 2.0 m at 0. 25-m intervals. The predominant frequency of vertical head movement was 2 Hz. In accordance with previous studies, there was a small head pitch rotation, which was compensatory for vertical head translation. The magnitude of the vertical head movements and the phase relationship between head translation and pitch were little affected by viewing distance, and tended to orient the naso-occipital axis of the head at a point approximately 1 m in front of the subject (the head fixation distance or HFD). In contrast, eye velocity was significantly affected by viewing distance. When viewing a far (2-m) target, vertical eye velocity was 180 degrees out of phase with head pitch velocity, with a gain of 0. 8. This indicated that the angular vestibulo-ocular reflex (aVOR) was generating the eye movement response. The major finding was that, at a close viewing distance (0.25 m), eye velocity was in phase with head pitch and compensatory for vertical head translation, suggesting that activation of the linear vestibulo-ocular reflex (lVOR) was contributing to the eye movement response. There was also a threefold increase in the magnitude of eye velocity when viewing near targets, which was consistent with the goal of maintaining gaze on target. The required vertical lVOR sensitivity to cancel an unmodified aVOR response and generate the observed eye velocity magnitude for near targets was almost 3 times that previously measured. Supplementary experiments were performed utilizing body-fixed active head pitch rotations at 1 and 2 Hz while viewing a head-fixed target. Results indicated that the interaction of smooth pursuit and the aVOR during visual suppression could modify both the gain and phase characteristics of the aVOR at frequencies encountered during locomotion. When walking, targets located closer than the HFD (1.0 m) would appear to move in the same direction as the head pitch, resulting in suppression of the aVOR. The results of the head-fixed target experiment suggest that phase modification of the aVOR during visual suppression could play a role in generating eye movements consistent with the goal of maintaining gaze on targets closer than the HFD, which would augment the lVOR response.

A prospective randomised comparative parallel study of amniotic membrane wound graft in the management of diabetic foot ulcers.

PubMed

Zelen, Charles M; Serena, Thomas E; Denoziere, Guilhem; Fetterolf, Donald E

2013-10-01

Our purpose was to compare healing characteristics of diabetic foot ulcers treated with dehydrated human amniotic membrane allografts (EpiFix®, MiMedx, Kennesaw, GA) versus standard of care. An IRB-approved, prospective, randomised, single-centre clinical trial was performed. Included were patients with a diabetic foot ulcer of at least 4-week duration without infection having adequate arterial perfusion. Patients were randomised to receive standard care alone or standard care with the addition of EpiFix. Wound size reduction and rates of complete healing after 4 and 6 weeks were evaluated. In the standard care group (n = 12) and the EpiFix group (n = 13) wounds reduced in size by a mean of 32.0% ± 47.3% versus 97.1% ± 7.0% (P < 0.001) after 4 weeks, whereas at 6 weeks wounds were reduced by -1.8% ± 70.3% versus 98.4% ± 5.8% (P < 0.001), standard care versus EpiFix, respectively. After 4 and 6 weeks of treatment the overall healing rate with application of EpiFix was shown to be 77% and 92%, respectively, whereas standard care healed 0% and 8% of the wounds (P < 0.001), respectively. Patients treated with EpiFix achieved superior healing rates over standard treatment alone. These results show that using EpiFix in addition to standard care is efficacious for wound healing. ©2013 The Authors. International Wound Journal published by John Wiley & Sons Ltd and Medicalhelplines.com Inc.

Frequency Diverse Array Radar

DTIC Science & Technology

2010-09-01

Postgraduate School Monterey, CA 93943-5000 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING /MONITORING AGENCY NAME( S ) AND ADDRESS(ES) N/A...given. Lastly, the radar applications of FDA are considered. The received power from a target at a fixed range is simulated in MATLAB and the

Visual focus stimulator aids in study of the eye's focusing action

NASA Technical Reports Server (NTRS)

Cornsweet, T. N.; Crane, H. D.

1970-01-01

Optical apparatus varies apparent distance of a target image from the eye by means of reflectors that are moved orthogonally to the optical axis between fixed lenses. Apparatus can be pointed at any object, test pattern, or other visual display.

First Monte Carlo analysis of fragmentation functions from single-inclusive e + e - annihilation

DOE PAGES

Sato, Nobuo; Ethier, J. J.; Melnitchouk, W.; ...

2016-12-02

Here, we perform the first iterative Monte Carlo (IMC) analysis of fragmentation functions constrained by all available data from single-inclusive $e^+ e^-$ annihilation into pions and kaons. The IMC method eliminates potential bias in traditional analyses based on single fits introduced by fixing parameters not well contrained by the data, and provides a statistically rigorous determination of uncertainties. Our analysis reveals specific features of fragmentation functions using the new IMC methodology and those obtained from previous analyses, especially for light quarks and for strange quark fragmentation to kaons.

Synthetic-Aperture Coherent Imaging From A Circular Path

NASA Technical Reports Server (NTRS)

Jin, Michael Y.

1995-01-01

Imaging algorithms based on exact point-target responses. Developed for use in reconstructing image of target from data gathered by radar, sonar, or other transmitting/receiving coherent-signal sensory apparatus following circular observation path around target. Potential applications include: Wide-beam synthetic-aperture radar (SAR) from aboard spacecraft in circular orbit around target planet; SAR from aboard airplane flying circular course at constant elevation around central ground point, toward which spotlight radar beam pointed; Ultrasonic reflection tomography in medical setting, using one transducer moving in circle around patient or else multiple transducers at fixed positions on circle around patient; and Sonar imaging of sea floor to high resolution, without need for large sensory apparatus.

Laser scanning system for object monitoring

DOEpatents

McIntyre, Timothy James [Knoxville, TN; Maxey, Lonnie Curtis [Powell, TN; Chiaro, Jr; John, Peter [Clinton, TN

2008-04-22

A laser scanner is located in a fixed position to have line-of-sight access to key features of monitored objects. The scanner rapidly scans pre-programmed points corresponding to the positions of retroreflecting targets affixed to the key features of the objects. The scanner is capable of making highly detailed scans of any portion of the field of view, permitting the exact location and identity of targets to be confirmed. The security of an object is verified by determining that the cooperative target is still present and that its position has not changed. The retroreflecting targets also modulate the reflected light for purposes of returning additional information back to the location of the scanner.

The effects of fixed-time reinforcement schedules on functional response classes: a translational study.

PubMed

Heinicke, Megan R; Carr, James E; LeBlanc, Linda A

2012-01-01

Research on functional response classes has applied significance because less severe forms of problem behavior have been found to co-occur with more severe forms. In addition, the most severe forms of problem behavior are sometimes targeted for intervention without monitoring other less severe forms. In such cases, it is unknown whether and how untreated forms of problem behavior covary with the targeted behaviors. The present study employed a translational procedure (with button presses as the target behavior) to investigate response covariation under noncontingent reinforcement with typically developing preschoolers. The results indicated that noncontingent reinforcement was generally effective in decreasing all response class members when only one member was targeted.