Open-Loop Flight Testing of COBALT Navigation and Sensor Technologies for Precise Soft Landing

NASA Technical Reports Server (NTRS)

Carson, John M., III; Restrepo, Caroline I.; Seubert, Carl R.; Amzajerdian, Farzin; Pierrottet, Diego F.; Collins, Steven M.; O'Neal, Travis V.; Stelling, Richard

2017-01-01

An open-loop flight test campaign of the NASA COBALT (CoOperative Blending of Autonomous Landing Technologies) payload was conducted onboard the Masten Xodiac suborbital rocket testbed. The payload integrates two complementary sensor technologies that together provide a spacecraft with knowledge during planetary descent and landing to precisely navigate and softly touchdown in close proximity to targeted surface locations. The two technologies are the Navigation Doppler Lidar (NDL), for high-precision velocity and range measurements, and the Lander Vision System (LVS) for map-relative state esti- mates. A specialized navigation filter running onboard COBALT fuses the NDL and LVS data in real time to produce a very precise Terrain Relative Navigation (TRN) solution that is suitable for future, autonomous planetary landing systems that require precise and soft landing capabilities. During the open-loop flight campaign, the COBALT payload acquired measurements and generated a precise navigation solution, but the Xodiac vehicle planned and executed its maneuvers based on an independent, GPS-based navigation solution. This minimized the risk to the vehicle during the integration and testing of the new navigation sensing technologies within the COBALT payload.

NIH announces the launch of 3 integrated precision medicine trials: ALCHEMIST

Cancer.gov

The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials, or ALCHEMIST, will identify early-stage lung cancer patients with tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against

Efficient Genome Editing in Induced Pluripotent Stem Cells with Engineered Nucleases In Vitro.

PubMed

Termglinchan, Vittavat; Seeger, Timon; Chen, Caressa; Wu, Joseph C; Karakikes, Ioannis

2017-01-01

Precision genome engineering is rapidly advancing the application of the induced pluripotent stem cells (iPSCs) technology for in vitro disease modeling of cardiovascular diseases. Targeted genome editing using engineered nucleases is a powerful tool that allows for reverse genetics, genome engineering, and targeted transgene integration experiments to be performed in a precise and predictable manner. However, nuclease-mediated homologous recombination is an inefficient process. Herein, we describe the development of an optimized method combining site-specific nucleases and the piggyBac transposon system for "seamless" genome editing in pluripotent stem cells with high efficiency and fidelity in vitro.

ALCHEMIST: Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials

Cancer.gov

ALCHEMIST represents three integrated, precision medicine trials that are designed to identify people with early-stage lung cancer who have tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against those mol

Space-time domain solutions of the wave equation by a non-singular boundary integral method and Fourier transform.

PubMed

Klaseboer, Evert; Sepehrirahnama, Shahrokh; Chan, Derek Y C

2017-08-01

The general space-time evolution of the scattering of an incident acoustic plane wave pulse by an arbitrary configuration of targets is treated by employing a recently developed non-singular boundary integral method to solve the Helmholtz equation in the frequency domain from which the space-time solution of the wave equation is obtained using the fast Fourier transform. The non-singular boundary integral solution can enforce the radiation boundary condition at infinity exactly and can account for multiple scattering effects at all spacings between scatterers without adverse effects on the numerical precision. More generally, the absence of singular kernels in the non-singular integral equation confers high numerical stability and precision for smaller numbers of degrees of freedom. The use of fast Fourier transform to obtain the time dependence is not constrained to discrete time steps and is particularly efficient for studying the response to different incident pulses by the same configuration of scatterers. The precision that can be attained using a smaller number of Fourier components is also quantified.

Precision Therapy of Head and Neck Squamous Cell Carcinoma.

PubMed

Polverini, P J; D'Silva, N J; Lei, Y L

2018-06-01

Precision medicine is an approach to disease prevention and treatment that takes into account genetic variability and environmental and lifestyle influences that are unique to each patient. It facilitates stratification of patient populations that vary in their susceptibility to disease and response to therapy. Shared databases and the implementation of new technology systems designed to advance the integration of this information will enable health care providers to more accurately predict and customize prevention and treatment strategies for patients. Although precision medicine has had a limited impact in most areas of medicine, it has been shown to be an increasingly successful approach to cancer therapy. Despite early promising results targeting aberrant signaling pathways or inhibitors designed to block tumor-driven processes such as angiogenesis, limited success emphasizes the need to discover new biomarkers and treatment targets that are more reliable in predicting response to therapy and result in better health outcomes. Recent successes in the use of immunity-inducing antibodies have stimulated increased interest in the use of precision immunotherapy of head and neck squamous cell carcinoma. Using next-generation sequencing, the precise profiling of tumor-infiltrating lymphocytes has great promise to identify hypoimmunogenic cancer that would benefit from a rationally designed combinatorial approach. Continued interrogation of tumors will reveal new actionable targets with increasing therapeutic efficacy and fulfill the promise of precision therapy of head and neck cancer.

Differential Phosphorylation of Smad1 Integrates BMP and Neurotrophin Pathways through Erk/Dusp in Axon Development

PubMed Central

Finelli, Mattéa J.; Murphy, Kevin J.; Chen, Lei; Zou, Hongyan

2013-01-01

SUMMARY Sensory axon development requires concerted actions of growth factors for the precise control of axonal outgrowth and target innervation. How developing sensory neurons integrate different cues is poorly understood. We demonstrate here that Smad1 activation is required for neurotrophin-mediated sensory axon growth in vitro and in vivo. Through differential phosphorylation, Smad1 exerts transcriptional selectivity to regulate the expression and activity of Erk1 and Erk2—two key neurotrophin effectors. Specifically, BMPs signal through carboxy-terminal phosphorylation of Smad1 (pSmad1C) to induce Erk1/2 transcription for enhanced neurotrophin responsiveness. Meanwhile, neurotrophin signaling results in linker phosphorylation of Smad1 (pSmad1L), which in turn upregulates an Erk-specific dual-specificity phosphatase, Dusp6, leading to reduced pErk1/2, and constituting a negative feedback loop to prevent axon overgrowth. Together, BMP and neurotrophin pathways are integrated in a tightly regulated signaling network with balanced ratio of Erk1/2 and pErk1/2 to direct the precise connections between sensory neurons and peripheral targets. PMID:23665221

A method to transfer an individual graphene flake to a target position with a precision of sub-micrometer

NASA Astrophysics Data System (ADS)

Wang, Yubing; Yin, Weihong; Han, Qin; Yang, Xiaohong; Ye, Han; Lü, Qianqian; Yin, Dongdong

2017-04-01

Graphene field-effect transistors have been intensively studied. However, in order to fabricate devices with more complicated structures, such as the integration with waveguide and other two-dimensional materials, we need to transfer the exfoliated graphene samples to a target position. Due to the small area of exfoliated graphene and its random distribution, the transfer method requires rather high precision. In this paper, we systematically study a method to selectively transfer mechanically exfoliated graphene samples to a target position with a precision of sub-micrometer. To characterize the doping level of this method, we transfer graphene flakes to pre-patterned metal electrodes, forming graphene field-effect transistors. The hole doping of graphene is calculated to be 2.16 × {10}12{{{cm}}}-2. In addition, we fabricate a waveguide-integrated multilayer graphene photodetector to demonstrate the viability and accuracy of this method. A photocurrent as high as 0.4 μA is obtained, corresponding to a photoresponsivity of 0.48 mA/W. The device performs uniformly in nine illumination cycles. Project supported by the National Key Research and Development Program of China (No. 2016YFB0402404), the High-Tech Research and Development Program of China (Nos. 2013AA031401, 2015AA016902, 2015AA016904), and the National Natural Foundation of China (Nos. 61674136, 61176053, 61274069, 61435002).

Dual-Responsive Molecular Probe for Tumor Targeted Imaging and Photodynamic Therapy

PubMed Central

Meng, Xiaoqing; Yang, Yueting; Zhou, Lihua; Zhang, li; Lv, Yalin; Li, Sanpeng; Wu, Yayun; Zheng, Mingbin; Li, Wenjun; Gao, Guanhui; Deng, Guanjun; Jiang, Tao; Ni, Dapeng; Gong, Ping; Cai, Lintao

2017-01-01

The precision oncology significantly relies on the development of multifunctional agents to integrate tumor targeting, imaging and therapeutics. In this study, a first small-molecule theranostic probe, RhoSSCy is constructed by conjugating 5′-carboxyrhodamines (Rho) and heptamethine cyanine IR765 (Cy) using a reducible disulfide linker and pH tunable amino-group to realize thiols/pH dual sensing. In vitro experiments verify that RhoSSCy is highly sensitive for quantitative analysis and imaging intracellular pH gradient and biothiols. Furthermore, RhoSSCy shows superb tumor targeted dual-modal imaging via near-infrared fluorescence (NIRF) and photoacoustic (PA). Importantly, RhoSSCy also induces strongly reactive oxygen species for tumor photodynamic therapy (PDT) with robust antitumor activity both in vitro and in vivo. Such versatile small-molecule theranostic probe may be promising for tumor targeted imaging and precision therapy. PMID:28638467

An integrated clinical and genomic information system for cancer precision medicine.

PubMed

Jang, Yeongjun; Choi, Taekjin; Kim, Jongho; Park, Jisub; Seo, Jihae; Kim, Sangok; Kwon, Yeajee; Lee, Seungjae; Lee, Sanghyuk

2018-04-20

Increasing affordability of next-generation sequencing (NGS) has created an opportunity for realizing genomically-informed personalized cancer therapy as a path to precision oncology. However, the complex nature of genomic information presents a huge challenge for clinicians in interpreting the patient's genomic alterations and selecting the optimum approved or investigational therapy. An elaborate and practical information system is urgently needed to support clinical decision as well as to test clinical hypotheses quickly. Here, we present an integrated clinical and genomic information system (CGIS) based on NGS data analyses. Major components include modules for handling clinical data, NGS data processing, variant annotation and prioritization, drug-target-pathway analysis, and population cohort explorer. We built a comprehensive knowledgebase of genes, variants, drugs by collecting annotated information from public and in-house resources. Structured reports for molecular pathology are generated using standardized terminology in order to help clinicians interpret genomic variants and utilize them for targeted cancer therapy. We also implemented many features useful for testing hypotheses to develop prognostic markers from mutation and gene expression data. Our CGIS software is an attempt to provide useful information for both clinicians and scientists who want to explore genomic information for precision oncology.

Targeted knock-in of an scFv-Fc antibody gene into the hprt locus of Chinese hamster ovary cells using CRISPR/Cas9 and CRIS-PITCh systems.

PubMed

Kawabe, Yoshinori; Komatsu, Shinya; Komatsu, Shodai; Murakami, Mai; Ito, Akira; Sakuma, Tetsushi; Nakamura, Takahiro; Yamamoto, Takashi; Kamihira, Masamichi

2018-05-01

Chinese hamster ovary (CHO) cells have been used as host cells for the production of pharmaceutical proteins. For the high and stable production of target proteins, the transgene should be integrated into a suitable genomic locus of host cells. Here, we generated knock-in CHO cells, in which transgene cassettes without a vector backbone sequence were integrated into the hprt locus of the CHO genome using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 and CRISPR-mediated precise integration into target chromosome (CRIS-PITCh) systems. We investigated the efficiency of targeted knock-in of transgenes using these systems. As a practical example, we generated knock-in CHO cells producing an scFv-Fc antibody using the CRIS-PITCh system mediated by microhomology sequences for targeting. We found that the CRIS-PITCh system can facilitate targeted knock-in for CHO cell engineering. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering.

PubMed

Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M Teresa; Buchholz, Frank

2016-07-22

Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets.

The stimulus integration area for horizontal vergence.

PubMed

Allison, Robert S; Howard, Ian P; Fang, Xueping

2004-06-01

Over what region of space are horizontal disparities integrated to form the stimulus for vergence? The vergence system might be expected to respond to disparities within a small area of interest to bring them into the range of precise stereoscopic processing. However, the literature suggests that disparities are integrated over a fairly large parafoveal area. We report the results of six experiments designed to explore the spatial characteristics of the stimulus for vergence. Binocular eye movements were recorded using magnetic search coils. Each dichoptic display consisted of a central target stimulus that the subject attempted to fuse, and a competing stimulus with conflicting disparity. In some conditions the target was stationary, providing a fixation stimulus. In other conditions, the disparity of the target changed to provide a vergence-tracking stimulus. The target and competing stimulus were combined in a variety of conditions including those in which (1) a transparent textured-disc target was superimposed on a competing textured background, (2) a textured-disc target filled the centre of a competing annular background, and (3) a small target was presented within the centre of a competing annular background of various inner diameters. In some conditions the target and competing stimulus were separated in stereoscopic depth. The results are consistent with a disparity integration area with a diameter of about 5 degrees. Stimuli beyond this integration area can drive vergence in their own right, but they do not appear to be summed or averaged with a central stimulus to form a combined disparity signal. A competing stimulus had less effect on vergence when separated from the target by a disparity pedestal. As a result, we propose that it may be more useful to think in terms of an integration volume for vergence rather than a two-dimensional retinal integration area.

Flight test integration and evaluation of the LANTIRN system on the F-15E

NASA Astrophysics Data System (ADS)

Presuhn, Gary G.; Zeis, Joseph E.

1991-08-01

In today's high threat arena of air combat, the need to fly low, penetrate enemy defenses, strike effectively, and safely return to base is more valid than ever. The F-15E is designed to accomplish just that type of mission scenario, regardless of weather and time of day. In order to accomplish this demanding profile, any such aircraft requires terrain-following equipment and precision target designation. The LANTIRN system on the F-15E is designed to fulfill that role. This paper examines the two major aspects of the LANTIRN system found on the F-15E: the Navigation Pod and the Targeting Pod, and investigates flight test issues during F-15E integration testing. The Navigation Pod consists of two major subsystems, the Fixed Imaging Navigation Sensor (FINS) and the terrain following radar (TFR). Discussion of the FINS centers around the integration issues of the system and its utility in the night low level environment, as determined through flight test. In providing a 'window on the world,' this aspect of the LANTIRN system provides unique capabilities in navigation as well as weapons delivery. The TFR, the other major subsystem, is a continuation of the F-111 and RF-4 terrain following systems. While an effective system, integration of the TFR into the F-15E has been a challenge to the flight test community, with many lessons to be learned. The Targeting Pod is the second component of the LANTIRN system. Its purpose is to acquire and designate a target through use of its selectable dual field of view infrared sensor and laser ranger/designator. The laser also provides terminal guidance capability for precision guided weapons. Integration of the Targeting Pod into the avionics suite of the F-15E has provided classic examples of systems flight testing, evaluating both the technical and performance aspects of the pod, as well as the key human factors interface. The overall intent of this paper is to describe avionics testing, as applied to low level navigation and targeting systems, and to discuss lessons learned in that process, both of a specific and a general nature.

Super-resolution imaging applied to moving object tracking

NASA Astrophysics Data System (ADS)

Swalaganata, Galandaru; Ratna Sulistyaningrum, Dwi; Setiyono, Budi

2017-10-01

Moving object tracking in a video is a method used to detect and analyze changes that occur in an object that being observed. Visual quality and the precision of the tracked target are highly wished in modern tracking system. The fact that the tracked object does not always seem clear causes the tracking result less precise. The reasons are low quality video, system noise, small object, and other factors. In order to improve the precision of the tracked object especially for small object, we propose a two step solution that integrates a super-resolution technique into tracking approach. First step is super-resolution imaging applied into frame sequences. This step was done by cropping the frame in several frame or all of frame. Second step is tracking the result of super-resolution images. Super-resolution image is a technique to obtain high-resolution images from low-resolution images. In this research single frame super-resolution technique is proposed for tracking approach. Single frame super-resolution was a kind of super-resolution that it has the advantage of fast computation time. The method used for tracking is Camshift. The advantages of Camshift was simple calculation based on HSV color that use its histogram for some condition and color of the object varies. The computational complexity and large memory requirements required for the implementation of super-resolution and tracking were reduced and the precision of the tracked target was good. Experiment showed that integrate a super-resolution imaging into tracking technique can track the object precisely with various background, shape changes of the object, and in a good light conditions.

Flexible integration of free-standing nanowires into silicon photonics.

PubMed

Chen, Bigeng; Wu, Hao; Xin, Chenguang; Dai, Daoxin; Tong, Limin

2017-06-14

Silicon photonics has been developed successfully with a top-down fabrication technique to enable large-scale photonic integrated circuits with high reproducibility, but is limited intrinsically by the material capability for active or nonlinear applications. On the other hand, free-standing nanowires synthesized via a bottom-up growth present great material diversity and structural uniformity, but precisely assembling free-standing nanowires for on-demand photonic functionality remains a great challenge. Here we report hybrid integration of free-standing nanowires into silicon photonics with high flexibility by coupling free-standing nanowires onto target silicon waveguides that are simultaneously used for precise positioning. Coupling efficiency between a free-standing nanowire and a silicon waveguide is up to ~97% in the telecommunication band. A hybrid nonlinear-free-standing nanowires-silicon waveguides Mach-Zehnder interferometer and a racetrack resonator for significantly enhanced optical modulation are experimentally demonstrated, as well as hybrid active-free-standing nanowires-silicon waveguides circuits for light generation. These results suggest an alternative approach to flexible multifunctional on-chip nanophotonic devices.Precisely assembling free-standing nanowires for on-demand photonic functionality remains a challenge. Here, Chen et al. integrate free-standing nanowires into silicon waveguides and show all-optical modulation and light generation on silicon photonic chips.

Islander: A database of precisely mapped genomic islands in tRNA and tmRNA genes

DOE PAGES

Hudson, Corey M.; Lau, Britney Y.; Williams, Kelly P.

2014-11-05

Genomic islands are mobile DNAs that are major agents of bacterial and archaeal evolution. Integration into prokaryotic chromosomes usually occurs site-specifically at tRNA or tmRNA gene (together, tDNA) targets, catalyzed by tyrosine integrases. This splits the target gene, yet sequences within the island restore the disrupted gene; the regenerated target and its displaced fragment precisely mark the endpoints of the island. We applied this principle to search for islands in genomic DNA sequences. Our algorithm identifies tDNAs, finds fragments of those tDNAs in the same replicon and removes unlikely candidate islands through a series of filters. A search for islandsmore » in 2168 whole prokaryotic genomes produced 3919 candidates. The website Islander (recently moved to http://bioinformatics.sandia.gov/islander/) presents these precisely mapped candidate islands, the gene content and the island sequence. The algorithm further insists that each island encode an integrase, and attachment site sequence identity is carefully noted; therefore, the database also serves in the study of integrase site-specificity and its evolution.« less

An Inertial Dual-State State Estimator for Precision Planetary Landing with Hazard Detection and Avoidance

NASA Technical Reports Server (NTRS)

Bishop, Robert H.; DeMars, Kyle; Trawny, Nikolas; Crain, Tim; Hanak, Chad; Carson, John M.; Christian, John

2016-01-01

The navigation filter architecture successfully deployed on the Morpheus flight vehicle is presented. The filter was developed as a key element of the NASA Autonomous Landing and Hazard Avoidance Technology (ALHAT) project and over the course of 15 free fights was integrated into the Morpheus vehicle, operations, and flight control loop. Flight testing completed by demonstrating autonomous hazard detection and avoidance, integration of an altimeter, surface relative velocity (velocimeter) and hazard relative navigation (HRN) measurements into the onboard dual-state inertial estimator Kalman flter software, and landing within 2 meters of the vertical testbed GPS-based navigation solution at the safe landing site target. Morpheus followed a trajectory that included an ascent phase followed by a partial descent-to-landing, although the proposed filter architecture is applicable to more general planetary precision entry, descent, and landings. The main new contribution is the incorporation of a sophisticated hazard relative navigation sensor-originally intended to locate safe landing sites-into the navigation system and employed as a navigation sensor. The formulation of a dual-state inertial extended Kalman filter was designed to address the precision planetary landing problem when viewed as a rendezvous problem with an intended landing site. For the required precision navigation system that is capable of navigating along a descent-to-landing trajectory to a precise landing, the impact of attitude errors on the translational state estimation are included in a fully integrated navigation structure in which translation state estimation is combined with attitude state estimation. The map tie errors are estimated as part of the process, thereby creating a dual-state filter implementation. Also, the filter is implemented using inertial states rather than states relative to the target. External measurements include altimeter, velocimeter, star camera, terrain relative navigation sensor, and a hazard relative navigation sensor providing information regarding hazards on a map generated on-the-fly.

Spectrum syntheses of high-resolution integrated light spectra of Galactic globular clusters

NASA Astrophysics Data System (ADS)

Sakari, Charli M.; Shetrone, Matthew; Venn, Kim; McWilliam, Andrew; Dotter, Aaron

2013-09-01

Spectrum syntheses for three elements (Mg, Na and Eu) in high-resolution integrated light spectra of the Galactic globular clusters 47 Tuc, M3, M13, NGC 7006 and M15 are presented, along with calibration syntheses of the solar and Arcturus spectra. Iron abundances in the target clusters are also derived from integrated light equivalent width analyses. Line profiles in the spectra of these five globular clusters are well fitted after careful consideration of the atomic and molecular spectral features, providing levels of precision that are better than equivalent width analyses of the same integrated light spectra, and that are comparable to the precision in individual stellar analyses. The integrated light abundances from the 5528 and 5711 Å Mg I lines, the 6154 and 6160 Å Na I lines, and the 6645 Å Eu II line fall within the observed ranges from individual stars; however, these integrated light abundances do not always agree with the average literature abundances. Tests with the second parameter clusters M3, M13 and NGC 7006 show that assuming an incorrect horizontal branch morphology is likely to have only a small ( ≲ 0.06 dex) effect on these Mg, Na and Eu abundances. These tests therefore show that integrated light spectrum syntheses can be applied to unresolved globular clusters over a wide range of metallicities and horizontal branch morphologies. Such high precision in integrated light spectrum syntheses is valuable for interpreting the chemical abundances of globular cluster systems around other galaxies.

Spatiotemporal genomic architecture informs precision oncology in glioblastoma

PubMed Central

Lee, Jin-Ku; Wang, Jiguang; Sa, Jason K.; Ladewig, Erik; Lee, Hae-Ock; Lee, In-Hee; Kang, Hyun Ju; Rosenbloom, Daniel S.; Camara, Pablo G.; Liu, Zhaoqi; van Nieuwenhuizen, Patrick; Jung, Sang Won; Choi, Seung Won; Kim, Junhyung; Chen, Andrew; Kim, Kyu-Tae; Shin, Sang; Seo, Yun Jee; Oh, Jin-Mi; Shin, Yong Jae; Park, Chul-Kee; Kong, Doo-Sik; Seol, Ho Jun; Blumberg, Andrew; Lee, Jung-Il; Iavarone, Antonio; Park, Woong-Yang; Rabadan, Raul; Nam, Do-Hyun

2017-01-01

Precision medicine in cancer proposes that genomic characterization of tumors can inform personalized targeted therapies1–5. This proposition, however, is complicated by spatial and temporal heterogeneity6–14. Here we study genomic and expression profiles across 127 multi-sector or longitudinal specimens from 52 glioblastoma (GBM) patients. Using bulk and single-cell data, we find that samples from the same tumor mass share genomic and expression signatures, while geographically separated multifocal tumors and/or long-term recurrent tumors are seeded from different clones. Chemical screening of patient-derived glioma cells (PDCs) shows that therapeutic response is associated to genetic similarity, and multifocal tumors enriched with PIK3CA mutations have a heterogeneous drug response pattern. Importantly, we show that targeting truncal events is more efficacious in reducing tumor burden. In summary, this work demonstrates that evolutionary inference from integrated genomic analysis in multi-sector biopsies can inform targeted therapeutic interventions for GBM patients. PMID:28263318

Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering

PubMed Central

Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M. Teresa; Buchholz, Frank

2016-01-01

Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets. PMID:27444945

Precision Landing and Hazard Avoidance Doman

NASA Technical Reports Server (NTRS)

Robertson, Edward A.; Carson, John M., III

2016-01-01

The Precision Landing and Hazard Avoidance (PL&HA) domain addresses the development, integration, testing, and spaceflight infusion of sensing, processing, and GN&C functions critical to the success and safety of future human and robotic exploration missions. PL&HA sensors also have applications to other mission events, such as rendezvous and docking. Autonomous PL&HA builds upon the core GN&C capabilities developed to enable soft, controlled landings on the Moon, Mars, and other solar system bodies. Through the addition of a Terrain Relative Navigation (TRN) function, precision landing within tens of meters of a map-based target is possible. The addition of a 3-D terrain mapping lidar sensor improves the probability of a safe landing via autonomous, real-time Hazard Detection and Avoidance (HDA). PL&HA significantly improves the probability of mission success and enhances access to sites of scientific interest located in challenging terrain. PL&HA can also utilize external navigation aids, such as navigation satellites and surface beacons. Advanced Lidar Sensors High precision ranging, velocimetry, and 3-D terrain mapping Terrain Relative Navigation (TRN) TRN compares onboard reconnaissance data with real-time terrain imaging data to update the S/C position estimate Hazard Detection and Avoidance (HDA) Generates a high-resolution, 3-D terrain map in real-time during the approach trajectory to identify safe landing targets Inertial Navigation During Terminal Descent High precision surface relative sensors enable accurate inertial navigation during terminal descent and a tightly controlled touchdown within meters of the selected safe landing target.

Optical, mechanical and electronic design and integration of POMM, a polarimeter for the Observatoire du mont Mégantic

NASA Astrophysics Data System (ADS)

Leclerc, Melanie R.; Côté, Patrice; Duchesne, François; Bastien, Pierre; Hernandez, Olivier; Colonna d'Istria, Pierre; Demers, Mathieu; Girard, Marc; Savard, Maxime; Lemieux, Dany; Thibault, Simon; Brousseau, Denis

2014-08-01

A polarimeter, to observe exoplanets in the visible and infrared, was built for the "Observatoire du Mont Mégantic" (OMM) to replace an existing instrument and reach 10-6 precision, a factor 100 improvement. The optical and mechanical designs are presented, with techniques used to precisely align the optical components and rotation axes to achieve the targeted precision. A photo-elastic modulator (PEM) and a lock-in amplifier are used to measure the polarization. The typical signal is a high DC superimposed to a very faint sinusoidal oscillation. Custom electronics was developed to measure the AC and DC amplitudes, and characterization results are presented.

Homologous Recombination-Independent Large Gene Cassette Knock-in in CHO Cells Using TALEN and MMEJ-Directed Donor Plasmids

PubMed Central

Sakuma, Tetsushi; Takenaga, Mitsumasa; Kawabe, Yoshinori; Nakamura, Takahiro; Kamihira, Masamichi; Yamamoto, Takashi

2015-01-01

Gene knock-in techniques have rapidly evolved in recent years, along with the development and maturation of genome editing technology using programmable nucleases. We recently reported a novel strategy for microhomology-mediated end-joining-dependent integration of donor DNA by using TALEN or CRISPR/Cas9 and optimized targeting vectors, named PITCh (Precise Integration into Target Chromosome) vectors. Here we describe TALEN and PITCh vector-mediated integration of long gene cassettes, including a single-chain Fv-Fc (scFv-Fc) gene, in Chinese hamster ovary (CHO) cells, with comparison of targeting and cloning efficiency among several donor design and culture conditions. We achieved 9.6-kb whole plasmid integration and 7.6-kb backbone-free integration into a defined genomic locus in CHO cells. Furthermore, we confirmed the reasonable productivity of recombinant scFv-Fc protein of the knock-in cells. Using our protocol, the knock-in cell clones could be obtained by a single transfection and a single limiting dilution using a 96-well plate, without constructing targeting vectors containing long homology arms. Thus, the study described herein provides a highly practical strategy for gene knock-in of large DNA in CHO cells, which accelerates high-throughput generation of cell lines stably producing any desired biopharmaceuticals, including huge antibody proteins. PMID:26473830

Homologous Recombination-Independent Large Gene Cassette Knock-in in CHO Cells Using TALEN and MMEJ-Directed Donor Plasmids.

PubMed

Sakuma, Tetsushi; Takenaga, Mitsumasa; Kawabe, Yoshinori; Nakamura, Takahiro; Kamihira, Masamichi; Yamamoto, Takashi

2015-10-09

Gene knock-in techniques have rapidly evolved in recent years, along with the development and maturation of genome editing technology using programmable nucleases. We recently reported a novel strategy for microhomology-mediated end-joining-dependent integration of donor DNA by using TALEN or CRISPR/Cas9 and optimized targeting vectors, named PITCh (Precise Integration into Target Chromosome) vectors. Here we describe TALEN and PITCh vector-mediated integration of long gene cassettes, including a single-chain Fv-Fc (scFv-Fc) gene, in Chinese hamster ovary (CHO) cells, with comparison of targeting and cloning efficiency among several donor design and culture conditions. We achieved 9.6-kb whole plasmid integration and 7.6-kb backbone-free integration into a defined genomic locus in CHO cells. Furthermore, we confirmed the reasonable productivity of recombinant scFv-Fc protein of the knock-in cells. Using our protocol, the knock-in cell clones could be obtained by a single transfection and a single limiting dilution using a 96-well plate, without constructing targeting vectors containing long homology arms. Thus, the study described herein provides a highly practical strategy for gene knock-in of large DNA in CHO cells, which accelerates high-throughput generation of cell lines stably producing any desired biopharmaceuticals, including huge antibody proteins.

Broadband laser ranging precision and accuracy experiments with PDV benchmarking

NASA Astrophysics Data System (ADS)

Catenacci, Jared; Daykin, Ed; Howard, Marylesa; Lalone, Brandon; Miller, Kirk

2017-06-01

Broadband laser ranging (BLR) is a developmental diagnostic designed to measure the precise position of surfaces and particle clouds moving at velocities of several kilometers per second. Recent single stage gas gun experiments were conducted to quantify the precision and accuracy possible with a typical BLR system. For these experiments, the position of a mirrored projectile is measured relative to the location of a stationary optical flat (uncoated window) mounted within the gun catch tank. Projectile velocity is constrained to one-dimensional motion within the gun barrel. A collimating probe is aligned to be orthogonal to both the target window and the mirrored impactor surface. The probe is used to simultaneously measure the position and velocity with a BLR and conventional Photonic Doppler Velocimetry (PDV) system. Since there is a negligible lateral component to the target velocity, coupled with strong signal returns from a mirrored surface, integrating the PDV measurement provides a high fidelity distance measurement reference to which the BLR measurement may be compared.

Tweaking Dendrimers and Dendritic Nanoparticles for Controlled Nano-bio Interactions: Potential Nanocarriers for Improved Cancer Targeting

PubMed Central

Bugno, Jason; Hsu, Hao-Jui; Hong, Seungpyo

2016-01-01

Nanoparticles have shown great promise in the treatment of cancer, with a demonstrated potential in targeted drug delivery. Among a myriad of nanocarriers that have been recently developed, dendrimers have attracted a great deal of scientific interests due to their unique chemical and structural properties that allow for precise engineering of their characteristics. Despite this, the clinical translation of dendrimers has been hindered due to their drawbacks, such as scale-up issues, rapid systemic elimination, inefficient tumor accumulation, and limited drug loading. In order to overcome these limitations, a series of reengineered dendrimers have been recently introduced using various approaches, including: i) modifications of structure and surfaces; ii) integration with linear polymers; and iii) hybridization with other types of nanocarriers. Chemical modifications and surface engineering have tailored dendrimers to improve their pharmacokinetics and tissue permeation. Copolymerization of dendritic polymers with linear polymers has resulted in various amphiphilic copolymers with self-assembly capabilities and improved drug loading efficiencies. Hybridization with other nanocarriers integrates advantageous characteristics of both systems, which includes prolonged plasma circulation times and enhanced tumor targeting. This review provides a comprehensive summary of the newly emerging drug delivery systems that involve reengineering of dendrimers in an effort to precisely control their nano-bio interactions, mitigating their inherent weaknesses. PMID:26453160

Harnessing Integrative Omics to Facilitate Molecular Imaging of the Human Epidermal Growth Factor Receptor Family for Precision Medicine.

PubMed

Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E

2017-01-01

Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.

Chemiresistive and Gravimetric Dual-Mode Gas Sensor toward Target Recognition and Differentiation.

PubMed

Chen, Yan; Zhang, Hao; Feng, Zhihong; Zhang, Hongxiang; Zhang, Rui; Yu, Yuanyuan; Tao, Jin; Zhao, Hongyuan; Guo, Wenlan; Pang, Wei; Duan, Xuexin; Liu, Jing; Zhang, Daihua

2016-08-24

We demonstrate a dual-mode gas sensor for simultaneous and independent acquisition of electrical and mechanical signals from the same gas adsorption event. The device integrates a graphene field-effect transistor (FET) with a piezoelectric resonator in a seamless manner by leveraging multiple structural and functional synergies. Dual signals resulting from independent physical processes, i.e., mass attachment and charge transfer can reflect intrinsic properties of gas molecules and potentially enable target recognition and quantification at the same time. Fabrication of the device is based on standard Integrated Circuit (IC) foundry processes and fully compatible with system-on-a-chip (SoC) integration to achieve extremely small form factors. In addition, the ability of simultaneous measurements of mass adsorption and charge transfer guides us to a more precise understanding of the interactions between graphene and various gas molecules. Besides its practical functions, the device serves as an effective tool to quantitatively investigate the physical processes and sensing mechanisms for a large library of sensing materials and target analytes.

Ambient Optomechanical Alignment and Pupil Metrology for the Flight Instruments Aboard the James Webb Space Telescope

NASA Technical Reports Server (NTRS)

Coulter, Phillip; Beaton, Alexander; Gum, Jeffrey S.; Hadjimichael, Theodore J.; Hayden, Joseph E.; Hummel, Susann; Hylan, Jason E.; Lee, David; Madison, Timothy J.; Maszkiewicz, Michael;

Integrated regulation of motor-driven organelle transport by scaffolding proteins.

PubMed

Fu, Meng-meng; Holzbaur, Erika L F

2014-10-01

Intracellular trafficking pathways, including endocytosis, autophagy, and secretion, rely on directed organelle transport driven by the opposing microtubule motor proteins kinesin and dynein. Precise spatial and temporal targeting of vesicles and organelles requires the integrated regulation of these opposing motors, which are often bound simultaneously to the same cargo. Recent progress demonstrates that organelle-associated scaffolding proteins, including Milton/TRAKs (trafficking kinesin-binding protein), JIP1, JIP3 (JNK-interacting proteins), huntingtin, and Hook1, interact with molecular motors to coordinate activity and sustain unidirectional transport. Scaffolding proteins also bind to upstream regulatory proteins, including kinases and GTPases, to modulate transport in the cell. This integration of regulatory control with motor activity allows for cargo-specific changes in the transport or targeting of organelles in response to cues from the complex cellular environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

A Precision Medicine Initiative for Alzheimer's disease: the road ahead to biomarker-guided integrative disease modeling.

PubMed

Hampel, H; O'Bryant, S E; Durrleman, S; Younesi, E; Rojkova, K; Escott-Price, V; Corvol, J-C; Broich, K; Dubois, B; Lista, S

2017-04-01

After intense scientific exploration and more than a decade of failed trials, Alzheimer's disease (AD) remains a fatal global epidemic. A traditional research and drug development paradigm continues to target heterogeneous late-stage clinically phenotyped patients with single 'magic bullet' drugs. Here, we propose that it is time for a paradigm shift towards the implementation of precision medicine (PM) for enhanced risk screening, detection, treatment, and prevention of AD. The overarching structure of how PM for AD can be achieved will be provided through the convergence of breakthrough technological advances, including big data science, systems biology, genomic sequencing, blood-based biomarkers, integrated disease modeling and P4 medicine. It is hypothesized that deconstructing AD into multiple genetic and biological subsets existing within this heterogeneous target population will provide an effective PM strategy for treating individual patients with the specific agent(s) that are likely to work best based on the specific individual biological make-up. The Alzheimer's Precision Medicine Initiative (APMI) is an international collaboration of leading interdisciplinary clinicians and scientists devoted towards the implementation of PM in Neurology, Psychiatry and Neuroscience. It is hypothesized that successful realization of PM in AD and other neurodegenerative diseases will result in breakthrough therapies, such as in oncology, with optimized safety profiles, better responder rates and treatment responses, particularly through biomarker-guided early preclinical disease-stage clinical trials.

Recurrent Targeted Genes of Hepatitis B Virus in the Liver Cancer Genomes Identified by a Next-Generation Sequencing–Based Approach

PubMed Central

Ding, Dong; Lou, Xiaoyan; Hua, Dasong; Yu, Wei; Li, Lisha; Wang, Jun; Gao, Feng; Zhao, Na; Ren, Guoping; Li, Lanjuan; Lin, Biaoyang

2012-01-01

Integration of the viral DNA into host chromosomes was found in most of the hepatitis B virus (HBV)–related hepatocellular carcinomas (HCCs). Here we devised a massive anchored parallel sequencing (MAPS) method using next-generation sequencing to isolate and sequence HBV integrants. Applying MAPS to 40 pairs of HBV–related HCC tissues (cancer and adjacent tissues), we identified 296 HBV integration events corresponding to 286 unique integration sites (UISs) with precise HBV–Human DNA junctions. HBV integration favored chromosome 17 and preferentially integrated into human transcript units. HBV targeted genes were enriched in GO terms: cAMP metabolic processes, T cell differentiation and activation, TGF beta receptor pathway, ncRNA catabolic process, and dsRNA fragmentation and cellular response to dsRNA. The HBV targeted genes include 7 genes (PTPRJ, CNTN6, IL12B, MYOM1, FNDC3B, LRFN2, FN1) containing IPR003961 (Fibronectin, type III domain), 7 genes (NRG3, MASP2, NELL1, LRP1B, ADAM21, NRXN1, FN1) containing IPR013032 (EGF-like region, conserved site), and three genes (PDE7A, PDE4B, PDE11A) containing IPR002073 (3′, 5′-cyclic-nucleotide phosphodiesterase). Enriched pathways include hsa04512 (ECM-receptor interaction), hsa04510 (Focal adhesion), and hsa04012 (ErbB signaling pathway). Fewer integration events were found in cancers compared to cancer-adjacent tissues, suggesting a clonal expansion model in HCC development. Finally, we identified 8 genes that were recurrent target genes by HBV integration including fibronectin 1 (FN1) and telomerase reverse transcriptase (TERT1), two known recurrent target genes, and additional novel target genes such as SMAD family member 5 (SMAD5), phosphatase and actin regulator 4 (PHACTR4), and RNA binding protein fox-1 homolog (C. elegans) 1 (RBFOX1). Integrating analysis with recently published whole-genome sequencing analysis, we identified 14 additional recurrent HBV target genes, greatly expanding the HBV recurrent target list. This global survey of HBV integration events, together with recently published whole-genome sequencing analyses, furthered our understanding of the HBV–related HCC. PMID:23236287

Transgene manipulation in zebrafish by using recombinases.

PubMed

Dong, Jie; Stuart, Gary W

2004-01-01

Although much remains to be done, our results to date suggest that efficient and precise genome engineering in zebrafish will be possible in the future by using Cre recombinase and SB transposase in combination with their respective target sites. In this study, we provide the first evidence that Cre recombinase can mediate effective site-specific deletion of transgenes in zebrafish. We found that the efficiency of target site utilization could approach 100%, independent of whether the target site was provided transiently by injection or stably within an integrated transgene. Microinjection of Cre mRNA appeared to be slightly more effective for this purpose than microinjection of Cre-expressing plasmid DNA. Our work has not yet progressed to the point where SB-mediated mobilization of our transgene constructs would be observed. However, a recent report has demonstrated that SB can enhance transgenesis rates sixfold over conventional methods by efficiently mediating multiple single-copy insertion of transgenes into the zebrafish genome (Davidson et al., 2003). Therefore, it seems likely that a combined system should eventually allow both SB-mediated transgene mobilization and Cre-mediated transgene modification. Our goal is to validate methods for the precise reengineering of the zebrafish genome by using a combination of Cre-loxP and SB transposon systems. These methods can be used to delete, replace, or mobilize large pieces of DNA or to modify the genome only when and where required by the investigator. For example, it should be possible to deliver particular RNAi genes to well-expressed chromosomal loci and then exchange them easily with alternative RNAi genes for the specific suppression of alternative targets. As a nonviral vector for gene therapy, the transposon component allows for the possibility of highly efficient integration, whereas the Cre-loxP component can target the integration and/or exchange of foreign DNA into specific sites within the genome. The specificity and efficiency of this system also make it ideal for applications in which precise genome modifications are required (e.g., stock improvement). Future work should establish whether alternative recombination systems (e.g., phiC31 integrase) can improve the utility of this system. After the fish system is fully established, it would be interesting to explore its application to genome engineering in other organisms.

Leveraging 3D chemical similarity, target and phenotypic data in the identification of drug-protein and drug-adverse effect associations.

PubMed

Vilar, Santiago; Hripcsak, George

2016-01-01

Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug-target and drug-adverse effect discovery. In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug-adverse effects. In the first step, we generated a system for multiple drug-target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects.

Network-based machine learning and graph theory algorithms for precision oncology.

PubMed

Zhang, Wei; Chien, Jeremy; Yong, Jeongsik; Kuang, Rui

2017-01-01

Network-based analytics plays an increasingly important role in precision oncology. Growing evidence in recent studies suggests that cancer can be better understood through mutated or dysregulated pathways or networks rather than individual mutations and that the efficacy of repositioned drugs can be inferred from disease modules in molecular networks. This article reviews network-based machine learning and graph theory algorithms for integrative analysis of personal genomic data and biomedical knowledge bases to identify tumor-specific molecular mechanisms, candidate targets and repositioned drugs for personalized treatment. The review focuses on the algorithmic design and mathematical formulation of these methods to facilitate applications and implementations of network-based analysis in the practice of precision oncology. We review the methods applied in three scenarios to integrate genomic data and network models in different analysis pipelines, and we examine three categories of network-based approaches for repositioning drugs in drug-disease-gene networks. In addition, we perform a comprehensive subnetwork/pathway analysis of mutations in 31 cancer genome projects in the Cancer Genome Atlas and present a detailed case study on ovarian cancer. Finally, we discuss interesting observations, potential pitfalls and future directions in network-based precision oncology.

Control of second-harmonic generation in doubly resonant aluminum nitride microrings to address a rubidium two-photon clock transition.

PubMed

Surya, Joshua B; Guo, Xiang; Zou, Chang-Ling; Tang, Hong X

2018-06-01

Nonlinear optical effects have been studied extensively in microresonators as more photonics applications transitions to integrated on-chip platforms. Due to low optical losses and small mode volumes, microresonators are demonstrably the state-of-the-art platform for second-harmonic generation (SHG). However, the working bandwidth of such microresonator-based devices is relatively small, presenting a challenge for applications where a specifically targeted wavelength needs to be addressed. In this Letter, we analyze the phase-matching window and resonance wavelength with respect to varying microring widths, radii, and temperatures. A chip with precise design parameters was fabricated with phase matching realized at the exact wavelength of a two-photon transition of Rb85. This procedure can be generalized to any target pump wavelength in the telecom band with picometer precision.

Human Microbiome and Learning Healthcare Systems: Integrating Research and Precision Medicine for Inflammatory Bowel Disease

PubMed Central

Chuong, Kim H.; Mack, David R.; Stintzi, Alain

2018-01-01

Abstract Healthcare institutions face widespread challenges of delivering high-quality and cost-effective care, while keeping up with rapid advances in biomedical knowledge and technologies. Moreover, there is increased emphasis on developing personalized or precision medicine targeted to individuals or groups of patients who share a certain biomarker signature. Learning healthcare systems (LHS) have been proposed for integration of research and clinical practice to fill major knowledge gaps, improve care, reduce healthcare costs, and provide precision care. To date, much discussion in this context has focused on the potential of human genomic data, and not yet on human microbiome data. Rapid advances in human microbiome research suggest that profiling of, and interventions on, the human microbiome can provide substantial opportunity for improved diagnosis, therapeutics, risk management, and risk stratification. In this study, we discuss a potential role for microbiome science in LHSs. We first review the key elements of LHSs, and discuss possibilities of Big Data and patient engagement. We then consider potentials and challenges of integrating human microbiome research into clinical practice as part of an LHS. With rapid growth in human microbiome research, patient-specific microbial data will begin to contribute in important ways to precision medicine. Hence, we discuss how patient-specific microbial data can help guide therapeutic decisions and identify novel effective approaches for precision care of inflammatory bowel disease. To the best of our knowledge, this expert analysis makes an original contribution with new insights poised at the emerging intersection of LHSs, microbiome science, and postgenomics medicine. PMID:28282257

Integrated cockpit design for the Army helicopter improvement program

NASA Technical Reports Server (NTRS)

Drennen, T.; Bowen, B.

1984-01-01

The main Army Helicopter Improvement Program (AHIP) mission is to navigate precisely, locate targets accurately, communicate their position to other battlefield elements, and to designate them for laser guided weapons. The onboard navigation and mast-mounted sight (MMS) avionics enable accurate tracking of current aircraft position and subsequent target location. The AHIP crewstation development was based on extensive mission/task analysis, function allocation, total system design, and test and verification. The avionics requirements to meet the mission was limited by the existing aircraft structural and performance characteristics and resultant space, weight, and power restrictions. These limitations and night operations requirement led to the use of night vision goggles. The combination of these requirements and limitations dictated an integrated control/display approach using multifunction displays and controls.

Precision Medicine in Head and Neck Cancer: Myth or Reality?

PubMed

Malone, Eoghan; Siu, Lillian L

2018-01-01

Standard treatment in head and neck squamous cell carcinoma (HNSCC) is limited currently with decisions being made primarily based on tumor location, histology, and stage. The role of the human papillomavirus in risk stratification is actively under clinical trial evaluations. The molecular complexity and intratumoral heterogeneity of the disease are not actively integrated into management decisions of HNSCC, despite a growing body of knowledge in these areas. The advent of the genomic era has delivered vast amounts of information regarding different cancer subtypes and is providing new therapeutic targets, which can potentially be elucidated using next-generation sequencing and other modern technologies. The task ahead is to expand beyond the existent armamentarium by exploiting beyond the genome and perform integrative analysis using innovative systems biology methods, with the goal to deliver effective precision medicine-based theragnostic options in HNSCC.

Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology

PubMed Central

Hart, Thomas; Dider, Shihab; Han, Weiwei; Xu, Hua; Zhao, Zhongming; Xie, Lei

2016-01-01

Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin’s molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally verified the interactions between metformin and our top-ranked kinase targets. Notably, kinases, particularly SGK1 and EGFR were identified as key molecular targets of metformin. Subsequently, we linked these putative binding targets to genes that do not directly bind to metformin but whose expressions are altered by metformin through protein-protein interactions, and identified network biomarkers of phenotypic response of metformin. The molecular targets and the key nodes in genetic networks are largely consistent with the existing experimental evidence. Their interactions can be affected by the observed cancer mutations. This study will shed new light into repurposing metformin for safe, effective, personalized therapies. PMID:26841718

Cas9-Guide RNA Directed Genome Editing in Soybean[OPEN

PubMed Central

Li, Zhongsen; Liu, Zhan-Bin; Xing, Aiqiu; Moon, Bryan P.; Koellhoffer, Jessica P.; Huang, Lingxia; Ward, R. Timothy; Clifton, Elizabeth; Falco, S. Carl; Cigan, A. Mark

2015-01-01

Recently discovered bacteria and archaea adaptive immune system consisting of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) endonuclease has been explored in targeted genome editing in different species. Streptococcus pyogenes Cas9-guide RNA (gRNA) was successfully applied to generate targeted mutagenesis, gene integration, and gene editing in soybean (Glycine max). Two genomic sites, DD20 and DD43 on chromosome 4, were mutagenized with frequencies of 59% and 76%, respectively. Sequencing randomly selected transgenic events confirmed that the genome modifications were specific to the Cas9-gRNA cleavage sites and consisted of small deletions or insertions. Targeted gene integrations through homology-directed recombination were detected by border-specific polymerase chain reaction analysis for both sites at callus stage, and one DD43 homology-directed recombination event was transmitted to T1 generation. T1 progenies of the integration event segregated according to Mendelian laws and clean homozygous T1 plants with the donor gene precisely inserted at the DD43 target site were obtained. The Cas9-gRNA system was also successfully applied to make a directed P178S mutation of acetolactate synthase1 gene through in planta gene editing. PMID:26294043

Differential phosphorylation of Smad1 integrates BMP and neurotrophin pathways through Erk/Dusp in axon development.

PubMed

Finelli, Mattéa J; Murphy, Kevin J; Chen, Lei; Zou, Hongyan

2013-05-30

Sensory axon development requires concerted actions of growth factors for the precise control of axonal outgrowth and target innervation. How developing sensory neurons integrate different cues is poorly understood. We demonstrate here that Smad1 activation is required for neurotrophin-mediated sensory axon growth in vitro and in vivo. Through differential phosphorylation, Smad1 exerts transcriptional selectivity to regulate the expression and activity of Erk1 and Erk2-two key neurotrophin effectors. Specifically, bone morphogenetic proteins (BMPs) signal through carboxy-terminal phosphorylation of Smad1 (pSmad1C) to induce Erk1/2 transcription for enhanced neurotrophin responsiveness. Meanwhile, neurotrophin signaling results in linker phosphorylation of Smad1 (pSmad1L), which in turn upregulates an Erk-specific dual-specificity phosphatase, Dusp6, leading to reduced pErk1/2 and constituting a negative-feedback loop for the prevention of axon overgrowth. Together, the BMP and neurotrophin pathways form a tightly regulated signaling network with a balanced ratio of Erk1/2 and pErk1/2 to direct the precise connections between sensory neurons and peripheral targets. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Precision instrument placement using a 4-DOF robot with integrated fiducials for minimally invasive interventions

NASA Astrophysics Data System (ADS)

Stenzel, Roland; Lin, Ralph; Cheng, Peng; Kronreif, Gernot; Kornfeld, Martin; Lindisch, David; Wood, Bradford J.; Viswanathan, Anand; Cleary, Kevin

2007-03-01

Minimally invasive procedures are increasingly attractive to patients and medical personnel because they can reduce operative trauma, recovery times, and overall costs. However, during these procedures, the physician has a very limited view of the interventional field and the exact position of surgical instruments. We present an image-guided platform for precision placement of surgical instruments based upon a small four degree-of-freedom robot (B-RobII; ARC Seibersdorf Research GmbH, Vienna, Austria). This platform includes a custom instrument guide with an integrated spiral fiducial pattern as the robot's end-effector, and it uses intra-operative computed tomography (CT) to register the robot to the patient directly before the intervention. The physician can then use a graphical user interface (GUI) to select a path for percutaneous access, and the robot will automatically align the instrument guide along this path. Potential anatomical targets include the liver, kidney, prostate, and spine. This paper describes the robotic platform, workflow, software, and algorithms used by the system. To demonstrate the algorithmic accuracy and suitability of the custom instrument guide, we also present results from experiments as well as estimates of the maximum error between target and instrument tip.

A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs

PubMed Central

Haslem, Derrick S.; Van Norman, S. Burke; Fulde, Gail; Knighton, Andrew J.; Belnap, Tom; Butler, Allison M.; Rhagunath, Sharanya; Newman, David; Gilbert, Heather; Tudor, Brian P.; Lin, Karen; Stone, Gary R.; Loughmiller, David L.; Mishra, Pravin J.; Srivastava, Rajendu; Ford, James M.; Nadauld, Lincoln D.

2017-01-01

Purpose: The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. Patients and Methods: We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). Results: The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group (P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group (P = .126). Conclusion: These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer. PMID:27601506

A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs.

PubMed

Haslem, Derrick S; Van Norman, S Burke; Fulde, Gail; Knighton, Andrew J; Belnap, Tom; Butler, Allison M; Rhagunath, Sharanya; Newman, David; Gilbert, Heather; Tudor, Brian P; Lin, Karen; Stone, Gary R; Loughmiller, David L; Mishra, Pravin J; Srivastava, Rajendu; Ford, James M; Nadauld, Lincoln D

2017-02-01

The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126). These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.

Robotic Observatory System Design-Specification Considerations for Achieving Long-Term Sustainable Precision Performance

NASA Astrophysics Data System (ADS)

Wray, J. D.

2003-05-01

The robotic observatory telescope must point precisely on the target object, and then track autonomously to a fraction of the FWHM of the system PSF for durations of ten to twenty minutes or more. It must retain this precision while continuing to function at rates approaching thousands of observations per night for all its years of useful life. These stringent requirements raise new challenges unique to robotic telescope systems design. Critical design considerations are driven by the applicability of the above requirements to all systems of the robotic observatory, including telescope and instrument systems, telescope-dome enclosure systems, combined electrical and electronics systems, environmental (e.g. seeing) control systems and integrated computer control software systems. Traditional telescope design considerations include the effects of differential thermal strain, elastic flexure, plastic flexure and slack or backlash with respect to focal stability, optical alignment and angular pointing and tracking precision. Robotic observatory design must holistically encapsulate these traditional considerations within the overall objective of maximized long-term sustainable precision performance. This overall objective is accomplished through combining appropriate mechanical and dynamical system characteristics with a full-time real-time telescope mount model feedback computer control system. Important design considerations include: identifying and reducing quasi-zero-backlash; increasing size to increase precision; directly encoding axis shaft rotation; pointing and tracking operation via real-time feedback between precision mount model and axis mounted encoders; use of monolithic construction whenever appropriate for sustainable mechanical integrity; accelerating dome motion to eliminate repetitive shock; ducting internal telescope air to outside dome; and the principal design criteria: maximizing elastic repeatability while minimizing slack, plastic deformation and hysteresis to facilitate long-term repeatably precise pointing and tracking performance.

Precise Quantitation of MicroRNA in a Single Cell with Droplet Digital PCR Based on Ligation Reaction.

PubMed

Tian, Hui; Sun, Yuanyuan; Liu, Chenghui; Duan, Xinrui; Tang, Wei; Li, Zhengping

2016-12-06

MicroRNA (miRNA) analysis in a single cell is extremely important because it allows deep understanding of the exact correlation between the miRNAs and cell functions. Herein, we wish to report a highly sensitive and precisely quantitative assay for miRNA detection based on ligation-based droplet digital polymerase chain reaction (ddPCR), which permits the quantitation of miRNA in a single cell. In this ligation-based ddPCR assay, two target-specific oligonucleotide probes can be simply designed to be complementary to the half-sequence of the target miRNA, respectively, which avoids the sophisticated design of reverse transcription and provides high specificity to discriminate a single-base difference among miRNAs with simple operations. After the miRNA-templated ligation, the ddPCR partitions individual ligated products into a water-in-oil droplet and digitally counts the fluorescence-positive and negative droplets after PCR amplification for quantification of the target molecules, which possesses the power of precise quantitation and robustness to variation in PCR efficiency. By integrating the advantages of the precise quantification of ddPCR and the simplicity of the ligation-based PCR, the proposed method can sensitively measure let-7a miRNA with a detection limit of 20 aM (12 copies per microliter), and even a single-base difference can be discriminated in let-7 family members. More importantly, due to its high selectivity and sensitivity, the proposed method can achieve precise quantitation of miRNAs in single-cell lysate. Therefore, the ligation-based ddPCR assay may serve as a useful tool to exactly reveal the miRNAs' actions in a single cell, which is of great importance for the study of miRNAs' biofunction as well as for the related biomedical studies.

Combining path integration and remembered landmarks when navigating without vision.

PubMed

Kalia, Amy A; Schrater, Paul R; Legge, Gordon E

2013-01-01

This study investigated the interaction between remembered landmark and path integration strategies for estimating current location when walking in an environment without vision. We asked whether observers navigating without vision only rely on path integration information to judge their location, or whether remembered landmarks also influence judgments. Participants estimated their location in a hallway after viewing a target (remembered landmark cue) and then walking blindfolded to the same or a conflicting location (path integration cue). We found that participants averaged remembered landmark and path integration information when they judged that both sources provided congruent information about location, which resulted in more precise estimates compared to estimates made with only path integration. In conclusion, humans integrate remembered landmarks and path integration in a gated fashion, dependent on the congruency of the information. Humans can flexibly combine information about remembered landmarks with path integration cues while navigating without visual information.

Combining Path Integration and Remembered Landmarks When Navigating without Vision

PubMed Central

Kalia, Amy A.; Schrater, Paul R.; Legge, Gordon E.

2013-01-01

This study investigated the interaction between remembered landmark and path integration strategies for estimating current location when walking in an environment without vision. We asked whether observers navigating without vision only rely on path integration information to judge their location, or whether remembered landmarks also influence judgments. Participants estimated their location in a hallway after viewing a target (remembered landmark cue) and then walking blindfolded to the same or a conflicting location (path integration cue). We found that participants averaged remembered landmark and path integration information when they judged that both sources provided congruent information about location, which resulted in more precise estimates compared to estimates made with only path integration. In conclusion, humans integrate remembered landmarks and path integration in a gated fashion, dependent on the congruency of the information. Humans can flexibly combine information about remembered landmarks with path integration cues while navigating without visual information. PMID:24039742

Hierarchical Brain Networks Active in Approach and Avoidance Goal Pursuit

PubMed Central

Spielberg, Jeffrey M.; Heller, Wendy; Miller, Gregory A.

2013-01-01

Effective approach/avoidance goal pursuit is critical for attaining long-term health and well-being. Research on the neural correlates of key goal-pursuit processes (e.g., motivation) has long been of interest, with lateralization in prefrontal cortex being a particularly fruitful target of investigation. However, this literature has often been limited by a lack of spatial specificity and has not delineated the precise aspects of approach/avoidance motivation involved. Additionally, the relationships among brain regions (i.e., network connectivity) vital to goal-pursuit remain largely unexplored. Specificity in location, process, and network relationship is vital for moving beyond gross characterizations of function and identifying the precise cortical mechanisms involved in motivation. The present paper integrates research using more spatially specific methodologies (e.g., functional magnetic resonance imaging) with the rich psychological literature on approach/avoidance to propose an integrative network model that takes advantage of the strengths of each of these literatures. PMID:23785328

Hierarchical brain networks active in approach and avoidance goal pursuit.

PubMed

Spielberg, Jeffrey M; Heller, Wendy; Miller, Gregory A

2013-01-01

Effective approach/avoidance goal pursuit is critical for attaining long-term health and well-being. Research on the neural correlates of key goal-pursuit processes (e.g., motivation) has long been of interest, with lateralization in prefrontal cortex being a particularly fruitful target of investigation. However, this literature has often been limited by a lack of spatial specificity and has not delineated the precise aspects of approach/avoidance motivation involved. Additionally, the relationships among brain regions (i.e., network connectivity) vital to goal-pursuit remain largely unexplored. Specificity in location, process, and network relationship is vital for moving beyond gross characterizations of function and identifying the precise cortical mechanisms involved in motivation. The present paper integrates research using more spatially specific methodologies (e.g., functional magnetic resonance imaging) with the rich psychological literature on approach/avoidance to propose an integrative network model that takes advantage of the strengths of each of these literatures.

Common-path low-coherence interferometry fiber-optic sensor guided microincision

NASA Astrophysics Data System (ADS)

Zhang, Kang; Kang, Jin U.

2011-09-01

We propose and demonstrate a common-path low-coherence interferometry (CP-LCI) fiber-optic sensor guided precise microincision. The method tracks the target surface and compensates the tool-to-surface relative motion with better than +/-5 μm resolution using a precision micromotor connected to the tool tip. A single-fiber distance probe integrated microdissector was used to perform an accurate 100 μm incision into the surface of an Intralipid phantom. The CP-LCI guided incision quality in terms of depth was evaluated afterwards using three-dimensional Fourier-domain optical coherence tomography imaging, which showed significant improvement of incision accuracy compared to free-hand-only operations.

Patient similarity for precision medicine: a systematic review.

PubMed

Parimbelli, E; Marini, S; Sacchi, L; Bellazzi, R

2018-06-01

Evidence-based medicine is the most prevalent paradigm adopted by physicians. Clinical practice guidelines typically define a set of recommendations together with eligibility criteria that restrict their applicability to a specific group of patients. The ever-growing size and availability of health-related data is currently challenging the broad definitions of guideline-defined patient groups. Precision medicine leverages on genetic, phenotypic, or psychosocial characteristics to provide precise identification of patient subsets for treatment targeting. Defining a patient similarity measure is thus an essential step to allow stratification of patients into clinically-meaningful subgroups. The present review investigates the use of patient similarity as a tool to enable precision medicine. 279 articles were analyzed along four dimensions: data types considered, clinical domains of application, data analysis methods, and translational stage of findings. Cancer-related research employing molecular profiling and standard data analysis techniques such as clustering constitute the majority of the retrieved studies. Chronic and psychiatric diseases follow as the second most represented clinical domains. Interestingly, almost one quarter of the studies analyzed presented a novel methodology, with the most advanced employing data integration strategies and being portable to different clinical domains. Integration of such techniques into decision support systems constitutes and interesting trend for future research. Copyright © 2018. Published by Elsevier Inc.

Precision medicine: In need of guidance and surveillance.

PubMed

Lin, Jian-Zhen; Long, Jun-Yu; Wang, An-Qiang; Zheng, Ying; Zhao, Hai-Tao

2017-07-28

Precision medicine, currently a hotspot in mainstream medicine, has been strongly promoted in recent years. With rapid technological development, such as next-generation sequencing, and fierce competition in molecular targeted drug exploitation, precision medicine represents an advance in science and technology; it also fulfills needs in public health care. The clinical translation and application of precision medicine - especially in the prevention and treatment of tumors - is far from satisfactory; however, the aims of precision medicine deserve approval. Thus, this medical approach is currently in its infancy; it has promising prospects, but it needs to overcome numbers of problems and deficiencies. It is expected that in addition to conventional symptoms and signs, precision medicine will define disease in terms of the underlying molecular characteristics and other environmental susceptibility factors. Those expectations should be realized by constructing a novel data network, integrating clinical data from individual patients and personal genomic background with existing research on the molecular makeup of diseases. In addition, multi-omics analysis and multi-discipline collaboration will become crucial elements in precision medicine. Precision medicine deserves strong support, and its development demands directed momentum. We propose three kinds of impetus (research, application and collaboration impetus) for such directed momentum toward promoting precision medicine and accelerating its clinical translation and application.

Precision medicine: In need of guidance and surveillance

PubMed Central

Lin, Jian-Zhen; Long, Jun-Yu; Wang, An-Qiang; Zheng, Ying; Zhao, Hai-Tao

2017-01-01

Precision medicine, currently a hotspot in mainstream medicine, has been strongly promoted in recent years. With rapid technological development, such as next-generation sequencing, and fierce competition in molecular targeted drug exploitation, precision medicine represents an advance in science and technology; it also fulfills needs in public health care. The clinical translation and application of precision medicine - especially in the prevention and treatment of tumors - is far from satisfactory; however, the aims of precision medicine deserve approval. Thus, this medical approach is currently in its infancy; it has promising prospects, but it needs to overcome numbers of problems and deficiencies. It is expected that in addition to conventional symptoms and signs, precision medicine will define disease in terms of the underlying molecular characteristics and other environmental susceptibility factors. Those expectations should be realized by constructing a novel data network, integrating clinical data from individual patients and personal genomic background with existing research on the molecular makeup of diseases. In addition, multi-omics analysis and multi-discipline collaboration will become crucial elements in precision medicine. Precision medicine deserves strong support, and its development demands directed momentum. We propose three kinds of impetus (research, application and collaboration impetus) for such directed momentum toward promoting precision medicine and accelerating its clinical translation and application. PMID:28811702

Temporal windows in visual processing: "prestimulus brain state" and "poststimulus phase reset" segregate visual transients on different temporal scales.

PubMed

Wutz, Andreas; Weisz, Nathan; Braun, Christoph; Melcher, David

2014-01-22

Dynamic vision requires both stability of the current perceptual representation and sensitivity to the accumulation of sensory evidence over time. Here we study the electrophysiological signatures of this intricate balance between temporal segregation and integration in vision. Within a forward masking paradigm with short and long stimulus onset asynchronies (SOA), we manipulated the temporal overlap of the visual persistence of two successive transients. Human observers enumerated the items presented in the second target display as a measure of the informational capacity read-out from this partly temporally integrated visual percept. We observed higher β-power immediately before mask display onset in incorrect trials, in which enumeration failed due to stronger integration of mask and target visual information. This effect was timescale specific, distinguishing between segregation and integration of visual transients that were distant in time (long SOA). Conversely, for short SOA trials, mask onset evoked a stronger visual response when mask and targets were correctly segregated in time. Examination of the target-related response profile revealed the importance of an evoked α-phase reset for the segregation of those rapid visual transients. Investigating this precise mapping of the temporal relationships of visual signals onto electrophysiological responses highlights how the stream of visual information is carved up into discrete temporal windows that mediate between segregated and integrated percepts. Fragmenting the stream of visual information provides a means to stabilize perceptual events within one instant in time.

Predicting drug-target interactions by dual-network integrated logistic matrix factorization

NASA Astrophysics Data System (ADS)

Hao, Ming; Bryant, Stephen H.; Wang, Yanli

2017-01-01

In this work, we propose a dual-network integrated logistic matrix factorization (DNILMF) algorithm to predict potential drug-target interactions (DTI). The prediction procedure consists of four steps: (1) inferring new drug/target profiles and constructing profile kernel matrix; (2) diffusing drug profile kernel matrix with drug structure kernel matrix; (3) diffusing target profile kernel matrix with target sequence kernel matrix; and (4) building DNILMF model and smoothing new drug/target predictions based on their neighbors. We compare our algorithm with the state-of-the-art method based on the benchmark dataset. Results indicate that the DNILMF algorithm outperforms the previously reported approaches in terms of AUPR (area under precision-recall curve) and AUC (area under curve of receiver operating characteristic) based on the 5 trials of 10-fold cross-validation. We conclude that the performance improvement depends on not only the proposed objective function, but also the used nonlinear diffusion technique which is important but under studied in the DTI prediction field. In addition, we also compile a new DTI dataset for increasing the diversity of currently available benchmark datasets. The top prediction results for the new dataset are confirmed by experimental studies or supported by other computational research.

Integration of Molecular Pathology, Epidemiology, and Social Science for Global Precision Medicine

PubMed Central

Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L.; Nishihara, Reiko; Tan, Andy S.; Kawachi, Ichiro; Ogino, Shuji

2015-01-01

Summary The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations, and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial, and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors, and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference, and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology, and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors, and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging, and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science. PMID:26636627

Optical mounts for harsh environments

NASA Astrophysics Data System (ADS)

Mimovich, Mark E.; Griffee, Jonathan C.; Goodding, James C.

2009-08-01

Development and testing of a lightweight-kinematic optical mount with integrated passive vibration-and-shock mitigation technologies and simple / robust optical alignment functionality is presented. Traditionally, optical mounts are designed for use in laboratory environments where the thermal-mechanical environments are carefully controlled to preserve beam path conditions and background disturbances are minimized to facilitate precise optically based measurements. Today's weapon and surveillance systems, however, have optical sensor suites where static and dynamic alignment performance in the presence of harsh operating environments is required to nearly the same precision and where the system cannot afford the mass of laboratory-grade stabilized mounting systems. Jitter and alignment stability is particularly challenging for larger optics operating within moving vehicles and aircraft where high shock and significant temperature excursions occur. The design intent is to have the mount be suitable for integration into existing defense and security optical systems while also targeting new commercial and military components for improved structural dynamic and thermal distortion performance. A mount suitable for moderate-sized optics and an integrated disturbance-optical metrology system are described. The mount design has performance enhancements derived from the integration of proven aerospace mechanical vibration and shock mitigation technologies (i.e. multi-axis passive isolation and integral damping), precision alignment adjustment and lock-out functionality, high dimensional stability materials and design practices which provide benign optical surface figure errors under harsh thermal-mechanical loading. Optical jitter, alignment, and wave-front performance testing of an eight-inch-aperture optical mount based on this design approach are presented to validate predicted performance improvements over an existing commercial off-the-shelf (COTS) design.

Integration of molecular pathology, epidemiology and social science for global precision medicine.

PubMed

Nishi, Akihiro; Milner, Danny A; Giovannucci, Edward L; Nishihara, Reiko; Tan, Andy S; Kawachi, Ichiro; Ogino, Shuji

2016-01-01

The precision medicine concept and the unique disease principle imply that each patient has unique pathogenic processes resulting from heterogeneous cellular genetic and epigenetic alterations and interactions between cells (including immune cells) and exposures, including dietary, environmental, microbial and lifestyle factors. As a core method field in population health science and medicine, epidemiology is a growing scientific discipline that can analyze disease risk factors and develop statistical methodologies to maximize utilization of big data on populations and disease pathology. The evolving transdisciplinary field of molecular pathological epidemiology (MPE) can advance biomedical and health research by linking exposures to molecular pathologic signatures, enhancing causal inference and identifying potential biomarkers for clinical impact. The MPE approach can be applied to any diseases, although it has been most commonly used in neoplastic diseases (including breast, lung and colorectal cancers) because of availability of various molecular diagnostic tests. However, use of state-of-the-art genomic, epigenomic and other omic technologies and expensive drugs in modern healthcare systems increases racial, ethnic and socioeconomic disparities. To address this, we propose to integrate molecular pathology, epidemiology and social science. Social epidemiology integrates the latter two fields. The integrative social MPE model can embrace sociology, economics and precision medicine, address global health disparities and inequalities, and elucidate biological effects of social environments, behaviors and networks. We foresee advancements of molecular medicine, including molecular diagnostics, biomedical imaging and targeted therapeutics, which should benefit individuals in a global population, by means of an interdisciplinary approach of integrative MPE and social health science.

Chemotherapy remains an essential element of personalized care for persons with lung cancers

PubMed Central

Hellmann, M. D.; Li, B. T.; Chaft, J. E.; Kris, M. G.

2016-01-01

Molecularly targeted and immunotherapies have improved the care of patients with lung cancers. These successes have rallied calls to replace or avoid chemotherapy. Yet, even in this era of precision medicine and exciting advances, cytotoxic chemotherapies remain an essential component of lung cancer treatment. In the setting of locoregional disease, chemotherapy is the only systemic therapy thus far proven to enhance curability when combined with surgery or radiation. In the metastatic setting, chemotherapy can improve the length and quality of life in many patients. Chemotherapy remains the mainstay of care for individuals whose cancers with oncogenic drivers have acquired resistance to targeted agents. Chemotherapy also has the potential to modulate the immune system to enhance the effectiveness of immune checkpoint inhibitors. In this context, chemotherapy should be framed as a critical component of the armamentarium available for optimizing cancer care rather than an unfortunate anachronism. We examine the role of chemotherapy with precision medicine in the current care of patients with lung cancers, as well as opportunities for future integration in combinations with targeted agents, angiogenesis inhibitors, immunotherapies, and antibody drug conjugates. PMID:27456296

Pico-coulomb charge measured at BELLA to percent-level precision using a Turbo-ICT

NASA Astrophysics Data System (ADS)

Nakamura, K.; Mittelberger, D. E.; Gonsalves, A. J.; Daniels, J.; Mao, H.-S.; Stulle, F.; Bergoz, J.; Leemans, W. P.

2016-03-01

Precise diagnostics of picocoulomb level particle bunches produced by laser plasma accelerators (LPAs) can be a significant challenge. Without proper care, the small signals associated with such bunches can be dominated by a background generated by laser, target, laser-plasma interaction and particle induced radiation. In this paper, we report on first charge measurements using the newly developed Turbo-ICT for LPAs. We outline the Turbo-ICT working principle, which allows precise sub-picocoulomb measurements even in the presence of significant background signals. A comparison of the Turbo-ICT, a conventional integrating current transformer (ICT) and a scintillating screen (Lanex) was carried out at the Berkeley Lab Laser Accelerator. Results show that the Turbo-ICT can measure sub-picocoulomb charge accurately and has significantly improved noise immunity compared to the ICT.

Monitoring femtosecond laser microscopic photothermolysis with multimodal microscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Huang, Yimei; Lui, Harvey; Zhao, Jianhua; McLean, David I.; Zeng, Haishan

2016-02-01

Photothermolysis induced by femtosecond (fs) lasers may be a promising modality in dermatology because of its advantages of high precision due to multiphoton absorption and deeper penetration due to the use of near infrared wavelengths. Although multiphoton absorption nonlinear effects are capable of precision targeting, the femtosecond laser photothermolysis could still have effects beyond the targeted area if a sufficiently high dose of laser light is used. Such unintended effects could be minimized by real time monitoring photothermolysis during the treatment. Targeted photothermolytic treatment of ex vivo mouse skin dermis was performed with tightly focused fs laser beams. Images of reflectance confocal microscopy (RCM), second harmonic generation (SHG), and two-photon fluorescence (TPF) of the mouse skins were obtained with integrated multimodal microscopy before, during, and after the laser treatment. The RCM, SHG, and TPF signal intensities of the treatment areas changed after high power femtosecond laser irradiation. The intensities of the RCM and SHG signals decreased when the tissue was damaged, while the intensity of the TPF signal increased when the photothermolysis was achieved. Moreover, the TPF signal was more susceptible to the degree of the photothermolysis than the RCM and SHG signals. The results suggested that multimodal microscopy is a potentially useful tool to monitor and assess the femtosecond laser treatment of the skin to achieve microscopic photothermolysis with high precision.

High-brightness displays in integrated weapon sight systems

NASA Astrophysics Data System (ADS)

Edwards, Tim; Hogan, Tim

2014-06-01

In the past several years Kopin has demonstrated the ability to provide ultra-high brightness, low power display solutions in VGA, SVGA, SXGA and 2k x 2k display formats. This paper will review various approaches for integrating high brightness overlay displays with existing direct view rifle sights and augmenting their precision aiming and targeting capability. Examples of overlay display systems solutions will be presented and discussed. This paper will review significant capability enhancements that are possible when augmenting the real-world as seen through a rifle sight with other soldier system equipment including laser range finders, ballistic computers and sensor systems.

A cost-effective monitoring technique in particle therapy via uncollimated prompt gamma peak integration

NASA Astrophysics Data System (ADS)

Krimmer, J.; Angellier, G.; Balleyguier, L.; Dauvergne, D.; Freud, N.; Hérault, J.; Létang, J. M.; Mathez, H.; Pinto, M.; Testa, E.; Zoccarato, Y.

2017-04-01

For the purpose of detecting deviations from the prescribed treatment during particle therapy, the integrals of uncollimated prompt gamma-ray timing distributions are investigated. The intention is to provide information, with a simple and cost-effective setup, independent from monitoring devices of the beamline. Measurements have been performed with 65 MeV protons at a clinical cyclotron. Prompt gamma-rays emitted from the target are identified by means of time-of-flight. The proton range inside the PMMA target has been varied via a modulator wheel. The measured variation of the prompt gamma peak integrals as a function of the modulator position is consistent with simulations. With detectors covering a solid angle of 25 msr (corresponding to a diameter of 3-4 in. at a distance of 50 cm from the beam axis) and 108 incident protons, deviations of a few per cent in the prompt gamma-ray count rate can be detected. For the present configuration, this change in the count rate corresponds to a 3 mm change in the proton range in a PMMA target. Furthermore, simulation studies show that a combination of the signals from multiple detectors may be used to detect a misplacement of the target. A different combination of these signals results in a precise number of the detected prompt gamma rays, which is independent on the actual target position.

New strategy for drug discovery by large-scale association analysis of molecular networks of different species.

PubMed

Zhang, Bo; Fu, Yingxue; Huang, Chao; Zheng, Chunli; Wu, Ziyin; Zhang, Wenjuan; Yang, Xiaoyan; Gong, Fukai; Li, Yuerong; Chen, Xiaoyu; Gao, Shuo; Chen, Xuetong; Li, Yan; Lu, Aiping; Wang, Yonghua

2016-02-25

The development of modern omics technology has not significantly improved the efficiency of drug development. Rather precise and targeted drug discovery remains unsolved. Here a large-scale cross-species molecular network association (CSMNA) approach for targeted drug screening from natural sources is presented. The algorithm integrates molecular network omics data from humans and 267 plants and microbes, establishing the biological relationships between them and extracting evolutionarily convergent chemicals. This technique allows the researcher to assess targeted drugs for specific human diseases based on specific plant or microbe pathways. In a perspective validation, connections between the plant Halliwell-Asada (HA) cycle and the human Nrf2-ARE pathway were verified and the manner by which the HA cycle molecules act on the human Nrf2-ARE pathway as antioxidants was determined. This shows the potential applicability of this approach in drug discovery. The current method integrates disparate evolutionary species into chemico-biologically coherent circuits, suggesting a new cross-species omics analysis strategy for rational drug development.

Precision Medicine for CRC Patients in the Veteran Population: State-of-the-Art, Challenges and Research Directions.

PubMed

Mohapatra, Shyam S; Batra, Surinder K; Bharadwaj, Srinivas; Bouvet, Michael; Cosman, Bard; Goel, Ajay; Jogunoori, Wilma; Kelley, Michael J; Mishra, Lopa; Mishra, Bibhuti; Mohapatra, Subhra; Patel, Bhaumik; Pisegna, Joseph R; Raufman, Jean-Pierre; Rao, Shuyun; Roy, Hemant; Scheuner, Maren; Singh, Satish; Vidyarthi, Gitanjali; White, Jon

2018-05-01

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to identify modalities that might ultimately lead to personalized cancer diagnosis and treatment. This review summarizes the findings of this VA field-based meeting, in which much of the current knowledge on CRC prescreening and treatment was discussed. It was concluded that there is a need and an opportunity to identify new targets for both the prevention of CRC and the development of effective therapies for advanced disease. Also, developing methods integrating genomic testing with tumoroid-based clinical drug response might lead to more accurate diagnosis and prognostication and more effective personalized treatment of CRC.

Metabolomics through the lens of precision cardiovascular medicine.

PubMed

Lam, Sin Man; Wang, Yuan; Li, Bowen; Du, Jie; Shui, Guanghou

2017-03-20

Metabolomics, which targets at the extensive characterization and quantitation of global metabolites from both endogenous and exogenous sources, has emerged as a novel technological avenue to advance the field of precision medicine principally driven by genomics-oriented approaches. In particular, metabolomics has revealed the cardinal roles that the environment exerts in driving the progression of major diseases threatening public health. Herein, the existent and potential applications of metabolomics in two key areas of precision cardiovascular medicine will be critically discussed: 1) the use of metabolomics in unveiling novel disease biomarkers and pathological pathways; 2) the contribution of metabolomics in cardiovascular drug development. Major issues concerning the statistical handling of big data generated by metabolomics, as well as its interpretation, will be briefly addressed. Finally, the need for integration of various omics branches and adopting a multi-omics approach to precision medicine will be discussed. Copyright © 2017 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

A novel platform for electromagnetic navigated ultrasound bronchoscopy (EBUS).

PubMed

Sorger, Hanne; Hofstad, Erlend Fagertun; Amundsen, Tore; Langø, Thomas; Leira, Håkon Olav

2016-08-01

Endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) of mediastinal lymph nodes is essential for lung cancer staging and distinction between curative and palliative treatment. Precise sampling is crucial. Navigation and multimodal imaging may improve the efficiency of EBUS-TBNA. We demonstrate a novel EBUS-TBNA navigation system in a dedicated airway phantom. Using a convex probe EBUS bronchoscope (CP-EBUS) with an integrated sensor for electromagnetic (EM) position tracking, we performed navigated CP-EBUS in a phantom. Preoperative computed tomography (CT) and real-time ultrasound (US) images were integrated into a navigation platform for EM navigated bronchoscopy. The coordinates of targets in CT and US volumes were registered in the navigation system, and the position deviation was calculated. The system visualized all tumor models and displayed their fused CT and US images in correct positions in the navigation system. Navigating the EBUS bronchoscope was fast and easy. Mean error observed between US and CT positions for 11 target lesions (37 measurements) was [Formula: see text] mm, maximum error was 5.9 mm. The feasibility of our novel navigated CP-EBUS system was successfully demonstrated. An EBUS navigation system is needed to meet future requirements of precise mediastinal lymph node mapping, and provides new opportunities for procedure documentation in EBUS-TBNA.

Intracellular generation of single-strand template increases the knock-in efficiency by combining CRISPR/Cas9 with AAV.

PubMed

Xiao, Qing; Min, Taishan; Ma, Shuangping; Hu, Lingna; Chen, Hongyan; Lu, Daru

2018-04-18

Targeted integration of transgenes facilitates functional genomic research and holds prospect for gene therapy. The established microhomology-mediated end-joining (MMEJ)-based strategy leads to the precise gene knock-in with easily constructed donor, yet the limited efficiency remains to be further improved. Here, we show that single-strand DNA (ssDNA) donor contributes to efficient increase of knock-in efficiency and establishes a method to achieve the intracellular linearization of long ssDNA donor. We identified that the CRISPR/Cas9 system is responsible for breaking double-strand DNA (dsDNA) of palindromic structure in inverted terminal repeats (ITRs) region of recombinant adeno-associated virus (AAV), leading to the inhibition of viral second-strand DNA synthesis. Combing Cas9 plasmids targeting genome and ITR with AAV donor delivery, the precise knock-in of gene cassette was achieved, with 13-14% of the donor insertion events being mediated by MMEJ in HEK 293T cells. This study describes a novel method to integrate large single-strand transgene cassettes into the genomes, increasing knock-in efficiency by 13.6-19.5-fold relative to conventional AAV-mediated method. It also provides a comprehensive solution to the challenges of complicated production and difficult delivery with large exogenous fragments.

Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

PubMed Central

Tasian, Sarah K; Loh, Mignon L; Hunger, Stephen P

2015-01-01

Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for development of new therapeutic approaches in the era of precision medicine. This review delineates the current genetic landscape of childhood ALL with emphasis upon patient outcomes with contemporary treatment regimens, as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. PMID:26194091

Mathematical model of bone drilling for virtual surgery system

NASA Astrophysics Data System (ADS)

Alaytsev, Innokentiy K.; Danilova, Tatyana V.; Manturov, Alexey O.; Mareev, Gleb O.; Mareev, Oleg V.

2018-04-01

The bone drilling is an essential part of surgeries in ENT and Dentistry. A proper training of drilling machine handling skills is impossible without proper modelling of the drilling process. Utilization of high precision methods like FEM is limited due to the requirement of 1000 Hz update rate for haptic feedback. The study presents a mathematical model of the drilling process that accounts the properties of materials, the geometry and the rotation rate of a burr to compute the removed material volume. The simplicity of the model allows for integrating it in the high-frequency haptic thread. The precision of the model is enough for a virtual surgery system targeted on the training of the basic surgery skills.

Common-path low-coherence interferometry fiber-optic sensor guided microincision

PubMed Central

Zhang, Kang; Kang, Jin U.

2011-01-01

We propose and demonstrate a common-path low-coherence interferometry (CP-LCI) fiber-optic sensor guided precise microincision. The method tracks the target surface and compensates the tool-to-surface relative motion with better than ±5 μm resolution using a precision micromotor connected to the tool tip. A single-fiber distance probe integrated microdissector was used to perform an accurate 100 μm incision into the surface of an Intralipid phantom. The CP-LCI guided incision quality in terms of depth was evaluated afterwards using three-dimensional Fourier-domain optical coherence tomography imaging, which showed significant improvement of incision accuracy compared to free-hand-only operations. PMID:21950912

A network-based drug repositioning infrastructure for precision cancer medicine through targeting significantly mutated genes in the human cancer genomes.

PubMed

Cheng, Feixiong; Zhao, Junfei; Fooksa, Michaela; Zhao, Zhongming

2016-07-01

Development of computational approaches and tools to effectively integrate multidomain data is urgently needed for the development of newly targeted cancer therapeutics. We proposed an integrative network-based infrastructure to identify new druggable targets and anticancer indications for existing drugs through targeting significantly mutated genes (SMGs) discovered in the human cancer genomes. The underlying assumption is that a drug would have a high potential for anticancer indication if its up-/down-regulated genes from the Connectivity Map tended to be SMGs or their neighbors in the human protein interaction network. We assembled and curated 693 SMGs in 29 cancer types and found 121 proteins currently targeted by known anticancer or noncancer (repurposed) drugs. We found that the approved or experimental cancer drugs could potentially target these SMGs in 33.3% of the mutated cancer samples, and this number increased to 68.0% by drug repositioning through surveying exome-sequencing data in approximately 5000 normal-tumor pairs from The Cancer Genome Atlas. Furthermore, we identified 284 potential new indications connecting 28 cancer types and 48 existing drugs (adjusted P < .05), with a 66.7% success rate validated by literature data. Several existing drugs (e.g., niclosamide, valproic acid, captopril, and resveratrol) were predicted to have potential indications for multiple cancer types. Finally, we used integrative analysis to showcase a potential mechanism-of-action for resveratrol in breast and lung cancer treatment whereby it targets several SMGs (ARNTL, ASPM, CTTN, EIF4G1, FOXP1, and STIP1). In summary, we demonstrated that our integrative network-based infrastructure is a promising strategy to identify potential druggable targets and uncover new indications for existing drugs to speed up molecularly targeted cancer therapeutics. © The Author 2016. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Search guidance is proportional to the categorical specificity of a target cue.

PubMed

Schmidt, Joseph; Zelinsky, Gregory J

2009-10-01

Visual search studies typically assume the availability of precise target information to guide search, often a picture of the exact target. However, search targets in the real world are often defined categorically and with varying degrees of visual specificity. In five target preview conditions we manipulated the availability of target visual information in a search task for common real-world objects. Previews were: a picture of the target, an abstract textual description of the target, a precise textual description, an abstract + colour textual description, or a precise + colour textual description. Guidance generally increased as information was added to the target preview. We conclude that the information used for search guidance need not be limited to a picture of the target. Although generally less precise, to the extent that visual information can be extracted from a target label and loaded into working memory, this information too can be used to guide search.

Characterization of anti-leukemia components from Indigo naturalis using comprehensive two-dimensional K562/cell membrane chromatography and in silico target identification.

PubMed

Wu, Xunxun; Chen, Xiaofei; Dan, Jia; Cao, Yan; Gao, Shouhong; Guo, Zhiying; Zerbe, Philipp; Chai, Yifeng; Diao, Yong; Zhang, Lei

2016-05-06

Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis, a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines.

Characterization of anti-leukemia components from Indigo naturalis using comprehensive two-dimensional K562/cell membrane chromatography and in silico target identification

PubMed Central

Wu, Xunxun; Chen, Xiaofei; Dan, Jia; Cao, Yan; Gao, Shouhong; Guo, Zhiying; Zerbe, Philipp; Chai, Yifeng; Diao, Yong; Zhang, Lei

2016-01-01

Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis, a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines. PMID:27150638

Novel Platform for MRI-Guided Convection-Enhanced Delivery of Therapeutics: Preclinical Validation in Nonhuman Primate Brain

PubMed Central

Richardson, R. Mark; Kells, Adrian P.; Martin, Alastair J.; Larson, Paul S.; Starr, Philip A.; Piferi, Peter G.; Bates, Geoffrey; Tansey, Lisa; Rosenbluth, Kathryn H.; Bringas, John R.; Berger, Mitchel S.; Bankiewicz, Krystof S.

2011-01-01

Background/Aims A skull-mounted aiming device and integrated software platform has been developed for MRI-guided neurological interventions. In anticipation of upcoming gene therapy clinical trials, we adapted this device for real-time convection-enhanced delivery of therapeutics via a custom-designed infusion cannula. The targeting accuracy of this delivery system and the performance of the infusion cannula were validated in nonhuman primates. Methods Infusions of gadoteridol were delivered to multiple brain targets and the targeting error was determined for each cannula placement. Cannula performance was assessed by analyzing gadoteridol distributions and by histological analysis of tissue damage. Results The average targeting error for all targets (n = 11) was 0.8 mm (95% CI = 0.14). For clinically relevant volumes, the distribution volume of gadoteridol increased as a linear function (R2 = 0.97) of the infusion volume (average slope = 3.30, 95% CI = 0.2). No infusions in any target produced occlusion, cannula reflux or leakage from adjacent tracts, and no signs of unexpected tissue damage were observed. Conclusions This integrated delivery platform allows real-time convection-enhanced delivery to be performed with a high level of precision, predictability and safety. This approach may improve the success rate for clinical trials involving intracerebral drug delivery by direct infusion. PMID:21494065

The Chronotron: A Neuron That Learns to Fire Temporally Precise Spike Patterns

PubMed Central

Florian, Răzvan V.

2012-01-01

In many cases, neurons process information carried by the precise timings of spikes. Here we show how neurons can learn to generate specific temporally precise output spikes in response to input patterns of spikes having precise timings, thus processing and memorizing information that is entirely temporally coded, both as input and as output. We introduce two new supervised learning rules for spiking neurons with temporal coding of information (chronotrons), one that provides high memory capacity (E-learning), and one that has a higher biological plausibility (I-learning). With I-learning, the neuron learns to fire the target spike trains through synaptic changes that are proportional to the synaptic currents at the timings of real and target output spikes. We study these learning rules in computer simulations where we train integrate-and-fire neurons. Both learning rules allow neurons to fire at the desired timings, with sub-millisecond precision. We show how chronotrons can learn to classify their inputs, by firing identical, temporally precise spike trains for different inputs belonging to the same class. When the input is noisy, the classification also leads to noise reduction. We compute lower bounds for the memory capacity of chronotrons and explore the influence of various parameters on chronotrons' performance. The chronotrons can model neurons that encode information in the time of the first spike relative to the onset of salient stimuli or neurons in oscillatory networks that encode information in the phases of spikes relative to the background oscillation. Our results show that firing one spike per cycle optimizes memory capacity in neurons encoding information in the phase of firing relative to a background rhythm. PMID:22879876

Precision Pointing Control System (PPCS) system design and analysis. [for gimbaled experiment platforms

NASA Technical Reports Server (NTRS)

Frew, A. M.; Eisenhut, D. F.; Farrenkopf, R. L.; Gates, R. F.; Iwens, R. P.; Kirby, D. K.; Mann, R. J.; Spencer, D. J.; Tsou, H. S.; Zaremba, J. G.

1972-01-01

The precision pointing control system (PPCS) is an integrated system for precision attitude determination and orientation of gimbaled experiment platforms. The PPCS concept configures the system to perform orientation of up to six independent gimbaled experiment platforms to design goal accuracy of 0.001 degrees, and to operate in conjunction with a three-axis stabilized earth-oriented spacecraft in orbits ranging from low altitude (200-2500 n.m., sun synchronous) to 24 hour geosynchronous, with a design goal life of 3 to 5 years. The system comprises two complementary functions: (1) attitude determination where the attitude of a defined set of body-fixed reference axes is determined relative to a known set of reference axes fixed in inertial space; and (2) pointing control where gimbal orientation is controlled, open-loop (without use of payload error/feedback) with respect to a defined set of body-fixed reference axes to produce pointing to a desired target.

A Road Map for Precision Medicine in the Epilepsies

PubMed Central

2015-01-01

Summary Technological advances have paved the way for accelerated genomic discovery and are bringing precision medicine clearly into view. Epilepsy research in particular is well-suited to serve as a model for the development and deployment of targeted therapeutics in precision medicine because of the rapidly expanding genetic knowledge base in epilepsy, the availability of good in vitro and in vivo model systems to efficiently study the biological consequences of genetic mutations, the ability to turn these models into effective drug screening platforms, and the establishment of collaborative research groups. Moving forward, it is critical that we strengthen these collaborations, particularly through integrated research platforms to provide robust analyses both for accurate personal genome analysis and gene and drug discovery. Similarly, the implementation of clinical trial networks will allow the expansion of patient sample populations with genetically defined epilepsy so that drug discovery can be translated into clinical practice. PMID:26416172

[Molecular-Genetic Diagnosis and Molecular-Targeted Therapy in Cancer: Challenges in the Era of Precision Medicine].

PubMed

Miyachi, Hayato

2015-10-01

Elucidation of the molecular pathogenesis of neoplasms and application of emerging technologies for testing and therapy have resulted in a series of paradigm shifts in patient care, from conventional to personalized medicine. This has been promoted by companion diagnostics and molecular targeted therapy, tailoring the treatment to the individual characteristics of each patient. Precision oncology has been accelerated by integrating the enhanced resolution of molecular analysis, mechanism clarity, and therapeutic relevance through genomic knowledge. In its clinical implementation, there are laboratory challenges concerning accurate measurement using stored samples, differentiation between driver and passenger mutations as well as between germline and somatic mutations, bioinformatics availability, practical decision-making algorithms, and ethical issues regarding incidental findings. The medical laboratory has a new role in providing not only testing services but also an instructive approach to users to ensure the sample quality and privacy protection of personal genome information, supporting the quality of patient practice based on laboratory diagnosis.

Target tracking system based on preliminary and precise two-stage compound cameras

NASA Astrophysics Data System (ADS)

Shen, Yiyan; Hu, Ruolan; She, Jun; Luo, Yiming; Zhou, Jie

2018-02-01

Early detection of goals and high-precision of target tracking is two important performance indicators which need to be balanced in actual target search tracking system. This paper proposed a target tracking system with preliminary and precise two - stage compound. This system using a large field of view to achieve the target search. After the target was searched and confirmed, switch into a small field of view for two field of view target tracking. In this system, an appropriate filed switching strategy is the key to achieve tracking. At the same time, two groups PID parameters are add into the system to reduce tracking error. This combination way with preliminary and precise two-stage compound can extend the scope of the target and improve the target tracking accuracy and this method has practical value.

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.

Precision medicine in oncology: New practice models and roles for oncology pharmacists.

PubMed

Walko, Christine; Kiel, Patrick J; Kolesar, Jill

2016-12-01

Three different precision medicine practice models developed by oncology pharmacists are described, including strategies for implementation and recommendations for educating the next generation of oncology pharmacy practitioners. Oncology is unique in that somatic mutations can both drive the development of a tumor and serve as a therapeutic target for treating the cancer. Precision medicine practice models are a forum through which interprofessional teams, including pharmacists, discuss tumor somatic mutations to guide patient-specific treatment. The University of Wisconsin, Indiana University, and Moffit Cancer Center have implemented precision medicine practice models developed and led by oncology pharmacists. Different practice models, including a clinic, a clinical consultation service, and a molecular tumor board (MTB), were adopted to enhance integration into health systems and payment structures. Although the practice models vary, commonalities of three models include leadership by the clinical pharmacist, specific therapeutic recommendations, procurement of medications for off-label use, and a research component. These three practice models function as interprofessional training sites for pharmacy and medical students and residents, providing an important training resource at these institutions. Key implementation strategies include interprofessional involvement, institutional support, integration into clinical workflow, and selection of model by payer mix. MTBs are a pathway for clinical implementation of genomic medicine in oncology and are an emerging practice model for oncology pharmacists. Because pharmacists must be prepared to participate fully in contemporary practice, oncology pharmacy residents must be trained in genomic oncology, schools of pharmacy should expand precision medicine and genomics education, and opportunities for continuing education in precision medicine should be made available to practicing pharmacists. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Survey of optimization techniques for nonlinear spacecraft trajectory searches

NASA Technical Reports Server (NTRS)

Wang, Tseng-Chan; Stanford, Richard H.; Sunseri, Richard F.; Breckheimer, Peter J.

1988-01-01

Mathematical analysis of the optimal search of a nonlinear spacecraft trajectory to arrive at a set of desired targets is presented. A high precision integrated trajectory program and several optimization software libraries are used to search for a converged nonlinear spacecraft trajectory. Several examples for the Galileo Jupiter Orbiter and the Ocean Topography Experiment (TOPEX) are presented that illustrate a variety of the optimization methods used in nonlinear spacecraft trajectory searches.

Advancements of diffraction-based overlay metrology for double patterning

NASA Astrophysics Data System (ADS)

Li, Jie; Kritsun, Oleg; Liu, Yongdong; Dasari, Prasad; Weher, Ulrich; Volkman, Catherine; Mazur, Martin; Hu, Jiangtao

2011-03-01

As the dimensions of integrated circuit continue to shrink, diffraction based overlay (DBO) technologies have been developed to address the tighter overlay control challenges. Previously data of high accuracy and high precision were reported for litho-etch-litho-etch double patterning (DP) process using normal incidence spectroscopic reflectometry on specially designed targets composed of 1D gratings in x and y directions. Two measurement methods, empirical algorithm (eDBO) using four pads per direction (2x4 target) and modeling based algorithm (mDBO) using two pads per direction (2x2 target) were performed. In this work, we apply DBO techniques to measure overlay errors for a different DP process, litho-freeze-litho-etch process. We explore the possibility of further reducing number of pads in a DBO target using mDBO. For standard targets composed of 1D gratings, we reported results for eDBO 2x4 targets, mDBO 2x2 targets, and mDBO 2x1 target. The results of all three types of targets are comparable in terms of accuracy, dynamic precision, and TIS. TMU (not including tool matching) is less than 0.1nm. In addition, we investigated the possibility of measuring overlay with one single pad that contains 2D gratings. We achieved good correlation to blossom measurements. TMU (not including tool matching) is ~ 0.2nm. To our best knowledge, this is the first time that DBO results are reported on a single pad. eDBO allows quick recipe setup but takes more space and measurement time. Although mDBO needs details of optical properties and modeling, it offers smaller total target size and much faster throughput, which is important in high volume manufacturing environment.

Fabrication of three-dimensional scaffolds using precision extrusion deposition with an assisted cooling device.

PubMed

Hamid, Q; Snyder, J; Wang, C; Timmer, M; Hammer, J; Guceri, S; Sun, W

2011-09-01

In the field of biofabrication, tissue engineering and regenerative medicine, there are many methodologies to fabricate a building block (scaffold) which is unique to the target tissue or organ that facilitates cell growth, attachment, proliferation and/or differentiation. Currently, there are many techniques that fabricate three-dimensional scaffolds; however, there are advantages, limitations and specific tissue focuses of each fabrication technique. The focus of this initiative is to utilize an existing technique and expand the library of biomaterials which can be utilized to fabricate three-dimensional scaffolds rather than focusing on a new fabrication technique. An expanded library of biomaterials will enable the precision extrusion deposition (PED) device to construct three-dimensional scaffolds with enhanced biological, chemical and mechanical cues that will benefit tissue generation. Computer-aided motion and extrusion drive the PED to precisely fabricate micro-scaled scaffolds with biologically inspired, porosity, interconnectivity and internal and external architectures. The high printing resolution, precision and controllability of the PED allow for closer mimicry of tissues and organs. The PED expands its library of biopolymers by introducing an assisting cooling (AC) device which increases the working extrusion temperature from 120 to 250 °C. This paper investigates the PED with the integrated AC's capabilities to fabricate three-dimensional scaffolds that support cell growth, attachment and proliferation. Studies carried out in this paper utilized a biopolymer whose melting point is established to be 200 °C. This polymer was selected to illustrate the newly developed device's ability to fabricate three-dimensional scaffolds from a new library of biopolymers. Three-dimensional scaffolds fabricated with the integrated AC device should illustrate structural integrity and ability to support cell attachment and proliferation.

Gene mutation-based and specific therapies in precision medicine.

PubMed

Wang, Xiangdong

2016-04-01

Precision medicine has been initiated and gains more and more attention from preclinical and clinical scientists. A number of key elements or critical parts in precision medicine have been described and emphasized to establish a systems understanding of precision medicine. The principle of precision medicine is to treat patients on the basis of genetic alterations after gene mutations are identified, although questions and challenges still remain before clinical application. Therapeutic strategies of precision medicine should be considered according to gene mutation, after biological and functional mechanisms of mutated gene expression or epigenetics, or the correspondent protein, are clearly validated. It is time to explore and develop a strategy to target and correct mutated genes by direct elimination, restoration, correction or repair of mutated sequences/genes. Nevertheless, there are still numerous challenges to integrating widespread genomic testing into individual cancer therapies and into decision making for one or another treatment. There are wide-ranging and complex issues to be solved before precision medicine becomes clinical reality. Thus, the precision medicine can be considered as an extension and part of clinical and translational medicine, a new alternative of clinical therapies and strategies, and have an important impact on disease cures and patient prognoses. © 2015 The Author. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Characterization of the targeting signal in mitochondrial β-barrel proteins

PubMed Central

Jores, Tobias; Klinger, Anna; Groß, Lucia E.; Kawano, Shin; Flinner, Nadine; Duchardt-Ferner, Elke; Wöhnert, Jens; Kalbacher, Hubert; Endo, Toshiya; Schleiff, Enrico; Rapaport, Doron

2016-01-01

Mitochondrial β-barrel proteins are synthesized on cytosolic ribosomes and must be specifically targeted to the organelle before their integration into the mitochondrial outer membrane. The signal that assures such precise targeting and its recognition by the organelle remained obscure. In the present study we show that a specialized β-hairpin motif is this long searched for signal. We demonstrate that a synthetic β-hairpin peptide competes with the import of mitochondrial β-barrel proteins and that proteins harbouring a β-hairpin peptide fused to passenger domains are targeted to mitochondria. Furthermore, a β-hairpin motif from mitochondrial proteins targets chloroplast β-barrel proteins to mitochondria. The mitochondrial targeting depends on the hydrophobicity of the β-hairpin motif. Finally, this motif interacts with the mitochondrial import receptor Tom20. Collectively, we reveal that β-barrel proteins are targeted to mitochondria by a dedicated β-hairpin element, and this motif is recognized at the organelle surface by the outer membrane translocase. PMID:27345737

First patients treated with a 1.5 T MRI-Linac: clinical proof of concept of a high-precision, high-field MRI guided radiotherapy treatment

NASA Astrophysics Data System (ADS)

Raaymakers, B. W.; Jürgenliemk-Schulz, I. M.; Bol, G. H.; Glitzner, M.; Kotte, A. N. T. J.; van Asselen, B.; de Boer, J. C. J.; Bluemink, J. J.; Hackett, S. L.; Moerland, M. A.; Woodings, S. J.; Wolthaus, J. W. H.; van Zijp, H. M.; Philippens, M. E. P.; Tijssen, R.; Kok, J. G. M.; de Groot-van Breugel, E. N.; Kiekebosch, I.; Meijers, L. T. C.; Nomden, C. N.; Sikkes, G. G.; Doornaert, P. A. H.; Eppinga, W. S. C.; Kasperts, N.; Kerkmeijer, L. G. W.; Tersteeg, J. H. A.; Brown, K. J.; Pais, B.; Woodhead, P.; Lagendijk, J. J. W.

2017-12-01

The integration of 1.5 T MRI functionality with a radiotherapy linear accelerator (linac) has been pursued since 1999 by the UMC Utrecht in close collaboration with Elekta and Philips. The idea behind this integrated device is to offer unrivalled, online and real-time, soft-tissue visualization of the tumour and the surroundings for more precise radiation delivery. The proof of concept of this device was given in 2009 by demonstrating simultaneous irradiation and MR imaging on phantoms, since then the device has been further developed and commercialized by Elekta. The aim of this work is to demonstrate the clinical feasibility of online, high-precision, high-field MRI guidance of radiotherapy using the first clinical prototype MRI-Linac. Four patients with lumbar spine bone metastases were treated with a 3 or 5 beam step-and-shoot IMRT plan. The IMRT plan was created while the patient was on the treatment table and based on the online 1.5 T MR images; pre-treatment CT was deformably registered to the online MRI to obtain Hounsfield values. Bone metastases were chosen as the first site as these tumors can be clearly visualized on MRI and the surrounding spine bone can be detected on the integrated portal imager. This way the portal images served as an independent verification of the MRI based guidance to quantify the geometric precision of radiation delivery. Dosimetric accuracy was assessed post-treatment from phantom measurements with an ionization chamber and film. Absolute doses were found to be highly accurate, with deviations ranging from 0.0% to 1.7% in the isocenter. The geometrical, MRI based targeting as confirmed using portal images was better than 0.5 mm, ranging from 0.2 mm to 0.4 mm. In conclusion, high precision, high-field, 1.5 T MRI guided radiotherapy is clinically feasible.

MultiMiTar: a novel multi objective optimization based miRNA-target prediction method.

PubMed

Mitra, Ramkrishna; Bandyopadhyay, Sanghamitra

2011-01-01

Machine learning based miRNA-target prediction algorithms often fail to obtain a balanced prediction accuracy in terms of both sensitivity and specificity due to lack of the gold standard of negative examples, miRNA-targeting site context specific relevant features and efficient feature selection process. Moreover, all the sequence, structure and machine learning based algorithms are unable to distribute the true positive predictions preferentially at the top of the ranked list; hence the algorithms become unreliable to the biologists. In addition, these algorithms fail to obtain considerable combination of precision and recall for the target transcripts that are translationally repressed at protein level. In the proposed article, we introduce an efficient miRNA-target prediction system MultiMiTar, a Support Vector Machine (SVM) based classifier integrated with a multiobjective metaheuristic based feature selection technique. The robust performance of the proposed method is mainly the result of using high quality negative examples and selection of biologically relevant miRNA-targeting site context specific features. The features are selected by using a novel feature selection technique AMOSA-SVM, that integrates the multi objective optimization technique Archived Multi-Objective Simulated Annealing (AMOSA) and SVM. MultiMiTar is found to achieve much higher Matthew's correlation coefficient (MCC) of 0.583 and average class-wise accuracy (ACA) of 0.8 compared to the others target prediction methods for a completely independent test data set. The obtained MCC and ACA values of these algorithms range from -0.269 to 0.155 and 0.321 to 0.582, respectively. Moreover, it shows a more balanced result in terms of precision and sensitivity (recall) for the translationally repressed data set as compared to all the other existing methods. An important aspect is that the true positive predictions are distributed preferentially at the top of the ranked list that makes MultiMiTar reliable for the biologists. MultiMiTar is now available as an online tool at www.isical.ac.in/~bioinfo_miu/multimitar.htm. MultiMiTar software can be downloaded from www.isical.ac.in/~bioinfo_miu/multimitar-download.htm.

Opto-mechanical system design of test system for near-infrared and visible target

NASA Astrophysics Data System (ADS)

Wang, Chunyan; Zhu, Guodong; Wang, Yuchao

2014-12-01

Guidance precision is the key indexes of the guided weapon shooting. The factors of guidance precision including: information processing precision, control system accuracy, laser irradiation accuracy and so on. The laser irradiation precision is an important factor. This paper aimed at the demand of the precision test of laser irradiator，and developed the laser precision test system. The system consists of modified cassegrain system, the wide range CCD camera, tracking turntable and industrial PC, and makes visible light and near infrared target imaging at the same time with a Near IR camera. Through the analysis of the design results, when it exposures the target of 1000 meters that the system measurement precision is43mm, fully meet the needs of the laser precision test.

Study of a Satellite Attitude Control System Using Integrating Gyros as Torque Sources

NASA Technical Reports Server (NTRS)

White, John S.; Hansen, Q. Marion

1961-01-01

This report considers the use of single-degree-of-freedom integrating gyros as torque sources for precise control of satellite attitude. Some general design criteria are derived and applied to the specific example of the Orbiting Astronomical Observatory. The results of the analytical design are compared with the results of an analog computer study and also with experimental results from a low-friction platform. The steady-state and transient behavior of the system, as determined by the analysis, by the analog study, and by the experimental platform agreed quite well. The results of this study show that systems using integrating gyros for precise satellite attitude control can be designed to have a reasonably rapid and well-damped transient response, as well as very small steady-state errors. Furthermore, it is shown that the gyros act as rate sensors, as well as torque sources, so that no rate stabilization networks are required, and when no error sensor is available, the vehicle is still rate stabilized. Hence, it is shown that a major advantage of a gyro control system is that when the target is occulted, an alternate reference is not required.

Activatable iRGD-based peptide monolith: Targeting, internalization, and fluorescence activation for precise tumor imaging.

PubMed

Cho, Hong-Jun; Lee, Sung-Jin; Park, Sung-Jun; Paik, Chang H; Lee, Sang-Myung; Kim, Sehoon; Lee, Yoon-Sik

2016-09-10

A disulfide-bridged cyclic RGD peptide, named iRGD (internalizing RGD, c(CRGDK/RGPD/EC)), is known to facilitate tumor targeting as well as tissue penetration. After the RGD motif-induced targeting on αv integrins expressed near tumor tissue, iRGD encounters proteolytic cleavage to expose the CendR motif that promotes penetration into cancer cells via the interaction with neuropilin-1. Based on these proteolytic cleavage and internalization mechanism, we designed an iRGD-based monolithic imaging probe that integrates multiple functions (cancer-specific targeting, internalization and fluorescence activation) within a small peptide framework. To provide the capability of activatable fluorescence signaling, we conjugated a fluorescent dye to the N-terminal of iRGD, which was linked to the internalizing sequence (CendR motif), and a quencher to the opposite C-terminal. It turned out that fluorescence activation of the dye/quencher-conjugated monolithic peptide probe requires dual (reductive and proteolytic) cleavages on both disulfide and amide bond of iRGD peptide. Furthermore, the cleavage of the iRGD peptide leading to fluorescence recovery was indeed operative depending on the tumor-related angiogenic receptors (αvβ3 integrin and neuropilin-1) in vitro as well as in vivo. Compared to an 'always fluorescent' iRGD control probe without quencher conjugation, the dye/quencher-conjugated activatable monolithic peptide probe visualized tumor regions more precisely with lower background noise after intravenous injection, owing to the multifunctional responses specific to tumor microenvironment. All these results, along with minimal in vitro and in vivo toxicity profiles, suggest potential of the iRGD-based activatable monolithic peptide probe as a promising imaging agent for precise tumor diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Execution of saccadic eye movements affects speed perception

PubMed Central

Goettker, Alexander; Braun, Doris I.; Schütz, Alexander C.; Gegenfurtner, Karl R.

2018-01-01

Due to the foveal organization of our visual system we have to constantly move our eyes to gain precise information about our environment. Doing so massively alters the retinal input. This is problematic for the perception of moving objects, because physical motion and retinal motion become decoupled and the brain has to discount the eye movements to recover the speed of moving objects. Two different types of eye movements, pursuit and saccades, are combined for tracking. We investigated how the way we track moving targets can affect the perceived target speed. We found that the execution of corrective saccades during pursuit initiation modifies how fast the target is perceived compared with pure pursuit. When participants executed a forward (catch-up) saccade they perceived the target to be moving faster. When they executed a backward saccade they perceived the target to be moving more slowly. Variations in pursuit velocity without corrective saccades did not affect perceptual judgments. We present a model for these effects, assuming that the eye velocity signal for small corrective saccades gets integrated with the retinal velocity signal during pursuit. In our model, the execution of corrective saccades modulates the integration of these two signals by giving less weight to the retinal information around the time of corrective saccades. PMID:29440494

The ENGAGE study: Integrating neuroimaging, virtual reality and smartphone sensing to understand self-regulation for managing depression and obesity in a precision medicine model.

PubMed

Williams, Leanne M; Pines, Adam; Goldstein-Piekarski, Andrea N; Rosas, Lisa G; Kullar, Monica; Sacchet, Matthew D; Gevaert, Olivier; Bailenson, Jeremy; Lavori, Philip W; Dagum, Paul; Wandell, Brian; Correa, Carlos; Greenleaf, Walter; Suppes, Trisha; Perry, L Michael; Smyth, Joshua M; Lewis, Megan A; Venditti, Elizabeth M; Snowden, Mark; Simmons, Janine M; Ma, Jun

2018-02-01

Precision medicine models for personalizing achieving sustained behavior change are largely outside of current clinical practice. Yet, changing self-regulatory behaviors is fundamental to the self-management of complex lifestyle-related chronic conditions such as depression and obesity - two top contributors to the global burden of disease and disability. To optimize treatments and address these burdens, behavior change and self-regulation must be better understood in relation to their neurobiological underpinnings. Here, we present the conceptual framework and protocol for a novel study, "Engaging self-regulation targets to understand the mechanisms of behavior change and improve mood and weight outcomes (ENGAGE)". The ENGAGE study integrates neuroscience with behavioral science to better understand the self-regulation related mechanisms of behavior change for improving mood and weight outcomes among adults with comorbid depression and obesity. We collect assays of three self-regulation targets (emotion, cognition, and self-reflection) in multiple settings: neuroimaging and behavioral lab-based measures, virtual reality, and passive smartphone sampling. By connecting human neuroscience and behavioral science in this manner within the ENGAGE study, we develop a prototype for elucidating the underlying self-regulation mechanisms of behavior change outcomes and their application in optimizing intervention strategies for multiple chronic diseases. Copyright © 2017. Published by Elsevier Ltd.

Improved prediction of drug-target interactions using regularized least squares integrating with kernel fusion technique.

PubMed

Hao, Ming; Wang, Yanli; Bryant, Stephen H

2016-02-25

Identification of drug-target interactions (DTI) is a central task in drug discovery processes. In this work, a simple but effective regularized least squares integrating with nonlinear kernel fusion (RLS-KF) algorithm is proposed to perform DTI predictions. Using benchmark DTI datasets, our proposed algorithm achieves the state-of-the-art results with area under precision-recall curve (AUPR) of 0.915, 0.925, 0.853 and 0.909 for enzymes, ion channels (IC), G protein-coupled receptors (GPCR) and nuclear receptors (NR) based on 10 fold cross-validation. The performance can further be improved by using a recalculated kernel matrix, especially for the small set of nuclear receptors with AUPR of 0.945. Importantly, most of the top ranked interaction predictions can be validated by experimental data reported in the literature, bioassay results in the PubChem BioAssay database, as well as other previous studies. Our analysis suggests that the proposed RLS-KF is helpful for studying DTI, drug repositioning as well as polypharmacology, and may help to accelerate drug discovery by identifying novel drug targets. Published by Elsevier B.V.

In vivo gene correction with targeted sequence substitution through microhomology-mediated end joining.

PubMed

Shin, Jeong Hong; Jung, Soobin; Ramakrishna, Suresh; Kim, Hyongbum Henry; Lee, Junwon

2018-07-07

Genome editing technology using programmable nucleases has rapidly evolved in recent years. The primary mechanism to achieve precise integration of a transgene is mainly based on homology-directed repair (HDR). However, an HDR-based genome-editing approach is less efficient than non-homologous end-joining (NHEJ). Recently, a microhomology-mediated end-joining (MMEJ)-based transgene integration approach was developed, showing feasibility both in vitro and in vivo. We expanded this method to achieve targeted sequence substitution (TSS) of mutated sequences with normal sequences using double-guide RNAs (gRNAs), and a donor template flanking the microhomologies and target sequence of the gRNAs in vitro and in vivo. Our method could realize more efficient sequence substitution than the HDR-based method in vitro using a reporter cell line, and led to the survival of a hereditary tyrosinemia mouse model in vivo. The proposed MMEJ-based TSS approach could provide a novel therapeutic strategy, in addition to HDR, to achieve gene correction from a mutated sequence to a normal sequence. Copyright © 2018 Elsevier Inc. All rights reserved.

A multi-landing pad DNA integration platform for mammalian cell engineering

PubMed Central

Gaidukov, Leonid; Wroblewska, Liliana; Teague, Brian; Nelson, Tom; Zhang, Xin; Liu, Yan; Jagtap, Kalpana; Mamo, Selamawit; Tseng, Wen Allen; Lowe, Alexis; Das, Jishnu; Bandara, Kalpanie; Baijuraj, Swetha; Summers, Nevin M; Zhang, Lin; Weiss, Ron

2018-01-01

Abstract Engineering mammalian cell lines that stably express many transgenes requires the precise insertion of large amounts of heterologous DNA into well-characterized genomic loci, but current methods are limited. To facilitate reliable large-scale engineering of CHO cells, we identified 21 novel genomic sites that supported stable long-term expression of transgenes, and then constructed cell lines containing one, two or three ‘landing pad’ recombination sites at selected loci. By using a highly efficient BxB1 recombinase along with different selection markers at each site, we directed recombinase-mediated insertion of heterologous DNA to selected sites, including targeting all three with a single transfection. We used this method to controllably integrate up to nine copies of a monoclonal antibody, representing about 100 kb of heterologous DNA in 21 transcriptional units. Because the integration was targeted to pre-validated loci, recombinant protein expression remained stable for weeks and additional copies of the antibody cassette in the integrated payload resulted in a linear increase in antibody expression. Overall, this multi-copy site-specific integration platform allows for controllable and reproducible insertion of large amounts of DNA into stable genomic sites, which has broad applications for mammalian synthetic biology, recombinant protein production and biomanufacturing. PMID:29617873

Autonomous integrated GPS/INS navigation experiment for OMV. Phase 1: Feasibility study

NASA Technical Reports Server (NTRS)

Upadhyay, Triveni N.; Priovolos, George J.; Rhodehamel, Harley

1990-01-01

The phase 1 research focused on the experiment definition. A tightly integrated Global Positioning System/Inertial Navigation System (GPS/INS) navigation filter design was analyzed and was shown, via detailed computer simulation, to provide precise position, velocity, and attitude (alignment) data to support navigation and attitude control requirements of future NASA missions. The application of the integrated filter was also shown to provide the opportunity to calibrate inertial instrument errors which is particularly useful in reducing INS error growth during times of GPS outages. While the Orbital Maneuvering Vehicle (OMV) provides a good target platform for demonstration and for possible flight implementation to provide improved capability, a successful proof-of-concept ground demonstration can be obtained using any simulated mission scenario data, such as Space Transfer Vehicle, Shuttle-C, Space Station.

Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

PubMed

Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

2016-01-01

Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

TAPIR, a web server for the prediction of plant microRNA targets, including target mimics.

PubMed

Bonnet, Eric; He, Ying; Billiau, Kenny; Van de Peer, Yves

2010-06-15

We present a new web server called TAPIR, designed for the prediction of plant microRNA targets. The server offers the possibility to search for plant miRNA targets using a fast and a precise algorithm. The precise option is much slower but guarantees to find less perfectly paired miRNA-target duplexes. Furthermore, the precise option allows the prediction of target mimics, which are characterized by a miRNA-target duplex having a large loop, making them undetectable by traditional tools. The TAPIR web server can be accessed at: http://bioinformatics.psb.ugent.be/webtools/tapir. Supplementary data are available at Bioinformatics online.

Theoretical integration and the psychology of sport injury prevention.

PubMed

Chan, Derwin King-Chung; Hagger, Martin S

2012-09-01

Integrating different theories of motivation to facilitate or predict behaviour change has received an increasing amount of attention within the health, sport and exercise science literature. A recent review article in Sports Medicine, by Keats, Emery and Finch presented an integrated model using two prominent theories in social psychology, self-determination theory (SDT) and the theory of planned behaviour (TPB), aimed at explaining and enhancing athletes' adherence to sport injury prevention. While echoing their optimistic views about the utility of these two theories to explain adherence in this area and the virtues of theoretical integration, we would like to seize this opportunity to clarify several conceptual principles arising from the authors' integration of the theories. Clarifying the theoretical assumptions and explaining precisely how theoretical integration works is crucial not only for improving the comprehensiveness of the integrated framework for predicting injury prevention behaviour, but also to aid the design of effective intervention strategies targeting behavioural adherence. In this article, we use the integration of SDT and TPB as an example to demonstrate how theoretical integration can advance the understanding of injury prevention behaviour in sport.

High-Precision Pinpointing of Luminescent Targets in Encoder-Assisted Scanning Microscopy Allowing High-Speed Quantitative Analysis.

PubMed

Zheng, Xianlin; Lu, Yiqing; Zhao, Jiangbo; Zhang, Yuhai; Ren, Wei; Liu, Deming; Lu, Jie; Piper, James A; Leif, Robert C; Liu, Xiaogang; Jin, Dayong

2016-01-19

Compared with routine microscopy imaging of a few analytes at a time, rapid scanning through the whole sample area of a microscope slide to locate every single target object offers many advantages in terms of simplicity, speed, throughput, and potential for robust quantitative analysis. Existing techniques that accommodate solid-phase samples incorporating individual micrometer-sized targets generally rely on digital microscopy and image analysis, with intrinsically low throughput and reliability. Here, we report an advanced on-the-fly stage scanning method to achieve high-precision target location across the whole slide. By integrating X- and Y-axis linear encoders to a motorized stage as the virtual "grids" that provide real-time positional references, we demonstrate an orthogonal scanning automated microscopy (OSAM) technique which can search a coverslip area of 50 × 24 mm(2) in just 5.3 min and locate individual 15 μm lanthanide luminescent microspheres with standard deviations of 1.38 and 1.75 μm in X and Y directions. Alongside implementation of an autofocus unit that compensates the tilt of a slide in the Z-axis in real time, we increase the luminescence detection efficiency by 35% with an improved coefficient of variation. We demonstrate the capability of advanced OSAM for robust quantification of luminescence intensities and lifetimes for a variety of micrometer-scale luminescent targets, specifically single down-shifting and upconversion microspheres, crystalline microplates, and color-barcoded microrods, as well as quantitative suspension array assays of biotinylated-DNA functionalized upconversion nanoparticles.

Submillisecond Optogenetic Control of Neuronal Firing with Two-Photon Holographic Photoactivation of Chronos

PubMed Central

Ronzitti, Emiliano; Conti, Rossella; Zampini, Valeria; Tanese, Dimitrii; Klapoetke, Nathan; Boyden, Edward S.; Papagiakoumou, Eirini

2017-01-01

Optogenetic neuronal network manipulation promises to unravel a long-standing mystery in neuroscience: how does microcircuit activity relate causally to behavioral and pathological states? The challenge to evoke spikes with high spatial and temporal complexity necessitates further joint development of light-delivery approaches and custom opsins. Two-photon (2P) light-targeting strategies demonstrated in-depth generation of action potentials in photosensitive neurons both in vitro and in vivo, but thus far lack the temporal precision necessary to induce precisely timed spiking events. Here, we show that efficient current integration enabled by 2P holographic amplified laser illumination of Chronos, a highly light-sensitive and fast opsin, can evoke spikes with submillisecond precision and repeated firing up to 100 Hz in brain slices from Swiss male mice. These results pave the way for optogenetic manipulation with the spatial and temporal sophistication necessary to mimic natural microcircuit activity. SIGNIFICANCE STATEMENT To reveal causal links between neuronal activity and behavior, it is necessary to develop experimental strategies to induce spatially and temporally sophisticated perturbation of network microcircuits. Two-photon computer generated holography (2P-CGH) recently demonstrated 3D optogenetic control of selected pools of neurons with single-cell accuracy in depth in the brain. Here, we show that exciting the fast opsin Chronos with amplified laser 2P-CGH enables cellular-resolution targeting with unprecedented temporal control, driving spiking up to 100 Hz with submillisecond onset precision using low laser power densities. This system achieves a unique combination of spatial flexibility and temporal precision needed to pattern optogenetically inputs that mimic natural neuronal network activity patterns. PMID:28972125

Research on polarization imaging information parsing method

NASA Astrophysics Data System (ADS)

Yuan, Hongwu; Zhou, Pucheng; Wang, Xiaolong

2016-11-01

Polarization information parsing plays an important role in polarization imaging detection. This paper focus on the polarization information parsing method: Firstly, the general process of polarization information parsing is given, mainly including polarization image preprocessing, multiple polarization parameters calculation, polarization image fusion and polarization image tracking, etc.; And then the research achievements of the polarization information parsing method are presented, in terms of polarization image preprocessing, the polarization image registration method based on the maximum mutual information is designed. The experiment shows that this method can improve the precision of registration and be satisfied the need of polarization information parsing; In terms of multiple polarization parameters calculation, based on the omnidirectional polarization inversion model is built, a variety of polarization parameter images are obtained and the precision of inversion is to be improve obviously; In terms of polarization image fusion , using fuzzy integral and sparse representation, the multiple polarization parameters adaptive optimal fusion method is given, and the targets detection in complex scene is completed by using the clustering image segmentation algorithm based on fractal characters; In polarization image tracking, the average displacement polarization image characteristics of auxiliary particle filtering fusion tracking algorithm is put forward to achieve the smooth tracking of moving targets. Finally, the polarization information parsing method is applied to the polarization imaging detection of typical targets such as the camouflage target, the fog and latent fingerprints.

Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.

PubMed

Aida, Tomomi; Nakade, Shota; Sakuma, Tetsushi; Izu, Yayoi; Oishi, Ayu; Mochida, Keiji; Ishikubo, Harumi; Usami, Takako; Aizawa, Hidenori; Yamamoto, Takashi; Tanaka, Kohichi

2016-11-28

Although CRISPR/Cas enables one-step gene cassette knock-in, assembling targeting vectors containing long homology arms is a laborious process for high-throughput knock-in. We recently developed the CRISPR/Cas-based precise integration into the target chromosome (PITCh) system for a gene cassette knock-in without long homology arms mediated by microhomology-mediated end-joining. Here, we identified exonuclease 1 (Exo1) as an enhancer for PITCh in human cells. By combining the Exo1 and PITCh-directed donor vectors, we achieved convenient one-step knock-in of gene cassettes and floxed allele both in human cells and mouse zygotes. Our results provide a technical platform for high-throughput knock-in.

The system integration and verification testing of an orbital maneuvering vehicle for an air bearing floor

NASA Technical Reports Server (NTRS)

Shields, N. L., Jr.; Martin, M. F.; Paulukaitis, K. R.; Haslam, J. W., Jr.; Henderson, D. E.

1986-01-01

The teleoperator and Robotics Evaluation Facility (TOREF) is composed of a 4,000 square foot precision air bearing floor, the Teleoperator Motion Base, the Target Motion and Support Simulator, the mock-ups of the Hubble Space Telescope, Multi-mission Modular Spacecraft, and the Orbital Maneuvering Vehicle (OMV). The TOREF and its general capabilities to support the OMV and other remote system simulations; the facility operating procedures and requirements; and the results of generic OMV investigations are summarized.

Differential GPS for air transport: Status

NASA Technical Reports Server (NTRS)

Hueschen, Richard M.

1993-01-01

The presentation presents background on what the Global Navigation Satellite System (GNSS) is, desired target dates for initial GNSS capabilities for aircraft operations, and a description of differential GPS (Global Positioning System). The presentation also presents an overview of joint flight tests conducted by LaRC and Honeywell on an integrated differential GPS/inertial reference unit (IRU) navigation system. The overview describes the system tested and the results of the flight tests. The last item presented is an overview of a current grant with Ohio University from LaRC which has the goal of developing a precision DGPS navigation system based on interferometry techniques. The fundamentals of GPS interferometry are presented and its application to determine attitude and heading and precision positioning are shown. The presentation concludes with the current status of the grant.

Computation as the mechanistic bridge between precision medicine and systems therapeutics.

PubMed

Hansen, J; Iyengar, R

2013-01-01

Over the past 50 years, like molecular cell biology, medicine and pharmacology have been driven by a reductionist approach. The focus on individual genes and cellular components as disease loci and drug targets has been a necessary step in understanding the basic mechanisms underlying tissue/organ physiology and drug action. Recent progress in genomics and proteomics, as well as advances in other technologies that enable large-scale data gathering and computational approaches, is providing new knowledge of both normal and disease states. Systems-biology approaches enable integration of knowledge from different types of data for precision medicine and systems therapeutics. In this review, we describe recent studies that contribute to these emerging fields and discuss how together these fields can lead to a mechanism-based therapy for individual patients.

Computation as the Mechanistic Bridge Between Precision Medicine and Systems Therapeutics

PubMed Central

Hansen, J; Iyengar, R

2014-01-01

Over the past 50 years, like molecular cell biology, medicine and pharmacology have been driven by a reductionist approach. The focus on individual genes and cellular components as disease loci and drug targets has been a necessary step in understanding the basic mechanisms underlying tissue/organ physiology and drug action. Recent progress in genomics and proteomics, as well as advances in other technologies that enable large-scale data gathering and computational approaches, is providing new knowledge of both normal and disease states. Systems-biology approaches enable integration of knowledge from different types of data for precision medicine and systems therapeutics. In this review, we describe recent studies that contribute to these emerging fields and discuss how together these fields can lead to a mechanism-based therapy for individual patients. PMID:23212109

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.

CT Guidance is Needed to Achieve Reproducible Positioning of the Mouse Head for Repeat Precision Cranial Irradiation

PubMed Central

Armour, M.; Ford, E.; Iordachita, I.; Wong, J.

2011-01-01

To study the effects of cranial irradiation, we have constructed an all-plastic mouse bed equipped with an immobilizing head holder. The bed integrates with our in-house Small Animal Radiation Research Platform (SARRP) for precision focal irradiation experiments and cone-beam CT. We assessed the reproducibility of our head holder to determine the need for CT based targeting in cranial irradiation studies. To measure the holder’s reproducibility, a C57BL/6 mouse was positioned and CT scanned nine times. Image sets were loaded into the Pinnacle3 radiation treatment planning system and were registered to one another by one investigator using rigid body alignment of the cranial regions. Rotational and translational offsets were measured. The average vector shift between scans was 0.80 ± 0.49 mm. Such a shift is too large to selectively treat subregions of the mouse brain. In response, we use onboard imaging to guide cranial irradiation applications that require sub-millimeter precision. PMID:20041766

PrecisePrimer: an easy-to-use web server for designing PCR primers for DNA library cloning and DNA shuffling.

PubMed

Pauthenier, Cyrille; Faulon, Jean-Loup

2014-07-01

PrecisePrimer is a web-based primer design software made to assist experimentalists in any repetitive primer design task such as preparing, cloning and shuffling DNA libraries. Unlike other popular primer design tools, it is conceived to generate primer libraries with popular PCR polymerase buffers proposed as pre-set options. PrecisePrimer is also meant to design primers in batches, such as for DNA libraries creation of DNA shuffling experiments and to have the simplest interface possible. It integrates the most up-to-date melting temperature algorithms validated with experimental data, and cross validated with other computational tools. We generated a library of primers for the extraction and cloning of 61 genes from yeast DNA genomic extract using default parameters. All primer pairs efficiently amplified their target without any optimization of the PCR conditions. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

CT guidance is needed to achieve reproducible positioning of the mouse head for repeat precision cranial irradiation.

PubMed

Armour, M; Ford, E; Iordachita, I; Wong, J

2010-01-01

To study the effects of cranial irradiation, we have constructed an all-plastic mouse bed equipped with an immobilizing head holder. The bed integrates with our in-house Small Animal Radiation Research Platform (SARRP) for precision focal irradiation experiments and cone-beam CT. We assessed the reproducibility of our head holder to determine the need for CT-based targeting in cranial irradiation studies. To measure the holder's reproducibility, a C57BL/6 mouse was positioned and CT-scanned nine times. Image sets were loaded into the Pinnacle(3) radiation treatment planning system and were registered to one another by one investigator using rigid body alignment of the cranial regions. Rotational and translational offsets were measured. The average vector shift between scans was 0.80 +/- 0.49 mm. Such a shift is too large to selectively treat subregions of the mouse brain. In response, we use onboard imaging to guide cranial irradiation applications that require sub-millimeter precision.

Integration of sparse electrophysiological measurements with preoperative MRI using 3D surface estimation in deep brain stimulation surgery

NASA Astrophysics Data System (ADS)

Husch, Andreas; Gemmar, Peter; Thunberg, Johan; Hertel, Frank

2017-03-01

Intraoperative microelectrode recordings (MER) have been used for several decades to guide neurosurgeons during the implantation of Deep Brain Stimulation (DBS) electrodes, especially when targeting the subthalamic nucleus (STN) to suppress the symptoms of Parkinson's Disease. The standard approach is to use an array of up to five MER electrodes in a fixed configuration. Interpretation of the recorded signals yields a spatially very sparse set of information about the morphology of the respective brain structures in the targeted area. However, no aid is currently available for surgeons to intraoperatively integrate this information with other data available on the patient's individual morphology (e.g. MR imaging data used for surgical planning). This integration might allow surgeons to better determine the most probable position of the electrodes within the target structure during surgery. This paper suggests a method for reconstructing a surface patch from the sparse MER dataset utilizing additional a priori knowledge about the geometrical configuration of the measurement electrodes. The conventional representation of MER measurements as intervals of target region/non-target region is therefore transformed into an equivalent boundary set representation, allowing ecient point-based calculations. Subsequently, the problem is to integrate the resulting patch with a preoperative model of the target structure, which can be formulated as registration problem minimizing a distance measure between the two surfaces. When restricting this registration procedure to translations, which is reasonable given certain geometric considerations, the problem can be solved globally by employing an exhaustive search with arbitrary precision in polynomial time. The proposed method is demonstrated using bilateral STN/Substantia Nigra segmentation data from preoperative MRIs of 17 Patients with simulated MER electrode placement. When using simulated data of heavily perturbed electrodes and subsequent MER measurements, our optimization resulted in an improvement of the electrode position within 1 mm of the ground truth in 80.29% of the cases.

Targets Mask U-Net for Wind Turbines Detection in Remote Sensing Images

NASA Astrophysics Data System (ADS)

Han, M.; Wang, H.; Wang, G.; Liu, Y.

2018-04-01

To detect wind turbines precisely and quickly in very high resolution remote sensing images (VHRRSI) we propose target mask U-Net. This convolution neural network (CNN), which is carefully designed to be a wide-field detector, models the pixel class assignment to wind turbines and their context information. The shadow, which is the context information of the target in this study, has been regarded as part of a wind turbine instance. We have trained the target mask U-Net on training dataset, which is composed of down sampled image blocks and instance mask blocks. Some post-processes have been integrated to eliminate wrong spots and produce bounding boxes of wind turbine instances. The evaluation metrics prove the reliability and effectiveness of our method for the average F1-score of our detection method is up to 0.97. The comparison of detection accuracy and time consuming with the weakly supervised targets detection method based on CNN illustrates the superiority of our method.

Target templates: the precision of mental representations affects attentional guidance and decision-making in visual search.

PubMed

Hout, Michael C; Goldinger, Stephen D

2015-01-01

When people look for things in the environment, they use target templates-mental representations of the objects they are attempting to locate-to guide attention and to assess incoming visual input as potential targets. However, unlike laboratory participants, searchers in the real world rarely have perfect knowledge regarding the potential appearance of targets. In seven experiments, we examined how the precision of target templates affects the ability to conduct visual search. Specifically, we degraded template precision in two ways: 1) by contaminating searchers' templates with inaccurate features, and 2) by introducing extraneous features to the template that were unhelpful. We recorded eye movements to allow inferences regarding the relative extents to which attentional guidance and decision-making are hindered by template imprecision. Our findings support a dual-function theory of the target template and highlight the importance of examining template precision in visual search.

Target templates: the precision of mental representations affects attentional guidance and decision-making in visual search

PubMed Central

Hout, Michael C.; Goldinger, Stephen D.

2014-01-01

When people look for things in the environment, they use target templates—mental representations of the objects they are attempting to locate—to guide attention and to assess incoming visual input as potential targets. However, unlike laboratory participants, searchers in the real world rarely have perfect knowledge regarding the potential appearance of targets. In seven experiments, we examined how the precision of target templates affects the ability to conduct visual search. Specifically, we degraded template precision in two ways: 1) by contaminating searchers’ templates with inaccurate features, and 2) by introducing extraneous features to the template that were unhelpful. We recorded eye movements to allow inferences regarding the relative extents to which attentional guidance and decision-making are hindered by template imprecision. Our findings support a dual-function theory of the target template and highlight the importance of examining template precision in visual search. PMID:25214306

An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology

NASA Astrophysics Data System (ADS)

Aravanis, Alexander M.; Wang, Li-Ping; Zhang, Feng; Meltzer, Leslie A.; Mogri, Murtaza Z.; Schneider, M. Bret; Deisseroth, Karl

2007-09-01

Neural interface technology has made enormous strides in recent years but stimulating electrodes remain incapable of reliably targeting specific cell types (e.g. excitatory or inhibitory neurons) within neural tissue. This obstacle has major scientific and clinical implications. For example, there is intense debate among physicians, neuroengineers and neuroscientists regarding the relevant cell types recruited during deep brain stimulation (DBS); moreover, many debilitating side effects of DBS likely result from lack of cell-type specificity. We describe here a novel optical neural interface technology that will allow neuroengineers to optically address specific cell types in vivo with millisecond temporal precision. Channelrhodopsin-2 (ChR2), an algal light-activated ion channel we developed for use in mammals, can give rise to safe, light-driven stimulation of CNS neurons on a timescale of milliseconds. Because ChR2 is genetically targetable, specific populations of neurons even sparsely embedded within intact circuitry can be stimulated with high temporal precision. Here we report the first in vivo behavioral demonstration of a functional optical neural interface (ONI) in intact animals, involving integrated fiberoptic and optogenetic technology. We developed a solid-state laser diode system that can be pulsed with millisecond precision, outputs 20 mW of power at 473 nm, and is coupled to a lightweight, flexible multimode optical fiber, ~200 µm in diameter. To capitalize on the unique advantages of this system, we specifically targeted ChR2 to excitatory cells in vivo with the CaMKIIα promoter. Under these conditions, the intensity of light exiting the fiber (~380 mW mm-2) was sufficient to drive excitatory neurons in vivo and control motor cortex function with behavioral output in intact rodents. No exogenous chemical cofactor was needed at any point, a crucial finding for in vivo work in large mammals. Achieving modulation of behavior with optical control of neuronal subtypes may give rise to fundamental network-level insights complementary to what electrode methodologies have taught us, and the emerging optogenetic toolkit may find application across a broad range of neuroscience, neuroengineering and clinical questions.

Precise integration of inducible transcriptional elements (PrIITE) enables absolute control of gene expression.

PubMed

Pinto, Rita; Hansen, Lars; Hintze, John; Almeida, Raquel; Larsen, Sylvester; Coskun, Mehmet; Davidsen, Johanne; Mitchelmore, Cathy; David, Leonor; Troelsen, Jesper Thorvald; Bennett, Eric Paul

2017-07-27

Tetracycline-based inducible systems provide powerful methods for functional studies where gene expression can be controlled. However, the lack of tight control of the inducible system, leading to leakiness and adverse effects caused by undesirable tetracycline dosage requirements, has proven to be a limitation. Here, we report that the combined use of genome editing tools and last generation Tet-On systems can resolve these issues. Our principle is based on precise integration of inducible transcriptional elements (coined PrIITE) targeted to: (i) exons of an endogenous gene of interest (GOI) and (ii) a safe harbor locus. Using PrIITE cells harboring a GFP reporter or CDX2 transcription factor, we demonstrate discrete inducibility of gene expression with complete abrogation of leakiness. CDX2 PrIITE cells generated by this approach uncovered novel CDX2 downstream effector genes. Our results provide a strategy for characterization of dose-dependent effector functions of essential genes that require absence of endogenous gene expression. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Passive range estimation using dual baseline triangulation

NASA Astrophysics Data System (ADS)

Pieper, Ronald J.; Cooper, Alfred W.; Pelegris, G.

1996-03-01

Modern combat systems based on active radar sensing suffer disadvantages against low-flying targets in cluttered backgrounds. Use of passive infrared sensors with these systems, either in cooperation or as an alternative, shows potential for improving target detection and declaration range for targets crossing the horizon. Realization of this potential requires fusion of target position data from dissimilar sensors, or passive sensor measurement of target range. The availability of passive sensors that can supply both range and bearing data on such targets would significantly extend the robustness of an integrated ship self-defense system. This paper considers a new method of range determination with passive sensors based on the principle of triangulation, extending the principle to two orthogonal baselines. The performance of single or double baseline triangulation depends on sensor bearing precision and direction to target. An expression for maximum triangulation range at a required accuracy is derived as a function of polar angle relative to the center of the dual-baseline system. Limitations in the dual- baseline model due to the geometrically assessed horizon are also considered.

High volume fabrication of laser targets using MEMS techniques

NASA Astrophysics Data System (ADS)

Spindloe, C.; Arthur, G.; Hall, F.; Tomlinson, S.; Potter, R.; Kar, S.; Green, J.; Higginbotham, A.; Booth, N.; Tolley, M. K.

2016-04-01

The latest techniques for the fabrication of high power laser targets, using processes developed for the manufacture of Micro-Electro-Mechanical System (MEMS) devices are discussed. These laser targets are designed to meet the needs of the increased shot numbers that are available in the latest design of laser facilities. Traditionally laser targets have been fabricated using conventional machining or coarse etching processes and have been produced in quantities of 10s to low 100s. Such targets can be used for high complexity experiments such as Inertial Fusion Energy (IFE) studies and can have many complex components that need assembling and characterisation with high precision. Using the techniques that are common to MEMS devices and integrating these with an existing target fabrication capability we are able to manufacture and deliver targets to these systems. It also enables us to manufacture novel targets that have not been possible using other techniques. In addition, developments in the positioning systems that are required to deliver these targets to the laser focus are also required and a system to deliver the target to a focus of an F2 beam at 0.1Hz is discussed.

Integrated navigation fusion strategy of INS/UWB for indoor carrier attitude angle and position synchronous tracking.

PubMed

Fan, Qigao; Wu, Yaheng; Hui, Jing; Wu, Lei; Yu, Zhenzhong; Zhou, Lijuan

2014-01-01

In some GPS failure conditions, positioning for mobile target is difficult. This paper proposed a new method based on INS/UWB for attitude angle and position synchronous tracking of indoor carrier. Firstly, error model of INS/UWB integrated system is built, including error equation of INS and UWB. And combined filtering model of INS/UWB is researched. Simulation results show that the two subsystems are complementary. Secondly, integrated navigation data fusion strategy of INS/UWB based on Kalman filtering theory is proposed. Simulation results show that FAKF method is better than the conventional Kalman filtering. Finally, an indoor experiment platform is established to verify the integrated navigation theory of INS/UWB, which is geared to the needs of coal mine working environment. Static and dynamic positioning results show that the INS/UWB integrated navigation system is stable and real-time, positioning precision meets the requirements of working condition and is better than any independent subsystem.

Self-Calibrated In-Process Photogrammetry for Large Raw Part Measurement and Alignment before Machining

PubMed Central

Mendikute, Alberto; Zatarain, Mikel; Bertelsen, Álvaro; Leizea, Ibai

2017-01-01

Photogrammetry methods are being used more and more as a 3D technique for large scale metrology applications in industry. Optical targets are placed on an object and images are taken around it, where measuring traceability is provided by precise off-process pre-calibrated digital cameras and scale bars. According to the 2D target image coordinates, target 3D coordinates and camera views are jointly computed. One of the applications of photogrammetry is the measurement of raw part surfaces prior to its machining. For this application, post-process bundle adjustment has usually been adopted for computing the 3D scene. With that approach, a high computation time is observed, leading in practice to time consuming and user dependent iterative review and re-processing procedures until an adequate set of images is taken, limiting its potential for fast, easy-to-use, and precise measurements. In this paper, a new efficient procedure is presented for solving the bundle adjustment problem in portable photogrammetry. In-process bundle computing capability is demonstrated on a consumer grade desktop PC, enabling quasi real time 2D image and 3D scene computing. Additionally, a method for the self-calibration of camera and lens distortion has been integrated into the in-process approach due to its potential for highest precision when using low cost non-specialized digital cameras. Measurement traceability is set only by scale bars available in the measuring scene, avoiding the uncertainty contribution of off-process camera calibration procedures or the use of special purpose calibration artifacts. The developed self-calibrated in-process photogrammetry has been evaluated both in a pilot case scenario and in industrial scenarios for raw part measurement, showing a total in-process computing time typically below 1 s per image up to a maximum of 2 s during the last stages of the computed industrial scenes, along with a relative precision of 1/10,000 (e.g., 0.1 mm error in 1 m) with an error RMS below 0.2 pixels at image plane, ranging at the same performance reported for portable photogrammetry with precise off-process pre-calibrated cameras. PMID:28891946

Self-Calibrated In-Process Photogrammetry for Large Raw Part Measurement and Alignment before Machining.

PubMed

Mendikute, Alberto; Yagüe-Fabra, José A; Zatarain, Mikel; Bertelsen, Álvaro; Leizea, Ibai

2017-09-09

Photogrammetry methods are being used more and more as a 3D technique for large scale metrology applications in industry. Optical targets are placed on an object and images are taken around it, where measuring traceability is provided by precise off-process pre-calibrated digital cameras and scale bars. According to the 2D target image coordinates, target 3D coordinates and camera views are jointly computed. One of the applications of photogrammetry is the measurement of raw part surfaces prior to its machining. For this application, post-process bundle adjustment has usually been adopted for computing the 3D scene. With that approach, a high computation time is observed, leading in practice to time consuming and user dependent iterative review and re-processing procedures until an adequate set of images is taken, limiting its potential for fast, easy-to-use, and precise measurements. In this paper, a new efficient procedure is presented for solving the bundle adjustment problem in portable photogrammetry. In-process bundle computing capability is demonstrated on a consumer grade desktop PC, enabling quasi real time 2D image and 3D scene computing. Additionally, a method for the self-calibration of camera and lens distortion has been integrated into the in-process approach due to its potential for highest precision when using low cost non-specialized digital cameras. Measurement traceability is set only by scale bars available in the measuring scene, avoiding the uncertainty contribution of off-process camera calibration procedures or the use of special purpose calibration artifacts. The developed self-calibrated in-process photogrammetry has been evaluated both in a pilot case scenario and in industrial scenarios for raw part measurement, showing a total in-process computing time typically below 1 s per image up to a maximum of 2 s during the last stages of the computed industrial scenes, along with a relative precision of 1/10,000 (e.g. 0.1 mm error in 1 m) with an error RMS below 0.2 pixels at image plane, ranging at the same performance reported for portable photogrammetry with precise off-process pre-calibrated cameras.

Active laser radar (lidar) for measurement of corresponding height and reflectance images

NASA Astrophysics Data System (ADS)

Froehlich, Christoph; Mettenleiter, M.; Haertl, F.

1997-08-01

For the survey and inspection of environmental objects, a non-tactile, robust and precise imaging of height and depth is the basis sensor technology. For visual inspection,surface classification, and documentation purposes, however, additional information concerning reflectance of measured objects is necessary. High-speed acquisition of both geometric and visual information is achieved by means of an active laser radar, supporting consistent 3D height and 2D reflectance images. The laser radar is an optical-wavelength system, and is comparable to devices built by ERIM, Odetics, and Perceptron, measuring the range between sensor and target surfaces as well as the reflectance of the target surface, which corresponds to the magnitude of the back scattered laser energy. In contrast to these range sensing devices, the laser radar under consideration is designed for high speed and precise operation in both indoor and outdoor environments, emitting a minimum of near-IR laser energy. It integrates a laser range measurement system and a mechanical deflection system for 3D environmental measurements. This paper reports on design details of the laser radar for surface inspection tasks. It outlines the performance requirements and introduces the measurement principle. The hardware design, including the main modules, such as the laser head, the high frequency unit, the laser beam deflection system, and the digital signal processing unit are discussed.the signal processing unit consists of dedicated signal processors for real-time sensor data preprocessing as well as a sensor computer for high-level image analysis and feature extraction. The paper focuses on performance data of the system, including noise, drift over time, precision, and accuracy with measurements. It discuses the influences of ambient light, surface material of the target, and ambient temperature for range accuracy and range precision. Furthermore, experimental results from inspection of buildings, monuments and industrial environments are presented. The paper concludes by summarizing results achieved in industrial environments and gives a short outlook to future work.

Tensor Factorization for Precision Medicine in Heart Failure with Preserved Ejection Fraction

PubMed Central

Luo, Yuan; Ahmad, Faraz S.; Shah, Sanjiv J.

2017-01-01

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome that may benefit from improved subtyping in order to better characterize its pathophysiology and to develop novel targeted therapies. The United States Precision Medicine Initiative comes amid the rapid growth in quantity and modality of clinical data for HFpEF patients ranging from deep phenotypic to trans-omic data. Tensor factorization, a form of machine learning, allows for the integration of multiple data modalities to derive clinically relevant HFpEF subtypes that may have significant differences in underlying pathophysiology and differential response to therapies. Tensor factorization also allows for better interpretability by supporting dimensionality reduction and identifying latent groups of data for meaningful summarization of both features and disease outcomes. In this narrative review, we analyze the modest literature on the application of tensor factorization to related biomedical fields including genotyping and phenotyping. Based on the cited work including work of our own, we suggest multiple tensor factorization formulations capable of integrating the deep phenotypic and trans-omic modalities of data for HFpEF, or accounting for interactions between genetic variants at different -omic hierarchies. We encourage extensive experimental studies to tackle challenges in applying tensor factorization for precision medicine in HFpEF, including effectively incorporating existing medical knowledge, properly accounting for uncertainty, and efficiently enforcing sparsity for better interpretability. PMID:28116551

Applications of RNA Indexes for Precision Oncology in Breast Cancer.

PubMed

Ma, Liming; Liang, Zirui; Zhou, Hui; Qu, Lianghu

2018-05-09

Precision oncology aims to offer the most appropriate treatments to cancer patients mainly based on their individual genetic information. Genomics has provided numerous valuable data on driver mutations and risk loci; however, it remains a formidable challenge to transform these data into therapeutic agents. Transcriptomics describes the multifarious expression patterns of both mRNAs and non-coding RNAs (ncRNAs), which facilitates the deciphering of genomic codes. In this review, we take breast cancer as an example to demonstrate the applications of these rich RNA resources in precision medicine exploration. These include the use of mRNA profiles in triple-negative breast cancer (TNBC) subtyping to inform corresponding candidate targeted therapies; current advancements and achievements of high-throughput RNA interference (RNAi) screening technologies in breast cancer; and microRNAs as functional signatures for defining cell identities and regulating the biological activities of breast cancer cells. We summarize the benefits of transcriptomic analyses in breast cancer management and propose that unscrambling the core signaling networks of cancer may be an important task of multiple-omic data integration for precision oncology. Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Field precision machining technology of target chamber in ICF lasers

NASA Astrophysics Data System (ADS)

Xu, Yuanli; Wu, Wenkai; Shi, Sucun; Duan, Lin; Chen, Gang; Wang, Baoxu; Song, Yugang; Liu, Huilin; Zhu, Mingzhi

2016-10-01

In ICF lasers, many independent laser beams are required to be positioned on target with a very high degree of accuracy during a shot. The target chamber provides a precision platform and datum reference for final optics assembly and target collimation and location system. The target chamber consists of shell with welded flanges, reinforced concrete pedestal, and lateral support structure. The field precision machining technology of target chamber in ICF lasers have been developed based on ShenGuangIII (SGIII). The same center of the target chamber is adopted in the process of design, fabrication, and alignment. The technologies of beam collimation and datum reference transformation are developed for the fabrication, positioning and adjustment of target chamber. A supporting and rotating mechanism and a special drilling machine are developed to bore the holes of ports. An adjustment mechanism is designed to accurately position the target chamber. In order to ensure the collimation requirements of the beam leading and focusing and the target positioning, custom-machined spacers are used to accurately correct the alignment error of the ports. Finally, this paper describes the chamber center, orientation, and centering alignment error measurements of SGIII. The measurements show the field precision machining of SGIII target chamber meet its design requirement. These information can be used on similar systems.

RC64, a Rad-Hard Many-Core High- Performance DSP for Space Applications

NASA Astrophysics Data System (ADS)

Ginosar, Ran; Aviely, Peleg; Gellis, Hagay; Liran, Tuvia; Israeli, Tsvika; Nesher, Roy; Lange, Fredy; Dobkin, Reuven; Meirov, Henri; Reznik, Dror

2015-09-01

RC64, a novel rad-hard 64-core signal processing chip targets DSP performance of 75 GMACs (16bit), 150 GOPS and 38 single precision GFLOPS while dissipating less than 10 Watts. RC64 integrates advanced DSP cores with a multi-bank shared memory and a hardware scheduler, also supporting DDR2/3 memory and twelve 3.125 Gbps full duplex high speed serial links using SpaceFibre and other protocols. The programming model employs sequential fine-grain tasks and a separate task map to define task dependencies. RC64 is implemented as a 300 MHz integrated circuit on a 65nm CMOS technology, assembled in hermetically sealed ceramic CCGA624 package and qualified to the highest space standards.

RC64, a Rad-Hard Many-Core High-Performance DSP for Space Applications

NASA Astrophysics Data System (ADS)

Ginosar, Ran; Aviely, Peleg; Liran, Tuvia; Alon, Dov; Mandler, Alberto; Lange, Fredy; Dobkin, Reuven; Goldberg, Miki

2014-08-01

RC64, a novel rad-hard 64-core signal processing chip targets DSP performance of 75 GMACs (16bit), 150 GOPS and 20 single precision GFLOPS while dissipating less than 10 Watts. RC64 integrates advanced DSP cores with a multi-bank shared memory and a hardware scheduler, also supporting DDR2/3 memory and twelve 2.5 Gbps full duplex high speed serial links using SpaceFibre and other protocols. The programming model employs sequential fine-grain tasks and a separate task map to define task dependencies. RC64 is implemented as a 300 MHz integrated circuit on a 65nm CMOS technology, assembled in hermetically sealed ceramic CCGA624 package and qualified to the highest space standards.

Combination of a proteomics approach and reengineering of meso scale network models for prediction of mode-of-action for tyrosine kinase inhibitors.

PubMed

Balabanov, Stefan; Wilhelm, Thomas; Venz, Simone; Keller, Gunhild; Scharf, Christian; Pospisil, Heike; Braig, Melanie; Barett, Christine; Bokemeyer, Carsten; Walther, Reinhard; Brümmendorf, Tim H; Schuppert, Andreas

2013-01-01

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs.

Combination of a Proteomics Approach and Reengineering of Meso Scale Network Models for Prediction of Mode-of-Action for Tyrosine Kinase Inhibitors

PubMed Central

Balabanov, Stefan; Wilhelm, Thomas; Venz, Simone; Keller, Gunhild; Scharf, Christian; Pospisil, Heike; Braig, Melanie; Barett, Christine; Bokemeyer, Carsten; Walther, Reinhard

2013-01-01

In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is of highest relevance. Recent approaches for identification of MoA have employed various techniques for modeling of well defined signaling pathways including structural information, changes in phenotypic behavior of cells and gene expression patterns after drug treatment. However, efficient approaches focusing on proteome wide data for the identification of MoA including interference with mutations are underrepresented. As mutations are key drivers of drug resistance in molecularly targeted tumor therapies, efficient analysis and modeling of downstream effects of mutations on drug MoA is a key to efficient development of improved targeted anti-cancer drugs. Here we present a combination of a global proteome analysis, reengineering of network models and integration of apoptosis data used to infer the mode-of-action of various tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) cell lines expressing wild type as well as TKI resistance conferring mutants of BCR-ABL. The inferred network models provide a tool to predict the main MoA of drugs as well as to grouping of drugs with known similar kinase inhibitory activity patterns in comparison to drugs with an additional MoA. We believe that our direct network reconstruction approach, demonstrated on proteomics data, can provide a complementary method to the established network reconstruction approaches for the preclinical modeling of the MoA of various types of targeted drugs in cancer treatment. Hence it may contribute to the more precise prediction of clinically relevant on- and off-target effects of TKIs. PMID:23326482

Seamless Genome Editing in Rice via Gene Targeting and Precise Marker Elimination.

PubMed

Nishizawa-Yokoi, Ayako; Saika, Hiroaki; Toki, Seiichi

2016-01-01

Positive-negative selection using hygromycin phosphotransferase (hpt) and diphtheria toxin A-fragment (DT-A) as positive and negative selection markers, respectively, allows enrichment of cells harboring target genes modified via gene targeting (GT). We have developed a successful GT system employing positive-negative selection and subsequent precise marker excision via the piggyBac transposon derived from the cabbage looper moth to introduce desired modifications into target genes in the rice genome. This approach could be applied to the precision genome editing of almost all endogenous genes throughout the genome, at least in rice.

Precision medicine and precision therapeutics: hedgehog signaling pathway, basal cell carcinoma and beyond.

PubMed

Mohan, Shalini V; Chang, Anne Lynn S

2014-06-01

Precision medicine and precision therapeutics is currently in its infancy with tremendous potential to improve patient care by better identifying individuals at risk for skin cancer and predict tumor responses to treatment. This review focuses on the Hedgehog signaling pathway, its critical role in the pathogenesis of basal cell carcinoma, and the emergence of targeted treatments for advanced basal cell carcinoma. Opportunities to utilize precision medicine are outlined, such as molecular profiling to predict basal cell carcinoma response to targeted therapy and to inform therapeutic decisions.

Imaging laser radar for high-speed monitoring of the environment

NASA Astrophysics Data System (ADS)

Froehlich, Christoph; Mettenleiter, M.; Haertl, F.

1998-01-01

In order to establish mobile robot operations and to realize survey and inspection tasks, robust and precise measurements of the geometry of the 3D environment is the basis sensor technology. For visual inspection, surface classification, and documentation purposes, however, additional information concerning reflectance of measured objects is necessary. High-speed acquisition of both geometric and visual information is achieved by means of an active laser radar, supporting consistent range and reflectance images. The laser radar developed at Zoller + Froehlich (ZF) is an optical-wavelength system measuring the range between sensor and target surface as well as the reflectance of the target surface, which corresponds to the magnitude of the back scattered laser energy. In contrast to other range sensing devices, the ZF system is designed for high-speed and high- performance operation in real indoor and outdoor environments, emitting a minimum of near-IR laser energy. It integrates a single-point laser measurement system and a mechanical deflection system for 3D environmental measurements. This paper reports details of the laser radar which is designed to cover requirements with medium range applications. It outlines the performance requirements and introduces the two-frequency phase-shift measurement principle. The hardware design of the single-point laser measurement system, including the main modulates, such as the laser head, the high frequency unit and the signal processing unit are discussed in detail. The paper focuses on performance data of the laser radar, including noise, drift over time, precision, and accuracy with measurements. It discusses the influences of ambient light, surface material of the target, and ambient temperature for range accuracy and range precision. Furthermore, experimental results from inspection of tunnels, buildings, monuments and industrial environments are presented. The paper concludes by summarizing results and gives a short outlook to future work.

Genetic Mutations and Epigenetic Modifications: Driving Cancer and Informing Precision Medicine

PubMed Central

Coyle, Krysta Mila; Boudreau, Jeanette E.

2017-01-01

Cancer treatment is undergoing a significant revolution from “one-size-fits-all” cytotoxic therapies to tailored approaches that precisely target molecular alterations. Precision strategies for drug development and patient stratification, based on the molecular features of tumors, are the next logical step in a long history of approaches to cancer therapy. In this review, we discuss the history of cancer treatment from generic natural extracts and radical surgical procedures to site-specific and combinatorial treatment regimens, which have incrementally improved patient outcomes. We discuss the related contributions of genetics and epigenetics to cancer progression and the response to targeted therapies and identify challenges and opportunities for the success of precision medicine. The identification of patients who will benefit from targeted therapies is more complex than simply identifying patients whose tumors harbour the targeted aberration, and intratumoral heterogeneity makes it difficult to determine if a precision therapy is successful during treatment. This heterogeneity enables tumors to develop resistance to targeted approaches; therefore, the rational combination of therapeutic agents will limit the threat of acquired resistance to therapeutic success. By incorporating the view of malignant transformation modulated by networks of genetic and epigenetic interactions, molecular strategies will enable precision medicine for effective treatment across cancer subtypes. PMID:28685150

Smart sensors II; Proceedings of the Seminar, San Diego, CA, July 31, August 1, 1980

NASA Astrophysics Data System (ADS)

Barbe, D. F.

1980-01-01

Topics discussed include technology for smart sensors, smart sensors for tracking and surveillance, and techniques and algorithms for smart sensors. Papers are presented on the application of very large scale integrated circuits to smart sensors, imaging charge-coupled devices for deep-space surveillance, ultra-precise star tracking using charge coupled devices, and automatic target identification of blurred images with super-resolution features. Attention is also given to smart sensors for terminal homing, algorithms for estimating image position, and the computational efficiency of multiple image registration algorithms.

Precision disablement aiming system

DOEpatents

Monda, Mark J.; Hobart, Clinton G.; Gladwell, Thomas Scott

2016-02-16

A disrupter to a target may be precisely aimed by positioning a radiation source to direct radiation towards the target, and a detector is positioned to detect radiation that passes through the target. An aiming device is positioned between the radiation source and the target, wherein a mechanical feature of the aiming device is superimposed on the target in a captured radiographic image. The location of the aiming device in the radiographic image is used to aim a disrupter towards the target.

Self-Assembled Smart Nanocarriers for Targeted Drug Delivery.

PubMed

Cui, Wei; Li, Junbai; Decher, Gero

2016-02-10

Nanostructured drug-carrier systems promise numerous benefits for drug delivery. They can be engineered to precisely control drug-release rates or to target specific sites within the body with a specific amount of therapeutic agent. However, to achieve the best therapeutic effects, the systems should be designed for carrying the optimum amount of a drug to the desired target where it should be released at the optimum rate for a specified time. Despite numerous attempts, fulfilling all of these requirements in a synergistic way remains a huge challenge. The trend in drug delivery is consequently directed toward integrated multifunctional carrier systems, providing selective recognition in combination with sustained or triggered release. Capsules as vesicular systems enable drugs to be confined for controlled release. Furthermore, carriers modified with recognition groups can enhance the capability of encapsulated drug efficacy. Here, recent advances are reviewed regarding designing and preparing assembled capsules with targeting ligands or size controllable for selective recognition in drug delivery. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Regulation of expression, activity and localization of fungal chitin synthases

PubMed Central

Rogg, Luise E.; Fortwendel, Jarrod R.; Juvvadi, Praveen R.; Steinbach, William J.

2013-01-01

The fungal cell wall represents an attractive target for pharmacologic inhibition, as many of the components are fungal-specific. Though targeted inhibition of β-glucan synthesis is effective treatment for certain fungal infections, the ability of the cell wall to dynamically compensate via the cell wall integrity pathway may limit overall efficacy. To date, chitin synthesis inhibitors have not been successfully deployed in the clinical setting. Fungal chitin synthesis is a complex and highly regulated process. Regulation of chitin synthesis occurs on multiple levels, thus targeting of these regulatory pathways may represent an exciting alternative approach. A variety of signaling pathways have been implicated in chitin synthase regulation, at both transcriptional and post-transcriptional levels. Recent research suggests that localization of chitin synthases likely represents a major regulatory mechanism. However, much of the regulatory machinery is not necessarily shared among different chitin synthases. Thus, an in depth understanding of the precise roles of each protein in cell wall maintenance and repair will be essential to identifying the most likely therapeutic targets. PMID:21526913

MRI-Guided Focused Ultrasound Surgery

PubMed Central

Jolesz, Ferenc A.

2014-01-01

MRI-guided focused ultrasound (MRgFUS) surgery is a noninvasive thermal ablation method that uses magnetic resonance imaging (MRI) for target definition, treatment planning, and closed-loop control of energy deposition. Integrating FUS and MRI as a therapy delivery system allows us to localize, target, and monitor in real time, and thus to ablate targeted tissue without damaging normal structures. This precision makes MRgFUS an attractive alternative to surgical resection or radiation therapy of benign and malignant tumors. Already approved for the treatment of uterine fibroids, MRgFUS is in ongoing clinical trials for the treatment of breast, liver, prostate, and brain cancer and for the palliation of pain in bone metastasis. In addition to thermal ablation, FUS, with or without the use of microbubbles, can temporarily change vascular or cell membrane permeability and release or activate various compounds for targeted drug delivery or gene therapy. A disruptive technology, MRgFUS provides new therapeutic approaches and may cause major changes in patient management and several medical disciplines. PMID:19630579

FIRESTORM: a collaborative network suite application for rapid sensor data processing and precise decisive responses

NASA Astrophysics Data System (ADS)

Kaniyantethu, Shaji

2011-06-01

This paper discusses the many features and composed technologies in Firestorm™ - a Distributed Collaborative Fires and Effects software. Modern response management systems capitalize on the capabilities of a plethora of sensors and its output for situational awareness. Firestorm utilizes a unique networked lethality approach by integrating unmanned air and ground vehicles to provide target handoff and sharing of data between humans and sensors. The system employs Bayesian networks for track management of sensor data, and distributed auction algorithms for allocating targets and delivering the right effect without information overload to the Warfighter. Firestorm Networked Effects Component provides joint weapon-target pairing, attack guidance, target selection standards, and other fires and effects components. Moreover, the open and modular architecture allows for easy integration with new data sources. Versatility and adaptability of the application enable it to devise and dispense a suitable response to a wide variety of scenarios. Recently, this application was used for detecting and countering a vehicle intruder with the help of radio frequency spotter sensor, command driven cameras, remote weapon system, portable vehicle arresting barrier, and an unmanned aerial vehicle - which confirmed the presence of the intruder, as well as provided lethal/non-lethal response and battle damage assessment. The completed demonstrations have proved Firestorm's™ validity and feasibility to predict, detect, neutralize, and protect key assets and/or area against a variety of possible threats. The sensors and responding assets can be deployed with numerous configurations to cover the various terrain and environmental conditions, and can be integrated to a number of platforms.

OncDRS: An integrative clinical and genomic data platform for enabling translational research and precision medicine

PubMed Central

Orechia, John; Pathak, Ameet; Shi, Yunling; Nawani, Aniket; Belozerov, Andrey; Fontes, Caitlin; Lakhiani, Camille; Jawale, Chetan; Patel, Chetansharan; Quinn, Daniel; Botvinnik, Dmitry; Mei, Eddie; Cotter, Elizabeth; Byleckie, James; Ullman-Cullere, Mollie; Chhetri, Padam; Chalasani, Poornima; Karnam, Purushotham; Beaudoin, Ronald; Sahu, Sandeep; Belozerova, Yelena; Mathew, Jomol P.

2015-01-01

We live in the genomic era of medicine, where a patient's genomic/molecular data is becoming increasingly important for disease diagnosis, identification of targeted therapy, and risk assessment for adverse reactions. However, decoding the genomic test results and integrating it with clinical data for retrospective studies and cohort identification for prospective clinical trials is still a challenging task. In order to overcome these barriers, we developed an overarching enterprise informatics framework for translational research and personalized medicine called Synergistic Patient and Research Knowledge Systems (SPARKS) and a suite of tools called Oncology Data Retrieval Systems (OncDRS). OncDRS enables seamless data integration, secure and self-navigated query and extraction of clinical and genomic data from heterogeneous sources. Within a year of release, the system has facilitated more than 1500 research queries and has delivered data for more than 50 research studies. PMID:27054074

Development of a cerebral circulation model for the automatic control of brain physiology.

PubMed

Utsuki, T

2015-01-01

In various clinical guidelines of brain injury, intracranial pressure (ICP), cerebral blood flow (CBF) and brain temperature (BT) are essential targets for precise management for brain resuscitation. In addition, the integrated automatic control of BT, ICP, and CBF is required for improving therapeutic effects and reducing medical costs and staff burden. Thus, a new model of cerebral circulation was developed in this study for integrative automatic control. With this model, the CBF and cerebral perfusion pressure of a normal adult male were regionally calculated according to cerebrovascular structure, blood viscosity, blood distribution, CBF autoregulation, and ICP. The analysis results were consistent with physiological knowledge already obtained with conventional studies. Therefore, the developed model is potentially available for the integrative control of the physiological state of the brain as a reference model of an automatic control system, or as a controlled object in various control simulations.

Transit light curves with finite integration time: Fisher information analysis

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

Price, Ellen M.; Rogers, Leslie A.

2014-10-10

Kepler has revolutionized the study of transiting planets with its unprecedented photometric precision on more than 150,000 target stars. Most of the transiting planet candidates detected by Kepler have been observed as long-cadence targets with 30 minute integration times, and the upcoming Transiting Exoplanet Survey Satellite will record full frame images with a similar integration time. Integrations of 30 minutes affect the transit shape, particularly for small planets and in cases of low signal to noise. Using the Fisher information matrix technique, we derive analytic approximations for the variances and covariances on the transit parameters obtained from fitting light curvemore » photometry collected with a finite integration time. We find that binning the light curve can significantly increase the uncertainties and covariances on the inferred parameters when comparing scenarios with constant total signal to noise (constant total integration time in the absence of read noise). Uncertainties on the transit ingress/egress time increase by a factor of 34 for Earth-size planets and 3.4 for Jupiter-size planets around Sun-like stars for integration times of 30 minutes compared to instantaneously sampled light curves. Similarly, uncertainties on the mid-transit time for Earth and Jupiter-size planets increase by factors of 3.9 and 1.4. Uncertainties on the transit depth are largely unaffected by finite integration times. While correlations among the transit depth, ingress duration, and transit duration all increase in magnitude with longer integration times, the mid-transit time remains uncorrelated with the other parameters. We provide code in Python and Mathematica for predicting the variances and covariances at www.its.caltech.edu/∼eprice.« less

Realizing drug repositioning by adapting a recommendation system to handle the process.

PubMed

Ozsoy, Makbule Guclin; Özyer, Tansel; Polat, Faruk; Alhajj, Reda

2018-04-12

Drug repositioning is the process of identifying new targets for known drugs. It can be used to overcome problems associated with traditional drug discovery by adapting existing drugs to treat new discovered diseases. Thus, it may reduce associated risk, cost and time required to identify and verify new drugs. Nowadays, drug repositioning has received more attention from industry and academia. To tackle this problem, researchers have applied many different computational methods and have used various features of drugs and diseases. In this study, we contribute to the ongoing research efforts by combining multiple features, namely chemical structures, protein interactions and side-effects to predict new indications of target drugs. To achieve our target, we realize drug repositioning as a recommendation process and this leads to a new perspective in tackling the problem. The utilized recommendation method is based on Pareto dominance and collaborative filtering. It can also integrate multiple data-sources and multiple features. For the computation part, we applied several settings and we compared their performance. Evaluation results show that the proposed method can achieve more concentrated predictions with high precision, where nearly half of the predictions are true. Compared to other state of the art methods described in the literature, the proposed method is better at making right predictions by having higher precision. The reported results demonstrate the applicability and effectiveness of recommendation methods for drug repositioning.

Method calibration of the model 13145 infrared target projectors

NASA Astrophysics Data System (ADS)

Huang, Jianxia; Gao, Yuan; Han, Ying

2014-11-01

The SBIR Model 13145 Infrared Target Projectors ( The following abbreviation Evaluation Unit ) used for characterizing the performances of infrared imaging system. Test items: SiTF, MTF, NETD, MRTD, MDTD, NPS. Infrared target projectors includes two area blackbodies, a 12 position target wheel, all reflective collimator. It provide high spatial frequency differential targets, Precision differential targets imaged by infrared imaging system. And by photoelectricity convert on simulate signal or digital signal. Applications software (IR Windows TM 2001) evaluate characterizing the performances of infrared imaging system. With regards to as a whole calibration, first differently calibration for distributed component , According to calibration specification for area blackbody to calibration area blackbody, by means of to amend error factor to calibration of all reflective collimator, radiance calibration of an infrared target projectors using the SR5000 spectral radiometer, and to analyze systematic error. With regards to as parameter of infrared imaging system, need to integrate evaluation method. According to regulation with -GJB2340-1995 General specification for military thermal imaging sets -testing parameters of infrared imaging system, the results compare with results from Optical Calibration Testing Laboratory . As a goal to real calibration performances of the Evaluation Unit.

Integrated titer plate-injector head for microdrop array preparation, storage and transfer

DOEpatents

Swierkowski, Stefan P.

2000-01-01

An integrated titer plate-injector head for preparing and storing two-dimensional (2-D) arrays of microdrops and for ejecting part or all of the microdrops and inserting same precisely into 2-D arrays of deposition sites with micrometer precision. The titer plate-injector head includes integrated precision formed nozzles with appropriate hydrophobic surface features and evaporative constraints. A reusable pressure head with a pressure equalizing feature is added to the titer plate to perform simultaneous precision sample ejection. The titer plate-injector head may be utilized in various applications including capillary electrophoresis, chemical flow injection analysis, microsample array preparation, etc.

Integrative methods for analyzing big data in precision medicine.

PubMed

Gligorijević, Vladimir; Malod-Dognin, Noël; Pržulj, Nataša

2016-03-01

We provide an overview of recent developments in big data analyses in the context of precision medicine and health informatics. With the advance in technologies capturing molecular and medical data, we entered the area of "Big Data" in biology and medicine. These data offer many opportunities to advance precision medicine. We outline key challenges in precision medicine and present recent advances in data integration-based methods to uncover personalized information from big data produced by various omics studies. We survey recent integrative methods for disease subtyping, biomarkers discovery, and drug repurposing, and list the tools that are available to domain scientists. Given the ever-growing nature of these big data, we highlight key issues that big data integration methods will face. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Infrared small target detection technology based on OpenCV

NASA Astrophysics Data System (ADS)

Liu, Lei; Huang, Zhijian

2013-05-01

Accurate and fast detection of infrared (IR) dim target has very important meaning for infrared precise guidance, early warning, video surveillance, etc. In this paper, some basic principles and the implementing flow charts of a series of algorithms for target detection are described. These algorithms are traditional two-frame difference method, improved three-frame difference method, background estimate and frame difference fusion method, and building background with neighborhood mean method. On the foundation of above works, an infrared target detection software platform which is developed by OpenCV and MFC is introduced. Three kinds of tracking algorithms are integrated in this software. In order to explain the software clearly, the framework and the function are described in this paper. At last, the experiments are performed for some real-life IR images. The whole algorithm implementing processes and results are analyzed, and those algorithms for detection targets are evaluated from the two aspects of subjective and objective. The results prove that the proposed method has satisfying detection effectiveness and robustness. Meanwhile, it has high detection efficiency and can be used for real-time detection.

Infrared small target detection technology based on OpenCV

NASA Astrophysics Data System (ADS)

Liu, Lei; Huang, Zhijian

2013-09-01

Accurate and fast detection of infrared (IR) dim target has very important meaning for infrared precise guidance, early warning, video surveillance, etc. In this paper, some basic principles and the implementing flow charts of a series of algorithms for target detection are described. These algorithms are traditional two-frame difference method, improved three-frame difference method, background estimate and frame difference fusion method, and building background with neighborhood mean method. On the foundation of above works, an infrared target detection software platform which is developed by OpenCV and MFC is introduced. Three kinds of tracking algorithms are integrated in this software. In order to explain the software clearly, the framework and the function are described in this paper. At last, the experiments are performed for some real-life IR images. The whole algorithm implementing processes and results are analyzed, and those algorithms for detection targets are evaluated from the two aspects of subjective and objective. The results prove that the proposed method has satisfying detection effectiveness and robustness. Meanwhile, it has high detection efficiency and can be used for real-time detection.

Precision medicine for advanced prostate cancer

PubMed Central

Mullane, Stephanie A.; Van Allen, Eliezer M.

2016-01-01

Purpose of review Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Recent findings Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Summary Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients. PMID:26909474

Precision medicine for advanced prostate cancer.

PubMed

Mullane, Stephanie A; Van Allen, Eliezer M

2016-05-01

Precision cancer medicine, the use of genomic profiling of patient tumors at the point-of-care to inform treatment decisions, is rapidly changing treatment strategies across cancer types. Precision medicine for advanced prostate cancer may identify new treatment strategies and change clinical practice. In this review, we discuss the potential and challenges of precision medicine in advanced prostate cancer. Although primary prostate cancers do not harbor highly recurrent targetable genomic alterations, recent reports on the genomics of metastatic castration-resistant prostate cancer has shown multiple targetable alterations in castration-resistant prostate cancer metastatic biopsies. Therapeutic implications include targeting prevalent DNA repair pathway alterations with PARP-1 inhibition in genomically defined subsets of patients, among other genomically stratified targets. In addition, multiple recent efforts have demonstrated the promise of liquid tumor profiling (e.g., profiling circulating tumor cells or cell-free tumor DNA) and highlighted the necessary steps to scale these approaches in prostate cancer. Although still in the initial phase of precision medicine for prostate cancer, there is extraordinary potential for clinical impact. Efforts to overcome current scientific and clinical barriers will enable widespread use of precision medicine approaches for advanced prostate cancer patients.

Update on the integrated histopathological and genetic classification of medulloblastoma – a practical diagnostic guideline

PubMed Central

Pietsch, Torsten; Haberler, Christine

2016-01-01

The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma. The genetically defined component comprises the four entities WNT-activated, SHH-activated and TP53 wildtype, SHH-activated and TP53 mutant, or non-WNT/non-SHH medulloblastoma. Robust and validated methods are available to allow a precise diagnosis of these medulloblastoma entities according to the updated WHO classification, and for differential diagnostic purposes. A combination of immunohistochemical markers including β-catenin, Yap1, p75-NGFR, Otx2, and p53, in combination with targeted sequencing and copy number assessment such as FISH analysis for MYC genes allows a precise assignment of patients for risk-adapted stratification. It also allows comparison to results of study cohorts in the past and provides a robust basis for further treatment refinement. PMID:27781424

Update on the integrated histopathological and genetic classification of medulloblastoma - a practical diagnostic guideline.

PubMed

Pietsch, Torsten; Haberler, Christine

The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma. The genetically defined component comprises the four entities WNT-activated, SHH-activated and TP53 wildtype, SHH-activated and TP53 mutant, or non-WNT/non-SHH medulloblastoma. Robust and validated methods are available to allow a precise diagnosis of these medulloblastoma entities according to the updated WHO classification, and for differential diagnostic purposes. A combination of immunohistochemical markers including β-catenin, Yap1, p75-NGFR, Otx2, and p53, in combination with targeted sequencing and copy number assessment such as FISH analysis for MYC genes allows a precise assignment of patients for risk-adapted stratification. It also allows comparison to results of study cohorts in the past and provides a robust basis for further treatment refinement.
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Design and Validation of Exoskeleton Actuated by Soft Modules toward Neurorehabilitation-Vision-Based Control for Precise Reaching Motion of Upper Limb.

PubMed

Oguntosin, Victoria W; Mori, Yoshiki; Kim, Hyejong; Nasuto, Slawomir J; Kawamura, Sadao; Hayashi, Yoshikatsu

2017-01-01

We demonstrated the design, production, and functional properties of the Exoskeleton Actuated by the Soft Modules (EAsoftM). Integrating the 3D printed exoskeleton with passive joints to compensate gravity and with active joints to rotate the shoulder and elbow joints resulted in ultra-light system that could assist planar reaching motion by using the vision-based control law. The EAsoftM can support the reaching motion with compliance realized by the soft materials and pneumatic actuation. In addition, the vision-based control law has been proposed for the precise control over the target reaching motion within the millimeter scale. Aiming at rehabilitation exercise for individuals, typically soft actuators have been developed for relatively small motions, such as grasping motion, and one of the challenges has been to extend their use for a wider range reaching motion. The proposed EAsoftM presented one possible solution for this challenge by transmitting the torque effectively along the anatomically aligned with a human body exoskeleton. The proposed integrated systems will be an ideal solution for neurorehabilitation where affordable, wearable, and portable systems are required to be customized for individuals with specific motor impairments.

Design and Validation of Exoskeleton Actuated by Soft Modules toward Neurorehabilitation—Vision-Based Control for Precise Reaching Motion of Upper Limb

PubMed Central

Oguntosin, Victoria W.; Mori, Yoshiki; Kim, Hyejong; Nasuto, Slawomir J.; Kawamura, Sadao; Hayashi, Yoshikatsu

2017-01-01

We demonstrated the design, production, and functional properties of the Exoskeleton Actuated by the Soft Modules (EAsoftM). Integrating the 3D printed exoskeleton with passive joints to compensate gravity and with active joints to rotate the shoulder and elbow joints resulted in ultra-light system that could assist planar reaching motion by using the vision-based control law. The EAsoftM can support the reaching motion with compliance realized by the soft materials and pneumatic actuation. In addition, the vision-based control law has been proposed for the precise control over the target reaching motion within the millimeter scale. Aiming at rehabilitation exercise for individuals, typically soft actuators have been developed for relatively small motions, such as grasping motion, and one of the challenges has been to extend their use for a wider range reaching motion. The proposed EAsoftM presented one possible solution for this challenge by transmitting the torque effectively along the anatomically aligned with a human body exoskeleton. The proposed integrated systems will be an ideal solution for neurorehabilitation where affordable, wearable, and portable systems are required to be customized for individuals with specific motor impairments. PMID:28736514

Composite adaptive control of belt polishing force for aero-engine blade

NASA Astrophysics Data System (ADS)

Zhsao, Pengbing; Shi, Yaoyao

2013-09-01

The existing methods for blade polishing mainly focus on robot polishing and manual grinding. Due to the difficulty in high-precision control of the polishing force, the blade surface precision is very low in robot polishing, in particular, quality of the inlet and exhaust edges can not satisfy the processing requirements. Manual grinding has low efficiency, high labor intensity and unstable processing quality, moreover, the polished surface is vulnerable to burn, and the surface precision and integrity are difficult to ensure. In order to further improve the profile accuracy and surface quality, a pneumatic flexible polishing force-exerting mechanism is designed and a dual-mode switching composite adaptive control(DSCAC) strategy is proposed, which combines Bang-Bang control and model reference adaptive control based on fuzzy neural network(MRACFNN) together. By the mode decision-making mechanism, Bang-Bang control is used to track the control command signal quickly when the actual polishing force is far away from the target value, and MRACFNN is utilized in smaller error ranges to improve the system robustness and control precision. Based on the mathematical model of the force-exerting mechanism, simulation analysis is implemented on DSCAC. Simulation results show that the output polishing force can better track the given signal. Finally, the blade polishing experiments are carried out on the designed polishing equipment. Experimental results show that DSCAC can effectively mitigate the influence of gas compressibility, valve dead-time effect, valve nonlinear flow, cylinder friction, measurement noise and other interference on the control precision of polishing force, which has high control precision, strong robustness, strong anti-interference ability and other advantages compared with MRACFNN. The proposed research achieves high-precision control of the polishing force, effectively improves the blade machining precision and surface consistency, and significantly reduces the surface roughness.

Precision wildlife medicine: applications of the human-centred precision medicine revolution to species conservation.

PubMed

Whilde, Jenny; Martindale, Mark Q; Duffy, David J

2017-05-01

The current species extinction crisis is being exacerbated by an increased rate of emergence of epizootic disease. Human-induced factors including habitat degradation, loss of biodiversity and wildlife population reductions resulting in reduced genetic variation are accelerating disease emergence. Novel, efficient and effective approaches are required to combat these epizootic events. Here, we present the case for the application of human precision medicine approaches to wildlife medicine in order to enhance species conservation efforts. We consider how the precision medicine revolution, coupled with the advances made in genomics, may provide a powerful and feasible approach to identifying and treating wildlife diseases in a targeted, effective and streamlined manner. A number of case studies of threatened species are presented which demonstrate the applicability of precision medicine to wildlife conservation, including sea turtles, amphibians and Tasmanian devils. These examples show how species conservation could be improved by using precision medicine techniques to determine novel treatments and management strategies for the specific medical conditions hampering efforts to restore population levels. Additionally, a precision medicine approach to wildlife health has in turn the potential to provide deeper insights into human health and the possibility of stemming and alleviating the impacts of zoonotic diseases. The integration of the currently emerging Precision Medicine Initiative with the concepts of EcoHealth (aiming for sustainable health of people, animals and ecosystems through transdisciplinary action research) and One Health (recognizing the intimate connection of humans, animal and ecosystem health and addressing a wide range of risks at the animal-human-ecosystem interface through a coordinated, collaborative, interdisciplinary approach) has great potential to deliver a deeper and broader interdisciplinary-based understanding of both wildlife and human diseases. © 2016 John Wiley & Sons Ltd.

Diffusion and perfusion weighted magnetic resonance imaging for tumor volume definition in radiotherapy of brain tumors.

PubMed

Guo, Lu; Wang, Gang; Feng, Yuanming; Yu, Tonggang; Guo, Yu; Bai, Xu; Ye, Zhaoxiang

2016-09-21

Accurate target volume delineation is crucial for the radiotherapy of tumors. Diffusion and perfusion magnetic resonance imaging (MRI) can provide functional information about brain tumors, and they are able to detect tumor volume and physiological changes beyond the lesions shown on conventional MRI. This review examines recent studies that utilized diffusion and perfusion MRI for tumor volume definition in radiotherapy of brain tumors, and it presents the opportunities and challenges in the integration of multimodal functional MRI into clinical practice. The results indicate that specialized and robust post-processing algorithms and tools are needed for the precise alignment of targets on the images, and comprehensive validations with more clinical data are important for the improvement of the correlation between histopathologic results and MRI parameter images.

Capturing a failure of an ASIC in-situ, using infrared radiometry and image processing software

NASA Technical Reports Server (NTRS)

Ruiz, Ronald P.

2003-01-01

Failures in electronic devices can sometimes be tricky to locate-especially if they are buried inside radiation-shielded containers designed to work in outer space. Such was the case with a malfunctioning ASIC (Application Specific Integrated Circuit) that was drawing excessive power at a specific temperature during temperature cycle testing. To analyze the failure, infrared radiometry (thermography) was used in combination with image processing software to locate precisely where the power was being dissipated at the moment the failure took place. The IR imaging software was used to make the image of the target and background, appear as unity. As testing proceeded and the failure mode was reached, temperature changes revealed the precise location of the fault. The results gave the design engineers the information they needed to fix the problem. This paper describes the techniques and equipment used to accomplish this failure analysis.

Patient Segmentation Analysis Offers Significant Benefits For Integrated Care And Support.

PubMed

Vuik, Sabine I; Mayer, Erik K; Darzi, Ara

2016-05-01

Integrated care aims to organize care around the patient instead of the provider. It is therefore crucial to understand differences across patients and their needs. Segmentation analysis that uses big data can help divide a patient population into distinct groups, which can then be targeted with care models and intervention programs tailored to their needs. In this article we explore the potential applications of patient segmentation in integrated care. We propose a framework for population strategies in integrated care-whole populations, subpopulations, and high-risk populations-and show how patient segmentation can support these strategies. Through international case examples, we illustrate practical considerations such as choosing a segmentation logic, accessing data, and tailoring care models. Important issues for policy makers to consider are trade-offs between simplicity and precision, trade-offs between customized and off-the-shelf solutions, and the availability of linked data sets. We conclude that segmentation can provide many benefits to integrated care, and we encourage policy makers to support its use. Project HOPE—The People-to-People Health Foundation, Inc.

Autonomous Rover Traverse and Precise Arm Placement on Remotely Designated Targets

NASA Technical Reports Server (NTRS)

Nesnas, Issa A.; Pivtoraiko, Mihail N.; Kelly, Alonzo; Fleder, Michael

2012-01-01

This software controls a rover platform to traverse rocky terrain autonomously, plan paths, and avoid obstacles using its stereo hazard and navigation cameras. It does so while continuously tracking a target of interest selected from 10 20 m away. The rover drives and tracks the target until it reaches the vicinity of the target. The rover then positions itself to approach the target, deploys its robotic arm, and places the end effector instrument on the designated target to within 2-3-cm accuracy of the originally selected target. This software features continuous navigation in a fairly rocky field in an outdoor environment and the ability to enable the rover to avoid large rocks and traverse over smaller ones. Using point-and-click mouse commands, a scientist designates targets in the initial imagery acquired from the rover s mast cameras. The navigation software uses stereo imaging, traversability analysis, path planning, trajectory generation, and trajectory execution. It also includes visual target tracking of a designated target selected from 10 m away while continuously navigating the rocky terrain. Improvements in this design include steering while driving, which uses continuous curvature paths. There are also several improvements to the traversability analyzer, including improved data fusion of traversability maps that result from pose estimation uncertainties, dealing with boundary effects to enable tighter maneuvers, and handling a wider range of obstacles. This work advances what has been previously developed and integrated on the Mars Exploration Rovers by using algorithms that are capable of traversing more rock-dense terrains, enabling tight, thread-the-needle maneuvers. These algorithms were integrated on the newly refurbished Athena Mars research rover, and were fielded in the JPL Mars Yard. Forty-three runs were conducted with targets at distances ranging from 5 to 15 m, and a success rate of 93% was achieved for placement of the instrument within 2-3 cm of the target.

Genomic deletions created upon LINE-1 retrotransposition.

PubMed

Gilbert, Nicolas; Lutz-Prigge, Sheila; Moran, John V

2002-08-09

LINE-1 (L1) retrotransposition continues to impact the human genome, yet little is known about how L1 integrates into DNA. Here, we developed a plasmid-based rescue system and have used it to recover 37 new L1 retrotransposition events from cultured human cells. Sequencing of the insertions revealed the usual L1 structural hallmarks; however, in four instances, retrotransposition generated large target site deletions. Remarkably, three of those resulted in the formation of chimeric L1s, containing the 5' end of an endogenous L1 fused precisely to our engineered L1. Thus, our data demonstrate multiple pathways for L1 integration in cultured cells, and show that L1 is not simply an insertional mutagen, but that its retrotransposition can result in significant deletions of genomic sequence.

Regression-Based Identification of Behavior-Encoding Neurons During Large-Scale Optical Imaging of Neural Activity at Cellular Resolution

PubMed Central

Miri, Andrew; Daie, Kayvon; Burdine, Rebecca D.; Aksay, Emre

2011-01-01

The advent of methods for optical imaging of large-scale neural activity at cellular resolution in behaving animals presents the problem of identifying behavior-encoding cells within the resulting image time series. Rapid and precise identification of cells with particular neural encoding would facilitate targeted activity measurements and perturbations useful in characterizing the operating principles of neural circuits. Here we report a regression-based approach to semiautomatically identify neurons that is based on the correlation of fluorescence time series with quantitative measurements of behavior. The approach is illustrated with a novel preparation allowing synchronous eye tracking and two-photon laser scanning fluorescence imaging of calcium changes in populations of hindbrain neurons during spontaneous eye movement in the larval zebrafish. Putative velocity-to-position oculomotor integrator neurons were identified that showed a broad spatial distribution and diversity of encoding. Optical identification of integrator neurons was confirmed with targeted loose-patch electrical recording and laser ablation. The general regression-based approach we demonstrate should be widely applicable to calcium imaging time series in behaving animals. PMID:21084686

Shooting for the Moon or Flying Too Near the Sun? Crossing the Value Rubicon in Precision Cancer Care.

PubMed

Lawler, Mark; French, Declan; Henderson, Raymond; Aggarwal, Ajay; Sullivan, Richard

In his last two State of the Union addresses, President Barack Obama has focused on the need to deliver innovative solutions to improve human health, through the Precision Medicine Initiative in 2015 and the recently announced Cancer Moonshot in 2016. Precision cancer care has delivered clear patient benefit, but even for high-impact medicines such as imatinib mesylate (Glivec) in chronic myeloid leukaemia, the excitement at the success of this practice-changing clinical intervention has been somewhat tempered by the escalating price of this 'poster child' for precision cancer medicine (PCM). Recent studies on the costs of cancer drugs have revealed significant price differentials, which are a major causative factor behind disparities in the access to new generations of immunological and molecularly targeted agents. In this perspective, we will discuss the benefits of PCM to modern cancer control, but also emphasise how increasing costs are rendering the current approaches to integrating the paradigm of PCM unsustainable. Despite the ever increasing pressure on cancer and health care budgets, innovation will and must continue. Value-based frameworks offer one of the most rational approaches for policymakers committed to improving cancer outcomes through a public health approach. © 2016 S. Karger AG, Basel.

Experimental new automatic tools for robotic stereotactic neurosurgery: towards "no hands" procedure of leads implantation into a brain target.

PubMed

Mazzone, P; Arena, P; Cantelli, L; Spampinato, G; Sposato, S; Cozzolino, S; Demarinis, P; Muscato, G

2016-07-01

The use of robotics in neurosurgery and, particularly, in stereotactic neurosurgery, is becoming more and more adopted because of the great advantages that it offers. Robotic manipulators easily allow to achieve great precision, reliability, and rapidity in the positioning of surgical instruments or devices in the brain. The aim of this work was to experimentally verify a fully automatic "no hands" surgical procedure. The integration of neuroimaging to data for planning the surgery, followed by application of new specific surgical tools, permitted the realization of a fully automated robotic implantation of leads in brain targets. An anthropomorphic commercial manipulator was utilized. In a preliminary phase, a software to plan surgery was developed, and the surgical tools were tested first during a simulation and then on a skull mock-up. In such a way, several tools were developed and tested, and the basis for an innovative surgical procedure arose. The final experimentation was carried out on anesthetized "large white" pigs. The determination of stereotactic parameters for the correct planning to reach the intended target was performed with the same technique currently employed in human stereotactic neurosurgery, and the robotic system revealed to be reliable and precise in reaching the target. The results of this work strengthen the possibility that a neurosurgeon may be substituted by a machine, and may represent the beginning of a new approach in the current clinical practice. Moreover, this possibility may have a great impact not only on stereotactic functional procedures but also on the entire domain of neurosurgery.

Analysis of calibration accuracy of cameras with different target sizes for large field of view

NASA Astrophysics Data System (ADS)

Zhang, Jin; Chai, Zhiwen; Long, Changyu; Deng, Huaxia; Ma, Mengchao; Zhong, Xiang; Yu, Huan

2018-03-01

Visual measurement plays an increasingly important role in the field o f aerospace, ship and machinery manufacturing. Camera calibration of large field-of-view is a critical part of visual measurement . For the issue a large scale target is difficult to be produced, and the precision can not to be guaranteed. While a small target has the advantage of produced of high precision, but only local optimal solutions can be obtained . Therefore, studying the most suitable ratio of the target size to the camera field of view to ensure the calibration precision requirement of the wide field-of-view is required. In this paper, the cameras are calibrated by a series of different dimensions of checkerboard calibration target s and round calibration targets, respectively. The ratios of the target size to the camera field-of-view are 9%, 18%, 27%, 36%, 45%, 54%, 63%, 72%, 81% and 90%. The target is placed in different positions in the camera field to obtain the camera parameters of different positions . Then, the distribution curves of the reprojection mean error of the feature points' restructure in different ratios are analyzed. The experimental data demonstrate that with the ratio of the target size to the camera field-of-view increas ing, the precision of calibration is accordingly improved, and the reprojection mean error changes slightly when the ratio is above 45%.

On the Impact of Localization and Density Control Algorithms in Target Tracking Applications for Wireless Sensor Networks

PubMed Central

Campos, Andre N.; Souza, Efren L.; Nakamura, Fabiola G.; Nakamura, Eduardo F.; Rodrigues, Joel J. P. C.

2012-01-01

Target tracking is an important application of wireless sensor networks. The networks' ability to locate and track an object is directed linked to the nodes' ability to locate themselves. Consequently, localization systems are essential for target tracking applications. In addition, sensor networks are often deployed in remote or hostile environments. Therefore, density control algorithms are used to increase network lifetime while maintaining its sensing capabilities. In this work, we analyze the impact of localization algorithms (RPE and DPE) and density control algorithms (GAF, A3 and OGDC) on target tracking applications. We adapt the density control algorithms to address the k-coverage problem. In addition, we analyze the impact of network density, residual integration with density control, and k-coverage on both target tracking accuracy and network lifetime. Our results show that DPE is a better choice for target tracking applications than RPE. Moreover, among the evaluated density control algorithms, OGDC is the best option among the three. Although the choice of the density control algorithm has little impact on the tracking precision, OGDC outperforms GAF and A3 in terms of tracking time. PMID:22969329

Enabling Technologies for Characterizing Exoplanet Systems with Exo-C

NASA Astrophysics Data System (ADS)

Cahoy, Kerri Lynn; Belikov, Ruslan; Stapelfeldt, Karl R.; Chakrabarti, Supriya; Trauger, John T.; Serabyn, Eugene; McElwain, Michael W.; Pong, Christopher M.; Brugarolas, Paul

2015-01-01

The Exoplanet Science and Technology Definition Team's Internal Coronagraph mission design, called 'Exo-C', utilizes several technologies that have advanced over the past decade with support from the Exoplanet Exploration Program. Following the flow of photons through the telescope, the science measurement is enabled by (i) a precision pointing system to keep the target exoplanet system precisely positioned on the detector during the integration time, (ii) high-performance coronagraphs to block the parent star's light so that the planet's reflected light can be detected, (iii) a wavefront control system to compensate for any wavefront errors such as those due to thermal or mechanical deformations in the optical path, especially errors with high spatial frequencies that could cause contrast-reducing speckles, and (iv) an integral field spectrograph (IFS) that provides moderate resolution spectra of the target exoplanets, permitting their characterization and comparison with models and other data sets. Technologies such as the wavefront control system and coronagraphs will also benefit from other funded efforts in progress, such as the Wide Field Infrared Survey Telescope Astrophysics Focused Telescope Assets (WFIRST-AFTA) program. Similarly, the Exo-C IFS will benefit from the Prototype Imaging Spectrograph for Coronagraphic Exoplanet Studies (PISCES) demonstration. We present specific examples for each of these technologies showing that the state of the art has advanced to levels that will meet the overall scientific, cost, and schedule requirements of the Exo-C mission. These capabilities have matured with testbed and/or ground-telescope demonstrations and have reached a technological readiness level (TRL) that supports their inclusion in the baseline design for potential flight at the end of this decade. While additional work remains to build and test flight-like components (that concurrently meet science as well as size, weight, power, and environmental requirements) and to integrate these subsystems together for a hardware-in-the-loop end-to-end demonstration, the overall readiness of the suite of enabling technologies makes a compelling case for Exo-C among the exoplanet direct imaging mission candidates.

Nitric oxide signaling: systems integration of oxygen balance in defense of cell integrity.

PubMed

Gong, Li; Pitari, Giovanni M; Schulz, Stephanie; Waldman, Scott A

2004-01-01

Nitric oxide has emerged as a ubiquitous signaling molecule subserving diverse pathophysiologic processes, including cardiovascular homeostasis and its decompensation in atherogenesis. Recent insights into molecular mechanisms regulating nitric oxide generation and the rich diversity of mechanisms by which it propagates signals reveal the role of this simple gas as a principle mediator of systems integration of oxygen balance. The molecular lexicon by which nitric oxide propagates signals encompasses the elements of posttranslational modification of proteins by redox-based nitrosylation of transition metal centers and free thiols. Spatial and temporal precision and specificity of signal initiation, amplification, and propagation are orchestrated by dynamic assembly of supramolecular complexes coupling nitric oxide production to upstream and downstream components in specific subcellular compartments. The concept of local paracrine signaling by nitric oxide over subcellular distances for short durations has expanded to include endocrine-like effects over anatomic spatial and temporal scales. From these insights emerges a role for nitric oxide in integrating system responses controlling oxygen supply and demand to defend cell integrity in the face of ischemic challenge. In this context, nitric oxide coordinates the respiratory cycle to acquire and deliver oxygen to target tissues by regulating hemoglobin function and vascular smooth muscle contractility and matches energy supply and demand by down-regulating energy-requiring functions while shifting metabolism to optimize energy production. Insights into mechanisms regulating nitric oxide production and signaling and their integration into responses mediating homeostasis place into specific relief the role of those processes in pathophysiology. Indeed, endothelial dysfunction associated with altered production of nitric oxide regulating tissue integrity contributes to the pathogenesis underlying atherogenesis. Moreover, this central role in pathophysiology identifies nitric oxide signaling as a key target for novel therapeutic interventions to minimize irreversible tissue damage associated with ischemic cardiovascular disease.

The XMM-Newton Science Archive and its integration into ESASky

NASA Astrophysics Data System (ADS)

Loiseau, N.; Baines, D.; Colomo, E.; Giordano, F.; Merín, B.; Racero, E.; Rodríguez, P.; Salgado, J.; Sarmiento, M.

2017-07-01

We describe the variety of functionalities of the XSA (XMM-Newton Science Archive) that allow to search and access the XMM-Newton data and catalogues. The web interface http://nxsa.esac.esa.int/ is very flexible allowing different kinds of searches by a single position or target name, or by a list of targets, with several selecting options (target type, text in the abstract, etc.), and with several display options. The resulting data can be easily broadcast to Virtual Observatory (VO) facilities for a first look analysis, or for cross-matching the results with info from other observatories. Direct access via URL or command line are also possible for scripts usage, or to link XMM-Newton data from other interfaces like Vizier, ADS, etc. The full metadata content of the XSA can be queried through the TAP (Table access Protocol) via ADQL (Astronomical Data Query Language). We present also the roadmap for future improvements of the XSA including the integration of the Upper Limit server, the on-the-fly data analysis, and the interactive visualization of EPIC sources spectra and light curves and RGS spectra, among other advanced features. Within this modern visualization philosophy XSA is also being integrated into ESASky (http://sky.esa.int). ESASky is the science-driven multi-wavelength discovery portal for all the ESA Astronomy Missions (Integral, HST, Herschel, Suzaku, Planck, etc.), and other space and ground telescope data. The system offers progressive multi-resolution all-sky projections of full mission datasets using HiPS, a new generation of HEALPix projections developed by CDS, precise footprints to connect to individual observations, and direct access to science-ready data from the underlying mission specific science archives. XMM-Newton EPIC and OM all-sky HiPS maps, catalogues and links to the observations are available through ESASky.

Threshold Differences on Figure and Ground: Gelb and Granit (1923)

PubMed Central

Kinateder, Max

2017-01-01

In 1923, Gelb and Granit, using a method of adjustment for a small red light, reported a lower threshold for the target when presented on a ground region than on an adjacent figural region. More recent work in perceptual organization has found precisely the opposite—a processing advantage seems to go to items presented on the figure, not the ground. Although Gelb and Granit continue to be cited for their finding, it has not previously been available as an English translation. Understanding their methodology and results is important for integrating early Gestalt theory with more recent investigations. PMID:28286640

Threshold Differences on Figure and Ground: Gelb and Granit (1923).

PubMed

Kinateder, Max; Nelson, Rolf

2017-01-01

In 1923, Gelb and Granit, using a method of adjustment for a small red light, reported a lower threshold for the target when presented on a ground region than on an adjacent figural region. More recent work in perceptual organization has found precisely the opposite-a processing advantage seems to go to items presented on the figure, not the ground. Although Gelb and Granit continue to be cited for their finding, it has not previously been available as an English translation. Understanding their methodology and results is important for integrating early Gestalt theory with more recent investigations.

Early detection and longitudinal imaging of cancer micrometastases using biofunctionalized rare-earth albumin nanocomposites

NASA Astrophysics Data System (ADS)

Zevon, M.; Kantamneni, H.; Ganapathy, V.; Higgins, L.; Mingozzi, M.; Pierce, M.; Riman, R.; Roth, C. M.; Moghe, P. V.

2016-05-01

Success of personalized medicine in cancer therapy depends on the ability to identify and molecularly phenotype tumors. Current clinical imaging techniques cannot be integrated with precision molecular medicine at the level of single cells or microlesions due to limited resolution. In this work we use molecularly targeted infrared emitting optical probes to identify and characterize metastatic microlesions prior to their detection with clinically relevant imaging modalities. These contrast agents form the basis of an in vivo optical imaging system capable of resolving internal microlesions, filling a critical unmet need in cancer imaging.

Lane-Level Vehicle Positioning : Integrating Diverse Systems for Precision and Reliability

DOT National Transportation Integrated Search

2013-05-13

Integrated global positioning system/inertial navigation system (GPS/INS) technology, the backbone of vehicle positioning systems, cannot provide the precision and reliability needed for vehicle-based, lane-level positioning in all driving environmen...

A Differential GPS Aided Ins for Aircraft Landings

DTIC Science & Technology

1995-12-01

Pseudolite during the Landing A pproach .................................................................................................. 4-9 4.2.1...for precision approaches, areas associated with accuracy, coverage, integrity availability, and aircraft integration must be studied and 1-3...publications [13,20,27,30,57,59] suggests very few studies have been performed which use an integrated INS/GPS for precision approaches. The majority of

Signal processor for processing ultrasonic receiver signals

DOEpatents

Fasching, George E.

1980-01-01

A signal processor is provided which uses an analog integrating circuit in conjunction with a set of digital counters controlled by a precision clock for sampling timing to provide an improved presentation of an ultrasonic transmitter/receiver signal. The signal is sampled relative to the transmitter trigger signal timing at precise times, the selected number of samples are integrated and the integrated samples are transferred and held for recording on a strip chart recorder or converted to digital form for storage. By integrating multiple samples taken at precisely the same time with respect to the trigger for the ultrasonic transmitter, random noise, which is contained in the ultrasonic receiver signal, is reduced relative to the desired useful signal.

Boundary regularized integral equation formulation of the Helmholtz equation in acoustics.

PubMed

Sun, Qiang; Klaseboer, Evert; Khoo, Boo-Cheong; Chan, Derek Y C

2015-01-01

A boundary integral formulation for the solution of the Helmholtz equation is developed in which all traditional singular behaviour in the boundary integrals is removed analytically. The numerical precision of this approach is illustrated with calculation of the pressure field owing to radiating bodies in acoustic wave problems. This method facilitates the use of higher order surface elements to represent boundaries, resulting in a significant reduction in the problem size with improved precision. Problems with extreme geometric aspect ratios can also be handled without diminished precision. When combined with the CHIEF method, uniqueness of the solution of the exterior acoustic problem is assured without the need to solve hypersingular integrals.

Boundary regularized integral equation formulation of the Helmholtz equation in acoustics

PubMed Central

Sun, Qiang; Klaseboer, Evert; Khoo, Boo-Cheong; Chan, Derek Y. C.

2015-01-01

A boundary integral formulation for the solution of the Helmholtz equation is developed in which all traditional singular behaviour in the boundary integrals is removed analytically. The numerical precision of this approach is illustrated with calculation of the pressure field owing to radiating bodies in acoustic wave problems. This method facilitates the use of higher order surface elements to represent boundaries, resulting in a significant reduction in the problem size with improved precision. Problems with extreme geometric aspect ratios can also be handled without diminished precision. When combined with the CHIEF method, uniqueness of the solution of the exterior acoustic problem is assured without the need to solve hypersingular integrals. PMID:26064591

Tissue-Specific Analysis of Pharmacological Pathways.

PubMed

Hao, Yun; Quinnies, Kayla; Realubit, Ronald; Karan, Charles; Tatonetti, Nicholas P

2018-06-19

Understanding the downstream consequences of pharmacologically targeted proteins is essential to drug design. Current approaches investigate molecular effects under tissue-naïve assumptions. Many target proteins, however, have tissue-specific expression. A systematic study connecting drugs to target pathways in in vivo human tissues is needed. We introduced a data-driven method that integrates drug-target relationships with gene expression, protein-protein interaction, and pathway annotation data. We applied our method to four independent genomewide expression datasets and built 467,396 connections between 1,034 drugs and 954 pathways in 259 human tissues or cell lines. We validated our results using data from L1000 and Pharmacogenomics Knowledgebase (PharmGKB), and observed high precision and recall. We predicted and tested anticoagulant effects of 22 compounds experimentally that were previously unknown, and used clinical data to validate these effects retrospectively. Our systematic study provides a better understanding of the cellular response to drugs and can be applied to many research topics in systems pharmacology. © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Tailored semiconductors for high-harmonic optoelectronics

NASA Astrophysics Data System (ADS)

Sivis, Murat; Taucer, Marco; Vampa, Giulio; Johnston, Kyle; Staudte, André; Naumov, Andrei Yu.; Villeneuve, D. M.; Ropers, Claus; Corkum, P. B.

2017-07-01

The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes.

Efficient Generation of Gene-Modified Pigs Harboring Precise Orthologous Human Mutation via CRISPR/Cas9-Induced Homology-Directed Repair in Zygotes.

PubMed

Zhou, Xiaoyang; Wang, Lulu; Du, Yinan; Xie, Fei; Li, Liang; Liu, Yu; Liu, Chuanhong; Wang, Shiqiang; Zhang, Shibing; Huang, Xingxu; Wang, Yong; Wei, Hong

2016-01-01

Precise genetic mutation of model animals is highly valuable for functional investigation of human mutations. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-induced homology-directed repair (HDR) is usually used for precise genetic mutation, being limited by the relatively low efficiency compared with that of non-homologous end joining (NHEJ). Although inhibition of NHEJ was shown to enhance HDR-derived mutation, in this work, without inhibition of NHEJ, we first generated gene-modified pigs harboring precise orthologous human mutation (Sox10 c.A325>T) via CRISPR/Cas9-induced HDR in zygotes using single-strand oligo DNA (ssODN) as template with an efficiency as high as 80%, indicating that pig zygotes exhibited high activities of HDR relative to NHEJ and were highly amendable to genetic mutation via CIRSPR/Cas9-induced HDR. Besides, we found a higher concentration of ssODN remarkably reduced HDR-derived mutation in pig zygotes, suggesting a possible balance for optimal HDR-derived mutation in zygotes between the excessive accessibility to HDR templates and the activities of HDR relative to NHEJ which appeared to be negatively correlated to ssODN concentration. In addition, the HDR-derived mutation, as well as those from NHEJ, extensively integrated into various tissues including gonad of founder pig without detected off-targeting, suggesting CRISPR/Cas9-induced HDR in zygotes is a reliable approach for precise genetic mutation in pigs. © 2015 WILEY PERIODICALS, INC.

Adaptive Environmental Source Localization and Tracking with Unknown Permittivity and Path Loss Coefficients †

PubMed Central

Fidan, Barış; Umay, Ilknur

2015-01-01

Accurate signal-source and signal-reflector target localization tasks via mobile sensory units and wireless sensor networks (WSNs), including those for environmental monitoring via sensory UAVs, require precise knowledge of specific signal propagation properties of the environment, which are permittivity and path loss coefficients for the electromagnetic signal case. Thus, accurate estimation of these coefficients has significant importance for the accuracy of location estimates. In this paper, we propose a geometric cooperative technique to instantaneously estimate such coefficients, with details provided for received signal strength (RSS) and time-of-flight (TOF)-based range sensors. The proposed technique is integrated to a recursive least squares (RLS)-based adaptive localization scheme and an adaptive motion control law, to construct adaptive target localization and adaptive target tracking algorithms, respectively, that are robust to uncertainties in aforementioned environmental signal propagation coefficients. The efficiency of the proposed adaptive localization and tracking techniques are both mathematically analysed and verified via simulation experiments. PMID:26690441

Software design and implementation of ship heave motion monitoring system based on MBD method

NASA Astrophysics Data System (ADS)

Yu, Yan; Li, Yuhan; Zhang, Chunwei; Kang, Won-Hee; Ou, Jinping

2015-03-01

Marine transportation plays a significant role in the modern transport sector due to its advantage of low cost, large capacity. It is being attached enormous importance to all over the world. Nowadays the related areas of product development have become an existing hot spot. DSP signal processors feature micro volume, low cost, high precision, fast processing speed, which has been widely used in all kinds of monitoring systems. But traditional DSP code development process is time-consuming, inefficiency, costly and difficult. MathWorks company proposed Model-based Design (MBD) to overcome these defects. By calling the target board modules in simulink library to compile and generate the corresponding code for the target processor. And then automatically call DSP integrated development environment CCS for algorithm validation on the target processor. This paper uses the MDB to design the algorithm for the ship heave motion monitoring system. It proves the effectiveness of the MBD run successfully on the processor.

[Application of target restoration space quantity and quantitative relation in precise esthetic prosthodontics].

PubMed

Haiyang, Yu; Tian, Luo

2016-06-01

Target restoration space (TRS) is the most precise space required for designing optimal prosthesis. TRS consists of an internal or external tooth space to confirm the esthetics and function of the final restoration. Therefore, assisted with quantitive analysis transfer, TRS quantitative analysis is a significant improvement for minimum tooth preparation. This article presents TRS quantity-related measurement, analysis, transfer, and internal relevance of three TR. classifications. Results reveal the close bond between precision and minimally invasive treatment. This study can be used to improve the comprehension and execution of precise esthetic prosthodontics.

Study on a two-dimensional scanning micro-mirror and its application in a MOEMS target detector.

PubMed

Zhang, Chi; You, Zheng; Huang, Hu; Li, Guanhua

2010-01-01

A two-dimensional (2D) scanning micro-mirror for target detection and measurement has been developed. This new micro-mirror is used in a MOEMS target detector to replace the conventional scanning detector. The micro-mirror is fabricated by MEMS process and actuated by a piezoelectric actuator. To achieve large deflection angles, the micro-mirror is excited in the resonance modes. It has two degrees of freedom and changes the direction of the emitted laser beam for a regional 2D scanning. For the deflection angles measurement, piezoresistors are integrated in the micro-mirror and the deflection angles of each direction can be detected independently and precisely. Based on the scanning micro-mirror and the phase-shift ranging technology, a MOEMS target detector has been developed in a size of 90 mm × 35 mm × 50 mm. The experiment shows that the target can be detected in the scanning field and the relative range and orientation can be measured by the MOEMS target detector. For the target distance up to 3 m with a field of view about 20° × 20°, the measurement resolution is about 10.2 cm in range, 0.15° in the horizontal direction and 0.22° in the vertical direction for orientation.

Study on a Two-Dimensional Scanning Micro-Mirror and Its Application in a MOEMS Target Detector

PubMed Central

Zhang, Chi; You, Zheng; Huang, Hu; Li, Guanhua

2010-01-01

A two-dimensional (2D) scanning micro-mirror for target detection and measurement has been developed. This new micro-mirror is used in a MOEMS target detector to replace the conventional scanning detector. The micro-mirror is fabricated by MEMS process and actuated by a piezoelectric actuator. To achieve large deflection angles, the micro-mirror is excited in the resonance modes. It has two degrees of freedom and changes the direction of the emitted laser beam for a regional 2D scanning. For the deflection angles measurement, piezoresistors are integrated in the micro-mirror and the deflection angles of each direction can be detected independently and precisely. Based on the scanning micro-mirror and the phase-shift ranging technology, a MOEMS target detector has been developed in a size of 90 mm × 35 mm × 50 mm. The experiment shows that the target can be detected in the scanning field and the relative range and orientation can be measured by the MOEMS target detector. For the target distance up to 3 m with a field of view about 20° × 20°, the measurement resolution is about 10.2 cm in range, 0.15° in the horizontal direction and 0.22° in the vertical direction for orientation. PMID:22163580

Molecular genetics and targeted therapeutics in biliary tract carcinoma.

PubMed

Marks, Eric I; Yee, Nelson S

2016-01-28

The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract.

Precision Interval Estimation of the Response Surface by Means of an Integrated Algorithm of Neural Network and Linear Regression

NASA Technical Reports Server (NTRS)

Lo, Ching F.

1999-01-01

The integration of Radial Basis Function Networks and Back Propagation Neural Networks with the Multiple Linear Regression has been accomplished to map nonlinear response surfaces over a wide range of independent variables in the process of the Modem Design of Experiments. The integrated method is capable to estimate the precision intervals including confidence and predicted intervals. The power of the innovative method has been demonstrated by applying to a set of wind tunnel test data in construction of response surface and estimation of precision interval.

A precision analogue integrator system for heavy current measurement in MFDC resistance spot welding

NASA Astrophysics Data System (ADS)

Xia, Yu-Jun; Zhang, Zhong-Dian; Xia, Zhen-Xin; Zhu, Shi-Liang; Zhang, Rui

2016-02-01

In order to control and monitor the quality of middle frequency direct current (MFDC) resistance spot welding (RSW), precision measurement of the welding current up to 100 kA is required, for which Rogowski coils are the only viable current transducers at present. Thus, a highly accurate analogue integrator is the key to restoring the converted signals collected from the Rogowski coils. Previous studies emphasised that the integration drift is a major factor that influences the performance of analogue integrators, but capacitive leakage error also has a significant impact on the result, especially in long-time pulse integration. In this article, new methods of measuring and compensating capacitive leakage error are proposed to fabricate a precision analogue integrator system for MFDC RSW. A voltage holding test is carried out to measure the integration error caused by capacitive leakage, and an original integrator with a feedback adder is designed to compensate capacitive leakage error in real time. The experimental results and statistical analysis show that the new analogue integrator system could constrain both drift and capacitive leakage error, of which the effect is robust to different voltage levels of output signals. The total integration error is limited within  ±0.09 mV s-1 0.005% s-1 or full scale at a 95% confidence level, which makes it possible to achieve the precision measurement of the welding current of MFDC RSW with Rogowski coils of 0.1% accuracy class.

Recce mission planning

NASA Astrophysics Data System (ADS)

York, Andrew M.

2000-11-01

The ever increasing sophistication of reconnaissance sensors reinforces the importance of timely, accurate, and equally sophisticated mission planning capabilities. Precision targeting and zero-tolerance for collateral damage and civilian casualties, stress the need for accuracy and timeliness. Recent events have highlighted the need for improvement in current planning procedures and systems. Annotating printed maps takes time and does not allow flexibility for rapid changes required in today's conflicts. We must give aircrew the ability to accurately navigate their aircraft to an area of interest, correctly position the sensor to obtain the required sensor coverage, adapt missions as required, and ensure mission success. The growth in automated mission planning system capability and the expansion of those systems to include dedicated and integrated reconnaissance modules, helps to overcome current limitations. Mission planning systems, coupled with extensive integrated visualization capabilities, allow aircrew to not only plan accurately and quickly, but know precisely when they will locate the target and visualize what the sensor will see during its operation. This paper will provide a broad overview of the current capabilities and describe how automated mission planning and visualization systems can improve and enhance the reconnaissance planning process and contribute to mission success. Think about the ultimate objective of the reconnaissance mission as we consider areas that technology can offer improvement. As we briefly review the fundamentals, remember where and how TAC RECCE systems will be used. Try to put yourself in the mindset of those who are on the front lines, working long hours at increasingly demanding tasks, trying to become familiar with new operating areas and equipment, while striving to minimize risk and optimize mission success. Technical advancements that can reduce the TAC RECCE timeline, simplify operations and instill Warfighter confidence, ultimately improve the desired outcome.

Fully automated laboratory and field-portable goniometer used for performing accurate and precise multiangular reflectance measurements

NASA Astrophysics Data System (ADS)

Harms, Justin D.; Bachmann, Charles M.; Ambeau, Brittany L.; Faulring, Jason W.; Ruiz Torres, Andres J.; Badura, Gregory; Myers, Emily

2017-10-01

Field-portable goniometers are created for a wide variety of applications. Many of these applications require specific types of instruments and measurement schemes and must operate in challenging environments. Therefore, designs are based on the requirements that are specific to the application. We present a field-portable goniometer that was designed for measuring the hemispherical-conical reflectance factor (HCRF) of various soils and low-growing vegetation in austere coastal and desert environments and biconical reflectance factors in laboratory settings. Unlike some goniometers, this system features a requirement for "target-plane tracking" to ensure that measurements can be collected on sloped surfaces, without compromising angular accuracy. The system also features a second upward-looking spectrometer to measure the spatially dependent incoming illumination, an integrated software package to provide full automation, an automated leveling system to ensure a standard frame of reference, a design that minimizes the obscuration due to self-shading to measure the opposition effect, and the ability to record a digital elevation model of the target region. This fully automated and highly mobile system obtains accurate and precise measurements of HCRF in a wide variety of terrain and in less time than most other systems while not sacrificing consistency or repeatability in laboratory environments.

Research into the usage of integrated jamming of IR weakening and smoke-screen resisting the IR imaging guided missiles

NASA Astrophysics Data System (ADS)

Wang, Long-tao; Jiang, Ning; Lv, Ming-shan

2015-10-01

With the emergence of the anti-ship missle with the capability of infrared imaging guidance, the traditional single jamming measures, because of the jamming mechanism and technical flaws or unsuitable use, greatly reduced the survival probability of the war-ship in the future naval battle. Intergrated jamming of IR weakening + smoke-screen Can not only make jamming to the search and tracking of IR imaging guidance system , but also has feasibility in conjunction, besides , which also make the best jamming effect. The research conclusion has important realistic meaning for raising the antimissile ability of surface ships. With the development of guidance technology, infrared guidance system has expanded by ir point-source homing guidance to infrared imaging guidance, Infrared imaging guidance has made breakthrough progress, Infrared imaging guidance system can use two-dimensional infrared image information of the target, achieve the precise tracking. Which has Higher guidance precision, better concealment, stronger anti-interference ability and could Target the key parts. The traditional single infrared smoke screen jamming or infrared decoy flare interference cannot be imposed effective interference. So, Research how to effectively fight against infrared imaging guided weapons threat measures and means, improving the surface ship antimissile ability is an urgent need to solve.

Animal and in silico models for the study of sarcomeric cardiomyopathies

PubMed Central

Duncker, Dirk J.; Bakkers, Jeroen; Brundel, Bianca J.; Robbins, Jeff; Tardiff, Jil C.; Carrier, Lucie

2015-01-01

Over the past decade, our understanding of cardiomyopathies has improved dramatically, due to improvements in screening and detection of gene defects in the human genome as well as a variety of novel animal models (mouse, zebrafish, and drosophila) and in silico computational models. These novel experimental tools have created a platform that is highly complementary to the naturally occurring cardiomyopathies in cats and dogs that had been available for some time. A fully integrative approach, which incorporates all these modalities, is likely required for significant steps forward in understanding the molecular underpinnings and pathogenesis of cardiomyopathies. Finally, novel technologies, including CRISPR/Cas9, which have already been proved to work in zebrafish, are currently being employed to engineer sarcomeric cardiomyopathy in larger animals, including pigs and non-human primates. In the mouse, the increased speed with which these techniques can be employed to engineer precise ‘knock-in’ models that previously took years to make via multiple rounds of homologous recombination-based gene targeting promises multiple and precise models of human cardiac disease for future study. Such novel genetically engineered animal models recapitulating human sarcomeric protein defects will help bridging the gap to translate therapeutic targets from small animal and in silico models to the human patient with sarcomeric cardiomyopathy. PMID:25600962

Fundamentals of precision medicine

PubMed Central

Divaris, Kimon

2018-01-01

Imagine a world where clinicians make accurate diagnoses and provide targeted therapies to their patients according to well-defined, biologically-informed disease subtypes, accounting for individual differences in genetic make-up, behaviors, cultures, lifestyles and the environment. This is not as utopic as it may seem. Relatively recent advances in science and technology have led to an explosion of new information on what underlies health and what constitutes disease. These novel insights emanate from studies of the human genome and microbiome, their associated transcriptomes, proteomes and metabolomes, as well as epigenomics and exposomics—such ‘omics data can now be generated at unprecedented depth and scale, and at rapidly decreasing cost. Making sense and integrating these fundamental information domains to transform health care and improve health remains a challenge—an ambitious, laudable and high-yield goal. Precision dentistry is no longer a distant vision; it is becoming part of the rapidly evolving present. Insights from studies of the human genome and microbiome, their associated transcriptomes, proteomes and metabolomes, and epigenomics and exposomics have reached an unprecedented depth and scale. Much more needs to be done, however, for the realization of precision medicine in the oral health domain. PMID:29227115

A Method for Assessing the Accuracy of a Photogrammetry System for Precision Deployable Structures

NASA Technical Reports Server (NTRS)

Moore, Ashley

2005-01-01

The measurement techniques used to validate analytical models of large deployable structures are an integral Part of the technology development process and must be precise and accurate. Photogrammetry and videogrammetry are viable, accurate, and unobtrusive methods for measuring such large Structures. Photogrammetry uses Software to determine the three-dimensional position of a target using camera images. Videogrammetry is based on the same principle, except a series of timed images are analyzed. This work addresses the accuracy of a digital photogrammetry system used for measurement of large, deployable space structures at JPL. First, photogrammetry tests are performed on a precision space truss test article, and the images are processed using Photomodeler software. The accuracy of the Photomodeler results is determined through, comparison with measurements of the test article taken by an external testing group using the VSTARS photogrammetry system. These two measurements are then compared with Australis photogrammetry software that simulates a measurement test to predict its accuracy. The software is then used to study how particular factors, such as camera resolution and placement, affect the system accuracy to help design the setup for the videogrammetry system that will offer the highest level of accuracy for measurement of deploying structures.

The consummatory origins of visually guided reaching in human infants: a dynamic integration of whole-body and upper-limb movements.

PubMed

Foroud, Afra; Whishaw, Ian Q

2012-06-01

Reaching-to-eat (skilled reaching) is a natural behaviour that involves reaching for, grasping and withdrawing a target to be placed into the mouth for eating. It is an action performed daily by adults and is among the first complex behaviours to develop in infants. During development, visually guided reaching becomes increasingly refined to the point that grasping of small objects with precision grips of the digits occurs at about one year of age. Integration of the hand, upper-limbs, and whole body are required for successful reaching, but the ontogeny of this integration has not been described. The present longitudinal study used Laban Movement Analysis, a behavioural descriptive method, to investigate the developmental progression of the use and integration of axial, proximal, and distal movements performed during visually guided reaching. Four infants (from 7 to 40 weeks age) were presented with graspable objects (toys or food items). The first prereaching stage was associated with activation of mouth, limb, and hand movements to a visually presented target. Next, reaching attempts consisted of first, the advancement of the head with an opening mouth and then with the head, trunk and opening mouth. Eventually, the axial movements gave way to the refined action of one upper-limb supported by axial adjustments. These findings are discussed in relation to the biological objective of reaching, the evolutionary origins of reaching, and the decomposition of reaching after neurological injury. Copyright © 2012 Elsevier B.V. All rights reserved.

Failure to Integrate Quantitative Measurement Methods of Ocular Inflammation Hampers Clinical Practice and Trials on New Therapies for Posterior Uveitis.

PubMed

Herbort, Carl P; Tugal-Tutkun, Ilknur; Neri, Piergiorgio; Pavésio, Carlos; Onal, Sumru; LeHoang, Phuc

2017-05-01

Uveitis is one of the fields in ophthalmology where a tremendous evolution took place in the past 25 years. Not only did we gain access to more efficient, more targeted, and better tolerated therapies, but also in parallel precise and quantitative measurement methods developed allowing the clinician to evaluate these therapies and adjust therapeutic intervention with a high degree of precision. Objective and quantitative measurement of the global level of intraocular inflammation became possible for most inflammatory diseases with direct or spill-over anterior chamber inflammation, thanks to laser flare photometry. The amount of retinal inflammation could be quantified by using fluorescein angiography to score retinal angiographic signs. Indocyanine green angiography gave imaging insight into the hitherto inaccessible choroidal compartment, rendering possible the quantification of choroiditis by scoring indocyanine green angiographic signs. Optical coherence tomography has enabled measurement and objective monitoring of retinal and choroidal thickness. This multimodal quantitative appraisal of intraocular inflammation represents an exquisite security in monitoring uveitis. What is enigmatic, however, is the slow pace with which these improvements are integrated in some areas. What is even more difficult to understand is the fact that clinical trials to assess new therapeutic agents still mostly rely on subjective parameters such as clinical evaluation of vitreous haze as a main endpoint; whereas a whole array of precise, quantitative, and objective modalities are available for the design of clinical studies. The scope of this work was to review the quantitative investigations that improved the management of uveitis in the past 2-3 decades.

High-Precision Image Aided Inertial Navigation with Known Features: Observability Analysis and Performance Evaluation

PubMed Central

Jiang, Weiping; Wang, Li; Niu, Xiaoji; Zhang, Quan; Zhang, Hui; Tang, Min; Hu, Xiangyun

2014-01-01

A high-precision image-aided inertial navigation system (INS) is proposed as an alternative to the carrier-phase-based differential Global Navigation Satellite Systems (CDGNSSs) when satellite-based navigation systems are unavailable. In this paper, the image/INS integrated algorithm is modeled by a tightly-coupled iterative extended Kalman filter (IEKF). Tightly-coupled integration ensures that the integrated system is reliable, even if few known feature points (i.e., less than three) are observed in the images. A new global observability analysis of this tightly-coupled integration is presented to guarantee that the system is observable under the necessary conditions. The analysis conclusions were verified by simulations and field tests. The field tests also indicate that high-precision position (centimeter-level) and attitude (half-degree-level)-integrated solutions can be achieved in a global reference. PMID:25330046

Precision oncology: origins, optimism, and potential.

PubMed

Prasad, Vinay; Fojo, Tito; Brada, Michael

2016-02-01

Imatinib, the first and arguably the best targeted therapy, became the springboard for developing drugs aimed at molecular targets deemed crucial to tumours. As this development unfolded, a revolution in the speed and cost of genetic sequencing occurred. The result--an armamentarium of drugs and an array of molecular targets--set the stage for precision oncology, a hypothesis that cancer treatment could be markedly improved if therapies were guided by a tumour's genomic alterations. Drawing lessons from the biological basis of cancer and recent empirical investigations, we take a more measured view of precision oncology's promise. Ultimately, the promise is not our concern, but the threshold at which we declare success. We review reports of precision oncology alongside those of precision diagnostics and novel radiotherapy approaches. Although confirmatory evidence is scarce, these interventions have been widely endorsed. We conclude that the current path will probably not be successful or, at a minimum, will have to undergo substantive adjustments before it can be successful. For the sake of patients with cancer, we hope one form of precision oncology will deliver on its promise. However, until confirmatory studies are completed, precision oncology remains unproven, and as such, a hypothesis in need of rigorous testing. Copyright © 2016 Elsevier Ltd. All rights reserved.

An Evaluation of Different Statistical Targets for Assembling Parallel Forms in Item Response Theory

PubMed Central

Ali, Usama S.; van Rijn, Peter W.

2015-01-01

Assembly of parallel forms is an important step in the test development process. Therefore, choosing a suitable theoretical framework to generate well-defined test specifications is critical. The performance of different statistical targets of test specifications using the test characteristic curve (TCC) and the test information function (TIF) was investigated. Test length, the number of test forms, and content specifications are considered as well. The TCC target results in forms that are parallel in difficulty, but not necessarily in terms of precision. Vice versa, test forms created using a TIF target are parallel in terms of precision, but not necessarily in terms of difficulty. As sometimes the focus is either on TIF or TCC, differences in either difficulty or precision can arise. Differences in difficulty can be mitigated by equating, but differences in precision cannot. In a series of simulations using a real item bank, the two-parameter logistic model, and mixed integer linear programming for automated test assembly, these differences were found to be quite substantial. When both TIF and TCC are combined into one target with manipulation to relative importance, these differences can be made to disappear.

A design of optical measurement laboratory for space-based illumination condition emulation

NASA Astrophysics Data System (ADS)

Xu, Rong; Zhao, Fei; Yang, Xin

2015-10-01

Space Objects Identification(SOI) and related technology have aroused wide attention from spacefaring nations due to the increasingly severe space environment. Multiple ground-based assets have been employed to acquire statistical survey data, detect faint debris, acquire photometric and spectroscopic data. Great efforts have been made to characterize different space objects using the statistical data acquired by telescopes. Furthermore, detailed laboratory data are needed to optimize the characterization of orbital debris and satellites via material composition and potential rotation axes, which calls for a high-precision and flexible optical measurement system. A typical method of taking optical measurements of a space object(or model) is to move light source and sensors through every possible orientation around it and keep the target still. However, moving equipments to accurate orientations in the air is difficult, especially for those large precise instruments sensitive to vibrations. Here, a rotation structure of "3+1" axes, with a three-axis turntable manipulating attitudes of the target and the sensor revolving around a single axis, is utilized to emulate every possible illumination condition in space, which can also avoid the inconvenience of moving large aparatus. Firstly, the source-target-sensor orientation of a real satellite was analyzed with vectors and coordinate systems built to illustrate their spatial relationship. By bending the Reference Coordinate Frame to the Phase Angle plane, the sensor only need to revolve around a single axis while the other three degrees of freedom(DOF) are associated with the Euler's angles of the satellite. Then according to practical engineering requirements, an integrated rotation system of four-axis structure is brought forward. Schemetic diagrams of the three-axis turntable and other equipments show an overview of the future laboratory layout. Finally, proposals on evironment arrangements, light source precautions and sensor selections are provided. Comparing to current methods, this design shows better effects on device simplication, automatic control and high-precision measurement.

Practical issues of biomarker-assisted targeted therapy in precision medicine and immuno-oncology era.

PubMed

Lee, Dae Ho

2018-01-01

The concept of precision medicine is not new, as multiplex and very sensitive methods, or next-generation sequencing and matched targeted cancer therapies, have come to clinical practice. Substantial progress has been made from the discovery to the development and clinical application of biomarkers and matched targeted therapies. However, there still remain many challenges and issues to be overcome in each step, from acquisition of tumour tissues through validation of biomarkers to the final decision on targeted therapy. This review will briefly touch on these issues, hoping to provide a better understanding and application of targeted therapy in cancer treatment in the era of precision medicine and immuno-oncology. It also helps to understand that the meaning or value of biomarker(s) and matched targeted therapy changes along with expansion of knowledge and advance of methodology, and constant efforts have to be made in evaluating the meaning and clinical value during the development and after the establishment of biomarkers or the approval of matched targeted therapies, which might be more complicated by the advent of new therapeutic agents and new diagnostic methods.

The Daya Bay antineutrino detector filling system and liquid mass measurement

NASA Astrophysics Data System (ADS)

Band, H. R.; Cherwinka, J. J.; Draeger, E.; Heeger, K. M.; Hinrichs, P.; Lewis, C. A.; Mattison, H.; McFarlane, M. C.; Webber, D. M.; Wenman, D.; Wang, W.; Wise, T.; Xiao, Q.

2013-09-01

The Daya Bay Reactor Neutrino Experiment has measured the neutrino mixing angle θ13 to world-leading precision. The experiment uses eight antineutrino detectors filled with 20-tons of gadolinium-doped liquid scintillator to detect antineutrinos emitted from the Daya Bay nuclear power plant through the inverse beta decay reaction. The precision measurement of sin22θ13 relies on the relative antineutrino interaction rates between detectors at near (400 m) and far (roughly 1.8 km) distances from the nuclear reactors. The measured interaction rate in each detector is directly proportional to the number of protons in the liquid scintillator target. A precision detector filling system was developed to simultaneously fill the three liquid zones of the antineutrino detectors and measure the relative target mass between detectors to < 0.02%. This paper describes the design, operation, and performance of the system and the resulting precision measurement of the detectors' target liquid masses.

Targeting 100! Advanced Energy Efficient Building Technologies for High Performance Hospitals: Executive Summary.

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

Burpee, Heather; Loveland, Joel; Helmers, Aaron

2015-09-02

This research, Targeting 100!, provides a conceptual framework and decision-making structure at a schematic design level of precision for hospital owners, architects and engineers to radically reduce energy use in hospitals. Following the goals of Architecture 2030 and The 2030 Challenge, it offers access to design strategies and the cost implications of those strategies for new hospitals to utilize 60% less energy. The name, Targeting 100!, comes from the 2030 Challenge energy reduction goal for hospitals; a 60% energy use reduction from typical acute care hospital targets approximately 100 KBtu/SF Year, thus the name “Targeting 100!”. Targeting 100! was developedmore » through funding partnerships with the US Department of Energy and the Northwest Energy Efficiency’s BetterBricks Initiative. The technical team was led by the University of Washington Integrated Design Lab supported by deep collaboration with Solarc Architecture and Engineering, TBD Cost Consultants, and NBBJ Architecture. Through extensive research and design development, Targeting 100! provides a framework for developing high performance healthcare projects today and into the future. An online tool houses a Targeting 100! knowlegebase and roadmap. It can be accessed at: www.idlseattle.com/t100. The webtool is structured from high-level overview materials to detailed library with modeling inputs and outputs, providing a comprehensive report of the background, data, and outcomes from the project.« less

Integration of parallel 13 C-labeling experiments and in silico pathway analysis for enhanced production of ascomycin.

PubMed

Qi, Haishan; Lv, Mengmeng; Song, Kejing; Wen, Jianping

2017-05-01

Herein, the hyper-producing strain for ascomycin was engineered based on 13 C-labeling experiments and elementary flux modes analysis (EFMA). First, the metabolism of non-model organism Streptomyces hygroscopicus var. ascomyceticus SA68 was investigated and an updated network model was reconstructed using 13 C- metabolic flux analysis. Based on the precise model, EFMA was further employed to predict genetic targets for higher ascomycin production. Chorismatase (FkbO) and pyruvate carboxylase (Pyc) were predicted as the promising overexpression and deletion targets, respectively. The corresponding mutant TD-FkbO and TD-ΔPyc exhibited the consistency effects between model prediction and experimental results. Finally, the combined genetic manipulations were performed, achieving a high-yield ascomycin engineering strain TD-ΔPyc-FkbO with production up to 610 mg/L, 84.8% improvement compared with the parent strain SA68. These results manifested that the integration of 13 C-labeling experiments and in silico pathway analysis could serve as a promising concept to enhance ascomycin production, as well as other valuable products. Biotechnol. Bioeng. 2017;114: 1036-1044. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Elimination of HIV-1 Genomes from Human T-lymphoid Cells by CRISPR/Cas9 Gene Editing

PubMed Central

Kaminski, Rafal; Chen, Yilan; Fischer, Tracy; Tedaldi, Ellen; Napoli, Alessandro; Zhang, Yonggang; Karn, Jonathan; Hu, Wenhui; Khalili, Kamel

2016-01-01

We employed an RNA-guided CRISPR/Cas9 DNA editing system to precisely remove the entire HIV-1 genome spanning between 5′ and 3′ LTRs of integrated HIV-1 proviral DNA copies from latently infected human CD4+ T-cells. Comprehensive assessment of whole-genome sequencing of HIV-1 eradicated cells ruled out any off-target effects by our CRISPR/Cas9 technology that might compromise the integrity of the host genome and further showed no effect on several cell health indices including viability, cell cycle and apoptosis. Persistent co-expression of Cas9 and the specific targeting guide RNAs in HIV-1-eradicated T-cells protected them against new infection by HIV-1. Lentivirus-delivered CRISPR/Cas9 significantly diminished HIV-1 replication in infected primary CD4+ T-cell cultures and drastically reduced viral load in ex vivo culture of CD4+ T-cells obtained from HIV-1 infected patients. Thus, gene editing using CRISPR/Cas9 may provide a new therapeutic path for eliminating HIV-1 DNA from CD4+ T-cells and potentially serve as a novel and effective platform toward curing AIDS. PMID:26939770

I feel you-monitoring environmental variables related to asthma in an integrated real-time frame.

PubMed

Berenguer, Anabela Gonçalves

2015-09-11

The study of asthma and other complex diseases has proven to be a "moving target" for researchers due to its complex aetiology, difficulty in definition, and immeasurable environmental effects. A large number of studies regarding the contribution of both genetic and environmental factors often result in contradictory results, in part due to the highly heterogeneous nature of asthma. Recent literature has focused on the epigenetic signatures of asthma caused by environmental factors, highlighting the importance of environment. However, unlike the genetic techniques, environmental assessment still lacks accuracy. A plausible solution for this problem would be an individual-based environmental exposure assessment, relying on new technologies such as personal real-time environmental sensors. This could prove to enable the assessment of the whole environmental exposure-or exposome-matching in terms of precision the genome that is emphasized in most studies so far. In addition, the measurement of the whole array of biological molecules, in response to the environment action, could help understand the context of the disease. The current perspective comprises a beyond-genetics integrated vision of omics technology coupled with real-time environmental measures targeting to enhance our comprehension of the disease genesis.

A calibration method based on virtual large planar target for cameras with large FOV

NASA Astrophysics Data System (ADS)

Yu, Lei; Han, Yangyang; Nie, Hong; Ou, Qiaofeng; Xiong, Bangshu

2018-02-01

In order to obtain high precision in camera calibration, a target should be large enough to cover the whole field of view (FOV). For cameras with large FOV, using a small target will seriously reduce the precision of calibration. However, using a large target causes many difficulties in making, carrying and employing the large target. In order to solve this problem, a calibration method based on the virtual large planar target (VLPT), which is virtually constructed with multiple small targets (STs), is proposed for cameras with large FOV. In the VLPT-based calibration method, first, the positions and directions of STs are changed several times to obtain a number of calibration images. Secondly, the VLPT of each calibration image is created by finding the virtual point corresponding to the feature points of the STs. Finally, intrinsic and extrinsic parameters of the camera are calculated by using the VLPTs. Experiment results show that the proposed method can not only achieve the similar calibration precision as those employing a large target, but also have good stability in the whole measurement area. Thus, the difficulties to accurately calibrate cameras with large FOV can be perfectly tackled by the proposed method with good operability.

VLT/PIONIER Imaging of Red Supergiant Stars

NASA Astrophysics Data System (ADS)

Montargès, Miguel

2018-04-01

PIONIER (Precision Integrated-Optics Near-infrared Imaging ExpeRiment) was the first 4-telescope instrument installed at the Very Large Telescope Interferometer (VLTI) in 2010. Benefiting from the multiple interferometric configurations available at the Cerro Paranal observatory, it can efficiently image stellar surfaces. With their large linear sizes, nearby red supergiant stars are among the most interesting targets for such instrument. Near infrared interferometry allows to study their surface in order to get a better understanding of their mass loss, mostly by constraining the characteristics of their photospheric features. I will review recent results obtain with VLTI/PIONIER on red supergiant stars, and emphasize the different techniques used to analyze these observations.

3D Bioprinting for Organ Regeneration

PubMed Central

Cui, Haitao; Nowicki, Margaret; Fisher, John P.; Zhang, Lijie Grace

2017-01-01

Regenerative medicine holds the promise of engineering functional tissues or organs to heal or replace abnormal and necrotic tissues/organs, offering hope for filling the gap between organ shortage and transplantation needs. Three-dimensional (3D) bioprinting is evolving into an unparalleled bio-manufacturing technology due to its high-integration potential for patient-specific designs, precise and rapid manufacturing capabilities with high resolution, and unprecedented versatility. It enables precise control over multiple compositions, spatial distributions, and architectural accuracy/complexity, therefore achieving effective recapitulation of microstructure, architecture, mechanical properties, and biological functions of target tissues and organs. Here we provide an overview of recent advances in 3D bioprinting technology, as well as design concepts of bioinks suitable for the bioprinting process. We focus on the applications of this technology for engineering living organs, focusing more specifically on vasculature, neural networks, the heart and liver. We conclude with current challenges and the technical perspective for further development of 3D organ bioprinting. PMID:27995751

Improvements in Space Surveillance Processing for Wide Field of View Optical Sensors

NASA Astrophysics Data System (ADS)

Sydney, P.; Wetterer, C.

2014-09-01

For more than a decade, an autonomous satellite tracking system at the Air Force Maui Optical and Supercomputing (AMOS) observatory has been generating routine astrometric measurements of Earth-orbiting Resident Space Objects (RSOs) using small commercial telescopes and sensors. Recent work has focused on developing an improved processing system, enhancing measurement performance and response while supporting other sensor systems and missions. This paper will outline improved techniques in scheduling, detection, astrometric and photometric measurements, and catalog maintenance. The processing system now integrates with Special Perturbation (SP) based astrodynamics algorithms, allowing covariance-based scheduling and more precise orbital estimates and object identification. A merit-based scheduling algorithm provides a global optimization framework to support diverse collection tasks and missions. The detection algorithms support a range of target tracking and camera acquisition rates. New comprehensive star catalogs allow for more precise astrometric and photometric calibrations including differential photometry for monitoring environmental changes. This paper will also examine measurement performance with varying tracking rates and acquisition parameters.

3D Bioprinting for Organ Regeneration.

PubMed

Cui, Haitao; Nowicki, Margaret; Fisher, John P; Zhang, Lijie Grace

2017-01-01

Regenerative medicine holds the promise of engineering functional tissues or organs to heal or replace abnormal and necrotic tissues/organs, offering hope for filling the gap between organ shortage and transplantation needs. Three-dimensional (3D) bioprinting is evolving into an unparalleled biomanufacturing technology due to its high-integration potential for patient-specific designs, precise and rapid manufacturing capabilities with high resolution, and unprecedented versatility. It enables precise control over multiple compositions, spatial distributions, and architectural accuracy/complexity, therefore achieving effective recapitulation of microstructure, architecture, mechanical properties, and biological functions of target tissues and organs. Here we provide an overview of recent advances in 3D bioprinting technology, as well as design concepts of bioinks suitable for the bioprinting process. We focus on the applications of this technology for engineering living organs, focusing more specifically on vasculature, neural networks, the heart and liver. We conclude with current challenges and the technical perspective for further development of 3D organ bioprinting. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterizing the Hypermutated Subtype of Advanced Prostate Cancer as a Predictive Biomarker for Precision Medicine

DTIC Science & Technology

2017-10-01

goal of this research is to characterize the mechanisms leading to hypermutated prostate cancer and to integrate tumor hypermutation status with... integrate tumor hypermutation status with clinical decision making and therapy to improve the care of men with advanced prostate cancer. Using Next-Gen...preparation of presentations that integrate prostate cancer patient clinical histories with genomic findings 1-36 Yes, see Prostate Precision Tumor

A comparative study of integrators for constructing ephemerides with high precision.

NASA Astrophysics Data System (ADS)

Huang, Tian-Yi

1990-09-01

There are four indexes for evaluating various integrators. They are the local truncation error, the numerical stability, the complexity of computation and the quality of adaptation. A review and a comparative study of several numerical integration methods, such as Adams, Cowell, Runge-Kutta-Fehlberg, Gragg-Bulirsch-Stoer extrapolation, Everhart, Taylor series and Krogh, which are popular for constructing ephemerides with high precision, has been worked out.

Accuracy optimization with wavelength tunability in overlay imaging technology

NASA Astrophysics Data System (ADS)

Lee, Honggoo; Kang, Yoonshik; Han, Sangjoon; Shim, Kyuchan; Hong, Minhyung; Kim, Seungyoung; Lee, Jieun; Lee, Dongyoung; Oh, Eungryong; Choi, Ahlin; Kim, Youngsik; Marciano, Tal; Klein, Dana; Hajaj, Eitan M.; Aharon, Sharon; Ben-Dov, Guy; Lilach, Saltoun; Serero, Dan; Golotsvan, Anna

2018-03-01

As semiconductor manufacturing technology progresses and the dimensions of integrated circuit elements shrink, overlay budget is accordingly being reduced. Overlay budget closely approaches the scale of measurement inaccuracies due to both optical imperfections of the measurement system and the interaction of light with geometrical asymmetries of the measured targets. Measurement inaccuracies can no longer be ignored due to their significant effect on the resulting device yield. In this paper we investigate a new approach for imaging based overlay (IBO) measurements by optimizing accuracy rather than contrast precision, including its effect over the total target performance, using wavelength tunable overlay imaging metrology. We present new accuracy metrics based on theoretical development and present their quality in identifying the measurement accuracy when compared to CD-SEM overlay measurements. The paper presents the theoretical considerations and simulation work, as well as measurement data, for which tunability combined with the new accuracy metrics is shown to improve accuracy performance.

Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

PubMed Central

Garza-Lombó, Carla; Gonsebatt, María E.

2016-01-01

The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

Site-Specific Editing of the Plasmodium falciparum Genome Using Engineered Zinc-Finger Nucleases

PubMed Central

Straimer, Judith; Lee, Marcus CS; Lee, Andrew H; Zeitler, Bryan; Williams, April E; Pearl, Jocelynn R; Zhang, Lei; Rebar, Edward J; Gregory, Philip D; Llinás, Manuel; Urnov, Fyodor D; Fidock, David A

2013-01-01

Malaria afflicts over 200 million people worldwide and its most lethal etiologic agent, Plasmodium falciparum, is evolving to resist even the latest-generation therapeutics. Efficient tools for genome-directed investigations of P. falciparum pathogenesis, including drug resistance mechanisms, are clearly required. Here we report rapid and targeted genetic engineering of this parasite, using zinc-finger nucleases (ZFNs) that produce a double-strand break in a user-defined locus and trigger homology-directed repair. Targeting an integrated egfp locus, we obtained gene deletion parasites with unprecedented speed (two weeks), both with and without direct selection. ZFNs engineered against the endogenous parasite gene pfcrt, responsible for chloroquine treatment escape, rapidly produced parasites that carried either an allelic replacement or a panel of specified point mutations. The efficiency, versatility and precision of this method will enable a diverse array of genome editing approaches to interrogate this human pathogen. PMID:22922501

Engineering and agronomy aspects of a long-term precision agriculture field experiment

USDA-ARS?s Scientific Manuscript database

Much research has been conducted on specific precision agriculture tools and implementation strategies, but little has been reported on long-term evaluation of integrated precision agriculture field experiments. In 2004 our research team developed and initiated a multi-faceted “precision agriculture...

Assembly and Multiplex Genome Integration of Metabolic Pathways in Yeast Using CasEMBLR.

PubMed

Jakočiūnas, Tadas; Jensen, Emil D; Jensen, Michael K; Keasling, Jay D

2018-01-01

Genome integration is a vital step for implementing large biochemical pathways to build a stable microbial cell factory. Although traditional strain construction strategies are well established for the model organism Saccharomyces cerevisiae, recent advances in CRISPR/Cas9-mediated genome engineering allow much higher throughput and robustness in terms of strain construction. In this chapter, we describe CasEMBLR, a highly efficient and marker-free genome engineering method for one-step integration of in vivo assembled expression cassettes in multiple genomic sites simultaneously. CasEMBLR capitalizes on the CRISPR/Cas9 technology to generate double-strand breaks in genomic loci, thus prompting native homologous recombination (HR) machinery to integrate exogenously derived homology templates. As proof-of-principle for microbial cell factory development, CasEMBLR was used for one-step assembly and marker-free integration of the carotenoid pathway from 15 exogenously supplied DNA parts into three targeted genomic loci. As a second proof-of-principle, a total of ten DNA parts were assembled and integrated in two genomic loci to construct a tyrosine production strain, and at the same time knocking out two genes. This new method complements and improves the field of genome engineering in S. cerevisiae by providing a more flexible platform for rapid and precise strain building.

Measurement of multiplicities of charged hadrons, pions and kaons in DIS at COMPASS

NASA Astrophysics Data System (ADS)

Mitrofanov, Nikolai

2018-04-01

Precise measurements of multiplicities of charged hadrons, pions and kaons in deep inelastic scattering were performed. The data were obtained by the COMPASS Collaboration by scattering 160 GeV muons off an isoscalar 6LiD target. The results were obtained in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y, and the fraction z of the virtual-photon energy carried by the produced hadron. A leading-order pQCD analysis was performed using the pion multiplicity results to extract quark fragmentation functions into pions. The results for the sum of the z-integrated multiplicities for pions and for kaons, differ from earlier results from the HERMES experiment. The results from the sum of the z-integrated K+ and K- multiplicities at high x point to a value of the non-strange quark fragmentation function larger than obtained by the earlier DSS fit.

DNA replication and cancer: From dysfunctional replication origin activities to therapeutic opportunities.

PubMed

Boyer, Anne-Sophie; Walter, David; Sørensen, Claus Storgaard

2016-06-01

A dividing cell has to duplicate its DNA precisely once during the cell cycle to preserve genome integrity avoiding the accumulation of genetic aberrations that promote diseases such as cancer. A large number of endogenous impacts can challenge DNA replication and cells harbor a battery of pathways to promote genome integrity during DNA replication. This includes suppressing new replication origin firing, stabilization of replicating forks, and the safe restart of forks to prevent any loss of genetic information. Here, we describe mechanisms by which oncogenes can interfere with DNA replication thereby causing DNA replication stress and genome instability. Further, we describe cellular and systemic responses to these insults with a focus on DNA replication restart pathways. Finally, we discuss the therapeutic potential of exploiting intrinsic replicative stress in cancer cells for targeted therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ultra low-cost, portable smartphone optosensors for mobile point-of-care diagnostics

NASA Astrophysics Data System (ADS)

Wang, Li-Ju; Chang, Yu-Chung; Sun, Rongrong; Li, Lei

2018-02-01

Smartphone optosensors with integrated optical components make mobile point-of-care (MPoC) diagnostics be done near patients' side. It'll especially have a significant impact on healthcare delivery in rural or remote areas. Current FDA-approved PoC devices achieving clinical level are still at high cost and not affordable in rural hospitals. We present a series of ultra low-cost smartphone optical sensing devices for mobile point-of-care diagnosis. Aiming different targeting analytes and sensing mechanisms, we developed custom required optical components for each smartphone optosensros. These optical devices include spectrum readers, colorimetric readers for microplate, lateral flow device readers, and chemiluminescence readers. By integrating our unique designed optical components into smartphone optosening platform, the anlaytes can be precisely detected. Clinical testing results show the clinical usability of our smartphone optosensors. Ultra low-cost portable smartphone optosensors are affordable for rural/remote doctors.

Application of CCD drift-scan photoelectric technique on monitoring GEO satellites

NASA Astrophysics Data System (ADS)

Yu, Yong; Zhao, Xiao-Fen; Luo, Hao; Mao, Yin-Dun; Tang, Zheng-Hong

2018-05-01

Geosynchronous Earth Orbit (GEO) satellites are widely used because of their unique characteristics of high-orbit and remaining permanently in the same area of the sky. Precise monitoring of GEO satellites can provide a key reference for the judgment of satellite operation status, the capture and identification of targets, and the analysis of collision warning. The observation using ground-based optical telescopes plays an important role in the field of monitoring GEO targets. Different from distant celestial bodies, there is a relative movement between the GEO target and the background reference stars, which makes the conventional observation method limited for long focal length telescopes. CCD drift-scan photoelectric technique is applied on monitoring GEO targets. In the case of parking the telescope, the good round images of the background reference stars and the GEO target at the same sky region can be obtained through the alternating observation of CCD drift-scan mode and CCD stare mode, so as to improve the precision of celestial positioning for the GEO target. Observation experiments of GEO targets were carried out with 1.56-meter telescope of Shanghai Astronomical Observatory. The results show that the application of CCD drift-scan photoelectric technique makes the precision of observing the GEO target reach the level of 0.2″, which gives full play to the advantage of the long focal length of the telescope. The effect of orbit improvement based on multi-pass of observations is obvious and the prediction precision of extrapolating to 72-h is in the order of several arc seconds in azimuth and elevation.

[Precision medicine : a required approach for the general internist].

PubMed

Waeber, Gérard; Cornuz, Jacques; Gaspoz, Jean-Michel; Guessous, Idris; Mooser, Vincent; Perrier, Arnaud; Simonet, Martine Louis

2017-01-18

The general internist cannot be a passive bystander of the anticipated medical revolution induced by precision medicine. This latter aims to improve the predictive and/or clinical course of an individual by integrating all biological, genetic, environmental, phenotypic and psychosocial knowledge of a person. In this article, national and international initiatives in the field of precision medicine are discussed as well as the potential financial, ethical and limitations of personalized medicine. The question is not to know if precision medicine will be part of everyday life but rather to integrate early the general internist in multidisciplinary teams to ensure optimal information and shared-decision process with patients and individuals.

PreCisIon: PREdiction of CIS-regulatory elements improved by gene's positION.

PubMed

Elati, Mohamed; Nicolle, Rémy; Junier, Ivan; Fernández, David; Fekih, Rim; Font, Julio; Képès, François

2013-02-01

Conventional approaches to predict transcriptional regulatory interactions usually rely on the definition of a shared motif sequence on the target genes of a transcription factor (TF). These efforts have been frustrated by the limited availability and accuracy of TF binding site motifs, usually represented as position-specific scoring matrices, which may match large numbers of sites and produce an unreliable list of target genes. To improve the prediction of binding sites, we propose to additionally use the unrelated knowledge of the genome layout. Indeed, it has been shown that co-regulated genes tend to be either neighbors or periodically spaced along the whole chromosome. This study demonstrates that respective gene positioning carries significant information. This novel type of information is combined with traditional sequence information by a machine learning algorithm called PreCisIon. To optimize this combination, PreCisIon builds a strong gene target classifier by adaptively combining weak classifiers based on either local binding sequence or global gene position. This strategy generically paves the way to the optimized incorporation of any future advances in gene target prediction based on local sequence, genome layout or on novel criteria. With the current state of the art, PreCisIon consistently improves methods based on sequence information only. This is shown by implementing a cross-validation analysis of the 20 major TFs from two phylogenetically remote model organisms. For Bacillus subtilis and Escherichia coli, respectively, PreCisIon achieves on average an area under the receiver operating characteristic curve of 70 and 60%, a sensitivity of 80 and 70% and a specificity of 60 and 56%. The newly predicted gene targets are demonstrated to be functionally consistent with previously known targets, as assessed by analysis of Gene Ontology enrichment or of the relevant literature and databases.

Pose measurement method and experiments for high-speed rolling targets in a wind tunnel.

PubMed

Jia, Zhenyuan; Ma, Xin; Liu, Wei; Lu, Wenbo; Li, Xiao; Chen, Ling; Wang, Zhengqu; Cui, Xiaochun

2014-12-12

High-precision wind tunnel simulation tests play an important role in aircraft design and manufacture. In this study, a high-speed pose vision measurement method is proposed for high-speed and rolling targets in a supersonic wind tunnel. To obtain images with high signal-to-noise ratio and avoid impacts on the aerodynamic shape of the rolling targets, a high-speed image acquisition method based on ultrathin retro-reflection markers is presented. Since markers are small-sized and some of them may be lost when the target is rolling, a novel markers layout with which markers are distributed evenly on the surface is proposed based on a spatial coding method to achieve highly accurate pose information. Additionally, a pose acquisition is carried out according to the mentioned markers layout after removing mismatching points by Case Deletion Diagnostics. Finally, experiments on measuring the pose parameters of high-speed targets in the laboratory and in a supersonic wind tunnel are conducted to verify the feasibility and effectiveness of the proposed method. Experimental results indicate that the position measurement precision is less than 0.16 mm, the pitching and yaw angle precision less than 0.132° and the roll angle precision 0.712°.

Deep-Dive Targeted Quantification for Ultrasensitive Analysis of Proteins in Nondepleted Human Blood Plasma/Serum and Tissues

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

Nie, Song; Shi, Tujin; Fillmore, Thomas L.

Mass spectrometry-based targeted proteomics (e.g., selected reaction monitoring, SRM) is emerging as an attractive alternative to immunoassays for protein quantification. Recently we have made significant progress in SRM sensitivity for enabling quantification of low ng/mL to sub-ng/mL level proteins in nondepleted human blood plasma/serum without affinity enrichment. However, precise quantification of extremely low abundant but biologically important proteins (e.g., ≤100 pg/mL in blood plasma/serum) using targeted proteomics approaches still remains challenging. To address this need, we have developed an antibody-independent Deep-Dive SRM (DD-SRM) approach that capitalizes on multidimensional high-resolution reversed-phase liquid chromatography (LC) separation for target peptide enrichment combined withmore » precise selection of target peptide fractions of interest, significantly improving SRM sensitivity by ~5 orders of magnitude when compared to conventional LC-SRM. Application of DD-SRM to human serum and tissue has been demonstrated to enable precise quantification of endogenous proteins at ~10 pg/mL level in nondepleted serum and at <10 copies per cell level in tissue. Thus, DD-SRM holds great promise for precisely measuring extremely low abundance proteins or protein modifications, especially when high-quality antibody is not available.« less

Pose Measurement Method and Experiments for High-Speed Rolling Targets in a Wind Tunnel

PubMed Central

Jia, Zhenyuan; Ma, Xin; Liu, Wei; Lu, Wenbo; Li, Xiao; Chen, Ling; Wang, Zhengqu; Cui, Xiaochun

2014-01-01

High-precision wind tunnel simulation tests play an important role in aircraft design and manufacture. In this study, a high-speed pose vision measurement method is proposed for high-speed and rolling targets in a supersonic wind tunnel. To obtain images with high signal-to-noise ratio and avoid impacts on the aerodynamic shape of the rolling targets, a high-speed image acquisition method based on ultrathin retro-reflection markers is presented. Since markers are small-sized and some of them may be lost when the target is rolling, a novel markers layout with which markers are distributed evenly on the surface is proposed based on a spatial coding method to achieve highly accurate pose information. Additionally, a pose acquisition is carried out according to the mentioned markers layout after removing mismatching points by Case Deletion Diagnostics. Finally, experiments on measuring the pose parameters of high-speed targets in the laboratory and in a supersonic wind tunnel are conducted to verify the feasibility and effectiveness of the proposed method. Experimental results indicate that the position measurement precision is less than 0.16 mm, the pitching and yaw angle precision less than 0.132° and the roll angle precision 0.712°. PMID:25615732

Specificity of Postural Sway to the Demands of a Precision Task at Sea

ERIC Educational Resources Information Center

Chen, Fu-Chen; Stoffregen, Thomas A.

2012-01-01

Mariners actively adjust their body orientation in response to ship motion. On a ship at sea, we evaluated relations between standing postural activity and the performance of a precision aiming task. Standing participants (experienced mariners) maintained the beam from a handheld laser on a target. Targets were large or small, thereby varying the…

2007 Precision Strike Annual Programs Review

DTIC Science & Technology

2007-04-25

Adapting our methods • Remaining a flexible combined-arms force • Enabling a generation of combat- experienced decision-makers by distributing...Sustain Propulsion Network RadioMEMS IMU Flexible Engagement Options Requirements Capabilities Precision Attack Missile (PAM) 67” (with Canister...Aimpoint 6 PAM Seeker Modes PAM’s Multiple Targeting Modes Increase Flexibility , Improve Lethality PAM’s Multiple Targeting Modes Increase Flexibility

Phage-Enabled Nanomedicine: From Probes to Therapeutics in Precision Medicine.

PubMed

Sunderland, Kegan S; Yang, Mingying; Mao, Chuanbin

2017-02-13

Both lytic and temperate bacteriophages (phages) can be applied in nanomedicine, in particular, as nanoprobes for precise disease diagnosis and nanotherapeutics for targeted disease treatment. Since phages are bacteria-specific viruses, they do not naturally infect eukaryotic cells and are not toxic to them. They can be genetically engineered to target nanoparticles, cells, tissues, and organs, and can also be modified with functional abiotic nanomaterials for disease diagnosis and treatment. This Review will summarize the current use of phage structures in many aspects of precision nanomedicine, including ultrasensitive biomarker detection, enhanced bioimaging for disease diagnosis, targeted drug and gene delivery, directed stem cell differentiation, accelerated tissue formation, effective vaccination, and nanotherapeutics for targeted disease treatment. We will also propose future directions in the area of phage-based nanomedicines, and discuss the state of phage-based clinical trials. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular genetics and targeted therapeutics in biliary tract carcinoma

PubMed Central

Marks, Eric I; Yee, Nelson S

2016-01-01

The primary malignancies of the biliary tract, cholangiocarcinoma and gallbladder cancer, often present at an advanced stage and are marginally sensitive to radiation and chemotherapy. Accumulating evidence indicates that molecularly targeted agents may provide new hope for improving treatment response in biliary tract carcinoma (BTC). In this article, we provide a critical review of the pathogenesis and genetic abnormalities of biliary tract neoplasms, in addition to discussing the current and emerging targeted therapeutics in BTC. Genetic studies of biliary tumors have identified the growth factors and receptors as well as their downstream signaling pathways that control the growth and survival of biliary epithelia. Target-specific monoclonal antibodies and small molecules inhibitors directed against the signaling pathways that drive BTC growth and invasion have been developed. Numerous clinical trials designed to test these agents as either monotherapy or in combination with conventional chemotherapy have been completed or are currently underway. Research focusing on understanding the molecular basis of biliary tumorigenesis will continue to identify for targeted therapy the key mutations that drive growth and invasion of biliary neoplasms. Additional strategies that have emerged for treating this malignant disease include targeting the epigenetic alterations of BTC and immunotherapy. By integrating targeted therapy with molecular profiles of biliary tumor, we hope to provide precision treatment for patients with malignant diseases of the biliary tract. PMID:26819503

Note: Eddy current displacement sensors independent of target conductivity.

PubMed

Wang, Hongbo; Li, Wei; Feng, Zhihua

2015-01-01

Eddy current sensors (ECSs) are widely used for non-contact displacement measurement. In this note, the quantitative error of an ECS caused by target conductivity was analyzed using a complex image method. The response curves (L-x) of the ECS with different targets were similar and could be overlapped by shifting the curves on x direction with √2δ/2. Both finite element analysis and experiments match well with the theoretical analysis, which indicates that the measured error of high precision ECSs caused by target conductivity can be completely eliminated, and the ECSs can measure different materials precisely without calibration.

Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases.

PubMed

Remy, Séverine; Tesson, Laurent; Menoret, Séverine; Usal, Claire; De Cian, Anne; Thepenier, Virginie; Thinard, Reynald; Baron, Daniel; Charpentier, Marine; Renaud, Jean-Baptiste; Buelow, Roland; Cost, Gregory J; Giovannangeli, Carine; Fraichard, Alexandre; Concordet, Jean-Paul; Anegon, Ignacio

2014-08-01

The generation of genetically modified animals is important for both research and commercial purposes. The rat is an important model organism that until recently lacked efficient genetic engineering tools. Sequence-specific nucleases, such as ZFNs, TALE nucleases, and CRISPR/Cas9 have allowed the creation of rat knockout models. Genetic engineering by homology-directed repair (HDR) is utilized to create animals expressing transgenes in a controlled way and to introduce precise genetic modifications. We applied TALE nucleases and donor DNA microinjection into zygotes to generate HDR-modified rats with large new sequences introduced into three different loci with high efficiency (0.62%-5.13% of microinjected zygotes). Two of these loci (Rosa26 and Hprt1) are known to allow robust and reproducible transgene expression and were targeted for integration of a GFP expression cassette driven by the CAG promoter. GFP-expressing embryos and four Rosa26 GFP rat lines analyzed showed strong and widespread GFP expression in most cells of all analyzed tissues. The third targeted locus was Ighm, where we performed successful exon exchange of rat exon 2 for the human one. At all three loci we observed HDR only when using linear and not circular donor DNA. Mild hypothermic (30°C) culture of zygotes after microinjection increased HDR efficiency for some loci. Our study demonstrates that TALE nuclease and donor DNA microinjection into rat zygotes results in efficient and reproducible targeted donor integration by HDR. This allowed creation of genetically modified rats in a work-, cost-, and time-effective manner. © 2014 Remy et al.; Published by Cold Spring Harbor Laboratory Press.

Efficient gene targeting by homology-directed repair in rat zygotes using TALE nucleases

PubMed Central

Remy, Séverine; Tesson, Laurent; Menoret, Séverine; Usal, Claire; De Cian, Anne; Thepenier, Virginie; Thinard, Reynald; Baron, Daniel; Charpentier, Marine; Renaud, Jean-Baptiste; Buelow, Roland; Cost, Gregory J.; Giovannangeli, Carine; Fraichard, Alexandre; Concordet, Jean-Paul; Anegon, Ignacio

2014-01-01

The generation of genetically modified animals is important for both research and commercial purposes. The rat is an important model organism that until recently lacked efficient genetic engineering tools. Sequence-specific nucleases, such as ZFNs, TALE nucleases, and CRISPR/Cas9 have allowed the creation of rat knockout models. Genetic engineering by homology-directed repair (HDR) is utilized to create animals expressing transgenes in a controlled way and to introduce precise genetic modifications. We applied TALE nucleases and donor DNA microinjection into zygotes to generate HDR-modified rats with large new sequences introduced into three different loci with high efficiency (0.62%–5.13% of microinjected zygotes). Two of these loci (Rosa26 and Hprt1) are known to allow robust and reproducible transgene expression and were targeted for integration of a GFP expression cassette driven by the CAG promoter. GFP-expressing embryos and four Rosa26 GFP rat lines analyzed showed strong and widespread GFP expression in most cells of all analyzed tissues. The third targeted locus was Ighm, where we performed successful exon exchange of rat exon 2 for the human one. At all three loci we observed HDR only when using linear and not circular donor DNA. Mild hypothermic (30°C) culture of zygotes after microinjection increased HDR efficiency for some loci. Our study demonstrates that TALE nuclease and donor DNA microinjection into rat zygotes results in efficient and reproducible targeted donor integration by HDR. This allowed creation of genetically modified rats in a work-, cost-, and time-effective manner. PMID:24989021

Frozen lattice and absorptive model for high angle annular dark field scanning transmission electron microscopy: A comparison study in terms of integrated intensity and atomic column position measurement.

PubMed

Alania, M; Lobato, I; Van Aert, S

2018-01-01

In this paper, both the frozen lattice (FL) and the absorptive potential (AP) approximation models are compared in terms of the integrated intensity and the precision with which atomic columns can be located from an image acquired using high angle annular dark field (HAADF) scanning transmission electron microscopy (STEM). The comparison is made for atoms of Cu, Ag, and Au. The integrated intensity is computed for both an isolated atomic column and an atomic column inside an FCC structure. The precision has been computed using the so-called Cramér-Rao Lower Bound (CRLB), which provides a theoretical lower bound on the variance with which parameters can be estimated. It is shown that the AP model results into accurate measurements for the integrated intensity only for small detector ranges under relatively low angles and for small thicknesses. In terms of the attainable precision, both methods show similar results indicating picometer range precision under realistic experimental conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Approach-Phase Precision Landing with Hazard Relative Navigation: Terrestrial Test Campaign Results of the Morpheus/ALHAT Project

NASA Technical Reports Server (NTRS)

Crain, Timothy P.; Bishop, Robert H.; Carson, John M., III; Trawny, Nikolas; Hanak, Chad; Sullivan, Jacob; Christian, John; DeMars, Kyle; Campbell, Tom; Getchius, Joel

2016-01-01

The Morpheus Project began in late 2009 as an ambitious e ort code-named Project M to integrate three ongoing multi-center NASA technology developments: humanoid robotics, liquid oxygen/liquid methane (LOX/LCH4) propulsion and Autonomous Precision Landing and Hazard Avoidance Technology (ALHAT) into a single engineering demonstration mission to be own to the Moon by 2013. The humanoid robot e ort was redirected to a deploy- ment of Robonaut 2 on the International Space Station in February of 2011 while Morpheus continued as a terrestrial eld test project integrating the existing ALHAT Project's tech- nologies into a sub-orbital ight system using the world's rst LOX/LCH4 main propulsion and reaction control system fed from the same blowdown tanks. A series of 33 tethered tests with the Morpheus 1.0 vehicle and Morpheus 1.5 vehicle were conducted from April 2011 - December 2013 before successful, sustained free ights with the primary Vertical Testbed (VTB) navigation con guration began with Free Flight 3 on December 10, 2013. Over the course of the following 12 free ights and 3 tethered ights, components of the ALHAT navigation system were integrated into the Morpheus vehicle, operations, and ight control loop. The ALHAT navigation system was integrated and run concurrently with the VTB navigation system as a reference and fail-safe option in ight (see touchdown position esti- mate comparisons in Fig. 1). Flight testing completed with Free Flight 15 on December 15, 2014 with a completely autonomous Hazard Detection and Avoidance (HDA), integration of surface relative and Hazard Relative Navigation (HRN) measurements into the onboard dual-state inertial estimator Kalman lter software, and landing within 2 meters of the VTB GPS-based navigation solution at the safe landing site target. This paper describes the Mor- pheus joint VTB/ALHAT navigation architecture, the sensors utilized during the terrestrial ight campaign, issues resolved during testing, and the navigation results from the ight tests.

Intelligent surgical laser system configuration and software implementation

NASA Astrophysics Data System (ADS)

Hsueh, Chi-Fu T.; Bille, Josef F.

1992-06-01

An intelligent surgical laser system, which can help the ophthalmologist to achieve higher precision and control during their procedures, has been developed by ISL as model CLS 4001. In addition to the laser and laser delivery system, the system is also equipped with a vision system (IPU), robotics motion control (MCU), and a tracking closed loop system (ETS) that tracks the eye in three dimensions (X, Y and Z). The initial patient setup is computer controlled with guidance from the vision system. The tracking system is automatically engaged when the target is in position. A multi-level tracking system is developed by integrating our vision and tracking systems which have been able to maintain our laser beam precisely on target. The capabilities of the automatic eye setup and the tracking in three dimensions provides for improved accuracy and measurement repeatability. The system is operated through the Surgical Control Unit (SCU). The SCU communicates with the IPU and the MCU through both ethernet and RS232. Various scanning pattern (i.e., line, curve, circle, spiral, etc.) can be selected with given parameters. When a warning is activated, a voice message is played that will normally require a panel touch acknowledgement. The reliability of the system is ensured in three levels: (1) hardware, (2) software real time monitoring, and (3) user. The system is currently under clinical validation.

Design of a Teleoperated Needle Steering System for MRI-guided Prostate Interventions

PubMed Central

Seifabadi, Reza; Iordachita, Iulian; Fichtinger, Gabor

2013-01-01

Accurate needle placement plays a key role in success of prostate biopsy and brachytherapy. During percutaneous interventions, the prostate gland rotates and deforms which may cause significant target displacement. In these cases straight needle trajectory is not sufficient for precise targeting. Although needle spinning and fast insertion may be helpful, they do not entirely resolve the issue. We propose robot-assisted bevel-tip needle steering under MRI guidance as a potential solution to compensate for the target displacement. MRI is chosen for its superior soft tissue contrast in prostate imaging. Due to the confined workspace of the MRI scanner and the requirement for the clinician to be present inside the MRI room during the procedure, we designed a MRI-compatible 2-DOF haptic device to command the needle steering slave robot which operates inside the scanner. The needle steering slave robot was designed to be integrated with a previously developed pneumatically actuated transperineal robot for MRI-guided prostate needle placement. We describe design challenges and present the conceptual design of the master and slave robots and the associated controller. PMID:24649480

A linear quadratic Gaussian with loop transfer recovery proximity operations autopilot for spacecraft. M.S. Thesis - MIT

NASA Technical Reports Server (NTRS)

Chen, George T.

1987-01-01

An automatic control scheme for spacecraft proximity operations is presented. The controller is capable of holding the vehicle at a prescribed location relative to a target, or maneuvering it to a different relative position using straight line-of-sight translations. The autopilot uses a feedforward loop to initiate and terminate maneuvers, and for operations at nonequilibrium set-points. A multivariate feedback loop facilitates precise position and velocity control in the presence of sensor noise. The feedback loop is formulated using the Linear Quadratic Gaussian (LQG) with Loop Transfer Recovery (LTR) design procedure. Linear models of spacecraft dynamics, adapted from Clohessey-Wiltshire Equations, are augmented and loop shaping techniques are applied to design a target feedback loop. The loop transfer recovery procedure is used to recover the frequency domain properties of the target feedback loop. The resulting compensator is integrated into an autopilot which is tested in a high fidelity Space Shuttle Simulator. The autopilot performance is evaluated for a variety of proximity operations tasks envisioned for future Shuttle flights.

The national ignition facility: path to ignition in the laboratory

NASA Astrophysics Data System (ADS)

Moses, E. I.; Bonanno, R. E.; Haynam, C. A.; Kauffman, R. L.; MacGowan, B. J.; Patterson, R. W., Jr.; Sawicki, R. H.; van Wonterghem, B. M.

2007-08-01

The National Ignition Facility (NIF) is a 192-beam laser facility presently under construction at LLNL. When completed, NIF will be a 1.8-MJ, 500-TW ultraviolet laser system. Its missions are to obtain fusion ignition and to perform high energy density experiments in support of the US nuclear weapons stockpile. Four of the NIF beams have been commissioned to demonstrate laser performance and to commission the target area including target and beam alignment and laser timing. During this time, NIF demonstrated on a single-beam basis that it will meet its performance goals and demonstrated its precision and flexibility for pulse shaping, pointing, timing and beam conditioning. It also performed four important experiments for Inertial Confinement Fusion and High Energy Density Science. Presently, the project is installing production hardware to complete the project in 2009 with the goal to begin ignition experiments in 2010. An integrated plan has been developed including the NIF operations, user equipment such as diagnostics and cryogenic target capability, and experiments and calculations to meet this goal. This talk will provide NIF status, the plan to complete NIF, and the path to ignition.

Dielectrophoretic focusing integrated pulsed laser activated cell sorting

NASA Astrophysics Data System (ADS)

Zhu, Xiongfeng; Kung, Yu-Chun; Wu, Ting-Hsiang; Teitell, Michael A.; Chiou, Pei-Yu

2017-08-01

We present a pulsed laser activated cell sorter (PLACS) integrated with novel sheathless size-independent dielectrophoretic (DEP) focusing. Microfluidic fluorescence activated cell sorting (μFACS) systems aim to provide a fully enclosed environment for sterile cell sorting and integration with upstream and downstream microfluidic modules. Among them, PLACS has shown a great potential in achieving comparable performance to commercial aerosol-based FACS (>90% purity at 25,000 cells sec-1). However conventional sheath flow focusing method suffers a severe sample dilution issue. Here we demonstrate a novel dielectrophoresis-integrated pulsed laser activated cell sorter (DEP-PLACS). It consists of a microfluidic channel with 3D electrodes laid out to provide a tunnel-shaped electric field profile along a 4cmlong channel for sheathlessly focusing microparticles/cells into a single stream in high-speed microfluidic flows. All focused particles pass through the fluorescence detection zone along the same streamline regardless of their sizes and types. Upon detection of target fluorescent particles, a nanosecond laser pulse is triggered and focused in a neighboring channel to generate a rapidly expanding cavitation bubble for precise sorting. DEP-PLACS has achieved a sorting purity of 91% for polystyrene beads at a throughput of 1,500 particle/sec.

Photolithography-Based Patterning of Liquid Metal Interconnects for Monolithically Integrated Stretchable Circuits.

PubMed

Park, Chan Woo; Moon, Yu Gyeong; Seong, Hyejeong; Jung, Soon Won; Oh, Ji-Young; Na, Bock Soon; Park, Nae-Man; Lee, Sang Seok; Im, Sung Gap; Koo, Jae Bon

2016-06-22

We demonstrate a new patterning technique for gallium-based liquid metals on flat substrates, which can provide both high pattern resolution (∼20 μm) and alignment precision as required for highly integrated circuits. In a very similar manner as in the patterning of solid metal films by photolithography and lift-off processes, the liquid metal layer painted over the whole substrate area can be selectively removed by dissolving the underlying photoresist layer, leaving behind robust liquid patterns as defined by the photolithography. This quick and simple method makes it possible to integrate fine-scale interconnects with preformed devices precisely, which is indispensable for realizing monolithically integrated stretchable circuits. As a way for constructing stretchable integrated circuits, we propose a hybrid configuration composed of rigid device regions and liquid interconnects, which is constructed on a rigid substrate first but highly stretchable after being transferred onto an elastomeric substrate. This new method can be useful in various applications requiring both high-resolution and precisely aligned patterning of gallium-based liquid metals.

An Anatomically Constrained Model for Path Integration in the Bee Brain.

PubMed

Stone, Thomas; Webb, Barbara; Adden, Andrea; Weddig, Nicolai Ben; Honkanen, Anna; Templin, Rachel; Wcislo, William; Scimeca, Luca; Warrant, Eric; Heinze, Stanley

2017-10-23

Path integration is a widespread navigational strategy in which directional changes and distance covered are continuously integrated on an outward journey, enabling a straight-line return to home. Bees use vision for this task-a celestial-cue-based visual compass and an optic-flow-based visual odometer-but the underlying neural integration mechanisms are unknown. Using intracellular electrophysiology, we show that polarized-light-based compass neurons and optic-flow-based speed-encoding neurons converge in the central complex of the bee brain, and through block-face electron microscopy, we identify potential integrator cells. Based on plausible output targets for these cells, we propose a complete circuit for path integration and steering in the central complex, with anatomically identified neurons suggested for each processing step. The resulting model circuit is thus fully constrained biologically and provides a functional interpretation for many previously unexplained architectural features of the central complex. Moreover, we show that the receptive fields of the newly discovered speed neurons can support path integration for the holonomic motion (i.e., a ground velocity that is not precisely aligned with body orientation) typical of bee flight, a feature not captured in any previously proposed model of path integration. In a broader context, the model circuit presented provides a general mechanism for producing steering signals by comparing current and desired headings-suggesting a more basic function for central complex connectivity, from which path integration may have evolved. Copyright © 2017 Elsevier Ltd. All rights reserved.

Search Filter Precision Can Be Improved By NOTing Out Irrelevant Content

PubMed Central

Wilczynski, Nancy L.; McKibbon, K. Ann; Haynes, R. Brian

2011-01-01

Background: Most methodologic search filters developed for use in large electronic databases such as MEDLINE have low precision. One method that has been proposed but not tested for improving precision is NOTing out irrelevant content. Objective: To determine if search filter precision can be improved by NOTing out the text words and index terms assigned to those articles that are retrieved but are off-target. Design: Analytic survey. Methods: NOTing out unique terms in off-target articles and testing search filter performance in the Clinical Hedges Database. Main Outcome Measures: Sensitivity, specificity, precision and number needed to read (NNR). Results: For all purpose categories (diagnosis, prognosis and etiology) except treatment and for all databases (MEDLINE, EMBASE, CINAHL and PsycINFO), constructing search filters that NOTed out irrelevant content resulted in substantive improvements in NNR (over four-fold for some purpose categories and databases). Conclusion: Search filter precision can be improved by NOTing out irrelevant content. PMID:22195215

Precision medicine of aneurysmal subarachnoid hemorrhage, vasospasm and delayed cerebral ischemia.

PubMed

Burrell, Christian; Avalon, Nicole E; Siegel, Jason; Pizzi, Michael; Dutta, Tumpa; Charlesworth, M Cristine; Freeman, William D

2016-11-01

Precision medicine provides individualized treatment of diseases through leveraging patient-to-patient variation. Aneurysmal subarachnoid hemorrhage carries tremendous morbidity and mortality with cerebral vasospasm and delayed cerebral ischemia proving devastating and unpredictable. Lack of treatment measures for these conditions could be improved through precision medicine. Areas covered: Discussed are the pathophysiology of CV and DCI, treatment guidelines, and evidence for precision medicine used for prediction and prevention of poor outcomes following aSAH. A PubMed search was performed using keywords cerebral vasospasm or delayed cerebral ischemia and either biomarkers, precision medicine, metabolomics, proteomics, or genomics. Over 200 peer-reviewed articles were evaluated. The studies presented cover biomarkers identified as predictive markers or therapeutic targets following aSAH. Expert commentary: The biomarkers reviewed here correlate with CV, DCI, and neurologic outcomes after aSAH. Though practical use in clinical management of aSAH is not well established, using these biomarkers as predictive tools or therapeutic targets demonstrates the potential of precision medicine.

Precise Correction of Disease Mutations in Induced Pluripotent Stem Cells Derived From Patients With Limb Girdle Muscular Dystrophy.

PubMed

Turan, Soeren; Farruggio, Alfonso P; Srifa, Waracharee; Day, John W; Calos, Michele P

2016-04-01

Limb girdle muscular dystrophies types 2B (LGMD2B) and 2D (LGMD2D) are degenerative muscle diseases caused by mutations in the dysferlin and alpha-sarcoglycan genes, respectively. Using patient-derived induced pluripotent stem cells (iPSC), we corrected the dysferlin nonsense mutation c.5713C>T; p.R1905X and the most common alpha-sarcoglycan mutation, missense c.229C>T; p.R77C, by single-stranded oligonucleotide-mediated gene editing, using the CRISPR/Cas9 gene-editing system to enhance the frequency of homology-directed repair. We demonstrated seamless, allele-specific correction at efficiencies of 0.7-1.5%. As an alternative, we also carried out precise gene addition strategies for correction of the LGMD2B iPSC by integration of wild-type dysferlin cDNA into the H11 safe harbor locus on chromosome 22, using dual integrase cassette exchange (DICE) or TALEN-assisted homologous recombination for insertion precise (THRIP). These methods employed TALENs and homologous recombination, and DICE also utilized site-specific recombinases. With DICE and THRIP, we obtained targeting efficiencies after selection of ~20%. We purified iPSC corrected by all methods and verified rescue of appropriate levels of dysferlin and alpha-sarcoglycan protein expression and correct localization, as shown by immunoblot and immunocytochemistry. In summary, we demonstrate for the first time precise correction of LGMD iPSC and validation of expression, opening the possibility of cell therapy utilizing these corrected iPSC.

Tunnel profile measurement by vision metrology toward application to NATM

NASA Astrophysics Data System (ADS)

Hattori, Susumu; Akimoto, Keiichi; Ono, Tetsu; Miura, Satoru

2003-05-01

The NATM, a widely used tunnel excavation method, requires precise periodical monitoring of deformations especially at fault zones, which tends to hamper traffics with conventional measurement means. In this paper vision metrology was applied to tunnel profile measurement with a view to developing a new method. Two hundred of Retro-targets are placed on a one-meter spacing lattice at a tunnel site of 7m in diameter and 15m in longitude, and 66 images were taken to cover the target field. The object space coordinates of targets obtained by bundle adjustment were compared with ones obtained by high-precision total station observation. The root mean square (RMS) of differences of coordinates was 0.548mm, which is precise enough for monitoring deformations for the NATM.

A fiducial skull marker for precise MRI-based stereotaxic surgery in large animal models.

PubMed

Glud, Andreas Nørgaard; Bech, Johannes; Tvilling, Laura; Zaer, Hamed; Orlowski, Dariusz; Fitting, Lise Moberg; Ziedler, Dora; Geneser, Michael; Sangill, Ryan; Alstrup, Aage Kristian Olsen; Bjarkam, Carsten Reidies; Sørensen, Jens Christian Hedemann

2017-06-15

Stereotaxic neurosurgery in large animals is used widely in different sophisticated models, where precision is becoming more crucial as desired anatomical target regions are becoming smaller. Individually calculated coordinates are necessary in large animal models with cortical and subcortical anatomical differences. We present a convenient method to make an MRI-visible skull fiducial for 3D MRI-based stereotaxic procedures in larger experimental animals. Plastic screws were filled with either copper-sulfate solution or MRI-visible paste from a commercially available cranial head marker. The screw fiducials were inserted in the animal skulls and T1 weighted MRI was performed allowing identification of the inserted skull marker. Both types of fiducial markers were clearly visible on the MRÍs. This allows high precision in the stereotaxic space. The use of skull bone based fiducial markers gives high precision for both targeting and evaluation of stereotaxic systems. There are no metal artifacts and the fiducial is easily removed after surgery. The fiducial marker can be used as a very precise reference point, either for direct targeting or in evaluation of other stereotaxic systems. Copyright © 2017 Elsevier B.V. All rights reserved.

Site-specific recombination for precise and clean transgene integration in plant genome. In: Touraev, A., Citovsky, V., Tzfira, T., Editors of book. Plant Transformation Technologies.

USDA-ARS?s Scientific Manuscript database

Plant Transformation Technologies is a comprehensive, authoritative book focusing on cutting-edge plant biotechnologies, offering in-depth, forward-looking information on methods for controlled and accurate genetic engineering. In response to ever-increasing pressure for precise and efficient integr...

Nanorobot Hardware Architecture for Medical Defense.

PubMed

Cavalcanti, Adriano; Shirinzadeh, Bijan; Zhang, Mingjun; Kretly, Luiz C

2008-05-06

This work presents a new approach with details on the integrated platform and hardware architecture for nanorobots application in epidemic control, which should enable real time in vivo prognosis of biohazard infection. The recent developments in the field of nanoelectronics, with transducers progressively shrinking down to smaller sizes through nanotechnology and carbon nanotubes, are expected to result in innovative biomedical instrumentation possibilities, with new therapies and efficient diagnosis methodologies. The use of integrated systems, smart biosensors, and programmable nanodevices are advancing nanoelectronics, enabling the progressive research and development of molecular machines. It should provide high precision pervasive biomedical monitoring with real time data transmission. The use of nanobioelectronics as embedded systems is the natural pathway towards manufacturing methodology to achieve nanorobot applications out of laboratories sooner as possible. To demonstrate the practical application of medical nanorobotics, a 3D simulation based on clinical data addresses how to integrate communication with nanorobots using RFID, mobile phones, and satellites, applied to long distance ubiquitous surveillance and health monitoring for troops in conflict zones. Therefore, the current model can also be used to prevent and save a population against the case of some targeted epidemic disease.

Accurate and efficient integration for molecular dynamics simulations at constant temperature and pressure

NASA Astrophysics Data System (ADS)

Lippert, Ross A.; Predescu, Cristian; Ierardi, Douglas J.; Mackenzie, Kenneth M.; Eastwood, Michael P.; Dror, Ron O.; Shaw, David E.

2013-10-01

In molecular dynamics simulations, control over temperature and pressure is typically achieved by augmenting the original system with additional dynamical variables to create a thermostat and a barostat, respectively. These variables generally evolve on timescales much longer than those of particle motion, but typical integrator implementations update the additional variables along with the particle positions and momenta at each time step. We present a framework that replaces the traditional integration procedure with separate barostat, thermostat, and Newtonian particle motion updates, allowing thermostat and barostat updates to be applied infrequently. Such infrequent updates provide a particularly substantial performance advantage for simulations parallelized across many computer processors, because thermostat and barostat updates typically require communication among all processors. Infrequent updates can also improve accuracy by alleviating certain sources of error associated with limited-precision arithmetic. In addition, separating the barostat, thermostat, and particle motion update steps reduces certain truncation errors, bringing the time-average pressure closer to its target value. Finally, this framework, which we have implemented on both general-purpose and special-purpose hardware, reduces software complexity and improves software modularity.

Multifunctional millimeter-wave radar system for helicopter safety

NASA Astrophysics Data System (ADS)

Goshi, Darren S.; Case, Timothy J.; McKitterick, John B.; Bui, Long Q.

2012-06-01

A multi-featured sensor solution has been developed that enhances the operational safety and functionality of small airborne platforms, representing an invaluable stride toward enabling higher-risk, tactical missions. This paper demonstrates results from a recently developed multi-functional sensor system that integrates a high performance millimeter-wave radar front end, an evidence grid-based integration processing scheme, and the incorporation into a 3D Synthetic Vision System (SVS) display. The front end architecture consists of a w-band real-beam scanning radar that generates a high resolution real-time radar map and operates with an adaptable antenna architecture currently configured with an interferometric capability for target height estimation. The raw sensor data is further processed within an evidence grid-based integration functionality that results in high-resolution maps in the region surrounding the platform. Lastly, the accumulated radar results are displayed in a fully rendered 3D SVS environment integrated with local database information to provide the best representation of the surrounding environment. The integrated system concept will be discussed and initial results from an experimental flight test of this developmental system will be presented. Specifically, the forward-looking operation of the system demonstrates the system's ability to produce high precision terrain mapping with obstacle detection and avoidance capability, showcasing the system's versatility in a true operational environment.

Cobalt: Development and Maturation of GN&C Technologies for Precision Landing

NASA Technical Reports Server (NTRS)

Carson, John M.; Restrepo, Carolina; Seubert, Carl; Amzajerdian, Farzin

2016-01-01

The CoOperative Blending of Autonomous Landing Technologies (COBALT) instrument is a terrestrial test platform for development and maturation of guidance, navigation and control (GN&C) technologies for precision landing. The project is developing a third-generation Langley Research Center (LaRC) navigation doppler lidar (NDL) for ultra-precise velocity and range measurements, which will be integrated and tested with the Jet Propulsion Laboratory (JPL) lander vision system (LVS) for terrain relative navigation (TRN) position estimates. These technologies together provide precise navigation knowledge that is critical for a controlled and precise touchdown. The COBALT hardware will be integrated in 2017 into the GN&C subsystem of the Xodiac rocket-propulsive vertical test bed (VTB) developed by Masten Space Systems, and two terrestrial flight campaigns will be conducted: one open-loop (i.e., passive) and one closed-loop (i.e., active).

Ethical considerations of neuro-oncology trial design in the era of precision medicine.

PubMed

Gupta, Saksham; Smith, Timothy R; Broekman, Marike L

2017-08-01

The field of oncology is currently undergoing a paradigm shift. Advances in the understanding of tumor biology and in tumor sequencing technology have contributed to the shift towards precision medicine, the therapeutic framework of targeting the individual oncogenic changes each tumor harbors. The success of precision medicine therapies, such as targeted kinase inhibitors and immunotherapies, in other cancers have motivated studies in brain cancers. The high specificity and cost of these therapies also encourage a shift in clinical trial design away from randomized control trials towards smaller, more exclusive early phase clinical trials. While these new trials advance the clinical application of increasingly precise and individualized therapies, their design brings ethical challenges . We review the pertinent ethical considerations for clinical trials of precision medicine in neuro-oncology and discuss methods to protect patients in this new era of trial design.

Precision Oncology beyond Targeted Therapy: Combining Omics Data with Machine Learning Matches the Majority of Cancer Cells to Effective Therapeutics.

PubMed

Ding, Michael Q; Chen, Lujia; Cooper, Gregory F; Young, Jonathan D; Lu, Xinghua

2018-02-01

Precision oncology involves identifying drugs that will effectively treat a tumor and then prescribing an optimal clinical treatment regimen. However, most first-line chemotherapy drugs do not have biomarkers to guide their application. For molecularly targeted drugs, using the genomic status of a drug target as a therapeutic indicator has limitations. In this study, machine learning methods (e.g., deep learning) were used to identify informative features from genome-scale omics data and to train classifiers for predicting the effectiveness of drugs in cancer cell lines. The methodology introduced here can accurately predict the efficacy of drugs, regardless of whether they are molecularly targeted or nonspecific chemotherapy drugs. This approach, on a per-drug basis, can identify sensitive cancer cells with an average sensitivity of 0.82 and specificity of 0.82; on a per-cell line basis, it can identify effective drugs with an average sensitivity of 0.80 and specificity of 0.82. This report describes a data-driven precision medicine approach that is not only generalizable but also optimizes therapeutic efficacy. The framework detailed herein, when successfully translated to clinical environments, could significantly broaden the scope of precision oncology beyond targeted therapies, benefiting an expanded proportion of cancer patients. Mol Cancer Res; 16(2); 269-78. ©2017 AACR . ©2017 American Association for Cancer Research.

Long-term impact of precision agriculture on a farmer’s field

USDA-ARS?s Scientific Manuscript database

Targeting management practices and inputs with precision agriculture has high potential to meet some of the grand challenges of sustainability in the coming century. Although potential is high, few studies have documented long-term effects of precision agriculture on crop production and environmenta...

In-line metrology for roll-to-roll UV assisted nanoimprint lithography using diffractometry

NASA Astrophysics Data System (ADS)

Kreuzer, Martin; Whitworth, Guy L.; Francone, Achille; Gomis-Bresco, Jordi; Kehagias, Nikolaos; Sotomayor-Torres, Clivia M.

2018-05-01

We describe and discuss the optical design of a diffractometer to carry out in-line quality control during roll-to-roll nanoimprinting. The tool measures diffractograms in reflection geometry, through an aspheric lens to gain fast, non-invasive information of any changes to the critical dimensions of target grating structures. A stepwise tapered linear grating with constant period was fabricated in order to detect the variation in grating linewidth through diffractometry. The minimum feature change detected was ˜40 nm to a precision of 10 nm. The diffractometer was then integrated with a roll-to-roll UV assisted nanoimprint lithography machine to gain dynamic measurements in situ.

Dramatic Enhancement of Genome Editing by CRISPR/Cas9 Through Improved Guide RNA Design

PubMed Central

Farboud, Behnom; Meyer, Barbara J.

2015-01-01

Success with genome editing by the RNA-programmed nuclease Cas9 has been limited by the inability to predict effective guide RNAs and DNA target sites. Not all guide RNAs have been successful, and even those that were, varied widely in their efficacy. Here we describe and validate a strategy for Caenorhabditis elegans that reliably achieved a high frequency of genome editing for all targets tested in vivo. The key innovation was to design guide RNAs with a GG motif at the 3′ end of their target-specific sequences. All guides designed using this simple principle induced a high frequency of targeted mutagenesis via nonhomologous end joining (NHEJ) and a high frequency of precise DNA integration from exogenous DNA templates via homology-directed repair (HDR). Related guide RNAs having the GG motif shifted by only three nucleotides showed severely reduced or no genome editing. We also combined the 3′ GG guide improvement with a co-CRISPR/co-conversion approach. For this co-conversion scheme, animals were only screened for genome editing at designated targets if they exhibited a dominant phenotype caused by Cas9-dependent editing of an unrelated target. Combining the two strategies further enhanced the ease of mutant recovery, thereby providing a powerful means to obtain desired genetic changes in an otherwise unaltered genome. PMID:25695951

Translating genomic discoveries to the clinic in pediatric oncology.

PubMed

Glade Bender, Julia; Verma, Anupam; Schiffman, Joshua D

2015-02-01

The present study describes the recent advances in the identification of targetable genomic alterations in pediatric cancers, along with the progress and associated challenges in translating these findings into therapeutic benefit. Each field within pediatric cancer has rapidly and comprehensively begun to define genomic targets in tumors that potentially can improve the clinical outcome of patients, including hematologic malignancies (leukemia and lymphoma), solid malignancies (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), and brain tumors (gliomas, ependymomas, and medulloblastomas). Although each tumor has specific and sometimes overlapping genomic targets, the translation to the clinic of new targeted trials and precision medicine protocols is still in its infancy. The first clinical tumor profiling studies in pediatric oncology have demonstrated feasibility and patient enthusiasm for the personalized medicine paradigm, but have yet to demonstrate clinical utility. Complexities influencing implementation include rapidly evolving sequencing technologies, tumor heterogeneity, and lack of access to targeted therapies. The return of incidental findings from the germline also remains a challenge, with evolving policy statements and accepted standards. The translation of genomic discoveries to the clinic in pediatric oncology continues to move forward at a brisk pace. Early adoption of genomics for tumor classification, risk stratification, and initial trials of targeted therapeutic agents has led to powerful results. As our experience grows in the integration of genomic and clinical medicine, the outcome for children with cancer should continue to improve.

Infrared dim and small target detecting and tracking method inspired by Human Visual System

NASA Astrophysics Data System (ADS)

Dong, Xiabin; Huang, Xinsheng; Zheng, Yongbin; Shen, Lurong; Bai, Shengjian

2014-01-01

Detecting and tracking dim and small target in infrared images and videos is one of the most important techniques in many computer vision applications, such as video surveillance and infrared imaging precise guidance. Recently, more and more algorithms based on Human Visual System (HVS) have been proposed to detect and track the infrared dim and small target. In general, HVS concerns at least three mechanisms including contrast mechanism, visual attention and eye movement. However, most of the existing algorithms simulate only a single one of the HVS mechanisms, resulting in many drawbacks of these algorithms. A novel method which combines the three mechanisms of HVS is proposed in this paper. First, a group of Difference of Gaussians (DOG) filters which simulate the contrast mechanism are used to filter the input image. Second, a visual attention, which is simulated by a Gaussian window, is added at a point near the target in order to further enhance the dim small target. This point is named as the attention point. Eventually, the Proportional-Integral-Derivative (PID) algorithm is first introduced to predict the attention point of the next frame of an image which simulates the eye movement of human being. Experimental results of infrared images with different types of backgrounds demonstrate the high efficiency and accuracy of the proposed method to detect and track the dim and small targets.

Robotic Stereotaxy in Cranial Neurosurgery: A Qualitative Systematic Review.

PubMed

Fomenko, Anton; Serletis, Demitre

2017-12-14

Modern-day stereotactic techniques have evolved to tackle the neurosurgical challenge of accurately and reproducibly accessing specific brain targets. Neurosurgical advances have been made in synergy with sophisticated technological developments and engineering innovations such as automated robotic platforms. Robotic systems offer a unique combination of dexterity, durability, indefatigability, and precision. To perform a systematic review of robotic integration for cranial stereotactic guidance in neurosurgery. Specifically, we comprehensively analyze the strengths and weaknesses of a spectrum of robotic technologies, past and present, including details pertaining to each system's kinematic specifications and targeting accuracy profiles. Eligible articles on human clinical applications of cranial robotic-guided stereotactic systems between 1985 and 2017 were extracted from several electronic databases, with a focus on stereotactic biopsy procedures, stereoelectroencephalography, and deep brain stimulation electrode insertion. Cranial robotic stereotactic systems feature serial or parallel architectures with 4 to 7 degrees of freedom, and frame-based or frameless registration. Indications for robotic assistance are diversifying, and include stereotactic biopsy, deep brain stimulation and stereoelectroencephalography electrode placement, ventriculostomy, and ablation procedures. Complication rates are low, and mainly consist of hemorrhage. Newer systems benefit from increasing targeting accuracy, intraoperative imaging ability, improved safety profiles, and reduced operating times. We highlight emerging future directions pertaining to the integration of robotic technologies into future neurosurgical procedures. Notably, a trend toward miniaturization, cost-effectiveness, frameless registration, and increasing safety and accuracy characterize successful stereotactic robotic technologies. Copyright © 2017 by the Congress of Neurological Surgeons

A long arm for ultrasound: a combined robotic focused ultrasound setup for magnetic resonance-guided focused ultrasound surgery.

PubMed

Krafft, Axel J; Jenne, Jürgen W; Maier, Florian; Stafford, R Jason; Huber, Peter E; Semmler, Wolfhard; Bock, Michael

2010-05-01

Focused ultrasound surgery (FUS) is a highly precise noninvasive procedure to ablate pathogenic tissue. FUS therapy is often combined with magnetic resonance (MR) imaging as MR imaging offers excellent target identification and allows for continuous monitoring of FUS induced temperature changes. As the dimensions of the ultrasound (US) focus are typically much smaller than the targeted volume, multiple sonications and focus repositioning are interleaved to scan the focus over the target volume. Focal scanning can be achieved electronically by using phased-array US transducers or mechanically by using dedicated mechanical actuators. In this study, the authors propose and evaluate the precision of a combined robotic FUS setup to overcome some of the limitations of the existing MRgFUS systems. Such systems are typically integrated into the patient table of the MR scanner and thus only provide an application of the US wave within a limited spatial range from below the patient. The fully MR-compatible robotic assistance system InnoMotion (InnoMedic GmbH, Herxheim, Germany) was originally designed for MR-guided interventions with needles. It offers five pneumatically driven degrees of freedom and can be moved over a wide range within the bore of the magnet. In this work, the robotic system was combined with a fixed-focus US transducer (frequency: 1.7 MHz; focal length: 68 mm, and numerical aperture: 0.44) that was integrated into a dedicated, in-house developed treatment unit for FUS application. A series of MR-guided focal scanning procedures was performed in a polyacrylamide-egg white gel phantom to assess the positioning accuracy of the combined FUS setup. In animal experiments with a 3-month-old domestic pig, the system's potential and suitability for MRgFUS was tested. In phantom experiments, a total targeting precision of about 3 mm was found, which is comparable to that of the existing MRgFUS systems. Focus positioning could be performed within a few seconds. During in vivo experiments, a defined pattern of single thermal lesions and a therapeutically relevant confluent thermal lesion could be created. The creation of local tissue necrosis by coagulation was confirmed by post-FUS MR imaging and histological examinations on the treated tissue sample. During all sonications in phantom and in vivo, reliable MR imaging and online MR thermometry could be performed without compromises due to operation of the combined robotic FUS setup. Compared to the existing MRgFUS systems, the combined robotic FUS approach offers a wide range of spatial flexibility so that highly flexible application of the US wave would be possible, for example, to avoid risk structures within the US field. The setup might help to realize new ways of patient access in MRgFUS therapy. The setup is compatible with any closed-bore MR system and does not require an especially designed patient table.

Predicting drug-target interactions using restricted Boltzmann machines.

PubMed

Wang, Yuhao; Zeng, Jianyang

2013-07-01

In silico prediction of drug-target interactions plays an important role toward identifying and developing new uses of existing or abandoned drugs. Network-based approaches have recently become a popular tool for discovering new drug-target interactions (DTIs). Unfortunately, most of these network-based approaches can only predict binary interactions between drugs and targets, and information about different types of interactions has not been well exploited for DTI prediction in previous studies. On the other hand, incorporating additional information about drug-target relationships or drug modes of action can improve prediction of DTIs. Furthermore, the predicted types of DTIs can broaden our understanding about the molecular basis of drug action. We propose a first machine learning approach to integrate multiple types of DTIs and predict unknown drug-target relationships or drug modes of action. We cast the new DTI prediction problem into a two-layer graphical model, called restricted Boltzmann machine, and apply a practical learning algorithm to train our model and make predictions. Tests on two public databases show that our restricted Boltzmann machine model can effectively capture the latent features of a DTI network and achieve excellent performance on predicting different types of DTIs, with the area under precision-recall curve up to 89.6. In addition, we demonstrate that integrating multiple types of DTIs can significantly outperform other predictions either by simply mixing multiple types of interactions without distinction or using only a single interaction type. Further tests show that our approach can infer a high fraction of novel DTIs that has been validated by known experiments in the literature or other databases. These results indicate that our approach can have highly practical relevance to DTI prediction and drug repositioning, and hence advance the drug discovery process. Software and datasets are available on request. Supplementary data are available at Bioinformatics online.

Schema generation in recurrent neural nets for intercepting a moving target.

PubMed

Fleischer, Andreas G

2010-06-01

The grasping of a moving object requires the development of a motor strategy to anticipate the trajectory of the target and to compute an optimal course of interception. During the performance of perception-action cycles, a preprogrammed prototypical movement trajectory, a motor schema, may highly reduce the control load. Subjects were asked to hit a target that was moving along a circular path by means of a cursor. Randomized initial target positions and velocities were detected in the periphery of the eyes, resulting in a saccade toward the target. Even when the target disappeared, the eyes followed the target's anticipated course. The Gestalt of the trajectories was dependent on target velocity. The prediction capability of the motor schema was investigated by varying the visibility range of cursor and target. Motor schemata were determined to be of limited precision, and therefore visual feedback was continuously required to intercept the moving target. To intercept a target, the motor schema caused the hand to aim ahead and to adapt to the target trajectory. The control of cursor velocity determined the point of interception. From a modeling point of view, a neural network was developed that allowed the implementation of a motor schema interacting with feedback control in an iterative manner. The neural net of the Wilson type consists of an excitation-diffusion layer allowing the generation of a moving bubble. This activation bubble runs down an eye-centered motor schema and causes a planar arm model to move toward the target. A bubble provides local integration and straightening of the trajectory during repetitive moves. The schema adapts to task demands by learning and serves as forward controller. On the basis of these model considerations the principal problem of embedding motor schemata in generalized control strategies is discussed.

Targeted Prostate Thermal Therapy with Catheter-Based Ultrasound Devices and MR Thermal Monitoring

NASA Astrophysics Data System (ADS)

Diederich, Chris; Ross, Anthony; Kinsey, Adam; Nau, Will H.; Rieke, Viola; Butts Pauly, Kim; Sommer, Graham

2006-05-01

Catheter-based ultrasound devices have significant advantages for thermal therapy procedures, including potential for precise spatial and dynamic control of heating patterns to conform to targeted volumes. Interstitial and transurethral ultrasound applicators, with associated treatment strategies, were developed for thermal ablation of prostate combined with MR thermal monitoring. Four types of multielement transurethral applicators were devised, each with different levels of selectivity and intended therapeutic goals: sectored tubular transducer devices with fixed directional heating patterns; planar and lightly focused curvilinear devices with narrow heating patterns; and multi-sectored tubular devices capable of dynamic angular control without applicator movement. These devices are integrated with a 4 mm delivery catheter, incorporate an inflatable cooling balloon (10 mm OD) for positioning within the prostate and capable of rotation via an MR-compatible motor. Similarly, interstitial devices (2.4 mm OD) have been developed for percutaneous implantation with fixed directional heating patterns (e.g., 180 deg.). In vivo experiments in canine prostate (n=15) under MR temperature imaging were used to evaluate the heating technology and develop treatment strategies. MR thermal imaging in a 0.5 T interventional MRI was used to monitor temperature contours and thermal dose in multiple slices through the target volume. Sectored transurethral devices produce directional coagulation zones, extending 15-20 mm radial distance to the outer prostate capsule. The curvilinear applicator produces distinct 2-3 mm wide lesions, and with sequential rotation and modulated dwell time can precisely conform thermal ablation to selected areas or the entire prostate gland. Multi-sectored transurethral applicators can dynamically control the angular heating profile and target large regions of the gland in short treatment times without applicator manipulation. Interstitial implants with directional devices can be used to effectively ablate the posterior peripheral zone of the gland while protecting the rectum. An implant with multi-sectored interstitial devices can effectively control the angular heating pattern without applicator rotation. The MR derived 52 °C and lethal thermal dose contours (t43=240 min) allowed for real-time control of the applicators and effectively defined the extent of thermal damage. Catheter-based ultrasound devices, combined with MR thermal monitoring, can produce relatively fast and precise thermal ablation of prostate, with potential for treatment of cancer or BPH.

Precise Determination of the Baseline Between the TerraSAR-X and TanDEM-X Satellites

NASA Astrophysics Data System (ADS)

Koenig, Rolf; Rothacher, Markus; Michalak, Grzegorz; Moon, Yongjin

TerraSAR-X, launched on June 15, 2007, and TanDEM-X, to be launched in September 2009, both carry the Tracking, Occultation and Ranging (TOR) category A payload instrument package. The TOR consists of a high-precision dual-frequency GPS receiver, called Integrated GPS Occultation Receiver (IGOR), for precise orbit determination and atmospheric sounding and a Laser retro-reflector (LRR) serving as target for the global Satellite Laser Ranging (SLR) ground station network. The TOR is supplied by the GeoForschungsZentrum Potsdam (GFZ) Germany, and the Center for Space Research (CSR), Austin, Texas. The objective of the German/US collaboration is twofold: provision of atmospheric profiles for use in numerical weather predictions and climate studies from the occultation data and precision SAR data processing based on precise orbits and atmospheric products. For the scientific objectives of the TanDEM- X mission, i.e., bi-static SAR together with TerraSAR-X, the dual-frequency GPS receiver is of vital importance for the millimeter level determination of the baseline or distance between the two spacecrafts. The paper discusses the feasibility of generating millimeter baselines by the example of GRACE, where for validation the distance between the two GRACE satellites is directly available from the micrometer-level intersatellite link measurements. The distance of the GRACE satellites is some 200 km, the distance of the TerraSAR-X/TanDEM-X formation will be some 200 meters. Therefore the proposed approach is then subject to a simulation of the foreseen TerraSAR-X/TanDEM-X formation. The effect of varying space environmental conditions, of possible phase center variations, multi path, and of varying center of mass of the spacecrafts are evaluated and discussed.

Precision Learning Assessment: An Alternative to Traditional Assessment Techniques.

ERIC Educational Resources Information Center

Caltagirone, Paul J.; Glover, Christopher E.

1985-01-01

A continuous and curriculum-based assessment method, Precision Learning Assessment (PLA), which integrates precision teaching and norm-referenced techniques, was applied to a math computation curriculum for 214 third graders. The resulting districtwide learning curves defining average annual progress through the computation curriculum provided…

Precision Medicine in Myelodysplastic Syndromes and Leukemias: Lessons from Sequential Mutations.

PubMed

Nazha, Aziz; Sekeres, Mikkael A

2017-01-14

Precision medicine can be simply defined as the identification of personalized treatment that matches patient-specific clinical and genomic characteristics. Since the completion of the Human Genome Project in 2003, significant advances have been made in our understanding of the genetic makeup of diseases, especially cancers. The identification of somatic mutations that can drive cancer has led to the development of therapies that specifically target the abnormal proteins derived from these mutations. This has led to a paradigm shift in our treatment methodology. Although some success has been achieved in targeting some genetic abnormalities, several challenges and limitations exist when applying precision-medicine concepts in leukemia and myelodysplastic syndromes. We review the current understanding of genomics in myelodysplastic syndromes (MDS) and leukemias and the limitations of precision-medicine concepts in MDS.

Flight Testing ALHAT Precision Landing Technologies Integrated Onboard the Morpheus Rocket Vehicle

NASA Technical Reports Server (NTRS)

Carson, John M. III; Robertson, Edward A.; Trawny, Nikolas; Amzajerdian, Farzin

2015-01-01

A suite of prototype sensors, software, and avionics developed within the NASA Autonomous precision Landing and Hazard Avoidance Technology (ALHAT) project were terrestrially demonstrated onboard the NASA Morpheus rocket-propelled Vertical Testbed (VTB) in 2014. The sensors included a LIDAR-based Hazard Detection System (HDS), a Navigation Doppler LIDAR (NDL) velocimeter, and a long-range Laser Altimeter (LAlt) that enable autonomous and safe precision landing of robotic or human vehicles on solid solar system bodies under varying terrain lighting conditions. The flight test campaign with the Morpheus vehicle involved a detailed integration and functional verification process, followed by tether testing and six successful free flights, including one night flight. The ALHAT sensor measurements were integrated into a common navigation solution through a specialized ALHAT Navigation filter that was employed in closed-loop flight testing within the Morpheus Guidance, Navigation and Control (GN&C) subsystem. Flight testing on Morpheus utilized ALHAT for safe landing site identification and ranking, followed by precise surface-relative navigation to the selected landing site. The successful autonomous, closed-loop flight demonstrations of the prototype ALHAT system have laid the foundation for the infusion of safe, precision landing capabilities into future planetary exploration missions.

Developmental differences in masked form priming are not driven by vocabulary growth.

PubMed

Bhide, Adeetee; Schlaggar, Bradley L; Barnes, Kelly Anne

2014-01-01

As children develop into skilled readers, they are able to more quickly and accurately distinguish between words with similar visual forms (i.e., they develop precise lexical representations). The masked form priming lexical decision task is used to test the precision of lexical representations. In this paradigm, a prime (which differs by one letter from the target) is briefly flashed before the target is presented. Participants make a lexical decision to the target. Primes can facilitate reaction time by partially activating the lexical entry for the target. If a prime is unable to facilitate reaction time, it is assumed that participants have a precise orthographic representation of the target and thus the prime is not a close enough match to activate its lexical entry. Previous developmental work has shown that children and adults' lexical decision times are facilitated by form primes preceding words from small neighborhoods (i.e., very few words can be formed by changing one letter in the original word; low N words), but only children are facilitated by form primes preceding words from large neighborhoods (high N words). It has been hypothesized that written vocabulary growth drives the increase in the precision of the orthographic representations; children may not know all of the neighbors of the high N words, making the words effectively low N for them. We tested this hypothesis by (1) equating the effective orthographic neighborhood size of the targets for children and adults and (2) testing whether age or vocabulary size was a better predictor of the extent of form priming. We found priming differences even when controlling for effective neighborhood size. Furthermore, age was a better predictor of form priming effects than was vocabulary size. Our findings provide no support for the hypothesis that growth in written vocabulary size gives rise to more precise lexical representations. We propose that the development of spelling ability may be a more important factor.

Development of an Integrated Thermocouple for the Accurate Sample Temperature Measurement During High Temperature Environmental Scanning Electron Microscopy (HT-ESEM) Experiments.

PubMed

Podor, Renaud; Pailhon, Damien; Ravaux, Johann; Brau, Henri-Pierre

2015-04-01

We have developed two integrated thermocouple (TC) crucible systems that allow precise measurement of sample temperature when using a furnace associated with an environmental scanning electron microscope (ESEM). Sample temperatures measured with these systems are precise (±5°C) and reliable. The TC crucible systems allow working with solids and liquids (silicate melts or ionic liquids), independent of the gas composition and pressure. These sample holder designs will allow end users to perform experiments at high temperature in the ESEM chamber with high precision control of the sample temperature.

Blind predictions of protein interfaces by docking calculations in CAPRI.

PubMed

Lensink, Marc F; Wodak, Shoshana J

2010-11-15

Reliable prediction of the amino acid residues involved in protein-protein interfaces can provide valuable insight into protein function, and inform mutagenesis studies, and drug design applications. A fast-growing number of methods are being proposed for predicting protein interfaces, using structural information, energetic criteria, or sequence conservation or by integrating multiple criteria and approaches. Overall however, their performance remains limited, especially when applied to nonobligate protein complexes, where the individual components are also stable on their own. Here, we evaluate interface predictions derived from protein-protein docking calculations. To this end we measure the overlap between the interfaces in models of protein complexes submitted by 76 participants in CAPRI (Critical Assessment of Predicted Interactions) and those of 46 observed interfaces in 20 CAPRI targets corresponding to nonobligate complexes. Our evaluation considers multiple models for each target interface, submitted by different participants, using a variety of docking methods. Although this results in a substantial variability in the prediction performance across participants and targets, clear trends emerge. Docking methods that perform best in our evaluation predict interfaces with average recall and precision levels of about 60%, for a small majority (60%) of the analyzed interfaces. These levels are significantly higher than those obtained for nonobligate complexes by most extant interface prediction methods. We find furthermore that a sizable fraction (24%) of the interfaces in models ranked as incorrect in the CAPRI assessment are actually correctly predicted (recall and precision ≥50%), and that these models contribute to 70% of the correct docking-based interface predictions overall. Our analysis proves that docking methods are much more successful in identifying interfaces than in predicting complexes, and suggests that these methods have an excellent potential of addressing the interface prediction challenge. © 2010 Wiley-Liss, Inc.

Pathogenesis and treatment of psoriasis: exploiting pathophysiological pathways for precision medicine.

PubMed

Alwan, Wisam; Nestle, Frank O

2015-01-01

Psoriasis is a common, chronic inflammatory skin disease associated with multi-system manifestations including arthritis and obesity. Our knowledge of the aetiology of the condition, including the key genomic, immune and environmental factors, has led to the development of targeted, precision therapies that alleviate patient morbidity. This article reviews the key pathophysiological pathways and therapeutic targets and highlights future areas of interest in psoriasis research.

Eye movements and manual interception of ballistic trajectories: effects of law of motion perturbations and occlusions.

PubMed

Delle Monache, Sergio; Lacquaniti, Francesco; Bosco, Gianfranco

2015-02-01

Manual interceptions are known to depend critically on integration of visual feedback information and experience-based predictions of the interceptive event. Within this framework, coupling between gaze and limb movements might also contribute to the interceptive outcome, since eye movements afford acquisition of high-resolution visual information. We investigated this issue by analyzing subjects' head-fixed oculomotor behavior during manual interceptions. Subjects moved a mouse cursor to intercept computer-generated ballistic trajectories either congruent with Earth's gravity or perturbed with weightlessness (0 g) or hypergravity (2 g) effects. In separate sessions, trajectories were either fully visible or occluded before interception to enforce visual prediction. Subjects' oculomotor behavior was classified in terms of amounts of time they gazed at different visual targets and of overall number of saccades. Then, by way of multivariate analyses, we assessed the following: (1) whether eye movement patterns depended on targets' laws of motion and occlusions; and (2) whether interceptive performance was related to the oculomotor behavior. First, we found that eye movement patterns depended significantly on targets' laws of motion and occlusion, suggesting predictive mechanisms. Second, subjects coupled differently oculomotor and interceptive behavior depending on whether targets were visible or occluded. With visible targets, subjects made smaller interceptive errors if they gazed longer at the mouse cursor. Instead, with occluded targets, they achieved better performance by increasing the target's tracking accuracy and by avoiding gaze shifts near interception, suggesting that precise ocular tracking provided better trajectory predictions for the interceptive response.

Validation of Laser-Induced Fluorescent Photogrammetric Targets on Membrane Structures

NASA Technical Reports Server (NTRS)

Jones, Thomas W.; Dorrington, Adrian A.; Shortis, Mark R.; Hendricks, Aron R.

2004-01-01

The need for static and dynamic characterization of a new generation of inflatable space structures requires the advancement of classical metrology techniques. A new photogrammetric-based method for non-contact ranging and surface profiling has been developed at NASA Langley Research Center (LaRC) to support modal analyses and structural validation of this class of space structures. This full field measurement method, known as Laser-Induced Fluorescence (LIF) photogrammetry, has previously yielded promising experimental results. However, data indicating the achievable measurement precision had not been published. This paper provides experimental results that indicate the LIF-photogrammetry measurement precision for three different target types used on a reflective membrane structure. The target types were: (1) non-contact targets generated using LIF, (2) surface attached retro-reflective targets, and (3) surface attached diffuse targets. Results from both static and dynamic investigations are included.

Evaluation of SMART sensor displays for multidimensional precision control of Space Shuttle remote manipulator

NASA Technical Reports Server (NTRS)

Bejczy, A. K.; Brown, J. W.; Lewis, J. L.

1982-01-01

An enhanced proximity sensor and display system was developed at the Jet Propulsion Laboratory (JPL) and tested on the full scale Space Shuttle Remote Manipulator at the Johnson Space Center (JSC) Manipulator Development Facility (MDF). The sensor system, integrated with a four-claw end effector, measures range error up to 6 inches, and pitch and yaw alignment errors within + or 15 deg., and displays error data on both graphic and numeric displays. The errors are referenced to the end effector control axes through appropriate data processing by a dedicated microcomputer acting on the sensor data in real time. Both display boxes contain a green lamp which indicates whether the combination of range, pitch and yaw errors will assure a successful grapple. More than 200 test runs were completed in early 1980 by three operators at JSC for grasping static and capturing slowly moving targets. The tests have indicated that the use of graphic/numeric displays of proximity sensor information improves precision control of grasp/capture range by more than a factor of two for both static and dynamic grapple conditions.

[Precise management of extraordinary agent wound by establishment of a multidisciplinary cooperation mechanism].

PubMed

Liu, Yi

2016-06-01

With the development of social economy, people's lifestyle has changed accompanied with the problem of population aging. The spectrum of disease also varied accordingly, thus led to complicated and varied wound aetiology, along with the formation of innumerably changed acute and chronic wounds. Therefore, it is hard to meet the requirement of multidisciplinary knowledge and technique in the diagnosis and treatment of some extraordinary agent wound with a single discipline. The extraordinary agent wound is caused by some uncommon or rare etiological factors, the specialty of which lays on the unique mechanism of wound formation, and a lot of disciplines were involved in the diagnosis and management of the wound. A unification of multiple disciplines is needed to integrate the relevant theory and technique to care the wound by giving consideration of the symptom and the aetiology. The primary diseases which induced the uncommon agent wound should be targeted and treated effectively; meanwhile, a comprehensive treatment combined with multiple new wound management techniques should be carried out to realize the objective of precise treatment.

Over forty years of bladder cancer glycobiology: Where do glycans stand facing precision oncology?

PubMed Central

Azevedo, Rita; Peixoto, Andreia; Gaiteiro, Cristiana; Fernandes, Elisabete; Neves, Manuel; Lima, Luís; Santos, Lúcio Lara; Ferreira, José Alexandre

2017-01-01

The high molecular heterogeneity of bladder tumours is responsible for significant variations in disease course, as well as elevated recurrence and progression rates, thereby hampering the introduction of more effective targeted therapeutics. The implementation of precision oncology settings supported by robust molecular models for individualization of patient management is warranted. This effort requires a comprehensive integration of large sets of panomics data that is yet to be fully achieved. Contributing to this goal, over 40 years of bladder cancer glycobiology have disclosed a plethora of cancer-specific glycans and glycoconjugates (glycoproteins, glycolipids, proteoglycans) accompanying disease progressions and dissemination. This review comprehensively addresses the main structural findings in the field and consequent biological and clinical implications. Given the cell surface and secreted nature of these molecules, we further discuss their potential for non-invasive detection and therapeutic development. Moreover, we highlight novel mass-spectrometry-based high-throughput analytical and bioinformatics tools to interrogate the glycome in the postgenomic era. Ultimately, we outline a roadmap to guide future developments in glycomics envisaging clinical implementation. PMID:29207682

Neural prostheses in clinical applications--trends from precision mechanics towards biomedical microsystems in neurological rehabilitation.

PubMed

Stieglitz, T; Schuettler, M; Koch, K P

2004-04-01

Neural prostheses partially restore body functions by technical nerve excitation after trauma or neurological diseases. External devices and implants have been developed since the early 1960s for many applications. Several systems have reached nowadays clinical practice: Cochlea implants help the deaf to hear, micturition is induced by bladder stimulators in paralyzed persons and deep brain stimulation helps patients with Parkinson's disease to participate in daily life again. So far, clinical neural prostheses are fabricated with means of precision mechanics. Since microsystem technology opens the opportunity to design and develop complex systems with a high number of electrodes to interface with the nervous systems, the opportunity for selective stimulation and complex implant scenarios seems to be feasible in the near future. The potentials and limitations with regard to biomedical microdevices are introduced and discussed in this paper. Target specifications are derived from existing implants and are discussed on selected applications that has been investigated in experimental research: a micromachined implant to interface a nerve stump with a sieve electrode, cuff electrodes with integrated electronics, and an epiretinal vision prosthesis.

MMEJ-assisted gene knock-in using TALENs and CRISPR-Cas9 with the PITCh systems.

PubMed

Sakuma, Tetsushi; Nakade, Shota; Sakane, Yuto; Suzuki, Ken-Ichi T; Yamamoto, Takashi

2016-01-01

Programmable nucleases enable engineering of the genome by utilizing endogenous DNA double-strand break (DSB) repair pathways. Although homologous recombination (HR)-mediated gene knock-in is well established, it cannot necessarily be applied in every cell type and organism because of variable HR frequencies. We recently reported an alternative method of gene knock-in, named the PITCh (Precise Integration into Target Chromosome) system, assisted by microhomology-mediated end-joining (MMEJ). MMEJ harnesses independent machinery from HR, and it requires an extremely short homologous sequence (5-25 bp) for DSB repair, resulting in precise gene knock-in with a more easily constructed donor vector. Here we describe a streamlined protocol for PITCh knock-in, including the design and construction of the PITCh vectors, and their delivery to either human cell lines by transfection or to frog embryos by microinjection. The construction of the PITCh vectors requires only a few days, and the entire process takes ∼ 1.5 months to establish knocked-in cells or ∼ 1 week from injection to early genotyping in frog embryos.

Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange

PubMed Central

Hmelo, Laura R.; Borlee, Bradley R.; Almblad, Henrik; Love, Michelle E.; Randall, Trevor E.; Tseng, Boo Shan; Lin, Chuyang; Irie, Yasuhiko; Storek, Kelly M.; Yang, Jaeun Jane; Siehnel, Richard J.; Howell, P. Lynne; Singh, Pradeep K.; Tolker-Nielsen, Tim; Parsek, Matthew R.; Schweizer, Herbert P.; Harrison, Joe J.

2016-01-01

Allelic exchange is an efficient method of bacterial genome engineering. This protocol describes the use of this technique to make gene knockouts and knockins, as well as single nucleotide insertions, deletions and substitutions in Pseudomonas aeruginosa. Unlike other approaches to allelic exchange, this protocol does not require heterologous recombinases to insert or excise selective markers from the target chromosome. Rather, positive and negative selection are enabled solely by suicide vector-encoded functions and host cell proteins. Here, mutant alleles, which are flanked by regions of homology to the recipient chromosome, are synthesized in vitro and then cloned into allelic exchange vectors using standard procedures. These suicide vectors are then introduced into recipient cells by conjugation. Homologous recombination then results in antibiotic resistant single-crossover mutants in which the plasmid has integrated site-specifically into the chromosome. Subsequently, unmarked double-crossover mutants are isolated directly using sucrose-mediated counter-selection. This two-step process yields seamless mutations that are precise to a single base pair of DNA. The entire procedure requires ~2 weeks. PMID:26492139

Improving OCD time to solution using Signal Response Metrology

NASA Astrophysics Data System (ADS)

Fang, Fang; Zhang, Xiaoxiao; Vaid, Alok; Pandev, Stilian; Sanko, Dimitry; Ramanathan, Vidya; Venkataraman, Kartik; Haupt, Ronny

2016-03-01

In recent technology nodes, advanced process and novel integration scheme have challenged the precision limits of conventional metrology; with critical dimensions (CD) of device reduce to sub-nanometer region. Optical metrology has proved its capability to precisely detect intricate details on the complex structures, however, conventional RCWA-based (rigorous coupled wave analysis) scatterometry has the limitations of long time-to-results and lack of flexibility to adapt to wide process variations. Signal Response Metrology (SRM) is a new metrology technique targeted to alleviate the consumption of engineering and computation resources by eliminating geometric/dispersion modeling and spectral simulation from the workflow. This is achieved by directly correlating the spectra acquired from a set of wafers with known process variations encoded. In SPIE 2015, we presented the results of SRM application in lithography metrology and control [1], accomplished the mission of setting up a new measurement recipe of focus/dose monitoring in hours. This work will demonstrate our recent field exploration of SRM implementation in 20nm technology and beyond, including focus metrology for scanner control; post etch geometric profile measurement, and actual device profile metrology.

A novel molecular diagnostics platform for somatic and germline precision oncology.

PubMed

Cabanillas, Rubén; Diñeiro, Marta; Castillo, David; Pruneda, Patricia C; Penas, Cristina; Cifuentes, Guadalupe A; de Vicente, Álvaro; Durán, Noelia S; Álvarez, Rebeca; Ordóñez, Gonzalo R; Cadiñanos, Juan

2017-07-01

Next-generation sequencing (NGS) opens new options in clinical oncology, from therapy selection to genetic counseling. However, realization of this potential not only requires succeeding in the bioinformatics and interpretation of the results, but also in their integration into the clinical practice. We have developed a novel NGS diagnostic platform aimed at detecting (1) somatic genomic alterations associated with the response to approved targeted cancer therapies and (2) germline mutations predisposing to hereditary malignancies. Next-generation sequencing libraries enriched in the exons of 215 cancer genes (97 for therapy selection and 148 for predisposition, with 30 informative for both applications), as well as selected introns from 17 genes involved in drug-related rearrangements, were prepared from 39 tumors (paraffin-embedded tissues/cytologies), 36 germline samples (blood) and 10 cell lines using hybrid capture. Analysis of NGS results was performed with specifically developed bioinformatics pipelines. The platform detects single-nucleotide variants (SNVs) and insertions/deletions (indels) with sensitivity and specificity >99.5% (allelic frequency ≥0.1), as well as copy-number variants (CNVs) and rearrangements. Somatic testing identified tailored approved targeted drugs in 35/39 tumors (89.74%), showing a diagnostic yield comparable to that of leading commercial platforms. A somatic EGFR p.E746_S752delinsA mutation in a mediastinal metastasis from a breast cancer prompted its anatomopathologic reassessment, its definite reclassification as a lung cancer and its treatment with gefitinib (partial response sustained for 15 months). Testing of 36 germline samples identified two pathogenic mutations (in CDKN2A and BRCA2 ). We propose a strategy for interpretation and reporting of results adaptable to the aim of the request, the availability of tumor and/or normal samples and the scope of the informed consent. With an adequate methodology, it is possible to translate to the clinical practice the latest advances in precision oncology, integrating under the same platform the identification of somatic and germline genomic alterations.

Gold deposits in metamorphic belts: Overview of current understanding, outstanding problems, future research, and exploration significance

USGS Publications Warehouse

Groves, D.I.; Goldfarb, R.J.; Robert, F.; Hart, C.J.R.

2003-01-01

Metamorphic belts are complex regions where accretion or collision has added to, or thickened, continental crust. Gold-rich deposits can be formed at all stages of orogen evolution, so that evolving metamorphic belts contain diverse gold deposit types that may be juxtaposed or overprint each other. This partly explains the high level of controversy on the origin of some deposit types, particularly those formed or overprinted/remobilized during the major compressional orogeny that shaped the final geometry of the hosting metamorphic belts. These include gold-dominated orogenic and intrusion-related deposits, but also particularly controversial gold deposits with atypical metal associations. There are a number of outstanding problems for all types of gold deposits in metamorphc belts. These include the following: (1) definitive classifications, (2) unequivocal recognition of fluid and metal sources, (3) understanding of fluid migration and focusing at all scales, (4) resolution of the precise role of granitoid magmatism, (5) precise gold-depositional mechanisms, particularly those producing high gold grades, and (6) understanding of the release of CO2-rich fluids from subducting slabs and subcreted oceanic crust and granitoid magmas at different crustal levels. Research needs to be better coordinated and more integrated, such that detailed fluid-inclusion, trace-element, and isotopic studies of both gold deposits and potential source rocks, using cutting-edge technology, are embedded in a firm geological framework at terrane to deposit scales. Ultimately, four-dimensional models need to be developed, involving high-quality, three-dimensional geological data combined with integrated chemical and fluid-flow modeling, to understand the total history of the hydrothermal systems involved. Such research, particularly that which can predict superior targets visible in data sets available to exploration companies before discovery, has obvious spin-offs for global- to deposit-scale targeting of deposits with superior size and grade in the covered terranes that will be the exploration focus of the twenty-first century.

Solving Ordinary Differential Equations

NASA Technical Reports Server (NTRS)

Krogh, F. T.

1987-01-01

Initial-value ordinary differential equation solution via variable order Adams method (SIVA/DIVA) package is collection of subroutines for solution of nonstiff ordinary differential equations. There are versions for single-precision and double-precision arithmetic. Requires fewer evaluations of derivatives than other variable-order Adams predictor/ corrector methods. Option for direct integration of second-order equations makes integration of trajectory problems significantly more efficient. Written in FORTRAN 77.

AACR precision medicine series: Highlights of the integrating clinical genomics and cancer therapy meeting.

PubMed

Maggi, Elaine; Montagna, Cristina

2015-12-01

The American Association for Cancer Research (AACR) Precision Medicine Series "Integrating Clinical Genomics and Cancer Therapy" took place June 13-16, 2015 in Salt Lake City, Utah. The conference was co-chaired by Charles L. Sawyers form Memorial Sloan Kettering Cancer Center in New York, Elaine R. Mardis form Washington University School of Medicine in St. Louis, and Arul M. Chinnaiyan from University of Michigan in Ann Arbor. About 500 clinicians, basic science investigators, bioinformaticians, and postdoctoral fellows joined together to discuss the current state of Clinical Genomics and the advances and challenges of integrating Next Generation Sequencing (NGS) technologies into clinical practice. The plenary sessions and panel discussions covered current platforms and sequencing approaches adopted for NGS assays of cancer genome at several national and international institutions, different approaches used to map and classify targetable sequence variants, and how information acquired with the sequencing of the cancer genome is used to guide treatment options. While challenges still exist from a technological perspective, it emerged that there exists considerable need for the development of tools to aid the identification of the therapy most suitable based on the mutational profile of the somatic cancer genome. The process to match patients to ongoing clinical trials is still complex. In addition, the need for centralized data repositories, preferably linked to well annotated clinical records, that aid sharing of sequencing information is central to begin understanding the contribution of variants of unknown significance to tumor etiology and response to therapy. Here we summarize the highlights of this stimulating four-day conference with a major emphasis on the open problems that the clinical genomics community is currently facing and the tools most needed for advancing this field. Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Precision Modeling Of Targets Using The VALUE Computer Program

NASA Astrophysics Data System (ADS)

Hoffman, George A.; Patton, Ronald; Akerman, Alexander

1989-08-01

The 1976-vintage LASERX computer code has been augmented to produce realistic electro-optical images of targets. Capabilities lacking in LASERX but recently incorporated into its VALUE successor include: •Shadows cast onto the ground •Shadows cast onto parts of the target •See-through transparencies (e.g.,canopies) •Apparent images due both to atmospheric scattering and turbulence •Surfaces characterized by multiple bi-directional reflectance functions VALUE provides not only realistic target modeling by its precise and comprehensive representation of all target attributes, but additionally VALUE is very user friendly. Specifically, setup of runs is accomplished by screen prompting menus in a sequence of queries that is logical to the user. VALUE also incorporates the Optical Encounter (OPEC) software developed by Tricor Systems,Inc., Elgin, IL.

Tailored semiconductors for high-harmonic optoelectronics.

PubMed

Sivis, Murat; Taucer, Marco; Vampa, Giulio; Johnston, Kyle; Staudte, André; Naumov, Andrei Yu; Villeneuve, D M; Ropers, Claus; Corkum, P B

2017-07-21

The advent of high-harmonic generation in gases 30 years ago set the foundation for attosecond science and facilitated ultrafast spectroscopy in atoms, molecules, and solids. We explore high-harmonic generation in the solid state by means of nanostructured and ion-implanted semiconductors. We use wavelength-selective microscopic imaging to map enhanced harmonic emission and show that the generation medium and the driving field can be locally tailored in solids by modifying the chemical composition and morphology. This enables the control of high-harmonic technology within precisely engineered solid targets. We demonstrate customized high-harmonic wave fields with wavelengths down to 225 nanometers (ninth-harmonic order of 2-micrometer laser pulses) and present an integrated Fresnel zone plate target in silicon, which leads to diffraction-limited self-focusing of the generated harmonics down to 1-micrometer spot sizes. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

A novel mitochondria-targeted two-photon fluorescent probe for dynamic and reversible detection of the redox cycles between peroxynitrite and glutathione.

PubMed

Sun, Chunlong; Du, Wen; Wang, Peng; Wu, Yang; Wang, Baoqin; Wang, Jun; Xie, Wenjun

2017-12-16

Redox homeostasis is important for maintenance of normal physiological functions within cells. Redox state of cells is primarily a consequence of precise balance between levels of reducing equivalents and reactive oxygen species. Redox homeostasis between peroxynitrite (ONOO - ) and glutathione (GSH) is closely associated with physiological and pathological processes, such as prolonged relaxation in vascular tissues and smooth muscle preparations, attenuation of hepatic necrosis, and activation of matrix metalloproteinase-2. We report a two-photon fluorescent probe (TP-Se) based on water-soluble carbazole-based compound, which integrates with organic selenium, to monitor changes in ONOO - /GSH levels in cells. This probe can reversibly respond to ONOO - and GSH and exhibits high selectivity, sensitivity, and mitochondrial targeting. The probe was successfully applied to visualize changes in redox cycles during ONOO - outbreak and antioxidant GSH repair in cells. The probe will lead to significant development on redox events involved in cellular redox regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

A transcription factor network coordinates attraction, repulsion, and adhesion combinatorially to control motor axon pathway selection.

PubMed

Zarin, Aref Arzan; Asadzadeh, Jamshid; Hokamp, Karsten; McCartney, Daniel; Yang, Long; Bashaw, Greg J; Labrador, Juan-Pablo

2014-03-19

Combinations of transcription factors (TFs) instruct precise wiring patterns in the developing nervous system; however, how these factors impinge on surface molecules that control guidance decisions is poorly understood. Using mRNA profiling, we identified the complement of membrane molecules regulated by the homeobox TF Even-skipped (Eve), the major determinant of dorsal motor neuron (dMN) identity in Drosophila. Combinatorial loss- and gain-of-function genetic analyses of Eve target genes indicate that the integrated actions of attractive, repulsive, and adhesive molecules direct eve-dependent dMN axon guidance. Furthermore, combined misexpression of Eve target genes is sufficient to partially restore CNS exit and can convert the guidance behavior of interneurons to that of dMNs. Finally, we show that a network of TFs, comprised of eve, zfh1, and grain, induces the expression of the Unc5 and Beaten-path guidance receptors and the Fasciclin 2 and Neuroglian adhesion molecules to guide individual dMN axons. Copyright © 2014 Elsevier Inc. All rights reserved.

A Transcription Factor Network Coordinates Attraction, Repulsion, and Adhesion Combinatorially to Control Motor Axon Pathway Selection

PubMed Central

Zarin, Aref Arzan; Asadzadeh, Jamshid; Hokamp, Karsten; McCartney, Daniel; Yang, Long; Bashaw, Greg J.; Labrador, Juan-Pablo

2014-01-01

SUMMARY Combinations of transcription factors (TFs) instruct precise wiring patterns in the developing nervous system; however, how these factors impinge on surface molecules that control guidance decisions is poorly understood. Using mRNA profiling, we identified the complement of membrane molecules regulated by the homeobox TF Even-skipped (Eve), the major determinant of dorsal motor neuron (dMN) identity in Drosophila. Combinatorial loss- and gain-of-function genetic analyses of Eve target genes indicate that the integrated actions of attractive, repulsive, and adhesive molecules direct eve-dependent dMN axon guidance. Furthermore, combined misexpression of Eve target genes is sufficient to partially restore CNS exit and can convert the guidance behavior of interneurons to that of dMNs. Finally, we show that a network of TFs, comprised of eve, zfh1, and grain, induces the expression of the Unc5 and Beaten-path guidance receptors and the Fasciclin 2 and Neuroglian adhesion molecules to guide individual dMN axons. PMID:24560702

Emerging Roles for the Lysosome in Lipid Metabolism.

PubMed

Thelen, Ashley M; Zoncu, Roberto

2017-11-01

Precise regulation of lipid biosynthesis, transport, and storage is key to the homeostasis of cells and organisms. Cells rely on a sophisticated but poorly understood network of vesicular and nonvesicular transport mechanisms to ensure efficient delivery of lipids to target organelles. The lysosome stands at the crossroads of this network due to its ability to process and sort exogenous and endogenous lipids. The lipid-sorting function of the lysosome is intimately connected to its recently discovered role as a metabolic command-and-control center, which relays multiple nutrient cues to the master growth regulator, mechanistic target of rapamycin complex (mTORC)1 kinase. In turn, mTORC1 potently drives anabolic processes, including de novo lipid synthesis, while inhibiting lipid catabolism. Here, we describe the dual role of the lysosome in lipid transport and biogenesis, and we discuss how integration of these two processes may play important roles both in normal physiology and in disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Combining Machine Learning Systems and Multiple Docking Simulation Packages to Improve Docking Prediction Reliability for Network Pharmacology

PubMed Central

Hsin, Kun-Yi; Ghosh, Samik; Kitano, Hiroaki

2013-01-01

Increased availability of bioinformatics resources is creating opportunities for the application of network pharmacology to predict drug effects and toxicity resulting from multi-target interactions. Here we present a high-precision computational prediction approach that combines two elaborately built machine learning systems and multiple molecular docking tools to assess binding potentials of a test compound against proteins involved in a complex molecular network. One of the two machine learning systems is a re-scoring function to evaluate binding modes generated by docking tools. The second is a binding mode selection function to identify the most predictive binding mode. Results from a series of benchmark validations and a case study show that this approach surpasses the prediction reliability of other techniques and that it also identifies either primary or off-targets of kinase inhibitors. Integrating this approach with molecular network maps makes it possible to address drug safety issues by comprehensively investigating network-dependent effects of a drug or drug candidate. PMID:24391846

Distribution and clinical impact of functional variants in 50,726 whole-exome sequences from the DiscovEHR study.

PubMed

Dewey, Frederick E; Murray, Michael F; Overton, John D; Habegger, Lukas; Leader, Joseph B; Fetterolf, Samantha N; O'Dushlaine, Colm; Van Hout, Cristopher V; Staples, Jeffrey; Gonzaga-Jauregui, Claudia; Metpally, Raghu; Pendergrass, Sarah A; Giovanni, Monica A; Kirchner, H Lester; Balasubramanian, Suganthi; Abul-Husn, Noura S; Hartzel, Dustin N; Lavage, Daniel R; Kost, Korey A; Packer, Jonathan S; Lopez, Alexander E; Penn, John; Mukherjee, Semanti; Gosalia, Nehal; Kanagaraj, Manoj; Li, Alexander H; Mitnaul, Lyndon J; Adams, Lance J; Person, Thomas N; Praveen, Kavita; Marcketta, Anthony; Lebo, Matthew S; Austin-Tse, Christina A; Mason-Suares, Heather M; Bruse, Shannon; Mellis, Scott; Phillips, Robert; Stahl, Neil; Murphy, Andrew; Economides, Aris; Skelding, Kimberly A; Still, Christopher D; Elmore, James R; Borecki, Ingrid B; Yancopoulos, George D; Davis, F Daniel; Faucett, William A; Gottesman, Omri; Ritchie, Marylyn D; Shuldiner, Alan R; Reid, Jeffrey G; Ledbetter, David H; Baras, Aris; Carey, David J

2016-12-23

The DiscovEHR collaboration between the Regeneron Genetics Center and Geisinger Health System couples high-throughput sequencing to an integrated health care system using longitudinal electronic health records (EHRs). We sequenced the exomes of 50,726 adult participants in the DiscovEHR study to identify ~4.2 million rare single-nucleotide variants and insertion/deletion events, of which ~176,000 are predicted to result in a loss of gene function. Linking these data to EHR-derived clinical phenotypes, we find clinical associations supporting therapeutic targets, including genes encoding drug targets for lipid lowering, and identify previously unidentified rare alleles associated with lipid levels and other blood level traits. About 3.5% of individuals harbor deleterious variants in 76 clinically actionable genes. The DiscovEHR data set provides a blueprint for large-scale precision medicine initiatives and genomics-guided therapeutic discovery. Copyright © 2016, American Association for the Advancement of Science.

The effects of selective and divided attention on sensory precision and integration.

PubMed

Odegaard, Brian; Wozny, David R; Shams, Ladan

2016-02-12

In our daily lives, our capacity to selectively attend to stimuli within or across sensory modalities enables enhanced perception of the surrounding world. While previous research on selective attention has studied this phenomenon extensively, two important questions still remain unanswered: (1) how selective attention to a single modality impacts sensory integration processes, and (2) the mechanism by which selective attention improves perception. We explored how selective attention impacts performance in both a spatial task and a temporal numerosity judgment task, and employed a Bayesian Causal Inference model to investigate the computational mechanism(s) impacted by selective attention. We report three findings: (1) in the spatial domain, selective attention improves precision of the visual sensory representations (which were relatively precise), but not the auditory sensory representations (which were fairly noisy); (2) in the temporal domain, selective attention improves the sensory precision in both modalities (both of which were fairly reliable to begin with); (3) in both tasks, selective attention did not exert a significant influence over the tendency to integrate sensory stimuli. Therefore, it may be postulated that a sensory modality must possess a certain inherent degree of encoding precision in order to benefit from selective attention. It also appears that in certain basic perceptual tasks, the tendency to integrate crossmodal signals does not depend significantly on selective attention. We conclude with a discussion of how these results relate to recent theoretical considerations of selective attention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Lung Cancer Precision Medicine Trials

Cancer.gov

Patients with lung cancer are benefiting from the boom in targeted and immune-based therapies. With a series of precision medicine trials, NCI is keeping pace with the rapidly changing treatment landscape for lung cancer.

2005 Precision Strike Technology Symposium

DTIC Science & Technology

2005-10-20

Radars in  Production  Mission Computer  Software   Functionality to drive Mission System Requirements  Liquid  Cooling   Expanded  Cooling   Capability and Flow...Targeting Demonstration Using the APL Precision Target Locator Demonstrator, Mr. Ben Huguenin and Mr. Joe Schissler, Johns Hopkins University, Applied ...Forces October 18-20, 2005 Kossiakoff Conference Center The Johns Hopkins University/ Applied Physics Laboratory, Laurel, MD David K. Sanders

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective.

PubMed

Chen, Guoli; Yang, Zhaohai; Eshleman, James R; Netto, George J; Lin, Ming-Tseh

2016-01-01

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional "one test-one drug" assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC.

Femtosecond lasers in ophthalmology: clinical applications in anterior segment surgery

NASA Astrophysics Data System (ADS)

Juhasz, Tibor; Nagy, Zoltan; Sarayba, Melvin; Kurtz, Ronald M.

2010-02-01

The human eye is a favored target for laser surgery due to its accessibility via the optically transparent ocular tissue. Femtosecond lasers with confined tissue effects and minimized collateral tissue damage are primary candidates for high precision intraocular surgery. The advent of compact diode-pumped femtosecond lasers, coupled with computer controlled beam delivery devices, enabled the development of high precision femtosecond laser for ophthalmic surgery. In this article, anterior segment femtosecond laser applications currently in clinical practice and investigation are reviewed. Corneal procedures evolved first and remain dominant due to easy targeting referenced from a contact surface, such as applanation lenses placed on the eye. Adding a high precision imaging technique, such as optical coherence tomography (OCT), can enable accurate targeting of tissue beyond the cornea, such as the crystalline lens. Initial clinical results of femtosecond laser cataract surgery are discussed in detail in the latter portion part of the article.

Conservative site-specific and single-copy transgenesis in human LINE-1 elements

PubMed Central

Vijaya Chandra, Shree Harsha; Makhija, Harshyaa; Peter, Sabrina; Myint Wai, Cho Mar; Li, Jinming; Zhu, Jindong; Ren, Zhonglu; D'Alcontres, Martina Stagno; Siau, Jia Wei; Chee, Sharon; Ghadessy, Farid John; Dröge, Peter

2016-01-01

Genome engineering of human cells plays an important role in biotechnology and molecular medicine. In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications. Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility. Phage λ integrase (Int) is a transgenesis tool that mediates conservative site-specific integration of 48 kb DNA into a safe harbor site of the bacterial genome. Here, we show that an Int variant precisely recombines large episomes into a sequence, termed attH4X, found in 1000 human Long INterspersed Elements-1 (LINE-1). We demonstrate single-copy transgenesis through attH4X-targeting in various cell lines including hESCs, with the flexibility of selecting clones according to transgene performance and downstream applications. This is exemplified with pluripotency reporter cassettes and constitutively expressed payloads that remain functional in LINE1-targeted hESCs and differentiated progenies. Furthermore, LINE-1 targeting does not induce DNA damage-response or chromosomal aberrations, and neither global nor localized endogenous gene expression is substantially affected. Hence, this simple transgene addition tool should become particularly useful for applications that require engineering of the human genome with multi-transgenes. PMID:26673710

Systematic approach identifies RHOA as a potential biomarker therapeutic target for Asian gastric cancer.

PubMed

Chang, Hae Ryung; Nam, Seungyoon; Lee, Jinhyuk; Kim, Jin-Hee; Jung, Hae Rim; Park, Hee Seo; Park, Sungjin; Ahn, Young Zoo; Huh, Iksoo; Balch, Curt; Ku, Ja-Lok; Powis, Garth; Park, Taesung; Jeong, Jin-Hyun; Kim, Yon Hui

2016-12-06

Gastric cancer (GC) is a highly heterogeneous disease, in dire need of specific, biomarker-driven cancer therapies. While the accumulation of cancer "Big Data" has propelled the search for novel molecular targets for GC, its specific subpathway and cellular functions vary from patient to patient. In particular, mutations in the small GTPase gene RHOA have been identified in recent genome-wide sequencing of GC tumors. Moreover, protein overexpression of RHOA was reported in Chinese populations, while RHOA mutations were found in Caucasian GC tumors. To develop evidence-based precision medicine for heterogeneous cancers, we established a systematic approach to integrate transcriptomic and genomic data. Predicted signaling subpathways were then laboratory-validated both in vitro and in vivo, resulting in the identification of new candidate therapeutic targets. Here, we show: i) differences in RHOA expression patterns, and its pathway activity, between Asian and Caucasian GC tumors; ii) in vitro and in vivo perturbed RHOA expression inhibits GC cell growth in high RHOA-expressing cell lines; iii) inverse correlation between RHOA and RHOB expression; and iv) an innovative small molecule design strategy for RHOA inhibitors. In summary, RHOA, and its oncogenic signaling pathway, represent a strong biomarker-driven therapeutic target for Asian GC. This comprehensive strategy represents a promising approach for the development of "hit" compounds.

An interval precise integration method for transient unbalance response analysis of rotor system with uncertainty

NASA Astrophysics Data System (ADS)

Fu, Chao; Ren, Xingmin; Yang, Yongfeng; Xia, Yebao; Deng, Wangqun

2018-07-01

A non-intrusive interval precise integration method (IPIM) is proposed in this paper to analyze the transient unbalance response of uncertain rotor systems. The transfer matrix method (TMM) is used to derive the deterministic equations of motion of a hollow-shaft overhung rotor. The uncertain transient dynamic problem is solved by combing the Chebyshev approximation theory with the modified precise integration method (PIM). Transient response bounds are calculated by interval arithmetic of the expansion coefficients. Theoretical error analysis of the proposed method is provided briefly, and its accuracy is further validated by comparing with the scanning method in simulations. Numerical results show that the IPIM can keep good accuracy in vibration prediction of the start-up transient process. Furthermore, the proposed method can also provide theoretical guidance to other transient dynamic mechanical systems with uncertainties.

Organ-on-a-Chip Systems: Microengineering to Biomimic Living Systems.

PubMed

Zheng, Fuyin; Fu, Fanfan; Cheng, Yao; Wang, Chunyan; Zhao, Yuanjin; Gu, Zhongze

2016-05-01

"Organ-on-a-chip" systems integrate microengineering, microfluidic technologies, and biomimetic principles to create key aspects of living organs faithfully, including critical microarchitecture, spatiotemporal cell-cell interactions, and extracellular microenvironments. This creative platform and its multiorgan integration recapitulating organ-level structures and functions can bring unprecedented benefits to a diversity of applications, such as developing human in vitro models for healthy or diseased organs, enabling the investigation of fundamental mechanisms in disease etiology and organogenesis, benefiting drug development in toxicity screening and target discovery, and potentially serving as replacements for animal testing. Recent advances in novel designs and examples for developing organ-on-a-chip platforms are reviewed. The potential for using this emerging technology in understanding human physiology including mechanical, chemical, and electrical signals with precise spatiotemporal controls are discussed. The current challenges and future directions that need to be pursued for these proof-of-concept studies are also be highlighted. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Drilling informatics: data-driven challenges of scientific drilling

NASA Astrophysics Data System (ADS)

Yamada, Yasuhiro; Kyaw, Moe; Saito, Sanny

2017-04-01

The primary aim of scientific drilling is to precisely understand the dynamic nature of the Earth. This is the reason why we investigate the subsurface materials (rock and fluid including microbial community) existing under particular environmental conditions. This requires sample collection and analytical data production from the samples, and in-situ data measurement at boreholes. Current available data comes from cores, cuttings, mud logging, geophysical logging, and exploration geophysics, but these datasets are difficult to be integrated because of their different kinds and scales. Now we are producing more useful datasets to fill the gap between the exiting data and extracting more information from such datasets and finally integrating the information. In particular, drilling parameters are very useful datasets as geomechanical properties. We believe such approach, 'drilling informatics', would be the most appropriate to obtain the comprehensive and dynamic picture of our scientific target, such as the seismogenic fault zone and the Moho discontinuity surface. This presentation introduces our initiative and current achievements of drilling informatics.

Spectral integration in primary auditory cortex attributable to temporally precise convergence of thalamocortical and intracortical input.

PubMed

Happel, Max F K; Jeschke, Marcus; Ohl, Frank W

2010-08-18

Primary sensory cortex integrates sensory information from afferent feedforward thalamocortical projection systems and convergent intracortical microcircuits. Both input systems have been demonstrated to provide different aspects of sensory information. Here we have used high-density recordings of laminar current source density (CSD) distributions in primary auditory cortex of Mongolian gerbils in combination with pharmacological silencing of cortical activity and analysis of the residual CSD, to dissociate the feedforward thalamocortical contribution and the intracortical contribution to spectral integration. We found a temporally highly precise integration of both types of inputs when the stimulation frequency was in close spectral neighborhood of the best frequency of the measurement site, in which the overlap between both inputs is maximal. Local intracortical connections provide both directly feedforward excitatory and modulatory input from adjacent cortical sites, which determine how concurrent afferent inputs are integrated. Through separate excitatory horizontal projections, terminating in cortical layers II/III, information about stimulus energy in greater spectral distance is provided even over long cortical distances. These projections effectively broaden spectral tuning width. Based on these data, we suggest a mechanism of spectral integration in primary auditory cortex that is based on temporally precise interactions of afferent thalamocortical inputs and different short- and long-range intracortical networks. The proposed conceptual framework allows integration of different and partly controversial anatomical and physiological models of spectral integration in the literature.

NASA Precision Landing Technologies Completes Initial Flight Tests on Vertical Testbed Rocket

NASA Image and Video Library

2017-04-19

This 2-minute, 40-second video shows how over the past 5 weeks, NASA and Masten Space Systems teams have prepared for and conducted sub-orbital rocket flight tests of next-generation lander navigation technology through the CoOperative Blending of Autonomous Landing Technologies (COBALT) project. The COBALT payload was integrated onto Masten’s rocket, Xodiac. The Xodiac vehicle used the Global Positioning System (GPS) for navigation during this first campaign, which was intentional to verify and refine COBALT system performance. The joint teams conducted numerous ground verification tests, made modifications in the process, practiced and refined operations’ procedures, conducted three tether tests, and have now flown two successful free flights. This successful, collaborative campaign has provided the COBALT and Xodiac teams with the valuable performance data needed to refine the systems and prepare them for the second flight test campaign this summer when the COBALT system will navigate the Xodiac rocket to a precision landing. The technologies within COBALT provide a spacecraft with knowledge during entry, descent, and landing that enables it to precisely navigate and softly land close to surface locations that have been previously too risky to target with current capabilities. The technologies will enable future exploration destinations on Mars, the moon, Europa, and other planets and moons. The two primary navigation components within COBALT include the Langley Research Center’s Navigation Doppler Lidar, which provides ultra-precise velocity and line-of-sight range measurements, and Jet Propulsion Laboratory’s Lander Vision System (LVS), which provides navigation estimates relative to an existing surface map. The integrated system is being flight tested onboard a Masten suborbital rocket vehicle called Xodiac. The COBALT project is led by the Johnson Space Center, with funding provided through the Game Changing Development, Flight Opportunities program, and Advanced Exploration Systems programs. Based at NASA’s Armstrong Flight Research Center in Edwards, CA, the Flight Opportunities program funds technology development flight tests on commercial suborbital space providers of which Masten is a vendor. The program has previously tested the LVS on the Masten rocket and validated the technology for the Mars 2020 rover.

Precision oncology in advanced cancer patients improves overall survival with lower weekly healthcare costs

PubMed Central

Haslem, Derrick S.; Chakravarty, Ingo; Fulde, Gail; Gilbert, Heather; Tudor, Brian P.; Lin, Karen; Ford, James M.; Nadauld, Lincoln D.

2018-01-01

The impact of precision oncology on guiding treatment decisions of late-stage cancer patients was previously studied in a retrospective analysis. However, the overall survival and costs were not previously evaluated. We report the overall survival and healthcare costs associated with precision oncology in these patients with advanced cancer. Building on a matched cohort study of 44 patients with metastatic cancer who received all of their care within a single institution, we evaluated the overall survival and healthcare costs for each patient. We analyzed the outcomes of 22 patients who received genomic testing and targeted therapy (precision oncology) between July 1, 2013 and January 31, 2015, and compared to 22 historically controlled patients (control) who received standard chemotherapy (N = 17) or best supportive care (N = 5). The median overall survival was 51.7 weeks for the targeted treatment group and 25.8 weeks for the control group (P = 0.008) when matching on age, gender, histological diagnosis and previous treatment lines. Average costs over the entire period were $2,720 per week for the targeted treatment group and $3,453 per week for the control group, (P = 0.036). A separate analysis of 1,814 patients with late-stage cancer diagnoses found that those who received a targeted cancer treatment (N = 93) had 6.9% lower costs in the last 3 months of life compared with those who did not. These findings suggest that precision oncology may improve overall survival for refractory cancer patients while lowering average per-week healthcare costs, resource utilization and end-of-life costs. PMID:29552312

Emission quantification using the tracer gas dispersion method: The influence of instrument, tracer gas species and source simulation.

PubMed

Delre, Antonio; Mønster, Jacob; Samuelsson, Jerker; Fredenslund, Anders M; Scheutz, Charlotte

2018-09-01

The tracer gas dispersion method (TDM) is a remote sensing method used for quantifying fugitive emissions by relying on the controlled release of a tracer gas at the source, combined with concentration measurements of the tracer and target gas plumes. The TDM was tested at a wastewater treatment plant for plant-integrated methane emission quantification, using four analytical instruments simultaneously and four different tracer gases. Measurements performed using a combination of an analytical instrument and a tracer gas, with a high ratio between the tracer gas release rate and instrument precision (a high release-precision ratio), resulted in well-defined plumes with a high signal-to-noise ratio and a high methane-to-tracer gas correlation factor. Measured methane emission rates differed by up to 18% from the mean value when measurements were performed using seven different instrument and tracer gas combinations. Analytical instruments with a high detection frequency and good precision were established as the most suitable for successful TDM application. The application of an instrument with a poor precision could only to some extent be overcome by applying a higher tracer gas release rate. A sideward misplacement of the tracer gas release point of about 250m resulted in an emission rate comparable to those obtained using a tracer gas correctly simulating the methane emission. Conversely, an upwind misplacement of about 150m resulted in an emission rate overestimation of almost 50%, showing the importance of proper emission source simulation when applying the TDM. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical Pharmacology Quality Assurance (CPQA) Program: Models for Longitudinal Analysis of Antiretroviral (ARV) Proficiency Testing for International Laboratories

PubMed Central

DiFrancesco, Robin; Rosenkranz, Susan L.; Taylor, Charlene R.; Pande, Poonam G.; Siminski, Suzanne M.; Jenny, Richard W.; Morse, Gene D.

2013-01-01

Among National Institutes of Health (NIH) HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals (ARV). Drug assay data are, in turn, entered into study-specific datasets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semi-annual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance (CPQA) program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1)assess the precision and accuracy of concentrations reported by individual CPLs; (2)determine factors associated with round-specific and long-term assay accuracy, precision and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21)drug concentration results reported for clinical trial samples by multiple CPLs).Using the CLIA acceptance of meeting criteria for ≥2/3 consecutive rounds, all ten laboratories that participated in three or more rounds per analyte maintained CLIA proficiency. Significant associations were present between magnitude of error and CPL (Kruskal Wallis [KW]p<0.001), and ARV (KW p<0.001). PMID:24052065

Clinical pharmacology quality assurance program: models for longitudinal analysis of antiretroviral proficiency testing for international laboratories.

PubMed

DiFrancesco, Robin; Rosenkranz, Susan L; Taylor, Charlene R; Pande, Poonam G; Siminski, Suzanne M; Jenny, Richard W; Morse, Gene D

2013-10-01

Among National Institutes of Health HIV Research Networks conducting multicenter trials, samples from protocols that span several years are analyzed at multiple clinical pharmacology laboratories (CPLs) for multiple antiretrovirals. Drug assay data are, in turn, entered into study-specific data sets that are used for pharmacokinetic analyses, merged to conduct cross-protocol pharmacokinetic analysis, and integrated with pharmacogenomics research to investigate pharmacokinetic-pharmacogenetic associations. The CPLs participate in a semiannual proficiency testing (PT) program implemented by the Clinical Pharmacology Quality Assurance program. Using results from multiple PT rounds, longitudinal analyses of recovery are reflective of accuracy and precision within/across laboratories. The objectives of this longitudinal analysis of PT across multiple CPLs were to develop and test statistical models that longitudinally: (1) assess the precision and accuracy of concentrations reported by individual CPLs and (2) determine factors associated with round-specific and long-term assay accuracy, precision, and bias using a new regression model. A measure of absolute recovery is explored as a simultaneous measure of accuracy and precision. Overall, the analysis outcomes assured 97% accuracy (±20% of the final target concentration of all (21) drug concentration results reported for clinical trial samples by multiple CPLs). Using the Clinical Laboratory Improvement Act acceptance of meeting criteria for ≥2/3 consecutive rounds, all 10 laboratories that participated in 3 or more rounds per analyte maintained Clinical Laboratory Improvement Act proficiency. Significant associations were present between magnitude of error and CPL (Kruskal-Wallis P < 0.001) and antiretroviral (Kruskal-Wallis P < 0.001).

Precision linear ramp function generator

DOEpatents

Jatko, W.B.; McNeilly, D.R.; Thacker, L.H.

1984-08-01

A ramp function generator is provided which produces a precise linear ramp function which is repeatable and highly stable. A derivative feedback loop is used to stabilize the output of an integrator in the forward loop and control the ramp rate. The ramp may be started from a selected baseline voltage level and the desired ramp rate is selected by applying an appropriate constant voltage to the input of the integrator.

Precision linear ramp function generator

DOEpatents

Jatko, W. Bruce; McNeilly, David R.; Thacker, Louis H.

1986-01-01

A ramp function generator is provided which produces a precise linear ramp unction which is repeatable and highly stable. A derivative feedback loop is used to stabilize the output of an integrator in the forward loop and control the ramp rate. The ramp may be started from a selected baseline voltage level and the desired ramp rate is selected by applying an appropriate constant voltage to the input of the integrator.

Notes From the Field: Secondary Task Precision for Cognitive Load Estimation During Virtual Reality Surgical Simulation Training.

PubMed

Rasmussen, Sebastian R; Konge, Lars; Mikkelsen, Peter T; Sørensen, Mads S; Andersen, Steven A W

2016-03-01

Cognitive load (CL) theory suggests that working memory can be overloaded in complex learning tasks such as surgical technical skills training, which can impair learning. Valid and feasible methods for estimating the CL in specific learning contexts are necessary before the efficacy of CL-lowering instructional interventions can be established. This study aims to explore secondary task precision for the estimation of CL in virtual reality (VR) surgical simulation and also investigate the effects of CL-modifying factors such as simulator-integrated tutoring and repeated practice. Twenty-four participants were randomized for visual assistance by a simulator-integrated tutor function during the first 5 of 12 repeated mastoidectomy procedures on a VR temporal bone simulator. Secondary task precision was found to be significantly lower during simulation compared with nonsimulation baseline, p < .001. Contrary to expectations, simulator-integrated tutoring and repeated practice did not have an impact on secondary task precision. This finding suggests that even though considerable changes in CL are reflected in secondary task precision, it lacks sensitivity. In contrast, secondary task reaction time could be more sensitive, but requires substantial postprocessing of data. Therefore, future studies on the effect of CL modifying interventions should weigh the pros and cons of the various secondary task measurements. © The Author(s) 2015.

Significance and integration of molecular diagnostics in the framework of veterinary practice.

PubMed

Aranaz, Alicia

2015-01-01

The field of molecular diagnostics in veterinary practice is rapidly evolving. An array of molecular techniques of different complexity is available to facilitate the fast and specific diagnosis of animal diseases. The choice for the adequate technique is dependent on the mission and attributions of the laboratory and requires both a knowledge of the molecular biology basis and of its limitations. The ability to quickly detect pathogens and their characteristics would allow for precise decision-making and target measures such as prophylaxis, appropriate therapy, and biosafety plans to control disease outbreaks. In practice, taking benefit of the huge amount of data that can be obtained using molecular techniques highlights the need of collaboration between veterinarians in the laboratory and practitioners.

Meso-scale controlled motion for a microfluidic drop ejector.

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

Galambos, Paul C.; Givler, Richard C.; Pohl, Kenneth Roy

2004-12-01

The objective of this LDRD was to develop a uniquely capable, novel droplet solution based manufacturing system built around a new MEMS drop ejector. The development all the working subsystems required was completed, leaving the integration of these subsystems into a working prototype still left to accomplish. This LDRD report will focus on the three main subsystems: (1) MEMS drop ejector--the MEMS ''sideshooter'' effectively ejected 0.25 pl drops at 10 m/s, (2) packaging--a compact ejector package based on a modified EMDIP (Electro-Microfluidic Dual In-line Package--SAND2002-1941) was fabricated, and (3) a vision/stage system allowing precise ejector package positioning in 3 dimensionsmore » above a target was developed.« less

A Precision Metrology System for the Hubble Space Telescope Wide Field Camera 3 Instrument

NASA Technical Reports Server (NTRS)

Toland, Ronald W.

2003-01-01

The Wide Field Camera 3 (WFC3) instrument for the Hubble Space Telescope (HST) will replace the current Wide Field and Planetary Camera 2 (WFPC2). By providing higher throughput and sensitivity than WFPC2, and operating from the near-IR to the near-UV, WFC3 will once again bring the performance of HST above that from ground-based observatories. Crucial to the integration of the WFC3 optical bench is a pair of 2-axis cathetometers used to view targets which cannot be seen by other means when the bench is loaded into its enclosure. The setup and calibration of these cathetometers is described, along with results from a comparison of the cathetometer system with other metrology techniques.

High-sensitivity gas-mapping 3D imager and method of operation

DOEpatents

Kreitinger, Aaron; Thorpe, Michael

2018-05-15

Measurement apparatuses and methods are disclosed for generating high-precision and -accuracy gas concentration maps that can be overlaid with 3D topographic images by rapidly scanning one or several modulated laser beams with a spatially-encoded transmitter over a scene to build-up imagery. Independent measurements of the topographic target distance and path-integrated gas concentration are combined to yield a map of the path-averaged concentration between the sensor and each point in the image. This type of image is particularly useful for finding localized regions of elevated (or anomalous) gas concentration making it ideal for large-area leak detection and quantification applications including: oil and gas pipeline monitoring, chemical processing facility monitoring, and environmental monitoring.

Spectrally and Radiometrically Stable Wide-Band on Board Calibration Source for In-Flight Data Validation in Imaging Spectroscopy Applications

NASA Technical Reports Server (NTRS)

Coles, J. B.; Richardson, Brandon S.; Eastwood, Michael L.; Sarture, Charles M.; Quetin, Gregory R.; Hernandez, Marco A.; Kroll, Linley A.; Nolte, Scott H.; Porter, Michael D.; Green, Robert O.

2011-01-01

The quality of the quantitative spectral data collected by an imaging spectrometer instrument is critically dependent upon the accuracy of the spectral and radiometric calibration of the system. In order for the collected spectra to be scientifically useful, the calibration of the instrument must be precisely known not only prior to but during data collection. Thus, in addition to a rigorous in-lab calibration procedure, the airborne instruments designed and built by the NASA/JPL Imaging Spectroscopy Group incorporate an on board calibrator (OBC) system with the instrument to provide auxiliary in-use system calibration data. The output of the OBC source illuminates a target panel on the backside of the foreoptics shutter both before and after data collection. The OBC and in-lab calibration data sets are then used to validate and post-process the collected spectral image data. The resulting accuracy of the spectrometer output data is therefore integrally dependent upon the stability of the OBC source. In this paper we describe the design and application of the latest iteration of this novel device developed at NASA/JPL which integrates a halogen-cycle source with a precisely designed fiber coupling system and a fiber-based intensity monitoring feedback loop. The OBC source in this Airborne Testbed Spectrometer was run over a period of 15 hours while both the radiometric and spectral stabilities of the output were measured and demonstrated stability to within 1% of nominal.

Precision Pointing Control to and Accurate Target Estimation of a Non-Cooperative Vehicle

NASA Technical Reports Server (NTRS)

VanEepoel, John; Thienel, Julie; Sanner, Robert M.

2006-01-01

In 2004, NASA began investigating a robotic servicing mission for the Hubble Space Telescope (HST). Such a mission would not only require estimates of the HST attitude and rates in order to achieve capture by the proposed Hubble Robotic Vehicle (HRV), but also precision control to achieve the desired rate and maintain the orientation to successfully dock with HST. To generalize the situation, HST is the target vehicle and HRV is the chaser. This work presents a nonlinear approach for estimating the body rates of a non-cooperative target vehicle, and coupling this estimation to a control scheme. Non-cooperative in this context relates to the target vehicle no longer having the ability to maintain attitude control or transmit attitude knowledge.

Localization Strategies in WSNs as applied to Landslide Monitoring (Invited)

NASA Astrophysics Data System (ADS)

Massa, A.; Robol, F.; Polo, A.; Giarola, E.; Viani, F.

2013-12-01

In the last years, heterogeneous integrated smart systems based on wireless sensor network (WSN) technology have been developed at the ELEDIA Research Center of the University of Trento [1]. One of the key features of WSNs as applied to distributed monitoring is that, while the capabilities of each single sensor node is limited, the implementation of cooperative schemes throughout the whole network enables the solution of even complex tasks, as the landslide monitoring. The capability of localizing targets respect to the position of the sensor nodes turns out to be fundamental in those application fields where relative movements arise. The main properties like the target typology, the movement characteristics, and the required localization resolution are different changing the reference scenario. However, the common key issue is still the localization of moving targets within the area covered by the sensor network. Many experiences were preparatory for the challenging activities in the field of landslide monitoring where the basic idea is mostly that of detecting slight soil movements. Among them, some examples of WSN-based systems experimentally applied to the localization of people [2] and wildlife [3] have been proposed. More recently, the WSN backbone as well as the investigated sensing technologies have been customized for monitoring superficial movements of the soil. The relative positions of wireless sensor nodes deployed where high probability of landslide exists is carefully monitored to forecast dangerous events. Multiple sensors like ultrasound, laser, high precision GPS, for the precise measurement of relative distances between the nodes of the network and the absolute positions respect to reference targets have been integrated in a prototype system. The millimeter accuracy in the position estimation enables the detection of small soil modifications and to infer the superficial evolution profile of the landslide. This information locally acquired also represent a fine tuning of large scale satellite acquisitions, usually adopted for remote sensing of landslides. The integration of dense and frequent WSN data within satellite image analysis will enhance the sensing capabilities leading to a multi-resolution and an highly space-time calibrated system. The WSN-based system has been preliminary tested in controlled environments in the ELEDIA laboratories and is now installed in a real test site where an active landslide is evolving. Preliminary data are here presented to assess the feasibility of the investigated solution in landslide monitoring and event forecasting. REFERENCES [1] M. Benedetti, L. Ioriatti, M. Martinelli, and F. Viani, 'Wireless sensor network: a pervasive technology for earth observation,' in IEEE Journal of Selected Topics in App. Earth Obs. And Remote Sens., vol. 3, no. 4, pp. 488-497, 2010. [2] F. Viani, M. Donelli, P. Rocca, G. Oliveri, D. Trinchero, and A. Massa, 'Localization, tracking and imaging of targets in wireless sensor networks,' Radio Science, vol. 46, no. 5, 2011. [3] F. Viani, F. Robol, M. Salucci, E. Giarola, S. De Vigili, M. Rocca, F. Boldrini, G. Benedetti, and A. Massa, 'WSN-based early alert system for preventing wildlife-vehicle collisions in Alps regions - From the laboratory test to the real-world implementation,' 7th European Conference on Antennas and Propagation 2013 (EUCAP2013), Gothenburg, Sweden, April 8-12, 2013.

Zinc finger nuclease-mediated precision genome editing of an endogenous gene in hexaploid bread wheat (Triticum aestivum) using a DNA repair template.

PubMed

Ran, Yidong; Patron, Nicola; Kay, Pippa; Wong, Debbie; Buchanan, Margaret; Cao, Ying-Ying; Sawbridge, Tim; Davies, John P; Mason, John; Webb, Steven R; Spangenberg, German; Ainley, William M; Walsh, Terence A; Hayden, Matthew J

2018-05-07

Sequence-specific nucleases have been used to engineer targeted genome modifications in various plants. While targeted gene knockouts resulting in loss of function have been reported with relatively high rates of success, targeted gene editing using an exogenously supplied DNA repair template and site-specific transgene integration has been more challenging. Here, we report the first application of zinc finger nuclease (ZFN)-mediated, nonhomologous end-joining (NHEJ)-directed editing of a native gene in allohexaploid bread wheat to introduce, via a supplied DNA repair template, a specific single amino acid change into the coding sequence of acetohydroxyacid synthase (AHAS) to confer resistance to imidazolinone herbicides. We recovered edited wheat plants having the targeted amino acid modification in one or more AHAS homoalleles via direct selection for resistance to imazamox, an AHAS-inhibiting imidazolinone herbicide. Using a cotransformation strategy based on chemical selection for an exogenous marker, we achieved a 1.2% recovery rate of edited plants having the desired amino acid change and a 2.9% recovery of plants with targeted mutations at the AHAS locus resulting in a loss-of-function gene knockout. The latter results demonstrate a broadly applicable approach to introduce targeted modifications into native genes for nonselectable traits. All ZFN-mediated changes were faithfully transmitted to the next generation. © 2018 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Targeting circuits

PubMed Central

Rajasethupathy, Priyamvada; Ferenczi, Emily; Deisseroth, Karl

2017-01-01

Current optogenetic methodology enables precise inhibition or excitation of neural circuits, spanning timescales as needed from the acute (milliseconds) to the chronic (many days or more), for experimental modulation of network activity and animal behavior. Such broad temporal versatility, unique to optogenetic control, is particularly powerful when combined with brain activity measurements that span both acute and chronic timescales as well. This enables, for instance, the study of adaptive circuit dynamics across the intact brain, and tuning interventions to match activity patterns naturally observed during behavior in the same individual. Although the impact of this approach has been greater on basic research than on clinical translation, it is natural to ask if specific neural circuit activity patterns discovered to be involved in controlling adaptive or maladaptive behaviors could become targets for treatment of neuropsychiatric diseases. Here we consider the landscape of such ideas related to therapeutic targeting of circuit dynamics, taking note of developments not only in optical but also in ultrasonic, magnetic, and thermal methods. We note the recent emergence of first-in-kind optogenetically-guided clinical outcomes, as well as opportunities related to the integration of interventions and readouts spanning diverse circuit-physiology, molecular, and behavioral modalities. PMID:27104976

Tumor acidity-activatable TAT targeted nanomedicine for enlarged fluorescence/magnetic resonance imaging-guided photodynamic therapy.

PubMed

Gao, Meng; Fan, Feng; Li, Dongdong; Yu, Yue; Mao, Kuirong; Sun, Tianmeng; Qian, Haisheng; Tao, Wei; Yang, Xianzhu

2017-07-01

Nanoparticles simultaneously integrated the photosensitizers and diagnostic agents represent an emerging approach for imaging-guided photodynamic therapy (PDT). However, the diagnostic sensitivity and therapeutic efficacy of nanoparticles as well as the heterogeneity of tumors pose tremendous challenges for clinical imaging-guided PDT treatment. Herein, a polymeric nanoparticle with tumor acidity (pH e )-activatable TAT targeting ligand that encapsulates the photosensitizer chlorin e6 (Ce6) and chelates contrast agent Gd 3+ is successfully developed for fluorescence/magnetic resonance (MR) dual-model imaging-guided precision PDT. We show clear evidence that the resulting nanoparticle DA TAT-NP [its TAT lysine residues' amines was modified by 2,3-dimethylmaleic anhydride (DA)] efficiently avoids the rapid clearance by reticuloendothelial system (RES) by masking of the TAT peptide, resulting in the significantly prolonged circulation time in the blood. Once accumulating in the tumor tissues, DA TAT-NP is reactivated by tumor acidity to promote cellular uptake, resulting in enlarged fluorescence/MR imaging signal intensity and elevated in vivo PDT therapeutic effect. This concept provides new avenues to design tumor acidity-activatable targeted nanoparticles for imaging-guided cancer therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

The national ignition facility: Path to ignition in the laboratory

NASA Astrophysics Data System (ADS)

Moses, E. I.; Bonanno, R. E.; Haynam, C. A.; Kauffman, R. L.; MacGowan, B. J.; Patterson, R. W., Jr.; Sawicki, R. H.; van Wonterghem, B. M.

2006-06-01

The National Ignition Facility (NIF) is a 192-beam laser facility presently under construction at LLNL. When completed, NIF will be a 1.8-MJ, 500-TW ultraviolet laser system. Its missions are to obtain fusion ignition and to perform high energy density experiments in support of the U.S. nuclear weapons stockpile. Four of the NIF beams have been commissioned to demonstrate laser performance and to commission the target area including target and beam alignment and laser timing. During this time, NIF demonstrated on a single-beam basis that it will meet its performance goals and demonstrated its precision and flexibility for pulse shaping, pointing, timing and beam conditioning. It also performed four important experiments for Inertial Confinement Fusion and High Energy Density Science. Presently, the project is installing production hardware to complete the project in 2009 with the goal to begin ignition experiments in 2010. An integrated plan has been developed including the NIF operations, user equipment such as diagnostics and cryogenic target capability, and experiments and calculations to meet this goal. This talk will provide NIF status, the plan to complete NIF, and the path to ignition.

The Bxb1 recombination system demonstrates heritable transmission of site-specific excision in Arabidopsis

PubMed Central

2012-01-01

Background The mycobacteriophage large serine recombinase Bxb1 catalyzes site-specific recombination between its corresponding attP and attB recognition sites. Previously, we and others have shown that Bxb1 has catalytic activity in various eukaryotic species including Nicotiana tabacum, Schizosaccharomyces pombe, insects and mammalian cells. Results In this work, the Bxb1 recombinase gene was transformed and constitutively expressed in Arabidopsis thaliana plants harboring a chromosomally integrated attP and attB-flanked target sequence. The Bxb1 recombinase successfully excised the target sequence in a conservative manner and the resulting recombination event was heritably transmitted to subsequent generations in the absence of the recombinase transgene. In addition, we also show that Bxb1 recombinase expressing plants can be manually crossed with att-flanked target transgenic plants to generate excised progeny. Conclusion The Bxb1 large serine recombinase performs site-specific recombination in Arabidopsis thaliana germinal tissue, producing stable lines free of unwanted DNA. The precise site-specific deletion produced by Bxb1 in planta demonstrates that this enzyme can be a useful tool for the genetic engineering of plants without selectable marker transgenes or other undesirable exogenous sequences. PMID:22436504

Optimal Audiovisual Integration in the Ventriloquism Effect But Pervasive Deficits in Unisensory Spatial Localization in Amblyopia.

PubMed

Richards, Michael D; Goltz, Herbert C; Wong, Agnes M F

2018-01-01

Classically understood as a deficit in spatial vision, amblyopia is increasingly recognized to also impair audiovisual multisensory processing. Studies to date, however, have not determined whether the audiovisual abnormalities reflect a failure of multisensory integration, or an optimal strategy in the face of unisensory impairment. We use the ventriloquism effect and the maximum-likelihood estimation (MLE) model of optimal integration to investigate integration of audiovisual spatial information in amblyopia. Participants with unilateral amblyopia (n = 14; mean age 28.8 years; 7 anisometropic, 3 strabismic, 4 mixed mechanism) and visually normal controls (n = 16, mean age 29.2 years) localized brief unimodal auditory, unimodal visual, and bimodal (audiovisual) stimuli during binocular viewing using a location discrimination task. A subset of bimodal trials involved the ventriloquism effect, an illusion in which auditory and visual stimuli originating from different locations are perceived as originating from a single location. Localization precision and bias were determined by psychometric curve fitting, and the observed parameters were compared with predictions from the MLE model. Spatial localization precision was significantly reduced in the amblyopia group compared with the control group for unimodal visual, unimodal auditory, and bimodal stimuli. Analyses of localization precision and bias for bimodal stimuli showed no significant deviations from the MLE model in either the amblyopia group or the control group. Despite pervasive deficits in localization precision for visual, auditory, and audiovisual stimuli, audiovisual integration remains intact and optimal in unilateral amblyopia.

Discrimination of curvature from motion during smooth pursuit eye movements and fixation.

PubMed

Ross, Nicholas M; Goettker, Alexander; Schütz, Alexander C; Braun, Doris I; Gegenfurtner, Karl R

2017-09-01

Smooth pursuit and motion perception have mainly been investigated with stimuli moving along linear trajectories. Here we studied the quality of pursuit movements to curved motion trajectories in human observers and examined whether the pursuit responses would be sensitive enough to discriminate various degrees of curvature. In a two-interval forced-choice task subjects pursued a Gaussian blob moving along a curved trajectory and then indicated in which interval the curve was flatter. We also measured discrimination thresholds for the same curvatures during fixation. Motion curvature had some specific effects on smooth pursuit properties: trajectories with larger amounts of curvature elicited lower open-loop acceleration, lower pursuit gain, and larger catch-up saccades compared with less curved trajectories. Initially, target motion curvatures were underestimated; however, ∼300 ms after pursuit onset pursuit responses closely matched the actual curved trajectory. We calculated perceptual thresholds for curvature discrimination, which were on the order of 1.5 degrees of visual angle (°) for a 7.9° curvature standard. Oculometric sensitivity to curvature discrimination based on the whole pursuit trajectory was quite similar to perceptual performance. Oculometric thresholds based on smaller time windows were higher. Thus smooth pursuit can quite accurately follow moving targets with curved trajectories, but temporal integration over longer periods is necessary to reach perceptual thresholds for curvature discrimination. NEW & NOTEWORTHY Even though motion trajectories in the real world are frequently curved, most studies of smooth pursuit and motion perception have investigated linear motion. We show that pursuit initially underestimates the curvature of target motion and is able to reproduce the target curvature ∼300 ms after pursuit onset. Temporal integration of target motion over longer periods is necessary for pursuit to reach the level of precision found in perceptual discrimination of curvature. Copyright © 2017 the American Physiological Society.

Aerospace Laser Ignition/Ablation Variable High Precision Thruster

NASA Technical Reports Server (NTRS)

Campbell, Jonathan W. (Inventor); Edwards, David L. (Inventor); Campbell, Jason J. (Inventor)

2015-01-01

A laser ignition/ablation propulsion system that captures the advantages of both liquid and solid propulsion. A reel system is used to move a propellant tape containing a plurality of propellant material targets through an ignition chamber. When a propellant target is in the ignition chamber, a laser beam from a laser positioned above the ignition chamber strikes the propellant target, igniting the propellant material and resulting in a thrust impulse. The propellant tape is advanced, carrying another propellant target into the ignition chamber. The propellant tape and ignition chamber are designed to ensure that each ignition event is isolated from the remaining propellant targets. Thrust and specific impulse may by precisely controlled by varying the synchronized propellant tape/laser speed. The laser ignition/ablation propulsion system may be scaled for use in small and large applications.

National Ignition Facility Target Chamber

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

Wavrik, R W; Cox, J R; Fleming, P J

2000-10-05

On June 11, 1999 the Department of Energy dedicated the single largest piece of the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory (LLNL) in Livermore, California. The ten (10) meter diameter aluminum target high vacuum chamber will serve as the working end of the largest laser in the world. The output of 192 laser beams will converge at the precise center of the chamber. The laser beams will enter the chamber in two by two arrays to illuminate 10 millimeter long gold cylinders called hohlraums enclosing 2 millimeter capsule containing deuterium, tritium and isotopes of hydrogen. The twomore » isotopes will fuse, thereby creating temperatures and pressures resembling those found only inside stars and in detonated nuclear weapons, but on a minute scale. The NIF Project will serve as an essential facility to insure safety and reliability of our nation's nuclear arsenal as well as demonstrating inertial fusion's contribution to creating electrical power. The paper will discuss the requirements that had to be addressed during the design, fabrication and testing of the target chamber. A team from Sandia National Laboratories (SNL) and LLNL with input from industry performed the configuration and basic design of the target chamber. The method of fabrication and construction of the aluminum target chamber was devised by Pitt-Des Moines, Inc. (PDM). PDM also participated in the design of the chamber in areas such as the Target Chamber Realignment and Adjustment System, which would allow realignment of the sphere laser beams in the event of earth settlement or movement from a seismic event. During the fabrication of the target chamber the sphericity tolerances had to be addressed for the individual plates. Procedures were developed for forming, edge preparation and welding of individual plates. Construction plans were developed to allow the field construction of the target chamber to occur parallel to other NIF construction activities. This was necessary to achieve the overall schedule. Plans had to be developed for the precise location and alignment of laser beam ports. Upon completion of the fabrication of the aluminum target chamber in a temporary structure the 130 ton sphere was moved from the temporary construction enclosure to its final location in the target building. Prior to the installation of a concrete shield and after completion of the welding of the chamber penetrations vacuum leak checking was performed to insure the vacuum integrity of target chamber. The entire spherical chamber external surface supports a 40 cm thick reinforced concrete shield after installation in the target building. The final task is a total survey of the laser ports and the contour machining of spacer plates so that laser devices attached to these ports meet the alignment criteria.« less

S193 radiometer brightness temperature precision/accuracy for SL2 and SL3

NASA Technical Reports Server (NTRS)

Pounds, D. J.; Krishen, K.

1975-01-01

The precision and accuracy with which the S193 radiometer measured the brightness temperature of ground scenes is investigated. Estimates were derived from data collected during Skylab missions. Homogeneous ground sites were selected and S193 radiometer brightness temperature data analyzed. The precision was expressed as the standard deviation of the radiometer acquired brightness temperature. Precision was determined to be 2.40 K or better depending on mode and target temperature.

Does precision decrease with set size?

PubMed Central

Mazyar, Helga; van den Berg, Ronald; Ma, Wei Ji

2012-01-01

The brain encodes visual information with limited precision. Contradictory evidence exists as to whether the precision with which an item is encoded depends on the number of stimuli in a display (set size). Some studies have found evidence that precision decreases with set size, but others have reported constant precision. These groups of studies differed in two ways. The studies that reported a decrease used displays with heterogeneous stimuli and tasks with a short-term memory component, while the ones that reported constancy used homogeneous stimuli and tasks that did not require short-term memory. To disentangle the effects of heterogeneity and short-memory involvement, we conducted two main experiments. In Experiment 1, stimuli were heterogeneous, and we compared a condition in which target identity was revealed before the stimulus display with one in which it was revealed afterward. In Experiment 2, target identity was fixed, and we compared heterogeneous and homogeneous distractor conditions. In both experiments, we compared an optimal-observer model in which precision is constant with set size with one in which it depends on set size. We found that precision decreases with set size when the distractors are heterogeneous, regardless of whether short-term memory is involved, but not when it is homogeneous. This suggests that heterogeneity, not short-term memory, is the critical factor. In addition, we found that precision exhibits variability across items and trials, which may partly be caused by attentional fluctuations. PMID:22685337

GTCBio's Precision Medicine Conference (July 7-8, 2016 - Boston, Massachusetts, USA).

PubMed

Cole, P

2016-09-01

GTCBio's Precision Medicine Conference met this year to outline the many steps forward that precision medicine and individualized genomics has made and the challenges it still faces in technological, modeling, and standards development, interoperability and compatibility advancements, and methods of economic and societal adoption. The conference was split into four sections, 'Overcoming Challenges in the Commercialization of Precision Medicine', 'Implementation of Precision Medicine: Strategies & Technologies', 'Integrating & Interpreting Personal Genomics, Big Data, & Bioinformatics' and 'Incentivizing Precision Medicine: Regulation & Reimbursement', with this report focusing on the final two subjects. Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.

A Measurement of the Parity-Violating Asymmetry in Aluminum and its Contribution to a Measurement of the Proton's Weak Charge

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

Magee, Joshua Allen

2016-05-01

The Q_weak experiment, which ran at the Thomas Jefferson National Accelerator Facility, made a precision measurement of the proton's weak charge, Q^p_W. The weak charge is extracted via a measurement of the parity-violating asymmetry in elastic electron-proton scattering from hydrogen at low momentum transfer (Q^2=0.025 GeV^2). This result is directly related to the electroweak mixing angle, sin^2(Theta_W), a fundamental parameter in the Standard Model of particle physics. This provides a precision test sensitive to new, as yet unknown, fundamental physics. This dissertation focuses on two central corrections to the Q_weak measurement: the target window contribution and sub-percent determination of themore » electron beam polarization. The aluminum target windows contribute approximately 30% of the measured asymmetry. Removal of this background requires precise measurements of both the elastic electron-aluminum scattering rate and its parity-violating asymmetry. The results reported here are the most precise measurement of the Q_weak target dilution and asymmetry to date. The parity-violating asymmetry for the aluminum alloy was found to be 1.6174 +/- 0.0704 (stat.) +/- 0.0113 (sys.) parts-per-million. The first sub-percent precision polarization measurements made from the Hall C Moller polarimeter are also reported, with systematic uncertainties of 0.84%.« less

Tightly coupled integration of ionosphere-constrained precise point positioning and inertial navigation systems.

PubMed

Gao, Zhouzheng; Zhang, Hongping; Ge, Maorong; Niu, Xiaoji; Shen, Wenbin; Wickert, Jens; Schuh, Harald

2015-03-10

The continuity and reliability of precise GNSS positioning can be seriously limited by severe user observation environments. The Inertial Navigation System (INS) can overcome such drawbacks, but its performance is clearly restricted by INS sensor errors over time. Accordingly, the tightly coupled integration of GPS and INS can overcome the disadvantages of each individual system and together form a new navigation system with a higher accuracy, reliability and availability. Recently, ionosphere-constrained (IC) precise point positioning (PPP) utilizing raw GPS observations was proven able to improve both the convergence and positioning accuracy of the conventional PPP using ionosphere-free combined observations (LC-PPP). In this paper, a new mode of tightly coupled integration, in which the IC-PPP instead of LC-PPP is employed, is implemented to further improve the performance of the coupled system. We present the detailed mathematical model and the related algorithm of the new integration of IC-PPP and INS. To evaluate the performance of the new tightly coupled integration, data of both airborne and vehicle experiments with a geodetic GPS receiver and tactical grade inertial measurement unit are processed and the results are analyzed. The statistics show that the new approach can further improve the positioning accuracy compared with both IC-PPP and the tightly coupled integration of the conventional PPP and INS.

[Progress in precision medicine: a scientific perspective].

PubMed

Wang, B; Li, L M

2017-01-10

Precision medicine is a new strategy for disease prevention and treatment by taking into account differences in genetics, environment and lifestyles among individuals and making precise diseases classification and diagnosis, which can provide patients with personalized, targeted prevention and treatment. Large-scale population cohort studies are fundamental for precision medicine research, and could produce best evidence for precision medicine practices. Current criticisms on precision medicine mainly focus on the very small proportion of benefited patients, the neglect of social determinants for health, and the possible waste of limited medical resources. In spite of this, precision medicine is still a most hopeful research area, and would become a health care practice model in the future.

Molecular Imaging and Precision Medicine in Breast Cancer.

PubMed

Chudgar, Amy V; Mankoff, David A

2017-01-01

Precision medicine, basing treatment approaches on patient traits and specific molecular features of disease processes, has an important role in the management of patients with breast cancer as targeted therapies continue to improve. PET imaging offers noninvasive information that is complementary to traditional tissue biomarkers, including information about tumor burden, tumor metabolism, receptor status, and proliferation. Several PET agents that image breast cancer receptors can visually demonstrate the extent and heterogeneity of receptor-positive disease and help predict which tumors are likely to respond to targeted treatments. This review presents applications of PET imaging in the targeted treatment of breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

The research of radar target tracking observed information linear filter method

NASA Astrophysics Data System (ADS)

Chen, Zheng; Zhao, Xuanzhi; Zhang, Wen

2018-05-01

Aiming at the problems of low precision or even precision divergent is caused by nonlinear observation equation in radar target tracking, a new filtering algorithm is proposed in this paper. In this algorithm, local linearization is carried out on the observed data of the distance and angle respectively. Then the kalman filter is performed on the linearized data. After getting filtered data, a mapping operation will provide the posteriori estimation of target state. A large number of simulation results show that this algorithm can solve above problems effectively, and performance is better than the traditional filtering algorithm for nonlinear dynamic systems.

Nanorobot Hardware Architecture for Medical Defense

PubMed Central

Cavalcanti, Adriano; Shirinzadeh, Bijan; Zhang, Mingjun; Kretly, Luiz C.

2008-01-01

This work presents a new approach with details on the integrated platform and hardware architecture for nanorobots application in epidemic control, which should enable real time in vivo prognosis of biohazard infection. The recent developments in the field of nanoelectronics, with transducers progressively shrinking down to smaller sizes through nanotechnology and carbon nanotubes, are expected to result in innovative biomedical instrumentation possibilities, with new therapies and efficient diagnosis methodologies. The use of integrated systems, smart biosensors, and programmable nanodevices are advancing nanoelectronics, enabling the progressive research and development of molecular machines. It should provide high precision pervasive biomedical monitoring with real time data transmission. The use of nanobioelectronics as embedded systems is the natural pathway towards manufacturing methodology to achieve nanorobot applications out of laboratories sooner as possible. To demonstrate the practical application of medical nanorobotics, a 3D simulation based on clinical data addresses how to integrate communication with nanorobots using RFID, mobile phones, and satellites, applied to long distance ubiquitous surveillance and health monitoring for troops in conflict zones. Therefore, the current model can also be used to prevent and save a population against the case of some targeted epidemic disease. PMID:27879858

The National Ignition Facility: alignment from construction to shot operations

NASA Astrophysics Data System (ADS)

Burkhart, S. C.; Bliss, E.; Di Nicola, P.; Kalantar, D.; Lowe-Webb, R.; McCarville, T.; Nelson, D.; Salmon, T.; Schindler, T.; Villanueva, J.; Wilhelmsen, K.

2010-08-01

The National Ignition Facility in Livermore, California, completed it's commissioning milestone on March 10, 2009 when it fired all 192 beams at a combined energy of 1.1 MJ at 351nm. Subsequently, a target shot series from August through December of 2009 culminated in scale ignition target design experiments up to 1.2 MJ in the National Ignition Campaign. Preparations are underway through the first half of of 2010 leading to DT ignition and gain experiments in the fall of 2010 into 2011. The top level requirement for beam pointing to target of 50μm rms is the culmination of 15 years of engineering design of a stable facility, commissioning of precision alignment, and precise shot operations controls. Key design documents which guided this project were published in the mid 1990's, driving systems designs. Precision Survey methods were used throughout construction, commissioning and operations for precision placement. Rigorous commissioning processes were used to ensure and validate placement and alignment throughout commissioning and in present day operations. Accurate and rapid system alignment during operations is accomplished by an impressive controls system to align and validate alignment readiness, assuring machine safety and productive experiments.

DNA Physical Properties and Nucleosome Positions Are Major Determinants of HIV-1 Integrase Selectivity

PubMed Central

Naughtin, Monica; Haftek-Terreau, Zofia; Xavier, Johan; Meyer, Sam; Silvain, Maud; Jaszczyszyn, Yan; Levy, Nicolas; Miele, Vincent; Benleulmi, Mohamed Salah; Ruff, Marc; Parissi, Vincent; Vaillant, Cédric; Lavigne, Marc

2015-01-01

Retroviral integrases (INs) catalyse the integration of the reverse transcribed viral DNA into the host cell genome. This process is selective, and chromatin has been proposed to be a major factor regulating this step in the viral life cycle. However, the precise underlying mechanisms are still under investigation. We have developed a new in vitro integration assay using physiologically-relevant, reconstituted genomic acceptor chromatin and high-throughput determination of nucleosome positions and integration sites, in parallel. A quantitative analysis of the resulting data reveals a chromatin-dependent redistribution of the integration sites and establishes a link between integration sites and nucleosome positions. The co-activator LEDGF/p75 enhanced integration but did not modify the integration sites under these conditions. We also conducted an in cellulo genome-wide comparative study of nucleosome positions and human immunodeficiency virus type-1 (HIV-1) integration sites identified experimentally in vivo. These studies confirm a preferential integration in nucleosome-covered regions. Using a DNA mechanical energy model, we show that the physical properties of DNA probed by IN binding are important in determining IN selectivity. These novel in vitro and in vivo approaches confirm that IN has a preference for integration into a nucleosome, and suggest the existence of two levels of IN selectivity. The first depends on the physical properties of the target DNA and notably, the energy required to fit DNA into the IN catalytic pocket. The second depends on the DNA deformation associated with DNA wrapping around a nucleosome. Taken together, these results indicate that HIV-1 IN is a shape-readout DNA binding protein. PMID:26075397

Current-day precision oncology: from cancer prevention, screening, drug development, and treatment - have we fallen short of the promise?

PubMed

Morgan, Gilberto; Aftimos, Philippe; Awada, Ahmad

2016-09-01

Precision oncology has been a strategy of prevention, screening, and treatment. Although much has been invested, have the results fallen so far short of the promise? The advancement of technology and research has opened new doors, yet a variety of pitfalls are present. This review presents the successes, failures, and opportunities of precision oncology in the current landscape. The use of targeted gene sequencing and the overwhelming results of superresponders have generated much excitement and support for precision oncology from the medical community. Despite notable successes, many challenges still pave the way of precision oncology: intratumoral heterogeneity, the need for serial biopsies, availability of treatments, target prioritization, ethical issues with germline incidental findings, medical education, clinical trial design, and costs. Precision oncology shows much potential through the use of next-generation sequencing and molecular advances, but does this potential warrant the investment? There are many obstacles on the way of this technology that should make us question if the investment (both monetary and man-hours) will live up to the promise. The review aims to not criticize this technology, but to give a realistic view of where we are, especially regarding cancer treatment and prevention.

Precision Medicine in Gastrointestinal Pathology.

PubMed

Wang, David H; Park, Jason Y

2016-05-01

-Precision medicine is the promise of individualized therapy and management of patients based on their personal biology. There are now multiple global initiatives to perform whole-genome sequencing on millions of individuals. In the United States, an early program was the Million Veteran Program, and a more recent proposal in 2015 by the president of the United States is the Precision Medicine Initiative. To implement precision medicine in routine oncology care, genetic variants present in tumors need to be matched with effective clinical therapeutics. When we focus on the current state of precision medicine for gastrointestinal malignancies, it becomes apparent that there is a mixed history of success and failure. -To present the current state of precision medicine using gastrointestinal oncology as a model. We will present currently available targeted therapeutics, promising new findings in clinical genomic oncology, remaining quality issues in genomic testing, and emerging oncology clinical trial designs. -Review of the literature including clinical genomic studies on gastrointestinal malignancies, clinical oncology trials on therapeutics targeted to molecular alterations, and emerging clinical oncology study designs. -Translating our ability to sequence thousands of genes into meaningful improvements in patient survival will be the challenge for the next decade.

A pre-protective strategy for precise tumor targeting and efficient photodynamic therapy with a switchable DNA/upconversion nanocomposite.

PubMed

Yu, Zhengze; Ge, Yegang; Sun, Qiaoqiao; Pan, Wei; Wan, Xiuyan; Li, Na; Tang, Bo

2018-04-14

Tumor-specific targeting based on folic acid (FA) is one of the most common and significant approaches in cancer therapy. However, the expression of folate receptors (FRs) in normal tissues will lead to unexpected targeting and unsatisfactory therapeutic effect. To address this issue, we develop a pre-protective strategy for precise tumor targeting and efficient photodynamic therapy (PDT) using a switchable DNA/upconversion nanocomposite, which can be triggered in the acidic tumor microenvironment. The DNA/upconversion nanocomposite is composed of polyacrylic acid (PAA) coated upconversion nanoparticles (UCNPs), the surface of which is modified using FA and chlorin e6 (Ce6) functionalized DNA sequences with different lengths. Initially, FA on the shorter DNA was protected by a longer DNA to prevent the bonding to FRs on normal cells. Once reaching the acidic tumor microenvironment, C base-rich longer DNA forms a C-quadruplex, resulting in the exposure of the FA groups and the bonding of FA and FRs on cancer cell membranes to achieve precise targeting. Simultaneously, the photosensitizer chlorin e6 (Ce6) gets close to the surface of UCNPs, enabling the excitation of Ce6 to generate singlet oxygen ( 1 O 2 ) under near infrared light via Förster resonance energy transfer (FRET). In vivo experiments indicated that higher tumor targeting efficiency was achieved and the tumor growth was greatly inhibited through the pre-protective strategy.

Collaborative Genomics Study Advances Precision Oncology

Cancer.gov

A collaborative study conducted by two Office of Cancer Genomics (OCG) initiatives highlights the importance of integrating structural and functional genomics programs to improve cancer therapies, and more specifically, contribute to precision oncology treatments for children.

2D projection-based software application for mobile C-arms optimises wire placement in the proximal femur - An experimental study.

PubMed

Swartman, B; Frere, D; Wei, W; Schnetzke, M; Beisemann, N; Keil, H; Franke, J; Grützner, P A; Vetter, S Y

2017-10-01

A new software application can be used without fixed reference markers or a registration process in wire placement. The aim was to compare placement of Kirschner wires (K-wires) into the proximal femur with the software application versus the conventional method without guiding. As study hypothesis, we assumed less placement attempts, shorter procedure time and shorter fluoroscopy time using the software. The same precision inside a proximal femur bone model using the software application was premised. The software detects a K-wire within the 2D fluoroscopic image. By evaluating its direction and tip location, it superimposes a trajectory on the image, visualizing the intended direction of the K-wire. The K-wire was positioned in 20 artificial bones with the use of software by one surgeon; 20 bones served as conventional controls. A brass thumb tack was placed into the femoral head and its tip targeted with the wire. Number of placement attempts, duration of the procedure, duration of fluoroscopy time and distance to the target in a postoperative 3D scan were recorded. Compared with the conventional method, use of the application showed fewer attempts for optimal wire placement (p=0.026), shorter duration of surgery (p=0.004), shorter fluoroscopy time (p=0.024) and higher precision (p=0.018). Final wire position was achieved in the first attempt in 17 out of 20 cases with the software and in 9 out of 20 cases with the conventional method. The study hypothesis was confirmed. The new application optimised the process of K-wire placement in the proximal femur in an artificial bone model while also improving precision. Benefits lie especially in the reduction of placement attempts and reduction of fluoroscopy time under the aspect of radiation protection. The software runs on a conventional image intensifier and can therefore be easily integrated into the daily surgical routine. Copyright © 2017 Elsevier Ltd. All rights reserved.

In silico polypharmacology of natural products.

PubMed

Fang, Jiansong; Liu, Chuang; Wang, Qi; Lin, Ping; Cheng, Feixiong

2017-04-27

Natural products with polypharmacological profiles have demonstrated promise as novel therapeutics for various complex diseases, including cancer. Currently, many gaps exist in our knowledge of which compounds interact with which targets, and experimentally testing all possible interactions is infeasible. Recent advances and developments of systems pharmacology and computational (in silico) approaches provide powerful tools for exploring the polypharmacological profiles of natural products. In this review, we introduce recent progresses and advances of computational tools and systems pharmacology approaches for identifying drug targets of natural products by focusing on the development of targeted cancer therapy. We survey the polypharmacological and systems immunology profiles of five representative natural products that are being considered as cancer therapies. We summarize various chemoinformatics, bioinformatics and systems biology resources for reconstructing drug-target networks of natural products. We then review currently available computational approaches and tools for prediction of drug-target interactions by focusing on five domains: target-based, ligand-based, chemogenomics-based, network-based and omics-based systems biology approaches. In addition, we describe a practical example of the application of systems pharmacology approaches by integrating the polypharmacology of natural products and large-scale cancer genomics data for the development of precision oncology under the systems biology framework. Finally, we highlight the promise of cancer immunotherapies and combination therapies that target tumor ecosystems (e.g. clones or 'selfish' sub-clones) via exploiting the immunological and inflammatory 'side' effects of natural products in the cancer post-genomics era. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors. | Office of Cancer Genomics

Cancer.gov

We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract.

Vigilante: Ultrafast Smart Sensor for Target Recognition and Precision Tracking in a Simulated CMD Scenario

NASA Technical Reports Server (NTRS)

Uldomkesmalee, Suraphol; Suddarth, Steven C.

1997-01-01

VIGILANTE is an ultrafast smart sensor testbed for generic Automatic Target Recognition (ATR) applications with a series of capability demonstration focussed on cruise missile defense (CMD). VIGILANTE's sensor/processor architecture is based on next-generation UV/visible/IR sensors and a tera-operations per second sugar-cube processor, as well as supporting airborne vehicle. Excellent results of efficient ATR methodologies that use an eigenvectors/neural network combination and feature-based precision tracking have been demonstrated in the laboratory environment.

Methods for Multiplex Template Sampling in Digital PCR Assays

PubMed Central

Petriv, Oleh I.; Heyries, Kevin A.; VanInsberghe, Michael; Walker, David; Hansen, Carl L.

2014-01-01

The efficient use of digital PCR (dPCR) for precision copy number analysis requires high concentrations of target molecules that may be difficult or impossible to obtain from clinical samples. To solve this problem we present a strategy, called Multiplex Template Sampling (MTS), that effectively increases template concentrations by detecting multiple regions of fragmented target molecules. Three alternative assay approaches are presented for implementing MTS analysis of chromosome 21, providing a 10-fold concentration enhancement while preserving assay precision. PMID:24854517

Methods for multiplex template sampling in digital PCR assays.

PubMed

Petriv, Oleh I; Heyries, Kevin A; VanInsberghe, Michael; Walker, David; Hansen, Carl L

2014-01-01

The efficient use of digital PCR (dPCR) for precision copy number analysis requires high concentrations of target molecules that may be difficult or impossible to obtain from clinical samples. To solve this problem we present a strategy, called Multiplex Template Sampling (MTS), that effectively increases template concentrations by detecting multiple regions of fragmented target molecules. Three alternative assay approaches are presented for implementing MTS analysis of chromosome 21, providing a 10-fold concentration enhancement while preserving assay precision.

Precision Robotic Assembly Machine

ScienceCinema

None

2017-12-09

The world's largest laser system is the National Ignition Facility (NIF), located at Lawrence Livermore National Laboratory. NIF's 192 laser beams are amplified to extremely high energy, and then focused onto a tiny target about the size of a BB, containing frozen hydrogen gas. The target must be perfectly machined to incredibly demanding specifications. The Laboratory's scientists and engineers have developed a device called the "Precision Robotic Assembly Machine" for this purpose. Its unique design won a prestigious R&D-100 award from R&D Magazine.

Closed-Loop Aeromaneuvering for a Mars Precision Landing

NASA Technical Reports Server (NTRS)

Smith, Roy; Boussalis, Dhemetrios; Hadaegh, Fred Y.

1997-01-01

Controlled aeromaneuvering is considered as a means of achieving a precisely targeted landing on Mars. This paper presents a preliminary study of the control issues. The candidate vehicle is the existing Mars Pathfinder augmented with roll thrusters and a center of mass offset actuator. These allow control of both bank angle and lift force, giving the ability to control the range and cross-track during the aeromaneuvering entry. A preliminary control system structure is proposed and a design simulation illustrates significant targeting improvement under closed-loop control.

The research and realization of digital management platform for ultra-precision optical elements within life-cycle

NASA Astrophysics Data System (ADS)

Wang, Juan; Wang, Jian; Li, Lijuan; Zhou, Kun

2014-08-01

In order to solve the information fusion, process integration, collaborative design and manufacturing for ultra-precision optical elements within life-cycle management, this paper presents a digital management platform which is based on product data and business processes by adopting the modern manufacturing technique, information technique and modern management technique. The architecture and system integration of the digital management platform are discussed in this paper. The digital management platform can realize information sharing and interaction for information-flow, control-flow and value-stream from user's needs to offline in life-cycle, and it can also enhance process control, collaborative research and service ability of ultra-precision optical elements.

Radiation Budget Instrument (RBI) for JPSS-2

NASA Technical Reports Server (NTRS)

Georgieva, Elena; Priestley, Kory; Dunn, Barry; Cageao, Richard; Barki, Anum; Osmundsen, Jim; Turczynski, Craig; Abedin, Nurul

2015-01-01

Radiation Budget Instrument (RBI) will be one of five instruments flying aboard the JPSS-2 spacecraft, a polar-orbiting sun-synchronous satellite in Low Earth Orbit. RBI is a passive remote sensing instrument that will follow the successful legacy of the Clouds and Earth's Radiant Energy System (CERES) instruments to make measurement of Earth's short and longwave radiation budget. The goal of RBI is to provide an independent measurement of the broadband reflected solar radiance and Earth's emitted thermal radiance by using three spectral bands (Shortwave, Longwave, and Total) that will have the same overlapped point spread function (PSF) footprint on Earth. To ensure precise NIST-traceable calibration in space the RBI sensor is designed to use a visible calibration target (VCT), a solar calibration target (SCT), and an infrared calibration target (ICT) containing phase change cells (PCC) to enable on-board temperature calibration. The VCT is a thermally controlled integrating sphere with space grade Spectralon covering the inner surface. Two sides of the sphere will have fiber-coupled laser diodes in the UV to IR wavelength region. An electrical substitution radiometer on the integrating sphere will monitor the long term stability of the sources and the possible degradation of the Spectralon in space. In addition the radiometric calibration operations will use the Spectralon diffusers of the SCT to provide accurate measurements of Solar degradation. All those stable on-orbit references will ensure that calibration stability is maintained over the RBI sensor lifetime. For the preflight calibration the RBI will view five calibration sources - two integrating spheres and three CrIS (Cross-track Infrared Sounder ) -like blackbodies whose outputs will be validated with NIST calibration approach. Thermopile are the selected detectors for the RBI. The sensor has a requirement to perform lunar calibration in addition to solar calibration in space in a way similar to CERES instruments approach. To monitor climate change and to get stable and traceable results, it is critical to assure stable calibration over instrument lifetime.

Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

NASA Astrophysics Data System (ADS)

Gutierrez, Alonso Navar

2007-12-01

Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the feasibility of delivering a simultaneously integrated subvolume boost to canine nasal tumors and was found to dramatically increase estimated 1-year tumor control probability (TCP) without increasing the dose to the eyes, so as to preserve vision, and to the brain, so as to prevent neuropathy.

The Photogrammetry Cube

NASA Technical Reports Server (NTRS)

2008-01-01

We can determine distances between objects and points of interest in 3-D space to a useful degree of accuracy from a set of camera images by using multiple camera views and reference targets in the camera s field of view (FOV). The core of the software processing is based on the previously developed foreign-object debris vision trajectory software (see KSC Research and Technology 2004 Annual Report, pp. 2 5). The current version of this photogrammetry software includes the ability to calculate distances between any specified point pairs, the ability to process any number of reference targets and any number of camera images, user-friendly editing features, including zoom in/out, translate, and load/unload, routines to help mark reference points with a Find function, while comparing them with the reference point database file, and a comprehensive output report in HTML format. In this system, scene reference targets are replaced by a photogrammetry cube whose exterior surface contains multiple predetermined precision 2-D targets. Precise measurement of the cube s 2-D targets during the fabrication phase eliminates the need for measuring 3-D coordinates of reference target positions in the camera's FOV, using for example a survey theodolite or a Faroarm. Placing the 2-D targets on the cube s surface required the development of precise machining methods. In response, 2-D targets were embedded into the surface of the cube and then painted black for high contrast. A 12-inch collapsible cube was developed for room-size scenes. A 3-inch, solid, stainless-steel photogrammetry cube was also fabricated for photogrammetry analysis of small objects.

The emerging potential for network analysis to inform precision cancer medicine.

PubMed

Ozturk, Kivilcim; Dow, Michelle; Carlin, Daniel E; Bejar, Rafael; Carter, Hannah

2018-06-14

Precision cancer medicine promises to tailor clinical decisions to patients using genomic information. Indeed, successes of drugs targeting genetic alterations in tumors, such as imatinib that targets BCR-ABL in chronic myelogenous leukemia, have demonstrated the power of this approach. However biological systems are complex, and patients may differ not only by the specific genetic alterations in their tumor, but by more subtle interactions among such alterations. Systems biology and more specifically, network analysis, provides a framework for advancing precision medicine beyond clinical actionability of individual mutations. Here we discuss applications of network analysis to study tumor biology, early methods for N-of-1 tumor genome analysis and the path for such tools to the clinic. Copyright © 2018. Published by Elsevier Ltd.

Molecular Diagnostics for Precision Medicine in Colorectal Cancer: Current Status and Future Perspective

PubMed Central

Chen, Guoli; Yang, Zhaohai; Eshleman, James R.; Netto, George J.

2016-01-01

Precision medicine, a concept that has recently emerged and has been widely discussed, emphasizes tailoring medical care to individuals largely based on information acquired from molecular diagnostic testing. As a vital aspect of precision cancer medicine, targeted therapy has been proven to be efficacious and less toxic for cancer treatment. Colorectal cancer (CRC) is one of the most common cancers and among the leading causes for cancer related deaths in the United States and worldwide. By far, CRC has been one of the most successful examples in the field of precision cancer medicine, applying molecular tests to guide targeted therapy. In this review, we summarize the current guidelines for anti-EGFR therapy, revisit the roles of pathologists in an era of precision cancer medicine, demonstrate the transition from traditional “one test-one drug” assays to multiplex assays, especially by using next-generation sequencing platforms in the clinical diagnostic laboratories, and discuss the future perspectives of tumor heterogeneity associated with anti-EGFR resistance and immune checkpoint blockage therapy in CRC. PMID:27699178

High precision triangular waveform generator

DOEpatents

Mueller, Theodore R.

1983-01-01

An ultra-linear ramp generator having separately programmable ascending and descending ramp rates and voltages is provided. Two constant current sources provide the ramp through an integrator. Switching of the current at current source inputs rather than at the integrator input eliminates switching transients and contributes to the waveform precision. The triangular waveforms produced by the waveform generator are characterized by accurate reproduction and low drift over periods of several hours. The ascending and descending slopes are independently selectable.

High-precision triangular-waveform generator

DOEpatents

Mueller, T.R.

1981-11-14

An ultra-linear ramp generator having separately programmable ascending and decending ramp rates and voltages is provided. Two constant current sources provide the ramp through an integrator. Switching of the current at current source inputs rather than at the integrator input eliminates switching transients and contributes to the waveform precision. The triangular waveforms produced by the waveform generator are characterized by accurate reproduction and low drift over periods of several hours. The ascending and descending slopes are independently selectable.

Precision mechatronics based on high-precision measuring and positioning systems and machines

NASA Astrophysics Data System (ADS)

Jäger, Gerd; Manske, Eberhard; Hausotte, Tino; Mastylo, Rostyslav; Dorozhovets, Natalja; Hofmann, Norbert

2007-06-01

Precision mechatronics is defined in the paper as the science and engineering of a new generation of high precision systems and machines. Nanomeasuring and nanopositioning engineering represents important fields of precision mechatronics. The nanometrology is described as the today's limit of the precision engineering. The problem, how to design nanopositioning machines with uncertainties as small as possible will be discussed. The integration of several optical and tactile nanoprobes makes the 3D-nanopositioning machine suitable for various tasks, such as long range scanning probe microscopy, mask and wafer inspection, nanotribology, nanoindentation, free form surface measurement as well as measurement of microoptics, precision molds, microgears, ring gauges and small holes.

Infrared small target detection based on directional zero-crossing measure

NASA Astrophysics Data System (ADS)

Zhang, Xiangyue; Ding, Qinghai; Luo, Haibo; Hui, Bin; Chang, Zheng; Zhang, Junchao

2017-12-01

Infrared small target detection under complex background and low signal-to-clutter ratio (SCR) condition is of great significance to the development on precision guidance and infrared surveillance. In order to detect targets precisely and extract targets from intricate clutters effectively, a detection method based on zero-crossing saliency (ZCS) map is proposed. The original map is first decomposed into different first-order directional derivative (FODD) maps by using FODD filters. Then the ZCS map is obtained by fusing all directional zero-crossing points. At last, an adaptive threshold is adopted to segment targets from the ZCS map. Experimental results on a series of images show that our method is effective and robust for detection under complex backgrounds. Moreover, compared with other five state-of-the-art methods, our method achieves better performance in terms of detection rate, SCR gain and background suppression factor.

Precision Medicine and PET/Computed Tomography: Challenges and Implementation.

PubMed

Subramaniam, Rathan M

2017-01-01

Precision Medicine is about selecting the right therapy for the right patient, at the right time, specific to the molecular targets expressed by disease or tumors, in the context of patient's environment and lifestyle. Some of the challenges for delivery of precision medicine in oncology include biomarkers for patient selection for enrichment-precision diagnostics, mapping out tumor heterogeneity that contributes to therapy failures, and early therapy assessment to identify resistance to therapies. PET/computed tomography offers solutions in these important areas of challenges and facilitates implementation of precision medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Problems, challenges and promises: perspectives on precision medicine.

PubMed

Duffy, David J

2016-05-01

The 'precision medicine (systems medicine)' concept promises to achieve a shift to future healthcare systems with a more proactive and predictive approach to medicine, where the emphasis is on disease prevention rather than the treatment of symptoms. The individualization of treatment for each patient will be at the centre of this approach, with all of a patient's medical data being computationally integrated and accessible. Precision medicine is being rapidly embraced by biomedical researchers, pioneering clinicians and scientific funding programmes in both the European Union (EU) and USA. Precision medicine is a key component of both Horizon 2020 (the EU Framework Programme for Research and Innovation) and the White House's Precision Medicine Initiative. Precision medicine promises to revolutionize patient care and treatment decisions. However, the participants in precision medicine are faced with a considerable central challenge. Greater volumes of data from a wider variety of sources are being generated and analysed than ever before; yet, this heterogeneous information must be integrated and incorporated into personalized predictive models, the output of which must be intelligible to non-computationally trained clinicians. Drawing primarily from the field of 'oncology', this article will introduce key concepts and challenges of precision medicine and some of the approaches currently being implemented to overcome these challenges. Finally, this article also covers the criticisms of precision medicine overpromising on its potential to transform patient care. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Precision CW laser automatic tracking system investigated

NASA Technical Reports Server (NTRS)

Lang, K. T.; Lucy, R. F.; Mcgann, E. J.; Peters, C. J.

1966-01-01

Precision laser tracker capable of tracking a low acceleration target to an accuracy of about 20 microradians rms is being constructed and tested. This laser tracking has the advantage of discriminating against other optical sources and the capability of simultaneously measuring range.

Large format focal plane array integration with precision alignment, metrology and accuracy capabilities

NASA Astrophysics Data System (ADS)

Neumann, Jay; Parlato, Russell; Tracy, Gregory; Randolph, Max

2015-09-01

Focal plane alignment for large format arrays and faster optical systems require enhanced precision methodology and stability over temperature. The increase in focal plane array size continues to drive the alignment capability. Depending on the optical system, the focal plane flatness of less than 25μm (.001") is required over transition temperatures from ambient to cooled operating temperatures. The focal plane flatness requirement must also be maintained in airborne or launch vibration environments. This paper addresses the challenge of the detector integration into the focal plane module and housing assemblies, the methodology to reduce error terms during integration and the evaluation of thermal effects. The driving factors influencing the alignment accuracy include: datum transfers, material effects over temperature, alignment stability over test, adjustment precision and traceability to NIST standard. The FPA module design and alignment methodology reduces the error terms by minimizing the measurement transfers to the housing. In the design, the proper material selection requires matched coefficient of expansion materials minimizes both the physical shift over temperature as well as lowering the stress induced into the detector. When required, the co-registration of focal planes and filters can achieve submicron relative positioning by applying precision equipment, interferometry and piezoelectric positioning stages. All measurements and characterizations maintain traceability to NIST standards. The metrology characterizes the equipment's accuracy, repeatability and precision of the measurements.

Targeted Proteomics Approach for Precision Plant Breeding.

PubMed

Chawade, Aakash; Alexandersson, Erik; Bengtsson, Therese; Andreasson, Erik; Levander, Fredrik

2016-02-05

Selected reaction monitoring (SRM) is a targeted mass spectrometry technique that enables precise quantitation of hundreds of peptides in a single run. This technique provides new opportunities for multiplexed protein biomarker measurements. For precision plant breeding, DNA-based markers have been used extensively, but the potential of protein biomarkers has not been exploited. In this work, we developed an SRM marker panel with assays for 104 potato (Solanum tuberosum) peptides selected using univariate and multivariate statistics. Thereafter, using random forest classification, the prediction markers were identified for Phytopthora infestans resistance in leaves, P. infestans resistance in tubers, and plant yield in potato leaf secretome samples. The results suggest that the marker panel has the predictive potential for three traits, two of which have no commercial DNA markers so far. Furthermore, the marker panel was also tested and found to be applicable to potato clones not used during the marker development. The proposed workflow is thus a proof-of-concept for targeted proteomics as an efficient readout in accelerated breeding for complex and agronomically important traits.

Linking rare and common disease: mapping clinical disease-phenotypes to ontologies in therapeutic target validation.

PubMed

Sarntivijai, Sirarat; Vasant, Drashtti; Jupp, Simon; Saunders, Gary; Bento, A Patrícia; Gonzalez, Daniel; Betts, Joanna; Hasan, Samiul; Koscielny, Gautier; Dunham, Ian; Parkinson, Helen; Malone, James

2016-01-01

The Centre for Therapeutic Target Validation (CTTV - https://www.targetvalidation.org/) was established to generate therapeutic target evidence from genome-scale experiments and analyses. CTTV aims to support the validity of therapeutic targets by integrating existing and newly-generated data. Data integration has been achieved in some resources by mapping metadata such as disease and phenotypes to the Experimental Factor Ontology (EFO). Additionally, the relationship between ontology descriptions of rare and common diseases and their phenotypes can offer insights into shared biological mechanisms and potential drug targets. Ontologies are not ideal for representing the sometimes associated type relationship required. This work addresses two challenges; annotation of diverse big data, and representation of complex, sometimes associated relationships between concepts. Semantic mapping uses a combination of custom scripting, our annotation tool 'Zooma', and expert curation. Disease-phenotype associations were generated using literature mining on Europe PubMed Central abstracts, which were manually verified by experts for validity. Representation of the disease-phenotype association was achieved by the Ontology of Biomedical AssociatioN (OBAN), a generic association representation model. OBAN represents associations between a subject and object i.e., disease and its associated phenotypes and the source of evidence for that association. The indirect disease-to-disease associations are exposed through shared phenotypes. This was applied to the use case of linking rare to common diseases at the CTTV. EFO yields an average of over 80% of mapping coverage in all data sources. A 42% precision is obtained from the manual verification of the text-mined disease-phenotype associations. This results in 1452 and 2810 disease-phenotype pairs for IBD and autoimmune disease and contributes towards 11,338 rare diseases associations (merged with existing published work [Am J Hum Genet 97:111-24, 2015]). An OBAN result file is downloadable at http://sourceforge.net/p/efo/code/HEAD/tree/trunk/src/efoassociations/. Twenty common diseases are linked to 85 rare diseases by shared phenotypes. A generalizable OBAN model for association representation is presented in this study. Here we present solutions to large-scale annotation-ontology mapping in the CTTV knowledge base, a process for disease-phenotype mining, and propose a generic association model, 'OBAN', as a means to integrate disease using shared phenotypes. EFO is released monthly and available for download at http://www.ebi.ac.uk/efo/.

Spike timing precision of neuronal circuits.

PubMed

Kilinc, Deniz; Demir, Alper

2018-06-01

Spike timing is believed to be a key factor in sensory information encoding and computations performed by the neurons and neuronal circuits. However, the considerable noise and variability, arising from the inherently stochastic mechanisms that exist in the neurons and the synapses, degrade spike timing precision. Computational modeling can help decipher the mechanisms utilized by the neuronal circuits in order to regulate timing precision. In this paper, we utilize semi-analytical techniques, which were adapted from previously developed methods for electronic circuits, for the stochastic characterization of neuronal circuits. These techniques, which are orders of magnitude faster than traditional Monte Carlo type simulations, can be used to directly compute the spike timing jitter variance, power spectral densities, correlation functions, and other stochastic characterizations of neuronal circuit operation. We consider three distinct neuronal circuit motifs: Feedback inhibition, synaptic integration, and synaptic coupling. First, we show that both the spike timing precision and the energy efficiency of a spiking neuron are improved with feedback inhibition. We unveil the underlying mechanism through which this is achieved. Then, we demonstrate that a neuron can improve on the timing precision of its synaptic inputs, coming from multiple sources, via synaptic integration: The phase of the output spikes of the integrator neuron has the same variance as that of the sample average of the phases of its inputs. Finally, we reveal that weak synaptic coupling among neurons, in a fully connected network, enables them to behave like a single neuron with a larger membrane area, resulting in an improvement in the timing precision through cooperation.

Pricise Target Geolocation Based on Integeration of Thermal Video Imagery and Rtk GPS in Uavs

NASA Astrophysics Data System (ADS)

Hosseinpoor, H. R.; Samadzadegan, F.; Dadras Javan, F.

2015-12-01

There are an increasingly large number of uses for Unmanned Aerial Vehicles (UAVs) from surveillance, mapping and target geolocation. However, most of commercial UAVs are equipped with low-cost navigation sensors such as C/A code GPS and a low-cost IMU on board, allowing a positioning accuracy of 5 to 10 meters. This low accuracy which implicates that it cannot be used in applications that require high precision data on cm-level. This paper presents a precise process for geolocation of ground targets based on thermal video imagery acquired by small UAV equipped with RTK GPS. The geolocation data is filtered using a linear Kalman filter, which provides a smoothed estimate of target location and target velocity. The accurate geo-locating of targets during image acquisition is conducted via traditional photogrammetric bundle adjustment equations using accurate exterior parameters achieved by on board IMU and RTK GPS sensors and Kalman filtering and interior orientation parameters of thermal camera from pre-flight laboratory calibration process.

Analysis of Photogrammetry Data from ISIM Mockup

NASA Technical Reports Server (NTRS)

Nowak, Maria; Hill, Mike

2007-01-01

During ground testing of the Integrated Science Instrument Module (ISIM) for the James Webb Space Telescope (JWST), the ISIM Optics group plans to use a Photogrammetry Measurement System for cryogenic calibration of specific target points on the ISIM composite structure and Science Instrument optical benches and other GSE equipment. This testing will occur in the Space Environmental Systems (SES) chamber at Goddard Space Flight Center. Close range photogrammetry is a 3 dimensional metrology system using triangulation to locate custom targets in 3 coordinates via a collection of digital photographs taken from various locations and orientations. These photos are connected using coded targets, special targets that are recognized by the software and can thus correlate the images to provide a 3 dimensional map of the targets, and scaled via well calibrated scale bars. Photogrammetry solves for the camera location and coordinates of the targets simultaneously through the bundling procedure contained in the V-STARS software, proprietary software owned by Geodetic Systems Inc. The primary objectives of the metrology performed on the ISIM mock-up were (1) to quantify the accuracy of the INCA3 photogrammetry camera on a representative full scale version of the ISIM structure at ambient temperature by comparing the measurements obtained with this camera to measurements using the Leica laser tracker system and (2), empirically determine the smallest increment of target position movement that can be resolved by the PG camera in the test setup, i.e., precision, or resolution. In addition, the geometrical details of the test setup defined during the mockup testing, such as target locations and camera positions, will contribute to the final design of the photogrammetry system to be used on the ISIM Flight Structure.

Target Discovery for Precision Medicine Using High-Throughput Genome Engineering.

PubMed

Guo, Xinyi; Chitale, Poonam; Sanjana, Neville E

2017-01-01

Over the past few years, programmable RNA-guided nucleases such as the CRISPR/Cas9 system have ushered in a new era of precision genome editing in diverse model systems and in human cells. Functional screens using large libraries of RNA guides can interrogate a large hypothesis space to pinpoint particular genes and genetic elements involved in fundamental biological processes and disease-relevant phenotypes. Here, we review recent high-throughput CRISPR screens (e.g. loss-of-function, gain-of-function, and targeting noncoding elements) and highlight their potential for uncovering novel therapeutic targets, such as those involved in cancer resistance to small molecular drugs and immunotherapies, tumor evolution, infectious disease, inborn genetic disorders, and other therapeutic challenges.

Research on the method of precise alignment technology of atmospheric laser communication

NASA Astrophysics Data System (ADS)

Chen, Wen-jian; Gao, Wei; Duan, Yuan-yuan; Ma, Shi-wei; Chen, Jian

2016-10-01

Atmosphere laser communication takes advantage of laser as the carrier transmitting the voice, data, and image information in the atmosphere. Because of its high reliability, strong anti-interference ability, the advantages of easy installation, it has great potential and development space in the communications field. In the process of establish communication, the capture, targeting and tracking of the communication signal is the key technology. This paper introduce a method of targeting the signal spot in the process of atmosphere laser communication, which through the way of making analog signal addition and subtraction directly and normalized to obtain the target azimuth information to drive the servo system to achieve precise alignment of tracking.

The precision problem in conservation and restoration

USGS Publications Warehouse

Hiers, J. Kevin; Jackson, Stephen T.; Hobbs, Richard J.; Bernhardt, Emily S.; Valentine, Leonie E.

2016-01-01

Within the varied contexts of environmental policy, conservation of imperilled species populations, and restoration of damaged habitats, an emphasis on idealized optimal conditions has led to increasingly specific targets for management. Overly-precise conservation targets can reduce habitat variability at multiple scales, with unintended consequences for future ecological resilience. We describe this dilemma in the context of endangered species management, stream restoration, and climate-change adaptation. Inappropriate application of conservation targets can be expensive, with marginal conservation benefit. Reduced habitat variability can limit options for managers trying to balance competing objectives with limited resources. Conservation policies should embrace habitat variability, expand decision-space appropriately, and support adaptation to local circumstances to increase ecological resilience in a rapidly changing world.

Ontological modelling of knowledge management for human-machine integrated design of ultra-precision grinding machine

NASA Astrophysics Data System (ADS)

Hong, Haibo; Yin, Yuehong; Chen, Xing

2016-11-01

Despite the rapid development of computer science and information technology, an efficient human-machine integrated enterprise information system for designing complex mechatronic products is still not fully accomplished, partly because of the inharmonious communication among collaborators. Therefore, one challenge in human-machine integration is how to establish an appropriate knowledge management (KM) model to support integration and sharing of heterogeneous product knowledge. Aiming at the diversity of design knowledge, this article proposes an ontology-based model to reach an unambiguous and normative representation of knowledge. First, an ontology-based human-machine integrated design framework is described, then corresponding ontologies and sub-ontologies are established according to different purposes and scopes. Second, a similarity calculation-based ontology integration method composed of ontology mapping and ontology merging is introduced. The ontology searching-based knowledge sharing method is then developed. Finally, a case of human-machine integrated design of a large ultra-precision grinding machine is used to demonstrate the effectiveness of the method.

Research and development of a control system for multi axis cooperative motion based on PMAC

NASA Astrophysics Data System (ADS)

Guo, Xiao-xiao; Dong, Deng-feng; Zhou, Wei-hu

2017-10-01

Based on Programmable Multi-axes Controller (PMAC), a design of a multi axis motion control system for the simulator of spatial targets' dynamic optical properties is proposed. According to analysis the properties of spatial targets' simulator motion control system, using IPC as the main control layer, TurboPMAC2 as the control layer to meet coordinated motion control, data acquisition and analog output. A simulator using 5 servomotors which is connected with speed reducers to drive the output axis was implemented to simulate the motion of both the sun and the space target. Based on PMAC using PID and a notch filter algorithm, negative feedback, the speed and acceleration feed forward algorithm to satisfy the axis' requirements of the good stability and high precision at low speeds. In the actual system, it shows that the velocity precision is higher than 0.04 s ° and the precision of repetitive positioning is better than 0.006° when each axis is at a low-speed. Besides, the system achieves the control function of multi axis coordinated motion. The design provides an important technical support for detecting spatial targets, also promoting the theoretical research.

Adeno-associated virus Rep-mediated targeting of integrase-defective retroviral vector DNA circles into human chromosome 19

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

Huang, Shuohao; Kawabe, Yoshinori; Ito, Akira

2012-01-06

Highlights: Black-Right-Pointing-Pointer Adeno-associated virus (AAV) is capable of targeted integration in human cells. Black-Right-Pointing-Pointer Integrase-defective retroviral vector (IDRV) enables a circular DNA delivery. Black-Right-Pointing-Pointer A targeted integration system of IDRV DNA using the AAV integration mechanism. Black-Right-Pointing-Pointer Targeted IDRV integration ameliorates the safety concerns for retroviral vectors. -- Abstract: Retroviral vectors have been employed in clinical trials for gene therapy owing to their relative large packaging capacity, alterable cell tropism, and chromosomal integration for stable transgene expression. However, uncontrollable integrations of transgenes are likely to cause safety issues, such as insertional mutagenesis. A targeted transgene integration system for retroviral vectors,more » therefore, is a straightforward way to address the insertional mutagenesis issue. Adeno-associated virus (AAV) is the only known virus capable of targeted integration in human cells. In the presence of AAV Rep proteins, plasmids possessing the p5 integration efficiency element (p5IEE) can be integrated into the AAV integration site (AAVS1) in the human genome. In this report, we describe a system that can target the circular DNA derived from non-integrating retroviral vectors to the AAVS1 site by utilizing the Rep/p5IEE integration mechanism. Our results showed that after G418 selection 30% of collected clones had retroviral DNA targeted at the AAVS1 site.« less

Relative receiver autonomous integrity monitoring for future GNSS-based aircraft navigation

NASA Astrophysics Data System (ADS)

Gratton, Livio Rafael

The Global Positioning System (GPS) has enabled reliable, safe, and practical aircraft positioning for en-route and non-precision phases of flight for more than a decade. Intense research is currently devoted to extending the use of Global Navigation Satellite Systems (GNSS), including GPS, to precision approach and landing operations. In this context, this work is focused on the development, analysis, and verification of the concept of Relative Receiver Autonomous Integrity Monitoring (RRAIM) and its potential applications to precision approach navigation. RRAIM fault detection algorithms are developed, and associated mathematical bounds on position error are derived. These are investigated as possible solutions to some current key challenges in precision approach navigation, discussed below. Augmentation systems serving continent-size areas (like the Wide Area Augmentation System or WAAS) allow certain precision approach operations within the covered region. More and better satellites, with dual frequency capabilities, are expected to be in orbit in the mid-term future, which will potentially allow WAAS-like capabilities worldwide with a sparse ground station network. Two main challenges in achieving this goal are (1) ensuring that navigation fault detection functions are fast enough to alert worldwide users of hazardously misleading information, and (2) minimizing situations in which navigation is unavailable because the user's local satellite geometry is insufficient for safe position estimation. Local augmentation systems (implemented at individual airports, like the Local Area Augmentation System or LAAS) have the potential to allow precision approach and landing operations by providing precise corrections to user-satellite range measurements. An exception to these capabilities arises during ionospheric storms (caused by solar activity), when hazardous situations can exist with residual range errors several orders of magnitudes higher than nominal. Until dual frequency civil GPS signals are available, the ability to provide integrity during ionospheric storms, without excessive loss of availability is a major challenge. For all users, with or without augmentation, some situations cause short duration losses of satellites in view. Two examples are aircraft banking during turns and ionospheric scintillation. The loss of range signals can translate into gaps in good satellite geometry, and the resulting challenge is to ensure navigation continuity by bridging these gaps, while simultaneously maintaining high integrity. It is shown that the RRAIM methods developed in this research can be applied to mitigate each of these obstacles to safe and reliable precision aircraft navigation.

Development of low-altitude remote sensing systems for crop production management

USDA-ARS?s Scientific Manuscript database

Precision agriculture accounts for within-field variability for targeted treatment rather than uniform treatment of an entire field. Precision agriculture is built on agricultural mechanization and state-of-the-art technologies of geographical information systems (GIS), global positioning systems (G...

Tightly Coupled Integration of Ionosphere-Constrained Precise Point Positioning and Inertial Navigation Systems

PubMed Central

Gao, Zhouzheng; Zhang, Hongping; Ge, Maorong; Niu, Xiaoji; Shen, Wenbin; Wickert, Jens; Schuh, Harald

2015-01-01

The continuity and reliability of precise GNSS positioning can be seriously limited by severe user observation environments. The Inertial Navigation System (INS) can overcome such drawbacks, but its performance is clearly restricted by INS sensor errors over time. Accordingly, the tightly coupled integration of GPS and INS can overcome the disadvantages of each individual system and together form a new navigation system with a higher accuracy, reliability and availability. Recently, ionosphere-constrained (IC) precise point positioning (PPP) utilizing raw GPS observations was proven able to improve both the convergence and positioning accuracy of the conventional PPP using ionosphere-free combined observations (LC-PPP). In this paper, a new mode of tightly coupled integration, in which the IC-PPP instead of LC-PPP is employed, is implemented to further improve the performance of the coupled system. We present the detailed mathematical model and the related algorithm of the new integration of IC-PPP and INS. To evaluate the performance of the new tightly coupled integration, data of both airborne and vehicle experiments with a geodetic GPS receiver and tactical grade inertial measurement unit are processed and the results are analyzed. The statistics show that the new approach can further improve the positioning accuracy compared with both IC-PPP and the tightly coupled integration of the conventional PPP and INS. PMID:25763647

Highlights from the WIN 2017 Symposium, 26-27 June 2017, Paris, France: 'Expediting Global Innovation in Precision Cancer Medicine'.

PubMed

Davies, Will

2017-01-01

The Worldwide Innovative Networking (WIN) symposium brings together representatives from academic institutions, pharmaceutical partners, technology companies and charitable organisations from across the globe for an annual summit, discussing ongoing research and the latest developments in precision medicine. Now, in its seventh year, the aims of the WIN consortium's annual meeting, to foster communication and collaboration between members and deliver clinical trial results that improve the care and outcomes of patients are presented in open dialogue to encourage debate and discussion. This year, the meeting was held in Paris, France from 26-27 June and consisted of six plenary sessions, two debates, and poster presentations from attendees. In keeping with the consortium's goals, presentations and posters focused on the development and integration of new therapies and updates in genome-based medicine. Among the presentations at this year's meeting, much of the focus fell on design and implementation of new designs of clinical trials, moving away from decades-long assessments of thousands of patients towards a nimble, adaptive design fitting the edicts of personalised medicine and delving into greater depths within genomic data, ranging beyond genome analysis to chart new targets in ligandomics, proteogenomics and more.

Programmable single-cell mammalian biocomputers.

PubMed

Ausländer, Simon; Ausländer, David; Müller, Marius; Wieland, Markus; Fussenegger, Martin

2012-07-05

Synthetic biology has advanced the design of standardized control devices that program cellular functions and metabolic activities in living organisms. Rational interconnection of these synthetic switches resulted in increasingly complex designer networks that execute input-triggered genetic instructions with precision, robustness and computational logic reminiscent of electronic circuits. Using trigger-controlled transcription factors, which independently control gene expression, and RNA-binding proteins that inhibit the translation of transcripts harbouring specific RNA target motifs, we have designed a set of synthetic transcription–translation control devices that could be rewired in a plug-and-play manner. Here we show that these combinatorial circuits integrated a two-molecule input and performed digital computations with NOT, AND, NAND and N-IMPLY expression logic in single mammalian cells. Functional interconnection of two N-IMPLY variants resulted in bitwise intracellular XOR operations, and a combinatorial arrangement of three logic gates enabled independent cells to perform programmable half-subtractor and half-adder calculations. Individual mammalian cells capable of executing basic molecular arithmetic functions isolated or coordinated to metabolic activities in a predictable, precise and robust manner may provide new treatment strategies and bio-electronic interfaces in future gene-based and cell-based therapies.

[Application of molecular diagnostic techniques in precision medicine of personalized treatment for colorectal cancer].

PubMed

Fu, Ji; Lin, Guole

2016-01-01

Precision medicine is to customize the treatment options for individual patient based on the personal genome information. Colorectal cancer (CRC) is one of the most common cancer worldwide. Molecular heterogeneity of CRC, which includes the MSI phenotype, hypermutation phenotype, and their relationship with clinical preferences, is believed to be one of the main factors responsible for the considerable variability in treatment response. The development of powerful next-generation sequencing (NGS) technologies allows us to further understand the biological behavior of colorectal cancer, and to analyze the prognosis and chemotherapeutic drug reactions by molecular diagnostic techniques, which can guide the clinical treatment. This paper will introduce the new findings in this field. Meanwhile we integrate the new progress of key pathways including EGFR, RAS, PI3K/AKT and VEGF, and the experience in selective patients through associated molecular diagnostic screening who gain better efficacy after target therapy. The technique for detecting circulating tumor DNA (ctDNA) is introduced here as well, which can identify patients with high risk for recurrence, and demonstrate the risk of chemotherapy resistance. Mechanism of tumor drug resistance may be revealed by dynamic observation of gene alteration during treatment.

Computational Insight into Protein Tyrosine Phosphatase 1B Inhibition: A Case Study of the Combined Ligand- and Structure-Based Approach.

PubMed

Zhang, Xiangyu; Jiang, Hailun; Li, Wei; Wang, Jian; Cheng, Maosheng

2017-01-01

Protein tyrosine phosphatase 1B (PTP1B) is an attractive target for treating cancer, obesity, and type 2 diabetes. In our work, the way of combined ligand- and structure-based approach was applied to analyze the characteristics of PTP1B enzyme and its interaction with competitive inhibitors. Firstly, the pharmacophore model of PTP1B inhibitors was built based on the common feature of sixteen compounds. It was found that the pharmacophore model consisted of five chemical features: one aromatic ring (R) region, two hydrophobic (H) groups, and two hydrogen bond acceptors (A). To further elucidate the binding modes of these inhibitors with PTP1B active sites, four docking programs (AutoDock 4.0, AutoDock Vina 1.0, standard precision (SP) Glide 9.7, and extra precision (XP) Glide 9.7) were used. The characteristics of the active sites were then described by the conformations of the docking results. In conclusion, a combination of various pharmacophore features and the integration information of structure activity relationship (SAR) can be used to design novel potent PTP1B inhibitors.

Implementation and results of an integrated data quality assurance protocol in a randomized controlled trial in Uttar Pradesh, India.

PubMed

Gass, Jonathon D; Misra, Anamika; Yadav, Mahendra Nath Singh; Sana, Fatima; Singh, Chetna; Mankar, Anup; Neal, Brandon J; Fisher-Bowman, Jennifer; Maisonneuve, Jenny; Delaney, Megan Marx; Kumar, Krishan; Singh, Vinay Pratap; Sharma, Narender; Gawande, Atul; Semrau, Katherine; Hirschhorn, Lisa R

2017-09-07

There are few published standards or methodological guidelines for integrating Data Quality Assurance (DQA) protocols into large-scale health systems research trials, especially in resource-limited settings. The BetterBirth Trial is a matched-pair, cluster-randomized controlled trial (RCT) of the BetterBirth Program, which seeks to improve quality of facility-based deliveries and reduce 7-day maternal and neonatal mortality and maternal morbidity in Uttar Pradesh, India. In the trial, over 6300 deliveries were observed and over 153,000 mother-baby pairs across 120 study sites were followed to assess health outcomes. We designed and implemented a robust and integrated DQA system to sustain high-quality data throughout the trial. We designed the Data Quality Monitoring and Improvement System (DQMIS) to reinforce six dimensions of data quality: accuracy, reliability, timeliness, completeness, precision, and integrity. The DQMIS was comprised of five functional components: 1) a monitoring and evaluation team to support the system; 2) a DQA protocol, including data collection audits and targets, rapid data feedback, and supportive supervision; 3) training; 4) standard operating procedures for data collection; and 5) an electronic data collection and reporting system. Routine audits by supervisors included double data entry, simultaneous delivery observations, and review of recorded calls to patients. Data feedback reports identified errors automatically, facilitating supportive supervision through a continuous quality improvement model. The five functional components of the DQMIS successfully reinforced data reliability, timeliness, completeness, precision, and integrity. The DQMIS also resulted in 98.33% accuracy across all data collection activities in the trial. All data collection activities demonstrated improvement in accuracy throughout implementation. Data collectors demonstrated a statistically significant (p = 0.0004) increase in accuracy throughout consecutive audits. The DQMIS was successful, despite an increase from 20 to 130 data collectors. In the absence of widely disseminated data quality methods and standards for large RCT interventions in limited-resource settings, we developed an integrated DQA system, combining auditing, rapid data feedback, and supportive supervision, which ensured high-quality data and could serve as a model for future health systems research trials. Future efforts should focus on standardization of DQA processes for health systems research. ClinicalTrials.gov identifier, NCT02148952 . Registered on 13 February 2014.

Recent Advances in Genome Editing Using CRISPR/Cas9.

PubMed

Ding, Yuduan; Li, Hong; Chen, Ling-Ling; Xie, Kabin

2016-01-01

The CRISPR (clustered regularly interspaced short palindromic repeat)-Cas9 (CRISPR-associated nuclease 9) system is a versatile tool for genome engineering that uses a guide RNA (gRNA) to target Cas9 to a specific sequence. This simple RNA-guided genome-editing technology has become a revolutionary tool in biology and has many innovative applications in different fields. In this review, we briefly introduce the Cas9-mediated genome-editing method, summarize the recent advances in CRISPR/Cas9 technology, and discuss their implications for plant research. To date, targeted gene knockout using the Cas9/gRNA system has been established in many plant species, and the targeting efficiency and capacity of Cas9 has been improved by optimizing its expression and that of its gRNA. The CRISPR/Cas9 system can also be used for sequence-specific mutagenesis/integration and transcriptional control of target genes. We also discuss off-target effects and the constraint that the protospacer-adjacent motif (PAM) puts on CRISPR/Cas9 genome engineering. To address these problems, a number of bioinformatic tools are available to help design specific gRNAs, and new Cas9 variants and orthologs with high fidelity and alternative PAM specificities have been engineered. Owing to these recent efforts, the CRISPR/Cas9 system is becoming a revolutionary and flexible tool for genome engineering. Adoption of the CRISPR/Cas9 technology in plant research would enable the investigation of plant biology at an unprecedented depth and create innovative applications in precise crop breeding.

Toward the development of portable miniature intelligent electronic color identification devices

NASA Astrophysics Data System (ADS)

Nicolau, Dan V., Jr.; Livingston, Peter; Jahshan, David; Evans, Rob

2004-03-01

The identification and differentiation of colours is a relatively problematic task for colour-impaired and partially vision-impaired persons and an impossible one for completely blind. In various contexts, this leads to a loss of independence or an increased risk of harm. The identification of colour using optoelectronic devices, on the other hand, can be done precisely and inexpensively. Additionally, breakthroughs in miniaturising and integrating colour sensors into biological systems may lead to significant advances in electronic implants for alleviating blindness. Here we present a functional handheld device developed for the identification of colour, intended for use by the vision-impaired. We discuss the features and limitations of the device and describe in detail one target application - the identification of different banknote denominations by the blind.

Targeting the untargeted in molecular phenomics with structurally-selective ion mobility-mass spectrometry.

PubMed

May, Jody Christopher; Gant-Branum, Randi Lee; McLean, John Allen

2016-06-01

Systems-wide molecular phenomics is rapidly expanding through technological advances in instrumentation and bioinformatics. Strategies such as structural mass spectrometry, which utilizes size and shape measurements with molecular weight, serve to characterize the sum of molecular expression in biological contexts, where broad-scale measurements are made that are interpreted through big data statistical techniques to reveal underlying patterns corresponding to phenotype. The data density, data dimensionality, data projection, and data interrogation are all critical aspects of these approaches to turn data into salient information. Untargeted molecular phenomics is already having a dramatic impact in discovery science from drug discovery to synthetic biology. It is evident that these emerging techniques will integrate closely in broad efforts aimed at precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Coherent, atomically thin transition-metal dichalcogenide superlattices with engineered strain

NASA Astrophysics Data System (ADS)

Xie, Saien; Tu, Lijie; Han, Yimo; Huang, Lujie; Kang, Kibum; Lao, Ka Un; Poddar, Preeti; Park, Chibeom; Muller, David A.; DiStasio, Robert A.; Park, Jiwoong

2018-03-01

Epitaxy forms the basis of modern electronics and optoelectronics. We report coherent atomically thin superlattices in which different transition metal dichalcogenide monolayers—despite large lattice mismatches—are repeated and laterally integrated without dislocations within the monolayer plane. Grown by an omnidirectional epitaxy, these superlattices display fully matched lattice constants across heterointerfaces while maintaining an isotropic lattice structure and triangular symmetry. This strong epitaxial strain is precisely engineered via the nanoscale supercell dimensions, thereby enabling broad tuning of the optical properties and producing photoluminescence peak shifts as large as 250 millielectron volts. We present theoretical models to explain this coherent growth and the energetic interplay governing the ripple formation in these strained monolayers. Such coherent superlattices provide building blocks with targeted functionalities at the atomically thin limit.

Systematic approach identifies RHOA as a potential biomarker therapeutic target for Asian gastric cancer

PubMed Central

Jung, Hae Rim; Park, Hee Seo; Park, Sungjin; Ahn, Young Zoo; Huh, Iksoo; Balch, Curt; Ku, Ja-Lok; Powis, Garth; Park, Taesung; Jeong, Jin-Hyun; Kim, Yon Hui

2016-01-01

Gastric cancer (GC) is a highly heterogeneous disease, in dire need of specific, biomarker-driven cancer therapies. While the accumulation of cancer “Big Data” has propelled the search for novel molecular targets for GC, its specific subpathway and cellular functions vary from patient to patient. In particular, mutations in the small GTPase gene RHOA have been identified in recent genome-wide sequencing of GC tumors. Moreover, protein overexpression of RHOA was reported in Chinese populations, while RHOA mutations were found in Caucasian GC tumors. To develop evidence-based precision medicine for heterogeneous cancers, we established a systematic approach to integrate transcriptomic and genomic data. Predicted signaling subpathways were then laboratory-validated both in vitro and in vivo, resulting in the identification of new candidate therapeutic targets. Here, we show: i) differences in RHOA expression patterns, and its pathway activity, between Asian and Caucasian GC tumors; ii) in vitro and in vivo perturbed RHOA expression inhibits GC cell growth in high RHOA-expressing cell lines; iii) inverse correlation between RHOA and RHOB expression; and iv) an innovative small molecule design strategy for RHOA inhibitors. In summary, RHOA, and its oncogenic signaling pathway, represent a strong biomarker-driven therapeutic target for Asian GC. This comprehensive strategy represents a promising approach for the development of “hit” compounds. PMID:27806312

Pathway Profiling and Rational Trial Design for Studies in Advanced Stage Cervical Carcinoma: A Review and a Perspective

PubMed Central

Scholl, Susy M. E.; Kenter, Gemma; Kurzeder, Christian; Beuzeboc, Philippe

2011-01-01

Multiple genetic abnormalities will have occurred in advanced cervical cancer and multiple targeting is likely to be needed to control tumor growth. To date, dominant therapeutic targets under scrutiny for cervical cancer treatment have been EGFR pathway and angiogenesis inhibition as well as anti-HPV vaccines. The potentially most effective targets to be blocked may be downstream from the membrane receptor or at the level of the nucleus. Alterations of the pathways involved in DNA repair and in checkpoint activations, as well as the specific site of HPV genome integration, appear worth assessing. For genetic mutational analysis, complete exon sequencing may become the norm in the future but at this stage frequent mutations (that matter) can be verified by PCR analysis. A precise documentation of relevant alterations of a large spectrum of protein biomarkers can be carried out by reverse phase protein array (RPPA) or by multiplex analysis. Clinical decision-making on the drug(s) of choice as a function of the biological alteration will need input from bio-informatics platforms as well as novel statistical designs. Endpoints are yet to be defined such as the loss (or reappearance) of a predictive biomarker. Single or dual targeting needs to be explored first in relevant preclinical animal and in xenograft models prior to clinical deployment. PMID:22091418

Robotic autopositioning of the operating microscope.

PubMed

Oppenlander, Mark E; Chowdhry, Shakeel A; Merkl, Brandon; Hattendorf, Guido M; Nakaji, Peter; Spetzler, Robert F

2014-06-01

Use of the operating microscope has become pervasive since its introduction to the neurosurgical world. Neuronavigation fused with the operating microscope has allowed accurate correlation of the focal point of the microscope and its location on the downloaded imaging study. However, the robotic ability of the Pentero microscope has not been utilized to orient the angle of the microscope or to change its focal length to hone in on a predefined target. To report a novel technology that allows automatic positioning of the operating microscope onto a set target and utilization of a planned trajectory, either determined with the StealthStation S7 by using preoperative imaging or intraoperatively with the microscope. By utilizing the current motorized capabilities of the Zeiss OPMI Pentero microscope, a robotic autopositioning feature was developed in collaboration with Surgical Technologies, Medtronic, Inc. (StealthStation S7). The system is currently being tested at the Barrow Neurological Institute. Three options were developed for automatically positioning the microscope: AutoLock Current Point, Align Parallel to Plan, and Point to Plan Target. These options allow the microscope to pivot around the lesion, hover in a set plane parallel to the determined trajectory, or rotate and point to a set target point, respectively. Integration of automatic microscope positioning into the operative workflow has potential to increase operative efficacy and safety. This technology is best suited for precise trajectories and entry points into deep-seated lesions.

LLE Review Quarterly Report (January-March 2002). Volume 90

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

Donaldson, William R.

2002-03-01

This volume of the LLE Review, covering January-March 2002, features “First Results from Cryogenic Target Implosions on OMEGA” by C. Stoeckl et al. (p. 49). This article describes initial results from direct-drive spherical cryogenic target implosions on the 60-beam OMEGA laser system. These experiments are part of the scientific base leading to direct-drive ignition implosions planned for the National Ignition Facility (NIF). Results shown include neutron yield, secondary-neutron and proton yields, the time of peak neutron emission, and both time-integrated and time-resolved x-ray images of the imploding core. The experimental values are compared with 1-D numerical simulations. The target withmore » an ice-layer nonuniformity of srms = 9 mm showed 30% of the 1-D predicted neutron yield. These initial results are encouraging for future cryogenic implosions on OMEGA and the NIF. Other articles in this issue are titled the following: Equation-of-State Measurements of Porous Materials on OMEGA: Numerical Modeling; Observations of Modulated Shock Waves in Solid Targets Driven by Spatially Modulated Laser Beams; Time-Dependent Electron Thermal Flux Inhibition in direct-Drive Laser Implosions; Precision Spectral Sculpting of Broadband FM Pulses Amplified in a Narrowband Medium; Electric-Field-Induced Motion of Polymer Cholesteric Liquid Crystal Flakes in a Moderately Conductive Fluid; and, Femtosecond Response of a Freestanding LT-GaAs Photoconductive Switch.« less

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.

COBALT CoOperative Blending of Autonomous Landing Technology

NASA Technical Reports Server (NTRS)

Carson, John M. III; Restrepo, Carolina I.; Robertson, Edward A.; Seubert, Carl R.; Amzajerdian, Farzin

2016-01-01

COBALT is a terrestrial test platform for development and maturation of GN&C (Guidance, Navigation and Control) technologies for PL&HA (Precision Landing and Hazard Avoidance). The project is developing a third generation, Langley Navigation Doppler Lidar (NDL) for ultra-precise velocity and range measurements, which will be integrated and tested with the JPL Lander Vision System (LVS) for Terrain Relative Navigation (TRN) position estimates. These technologies together provide navigation that enables controlled precision landing. The COBALT hardware will be integrated in 2017 into the GN&C subsystem of the Xodiac rocket-propulsive Vertical Test Bed (VTB) developed by Masten Space Systems (MSS), and two terrestrial flight campaigns will be conducted: one open-loop (i.e., passive) and one closed-loop (i.e., active).

Precision medicine driven by cancer systems biology.

PubMed

Filipp, Fabian V

2017-03-01

Molecular insights from genome and systems biology are influencing how cancer is diagnosed and treated. We critically evaluate big data challenges in precision medicine. The melanoma research community has identified distinct subtypes involving chronic sun-induced damage and the mitogen-activated protein kinase driver pathway. In addition, despite low mutation burden, non-genomic mitogen-activated protein kinase melanoma drivers are found in membrane receptors, metabolism, or epigenetic signaling with the ability to bypass central mitogen-activated protein kinase molecules and activating a similar program of mitogenic effectors. Mutation hotspots, structural modeling, UV signature, and genomic as well as non-genomic mechanisms of disease initiation and progression are taken into consideration to identify resistance mutations and novel drug targets. A comprehensive precision medicine profile of a malignant melanoma patient illustrates future rational drug targeting strategies. Network analysis emphasizes an important role of epigenetic and metabolic master regulators in oncogenesis. Co-occurrence of driver mutations in signaling, metabolic, and epigenetic factors highlights how cumulative alterations of our genomes and epigenomes progressively lead to uncontrolled cell proliferation. Precision insights have the ability to identify independent molecular pathways suitable for drug targeting. Synergistic treatment combinations of orthogonal modalities including immunotherapy, mitogen-activated protein kinase inhibitors, epigenetic inhibitors, and metabolic inhibitors have the potential to overcome immune evasion, side effects, and drug resistance.

Targeting an asteroid: The DSPSE encounter with asteroid 1620 Geographos

NASA Technical Reports Server (NTRS)

Yeomans, Donald K.

1993-01-01

Accurate targeting of the Deep Space Program Science Experiment (DSPSE) spacecraft to achieve a 100 km sunward flyby of asteroid 1620 Geographos will require that the ground-based ephemeris of Geographos be well known in advance of the encounter. Efforts are underway to ensure that precision optical and radar observations are available for the final asteroid orbit update that takes place several hours prior to the DSPSE flyby. Because the asteroid passes very close to the Earth six days prior to the DSPSE encounter, precision ground-based optical and radar observations should be available. These ground-based data could reduce the asteroid's position uncertainties (1-sigma) to about 10 km. This ground-based target ephemeris error estimate is far lower than for any previous comet or asteroid that has been under consideration as a mission target.

Pricise Target Geolocation and Tracking Based on Uav Video Imagery

NASA Astrophysics Data System (ADS)

Hosseinpoor, H. R.; Samadzadegan, F.; Dadrasjavan, F.

2016-06-01

There is an increasingly large number of applications for Unmanned Aerial Vehicles (UAVs) from monitoring, mapping and target geolocation. However, most of commercial UAVs are equipped with low-cost navigation sensors such as C/A code GPS and a low-cost IMU on board, allowing a positioning accuracy of 5 to 10 meters. This low accuracy cannot be used in applications that require high precision data on cm-level. This paper presents a precise process for geolocation of ground targets based on thermal video imagery acquired by small UAV equipped with RTK GPS. The geolocation data is filtered using an extended Kalman filter, which provides a smoothed estimate of target location and target velocity. The accurate geo-locating of targets during image acquisition is conducted via traditional photogrammetric bundle adjustment equations using accurate exterior parameters achieved by on board IMU and RTK GPS sensors, Kalman filtering and interior orientation parameters of thermal camera from pre-flight laboratory calibration process. The results of this study compared with code-based ordinary GPS, indicate that RTK observation with proposed method shows more than 10 times improvement of accuracy in target geolocation.

Precision Strike Annual Programs Review

DTIC Science & Technology

2008-04-16

SW For Precise Targeting 8 “Secure the High Ground” Evolution of Deployable HEL Weapons Capability THEL ACTD C5 Galaxy HEL TD C17 Globemaster Future...Security Ranger Training Maritime Ops CT Coastal SecurityERITREA African Union CA Wells, Schools MED / VETCAPs CA MED / VET Bilateral Military

Kinesthetic information facilitates saccades towards proprioceptive-tactile targets.

PubMed

Voudouris, Dimitris; Goettker, Alexander; Mueller, Stefanie; Fiehler, Katja

2016-05-01

Saccades to somatosensory targets have longer latencies and are less accurate and precise than saccades to visual targets. Here we examined how different somatosensory information influences the planning and control of saccadic eye movements. Participants fixated a central cross and initiated a saccade as fast as possible in response to a tactile stimulus that was presented to either the index or the middle fingertip of their unseen left hand. In a static condition, the hand remained at a target location for the entire block of trials and the stimulus was presented at a fixed time after an auditory tone. Therefore, the target location was derived only from proprioceptive and tactile information. In a moving condition, the hand was first actively moved to the same target location and the stimulus was then presented immediately. Thus, in the moving condition additional kinesthetic information about the target location was available. We found shorter saccade latencies in the moving compared to the static condition, but no differences in accuracy or precision of saccadic endpoints. In a second experiment, we introduced variable delays after the auditory tone (static condition) or after the end of the hand movement (moving condition) in order to reduce the predictability of the moment of the stimulation and to allow more time to process the kinesthetic information. Again, we found shorter latencies in the moving compared to the static condition but no improvement in saccade accuracy or precision. In a third experiment, we showed that the shorter saccade latencies in the moving condition cannot be explained by the temporal proximity between the relevant event (auditory tone or end of hand movement) and the moment of the stimulation. Our findings suggest that kinesthetic information facilitates planning, but not control, of saccadic eye movements to proprioceptive-tactile targets. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hitts Law? A test of the relationship between information load and movement precision

NASA Technical Reports Server (NTRS)

Zaleski, M.; Moray, N.

1986-01-01

Recent technological developments have made viable a man-machine interface heavily dependent on graphics and pointing devices. This has led to new interest in classical reaction and movement time work by Human Factors specialists. Two experiments were designed and run to test the dependence of target capture time on information load (Hitt's Law) and movement precision (Fitts' Law). The proposed model linearly combines Hitt's and Fitts' results into a combination law which then might be called Hitts' Law. Subjects were required to react to stimuli by manipulating a joystick so as to cause a cursor to capture a target on a CRT screen. Response entropy and the relative precision of the capture movement were crossed in a factorial design and data obtained that were found to support the model.

Towards Precision Medicine in the Clinic: From Biomarker Discovery to Novel Therapeutics.

PubMed

Collins, Dearbhaile C; Sundar, Raghav; Lim, Joline S J; Yap, Timothy A

2017-01-01

Precision medicine continues to be the benchmark to which we strive in cancer research. Seeking out actionable aberrations that can be selectively targeted by drug compounds promises to optimize treatment efficacy and minimize toxicity. Utilizing these different targeted agents in combination or in sequence may further delay resistance to treatments and prolong antitumor responses. Remarkable progress in the field of immunotherapy adds another layer of complexity to the management of cancer patients. Corresponding advances in companion biomarker development, novel methods of serial tumor assessments, and innovative trial designs act synergistically to further precision medicine. Ongoing hurdles such as clonal evolution, intra- and intertumor heterogeneity, and varied mechanisms of drug resistance continue to be challenges to overcome. Large-scale data-sharing and collaborative networks using next-generation sequencing (NGS) platforms promise to take us further into the cancer 'ome' than ever before, with the goal of achieving successful precision medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

Design and Validation of CRISPR/Cas9 Systems for Targeted Gene Modification in Induced Pluripotent Stem Cells.

PubMed

Lee, Ciaran M; Zhu, Haibao; Davis, Timothy H; Deshmukh, Harshahardhan; Bao, Gang

2017-01-01

The CRISPR/Cas9 system is a powerful tool for precision genome editing. The ability to accurately modify genomic DNA in situ with single nucleotide precision opens up new possibilities for not only basic research but also biotechnology applications and clinical translation. In this chapter, we outline the procedures for design, screening, and validation of CRISPR/Cas9 systems for targeted modification of coding sequences in the human genome and how to perform genome editing in induced pluripotent stem cells with high efficiency and specificity.

Analog-to-digital conversion techniques for precision photometry

NASA Technical Reports Server (NTRS)

Opal, Chet B.

1988-01-01

Three types of analog-to-digital converters are described: parallel, successive-approximation, and integrating. The functioning of comparators and sample-and-hold amplifiers is explained. Differential and integral linearity are defined, and good and bad examples are illustrated. The applicability and relative advantages of the three types of converters for precision astronomical photometric measurements are discussed. For most measurements, integral linearity is more important than differential linearity. Successive-approximation converters should be used with multielement solid state detectors because of their high speed, but dual slope integrating converters may be superior for use with single element solid state detectors where speed of digitization is not a factor. In all cases, the input signal should be tailored so that they occupy the upper part of the converter's dynamic range; this can be achieved by providing adjustable gain, or better by varying the integration time of the observation if possible.

Dedicated magnetic resonance imaging in the radiotherapy clinic.

PubMed

Karlsson, Mikael; Karlsson, Magnus G; Nyholm, Tufve; Amies, Christopher; Zackrisson, Björn

2009-06-01

To introduce a novel technology arrangement in an integrated environment and outline the logistics model needed to incorporate dedicated magnetic resonance (MR) imaging in the radiotherapy workflow. An initial attempt was made to analyze the value and feasibility of MR-only imaging compared to computed tomography (CT) imaging, testing the assumption that MR is a better choice for target and healthy tissue delineation in radiotherapy. A 1.5-T MR unit with a 70-cm-bore size was installed close to a linear accelerator, and a special trolley was developed for transporting patients who were fixated in advance between the MR unit and the accelerator. New MR-based workflow procedures were developed and evaluated. MR-only treatment planning has been facilitated, thus avoiding all registration errors between CT and MR scans, but several new aspects of MR imaging must be considered. Electron density information must be obtained by other methods. Generation of digitally reconstructed radiographs (DRR) for x-ray setup verification is not straight forward, and reliable corrections of geometrical distortions must be applied. The feasibility of MR imaging virtual simulation has been demonstrated, but a key challenge to overcome is correct determination of the skeleton, which is often needed for the traditional approach of beam modeling. The trolley solution allows for a highly precise setup for soft tissue tumors without the invasive handling of radiopaque markers. The new logistics model with an integrated MR unit is efficient and will allow for improved tumor definition and geometrical precision without a significant loss of dosimetric accuracy. The most significant development needed is improved bone imaging.

Next-generation phenotyping: requirements and strategies for enhancing our understanding of genotype-phenotype relationships and its relevance to crop improvement.

PubMed

Cobb, Joshua N; Declerck, Genevieve; Greenberg, Anthony; Clark, Randy; McCouch, Susan

2013-04-01

More accurate and precise phenotyping strategies are necessary to empower high-resolution linkage mapping and genome-wide association studies and for training genomic selection models in plant improvement. Within this framework, the objective of modern phenotyping is to increase the accuracy, precision and throughput of phenotypic estimation at all levels of biological organization while reducing costs and minimizing labor through automation, remote sensing, improved data integration and experimental design. Much like the efforts to optimize genotyping during the 1980s and 1990s, designing effective phenotyping initiatives today requires multi-faceted collaborations between biologists, computer scientists, statisticians and engineers. Robust phenotyping systems are needed to characterize the full suite of genetic factors that contribute to quantitative phenotypic variation across cells, organs and tissues, developmental stages, years, environments, species and research programs. Next-generation phenotyping generates significantly more data than previously and requires novel data management, access and storage systems, increased use of ontologies to facilitate data integration, and new statistical tools for enhancing experimental design and extracting biologically meaningful signal from environmental and experimental noise. To ensure relevance, the implementation of efficient and informative phenotyping experiments also requires familiarity with diverse germplasm resources, population structures, and target populations of environments. Today, phenotyping is quickly emerging as the major operational bottleneck limiting the power of genetic analysis and genomic prediction. The challenge for the next generation of quantitative geneticists and plant breeders is not only to understand the genetic basis of complex trait variation, but also to use that knowledge to efficiently synthesize twenty-first century crop varieties.

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

PubMed

Bousquet, J; Anto, J M; Akdis, M; Auffray, C; Keil, T; Momas, I; Postma, D S; Valenta, R; Wickman, M; Cambon-Thomsen, A; Haahtela, T; Lambrecht, B N; Lodrup Carlsen, K C; Koppelman, G H; Sunyer, J; Zuberbier, T; Annesi-Maesano, I; Arno, A; Bindslev-Jensen, C; De Carlo, G; Forastiere, F; Heinrich, J; Kowalski, M L; Maier, D; Melén, E; Palkonen, S; Smit, H A; Standl, M; Wright, J; Asarnoj, A; Benet, M; Ballardini, N; Garcia-Aymerich, J; Gehring, U; Guerra, S; Hohman, C; Kull, I; Lupinek, C; Pinart, M; Skrindo, I; Westman, M; Smagghe, D; Akdis, C; Albang, R; Anastasova, V; Anderson, N; Bachert, C; Ballereau, S; Ballester, F; Basagana, X; Bedbrook, A; Bergstrom, A; von Berg, A; Brunekreef, B; Burte, E; Carlsen, K H; Chatzi, L; Coquet, J M; Curin, M; Demoly, P; Eller, E; Fantini, M P; Gerhard, B; Hammad, H; von Hertzen, L; Hovland, V; Jacquemin, B; Just, J; Keller, T; Kerkhof, M; Kiss, R; Kogevinas, M; Koletzko, S; Lau, S; Lehmann, I; Lemonnier, N; McEachan, R; Mäkelä, M; Mestres, J; Minina, E; Mowinckel, P; Nadif, R; Nawijn, M; Oddie, S; Pellet, J; Pin, I; Porta, D; Rancière, F; Rial-Sebbag, A; Saeys, Y; Schuijs, M J; Siroux, V; Tischer, C G; Torrent, M; Varraso, R; De Vocht, J; Wenger, K; Wieser, S; Xu, C

2016-11-01

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

In-airway molecular flow sensing: A new technology for continuous, noninvasive monitoring of oxygen consumption in critical care.

PubMed

Ciaffoni, Luca; O'Neill, David P; Couper, John H; Ritchie, Grant A D; Hancock, Gus; Robbins, Peter A

2016-08-01

There are no satisfactory methods for monitoring oxygen consumption in critical care. To address this, we adapted laser absorption spectroscopy to provide measurements of O2, CO2, and water vapor within the airway every 10 ms. The analyzer is integrated within a novel respiratory flow meter that is an order of magnitude more precise than other flow meters. Such precision, coupled with the accurate alignment of gas concentrations with respiratory flow, makes possible the determination of O2 consumption by direct integration over time of the product of O2 concentration and flow. The precision is illustrated by integrating the balance gas (N2 plus Ar) flow and showing that this exchange was near zero. Measured O2 consumption changed by <5% between air and O2 breathing. Clinical capability was illustrated by recording O2 consumption during an aortic aneurysm repair. This device now makes easy, accurate, and noninvasive measurement of O2 consumption for intubated patients in critical care possible.

Practice innovation: the need for nimble data platforms to implement precision oncology care.

PubMed

Elfiky, Aymen; Zhang, Dongyang; Krishnan Nair, Hari K

2015-01-01

Given the drive toward personalized, value-based, and coordinated cancer care delivery, modern knowledge-based practice is being shaped within the context of an increasingly technology-driven healthcare landscape. The ultimate promise of 'precision medicine' is predicated on taking advantage of the range of new capabilities for integrating disease- and individual-specific data to define new taxonomies as part of a systems-based knowledge network. Specifically, with cancer being a constantly evolving complex disease process, proper care of an individual will require the ability to seamlessly integrate multi-dimensional 'omic' and clinical data. Importantly, however, the challenges of curating knowledge from multiple dynamic data sources and translating to practice at the point-of-care highlight parallel needs. As patients, caregivers, and their environments become more proactive in clinical care and management, practical success of precision medicine is equally dependent on the development of proper infrastructures for evolving data integration, platforms for knowledge representation in a clinically-relevant context, and implementation within a provider's work-life and workflow.

In-airway molecular flow sensing: A new technology for continuous, noninvasive monitoring of oxygen consumption in critical care

PubMed Central

Ciaffoni, Luca; O’Neill, David P.; Couper, John H.; Ritchie, Grant A. D.; Hancock, Gus; Robbins, Peter A.

2016-01-01

There are no satisfactory methods for monitoring oxygen consumption in critical care. To address this, we adapted laser absorption spectroscopy to provide measurements of O2, CO2, and water vapor within the airway every 10 ms. The analyzer is integrated within a novel respiratory flow meter that is an order of magnitude more precise than other flow meters. Such precision, coupled with the accurate alignment of gas concentrations with respiratory flow, makes possible the determination of O2 consumption by direct integration over time of the product of O2 concentration and flow. The precision is illustrated by integrating the balance gas (N2 plus Ar) flow and showing that this exchange was near zero. Measured O2 consumption changed by <5% between air and O2 breathing. Clinical capability was illustrated by recording O2 consumption during an aortic aneurysm repair. This device now makes easy, accurate, and noninvasive measurement of O2 consumption for intubated patients in critical care possible. PMID:27532048

Present situation and trend of precision guidance technology and its intelligence

NASA Astrophysics Data System (ADS)

Shang, Zhengguo; Liu, Tiandong

2017-11-01

This paper first introduces the basic concepts of precision guidance technology and artificial intelligence technology. Then gives a brief introduction of intelligent precision guidance technology, and with the help of development of intelligent weapon based on deep learning project in foreign: LRASM missile project, TRACE project, and BLADE project, this paper gives an overview of the current foreign precision guidance technology. Finally, the future development trend of intelligent precision guidance technology is summarized, mainly concentrated in the multi objectives, intelligent classification, weak target detection and recognition, intelligent between complex environment intelligent jamming and multi-source, multi missile cooperative fighting and other aspects.

Integration of vegetation community spatial data into a prescribed fire planning process at Shenandoah National Park, Virginia (USA)

USGS Publications Warehouse

Young, John A.; Mahan, Carolyn G.; Forder, Melissa

2017-01-01

Many eastern forest communities depend on fire for regeneration or are enhanced by fire as a restoration practice. However, the use of prescribed fire in the mesic forested environments and the densely populated regions of the eastern United States has been limited. The objective of our research was to develop a science-based approach to prioritizing the use of prescribed fire in appropriate forest types in the eastern United States based on a set of desired management outcomes. Through a process of expert elicitation and data analysis, we assessed and integrated recent vegetation community mapping results along with other available spatial data layers into a spatial prioritization tool for prescribed fire planning at Shenandoah National Park (Virginia, USA). The integration of vegetation spatial data allowed for development of per-pixel priority rankings and exclusion areas enabling precise targeting of fire management activities on the ground, as well as a park-wide ranking of fire planning compartments. We demonstrate the use and evaluation of this approach through implementation and monitoring of a prescribed burn and show that progress is being made toward desired conditions. Integration of spatial data into the fire planning process has served as a collaborative tool for the implementation of prescribed fire projects, which assures projects will be planned in the most appropriate areas to meet objectives that are supported by current science.

Public health and precision medicine share a goal.

PubMed

Vaithinathan, Asokan G; Asokan, Vanitha

2017-05-01

The advances made in genomics and molecular tools aid public health programs in the investigation of outbreaks and control of diseases by taking advantage of the precision medicine. Precision medicine means "segregating the individuals into subpopulations who vary in their disease susceptibility and response to a precise treatment" and not merely designing of drugs or creation of medical devices. By 2017, the United Kingdom 100,000 Genomes Project is expected to sequence 100,000 genomes from 70,000 patients. Similarly, the Precision Medicine Initiative of the United States plans to increase population-based genome sequencing and link it with clinical data. A national cohort of around 1 million people is to be established in the long term, to investigate the genetic and environmental determinants of health and disease, and further integrated to their electronic health records that are optional. Precision public health can be seen as administering the right intervention to the needy population at an appropriate time. Precision medicine originates from a wet-lab while evidence-based medicine is nurtured in a clinic. Linking the quintessential basic science research and clinical practice is necessary. In addition, new technologies to employ and analyze data in an integrated and dynamic way are essential for public health and precision medicine. The transition from evidence-based approach in public health to genomic approach to individuals with a paradigm shift of a "reactive" medicine to a more "proactive" and personalized health care may sound exceptional. However, a population perspective is needed for the precision medicine to succeed. © 2016 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Simultaneous non-contiguous deletions using large synthetic DNA and site-specific recombinases

PubMed Central

Krishnakumar, Radha; Grose, Carissa; Haft, Daniel H.; Zaveri, Jayshree; Alperovich, Nina; Gibson, Daniel G.; Merryman, Chuck; Glass, John I.

2014-01-01

Toward achieving rapid and large scale genome modification directly in a target organism, we have developed a new genome engineering strategy that uses a combination of bioinformatics aided design, large synthetic DNA and site-specific recombinases. Using Cre recombinase we swapped a target 126-kb segment of the Escherichia coli genome with a 72-kb synthetic DNA cassette, thereby effectively eliminating over 54 kb of genomic DNA from three non-contiguous regions in a single recombination event. We observed complete replacement of the native sequence with the modified synthetic sequence through the action of the Cre recombinase and no competition from homologous recombination. Because of the versatility and high-efficiency of the Cre-lox system, this method can be used in any organism where this system is functional as well as adapted to use with other highly precise genome engineering systems. Compared to present-day iterative approaches in genome engineering, we anticipate this method will greatly speed up the creation of reduced, modularized and optimized genomes through the integration of deletion analyses data, transcriptomics, synthetic biology and site-specific recombination. PMID:24914053

New diagnostic methods for pneumonia in the ICU.

PubMed

Douglas, Ivor S

2016-04-01

Pneumonia leading to severe sepsis and critical illness including respiratory failure remains a common and therapeutically challenging diagnosis. Current clinical approaches to surveillance, early detection, and conventional culture-based microbiology are inadequate for optimal targeted antibiotic treatment and stewardship. Efforts to enhance diagnosis of community-acquired and health care-acquired pneumonia, including ventilator-associated pneumonia (VAP), are the focus of recent studies reviewed here. Newer surveillance definitions are sensitive for pneumonia in the ICU including VAP but consistently underdetect patients that are clinically shown to have bacterial VAP based on clinical diagnostic criteria and response to antibiotic treatment. Routinely measured plasma biomarkers, including procalcitonin and C-reactive protein, lack sufficient precision and predictive accuracy to inform diagnosis. Novel rapid microbiological diagnostics, including nucleic-acid amplification, mass spectrometry, and fluorescence microscopy-based technologies are promising approaches for the future. Exhaled breath biomarkers, including measurement of volatile organic compounds, represent a future approach. The integration of novel diagnostics for rapid microbial identification, resistance phenotyping, and antibiotic sensitivity testing into usual care practice could significantly transform the care of patients and potentially inform significantly improved targeted antimicrobial selection, de-escalation, and stewardship.

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

PubMed Central

Luo, Dandan; Carter, Kevin A.; Miranda, Dyego

2016-01-01

Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non‐ionizing radiation to well‐defined target tissue volumes. Light‐based therapies including photodynamic therapy (PDT) and laser‐induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically. Chemotherapy can enhance the efficacy of PDT by targeting surviving cancer cells or by inhibiting regrowth of damaged tumor blood vessels. Alternatively, PDT‐mediated vascular permeabilization has been shown to enhance the deposition of nanoparticulate drugs into tumors for enhanced accumulation and efficacy. Integrated nanoparticles have been reported that combine photosensitizers and drugs into a single agent. More recently, light‐activated nanoparticles have been developed that release their payload in response to light irradiation to achieve improved drug bioavailability with superior efficacy. CPT can potently eradicate tumors with precise spatial control, and further clinical testing is warranted. PMID:28105389

Computational and Experimental Studies of Electrospray Deposition of Nanoparticle Suspensions

NASA Astrophysics Data System (ADS)

Yong, Xin; Li, Ao; Brown, Nicholas; Zhao, Mingfei; Zhu, Yaqun; German, Guy; Chiarot, Paul

2017-11-01

Electrospray offers unique capabilities for deploying colloidal suspensions to create nanoparticle films and coatings. It can deliver precise quantities of particles in a dry state and overcomes many limitations of other technologies. We integrate simulations and experiments to elucidate the relationship between the key operating parameters and the structure of an electrospray deposit. We investigate the role of the electrospray time, the target substrate properties, and the polydispersity of the colloidal suspensions. The deposition patterns are similar for all spray times and substrates. In particular, the deposited particles segregate to the center and edge of a deposit, leaving a depletion region in between. Using a Lagrangian particle tracking method with convective droplet evaporation, we highlight the critical role of the space charge interactions inside the plume in governing the trajectory of the emitted particles and the ensuing deposit morphology. The microstructure of a deposit is also influenced by the electrical conductivity of the target substrate. The residual charges on the particles deposited on to a dielectric substrate influence the deposition of subsequent in-flight particles.

Integrating RNA sequencing into neuro-oncology practice.

PubMed

Rogawski, David S; Vitanza, Nicholas A; Gauthier, Angela C; Ramaswamy, Vijay; Koschmann, Carl

2017-11-01

Malignant tumors of the central nervous system (CNS) cause substantial morbidity and mortality, yet efforts to optimize chemo- and radiotherapy have largely failed to improve dismal prognoses. Over the past decade, RNA sequencing (RNA-seq) has emerged as a powerful tool to comprehensively characterize the transcriptome of CNS tumor cells in one high-throughput step, leading to improved understanding of CNS tumor biology and suggesting new routes for targeted therapies. RNA-seq has been instrumental in improving the diagnostic classification of brain tumors, characterizing oncogenic fusion genes, and shedding light on intratumor heterogeneity. Currently, RNA-seq is beginning to be incorporated into regular neuro-oncology practice in the form of precision neuro-oncology programs, which use information from tumor sequencing to guide implementation of personalized targeted therapies. These programs show great promise in improving patient outcomes for tumors where single agent trials have been ineffective. As RNA-seq is a relatively new technique, many further applications yielding new advances in CNS tumor research and management are expected in the coming years. Copyright © 2017 Elsevier Inc. All rights reserved.

Recent advances in the development of new transgenic animal technology.

PubMed

Miao, Xiangyang

2013-03-01

Transgenic animal technology is one of the fastest growing biotechnology areas. It is used to integrate exogenous genes into the animal genome by genetic engineering technology so that these genes can be inherited and expressed by offspring. The transgenic efficiency and precise control of gene expression are the key limiting factors in the production of transgenic animals. A variety of transgenic technologies are available. Each has its own advantages and disadvantages and needs further study because of unresolved technical and safety issues. Further studies will allow transgenic technology to explore gene function, animal genetic improvement, bioreactors, animal disease models, and organ transplantation. This article reviews the recently developed animal transgenic technologies, including the germ line stem cell-mediated method to improve efficiency, gene targeting to improve accuracy, RNA interference-mediated gene silencing technology, zinc-finger nuclease gene targeting technology and induced pluripotent stem cell technology. These new transgenic techniques can provide a better platform to develop transgenic animals for breeding new animal varieties and promote the development of medical sciences, livestock production, and other fields.

Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9.

PubMed

Li, Hongmei Lisa; Fujimoto, Naoko; Sasakawa, Noriko; Shirai, Saya; Ohkame, Tokiko; Sakuma, Tetsushi; Tanaka, Michihiro; Amano, Naoki; Watanabe, Akira; Sakurai, Hidetoshi; Yamamoto, Takashi; Yamanaka, Shinya; Hotta, Akitsu

2015-01-13

Duchenne muscular dystrophy (DMD) is a severe muscle-degenerative disease caused by a mutation in the dystrophin gene. Genetic correction of patient-derived induced pluripotent stem cells (iPSCs) by TALENs or CRISPR-Cas9 holds promise for DMD gene therapy; however, the safety of such nuclease treatment must be determined. Using a unique k-mer database, we systematically identified a unique target region that reduces off-target sites. To restore the dystrophin protein, we performed three correction methods (exon skipping, frameshifting, and exon knockin) in DMD-patient-derived iPSCs, and found that exon knockin was the most effective approach. We further investigated the genomic integrity by karyotyping, copy number variation array, and exome sequencing to identify clones with a minimal mutation load. Finally, we differentiated the corrected iPSCs toward skeletal muscle cells and successfully detected the expression of full-length dystrophin protein. These results provide an important framework for developing iPSC-based gene therapy for genetic disorders using programmable nucleases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Flight evaluation of differential GPS aided inertial navigation systems

NASA Technical Reports Server (NTRS)

Mcnally, B. David; Paielli, Russell A.; Bach, Ralph E., Jr.; Warner, David N., Jr.

1992-01-01

Algorithms are described for integration of Differential Global Positioning System (DGPS) data with Inertial Navigation System (INS) data to provide an integrated DGPS/INS navigation system. The objective is to establish the benefits that can be achieved through various levels of integration of DGPS with INS for precision navigation. An eight state Kalman filter integration was implemented in real-time on a twin turbo-prop transport aircraft to evaluate system performance during terminal approach and landing operations. A fully integrated DGPS/INS system is also presented which models accelerometer and rate-gyro measurement errors plus position, velocity, and attitude errors. The fully integrated system was implemented off-line using range-domain (seventeen-state) and position domain (fifteen-state) Kalman filters. Both filter integration approaches were evaluated using data collected during the flight test. Flight-test data consisted of measurements from a 5 channel Precision Code GPS receiver, a strap-down Inertial Navigation Unit (INU), and GPS satellite differential range corrections from a ground reference station. The aircraft was laser tracked to determine its true position. Results indicate that there is no significant improvement in positioning accuracy with the higher levels of DGPS/INS integration. All three systems provided high-frequency (e.g., 20 Hz) estimates of position and velocity. The fully integrated system provided estimates of inertial sensor errors which may be used to improve INS navigation accuracy should GPS become unavailable, and improved estimates of acceleration, attitude, and body rates which can be used for guidance and control. Precision Code DGPS/INS positioning accuracy (root-mean-square) was 1.0 m cross-track and 3.0 m vertical. (This AGARDograph was sponsored by the Guidance and Control Panel.)

SpecOp: Optimal Extraction Software for Integral Field Unit Spectrographs

NASA Astrophysics Data System (ADS)

McCarron, Adam; Ciardullo, Robin; Eracleous, Michael

2018-01-01

The Hobby-Eberly Telescope’s new low resolution integral field spectrographs, LRS2-B and LRS2-R, each cover a 12”x6” area on the sky with 280 fibers and generate spectra with resolutions between R=1100 and R=1900. To extract 1-D spectra from the instrument’s 3D data cubes, a program is needed that is flexible enough to work for a wide variety of targets, including continuum point sources, emission line sources, and compact sources embedded in complex backgrounds. We therefore introduce SpecOp, a user-friendly python program for optimally extracting spectra from integral-field unit spectrographs. As input, SpecOp takes a sky-subtracted data cube consisting of images at each wavelength increment set by the instrument’s spectral resolution, and an error file for each count measurement. All of these files are generated by the current LRS2 reduction pipeline. The program then collapses the cube in the image plane using the optimal extraction algorithm detailed by Keith Horne (1986). The various user-selected options include the fraction of the total signal enclosed in a contour-defined region, the wavelength range to analyze, and the precision of the spatial profile calculation. SpecOp can output the weighted counts and errors at each wavelength in various table formats using python’s astropy package. We outline the algorithm used for extraction and explain how the software can be used to easily obtain high-quality 1-D spectra. We demonstrate the utility of the program by applying it to spectra of a variety of quasars and AGNs. In some of these targets, we extract the spectrum of a nuclear point source that is superposed on a spatially extended galaxy.

Recent advances of controlled drug delivery using microfluidic platforms.

PubMed

Sanjay, Sharma T; Zhou, Wan; Dou, Maowei; Tavakoli, Hamed; Ma, Lei; Xu, Feng; Li, XiuJun

2018-03-15

Conventional systematically-administered drugs distribute evenly throughout the body, get degraded and excreted rapidly while crossing many biological barriers, leaving minimum amounts of the drugs at pathological sites. Controlled drug delivery aims to deliver drugs to the target sites at desired rates and time, thus enhancing the drug efficacy, pharmacokinetics, and bioavailability while maintaining minimal side effects. Due to a number of unique advantages of the recent microfluidic lab-on-a-chip technology, microfluidic lab-on-a-chip has provided unprecedented opportunities for controlled drug delivery. Drugs can be efficiently delivered to the target sites at desired rates in a well-controlled manner by microfluidic platforms via integration, implantation, localization, automation, and precise control of various microdevice parameters. These features accordingly make reproducible, on-demand, and tunable drug delivery become feasible. On-demand self-tuning dynamic drug delivery systems have shown great potential for personalized drug delivery. This review presents an overview of recent advances in controlled drug delivery using microfluidic platforms. The review first briefly introduces microfabrication techniques of microfluidic platforms, followed by detailed descriptions of numerous microfluidic drug delivery systems that have significantly advanced the field of controlled drug delivery. Those microfluidic systems can be separated into four major categories, namely drug carrier-free micro-reservoir-based drug delivery systems, highly integrated carrier-free microfluidic lab-on-a-chip systems, drug carrier-integrated microfluidic systems, and microneedles. Microneedles can be further categorized into five different types, i.e. solid, porous, hollow, coated, and biodegradable microneedles, for controlled transdermal drug delivery. At the end, we discuss current limitations and future prospects of microfluidic platforms for controlled drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

Hyperspectral imagery for mapping crop yield for precision agriculture

USDA-ARS?s Scientific Manuscript database

Crop yield is perhaps the most important piece of information for crop management in precision agriculture. It integrates the effects of various spatial variables such as soil properties, topographic attributes, tillage, plant population, fertilization, irrigation, and pest infestations. A yield map...

Integration of virtual and real scenes within an integral 3D imaging environment

NASA Astrophysics Data System (ADS)

Ren, Jinsong; Aggoun, Amar; McCormick, Malcolm

2002-11-01

The Imaging Technologies group at De Montfort University has developed an integral 3D imaging system, which is seen as the most likely vehicle for 3D television avoiding psychological effects. To create real fascinating three-dimensional television programs, a virtual studio that performs the task of generating, editing and integrating the 3D contents involving virtual and real scenes is required. The paper presents, for the first time, the procedures, factors and methods of integrating computer-generated virtual scenes with real objects captured using the 3D integral imaging camera system. The method of computer generation of 3D integral images, where the lens array is modelled instead of the physical camera is described. In the model each micro-lens that captures different elemental images of the virtual scene is treated as an extended pinhole camera. An integration process named integrated rendering is illustrated. Detailed discussion and deep investigation are focused on depth extraction from captured integral 3D images. The depth calculation method from the disparity and the multiple baseline method that is used to improve the precision of depth estimation are also presented. The concept of colour SSD and its further improvement in the precision is proposed and verified.

NATALIE: A 32 detector integrated acquisition system to characterize laser produced energetic particles with nuclear techniques

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

Tarisien, M.; Plaisir, C.; Gobet, F.

2011-02-15

We present a stand-alone system to characterize the high-energy particles emitted in the interaction of ultrahigh intensity laser pulses with matter. According to the laser and target characteristics, electrons or protons are produced with energies higher than a few mega electron volts. Selected material samples can, therefore, be activated via nuclear reactions. A multidetector, named NATALIE, has been developed to count the {beta}{sup +} activity of these irradiated samples. The coincidence technique used, designed in an integrated system, results in very low background in the data, which is required for low activity measurements. It, therefore, allows a good precision onmore » the nuclear activation yields of the produced radionuclides. The system allows high counting rates and online correction of the dead time. It also provides, online, a quick control of the experiment. Geant4 simulations are used at different steps of the data analysis to deduce, from the measured activities, the energy and angular distributions of the laser-induced particle beams. Two applications are presented to illustrate the characterization of electrons and protons.« less

Development of a slicer integral field unit for the existing optical spectrograph FOCAS: progress

NASA Astrophysics Data System (ADS)

Ozaki, Shinobu; Tanaka, Yoko; Hattori, Takashi; Mitsui, Kenji; Fukushima, Mitsuhiro; Okada, Norio; Obuchi, Yoshiyuki; Tsuzuki, Toshihiro; Miyazaki, Satoshi; Yamashita, Takuya

2014-07-01

We are developing an integral field unit (IFU) with an image slicer for the existing optical spectrograph, Faint Object Camera And Spectrograph (FOCAS), on the Subaru Telescope. The slice width is 0.43 arcsec, the slice number is 23, and the field of view is 13.5 × 9.89 arcsec2. Sky spectrum separated by about 5.7 arcmin from an object field can be simultaneously obtained, which allows us precise background subtraction. Slice mirrors, pupil mirrors and slit mirrors are all glass, and their mirror surfaces are fabricated by polishing. Our IFU is about 200 mm × 300 mm × 80 mm in size and 1 kg in weight. It is installed into a mask storage in FOCAS along with one or two mask plates, and inserted into the optical path by using the existing mask exchange mechanism. This concept allow us flexible operation such as Targets of Opportunity observations. High reflectivity of multilayer dielectric coatings offers high throughput (>80%) of the IFU. In this paper, we will report a final optical layout, its performances, and results of prototyping works.

Unraveling the complexities of invasive multimodality neuromonitoring.

PubMed

Sinha, Saurabh; Hudgins, Eric; Schuster, James; Balu, Ramani

2017-11-01

Acute brain injuries are a major cause of death and disability worldwide. Survivors of life-threatening brain injury often face a lifetime of dependent care, and novel approaches that improve outcome are sorely needed. A delayed cascade of brain damage, termed secondary injury, occurs hours to days and even weeks after the initial insult. This delayed phase of injury provides a crucial window for therapeutic interventions that could limit brain damage and improve outcome. A major barrier in the ability to prevent and treat secondary injury is that physicians are often unable to target therapies to patients' unique cerebral physiological disruptions. Invasive neuromonitoring with multiple complementary physiological monitors can provide useful information to enable this tailored, precision approach to care. However, integrating the multiple streams of time-varying data is challenging and often not possible during routine bedside assessment. The authors review and discuss the principles and evidence underlying several widely used invasive neuromonitors. They also provide a framework for integrating data for clinical decision making and discuss future developments in informatics that may allow new treatment paradigms to be developed.

Ppbv-Level Ethane Detection Using Quartz-Enhanced Photoacoustic Spectroscopy with a Continuous-Wave, Room Temperature Interband Cascade Laser

PubMed Central

Li, Chunguang; Dong, Lei; Zheng, Chuantao; Lin, Jun; Wang, Yiding

2018-01-01

A ppbv-level quartz-enhanced photoacoustic spectroscopy (QEPAS)-based ethane (C2H6) sensor was demonstrated by using a 3.3 μm continuous-wave (CW), distributed feedback (DFB) interband cascade laser (ICL). The ICL was employed for targeting a strong C2H6 absorption line located at 2996.88 cm−1 in its fundamental absorption band. Wavelength modulation spectroscopy (WMS) combined with the second harmonic (2f) detection technique was utilized to increase the signal-to-noise ratio (SNR) and simplify data acquisition and processing. Gas pressure and laser frequency modulation depth were optimized to be 100 Torr and 0.106 cm−1, respectively, for maximizing the 2f signal amplitude. Performance of the QEPAS sensor was evaluated using specially prepared C2H6 samples. A detection limit of 11 parts per billion in volume (ppbv) was obtained with a 1-s integration time based on an Allan-Werle variance analysis, and the detection precision can be further improved to ~1.5 ppbv by increasing the integration time up to 230 s. PMID:29495610

Design of a Compact Actuation and Control System for Flexible Medical Robots.

PubMed

Morimoto, Tania K; Hawkes, Elliot Wright; Okamura, Allison M

2017-07-01

Flexible medical robots can improve surgical procedures by decreasing invasiveness and increasing accessibility within the body. Using preoperative images, these robots can be designed to optimize a procedure for a particular patient. To minimize invasiveness and maximize biocompatibility, the actuation units of flexible medical robots should be placed fully outside the patient's body. In this letter, we present a novel, compact, lightweight, modular actuation, and control system for driving a class of these flexible robots, known as concentric tube robots. A key feature of the design is the use of three-dimensional printed waffle gears to enable compact control of two degrees of freedom within each module. We measure the precision and accuracy of a single actuation module and demonstrate the ability of an integrated set of three actuation modules to control six degrees of freedom. The integrated system drives a three-tube concentric tube robot to reach a final tip position that is on average less than 2 mm from a given target. In addition, we show a handheld manifestation of the device and present its potential applications.

Deep Proton Writing for the rapid prototyping of polymer micro-components for optical interconnects and optofluidics

NASA Astrophysics Data System (ADS)

Van Erps, Jürgen; Vervaeke, Michael; Ottevaere, Heidi; Hermanne, Alex; Thienpont, Hugo

2013-07-01

The use of photonics in data communication and numerous other industrial applications brought plenty of prospects for innovation and opened up different unexplored market opportunities. This is a major driving force for the fabrication of micro-optical and micro-mechanical structures and their accurate alignment and integration into opto-mechanical modules and systems. To this end, we present Deep Proton Writing (DPW) as a powerful rapid prototyping technology for such micro-components. The DPW process consists of bombarding polymer samples (PMMA or SU-8) with swift protons, which results after chemical processing steps in high-quality micro-optical components. One of the strengths of the DPW micro-fabrication technology is the ability to fabricate monolithic building blocks that include micro-optical and mechanical functionalities which can be precisely integrated into more complex photonic systems. In this paper we comment on how we shifted from using 8.3 to 16.5 MeV protons for DPW and give some examples of micro-optical and micro-mechanical components recently fabricated through DPW, targeting applications in optical interconnections and in optofluidics.

A decade of precision agriculture impacts on grain yield and yield variation

USDA-ARS?s Scientific Manuscript database

Targeting management practices and inputs with precision agriculture has high potential to meet some of the grand challenges of sustainability in the coming century, including simultaneously improving crop yields and reducing environmental impacts. Although the potential is high, few studies have do...

Delay times of a LiDAR-guided precision sprayer control system

USDA-ARS?s Scientific Manuscript database

Accurate flow control systems in triggering sprays against detected targets are needed for precision variable-rate sprayer development. System delay times due to the laser-sensor data buffer, software operation, and hydraulic-mechanical component response were determined for a control system used fo...

Biotemplated Morpho Butterfly Wings for Tunable Structurally Colored Photocatalysts.

PubMed

Rodríguez, Robin E; Agarwal, Sneha P; An, Shun; Kazyak, Eric; Das, Debashree; Shang, Wen; Skye, Rachael; Deng, Tao; Dasgupta, Neil P

2018-02-07

Morpho sulkowskyi butterfly wings contain naturally occurring hierarchical nanostructures that produce structural coloration. The high aspect ratio and surface area of these wings make them attractive nanostructured templates for applications in solar energy and photocatalysis. However, biomimetic approaches to replicate their complex structural features and integrate functional materials into their three-dimensional framework are highly limited in precision and scalability. Herein, a biotemplating approach is presented that precisely replicates Morpho nanostructures by depositing nanocrystalline ZnO coatings onto wings via low-temperature atomic layer deposition (ALD). This study demonstrates the ability to precisely tune the natural structural coloration while also integrating multifunctionality by imparting photocatalytic activity onto fully intact Morpho wings. Optical spectroscopy and finite-difference time-domain numerical modeling demonstrate that ALD ZnO coatings can rationally tune the structural coloration across the visible spectrum. These structurally colored photocatalysts exhibit an optimal coating thickness to maximize photocatalytic activity, which is attributed to trade-offs between light absorption and catalytic quantum yield with increasing coating thickness. These multifunctional photocatalysts present a new approach to integrating solar energy harvesting into visually attractive surfaces that can be integrated into building facades or other macroscopic structures to impart aesthetic appeal.

Precision medicine for nurses: 101.

PubMed

Lemoine, Colleen

2014-05-01

To introduce the key concepts and terms associated with precision medicine and support understanding of future developments in the field by providing an overview and history of precision medicine, related ethical considerations, and nursing implications. Current nursing, medical and basic science literature. Rapid progress in understanding the oncogenic drivers associated with cancer is leading to a shift toward precision medicine, where treatment is based on targeting specific genetic and epigenetic alterations associated with a particular cancer. Nurses will need to embrace the paradigm shift to precision medicine, expend the effort necessary to learn the essential terminology, concepts and principles, and work collaboratively with physician colleagues to best position our patients to maximize the potential that precision medicine can offer. Copyright © 2014 Elsevier Inc. All rights reserved.

Evaluation and selection of anatomic sites for magnetic resonance imaging-guided mild hyperthermia therapy: a healthy volunteer study.

PubMed

V V N Kothapalli, Satya; Altman, Michael B; Zhu, Lifei; Partanen, Ari; Cheng, Galen; Gach, H Michael; Straube, William; Zoberi, Imran; Hallahan, Dennis E; Chen, Hong

2018-01-04

Since mild hyperthermia therapy (MHT) requires maintaining the temperature within a narrow window (e.g. 40-43 °C) for an extended duration (up to 1 h), accurate and precise temperature measurements are essential for ensuring safe and effective treatment. This study evaluated the precision and accuracy of MR thermometry in healthy volunteers at different anatomical sites for long scan times. A proton resonance frequency shift method was used for MR thermometry. Eight volunteers were subjected to a 5-min scanning protocol, targeting chest wall, bladder wall, and leg muscles. Six volunteers were subjected to a 30-min scanning protocol and three volunteers were subjected to a 60-min scanning protocol, both targeting the leg muscles. The precision and accuracy of the MR thermometry were quantified. Both the mean precision and accuracy <1 °C were used as criteria for acceptable thermometry. Drift-corrected MR thermometry measurements based on 5-min scans of the chest wall, bladder wall, and leg muscles had accuracies of 1.41 ± 0.65, 1.86 ± 1.20, and 0.34 ± 0.44 °C, and precisions of 2.30 ± 1.21, 1.64 ± 0.56, and 0.48 ± 0.05 °C, respectively. Measurements based on 30-min scans of the leg muscles had accuracy and precision of 0.56 ± 0.05 °C and 0.42 ± 0.50 °C, respectively, while the 60-min scans had accuracy and precision of 0.49 ± 0.03 °C and 0.56 ± 0.05 °C, respectively. Respiration, cardiac, and digestive-related motion pose challenges to MR thermometry of the chest wall and bladder wall. The leg muscles had satisfactory temperature accuracy and precision per the chosen criteria. These results indicate that extremity locations may be preferable targets for MR-guided MHT using the existing MR thermometry technique.

Generation of novel resistance genes using mutation and targeted gene editing.

PubMed

Gal-On, Amit; Fuchs, Marc; Gray, Stewart

2017-10-01

Classical breeding for virus resistance is a lengthy process and is restricted by the availability of resistance genes. Precise genome editing is a 'dream technology' to improve plants for virus resistance and these tools have opened new and very promising ways to generate virus resistant plants by disrupting host susceptibility genes, or by increasing the expression of viral resistance genes. However, precise targets must be identified and their roles understood to minimize potential negative effects on the plant. Nonetheless, the opportunities for genome editing are expanding, as are the technologies to generate effective and broad-spectrum resistance against plant viruses. Here we provide insights into recent progress related to gene targets and gene editing technologies. Published by Elsevier B.V.

The Precision Problem in Conservation and Restoration.

PubMed

Hiers, J Kevin; Jackson, Stephen T; Hobbs, Richard J; Bernhardt, Emily S; Valentine, Leonie E

2016-11-01

Within the varied contexts of environmental policy, conservation of imperilled species populations, and restoration of damaged habitats, an emphasis on idealized optimal conditions has led to increasingly specific targets for management. Overly-precise conservation targets can reduce habitat variability at multiple scales, with unintended consequences for future ecological resilience. We describe this dilemma in the context of endangered species management, stream restoration, and climate-change adaptation. Inappropriate application of conservation targets can be expensive, with marginal conservation benefit. Reduced habitat variability can limit options for managers trying to balance competing objectives with limited resources. Conservation policies should embrace habitat variability, expand decision-space appropriately, and support adaptation to local circumstances to increase ecological resilience in a rapidly changing world. Copyright © 2016 Elsevier Ltd. All rights reserved.

Theranostics of prostate cancer: from molecular imaging to precision molecular radiotherapy targeting the prostate specific membrane antigen.

PubMed

Kulkarni, Harshad R; Singh, Aviral; Langbein, Thomas; Schuchardt, Christiane; Mueller, Dirk; Zhang, Jingjing; Lehmann, Coline; Baum, Richard P

2018-06-01

Alterations at the molecular level are a hallmark of cancer. Prostate cancer is associated with the overexpression of prostate-specific membrane antigen (PSMA) in a majority of cases, predominantly in advanced tumors, increasing with the grade or Gleason's score. PSMA can be selectively targeted using radiolabeled PSMA ligands. These small molecules binding the PSMA can be radiolabeled with γ-emitters like 99m Tc and 111 In or positron emitters like 68 Ga and 18 F for diagnosis as well as with their theranostic pairs such as 177 Lu (β-emitter) or 225 Ac (α-emitter) for therapy. This review summarizes the theranostic role of PSMA ligands for molecular imaging and targeted molecular radiotherapy, moving towards precision oncology.

The first clinical implementation of a real-time six degree of freedom target tracking system during radiation therapy based on Kilovoltage Intrafraction Monitoring (KIM).

PubMed

Nguyen, Doan Trang; O'Brien, Ricky; Kim, Jung-Ha; Huang, Chen-Yu; Wilton, Lee; Greer, Peter; Legge, Kimberley; Booth, Jeremy T; Poulsen, Per Rugaard; Martin, Jarad; Keall, Paul J

2017-04-01

We present the first clinical implementation of a real-time six-degree of freedom (6DoF) Kilovoltage Intrafraction Monitoring (KIM) system which tracks the cancer target translational and rotational motions during treatment. The method was applied to measure and correct for target motion during stereotactic body radiotherapy (SBRT) for prostate cancer. Patient: A patient with prostate adenocarcinoma undergoing SBRT with 36.25Gy, delivered in 5 fractions was enrolled in the study. 6DoF KIM technology: 2D positions of three implanted gold markers in each of the kV images (125kV, 10mA at 11Hz) were acquired continuously during treatment. The 2D→3D target position estimation was based on a probability distribution function. The 3D→6DoF target rotation was calculated using an iterative closest point algorithm. The accuracy and precision of the KIM method was measured by comparing the real-time results with kV-MV triangulation. Of the five treatment fractions, KIM was utilised successfully in four fractions. The intrafraction prostate motion resulted in three couch shifts in two fractions when the prostate motion exceeded the pre-set action threshold of 2mm for more than 5s. KIM translational accuracy and precision were 0.3±0.6mm, -0.2±0.3mm and 0.2±0.7mm in the Left-Right (LR), Superior-Inferior (SI) and Anterior-Posterior (AP) directions, respectively. The KIM rotational accuracy and precision were 0.8°±2.0°, -0.5°±3.3° and 0.3°±1.6° in the roll, pitch and yaw directions, respectively. This treatment represents, to the best of our knowledge, the first time a cancer patient's tumour position and rotation have been monitored in real-time during treatment. The 6 DoF KIM system has sub-millimetre accuracy and precision in all three translational axes, and less than 1° accuracy and 4° precision in all three rotational axes. Copyright © 2017 Elsevier B.V. All rights reserved.

Precision Control and Maneuvering of the Phoenix Autonomous Underwater Vehicle for Entering a Recovery Tube

DTIC Science & Technology

1996-09-01

T1wo such modes have buen iinrylvni teted: a full target-track mode0 and a target- edge-track mode. Whun using thc full target-track mode the sonai ...direction is reversed. Rather than tracking across the target all the way to the opposing edge, however, the sonai is scanned only until three returns

A miniaturized multipurpose platform for rapid, label-free, and simultaneous separation, patterning, and in vitro culture of primary and rare cells.

PubMed

Didar, Tohid Fatanat; Bowey, Kristen; Almazan, Guillermina; Tabrizian, Maryam

2014-02-01

Given that current cell isolation techniques are expensive, time consuming, yield low isolation purities, and/or alter target cell properties, a versatile, cost effective, and easy-to-operate microchip with the capability to simultaneously separate, capture, pattern, and culture rare and primary cells in vitro is developed. The platform is based on target cell adhesion onto the micro-fabricated interfaces produced by microcontact printing of cell-specific antibodies. Results show over 95% separation efficiency in less than 10 min for the separation of oligodendrocyte progenitor cells (OPCs) and cardiomyocytes from rat brain and heart mixtures, respectively. Target cell attachment and single cell spreading can be precisely controlled on the basis of the designed patterns. Both cell types can maintain their biofunctionality. Indeed, isolated OPCs can proliferate and differentiate into mature oligodendrocytes, while isolated cardiomyocytes retain their contractile properties on the separation platform. Successful separation of two dissimilar cell types present in varying concentrations in their respective cell mixtures and the demonstration of their integrity after separation open new avenues for time and cost-effective sorting of various cell types using the developed miniaturized platform. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systems-level modeling of mycobacterial metabolism for the identification of new (multi-)drug targets.

PubMed

Rienksma, Rienk A; Suarez-Diez, Maria; Spina, Lucie; Schaap, Peter J; Martins dos Santos, Vitor A P

2014-12-01

Systems-level metabolic network reconstructions and the derived constraint-based (CB) mathematical models are efficient tools to explore bacterial metabolism. Approximately one-fourth of the Mycobacterium tuberculosis (Mtb) genome contains genes that encode proteins directly involved in its metabolism. These represent potential drug targets that can be systematically probed with CB models through the prediction of genes essential (or the combination thereof) for the pathogen to grow. However, gene essentiality depends on the growth conditions and, so far, no in vitro model precisely mimics the host at the different stages of mycobacterial infection, limiting model predictions. These limitations can be circumvented by combining expression data from in vivo samples with a validated CB model, creating an accurate description of pathogen metabolism in the host. To this end, we present here a thoroughly curated and extended genome-scale CB metabolic model of Mtb quantitatively validated using 13C measurements. We describe some of the efforts made in integrating CB models and high-throughput data to generate condition specific models, and we will discuss challenges ahead. This knowledge and the framework herein presented will enable to identify potential new drug targets, and will foster the development of optimal therapeutic strategies. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Towards frameless maskless SRS through real-time 6DoF robotic motion compensation.

PubMed

Belcher, Andrew H; Liu, Xinmin; Chmura, Steven; Yenice, Kamil; Wiersma, Rodney D

2017-11-13

Stereotactic radiosurgery (SRS) uses precise dose placement to treat conditions of the CNS. Frame-based SRS uses a metal head ring fixed to the patient's skull to provide high treatment accuracy, but patient comfort and clinical workflow may suffer. Frameless SRS, while potentially more convenient, may increase uncertainty of treatment accuracy and be physiologically confining to some patients. By incorporating highly precise robotics and advanced software algorithms into frameless treatments, we present a novel frameless and maskless SRS system where a robot provides real-time 6DoF head motion stabilization allowing positional accuracies to match or exceed those of traditional frame-based SRS. A 6DoF parallel kinematics robot was developed and integrated with a real-time infrared camera in a closed loop configuration. A novel compensation algorithm was developed based on an iterative closest-path correction approach. The robotic SRS system was tested on six volunteers, whose motion was monitored and compensated for in real-time over 15 min simulated treatments. The system's effectiveness in maintaining the target's 6DoF position within preset thresholds was determined by comparing volunteer head motion with and without compensation. Comparing corrected and uncorrected motion, the 6DoF robotic system showed an overall improvement factor of 21 in terms of maintaining target position within 0.5 mm and 0.5 degree thresholds. Although the system's effectiveness varied among the volunteers examined, for all volunteers tested the target position remained within the preset tolerances 99.0% of the time when robotic stabilization was used, compared to 4.7% without robotic stabilization. The pre-clinical robotic SRS compensation system was found to be effective at responding to sub-millimeter and sub-degree cranial motions for all volunteers examined. The system's success with volunteers has demonstrated its capability for implementation with frameless and maskless SRS treatments, potentially able to achieve the same or better treatment accuracies compared to traditional frame-based approaches.

Progress integrating ID-TIMS U-Pb geochronology with accessory mineral geochemistry: towards better accuracy and higher precision time

NASA Astrophysics Data System (ADS)

Schoene, B.; Samperton, K. M.; Crowley, J. L.; Cottle, J. M.

2012-12-01

It is increasingly common that hand samples of plutonic and volcanic rocks contain zircon with dates that span between zero and >100 ka. This recognition comes from the increased application of U-series geochronology on young volcanic rocks and the increased precision to better than 0.1% on single zircons by the U-Pb ID-TIMS method. It has thus become more difficult to interpret such complicated datasets in terms of ashbed eruption or magma emplacement, which are critical constraints for geochronologic applications ranging from biotic evolution and the stratigraphic record to magmatic and metamorphic processes in orogenic belts. It is important, therefore, to develop methods that aid in interpreting which minerals, if any, date the targeted process. One promising tactic is to better integrate accessory mineral geochemistry with high-precision ID-TIMS U-Pb geochronology. These dual constraints can 1) identify cogenetic populations of minerals, and 2) record magmatic or metamorphic fluid evolution through time. Goal (1) has been widely sought with in situ geochronology and geochemical analysis but is limited by low-precision dates. Recent work has attempted to bridge this gap by retrieving the typically discarded elution from ion exchange chemistry that precedes ID-TIMS U-Pb geochronology and analyzing it by ICP-MS (U-Pb TIMS-TEA). The result integrates geochemistry and high-precision geochronology from the exact same volume of material. The limitation of this method is the relatively coarse spatial resolution compared to in situ techniques, and thus averages potentially complicated trace element profiles through single minerals or mineral fragments. In continued work, we test the effect of this on zircon by beginning with CL imaging to reveal internal zonation and growth histories. This is followed by in situ LA-ICPMS trace element transects of imaged grains to reveal internal geochemical zonation. The same grains are then removed from grain-mount, fragmented, and analyzed by U-Pb TIMS-TEA. In situ trace element transects are used to model predicted TIMS-TEA trace element concentrations to test whether complicated trace element profiles undermine U-Pb TIMS-TEA data. We find good agreement between predicted and measured TIMS-TEA data, and can argue that the measured ID-TIMS U-Pb date corresponds to the time at which the geochemical signature measured by TIMS-TEA was acquired. Thus, in a hypothetical magma that is differentiating through AFC processes on timescales resolvable by geochronology, U-Pb TIMS-TEA should usually be a robust indicator of magma evolution through time. We present data from two ca. 40-30 Ma alpine intrusions from northern Italy: the southern Adamello batholith and the Bergell intrusion. The relatively young age of these intrusions permits uncertainties on individual zircon or zircon fragments as good as 10 ka, while zircon populations from individual hand samples often record zircon growth of >200 ka. Using the methodologies described above, we explore whether these zircons record in situ magmatic differentiation or introduction of antecrystic zircon to magma batches, and integrate these data to gain a better understanding of magma storage, differentiation and emplacement as a function of pressure, temperature, and time. These methods are a promising step towards interpreting complicated geochronologic data in ashbed samples as well through a better understanding of magmatic processes that precede eruption.

Cone beam computed tomography image guidance system for a dedicated intracranial radiosurgery treatment unit.

PubMed

Ruschin, Mark; Komljenovic, Philip T; Ansell, Steve; Ménard, Cynthia; Bootsma, Gregory; Cho, Young-Bin; Chung, Caroline; Jaffray, David

2013-01-01

Image guidance has improved the precision of fractionated radiation treatment delivery on linear accelerators. Precise radiation delivery is particularly critical when high doses are delivered to complex shapes with steep dose gradients near critical structures, as is the case for intracranial radiosurgery. To reduce potential geometric uncertainties, a cone beam computed tomography (CT) image guidance system was developed in-house to generate high-resolution images of the head at the time of treatment, using a dedicated radiosurgery unit. The performance and initial clinical use of this imaging system are described. A kilovoltage cone beam CT system was integrated with a Leksell Gamma Knife Perfexion radiosurgery unit. The X-ray tube and flat-panel detector are mounted on a translational arm, which is parked above the treatment unit when not in use. Upon descent, a rotational axis provides 210° of rotation for cone beam CT scans. Mechanical integrity of the system was evaluated over a 6-month period. Subsequent clinical commissioning included end-to-end testing of targeting performance and subjective image quality performance in phantoms. The system has been used to image 2 patients, 1 of whom received single-fraction radiosurgery and 1 who received 3 fractions, using a relocatable head frame. Images of phantoms demonstrated soft tissue contrast visibility and submillimeter spatial resolution. A contrast difference of 35 HU was easily detected at a calibration dose of 1.2 cGy (center of head phantom). The shape of the mechanical flex vs scan angle was highly reproducible and exhibited <0.2 mm peak-to-peak variation. With a 0.5-mm voxel pitch, the maximum targeting error was 0.4 mm. Images of 2 patients were analyzed offline and submillimeter agreement was confirmed with conventional frame. A cone beam CT image guidance system was successfully adapted to a radiosurgery unit. The system is capable of producing high-resolution images of bone and soft tissue. The system is in clinical use and provides excellent image guidance without invasive frames. Copyright © 2013 Elsevier Inc. All rights reserved.

Neural control and precision of flight muscle activation in Drosophila.

PubMed

Lehmann, Fritz-Olaf; Bartussek, Jan

2017-01-01

Precision of motor commands is highly relevant in a large context of various locomotor behaviors, including stabilization of body posture, heading control and directed escape responses. While posture stability and heading control in walking and swimming animals benefit from high friction via ground reaction forces and elevated viscosity of water, respectively, flying animals have to cope with comparatively little aerodynamic friction on body and wings. Although low frictional damping in flight is the key to the extraordinary aerial performance and agility of flying birds, bats and insects, it challenges these animals with extraordinary demands on sensory integration and motor precision. Our review focuses on the dynamic precision with which Drosophila activates its flight muscular system during maneuvering flight, considering relevant studies on neural and muscular mechanisms of thoracic propulsion. In particular, we tackle the precision with which flies adjust power output of asynchronous power muscles and synchronous flight control muscles by monitoring muscle calcium and spike timing within the stroke cycle. A substantial proportion of the review is engaged in the significance of visual and proprioceptive feedback loops for wing motion control including sensory integration at the cellular level. We highlight that sensory feedback is the basis for precise heading control and body stability in flies.

VizieR Online Data Catalog: NGC 2264, NGC 2547 and NGC 2516 stellar radii (Jackson+, 2016)

NASA Astrophysics Data System (ADS)

Jackson, R. J.; Jeffries, R. D.; Randich, S.; Bragaglia, A.; Carraro, G.; Costado, M. T.; Flaccomio, E.; Lanzafame; Lardo, C.; Monaco, L.; Morbidelli, L.; Smiljanic, R.; Zaggia, S.

2015-11-01

File Table1.dat contains Photometric and spectroscopic data of GES Survey targets in clusters in NGC 2547, NGC 2516, NGC 22264 downloaded from the Edinburugh GES archive (http://ges/roe.ac.uk/) . Photometric data comprised the (Cousins) I magnitude and 2MASS J, H and K magnitudes. Spectroscopic data comprises the signal to noise ratio, S/N of the target spectrum, the radial velocity, RV (in km/s), the projected equatorial velocity, vsini (in km/s), the number of separate observations co-added to produce the target spectrum and the log of effective temperature (logTeff) of the template spectrum fitted to measure RV and vsini. The absolute precision in RV, pRV (in km/s) and relative precision vsini (pvsini) were estimated, as a function of the logTeff, vsini and S/N, using the prescription described in Jackson et al. (2015A&A...580A..75J, Cat. J/A+A/580/A75). File Table3.dat contains measured and calculated properties of cluster targets with resolved vsini and a reported rotation period. The cluster name, right ascension, RA (deg) and declination, Dec (deg) are given for targets with measured periods given in the literature. Dynamic properties comprise: the radial velocity, RV (in km/s), the absolute precision in RV, pRV (km/s), the projected equatorial velocity, vsini (in km/s), the relative precision in vsini (pvsini) and the rotational period (in days). Also shown are values of absolute K magnitude, MK log of luminosity, log L (in solar units) and probability of cluster membership estimated using cluster data given in the text. Period shows reported values of cluster taken from the literature Estimated values of the projected radius, Rsini (in Rsolar) and uncertainty in projected radius, e_Rsini (in Rsolar) are given for targets where vsini>5km/s and pvsini>0.2. The final column shows a flag which is set to 1 for targets in cluster NGC 2264 where a (H-K) versus (J-H) colour-colour plot indicates possible infra-red excess. Period shows reported values of cluster taken from the literature (2 data files).

The impact of early visual cortex transcranial magnetic stimulation on visual working memory precision and guess rate.

PubMed

Rademaker, Rosanne L; van de Ven, Vincent G; Tong, Frank; Sack, Alexander T

2017-01-01

Neuroimaging studies have demonstrated that activity patterns in early visual areas predict stimulus properties actively maintained in visual working memory. Yet, the mechanisms by which such information is represented remain largely unknown. In this study, observers remembered the orientations of 4 briefly presented gratings, one in each quadrant of the visual field. A 10Hz Transcranial Magnetic Stimulation (TMS) triplet was applied directly at stimulus offset, or midway through a 2-second delay, targeting early visual cortex corresponding retinotopically to a sample item in the lower hemifield. Memory for one of the four gratings was probed at random, and participants reported this orientation via method of adjustment. Recall errors were smaller when the visual field location targeted by TMS overlapped with that of the cued memory item, compared to errors for stimuli probed diagonally to TMS. This implied topographic storage of orientation information, and a memory-enhancing effect at the targeted location. Furthermore, early pulses impaired performance at all four locations, compared to late pulses. Next, response errors were fit empirically using a mixture model to characterize memory precision and guess rates. Memory was more precise for items proximal to the pulse location, irrespective of pulse timing. Guesses were more probable with early TMS pulses, regardless of stimulus location. Thus, while TMS administered at the offset of the stimulus array might disrupt early-phase consolidation in a non-topographic manner, TMS also boosts the precise representation of an item at its targeted retinotopic location, possibly by increasing attentional resources or by injecting a beneficial amount of noise.

The impact of early visual cortex transcranial magnetic stimulation on visual working memory precision and guess rate

PubMed Central

van de Ven, Vincent G.; Tong, Frank; Sack, Alexander T.

2017-01-01

Neuroimaging studies have demonstrated that activity patterns in early visual areas predict stimulus properties actively maintained in visual working memory. Yet, the mechanisms by which such information is represented remain largely unknown. In this study, observers remembered the orientations of 4 briefly presented gratings, one in each quadrant of the visual field. A 10Hz Transcranial Magnetic Stimulation (TMS) triplet was applied directly at stimulus offset, or midway through a 2-second delay, targeting early visual cortex corresponding retinotopically to a sample item in the lower hemifield. Memory for one of the four gratings was probed at random, and participants reported this orientation via method of adjustment. Recall errors were smaller when the visual field location targeted by TMS overlapped with that of the cued memory item, compared to errors for stimuli probed diagonally to TMS. This implied topographic storage of orientation information, and a memory-enhancing effect at the targeted location. Furthermore, early pulses impaired performance at all four locations, compared to late pulses. Next, response errors were fit empirically using a mixture model to characterize memory precision and guess rates. Memory was more precise for items proximal to the pulse location, irrespective of pulse timing. Guesses were more probable with early TMS pulses, regardless of stimulus location. Thus, while TMS administered at the offset of the stimulus array might disrupt early-phase consolidation in a non-topographic manner, TMS also boosts the precise representation of an item at its targeted retinotopic location, possibly by increasing attentional resources or by injecting a beneficial amount of noise. PMID:28384347

High Precision Edge Detection Algorithm for Mechanical Parts

NASA Astrophysics Data System (ADS)

Duan, Zhenyun; Wang, Ning; Fu, Jingshun; Zhao, Wenhui; Duan, Boqiang; Zhao, Jungui

2018-04-01

High precision and high efficiency measurement is becoming an imperative requirement for a lot of mechanical parts. So in this study, a subpixel-level edge detection algorithm based on the Gaussian integral model is proposed. For this purpose, the step edge normal section line Gaussian integral model of the backlight image is constructed, combined with the point spread function and the single step model. Then gray value of discrete points on the normal section line of pixel edge is calculated by surface interpolation, and the coordinate as well as gray information affected by noise is fitted in accordance with the Gaussian integral model. Therefore, a precise location of a subpixel edge was determined by searching the mean point. Finally, a gear tooth was measured by M&M3525 gear measurement center to verify the proposed algorithm. The theoretical analysis and experimental results show that the local edge fluctuation is reduced effectively by the proposed method in comparison with the existing subpixel edge detection algorithms. The subpixel edge location accuracy and computation speed are improved. And the maximum error of gear tooth profile total deviation is 1.9 μm compared with measurement result with gear measurement center. It indicates that the method has high reliability to meet the requirement of high precision measurement.

Digital PCR Modeling for Maximal Sensitivity, Dynamic Range and Measurement Precision

PubMed Central

Majumdar, Nivedita; Wessel, Thomas; Marks, Jeffrey

2015-01-01

The great promise of digital PCR is the potential for unparalleled precision enabling accurate measurements for genetic quantification. A challenge associated with digital PCR experiments, when testing unknown samples, is to perform experiments at dilutions allowing the detection of one or more targets of interest at a desired level of precision. While theory states that optimal precision (Po) is achieved by targeting ~1.59 mean copies per partition (λ), and that dynamic range (R) includes the space spanning one positive (λL) to one negative (λU) result from the total number of partitions (n), these results are tempered for the practitioner seeking to construct digital PCR experiments in the laboratory. A mathematical framework is presented elucidating the relationships between precision, dynamic range, number of partitions, interrogated volume, and sensitivity in digital PCR. The impact that false reaction calls and volumetric variation have on sensitivity and precision is next considered. The resultant effects on sensitivity and precision are established via Monte Carlo simulations reflecting the real-world likelihood of encountering such scenarios in the laboratory. The simulations provide insight to the practitioner on how to adapt experimental loading concentrations to counteract any one of these conditions. The framework is augmented with a method of extending the dynamic range of digital PCR, with and without increasing n, via the use of dilutions. An example experiment demonstrating the capabilities of the framework is presented enabling detection across 3.33 logs of starting copy concentration. PMID:25806524

Unexpected arousal modulates the influence of sensory noise on confidence

PubMed Central

Allen, Micah; Frank, Darya; Schwarzkopf, D Samuel; Fardo, Francesca; Winston, Joel S; Hauser, Tobias U; Rees, Geraint

2016-01-01

Human perception is invariably accompanied by a graded feeling of confidence that guides metacognitive awareness and decision-making. It is often assumed that this arises solely from the feed-forward encoding of the strength or precision of sensory inputs. In contrast, interoceptive inference models suggest that confidence reflects a weighted integration of sensory precision and expectations about internal states, such as arousal. Here we test this hypothesis using a novel psychophysical paradigm, in which unseen disgust-cues induced unexpected, unconscious arousal just before participants discriminated motion signals of variable precision. Across measures of perceptual bias, uncertainty, and physiological arousal we found that arousing disgust cues modulated the encoding of sensory noise. Furthermore, the degree to which trial-by-trial pupil fluctuations encoded this nonlinear interaction correlated with trial level confidence. Our results suggest that unexpected arousal regulates perceptual precision, such that subjective confidence reflects the integration of both external sensory and internal, embodied states. DOI: http://dx.doi.org/10.7554/eLife.18103.001 PMID:27776633

A primer on precision medicine informatics.

PubMed

Sboner, Andrea; Elemento, Olivier

2016-01-01

In this review, we describe key components of a computational infrastructure for a precision medicine program that is based on clinical-grade genomic sequencing. Specific aspects covered in this review include software components and hardware infrastructure, reporting, integration into Electronic Health Records for routine clinical use and regulatory aspects. We emphasize informatics components related to reproducibility and reliability in genomic testing, regulatory compliance, traceability and documentation of processes, integration into clinical workflows, privacy requirements, prioritization and interpretation of results to report based on clinical needs, rapidly evolving knowledge base of genomic alterations and clinical treatments and return of results in a timely and predictable fashion. We also seek to differentiate between the use of precision medicine in germline and cancer. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Precise small molecule recognition of a toxic CUG RNA repeat expansion

PubMed Central

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-01-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)exp) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)exp. In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)exp in its natural context. PMID:27941760

Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

PubMed

Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

2017-02-01

Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG) exp ) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG) exp . In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG) exp and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG) exp in its natural context.

The functional consequences of social distraction: Attention and memory for complex scenes.

PubMed

Doherty, Brianna Ruth; Patai, Eva Zita; Duta, Mihaela; Nobre, Anna Christina; Scerif, Gaia

2017-01-01

Cognitive scientists have long proposed that social stimuli attract visual attention even when task irrelevant, but the consequences of this privileged status for memory are unknown. To address this, we combined computational approaches, eye-tracking methodology, and individual-differences measures. Participants searched for targets in scenes containing social or non-social distractors equated for low-level visual salience. Subsequent memory precision for target locations was tested. Individual differences in autistic traits and social anxiety were also measured. Eye-tracking revealed significantly more attentional capture to social compared to non-social distractors. Critically, memory precision for target locations was poorer for social scenes. This effect was moderated by social anxiety, with anxious individuals remembering target locations better under conditions of social distraction. These findings shed further light onto the privileged attentional status of social stimuli and its functional consequences on memory across individuals. Copyright © 2016. Published by Elsevier B.V.

Tumour homing and therapeutic effect of colloidal nanoparticles depend on the number of attached antibodies

PubMed Central

Colombo, Miriam; Fiandra, Luisa; Alessio, Giulia; Mazzucchelli, Serena; Nebuloni, Manuela; De Palma, Clara; Kantner, Karsten; Pelaz, Beatriz; Rotem, Rany; Corsi, Fabio; Parak, Wolfgang J.; Prosperi, Davide

2016-01-01

Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect. PMID:27991503

A new type industrial total station based on target automatic collimation

NASA Astrophysics Data System (ADS)

Lao, Dabao; Zhou, Weihu; Ji, Rongyi; Dong, Dengfeng; Xiong, Zhi; Wei, Jiang

2018-01-01

In the case of industrial field measurement, the present measuring instruments work with manual operation and collimation, which give rise to low efficiency for field measurement. In order to solve the problem, a new type industrial total station is presented in this paper. The new instrument can identify and trace cooperative target automatically, in the mean time, coordinate of the target is measured in real time. For realizing the system, key technology including high precision absolutely distance measurement, small high accuracy angle measurement, target automatic collimation with vision, and quick precise controlling should be worked out. After customized system assemblage and adjustment, the new type industrial total station will be established. As the experiments demonstrated, the coordinate accuracy of the instrument is under 15ppm in the distance of 60m, which proved that the measuring system is feasible. The result showed that the total station can satisfy most industrial field measurement requirements.

Heliostat calibration using attached cameras and artificial targets

NASA Astrophysics Data System (ADS)

Burisch, Michael; Sanchez, Marcelino; Olarra, Aitor; Villasante, Cristobal

2016-05-01

The efficiency of the solar field greatly depends on the ability of the heliostats to precisely reflect solar radiation onto a central receiver. To control the heliostats with such a precision requires the accurate knowledge of the motion of each of them. The motion of each heliostat can be described by a set of parameters, most notably the position and axis configuration. These parameters have to be determined individually for each heliostat during a calibration process. With the ongoing development of small sized heliostats, the ability to automatically perform such a calibration becomes more and more crucial as possibly hundreds of thousands of heliostats are involved. Furthermore, efficiency becomes an important factor as small sized heliostats potentially have to be recalibrated far more often, due to the limited stability of the components. In the following we present an automatic calibration procedure using cameras attached to each heliostat which are observing different targets spread throughout the solar field. Based on a number of observations of these targets under different heliostat orientations, the parameters describing the heliostat motion can be estimated with high precision.

Deterministic bead-in-droplet ejection utilizing an integrated plug-in bead dispenser for single bead-based applications

NASA Astrophysics Data System (ADS)

Kim, Hojin; Choi, In Ho; Lee, Sanghyun; Won, Dong-Joon; Oh, Yong Suk; Kwon, Donghoon; Sung, Hyung Jin; Jeon, Sangmin; Kim, Joonwon

2017-04-01

This paper presents a deterministic bead-in-droplet ejection (BIDE) technique that regulates the precise distribution of microbeads in an ejected droplet. The deterministic BIDE was realized through the effective integration of a microfluidic single-particle handling technique with a liquid dispensing system. The integrated bead dispenser facilitates the transfer of the desired number of beads into a dispensing volume and the on-demand ejection of bead-encapsulated droplets. Single bead-encapsulated droplets were ejected every 3 s without any failure. Multiple-bead dispensing with deterministic control of the number of beads was demonstrated to emphasize the originality and quality of the proposed dispensing technique. The dispenser was mounted using a plug-socket type connection, and the dispensing process was completely automated using a programmed sequence without any microscopic observation. To demonstrate a potential application of the technique, bead-based streptavidin-biotin binding assay in an evaporating droplet was conducted using ultralow numbers of beads. The results evidenced the number of beads in the droplet crucially influences the reliability of the assay. Therefore, the proposed deterministic bead-in-droplet technology can be utilized to deliver desired beads onto a reaction site, particularly to reliably and efficiently enrich and detect target biomolecules.

Deterministic bead-in-droplet ejection utilizing an integrated plug-in bead dispenser for single bead-based applications.

PubMed

Kim, Hojin; Choi, In Ho; Lee, Sanghyun; Won, Dong-Joon; Oh, Yong Suk; Kwon, Donghoon; Sung, Hyung Jin; Jeon, Sangmin; Kim, Joonwon

2017-04-10

This paper presents a deterministic bead-in-droplet ejection (BIDE) technique that regulates the precise distribution of microbeads in an ejected droplet. The deterministic BIDE was realized through the effective integration of a microfluidic single-particle handling technique with a liquid dispensing system. The integrated bead dispenser facilitates the transfer of the desired number of beads into a dispensing volume and the on-demand ejection of bead-encapsulated droplets. Single bead-encapsulated droplets were ejected every 3 s without any failure. Multiple-bead dispensing with deterministic control of the number of beads was demonstrated to emphasize the originality and quality of the proposed dispensing technique. The dispenser was mounted using a plug-socket type connection, and the dispensing process was completely automated using a programmed sequence without any microscopic observation. To demonstrate a potential application of the technique, bead-based streptavidin-biotin binding assay in an evaporating droplet was conducted using ultralow numbers of beads. The results evidenced the number of beads in the droplet crucially influences the reliability of the assay. Therefore, the proposed deterministic bead-in-droplet technology can be utilized to deliver desired beads onto a reaction site, particularly to reliably and efficiently enrich and detect target biomolecules.

Deterministic bead-in-droplet ejection utilizing an integrated plug-in bead dispenser for single bead–based applications

PubMed Central

Kim, Hojin; Choi, In Ho; Lee, Sanghyun; Won, Dong-Joon; Oh, Yong Suk; Kwon, Donghoon; Sung, Hyung Jin; Jeon, Sangmin; Kim, Joonwon

2017-01-01

This paper presents a deterministic bead-in-droplet ejection (BIDE) technique that regulates the precise distribution of microbeads in an ejected droplet. The deterministic BIDE was realized through the effective integration of a microfluidic single-particle handling technique with a liquid dispensing system. The integrated bead dispenser facilitates the transfer of the desired number of beads into a dispensing volume and the on-demand ejection of bead-encapsulated droplets. Single bead–encapsulated droplets were ejected every 3 s without any failure. Multiple-bead dispensing with deterministic control of the number of beads was demonstrated to emphasize the originality and quality of the proposed dispensing technique. The dispenser was mounted using a plug-socket type connection, and the dispensing process was completely automated using a programmed sequence without any microscopic observation. To demonstrate a potential application of the technique, bead-based streptavidin–biotin binding assay in an evaporating droplet was conducted using ultralow numbers of beads. The results evidenced the number of beads in the droplet crucially influences the reliability of the assay. Therefore, the proposed deterministic bead-in-droplet technology can be utilized to deliver desired beads onto a reaction site, particularly to reliably and efficiently enrich and detect target biomolecules. PMID:28393911

High-precision ground-based photometry of exoplanets

NASA Astrophysics Data System (ADS)

de Mooij, Ernst J. W.; Jayawardhana, Ray

2013-04-01

High-precision photometry of transiting exoplanet systems has contributed significantly to our understanding of the properties of their atmospheres. The best targets are the bright exoplanet systems, for which the high number of photons allow very high signal-to-noise ratios. Most of the current instruments are not optimised for these high-precision measurements, either they have a large read-out overhead to reduce the readnoise and/or their field-of-view is limited, preventing simultaneous observations of both the target and a reference star. Recently we have proposed a new wide-field imager for the Observatoir de Mont-Megantic optimised for these bright systems (PI: Jayawardhana). The instruments has a dual beam design and a field-of-view of 17' by 17'. The cameras have a read-out time of 2 seconds, significantly reducing read-out overheads. Over the past years we have obtained significant experience with how to reach the high precision required for the characterisation of exoplanet atmospheres. Based on our experience we provide the following advice: Get the best calibrations possible. In the case of bad weather, characterise the instrument (e.g. non-linearity, dome flats, bias level), this is vital for better understanding of the science data. Observe the target for as long as possible, the out-of-transit baseline is as important as the transit/eclipse itself. A short baseline can lead to improperly corrected systematic and mis-estimation of the red-noise. Keep everything (e.g. position on detector, exposure time) as stable as possible. Take care that the defocus is not too strong. For a large defocus, the contribution of the total flux from the sky-background in the aperture could well exceed that of the target, resulting in very strict requirements on the precision at which the background is measured.

Target Context Specification Can Reduce Costs in Nonfocal Prospective Memory

ERIC Educational Resources Information Center

Lourenço, Joana S.; White, Katherine; Maylor, Elizabeth A.

2013-01-01

Performing a nonfocal prospective memory (PM) task results in a cost to ongoing task processing, but the precise nature of the monitoring processes involved remains unclear. We investigated whether target context specification (i.e., explicitly associating the PM target with a subset of ongoing stimuli) can trigger trial-by-trial changes in task…

The iso-response method: measuring neuronal stimulus integration with closed-loop experiments

PubMed Central

Gollisch, Tim; Herz, Andreas V. M.

2012-01-01

Throughout the nervous system, neurons integrate high-dimensional input streams and transform them into an output of their own. This integration of incoming signals involves filtering processes and complex non-linear operations. The shapes of these filters and non-linearities determine the computational features of single neurons and their functional roles within larger networks. A detailed characterization of signal integration is thus a central ingredient to understanding information processing in neural circuits. Conventional methods for measuring single-neuron response properties, such as reverse correlation, however, are often limited by the implicit assumption that stimulus integration occurs in a linear fashion. Here, we review a conceptual and experimental alternative that is based on exploring the space of those sensory stimuli that result in the same neural output. As demonstrated by recent results in the auditory and visual system, such iso-response stimuli can be used to identify the non-linearities relevant for stimulus integration, disentangle consecutive neural processing steps, and determine their characteristics with unprecedented precision. Automated closed-loop experiments are crucial for this advance, allowing rapid search strategies for identifying iso-response stimuli during experiments. Prime targets for the method are feed-forward neural signaling chains in sensory systems, but the method has also been successfully applied to feedback systems. Depending on the specific question, “iso-response” may refer to a predefined firing rate, single-spike probability, first-spike latency, or other output measures. Examples from different studies show that substantial progress in understanding neural dynamics and coding can be achieved once rapid online data analysis and stimulus generation, adaptive sampling, and computational modeling are tightly integrated into experiments. PMID:23267315

An object-mediated updating account of insensitivity to transsaccadic change

PubMed Central

Tas, A. Caglar; Moore, Cathleen M.; Hollingworth, Andrew

2012-01-01

Recent evidence has suggested that relatively precise information about the location and visual form of a saccade target object is retained across a saccade. However, this information appears to be available for report only when the target is removed briefly, so that the display is blank when the eyes land. We hypothesized that the availability of precise target information is dependent on whether a post-saccade object is mapped to the same object representation established for the presaccade target. If so, then the post-saccade features of the target overwrite the presaccade features, a process of object mediated updating in which visual masking is governed by object continuity. In two experiments, participants' sensitivity to the spatial displacement of a saccade target was improved when that object changed surface feature properties across the saccade, consistent with the prediction of the object-mediating updating account. Transsaccadic perception appears to depend on a mechanism of object-based masking that is observed across multiple domains of vision. In addition, the results demonstrate that surface-feature continuity contributes to visual stability across saccades. PMID:23092946

Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?

PubMed

Chung, Clement; Ma, Hilary

2017-09-01

Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not changed significantly over the last few decades. We present a nonexhaustive summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways. Some of these targets may be used as predictive biomarkers for the development of novel targeted therapies that depart significantly from conventional chemotherapy, the current mainstay for the treatment of acute leukemias. Established leukemia-specific predictive biomarkers for precision medicine include those genetic lesions such as BCR-ABL1 for Philadelphia-positive acute lymphoblastic leukemia and PML-RARα for acute promyelocytic leukemia. Evidence indicates that targeted therapy for FLT-ITD gene mutations with small-molecule tyrosine kinase inhibitors can extend its use from relapsed disease to up-front induction therapy. Core-binding factor acute myeloid leukemia in adults predicts benefit with high-dose cytarabine in the absence of KIT mutation. Although risk-adapted therapy based on genetic abnormalities in acute leukemias has allowed the beginning of personalized treatment and selective use of hematopoietic stem cell transplantation, the prognostic and/or predictive value of many novel mutations of the acute leukemic genome is yet to be elucidated. Many challenges lie ahead in targeted therapies due to overlapping of chromosomal and molecular lesions as well as other limiting factors. Future work should focus on the understanding of pathogenetic changes that lead to leukemogenesis, which may guide the rational design of new targeted therapies and make the drive toward precision medicine for acute leukemias one step closer. © 2017 Pharmacotherapy Publications, Inc.

Integration of autopatching with automated pipette and cell detection in vitro

PubMed Central

Wu (吴秋雨), Qiuyu; Kolb, Ilya; Callahan, Brendan M.; Su, Zhaolun; Stoy, William; Kodandaramaiah, Suhasa B.; Neve, Rachael; Zeng, Hongkui; Boyden, Edward S.; Forest, Craig R.

2016-01-01

Patch clamp is the main technique for measuring electrical properties of individual cells. Since its discovery in 1976 by Neher and Sakmann, patch clamp has been instrumental in broadening our understanding of the fundamental properties of ion channels and synapses in neurons. The conventional patch-clamp method requires manual, precise positioning of a glass micropipette against the cell membrane of a visually identified target neuron. Subsequently, a tight “gigaseal” connection between the pipette and the cell membrane is established, and suction is applied to establish the whole cell patch configuration to perform electrophysiological recordings. This procedure is repeated manually for each individual cell, making it labor intensive and time consuming. In this article we describe the development of a new automatic patch-clamp system for brain slices, which integrates all steps of the patch-clamp process: image acquisition through a microscope, computer vision-based identification of a patch pipette and fluorescently labeled neurons, micromanipulator control, and automated patching. We validated our system in brain slices from wild-type and transgenic mice expressing channelrhodopsin 2 under the Thy1 promoter (line 18) or injected with a herpes simplex virus-expressing archaerhodopsin, ArchT. Our computer vision-based algorithm makes the fluorescent cell detection and targeting user independent. Compared with manual patching, our system is superior in both success rate and average trial duration. It provides more reliable trial-to-trial control of the patching process and improves reproducibility of experiments. PMID:27385800

Method for the numerical integration of equations of perturbed satellite motion in problems of space geodesy

NASA Astrophysics Data System (ADS)

Plakhov, Iu. V.; Mytsenko, A. V.; Shel'Pov, V. A.

A numerical integration method is developed that is more accurate than Everhart's (1974) implicit single-sequence approach for integrating orbits. This method can be used to solve problems of space geodesy based on the use of highly precise laser observations.

EVEREST: Pixel Level Decorrelation of K2 Light Curves

NASA Astrophysics Data System (ADS)

Luger, Rodrigo; Agol, Eric; Kruse, Ethan; Barnes, Rory; Becker, Andrew; Foreman-Mackey, Daniel; Deming, Drake

2016-10-01

We present EPIC Variability Extraction and Removal for Exoplanet Science Targets (EVEREST), an open-source pipeline for removing instrumental noise from K2 light curves. EVEREST employs a variant of pixel level decorrelation to remove systematics introduced by the spacecraft’s pointing error and a Gaussian process to capture astrophysical variability. We apply EVEREST to all K2 targets in campaigns 0-7, yielding light curves with precision comparable to that of the original Kepler mission for stars brighter than {K}p≈ 13, and within a factor of two of the Kepler precision for fainter targets. We perform cross-validation and transit injection and recovery tests to validate the pipeline, and compare our light curves to the other de-trended light curves available for download at the MAST High Level Science Products archive. We find that EVEREST achieves the highest average precision of any of these pipelines for unsaturated K2 stars. The improved precision of these light curves will aid in exoplanet detection and characterization, investigations of stellar variability, asteroseismology, and other photometric studies. The EVEREST pipeline can also easily be applied to future surveys, such as the TESS mission, to correct for instrumental systematics and enable the detection of low signal-to-noise transiting exoplanets. The EVEREST light curves and the source code used to generate them are freely available online.

Applications of CRISPR genome editing technology in drug target identification and validation.

PubMed

Lu, Quinn; Livi, George P; Modha, Sundip; Yusa, Kosuke; Macarrón, Ricardo; Dow, David J

2017-06-01

The analysis of pharmaceutical industry data indicates that the major reason for drug candidates failing in late stage clinical development is lack of efficacy, with a high proportion of these due to erroneous hypotheses about target to disease linkage. More than ever, there is a requirement to better understand potential new drug targets and their role in disease biology in order to reduce attrition in drug development. Genome editing technology enables precise modification of individual protein coding genes, as well as noncoding regulatory sequences, enabling the elucidation of functional effects in human disease relevant cellular systems. Areas covered: This article outlines applications of CRISPR genome editing technology in target identification and target validation studies. Expert opinion: Applications of CRISPR technology in target validation studies are in evidence and gaining momentum. Whilst technical challenges remain, we are on the cusp of CRISPR being applied in complex cell systems such as iPS derived differentiated cells and stem cell derived organoids. In the meantime, our experience to date suggests that precise genome editing of putative targets in primary cell systems is possible, offering more human disease relevant systems than conventional cell lines.

Molecular model of cannabis sensitivity in developing neuronal circuits

PubMed Central

Keimpema, Erik; Mackie, Ken; Harkany, Tibor

2011-01-01

Prenatal cannabis exposure can complicate in utero development of the nervous system. Cannabis impacts the formation and functions of neuronal circuitries by targeting cannabinoid receptors. Endocannabinoid signaling emerges as a signaling cassette to orchestrate neuronal differentiation programs through the precisely timed interaction of endocannabinoid ligands with their cognate cannabinoid receptors. By indiscriminately prolonging the ‘switched-on’ period of cannabinoid receptors, cannabis can hijack endocannabinoid signals to evoke molecular rearrangements, leading to the erroneous wiring of neuronal networks. Here, we formulate a hierarchical network design necessary and sufficient to describe molecular underpinnings of cannabis-induced neural growth defects. We integrate signalosome components deduced from genome- and proteome-wide arrays and candidate analyses to propose a mechanistic hypothesis on how cannabis-induced ectopic cannabinoid receptor activity overrides physiological neurodevelopmental endocannabinoid signals, affecting the timely formation of synapses. PMID:21757242