Neuronal hyperexcitability in the ventral posterior thalamus of neuropathic rats: modality selective effects of pregabalin.

PubMed

Patel, Ryan; Dickenson, Anthony H

2016-07-01

Neuropathic pain represents a substantial clinical challenge; understanding the underlying neural mechanisms and back-translation of therapeutics could aid targeting of treatments more effectively. The ventral posterior thalamus (VP) is the major termination site for the spinothalamic tract and relays nociceptive activity to the somatosensory cortex; however, under neuropathic conditions, it is unclear how hyperexcitability of spinal neurons converges onto thalamic relays. This study aimed to identify neural substrates of hypersensitivity and the influence of pregabalin on central processing. In vivo electrophysiology was performed to record from VP wide dynamic range (WDR) and nociceptive-specific (NS) neurons in anesthetized spinal nerve-ligated (SNL), sham-operated, and naive rats. In neuropathic rats, WDR neurons had elevated evoked responses to low- and high-intensity punctate mechanical stimuli, dynamic brushing, and innocuous and noxious cooling, but less so to heat stimulation, of the receptive field. NS neurons in SNL rats also displayed increased responses to noxious punctate mechanical stimulation, dynamic brushing, noxious cooling, and noxious heat. Additionally, WDR, but not NS, neurons in SNL rats exhibited substantially higher rates of spontaneous firing, which may correlate with ongoing pain. The ratio of WDR-to-NS neurons was comparable between SNL and naive/sham groups, suggesting relatively few NS neurons gain sensitivity to low-intensity stimuli leading to a "WDR phenotype." After neuropathy was induced, the proportion of cold-sensitive WDR and NS neurons increased, supporting the suggestion that changes in frequency-dependent firing and population coding underlie cold hypersensitivity. In SNL rats, pregabalin inhibited mechanical and heat responses but not cold-evoked or elevated spontaneous activity. Copyright © 2016 the American Physiological Society.

Motor cortex stimulation for movement disorders.

PubMed

Cioni, Beatrice; Tufo, Tommaso; Bentivoglio, Annarita; Trevisi, Gianluca; Piano, Carla

2016-06-01

Motor cortex stimulation (MCS) was introduced by Tsubokawa in 1991 1 for the treatment of thalamic pain, after coming to the conclusion that the hyperactivity of thalamic neurons after spino-thalamic tractotomy was inhibited by stimulation of the motor cortex. MCS has been reported not only to be effective on pain, but also to improve movement disorders such as Parkinson's disease, tremor, dystonia, poststroke movement disorders and hemiparesis. Most of these publications are case reports or small series, and the real impact of MCS on movement disorders remains to be determined. In order to clarify this point, we conducted a PubMed search from 1991 to 2016 using established MeSH words. A total of 40 papers were selected and examined. Furthermore, personal experience with MCS for Parkinson's disease and akinesia, is reported. Only four studies were randomized controlled clinical trials: three out of four failed to demonstrate the efficacy of MCS at short term. At long term, MCS seems to show a clinical positive effect in the studies prolonged in an open observational trial.

Responses of spinothalamic lamina I neurons to repeated brief contact heat stimulation in the cat.

PubMed

Craig, A D; Andrew, D

2002-04-01

It was recently shown that repeated heat stimulation, using brief contacts (<1 s) with a preheated thermode at sufficiently short interstimulus intervals (ISIs <5 s) and high temperatures (> or =51 degrees C), will elicit in humans a sensation of rapidly augmenting "second" (burning) pain with only a weak "first" (sharp) pain sensation. Most strikingly, at short intertrial intervals (ITIs >5 s) such summation will reset, or begin again at baseline. In the present experiments, the responses of nociceptive lamina I spinothalamic (STT) neurons in the lumbosacral dorsal horn of barbiturate-anesthetized cats were examined using this repeated brief contact heat paradigm. The neurons were classified as nociceptive-specific (NS, n = 8) or polymodal nociceptive (HPC, n = 8) based on their responses to quantitative thermal stimuli; all had receptive fields on the glabrous ventral hindpaw. A pneumatic piston was used to apply a thermode preheated to 34, 46, 49, 53, or 58 degrees C with a contact dwell time of approximately 0.7 s to the ventral hindpaw repeatedly (15 times) at ISIs of 2, 3, and 5 s, with 3-5 min between trials. The mean responses of the 16 nociceptive lamina I STT cells showed rapid temporal summation that was directly dependent on temperature and inversely dependent on ISI, with the greatest increases occurring between the 3rd and 10th contacts. The temporal profiles of this family of curves correspond with the psychophysical data on human sensation. Further analysis showed that this summation was due to the HPC cells, which all showed strong summation; in contrast, the NS cells showed little, if any. The HPC responses to the repeated heat stimuli lagged each contact by approximately 1 s, consistent with the strong, monosynaptic C-fiber input that is characteristic of HPC cells and also with the dependence of second pain on C-fiber nociceptors. HPC cells also displayed the reset phenomenon at short ITIs, again in correspondence with the psychophysical data. The summation and the reset displayed by HPC cells were not related to skin temperature. Thus the results presented in this study, together with those in the preceding article, demonstrate a double dissociation indicating that NS and HPC lamina I STT cells can subserve the qualitatively distinct sensations of first (sharp) and second (burning) pain, respectively. These findings support the concept that the lamina I STT projection comprises several discrete sensory channels that are integrated in the forebrain to generate distinct sensations.

The Neurobiology and Psychiatric Perspective of Vaginismus: Linking the Pharmacological and Psycho-Social Interventions.

PubMed

Kadir, Zuri Shahidii; Sidi, Hatta; Kumar, Jaya; Das, Srijit; Midin, Marhani; Baharuddin, Najwa

2018-01-01

Vaginismus is an involuntary muscle contraction of the outer third of vaginal barrel causing sexual penetration almost impossible. It is generally classified under sexual pain disorder (SPD). In Diagnostic and Statistical Manual, 5th edition (DSM-5), it is classified under the new rubric of Genito-Pelvic Pain/Sexual Penetration Disorder. This fear-avoidance condition poses an ongoing significant challenge to the medical and health professionals due to the very demanding needs in health care despite its unpredictable prognosis. The etiology of vaginismus is complex: through multiple biopsycho- social processes, involving bidirectional connections between pelvic-genital (local) and higher mental function (central regulation). It has robust neural and psychological-cognitive loop feedback involvement. The internal neural circuit involves an inter-play of at least two-pathway systems, i.e. both "quick threat assessment" of occipital-limbic-occipital-prefrontal-pelvic-genital; and the chronic pain pathways through the genito-spinothalamic-parietal-pre-frontal system, respectively. In this review, a neurobiology root of vaginismus is deliberated with the central role of an emotional-regulating amygdala, and other neural loop, i.e. hippocampus and neo-cortex in the core psychopathology of fear, disgust, and sexual avoidance. Many therapists view vaginismus as a neglected art-and-science which demands a better and deeper understanding on the clinico-pathological correlation to enhance an effective model for the bio-psycho-social treatment. As vaginismus has a strong presentation in psychopathology, i.e. fear of penetration, phobic avoidance, disgust, and anticipatory anxiety, we highlighted a practical psychiatric approach to the clinical management of vaginismus, based on the current core knowledge in the perspective of neuroscience. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Jaundice associated pruritis: a review of pathophysiology and treatment.

PubMed

Bassari, Ramez; Koea, Jonathan B

2015-02-07

To review the underlying pathophysiology and currently available treatments for pruritis associated with jaundice. English language literature was reviewed using MEDLINE, PubMed, EMBASE and clinicaltrials.gov for papers and trails addressing the pathophysiology and potential treatments for pruritis associated with jaundice. Recent advances in the understanding of the peripheral anatomy of itch transmission have defined a histamine stimulated pathway and a cowhage stimulated pathway with sensation conveyed centrally via the contralateral spinothalamic tract. Centrally, cowhage and histamine stimulated neurons terminate widely within the thalamus and sensorimotor cortex. The causative factors for itch in jaundice have not been clarified although endogenous opioids, serotonin, steroid and lysophosphatidic acid all play a role. Current guidelines for the treatment of itching in jaundice recommend initial management with biliary drainage where possible and medical management with ursodeoxycholic acid, followed by cholestyramine, rifampicin, naltrexone and sertraline. Other than biliary drainage no single treatment has proved universally effective. Pruritis associated with jaundice is a common but poorly understood condition for which biliary drainage is the most effective therapy. Pharmacological therapy has advanced but remains variably effective.

Jaundice associated pruritis: A review of pathophysiology and treatment

PubMed Central

Bassari, Ramez; Koea, Jonathan B

2015-01-01

To review the underlying pathophysiology and currently available treatments for pruritis associated with jaundice. English language literature was reviewed using MEDLINE, PubMed, EMBASE and clinicaltrials.gov for papers and trails addressing the pathophysiology and potential treatments for pruritis associated with jaundice. Recent advances in the understanding of the peripheral anatomy of itch transmission have defined a histamine stimulated pathway and a cowhage stimulated pathway with sensation conveyed centrally via the contralateral spinothalamic tract. Centrally, cowhage and histamine stimulated neurons terminate widely within the thalamus and sensorimotor cortex. The causative factors for itch in jaundice have not been clarified although endogenous opioids, serotonin, steroid and lysophosphatidic acid all play a role. Current guidelines for the treatment of itching in jaundice recommend initial management with biliary drainage where possible and medical management with ursodeoxycholic acid, followed by cholestyramine, rifampicin, naltrexone and sertraline. Other than biliary drainage no single treatment has proved universally effective. Pruritis associated with jaundice is a common but poorly understood condition for which biliary drainage is the most effective therapy. Pharmacological therapy has advanced but remains variably effective. PMID:25663760

From innervation density to tactile acuity: 1. Spatial representation.

PubMed

Brown, Paul B; Koerber, H Richard; Millecchia, Ronald

2004-06-11

We tested the hypothesis that the population receptive field representation (a superposition of the excitatory receptive field areas of cells responding to a tactile stimulus) provides spatial information sufficient to mediate one measure of static tactile acuity. In psychophysical tests, two-point discrimination thresholds on the hindlimbs of adult cats varied as a function of stimulus location and orientation, as they do in humans. A statistical model of the excitatory low threshold mechanoreceptive fields of spinocervical, postsynaptic dorsal column and spinothalamic tract neurons was used to simulate the population receptive field representations in this neural population of the one- and two-point stimuli used in the psychophysical experiments. The simulated and observed thresholds were highly correlated. Simulated and observed thresholds' relations to physiological and anatomical variables such as stimulus location and orientation, receptive field size and shape, map scale, and innervation density were strikingly similar. Simulated and observed threshold variations with receptive field size and map scale obeyed simple relationships predicted by the signal detection model, and were statistically indistinguishable from each other. The population receptive field representation therefore contains information sufficient for this discrimination.

A population of large neurons in laminae III and IV of the rat spinal cord that have long dorsal dendrites and lack the neurokinin 1 receptor

PubMed Central

Polgár, Erika; Thomson, Suzanne; Maxwell, David J; Al-Khater, Khulood; Todd, Andrew J

2007-01-01

The dorsal horn of the rat spinal cord contains a population of large neurons with cell bodies in laminae III or IV, that express the neurokinin 1 receptor (NK1r) and have long dorsal dendrites that branch extensively within the superficial laminae. In this study, we have identified a separate population of neurons that have similar dendritic morphology, but lack the NK1r. These cells also differ from the NK1r-expressing neurons in that they have significantly fewer contacts from substance P-containing axons and are not retrogradely labelled following injection of tracer into the caudal ventrolateral medulla. We also provide evidence that these cells do not belong to the postsynaptic dorsal column pathway or the spinothalamic tract. It is therefore likely that these cells do not have supraspinal projections. They may provide a route through which information transmitted by C fibres that lack neuropeptides is conveyed to deeper laminae. The present findings demonstrate the need for caution when attempting to classify neurons solely on the basis of somatodendritic morphology. PMID:17880393

Spinal cheiro-oral syndrome: a common neurological entity in an unusual site.

PubMed

Lin, Hung-Sheng; Yin, Hsin-Ling; Chui, Chi; Lui, Chun-Chung; Chen, Wei-Hsi

2011-01-01

Cheiro-oral syndrome (COS) is an established neurological entity characterized by a sensory impairment confined to the mouth angle and ipsilateral finger(s)/ hand. The current understanding of localization is a concomitant involvement of the spinothalamic and trigeminothalamic tract between the cortex and pons. The cervical spinal cord has not been mentioned in this situation yet, and this unusual location may heretofore increase the risk of misdiagnosis. Six patients who presented with unilateral COS due to cervical cord disorder are reported. All patients were women and their age ranged between 42 and 70 years. Their neurological deficits included unilateral paraesthesiae restricted to cheirooral distribution, positive radicular sign, and mild change of tendon reflex. Cervical spinal stenosis at middle/lower cervical spine with variable magnitude of cord compression and intrinsic cord damage was found. A diagnostic dilemma obviously arises from the lack of tangible neurological signs or typical pattern of myelopathy, in addition to the previous concept of cerebral involvement. A benign course ensued in all reported patients. Cheiro-oral syndrome can be an early neurological sign for cervical cord disorder; it further suggests that it is a strong neurological but weak localizing sign. A reciprocal influence of multiple factors is considered to generate COS at the cervical cord. Therefore, an absence of brain pathology should lead to a thorough examination of the cervical cord in case of COS.

Organization of diencephalic projections from the medullary subnucleus reticularis dorsalis and the adjacent cuneate nucleus: a retrograde and anterograde tracer study in the rat.

PubMed

Villanueva, L; Desbois, C; Le Bars, D; Bernard, J F

1998-01-05

The distribution and organization of diencephalic projections from the subnucleus reticularis dorsalis (SRD) and the neighbouring cuneate nucleus (Cu) were studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin in SRD and Cu and wheat germ agglutinin-apo horseradish peroxidase-gold in some selected thalamic areas. As previously reported, the efferent projections from the Cu were essentially contralateral and terminated mainly in the ventroposterolateral thalamic nucleus. Less dense terminals from the Cu were also observed in the posterior thalamic group, the ventral aspect of the zona incerta and the caudal and dorsal portion of the reuniens area. Retrograde tracer injections in the medial ventroposterolateral thalamic nucleus labeled numerous cells in the contralateral Cu, with a smaller number in the gracile nucleus. From the SRD, terminals were observed in the lateral aspect of the ventromedial thalamic nucleus, the lateral parafascicular area and, to a lesser extent, in the ventral aspect of the zona incerta and the core of the reuniens area. Retrograde tracer injections in the lateral part of the ventromedial thalamic nucleus labeled cells in the caudal medulla, many of which were located in the dorsal-most aspect of the SRD throughout its caudo-rostral extent. The existence of SRD-thalamic connections reinforces the idea that the caudal reticular formation is an important nociceptive relay to the thalamus. Our data shed new light on old hypotheses suggesting that, in addition to spino-thalamic pathways, spino-reticulo-thalamic pathways may play an important role in distributing pain signals to the forebrain.

Desalted deep-sea water improves cognitive function in mice by increasing the production of insulin-like growth factor-I in the hippocampus.

PubMed

Harada, Naoaki; Zhao, Juan; Kurihara, Hiroki; Nakagata, Naomi; Okajima, Kenji

2011-08-01

The stimulation of sensory neurons in the gastrointestinal (GI) tract improves cognitive function by increasing the hippocampal production of insulin-like growth factor-I (IGF-I) in mice. In the current study, we examined whether oral administration of desalted deep-sea water (DSW) increases the hippocampal production of IGF-I by stimulating sensory neurons in the GI tract, thereby improving cognitive function in mice. Desalted DSW increased calcitonin gene-related peptide (CGRP) release from dorsal root ganglion (DRG) neurons isolated from wild-type (WT) mice by activating transient receptor potential vanilloid 1. The plasma levels of IGF-I and tissue levels of CGRP, IGF-I, and IGF-I mRNA in the hippocampus were increased by oral administration of desalted DSW in WT mice. In these animals, nociceptive information originating from the GI tract was transmitted to the hippocampus via the spinothalamic pathway. Improvement of spatial learning was observed in WT mice after administration of desalted DSW. Distilled DSW showed results similar to those of desalted DSW in vitro and in vivo. None of the effects of desalted DSW in WT mice were observed after the administration of desalted DSW in CGRP-knockout (CGRP-/-) mice. No volatile compounds were detected in distilled DSW on GC-MS analysis. These observations suggest that desalted DSW may increase the hippocampal IGF-I production via sensory neuron stimulation in the Gl tract, thereby improving cognitive function in mice. Such effects of desalted DSW might not be dependent on the minerals but are dependent on the function of the water molecule itself. Copyright © 2011 Mosby, Inc. All rights reserved.

[Electrophysiological testing in spinal cord tumors].

PubMed

André-Obadia, N; Mauguière, F

2017-11-01

Evoked potentials (EPs) are useful to evaluate the functional impairment of motor and somatosensory pathways in spinal cord tumors. Conduction through pyramidal tracts is evaluated by motor EPs (MEPs) elicited by transcranial stimulation, magnetic for awake patients or electric in the operating room. Somatosensory EPs (SEPs) and laser EPs (LEPs) are complementary procedures to explore conduction in dorsal columns and spinothalamic tracts, respectively. MEPs as well as SEPs show conduction abnormalities in about 60% of cases with a sensitivity that increases up to 70% when both procedures are carried out. Abnormalities are observed in the absence of any clinical sign in respectively 7% and 15% of cases for MEPs and SEPs. Multilevel stimulations for SEPs recordings permit to detect segmental dysfunction in 70% in case of cervical TIM, even in the absence of clinical signs. LEPs are useful in specific clinical situations: they allow a dermatomal stimulation and are correlated to segmental thermoalgic anaesthesia. Electrophysiological testing plays an important role in the diagnostic and therapeutic strategy: before surgery, MEPs and SEPs objectively evaluate the functional impairment directly related to the lesion. They also help by permitting a follow-up, either before surgery when the surgical decision is delayed because of a good clinical tolerance of the lesion, or after operation to evaluate the functional evolution. Intraoperative monitoring of MEPs and SEPs allows informing the surgeon about the impact on each surgical manipulation. No prospective randomized study has been performed to date to compare clinical evolution after surgery with or without monitoring. Nevertheless, a wide consensus became established in favor of monitoring to limit the risk of postoperative definite deficit and to permit an optimal surgical resection without risk when responses are preserved. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Does hemiplegic shoulder pain share clinical and sensory characteristics with central neuropathic pain? A comparative study.

PubMed

Zeilig, Gabi; Rivel, Michal; Doron, Dana; Defrin, Ruth

2016-10-01

Hemiplegic shoulder pain (HSP) is a common poststroke complication and is considered to be a chronic pain syndrome. It is negatively correlated with the functional recovery of the affected arm and the quality of life of the individual. It also leads to a longer length of stay in rehabilitation. Today, there is no consensus as to the underlying mechanism causing HSP, making the syndrome difficult to treat. The aim of this study was to compare the clinical and sensory profile of individuals with HSP to that of individuals with established central neuropathic pain (CNP) in order to identify common features and the presence of neuropathic components in HSP. Cross sectional controlled study. Outpatient rehabilitation clinics. Sixteen chronic HSP patients and 18 chronic CNP patients with spinal cord injury (SCI-CNP). The chronic pain characteristics, thresholds of thermal and tactile sensations and presence of pathological sensations were compared between groups, and between painful and pain free body regions within groups. Correlations were calculated between HSP intensity and sensory and musculoskeletal characteristics. Patients with HSP and patients with SCI-CNP had similar decrease of thermal sensibility in the painful compared to intact body regions and both groups presented similar rates of pathological sensations in painful regions. HSP and SCI-CNP differed however, in the quality of pain and aggravating factors. Significant correlations were found between HSP intensity and heat-pain threshold, presence of subluxation and spasticity. The similarities between HSP and SCI-CNP and the altered spinothalamic function and sensitization suggest that HSP has neuropathic components in its mechanism. Nevertheless, the unique features of HSP point towards additional possible mechanisms. The use of specific therapy options for neuropathic pain should be considered when treating patients with HSP.

An inhibitory interaction of human cortical responses to stimuli preferentially exciting Aδ or C fibers

PubMed Central

Tran, Tuan D.; Matre, Dagfinn; Casey, Kenneth L.

2008-01-01

Finely myelinated (type Aδ) and unmyelinated (type C) fibers are the major afferent inputs to spinothalamic tract neurons mediating sensory and reflex responses to noxious and thermal stimuli. These two fiber types differ in their sensory and biophysical properties, raising questions about the interaction of their supraspinal responses. Therefore, we investigated the interaction of cortical responses to stimuli that preferentially excite these fibers in human subjects using evoked potential recordings in a paired conditioning stimulation (CS) and test stimulation (TS) paradigm. There were two experiments, one with Aδ as CS and C as TS (Aδ-C) and another with these stimuli reversed (C-Aδ). We used intra-epidermal electrical pulses applied to the dorsal left hand at 2 and 1 × pinprick threshold (pp) for the preferential stimulation of Aδ fibers and 37 – 50°C contact heat pulses applied to the left or right thenar and left hypothenar eminences for the preferential stimulation of C fibers. We found that the cortical response to preferential Aδ or C fiber stimulation was attenuated whenever either cortical response preceded the other. Standardized values of peak and integrated amplitudes were < 1 in all paring conditions and in all subjects in both experiments. The suppressive effect varied in magnitude with the intensity of the conditioning stimulus in both Aδ-C and C-Aδ experiments. Furthermore, intra-segmental interaction was differentially effective for Aδ conditioning, (peak amplitude, p < 0.008; ANOVA). Our experiments provide the first neurophysiological evidence for a somatotopically distributed, mutually suppressive interaction between cortical responses to preferentially activated Aδ and C afferents in humans. This suppressive interaction of cortical responses suggests contrasting and possibly mutually exclusive sensori-motor functions mediated through the Aδ and C fiber afferent channels. PMID:18308475

Targeting, Air Force Doctrine Document 2-1.9

DTIC Science & Technology

2006-06-08

Target system analysis ( TSA ), as its name implies, approaches targets and target sets as systems to determine vulnerabilities and exploitable...weaknesses. Targeteers review how a functional target system works as a whole and analyze the interactions between components. TSA takes a system-of...effectiveness of target development. TSA begins in peacetime, before the commencement of conflict, and is accomplished with federated support and

Flight control system design factors for applying automated testing techniques

NASA Technical Reports Server (NTRS)

Sitz, Joel R.; Vernon, Todd H.

1990-01-01

The principal design features and operational experiences of the X-29 forward-swept-wing aircraft and F-18 high alpha research vehicle (HARV) automated test systems are discussed. It is noted that operational experiences in developing and using these automated testing techniques have highlighted the need for incorporating target system features to improve testability. Improved target system testability can be accomplished with the addition of nonreal-time and real-time features. Online access to target system implementation details, unobtrusive real-time access to internal user-selectable variables, and proper software instrumentation are all desirable features of the target system. Also, test system and target system design issues must be addressed during the early stages of the target system development. Processing speeds of up to 20 million instructions/s and the development of high-bandwidth reflective memory systems have improved the ability to integrate the target system and test system for the application of automated testing techniques. It is concluded that new methods of designing testability into the target systems are required.

Target isolation system, high power laser and laser peening method and system using same

DOEpatents

Dane, C. Brent; Hackel, Lloyd A.; Harris, Fritz

2007-11-06

A system for applying a laser beam to work pieces, includes a laser system producing a high power output beam. Target delivery optics are arranged to deliver the output beam to a target work piece. A relay telescope having a telescope focal point is placed in the beam path between the laser system and the target delivery optics. The relay telescope relays an image between an image location near the output of the laser system and an image location near the target delivery optics. A baffle is placed at the telescope focal point between the target delivery optics and the laser system to block reflections from the target in the target delivery optics from returning to the laser system and causing damage.

Spatiotemporal trajectories of reactivation of somatosensory cortex by direct and secondary pathways after dorsal column lesions in squirrel monkeys

PubMed Central

Qi, Hui-Xin; Wang, Feng; Liao, Chia-Chi; Friedman, Robert M.; Tang, Chaohui; Kaas, Jon H.; Avison, Malcolm J.

2016-01-01

After lesions of the somatosensory dorsal column (DC) pathway, the cortical hand representation can become unresponsive to tactile stimuli, but considerable responsiveness returns over weeks of post-lesion recovery. The reactivation suggests that preserved subthreshold sensory inputs become potentiated and axon sprouting occurs over time to mediate recovery. Here, we studied the recovery process in 3 squirrel monkeys, using high-resolution fMRI CBV-fMRI mapping of contralateral somatosensory cortex responsiveness to stimulation of distal finger pads with low and high level electrocutaneous stimulation (ES) before and 2, 4, and 6 weeks after a high cervical level contralateral DC lesion. Both low and high intensity ES of digits revealed the expected somatotopy of the area 3b hand representation in pre-lesion monkeys, while in areas 1 and 3a, high intensity stimulation was more effective in activating somatotopic patterns. Six weeks post-lesion, and irrespective of the severity of loss of direct DC inputs (98%, 79%, 40%), somatosensory cortical area 3b of all three animals showed near complete recovery in terms of somatotopy and responsiveness to low and high intensity ES. However there was significant variability in the patterns and amplitudes of reactivation of individual digit territories within and between animals, reflecting differences in the degree of permanent and/or transient silencing of primary DC and secondary inputs 2 weeks post-lesion, and their spatio-temporal trajectories of recovery between 2 and 6 weeks. Similar variations in the silencing and recovery of somatotopy and responsiveness to high intensity ES in areas 3a and 1 are consistent with inter-individual differences in collateral damage to and recovery of secondary (e.g. spinothalamic) pathways. Thus, cortical deactivation and subsequent reactivation depends not only on the degree of DC lesion, but also on the severity and duration of loss of secondary as well as primary inputs revealed by low and high intensity ES. PMID:27523450

High predictive value of brain MRI imaging in primary mitochondrial respiratory chain deficiency.

PubMed

de Beaurepaire, Isaure; Grévent, David; Rio, Marlène; Desguerre, Isabelle; de Lonlay, Pascale; Levy, Raphaël; Dangouloff-Ros, Volodia; Bonnefont, Jean-Paul; Barcia, Giulia; Funalot, Benoit; Besmond, Claude; Metodiev, Metodi D; Ruzzenente, Benedetta; Assouline, Zahra; Munnich, Arnold; Rötig, Agnès; Boddaert, Nathalie

2018-06-01

Because the mitochondrial respiratory chain (RC) is ubiquitous, its deficiency can theoretically give rise to any symptom in any organ or tissue at any age with any mode of inheritance, owing to the twofold genetic origin of respiratory enzyme machinery, that is, nuclear and mitochondrial. Not all respiratory enzyme deficiencies are primary and secondary or artefactual deficiency is frequently observed, leading to a number of misleading conclusions and inappropriate investigations in clinical practice. This study is aimed at investigating the potential role of brain MRI in distinguishing primary RC deficiency from phenocopies and other aetiologies. Starting from a large series of 189 patients (median age: 3.5 years (8 days-56 years), 58% males) showing signs of RC enzyme deficiency, for whom both brain MRIs and disease-causing mutations were available, we retrospectively studied the positive predictive value (PPV) and the positive likelihood ratio (LR+) of brain MRI imaging and its ability to discriminate between two groups: primary deficiency of the mitochondrial RC machinery and phenocopies. Detection of (1) brainstem hyperintensity with basal ganglia involvement (P≤0.001) and (2) lactate peak with either brainstem or basal ganglia hyperintensity was highly suggestive of primary RC deficiency (P≤0.01). Fourteen items had a PPV>95% and LR+ was greater than 9 for seven signs. Biallelic SLC19A3 mutations represented the main differential diagnosis. Non-significant differences between the two groups were found for cortical/subcortical atrophy, leucoencephalopathy and involvement of caudate nuclei, spinothalamic tract and corpus callosum. Based on these results and owing to invasiveness of skeletal muscle biopsies and cost of high-throughput DNA sequencing, we suggest giving consideration to brain MRI imaging as a diagnostic marker and an informative investigation to be performed in patients showing signs of RC enzyme deficiency. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Uneventful upper cervical manipulation in the presence of a damaged vertebral artery.

PubMed

Michaud, Thomas C

2002-09-01

To discuss a case in which a patient with a previously injured vertebral artery underwent manipulation in the upper cervical spine without alteration of her symptom pattern. The literature concerning the relative safety of specific upper cervical manipulative techniques is reviewed. A 42-year-old woman had a 3-week history of unilateral suboccipital pain that she related to a sudden twisting of her head and neck that occurred while she was putting sheets of drywall on top of her car. Subsequent examination by a neurologist 2 weeks later was unremarkable, and a tension-type headache was diagnosed. Approximately 10 days later (3 weeks after injury), a single high-velocity upper-cervical manipulation (incorporating slight rotation and full lateral flexion) was performed with no change in her symptom pattern. Two weeks after that, the patient had development of a lateral medullary syndrome (also known as Wallenberg syndrome) after she briefly extended and rotated her upper cervical spine while painting a ceiling. The patient was treated with anticoagulant therapy, and the lateral medullary infarct healed without incident. The spinocerebellar and subtle motor symptoms also resolved, but the ipsilateral suboccipital headache and the loss of temperature sensation associated with the spinothalamic tract lesion were still present 9 months later. This case report demonstrates that vigorous manipulation of the upper cervical spine is possible without injuring an already damaged vertebral artery. It is suggested that the line of drive used during the single manipulation, almost pure lateral flexion with slight rotation, was responsible for the apparent innocuous response. Guidelines for the evaluation and management of vertebral artery dissection are reviewed. Because it is currently impossible to identify patients at risk of having a dissected vertebral artery with standard in-office examination procedures, rotational manipulation of the upper cervical spine should be abandoned by all practitioners, and schools should remove such techniques from their curriculums.

Real-time target tracking and locating system for UAV

NASA Astrophysics Data System (ADS)

Zhang, Chao; Tang, Linbo; Fu, Huiquan; Li, Maowen

2017-07-01

In order to achieve real-time target tracking and locating for UAV, a reliable processing system is built on the embedded platform. Firstly, the video image is acquired in real time by the photovoltaic system on the UAV. When the target information is known, KCF tracking algorithm is adopted to track the target. Then, the servo is controlled to rotate with the target, when the target is in the center of the image, the laser ranging module is opened to obtain the distance between the UAV and the target. Finally, to combine with UAV flight parameters obtained by BeiDou navigation system, through the target location algorithm to calculate the geodetic coordinates of the target. The results show that the system is stable for real-time tracking of targets and positioning.

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.

Detection technique of targets for missile defense system

NASA Astrophysics Data System (ADS)

Guo, Hua-ling; Deng, Jia-hao; Cai, Ke-rong

2009-11-01

Ballistic missile defense system (BMDS) is a weapon system for intercepting enemy ballistic missiles. It includes ballistic-missile warning system, target discrimination system, anti-ballistic-missile guidance systems, and command-control communication system. Infrared imaging detection and laser imaging detection are widely used in BMDS for surveillance, target detection, target tracking, and target discrimination. Based on a comprehensive review of the application of target-detection techniques in the missile defense system, including infrared focal plane arrays (IRFPA), ground-based radar detection technology, 3-dimensional imaging laser radar with a photon counting avalanche photodiode (APD) arrays and microchip laser, this paper focuses on the infrared and laser imaging detection techniques in missile defense system, as well as the trends for their future development.

Comparison of Deep Brain Stimulation Lead Targeting Accuracy and Procedure Duration between 1.5- and 3-Tesla Interventional Magnetic Resonance Imaging Systems: An Initial 12-Month Experience.

PubMed

Southwell, Derek G; Narvid, Jared A; Martin, Alastair J; Qasim, Salman E; Starr, Philip A; Larson, Paul S

2016-01-01

Interventional magnetic resonance imaging (iMRI) allows deep brain stimulator lead placement under general anesthesia. While the accuracy of lead targeting has been described for iMRI systems utilizing 1.5-tesla magnets, a similar assessment of 3-tesla iMRI procedures has not been performed. To compare targeting accuracy, the number of lead targeting attempts, and surgical duration between procedures performed on 1.5- and 3-tesla iMRI systems. Radial targeting error, the number of targeting attempts, and procedure duration were compared between surgeries performed on 1.5- and 3-tesla iMRI systems (SmartFrame and ClearPoint systems). During the first year of operation of each system, 26 consecutive leads were implanted using the 1.5-tesla system, and 23 consecutive leads were implanted using the 3-tesla system. There was no significant difference in radial error (Mann-Whitney test, p = 0.26), number of lead placements that required multiple targeting attempts (Fisher's exact test, p = 0.59), or bilateral procedure durations between surgeries performed with the two systems (p = 0.15). Accurate DBS lead targeting can be achieved with iMRI systems utilizing either 1.5- or 3-tesla magnets. The use of a 3-tesla magnet, however, offers improved visualization of the target structures and allows comparable accuracy and efficiency of placement at the selected targets. © 2016 S. Karger AG, Basel.

Vision-Based Target Finding and Inspection of a Ground Target Using a Multirotor UAV System.

PubMed

Hinas, Ajmal; Roberts, Jonathan M; Gonzalez, Felipe

2017-12-17

In this paper, a system that uses an algorithm for target detection and navigation and a multirotor Unmanned Aerial Vehicle (UAV) for finding a ground target and inspecting it closely is presented. The system can also be used for accurate and safe delivery of payloads or spot spraying applications in site-specific crop management. A downward-looking camera attached to a multirotor is used to find the target on the ground. The UAV descends to the target and hovers above the target for a few seconds to inspect the target. A high-level decision algorithm based on an OODA (observe, orient, decide, and act) loop was developed as a solution to address the problem. Navigation of the UAV was achieved by continuously sending local position messages to the autopilot via Mavros. The proposed system performed hovering above the target in three different stages: locate, descend, and hover. The system was tested in multiple trials, in simulations and outdoor tests, from heights of 10 m to 40 m. Results show that the system is highly reliable and robust to sensor errors, drift, and external disturbance.

Resolution verification targets for airborne and spaceborne imaging systems at the Stennis Space Center

NASA Astrophysics Data System (ADS)

McKellip, Rodney; Yuan, Ding; Graham, William; Holland, Donald E.; Stone, David; Walser, William E.; Mao, Chengye

1997-06-01

The number of available spaceborne and airborne systems will dramatically increase over the next few years. A common systematic approach toward verification of these systems will become important for comparing the systems' operational performance. The Commercial Remote Sensing Program at the John C. Stennis Space Center (SSC) in Mississippi has developed design requirements for a remote sensing verification target range to provide a means to evaluate spatial, spectral, and radiometric performance of optical digital remote sensing systems. The verification target range consists of spatial, spectral, and radiometric targets painted on a 150- by 150-meter concrete pad located at SSC. The design criteria for this target range are based upon work over a smaller, prototypical target range at SSC during 1996. This paper outlines the purpose and design of the verification target range based upon an understanding of the systems to be evaluated as well as data analysis results from the prototypical target range.

Network Analysis of Drug-target Interactions: A Study on FDA-approved New Molecular Entities Between 2000 to 2015.

PubMed

Lin, Hui-Heng; Zhang, Le-Le; Yan, Ru; Lu, Jin-Jian; Hu, Yuanjia

2017-09-25

The U.S. Food and Drug Administration (FDA) approves new drugs every year. Drug targets are some of the most important interactive molecules for drugs, as they have a significant impact on the therapeutic effects of drugs. In this work, we thoroughly analyzed the data of small molecule drugs approved by the U.S. FDA between 2000 and 2015. Specifically, we focused on seven classes of new molecular entity (NME) classified by the anatomic therapeutic chemical (ATC) classification system. They were NMEs and their corresponding targets for the cardiovascular system, respiratory system, nerve system, general anti-infective systemic, genito-urinary system and sex hormones, alimentary tract and metabolisms, and antineoplastic and immunomodulating agents. To study the drug-target interaction on the systems level, we employed network topological analysis and multipartite network projections. As a result, the drug-target relations of different kinds of drugs were comprehensively characterized and global pictures of drug-target, drug-drug, and target-target interactions were visualized and analyzed from the perspective of network models.

Biodegradable polymers for targeted delivery of anti-cancer drugs.

PubMed

Doppalapudi, Sindhu; Jain, Anjali; Domb, Abraham J; Khan, Wahid

2016-06-01

Biodegradable polymers have been used for more than three decades in cancer treatment and have received increased interest in recent years. A range of biodegradable polymeric drug delivery systems designed for localized and systemic administration of therapeutic agents as well as tumor-targeting macromolecules has entered into the clinical phase of development, indicating the significance of biodegradable polymers in cancer therapy. This review elaborates upon applications of biodegradable polymers in the delivery and targeting of anti-cancer agents. Design of various drug delivery systems based on biodegradable polymers has been described. Moreover, the indication of polymers in the targeted delivery of chemotherapeutic drugs via passive, active targeting, and localized drug delivery are also covered. Biodegradable polymer-based drug delivery systems have the potential to deliver the payload to the target and can enhance drug availability at desired sites. Systemic toxicity and serious side effects observed with conventional cancer therapeutics can be significantly reduced with targeted polymeric systems. Still, there are many challenges that need to be met with respect to the degradation kinetics of the system, diffusion of drug payload within solid tumors, targeting tumoral tissue and tumor heterogeneity.

Metrology Camera System Using Two-Color Interferometry

NASA Technical Reports Server (NTRS)

Dubovitsky, Serge; Liebe, Carl Christian; Peters, Robert; Lay, Oliver

2007-01-01

A metrology system that contains no moving parts simultaneously measures the bearings and ranges of multiple reflective targets in its vicinity, enabling determination of the three-dimensional (3D) positions of the targets with submillimeter accuracy. The system combines a direction-measuring metrology camera and an interferometric range-finding subsystem. Because the system is based partly on a prior instrument denoted the Modulation Sideband Technology for Absolute Ranging (MSTAR) sensor and because of its 3D capability, the system is denoted the MSTAR3D. Developed for use in measuring the shape (for the purpose of compensating for distortion) of large structures like radar antennas, it can also be used to measure positions of multiple targets in the course of conventional terrestrial surveying. A diagram of the system is shown in the figure. One of the targets is a reference target having a known, constant distance with respect to the system. The system comprises a laser for generating local and target beams at a carrier frequency; a frequency shifting unit to introduce a frequency shift offset between the target and local beams; a pair of high-speed modulators that apply modulation to the carrier frequency in the local and target beams to produce a series of modulation sidebands, the highspeed modulators having modulation frequencies of FL and FM; a target beam launcher that illuminates the targets with the target beam; optics and a multipixel photodetector; a local beam launcher that launches the local beam towards the multi-pixel photodetector; a mirror for projecting to the optics a portion of the target beam reflected from the targets, the optics being configured to focus the portion of the target beam at the multi-pixel photodetector; and a signal-processing unit connected to the photodetector. The portion of the target beam reflected from the targets produces spots on the multi-pixel photodetector corresponding to the targets, respectively, and the signal-processing unit centroids the spots to determine bearings of the targets, respectively. As the spots oscillate in intensity because they are mixed with the local laser beam that is flood illuminating the focal plane, the phase of oscillation of each spot is measured, the phase of sidebands in the oscillation of each spot being proportional to a distance to the corresponding target relative to the reference target A.

Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

PubMed

Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

2016-05-01

Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

Simple Monitoring of Gene Targeting Efficiency in Human Somatic Cell Lines Using the PIGA Gene

PubMed Central

Karnan, Sivasundaram; Konishi, Yuko; Ota, Akinobu; Takahashi, Miyuki; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki

2012-01-01

Gene targeting in most of human somatic cell lines has been labor-intensive because of low homologous recombination efficiency. The development of an experimental system that permits a facile evaluation of gene targeting efficiency in human somatic cell lines is the first step towards the improvement of this technology and its application to a broad range of cell lines. In this study, we utilized phosphatidylinositol glycan anchor biosynthesis class A (PIGA), a gene essential for the synthesis of glycosylphosphatidyl inositol (GPI) anchors, as a reporter of gene targeting events in human somatic cell lines. Targeted disruption of PIGA was quantitatively detected with FLAER, a reagent that specifically binds to GPI anchors. Using this PIGA-based reporter system, we successfully detected adeno-associated virus (AAV)-mediated gene targeting events both with and without promoter-trap enrichment of gene-targeted cell population. The PIGA-based reporter system was also capable of reproducing previous findings that an AAV-mediated gene targeting achieves a remarkably higher ratio of homologous versus random integration (H/R ratio) of targeting vectors than a plasmid-mediated gene targeting. The PIGA-based system also detected an approximately 2-fold increase in the H/R ratio achieved by a small negative selection cassette introduced at the end of the AAV-based targeting vector with a promoter-trap system. Thus, our PIGA-based system is useful for monitoring AAV-mediated gene targeting and will assist in improving gene targeting technology in human somatic cell lines. PMID:23056640

Design strategies and applications of circulating cell-mediated drug delivery systems.

PubMed

Su, Yixue; Xie, Zhiwei; Kim, Gloria B; Dong, Cheng; Yang, Jian

2015-01-01

Drug delivery systems, particularly nanomaterial-based drug delivery systems, possess a tremendous amount of potential to improve diagnostic and therapeutic effects of drugs. Controlled drug delivery targeted to a specific disease is designed to significantly improve the pharmaceutical effects of drugs and reduce their side effects. Unfortunately, only a few targeted drug delivery systems can achieve high targeting efficiency after intravenous injection, even with the development of numerous surface markers and targeting modalities. Thus, alternative drug and nanomedicine targeting approaches are desired. Circulating cells, such as erythrocytes, leukocytes, and stem cells, present innate disease sensing and homing properties. Hence, using living cells as drug delivery carriers has gained increasing interest in recent years. This review highlights the recent advances in the design of cell-mediated drug delivery systems and targeting mechanisms. The approaches of drug encapsulation/conjugation to cell-carriers, cell-mediated targeting mechanisms, and the methods of controlled drug release are elaborated here. Cell-based "live" targeting and delivery could be used to facilitate a more specific, robust, and smart payload distribution for the next-generation drug delivery systems.

Repetitive output laser system and method using target reflectivity

DOEpatents

Johnson, Roy R.

1978-01-01

An improved laser system and method for implosion of a thermonuclear fuel pellet in which that portion of a laser pulse reflected by the target pellet is utilized in the laser system to initiate a succeeding target implosion, and in which the energy stored in the laser system to amplify the initial laser pulse, but not completely absorbed thereby, is used to amplify succeeding laser pulses initiated by target reflection.

Navy Acquisition: Development of the AN/BSY-1 Combat System

DTIC Science & Technology

1992-01-01

AN/BSY-1, a computer-based combat system, is designed to detect, classify, track, and launch weapons at enemy surface, subsurface, and land targets. The Navy expects the AN/BSY-1 system to locate targets sooner than previous systems, allow operators to perform multiple tasks and address multiple targets concurrently, and reduce the time between detecting a target and launching weapons. The Navy has contracted with the International Business Machines (IBM) Corporation for 23 AN/BSY-1 systems, maintenance and operational trainers, and a software

Video Guidance Sensors Using Remotely Activated Targets

NASA Technical Reports Server (NTRS)

Bryan, Thomas C.; Howard, Richard T.; Book, Michael L.

2004-01-01

Four updated video guidance sensor (VGS) systems have been proposed. As described in a previous NASA Tech Briefs article, a VGS system is an optoelectronic system that provides guidance for automated docking of two vehicles. The VGS provides relative position and attitude (6-DOF) information between the VGS and its target. In the original intended application, the two vehicles would be spacecraft, but the basic principles of design and operation of the system are applicable to aircraft, robots, objects maneuvered by cranes, or other objects that may be required to be aligned and brought together automatically or under remote control. In the first two of the four VGS systems as now proposed, the tracked vehicle would include active targets that would light up on command from the tracking vehicle, and a video camera on the tracking vehicle would be synchronized with, and would acquire images of, the active targets. The video camera would also acquire background images during the periods between target illuminations. The images would be digitized and the background images would be subtracted from the illuminated-target images. Then the position and orientation of the tracked vehicle relative to the tracking vehicle would be computed from the known geometric relationships among the positions of the targets in the image, the positions of the targets relative to each other and to the rest of the tracked vehicle, and the position and orientation of the video camera relative to the rest of the tracking vehicle. The major difference between the first two proposed systems and prior active-target VGS systems lies in the techniques for synchronizing the flashing of the active targets with the digitization and processing of image data. In the prior active-target VGS systems, synchronization was effected, variously, by use of either a wire connection or the Global Positioning System (GPS). In three of the proposed VGS systems, the synchronizing signal would be generated on, and transmitted from, the tracking vehicle. In the first proposed VGS system, the tracking vehicle would transmit a pulse of light. Upon reception of the pulse, circuitry on the tracked vehicle would activate the target lights. During the pulse, the target image acquired by the camera would be digitized. When the pulse was turned off, the target lights would be turned off and the background video image would be digitized. The second proposed system would function similarly to the first proposed system, except that the transmitted synchronizing signal would be a radio pulse instead of a light pulse. In this system, the signal receptor would be a rectifying antenna. If the signal contained sufficient power, the output of the rectifying antenna could be used to activate the target lights, making it unnecessary to include a battery or other power supply for the targets on the tracked vehicle.

Impact of 4D image quality on the accuracy of target definition.

PubMed

Nielsen, Tine Bjørn; Hansen, Christian Rønn; Westberg, Jonas; Hansen, Olfred; Brink, Carsten

2016-03-01

Delineation accuracy of target shape and position depends on the image quality. This study investigates whether the image quality on standard 4D systems has an influence comparable to the overall delineation uncertainty. A moving lung target was imaged using a dynamic thorax phantom on three different 4D computed tomography (CT) systems and a 4D cone beam CT (CBCT) system using pre-defined clinical scanning protocols. Peak-to-peak motion and target volume were registered using rigid registration and automatic delineation, respectively. A spatial distribution of the imaging uncertainty was calculated as the distance deviation between the imaged target and the true target shape. The measured motions were smaller than actual motions. There were volume differences of the imaged target between respiration phases. Imaging uncertainties of >0.4 cm were measured in the motion direction which showed that there was a large distortion of the imaged target shape. Imaging uncertainties of standard 4D systems are of similar size as typical GTV-CTV expansions (0.5-1 cm) and contribute considerably to the target definition uncertainty. Optimising and validating 4D systems is recommended in order to obtain the most optimal imaged target shape.

Antares reference telescope system

NASA Astrophysics Data System (ADS)

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

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

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

Nishikino, Masaharu; Ochi, Yoshihiro; Hasegawa, Noboru

A highly coherent 13.9 nm x-ray laser (XRL) is generated under an oscillator-amplifier configuration using a new tape target system and a driver laser system with a 0.1 Hz repetition rate. The output energy is comparable to the XRL generated with a silver-deposited slab target, and the pointing stability using the new tape target system is better than conventional slab targets.

The simulation study on optical target laser active detection performance

NASA Astrophysics Data System (ADS)

Li, Ying-chun; Hou, Zhao-fei; Fan, Youchen

2014-12-01

According to the working principle of laser active detection system, the paper establishes the optical target laser active detection simulation system, carry out the simulation study on the detection process and detection performance of the system. For instance, the performance model such as the laser emitting, the laser propagation in the atmosphere, the reflection of optical target, the receiver detection system, the signal processing and recognition. We focus on the analysis and modeling the relationship between the laser emitting angle and defocus amount and "cat eye" effect echo laser in the reflection of optical target. Further, in the paper some performance index such as operating range, SNR and the probability of the system have been simulated. The parameters including laser emitting parameters, the reflection of the optical target and the laser propagation in the atmosphere which make a great influence on the performance of the optical target laser active detection system. Finally, using the object-oriented software design methods, the laser active detection system with the opening type, complete function and operating platform, realizes the process simulation that the detection system detect and recognize the optical target, complete the performance simulation of each subsystem, and generate the data report and the graph. It can make the laser active detection system performance models more intuitive because of the visible simulation process. The simulation data obtained from the system provide a reference to adjust the structure of the system parameters. And it provides theoretical and technical support for the top level design of the optical target laser active detection system and performance index optimization.

Performance assessment techniques for Doppler radar physiological sensors.

PubMed

Hafner, Noah; Lubecke, Victor

2009-01-01

This paper presents a technique for assessing the performance of continuous wave Doppler radar systems for physiological sensing. The technique includes an artificial target for testing physiological sensing radar systems with motion analogous to human heart movement and software algorithms leveraging the capabilities of this target to simply test radar system performance. The mechanical target provides simple to complex patterns of motion that are stable and repeatable. Details of radar system performance can be assessed and the effects of configuration changes that might not appear with a human target can be observed when using this mechanical target.

Estimate of the influence of muzzle smoke on function range of infrared system

NASA Astrophysics Data System (ADS)

Luo, Yan-ling; Wang, Jun; Wu, Jiang-hui; Wu, Jun; Gao, Meng; Gao, Fei; Zhao, Yu-jie; Zhang, Lei

2013-09-01

Muzzle smoke produced by weapons shooting has important influence on infrared (IR) system while detecting targets. Based on the theoretical model of detecting spot targets and surface targets of IR system while there is muzzle smoke, the function range for detecting spot targets and surface targets are deduced separately according to the definition of noise equivalent temperature difference(NETD) and minimum resolution temperature difference(MRTD). Also parameters of muzzle smoke affecting function range of IR system are analyzed. Base on measured data of muzzle smoke for single shot, the function range of an IR system for detecting typical targets are calculated separately while there is muzzle smoke and there is no muzzle smoke at 8-12 micron waveband. For our IR system function range has reduced by over 10% for detecting tank if muzzle smoke exists. The results will provide evidence for evaluating the influence of muzzle smoke on IR system and will help researchers to improve ammo craftwork.

Decoupled tracking and thermal monitoring of non-stationary targets.

PubMed

Tan, Kok Kiong; Zhang, Yi; Huang, Sunan; Wong, Yoke San; Lee, Tong Heng

2009-10-01

Fault diagnosis and predictive maintenance address pertinent economic issues relating to production systems as an efficient technique can continuously monitor key health parameters and trigger alerts when critical changes in these variables are detected, before they lead to system failures and production shutdowns. In this paper, we present a decoupled tracking and thermal monitoring system which can be used on non-stationary targets of closed systems such as machine tools. There are three main contributions from the paper. First, a vision component is developed to track moving targets under a monitor. Image processing techniques are used to resolve the target location to be tracked. Thus, the system is decoupled and applicable to closed systems without the need for a physical integration. Second, an infrared temperature sensor with a built-in laser for locating the measurement spot is deployed for non-contact temperature measurement of the moving target. Third, a predictive motion control system holds the thermal sensor and follows the moving target efficiently to enable continuous temperature measurement and monitoring.

Virtual targeting in three-dimensional space with sound and light interference

NASA Astrophysics Data System (ADS)

Chua, Florence B.; DeMarco, Robert M.; Bergen, Michael T.; Short, Kenneth R.; Servatius, Richard J.

2006-05-01

Law enforcement and the military are critically concerned with the targeting and firing accuracy of opponents. Stimuli which impede opponent targeting and firing accuracy can be incorporated into defense systems. An automated virtual firing range was developed to assess human targeting accuracy under conditions of sound and light interference, while avoiding dangers associated with live fire. This system has the ability to quantify sound and light interference effects on targeting and firing accuracy in three dimensions. This was achieved by development of a hardware and software system that presents the subject with a sound or light target, preceded by a sound or light interference. SonyXplod. TM 4-way speakers present sound interference and sound targeting. The Martin ® MiniMAC TM Profile operates as a source of light interference, while a red laser light serves as a target. A tracking system was created to monitor toy gun movement and firing in three-dimensional space. Data are collected via the Ascension ® Flock of Birds TM tracking system and a custom National Instrument ® LabVIEW TM 7.0 program to monitor gun movement and firing. A test protocol examined system parameters. Results confirm that the system enables tracking of virtual shots from a fired simulation gun to determine shot accuracy and location in three dimensions.

A system for the measurement of gene targeting efficiency in human cell lines using an antibiotic resistance-GFP fusion gene.

PubMed

Konishi, Yuko; Karnan, Sivasundaram; Takahashi, Miyuki; Ota, Akinobu; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki

2012-09-01

Gene targeting in a broad range of human somatic cell lines has been hampered by inefficient homologous recombination. To improve this technology and facilitate its widespread application, it is critical to first have a robust and efficient research system for measuring gene targeting efficiency. Here, using a fusion gene consisting of hygromycin B phosphotransferase and 3'-truncated enhanced GFP (HygR-5' EGFP) as a reporter gene, we created a molecular system monitoring the ratio of homologous to random integration (H/R ratio) of targeting vectors into the genome. Cell clones transduced with a reporter vector containing HygR-5' EGFP were efficiently established from two human somatic cell lines. Established HygR-5' EGFP reporter clones retained their capacity to monitor gene targeting efficiency for a longer duration than a conventional reporter system using an unfused 5' EGFP gene. With the HygR-5' EGFP reporter system, we reproduced previous findings of gene targeting frequency being up-regulated by the use of an adeno-associated viral (AAV) backbone, a promoter-trap system, or a longer homology arm in a targeting vector, suggesting that this system accurately monitors H/R ratio. Thus, our HygR-5' EGFP reporter system will assist in the development of an efficient AAV-based gene targeting technology.

Research on regional intrusion prevention and control system based on target tracking

NASA Astrophysics Data System (ADS)

Liu, Yanfei; Wang, Jieling; Jiang, Ke; He, Yanhui; Wu, Zhilin

2017-08-01

In view of the fact that China’s border is very long and the border prevention and control measures are single, we designed a regional intrusion prevention and control system which based on target-tracking. The system consists of four parts: solar panel, radar, electro-optical equipment, unmanned aerial vehicle and intelligent tracking platform. The solar panel provides independent power for the entire system. The radar detects the target in real time and realizes the high precision positioning of suspicious targets, then through the linkage of electro-optical equipment, it can achieve full-time automatic precise tracking of targets. When the target appears within the range of detection, the drone will be launched to continue the tracking. The system is mainly to realize the full time, full coverage, whole process integration and active realtime control of the border area.

Active Multimodal Sensor System for Target Recognition and Tracking

PubMed Central

Zhang, Guirong; Zou, Zhaofan; Liu, Ziyue; Mao, Jiansen

2017-01-01

High accuracy target recognition and tracking systems using a single sensor or a passive multisensor set are susceptible to external interferences and exhibit environmental dependencies. These difficulties stem mainly from limitations to the available imaging frequency bands, and a general lack of coherent diversity of the available target-related data. This paper proposes an active multimodal sensor system for target recognition and tracking, consisting of a visible, an infrared, and a hyperspectral sensor. The system makes full use of its multisensor information collection abilities; furthermore, it can actively control different sensors to collect additional data, according to the needs of the real-time target recognition and tracking processes. This level of integration between hardware collection control and data processing is experimentally shown to effectively improve the accuracy and robustness of the target recognition and tracking system. PMID:28657609

Systems and Methods for Correcting Optical Reflectance Measurements

NASA Technical Reports Server (NTRS)

Yang, Ye (Inventor); Shear, Michael A. (Inventor); Soller, Babs R. (Inventor); Soyemi, Olusola O. (Inventor)

2014-01-01

We disclose measurement systems and methods for measuring analytes in target regions of samples that also include features overlying the target regions. The systems include: (a) a light source; (b) a detection system; (c) a set of at least first, second, and third light ports which transmit light from the light source to a sample and receive and direct light reflected from the sample to the detection system, generating a first set of data including information corresponding to both an internal target within the sample and features overlying the internal target, and a second set of data including information corresponding to features overlying the internal target; and (d) a processor configured to remove information characteristic of the overlying features from the first set of data using the first and second sets of data to produce corrected information representing the internal target.

Systems and methods for correcting optical reflectance measurements

NASA Technical Reports Server (NTRS)

Yang, Ye (Inventor); Soller, Babs R. (Inventor); Soyemi, Olusola O. (Inventor); Shear, Michael A. (Inventor)

2009-01-01

We disclose measurement systems and methods for measuring analytes in target regions of samples that also include features overlying the target regions. The systems include: (a) a light source; (b) a detection system; (c) a set of at least first, second, and third light ports which transmit light from the light source to a sample and receive and direct light reflected from the sample to the detection system, generating a first set of data including information corresponding to both an internal target within the sample and features overlying the internal target, and a second set of data including information corresponding to features overlying the internal target; and (d) a processor configured to remove information characteristic of the overlying features from the first set of data using the first and second sets of data to produce corrected information representing the internal target.

Experiment research on infrared targets signature in mid and long IR spectral bands

NASA Astrophysics Data System (ADS)

Wang, Chensheng; Hong, Pu; Lei, Bo; Yue, Song; Zhang, Zhijie; Ren, Tingting

2013-09-01

Since the infrared imaging system has played a significant role in the military self-defense system and fire control system, the radiation signature of IR target becomes an important topic in IR imaging application technology. IR target signature can be applied in target identification, especially for small and dim targets, as well as the target IR thermal design. To research and analyze the targets IR signature systematically, a practical and experimental project is processed under different backgrounds and conditions. An infrared radiation acquisition system based on a MWIR cooled thermal imager and a LWIR cooled thermal imager is developed to capture the digital infrared images. Furthermore, some instruments are introduced to provide other parameters. According to the original image data and the related parameters in a certain scene, the IR signature of interested target scene can be calculated. Different background and targets are measured with this approach, and a comparison experiment analysis shall be presented in this paper as an example. This practical experiment has proved the validation of this research work, and it is useful in detection performance evaluation and further target identification research.

Liquid Hydrogen Target Experience at SLAC

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

Weisend, J.G.; Boyce, R.; Candia, A.

2005-08-29

Liquid hydrogen targets have played a vital role in the physics program at SLAC for the past 40 years. These targets have ranged from small ''beer can'' targets to the 1.5 m long E158 target that was capable of absorbing up to 800 W without any significant density changes. Successful use of these targets has required the development of thin wall designs, liquid hydrogen pumps, remote positioning and alignment systems, safety systems, control and data acquisition systems, cryogenic cooling circuits and heat exchangers. Detailed operating procedures have been created to ensure safety and operational reliability. This paper surveys the evolutionmore » of liquid hydrogen targets at SLAC and discusses advances in several of the enabling technologies that made these targets possible.« less

Immunoconjugates and long circulating systems: Origins, current state of the art and future directions☆

PubMed Central

Koshkaryev, Alexander; Sawant, Rupa; Deshpande, Madhura; Torchilin, Vladimir

2012-01-01

Significant progress has been made recently in the area of immunoconjugated drugs and drug delivery systems (DDS). The immuno-modification of either the drug or DDS has proven to be a very promising approach that has significantly improved the targeted accumulation in pathological sites while decreasing its undesirable side effects in healthy tissues. The arrangement for both prolonged life in the circulation and specific target recognition represents another potent strategy in the development of immuno-targeted systems. The longevity of immuno-targeted DDS such as immunoliposomes and immunomicelles improves their targetability even in the presence of the additional passive accumulation in areas with a compromised vasculature. The added use of the immuno-targeted systems takes advantage of the specific microenvironment of pathological sites including lowered pH, increased temperature, and variation in the enzymatic activity. “Smart” stimulus-responsive systems combine different valuable functionalities including PEG-protection, targeting antibody, cell-penetration, and stimulus-sensitive functions. In this review we examined the evolution, current status and future directions in the area of therapeutical immunoconjugates and long-circulating immuno-targeted DDS. PMID:22964425

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-08-02

Hybrid-drive implosion systems (20,40) for ICF targets (10,22,42) are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator (12) surroundingly disposed around fusion fuel (14). The ablator is first compressed to higher density by a laser system (24), or by an ion beam system (44), that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system (30,48) that is optimized for this second phase of operation of the target. The fusion fuel (14) is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion.

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, James W.

1988-01-01

Hybrid-drive implosion systems (20,40) for ICF targets (10,22,42) are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator (12) surroundingly disposed around fusion fuel (14). The ablator is first compressed to higher density by a laser system (24), or by an ion beam system (44), that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system (30,48) that is optimized for this second phase of operation of the target. The fusion fuel (14) is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion.

Hybrid-drive implosion system for ICF targets

DOEpatents

Mark, J.W.K.

1987-10-14

Hybrid-drive implosion systems for ICF targets are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator surroundingly disposed around fusion fuel. The ablator is first compressed to higher density by a laser system, or by an ion beam system, that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system that is optimized for this second phase of operation of the target. The fusion fuel is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion. 3 figs.

Structural systems pharmacology: a new frontier in discovering novel drug targets.

PubMed

Tan, Hepan; Ge, Xiaoxia; Xie, Lei

2013-08-01

The modern target-based drug discovery process, characterized by the one-drug-one-gene paradigm, has been of limited success. In contrast, phenotype-based screening produces thousands of active compounds but gives no hint as to what their molecular targets are or which ones merit further research. This presents a question: What is a suitable target for an efficient and safe drug? In this paper, we argue that target selection should take into account the proteome-wide energetic and kinetic landscape of drug-target interactions, as well as their cellular and organismal consequences. We propose a new paradigm of structural systems pharmacology to deconvolute the molecular targets of successful drugs as well as to identify druggable targets and their drug-like binders. Here we face two major challenges in structural systems pharmacology: How do we characterize and analyze the structural and energetic origins of drug-target interactions on a proteome scale? How do we correlate the dynamic molecular interactions to their in vivo activity? We will review recent advances in developing new computational tools for biophysics, bioinformatics, chemoinformatics, and systems biology related to the identification of genome-wide target profiles. We believe that the integration of these tools will realize structural systems pharmacology, enabling us to both efficiently develop effective therapeutics for complex diseases and combat drug resistance.

Method for controlling a vehicle with two or more independently steered wheels

DOEpatents

Reister, D.B.; Unseren, M.A.

1995-03-28

A method is described for independently controlling each steerable drive wheel of a vehicle with two or more such wheels. An instantaneous center of rotation target and a tangential velocity target are inputs to a wheel target system which sends the velocity target and a steering angle target for each drive wheel to a pseudo-velocity target system. The pseudo-velocity target system determines a pseudo-velocity target which is compared to a current pseudo-velocity to determine a pseudo-velocity error. The steering angle targets and the steering angles are inputs to a steering angle control system which outputs to the steering angle encoders, which measure the steering angles. The pseudo-velocity error, the rate of change of the pseudo-velocity error, and the wheel slip between each pair of drive wheels are used to calculate intermediate control variables which, along with the steering angle targets are used to calculate the torque to be applied at each wheel. The current distance traveled for each wheel is then calculated. The current wheel velocities and steering angle targets are used to calculate the cumulative and instantaneous wheel slip and the current pseudo-velocity. 6 figures.

System-level multi-target drug discovery from natural products with applications to cardiovascular diseases.

PubMed

Zheng, Chunli; Wang, Jinan; Liu, Jianling; Pei, Mengjie; Huang, Chao; Wang, Yonghua

2014-08-01

The term systems pharmacology describes a field of study that uses computational and experimental approaches to broaden the view of drug actions rooted in molecular interactions and advance the process of drug discovery. The aim of this work is to stick out the role that the systems pharmacology plays across the multi-target drug discovery from natural products for cardiovascular diseases (CVDs). Firstly, based on network pharmacology methods, we reconstructed the drug-target and target-target networks to determine the putative protein target set of multi-target drugs for CVDs treatment. Secondly, we reintegrated a compound dataset of natural products and then obtained a multi-target compounds subset by virtual-screening process. Thirdly, a drug-likeness evaluation was applied to find the ADME-favorable compounds in this subset. Finally, we conducted in vitro experiments to evaluate the reliability of the selected chemicals and targets. We found that four of the five randomly selected natural molecules can effectively act on the target set for CVDs, indicating the reasonability of our systems-based method. This strategy may serve as a new model for multi-target drug discovery of complex diseases.

Clinical, pathological and functional characterization of riboflavin-responsive neuropathy

PubMed Central

Manole, Andreea; Jaunmuktane, Zane; Hargreaves, Iain; Ludtmann, Marthe H R; Salpietro, Vincenzo; Bello, Oscar D; Pope, Simon; Pandraud, Amelie; Horga, Alejandro; Scalco, Renata S; Li, Abi; Ashokkumar, Balasubramaniem; Lourenço, Charles M; Heales, Simon; Horvath, Rita; Chinnery, Patrick F; Toro, Camilo; Singleton, Andrew B; Jacques, Thomas S; Abramov, Andrey Y; Muntoni, Francesco; Hanna, Michael G; Reilly, Mary M; Revesz, Tamas; Kullmann, Dimitri M

2017-01-01

Abstract Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency, neuropathology and downstream consequences of riboflavin transporter mutations are unclear. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between riboflavin transporter mutations and Brown-Vialetto-Van Laere syndrome, identifying 22 pathogenic mutations in SLC52A2 and SLC52A3, 14 of which were novel. Brain and spinal cord neuropathological examination of two cases with SLC52A3 mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column–medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain, we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this using in vitro and in vivo models. Electron transport chain complex I and complex II activity were decreased in SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila melanogaster riboflavin transporter homologue revealed reduced levels of riboflavin, downstream metabolites, and electron transport chain complex I activity. This in turn led to abnormal mitochondrial membrane potential, respiratory chain activity and morphology. Riboflavin transporter knockdown in Drosophila also resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings expand the genetic, clinical and neuropathological features of Brown-Vialetto-Van Laere syndrome, implicate mitochondrial dysfunction as a downstream consequence of riboflavin transporter gene defects, and validate riboflavin esters as a potential therapeutic strategy. PMID:29053833

Cold-evoked potentials - Ready for clinical use?

PubMed

Hüllemann, P; Nerdal, A; Binder, A; Helfert, S; Reimer, M; Baron, R

2016-11-01

Cold-evoked potentials (CEPs) are known to assess the integrity of A-delta fibres and the spinothalamic tract. Nevertheless, the clinical value was not investigated previously. The aim of this study was to measure CEPs in 16 healthy subjects from the face, hand and foot sole and to investigate whether CEPs reliably detect A-delta fibre abnormalities. Swift cold stimuli were applied to the skin with a commercially available thermode, which cooled down from 30 to 25 °C in approximately 0.5 s. CEP latencies (N1, N2 and P2) and amplitudes (N1, N2/P2) were recorded with EEG. Reversible A-fibre function loss was induced by applying a selective A-fibre block at the superficial radial nerve. In all 16 subjects CEPs could be recorded from all locations; N2, P2 mean latencies were 276.4 ± 38.9 and 389.8 ± 52.5 (face), 318.6 ± 31.6 ms and 477.7 ± 43.6 (hand), and 627.6 ± 84.4 and 774.2 ± 94.0 (foot sole). N2/P2 amplitudes were 10.7 ± 4.1, 11.3 ± 4.1 and 7.5 ± 4.1 μV. During A-fibre block no CEPs were detectable in the grand average, which restored 10 min after block removal. CEPs were reliably recorded in healthy subjects at the hand, face and foot. Experimentally induced reversible A-delta fibre function loss was detected by CEPs. Functional recovery was assessed as well. This study is basis for further CEP evaluation studies and might be the first step for implementing CEPs in clinical routine for the early diagnosis of small-fibre disease. WHAT DOES THIS STUDY ADD?: Cold-evoked potentials are capable of reliably measuring A-delta fibre integrity, loss of function and functional recovery in healthy subjects, which is an essential prerequisite for diagnostic use in patients with small-fibre disease. © 2016 European Pain Federation - EFIC®.

Clinical, pathological and functional characterization of riboflavin-responsive neuropathy.

PubMed

Manole, Andreea; Jaunmuktane, Zane; Hargreaves, Iain; Ludtmann, Marthe H R; Salpietro, Vincenzo; Bello, Oscar D; Pope, Simon; Pandraud, Amelie; Horga, Alejandro; Scalco, Renata S; Li, Abi; Ashokkumar, Balasubramaniem; Lourenço, Charles M; Heales, Simon; Horvath, Rita; Chinnery, Patrick F; Toro, Camilo; Singleton, Andrew B; Jacques, Thomas S; Abramov, Andrey Y; Muntoni, Francesco; Hanna, Michael G; Reilly, Mary M; Revesz, Tamas; Kullmann, Dimitri M; Jepson, James E C; Houlden, Henry

2017-11-01

Brown-Vialetto-Van Laere syndrome represents a phenotypic spectrum of motor, sensory, and cranial nerve neuropathy, often with ataxia, optic atrophy and respiratory problems leading to ventilator-dependence. Loss-of-function mutations in two riboflavin transporter genes, SLC52A2 and SLC52A3, have recently been linked to Brown-Vialetto-Van Laere syndrome. However, the genetic frequency, neuropathology and downstream consequences of riboflavin transporter mutations are unclear. By screening a large cohort of 132 patients with early-onset severe sensory, motor and cranial nerve neuropathy we confirmed the strong genetic link between riboflavin transporter mutations and Brown-Vialetto-Van Laere syndrome, identifying 22 pathogenic mutations in SLC52A2 and SLC52A3, 14 of which were novel. Brain and spinal cord neuropathological examination of two cases with SLC52A3 mutations showed classical symmetrical brainstem lesions resembling pathology seen in mitochondrial disease, including severe neuronal loss in the lower cranial nerve nuclei, anterior horns and corresponding nerves, atrophy of the spinothalamic and spinocerebellar tracts and posterior column-medial lemniscus pathways. Mitochondrial dysfunction has previously been implicated in an array of neurodegenerative disorders. Since riboflavin metabolites are critical components of the mitochondrial electron transport chain, we hypothesized that reduced riboflavin transport would result in impaired mitochondrial activity, and confirmed this using in vitro and in vivo models. Electron transport chain complex I and complex II activity were decreased in SLC52A2 patient fibroblasts, while global knockdown of the single Drosophila melanogaster riboflavin transporter homologue revealed reduced levels of riboflavin, downstream metabolites, and electron transport chain complex I activity. This in turn led to abnormal mitochondrial membrane potential, respiratory chain activity and morphology. Riboflavin transporter knockdown in Drosophila also resulted in severely impaired locomotor activity and reduced lifespan, mirroring patient pathology, and these phenotypes could be partially rescued using a novel esterified derivative of riboflavin. Our findings expand the genetic, clinical and neuropathological features of Brown-Vialetto-Van Laere syndrome, implicate mitochondrial dysfunction as a downstream consequence of riboflavin transporter gene defects, and validate riboflavin esters as a potential therapeutic strategy. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain.

Characterization of Macrophage/Microglial Activation and Effect of Photobiomodulation in the Spared Nerve Injury Model of Neuropathic Pain.

PubMed

Kobiela Ketz, Ann; Byrnes, Kimberly R; Grunberg, Neil E; Kasper, Christine E; Osborne, Lisa; Pryor, Brian; Tosini, Nicholas L; Wu, Xingjia; Anders, Juanita J

2017-05-01

Neuropathic pain is common and debilitating with limited effective treatments. Macrophage/microglial activation along ascending somatosensory pathways following peripheral nerve injury facilitates neuropathic pain. However, polarization of macrophages/microglia in neuropathic pain is not well understood. Photobiomodulation treatment has been used to decrease neuropathic pain, has anti-inflammatory effects in spinal injury and wound healing models, and modulates microglial polarization in vitro. Our aim was to characterize macrophage/microglia response after peripheral nerve injury and modulate the response with photobiomodulation. Adult male Sprague-Dawley rats were randomly assigned to sham (N = 13), spared nerve injury (N = 13), or injury + photobiomodulation treatment groups (N = 7). Mechanical hypersensitivity was assessed with electronic von Frey. Photobiomodulation (980 nm) was applied to affected hind paw (output power 1 W, 20 s, 41cm above skin, power density 43.25 mW/cm 2 , dose 20 J), dorsal root ganglia (output power 4.5W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 85.5 J), and spinal cord regions (output power 1.5 W, 19s, in skin contact, power density 43.25 mW/cm 2 , dose 28.5 J) every other day from day 7-30 post-operatively. Immunohistochemistry characterized macrophage/microglial activation. Injured groups demonstrated mechanical hypersensitivity 1-30 days post-operatively. Photobiomodulation-treated animals began to recover after two treatments; at day 26, mechanical sensitivity reached baseline. Peripheral nerve injury caused region-specific macrophages/microglia activation along spinothalamic and dorsal-column medial lemniscus pathways. A pro-inflammatory microglial marker was expressed in the spinal cord of injured rats compared to photobiomodulation-treated and sham group. Photobiomodulation-treated dorsal root ganglion macrophages expressed anti-inflammatory markers. Photobiomodulation effectively reduced mechanical hypersensitivity, potentially through modulating macrophage/microglial activation to an anti-inflammatory phenotype. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. 2016. This work is written by US Government employees and is in the public domain in the US.

Sensor-guided threat countermeasure system

DOEpatents

Stuart, Brent C.; Hackel, Lloyd A.; Hermann, Mark R.; Armstrong, James P.

2012-12-25

A countermeasure system for use by a target to protect against an incoming sensor-guided threat. The system includes a laser system for producing a broadband beam and means for directing the broadband beam from the target to the threat. The countermeasure system comprises the steps of producing a broadband beam and directing the broad band beam from the target to blind or confuse the incoming sensor-guided threat.

Cytotoxic Chromosomal Targeting by CRISPR/Cas Systems Can Reshape Bacterial Genomes and Expel or Remodel Pathogenicity Islands

PubMed Central

Vercoe, Reuben B.; Chang, James T.; Dy, Ron L.; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S.; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R.; Fineran, Peter C.

2013-01-01

In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas–mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA–targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity. PMID:23637624

Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and expel or remodel pathogenicity islands.

PubMed

Vercoe, Reuben B; Chang, James T; Dy, Ron L; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R; Fineran, Peter C

2013-04-01

In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas-mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA-targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity.

Automated target recognition using passive radar and coordinated flight models

NASA Astrophysics Data System (ADS)

Ehrman, Lisa M.; Lanterman, Aaron D.

2003-09-01

Rather than emitting pulses, passive radar systems rely on illuminators of opportunity, such as TV and FM radio, to illuminate potential targets. These systems are particularly attractive since they allow receivers to operate without emitting energy, rendering them covert. Many existing passive radar systems estimate the locations and velocities of targets. This paper focuses on adding an automatic target recognition (ATR) component to such systems. Our approach to ATR compares the Radar Cross Section (RCS) of targets detected by a passive radar system to the simulated RCS of known targets. To make the comparison as accurate as possible, the received signal model accounts for aircraft position and orientation, propagation losses, and antenna gain patterns. The estimated positions become inputs for an algorithm that uses a coordinated flight model to compute probable aircraft orientation angles. The Fast Illinois Solver Code (FISC) simulates the RCS of several potential target classes as they execute the estimated maneuvers. The RCS is then scaled by the Advanced Refractive Effects Prediction System (AREPS) code to account for propagation losses that occur as functions of altitude and range. The Numerical Electromagnetic Code (NEC2) computes the antenna gain pattern, so that the RCS can be further scaled. The Rician model compares the RCS of the illuminated aircraft with those of the potential targets. This comparison results in target identification.

Advanced MicroObserver UGS integration with and cueing of the BattleHawk squad level loitering munition and UAV

NASA Astrophysics Data System (ADS)

Steadman, Bob; Finklea, John; Kershaw, James; Loughman, Cathy; Shaffner, Patti; Frost, Dean; Deller, Sean

2014-06-01

Textron's Advanced MicroObserver(R) is a next generation remote unattended ground sensor system (UGS) for border security, infrastructure protection, and small combat unit security. The original MicroObserver(R) is a sophisticated seismic sensor system with multi-node fusion that supports target tracking. This system has been deployed in combat theaters. The system's seismic sensor nodes are uniquely able to be completely buried (including antennas) for optimal covertness. The advanced version adds a wireless day/night Electro-Optic Infrared (EOIR) system, cued by seismic tracking, with sophisticated target discrimination and automatic frame capture features. Also new is a field deployable Gateway configurable with a variety of radio systems and flexible networking, an important upgrade that enabled the research described herein. BattleHawkTM is a small tube launched Unmanned Air Vehicle (UAV) with a warhead. Using transmitted video from its EOIR subsystem an operator can search for and acquire a target day or night, select a target for attack, and execute terminal dive to destroy the target. It is designed as a lightweight squad level asset carried by an individual infantryman. Although BattleHawk has the best loiter time in its class, it's still relatively short compared to large UAVs. Also it's a one-shot asset in its munition configuration. Therefore Textron Defense Systems conducted research, funded internally, to determine if there was military utility in having the highly persistent MicroObserver(R) system cue BattleHawk's launch and vector it to beyond visual range targets for engagement. This paper describes that research; the system configuration implemented, and the results of field testing that was performed on a government range early in 2013. On the integrated system that was implemented, MicroObserver(R) seismic detections activated that system's camera which then automatically captured images of the target. The geo-referenced and time-tagged MicroObserver(R) target reports and images were then automatically forwarded to the BattleHawk Android-based controller. This allowed the operator to see the intruder (classified and geo-located) on the map based display, assess the intruder as likely hostile (via the image), and launch BattleHawk with the pre-loaded target coordinates. The operator was thus able to quickly acquire the intended target (without a search) and initiate target engagement immediately. System latencies were a major concern encountered during the research.

CRISPRTarget

PubMed Central

Biswas, Ambarish; Gagnon, Joshua N.; Brouns, Stan J.J.; Fineran, Peter C.; Brown, Chris M.

2013-01-01

The bacterial and archaeal CRISPR/Cas adaptive immune system targets specific protospacer nucleotide sequences in invading organisms. This requires base pairing between processed CRISPR RNA and the target protospacer. For type I and II CRISPR/Cas systems, protospacer adjacent motifs (PAM) are essential for target recognition, and for type III, mismatches in the flanking sequences are important in the antiviral response. In this study, we examine the properties of each class of CRISPR. We use this information to provide a tool (CRISPRTarget) that predicts the most likely targets of CRISPR RNAs (http://bioanalysis.otago.ac.nz/CRISPRTarget). This can be used to discover targets in newly sequenced genomic or metagenomic data. To test its utility, we discover features and targets of well-characterized Streptococcus thermophilus and Sulfolobus solfataricus type II and III CRISPR/Cas systems. Finally, in Pectobacterium species, we identify new CRISPR targets and propose a model of temperate phage exposure and subsequent inhibition by the type I CRISPR/Cas systems. PMID:23492433

Development of a machine vision system for automated structural assembly

NASA Technical Reports Server (NTRS)

Sydow, P. Daniel; Cooper, Eric G.

1992-01-01

Research is being conducted at the LaRC to develop a telerobotic assembly system designed to construct large space truss structures. This research program was initiated within the past several years, and a ground-based test-bed was developed to evaluate and expand the state of the art. Test-bed operations currently use predetermined ('taught') points for truss structural assembly. Total dependence on the use of taught points for joint receptacle capture and strut installation is neither robust nor reliable enough for space operations. Therefore, a machine vision sensor guidance system is being developed to locate and guide the robot to a passive target mounted on the truss joint receptacle. The vision system hardware includes a miniature video camera, passive targets mounted on the joint receptacles, target illumination hardware, and an image processing system. Discrimination of the target from background clutter is accomplished through standard digital processing techniques. Once the target is identified, a pose estimation algorithm is invoked to determine the location, in three-dimensional space, of the target relative to the robots end-effector. Preliminary test results of the vision system in the Automated Structural Assembly Laboratory with a range of lighting and background conditions indicate that it is fully capable of successfully identifying joint receptacle targets throughout the required operational range. Controlled optical bench test results indicate that the system can also provide the pose estimation accuracy to define the target position.

Texture-based measurement of spatial frequency response using the dead leaves target: extensions, and application to real camera systems

NASA Astrophysics Data System (ADS)

McElvain, Jon; Campbell, Scott P.; Miller, Jonathan; Jin, Elaine W.

2010-01-01

The dead leaves model was recently introduced as a method for measuring the spatial frequency response (SFR) of camera systems. The target consists of a series of overlapping opaque circles with a uniform gray level distribution and radii distributed as r-3. Unlike the traditional knife-edge target, the SFR derived from the dead leaves target will be penalized for systems that employ aggressive noise reduction. Initial studies have shown that the dead leaves SFR correlates well with sharpness/texture blur preference, and thus the target can potentially be used as a surrogate for more expensive subjective image quality evaluations. In this paper, the dead leaves target is analyzed for measurement of camera system spatial frequency response. It was determined that the power spectral density (PSD) of the ideal dead leaves target does not exhibit simple power law dependence, and scale invariance is only loosely obeyed. An extension to the ideal dead leaves PSD model is proposed, including a correction term to account for system noise. With this extended model, the SFR of several camera systems with a variety of formats was measured, ranging from 3 to 10 megapixels; the effects of handshake motion blur are also analyzed via the dead leaves target.

Hitting and missing targets by ambulance services for emergency calls: effects of different systems of performance measurement within the UK

PubMed Central

Bevan, Gwyn; Hamblin, Richard

2009-01-01

Following devolution, differences developed between UK countries in systems of measuring performance against a common target that ambulance services ought to respond to 75% of calls for what may be immediately life threatening emergencies (category A calls) within 8 minutes. Only in England was this target integral to a ranking system of ‘star rating’, which inflicted reputational damage on services that failed to hit targets, and only in England has this target been met. In other countries, the target has been missed by such large margins that services would have been publicly reported as failing, if they had been covered by the English system of star ratings. The paper argues that this case-study adds to evidence from comparisons of different systems of hospital performance measurement that, to have an effect, these systems need to be designed to inflict reputational damage on those that have performed poorly; and it explores implications of this hypothesis. The paper also asks questions about the adequacy of systems of performance measurement of ambulance services in UK countries. PMID:19381327

Hitting the Target: Target Setting and Information Systems for the Learning and Skills Sector.

ERIC Educational Resources Information Center

Owen, Jane; Alterman, Jeff

The use of target setting in conjunction with good information systems in colleges and work-based learning (WBL) providers can lead to improved service provisions across the sector in the United Kingdom. Target setting must be carried out in a systematic way in which providers must develop target- setting processes with a focus on learner success;…

A small molecule nanodrug consisting of amphiphilic targeting ligand-chemotherapy drug conjugate for targeted cancer therapy.

PubMed

Mou, Quanbing; Ma, Yuan; Zhu, Xinyuan; Yan, Deyue

2016-05-28

Targeted drug delivery is a broadly applicable approach for cancer therapy. However, the nanocarrier-based targeted delivery system suffers from batch-to-batch variation, quality concerns and carrier-related toxicity issues. Thus, to develop a carrier-free targeted delivery system with nanoscale characteristics is very attractive. Here, a novel targeting small molecule nanodrug self-delivery system consisting of targeting ligand and chemotherapy drug was constructed, which combined the advantages of small molecules and nano-assemblies together and showed excellent targeting ability and long blood circulation time with well-defined structure, high drug loading ratio and on-demand drug release behavior. As a proof-of-concept, lactose (Lac) and doxorubicin (DOX) were chosen as the targeting ligand and chemotherapy drug, respectively. Lac and DOX were conjugated through a pH-responsive hydrazone group. For its intrinsic amphiphilic property, Lac-DOX conjugate could self-assemble into nanoparticles in water. Both in vitro and in vivo assays indicated that Lac-DOX nanoparticles exhibited enhanced anticancer activity and weak side effects. This novel active targeting nanodrug delivery system shows great potential in cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Use of a compact range approach to evaluate rf and dual-mode missiles

NASA Astrophysics Data System (ADS)

Willis, Kenneth E.; Weiss, Yosef

2000-07-01

This paper describes a hardware-in-the-loop (HWIL) system developed for testing Radio Frequency (RF), Infra-Red (IR), and Dual-Mode missile seekers. The system consists of a unique hydraulic five-axis (three seeker axes plus two target axes) Flight Motion Table (FMT), an off-axis parabolic reflector, and electronics required to generate the signals to the RF feeds. RF energy that simulates the target is fed into the reflector from three orthogonal feeds mounted on the inner target axis, at the focal point area of the parabolic reflector. The parabolic reflector, together with the three RF feeds (the Compact Range), effectively produces a far-field image of the target. Both FMT target axis motion and electronic control of the RF beams (deflection) modify the simulated line-of-sight target angles. Multiple targets, glint, multi-path, ECM, and clutter can be introduced electronically. To evaluate dual-mode seekers, the center section of the parabolic reflector is replaced with an IR- transparent, but RF-reflective section. An IR scene projector mounts to the FMT target axes, with its image focused on the intersection of the FMT seeker axes. The system eliminates the need for a large anechoic chamber and 'Target Wall' or target motion system used with conventional HWIL systems. This reduces acquisition and operating costs of the facility.

Allegany Ballistics Lab: sensor test target system

NASA Astrophysics Data System (ADS)

Eaton, Deran S.

2011-06-01

Leveraging the Naval Surface Warfare Center, Indian Head Division's historical experience in weapon simulation, Naval Sea Systems Command commissioned development of a remote-controlled, digitally programmable Sensor Test Target as part of a modern, outdoor hardware-in-the-loop test system for ordnance-related guidance, navigation and control systems. The overall Target system design invokes a sciences-based, "design of automated experiments" approach meant to close the logistical distance between sensor engineering and developmental T&E in outdoor conditions over useful real world distances. This enables operating modes that employ broad spectrum electromagnetic energy in many a desired combination, variably generated using a Jet Engine Simulator, a multispectral infrared emitter array, optically enhanced incandescent Flare Simulators, Emitter/Detector mounts, and an RF corner reflector kit. As assembled, the recently tested Sensor Test Target prototype being presented can capably provide a full array of useful RF and infrared target source simulations for RDT&E use with developmental and existing sensors. Certain Target technologies are patent pending, with potential spinoffs in aviation, metallurgy and biofuels processing, while others are variations on well-established technology. The Sensor Test Target System is planned for extended installation at Allegany Ballistics Laboratory (Rocket Center, WV).

Real-Time Target Motion Animation for Missile Warning System Testing

DTIC Science & Technology

2006-04-01

T. Perkins, R. Sundberg, J. Cordell, Z. Tun , and M. Owen, Real-time Target Motion Animation for Missile Warning System Testing, Proc. SPIE Vol 6208...Z39-18 Real-time target motion animation for missile warning system testing Timothy Perkins*a, Robert Sundberga, John Cordellb, Zaw Tunb, Mark

A Systems Biology-Based Investigation into the Pharmacological Mechanisms of Sheng-ma-bie-jia-tang Acting on Systemic Lupus Erythematosus by Multi-Level Data Integration.

PubMed

Huang, Lin; Lv, Qi; Liu, Fenfen; Shi, Tieliu; Wen, Chengping

2015-11-12

Sheng-ma-bie-jia-tang (SMBJT) is a Traditional Chinese Medicine (TCM) formula that is widely used for the treatment of Systemic Lupus Erythematosus (SLE) in China. However, molecular mechanism behind this formula remains unknown. Here, we systematically analyzed targets of the ingredients in SMBJT to evaluate its potential molecular mechanism. First, we collected 1,267 targets from our previously published database, the Traditional Chinese Medicine Integrated Database (TCMID). Next, we conducted gene ontology and pathway enrichment analyses for these targets and determined that they were enriched in metabolism (amino acids, fatty acids, etc.) and signaling pathways (chemokines, Toll-like receptors, adipocytokines, etc.). 96 targets, which are known SLE disease proteins, were identified as essential targets and the rest 1,171 targets were defined as common targets of this formula. The essential targets directly interacted with SLE disease proteins. Besides, some common targets also had essential connections to both key targets and SLE disease proteins in enriched signaling pathway, e.g. toll-like receptor signaling pathway. We also found distinct function of essential and common targets in immune system processes. This multi-level approach to deciphering the underlying mechanism of SMBJT treatment of SLE details a new perspective that will further our understanding of TCM formulas.

Production of .sup.64 Cu and other radionuclides using a charged-particle accelerator

DOEpatents

Welch, Michael J.; McCarthy, Deborah W.; Shefer, Ruth E.; Klinkowstein, Robert E.

2000-01-01

Radionuclides are produced according to the present invention at commercially significant yields and at specific activities which are suitable for use in radiodiagnostic agents such as PET imaging agents and radiotherapeutic agents and/or compositions. In the method and system of the present invention, a solid target having an isotopically enriched target layer electroplated on an inert substrate is positioned in a specially designed target holder and irradiated with a charged-particle beam. The beam is preferably generated using an accelerator such as a biomedical cyclotron at energies ranging from about 5 MeV to about 25 MeV. The target is preferably directly irradiated, without an intervening attenuating foil, and with the charged particle beam impinging an area which substantially matches the target area. The irradiated target is remotely and automatically transferred from the target holder, preferably without transferring any target holder subassemblies, to a conveyance system which is preferably a pneumatic or hydraulic conveyance system, and then further transferred to an automated separation system. The system is effective for processing a single target or a plurality of targets. After separation, the unreacted target material can be recycled for preparation of other targets. In a preferred application of the invention, a biomedical cyclotron has been used to produce over 500 mCi of .sup.64 Cu having a specific activity of over 300 mCi/.mu.g Cu according to the reaction .sup.64 Ni(p,n).sup.64 Cu. These results indicate that accelerator-produced .sup.64 Cu is suitable for radiopharmaceutical diagnostic and therapeutic applications.

Multiple-target tracking implementation in the ebCMOS camera system: the LUSIPHER prototype

NASA Astrophysics Data System (ADS)

Doan, Quang Tuyen; Barbier, Remi; Dominjon, Agnes; Cajgfinger, Thomas; Guerin, Cyrille

2012-06-01

The domain of the low light imaging systems progresses very fast, thanks to detection and electronic multiplication technology evolution, such as the emCCD (electron multiplying CCD) or the ebCMOS (electron bombarded CMOS). We present an ebCMOS camera system that is able to track every 2 ms more than 2000 targets with a mean number of photons per target lower than two. The point light sources (targets) are spots generated by a microlens array (Shack-Hartmann) used in adaptive optics. The Multiple-Target-Tracking designed and implemented on a rugged workstation is described. The results and the performances of the system on the identification and tracking are presented and discussed.

Tumor target amplification: Implications for nano drug delivery systems.

PubMed

Seidi, Khaled; Neubauer, Heidi A; Moriggl, Richard; Jahanban-Esfahlan, Rana; Javaheri, Tahereh

2018-04-10

Tumor cells overexpress surface markers which are absent from normal cells. These tumor-restricted antigenic signatures are a fundamental basis for distinguishing on-target from off-target cells for ligand-directed targeting of cancer cells. Unfortunately, tumor heterogeneity impedes the establishment of a solid expression pattern for a given target marker, leading to drastic changes in quality (availability) and quantity (number) of the target. Consequently, a subset of cancer cells remains untargeted during the course of treatment, which subsequently promotes drug-resistance and cancer relapse. Since target inefficiency is only problematic for cancer treatment and not for treatment of other pathological conditions such as viral/bacterial infections, target amplification or the generation of novel targets is key to providing eligible antigenic markers for effective targeted therapy. This review summarizes the limitations of current ligand-directed targeting strategies and provides a comprehensive overview of tumor target amplification strategies, including self-amplifying systems, dual targeting, artificial markers and peptide modification. We also discuss the therapeutic and diagnostic potential of these approaches, the underlying mechanism(s) and established methodologies, mostly in the context of different nanodelivery systems, to facilitate more effective ligand-directed cancer cell monitoring and targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

Ideology and gender: observers' system justification and targets' gender as interactive predictors of citizenship expectations.

PubMed

Chiaburu, Dan S; Harris, T Brad; Smith, Troy A

2014-01-01

We integrate system justification and social role theory to explain how observers' system justification and target employees' gender interact to predict observers' expectations of targets' sportsmanship citizenship behaviors. In contrast with social role theory predictions, observers did not expect greater levels of sportsmanship from women compared to men. Yet observers expected more sportsmanship from women (a) when observers were ideologically motivated by gender-specific beliefs (gender-specific system justification; Study 1) and (b) when system justification was cued experimentally (Study 2). A heretofore-unexamined aspect, observers' ideology, modifies their expectations of sportsmanship citizenship across target genders. This has implications for system justification, social role, and organizational citizenship theoretical perspectives.

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems.

PubMed

Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Badshah, Shaikh Atik; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

2015-10-09

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

Extracting 3d Semantic Information from Video Surveillance System Using Deep Learning

NASA Astrophysics Data System (ADS)

Zhang, J. S.; Cao, J.; Mao, B.; Shen, D. Q.

2018-04-01

At present, intelligent video analysis technology has been widely used in various fields. Object tracking is one of the important part of intelligent video surveillance, but the traditional target tracking technology based on the pixel coordinate system in images still exists some unavoidable problems. Target tracking based on pixel can't reflect the real position information of targets, and it is difficult to track objects across scenes. Based on the analysis of Zhengyou Zhang's camera calibration method, this paper presents a method of target tracking based on the target's space coordinate system after converting the 2-D coordinate of the target into 3-D coordinate. It can be seen from the experimental results: Our method can restore the real position change information of targets well, and can also accurately get the trajectory of the target in space.

Polarized Solid State Target

NASA Astrophysics Data System (ADS)

Dutz, Hartmut; Goertz, Stefan; Meyer, Werner

2017-01-01

The polarized solid state target is an indispensable experimental tool to study single and double polarization observables at low intensity particle beams like tagged photons. It was one of the major components of the Crystal-Barrel experiment at ELSA. Besides the operation of the 'CB frozen spin target' within the experimental program of the Crystal-Barrel collaboration both collaborative groups of the D1 project, the polarized target group of the Ruhr Universität Bochum and the Bonn polarized target group, have made significant developments in the field of polarized targets within the CRC16. The Bonn polarized target group has focused its work on the development of technically challenging polarized solid target systems towards the so called '4π continuous mode polarized target' to operate them in combination with 4π-particle detection systems. In parallel, the Bochum group has developed various highly polarized deuterated target materials and high precision NMR-systems, in the meantime used for polarization experiments at CERN, JLAB and MAMI, too.

Virtual target tracking (VTT) as applied to mobile satellite communication networks

NASA Astrophysics Data System (ADS)

Amoozegar, Farid

1999-08-01

Traditionally, target tracking has been used for aerospace applications, such as, tracking highly maneuvering targets in a cluttered environment for missile-to-target intercept scenarios. Although the speed and maneuvering capability of current aerospace targets demand more efficient algorithms, many complex techniques have already been proposed in the literature, which primarily cover the defense applications of tracking methods. On the other hand, the rapid growth of Global Communication Systems, Global Information Systems (GIS), and Global Positioning Systems (GPS) is creating new and more diverse challenges for multi-target tracking applications. Mobile communication and computing can very well appreciate a huge market for Cellular Communication and Tracking Devices (CCTD), which will be tracking networked devices at the cellular level. The objective of this paper is to introduce a new concept, i.e., Virtual Target Tracking (VTT) for commercial applications of multi-target tracking algorithms and techniques as applied to mobile satellite communication networks. It would be discussed how Virtual Target Tracking would bring more diversity to target tracking research.

Heterogeneous Defensive Naval Weapon Assignment To Swarming Threats In Real Time

DTIC Science & Technology

2016-03-01

threat Damage potential of target t if it hits the ship [integer from 0 to 3] _ ttarget phit Probability that target t hits the ship [probability...secondary weapon systems on target t [integer] _ tsec phit Probability that secondary weapon systems launched from target t hit the ship...pairing. These parameters are calculated as follows: 310 _ _t t tpriority target threat target phit = × × (3.1) 3_ 10 _ _t t tsec priority sec

Ion implantation system and process for ultrasensitive determination of target isotopes

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

Farmer, III, Orville T.; Liezers, Martin

2016-09-13

A system and process are disclosed for ultrasensitive determination of target isotopes of analytical interest in a sample. Target isotopes may be implanted in an implant area on a high-purity substrate to pre-concentrate the target isotopes free of contaminants. A known quantity of a tracer isotope may also be implanted. Target isotopes and tracer isotopes may be determined in a mass spectrometer. The present invention provides ultrasensitive determination of target isotopes in the sample.

Moving Target Techniques: Cyber Resilience throught Randomization, Diversity, and Dynamism

DTIC Science & Technology

2017-03-03

Moving Target Techniques: Cyber Resilience through Randomization, Diversity, and Dynamism Hamed Okhravi and Howard Shrobe Overview: The static...nature of computer systems makes them vulnerable to cyber attacks. Consider a situation where an attacker wants to compromise a remote system running... cyber resilience that attempts to rebalance the cyber landscape is known as cyber moving target (MT) (or just moving target) techniques. Moving target

Space-based infrared sensors of space target imaging effect analysis

NASA Astrophysics Data System (ADS)

Dai, Huayu; Zhang, Yasheng; Zhou, Haijun; Zhao, Shuang

2018-02-01

Target identification problem is one of the core problem of ballistic missile defense system, infrared imaging simulation is an important means of target detection and recognition. This paper first established the space-based infrared sensors ballistic target imaging model of point source on the planet's atmosphere; then from two aspects of space-based sensors camera parameters and target characteristics simulated atmosphere ballistic target of infrared imaging effect, analyzed the camera line of sight jitter, camera system noise and different imaging effects of wave on the target.

Customer systems group 1996 target summaries: Information systems and telecommunications. Revision 4

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

NONE

1995-06-15

The target summaries give planning information on the new business systems development; customer service applications and infrastructure; and advanced information systems and telecommunications research, architecture and standards factions of Information Systems & Telecommunications.

Integration of systems biology with bioprocess engineering: L: -threonine production by systems metabolic engineering of Escherichia coli.

PubMed

Lee, Sang Yup; Park, Jin Hwan

2010-01-01

Random mutation and selection or targeted metabolic engineering without consideration of its impact on the entire metabolic and regulatory networks can unintentionally cause genetic alterations in the region, which is not directly related to the target metabolite. This is one of the reasons why strategies for developing industrial strains are now shifted towards targeted metabolic engineering based on systems biology, which is termed systems metabolic engineering. Using systems metabolic engineering strategies, all the metabolic engineering works are conducted in systems biology framework, whereby entire metabolic and regulatory networks are thoroughly considered in an integrated manner. The targets for purposeful engineering are selected after all possible effects on the entire metabolic and regulatory networks are thoroughly considered. Finally, the strain, which is capable of producing the target metabolite to a high level close to the theoretical maximum value, can be constructed. Here we review strategies and applications of systems biology successfully implemented on bioprocess engineering, with particular focus on developing L: -threonine production strains of Escherichia coli.

Targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system.

PubMed

Liang, Zhen; Zhang, Kang; Chen, Kunling; Gao, Caixia

2014-02-20

Transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems have emerged as powerful tools for genome editing in a variety of species. Here, we report, for the first time, targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system. We designed five TALENs targeting 4 genes, namely ZmPDS, ZmIPK1A, ZmIPK, ZmMRP4, and obtained targeting efficiencies of up to 23.1% in protoplasts, and about 13.3% to 39.1% of the transgenic plants were somatic mutations. Also, we constructed two gRNAs targeting the ZmIPK gene in maize protoplasts, at frequencies of 16.4% and 19.1%, respectively. In addition, the CRISPR/Cas system induced targeted mutations in Z. mays protoplasts with efficiencies (13.1%) similar to those obtained with TALENs (9.1%). Our results show that both TALENs and the CRISPR/Cas system can be used for genome modification in maize. Copyright © 2013. Published by Elsevier Ltd.

An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets.

PubMed

Bradley, Stuart

2015-11-20

Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an "actuator" interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator "firings") to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a "cost function" is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs.

Real-Time Implementation of an Asynchronous Vision-Based Target Tracking System for an Unmanned Aerial Vehicle

DTIC Science & Technology

2007-06-01

Chin Khoon Quek. “Vision Based Control and Target Range Estimation for Small Unmanned Aerial Vehicle.” Master’s Thesis, Naval Postgraduate School...December 2005. [6] Kwee Chye Yap. “Incorporating Target Mensuration System for Target Motion Estimation Along a Road Using Asynchronous Filter

A simultaneously calibration approach for installation and attitude errors of an INS/GPS/LDS target tracker.

PubMed

Cheng, Jianhua; Chen, Daidai; Sun, Xiangyu; Wang, Tongda

2015-02-04

To obtain the absolute position of a target is one of the basic topics for non-cooperated target tracking problems. In this paper, we present a simultaneously calibration method for an Inertial navigation system (INS)/Global position system (GPS)/Laser distance scanner (LDS) integrated system based target positioning approach. The INS/GPS integrated system provides the attitude and position of observer, and LDS offers the distance between the observer and the target. The two most significant errors are taken into jointly consideration and analyzed: (1) the attitude measure error of INS/GPS; (2) the installation error between INS/GPS and LDS subsystems. Consequently, a INS/GPS/LDS based target positioning approach considering these two errors is proposed. In order to improve the performance of this approach, a novel calibration method is designed to simultaneously estimate and compensate these two main errors. Finally, simulations are conducted to access the performance of the proposed target positioning approach and the designed simultaneously calibration method.

Anomalies in target-controlled infusion: an analysis after 20 years of clinical use.

PubMed

Engbers, F H M; Dahan, A

2018-05-01

Although target-controlled infusion has been in use for more than two decades, its benefits are being obscured by anomalies in clinical practice caused by a number of important problems. These include: a variety of pharmacokinetic models available in open target-controlled infusion systems, which often confuse the user; the extrapolation of anthropomorphic data which provokes anomalous adjustments of dosing by such systems; and the uncertainty of regulatory requirements for the application of target-controlled infusion which causes uncontrolled exploitation of drugs and pharmacokinetic models in target-controlled infusion devices. Comparison of performance of pharmacokinetic models is complex and mostly inconclusive. However, a specific behaviour of a model in a target-controlled infusion system that is neither intended nor supported by scientific data can be considered an artefact or anomaly. Several of these anomalies can be identified in the current commercially available target-controlled infusion systems and are discussed in this review. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

A new comprehensive method for detection of livestock-related pathogenic viruses using a target enrichment system.

PubMed

Oba, Mami; Tsuchiaka, Shinobu; Omatsu, Tsutomu; Katayama, Yukie; Otomaru, Konosuke; Hirata, Teppei; Aoki, Hiroshi; Murata, Yoshiteru; Makino, Shinji; Nagai, Makoto; Mizutani, Tetsuya

2018-01-08

We tested usefulness of a target enrichment system SureSelect, a comprehensive viral nucleic acid detection method, for rapid identification of viral pathogens in feces samples of cattle, pigs and goats. This system enriches nucleic acids of target viruses in clinical/field samples by using a library of biotinylated RNAs with sequences complementary to the target viruses. The enriched nucleic acids are amplified by PCR and subjected to next generation sequencing to identify the target viruses. In many samples, SureSelect target enrichment method increased efficiencies for detection of the viruses listed in the biotinylated RNA library. Furthermore, this method enabled us to determine nearly full-length genome sequence of porcine parainfluenza virus 1 and greatly increased Breadth, a value indicating the ratio of the mapping consensus length in the reference genome, in pig samples. Our data showed usefulness of SureSelect target enrichment system for comprehensive analysis of genomic information of various viruses in field samples. Copyright © 2017 Elsevier Inc. All rights reserved.

An improved Red/ET recombineering system and mouse ES cells culture conditions for the generation of targeted mutant mice.

PubMed

Kumagai, Katsuyoshi; Takanashi, Masakatsu; Ohno, Shin-Ichiro; Kuroda, Masahiko; Sudo, Katsuko

2017-05-03

Targeted mutant mice generated on a C57BL/6 background are powerful tools for analysis of the biological functions of genes, and gene targeting technologies using mouse embryonic stem (ES) cells have been used to generate such mice. Recently, a bacterial artificial chromosome (BAC) recombineering system was established for the construction of targeting vectors. However, gene retrieval from BACs for the generation of gene targeting vectors using this system remains difficult. Even when construction of a gene targeting vector is successful, the efficiency of production of targeted mutant mice from ES cells derived from C57BL/6 mice are poor. Therefore, in this study, we first improved the strategy for the retrieval of genes from BACs and their transfer into a DT-A plasmid, for the generation of gene targeting vectors using the BAC recombineering system. Then, we attempted to generate targeted mutant mice from ES cell lines derived from C57BL/6 mice, by culturing in serum-free medium. In conclusion, we established an improved strategy for the efficient generation of targeted mutant mice on a C57BL/6 background, which are useful for the in vivo analysis of gene functions and regulation.

Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

PubMed Central

Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Atik Badshah, Shaikh; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

2015-01-01

Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. PMID:26473828

Finding off-targets, biological pathways, and target diseases for chymase inhibitors via structure-based systems biology approach.

PubMed

Arooj, Mahreen; Sakkiah, Sugunadevi; Cao, Guang Ping; Kim, Songmi; Arulalapperumal, Venkatesh; Lee, Keun Woo

2015-07-01

Off-target binding connotes the binding of a small molecule of therapeutic significance to a protein target in addition to the primary target for which it was proposed. Progressively such off-targeting is emerging to be regular practice to reveal side effects. Chymase is an enzyme of hydrolase class that catalyzes hydrolysis of peptide bonds. A link between heart failure and chymase is ascribed, and a chymase inhibitor is in clinical phase II for treatment of heart failure. However, the underlying mechanisms of the off-target effects of human chymase inhibitors are still unclear. Here, we develop a robust computational strategy that is applicable to any enzyme system and that allows the prediction of drug effects on biological processes. Putative off-targets for chymase inhibitors were identified through various structural and functional similarity analyses along with molecular docking studies. Finally, literature survey was performed to incorporate these off-targets into biological pathways and to establish links between pathways and particular adverse effects. Off-targets of chymase inhibitors are linked to various biological pathways such as classical and lectin pathways of complement system, intrinsic and extrinsic pathways of coagulation cascade, and fibrinolytic system. Tissue kallikreins, granzyme M, neutrophil elastase, and mesotrypsin are also identified as off-targets. These off-targets and their associated pathways are elucidated for the effects of inflammation, cancer, hemorrhage, thrombosis, and central nervous system diseases (Alzheimer's disease). Prospectively, our approach is helpful not only to better understand the mechanisms of chymase inhibitors but also for drug repurposing exercises to find novel uses for these inhibitors. © 2014 Wiley Periodicals, Inc.

USGS aerial resolution targets.

USGS Publications Warehouse

Salamonowicz, P.H.

1982-01-01

It is necessary to measure the achievable resolution of any airborne sensor that is to be used for metric purposes. Laboratory calibration facilities may be inadequate or inappropriate for determining the resolution of non-photographic sensors such as optical-mechanical scanners, television imaging tubes, and linear arrays. However, large target arrays imaged in the field can be used in testing such systems. The USGS has constructed an array of resolution targets in order to permit field testing of a variety of airborne sensing systems. The target array permits any interested organization with an airborne sensing system to accurately determine the operational resolution of its system. -from Author

Recent Advances in Nanoparticle-Based Targeted Drug-Delivery Systems Against Cancer and Role of Tumor Microenvironment.

PubMed

Ashfaq, Usman Ali; Riaz, Muhammad; Yasmeen, Erum; Yousaf, Muhammad Zubair

2017-01-01

Cancer is one of the major causes of death worldwide. The silent activation of cellular factors responsible for deviation from normal regulatory pathways leads to the development of cancer. Nano-biotechnology is a novel drug-delivery system with high potential of efficacy and accuracy to target lethal cancers. Various biocompatible nanoparticle (NP)-based drug-delivery systems such as liposomes, dendrimers, micelles, silica, quantum dots, and magnetic, gold, and carbon nanotubes have already been reported for successful targeted cancer treatment. NPs are functionalized with different biological molecules, peptides, antibody, and protein ligands for targeted drug delivery. These systems include a hydrophilic central core, a target-oriented biocompatible outer layer, and a middle hydrophobic core where the drug destined to reach target site resides. Most of the NPs have the ability to maintain their structural shape and are constructed according to the cancer microenvironment. The self-assembling and colloidal properties of NPs have caused them to become the best vehicles for targeted drug delivery. The tumor microenvironment (TME) plays a major role in cancer progression, detection, and treatment. Due to its continuous complex behavior, the TME can hinder delivery systems, thus halting cancer treatment. Nonetheless, a successful biophysiological interaction between the NPs and the TME results in targeted release of drugs. Currently, a number of drugs and NP-based delivery systems against cancer are in clinical and preclinical trials and a few have been approved by Food and Drug Administration (FDA); for example: taxol, doxil, cerubidine, and adrucil. This review summarizes topical advances about the drugs being used for cancer treatment, their targeted delivery systems based on NPs, and the role of TME in this connection.

Nanoparticles that Communicate In Vivo to Amplify Tumour Targeting

PubMed Central

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2012-01-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability for communication to improve targeting in biological systems, such inflammatory cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘Signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally active the coagulation cascade to broadcast tumour location to clot-targeted ‘Receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed from multiple types of Signalling and Receiving modules, can transmit information via multiple molecular pathways in coagulation, can operate autonomously, and can target over 40-fold higher doses of chemotherapeutics to tumours than non-communicating controls. PMID:21685903

Dual pancreas- and lung-targeting therapy for local and systemic complications of acute pancreatitis mediated by a phenolic propanediamine moiety.

PubMed

Li, Jianbo; Zhang, Jinjie; Fu, Yao; Sun, Xun; Gong, Tao; Jiang, Jinghui; Zhang, Zhirong

2015-08-28

To inhibit both the local and systemic complications with acute pancreatitis, an effective therapy requires a drug delivery system that can efficiently overcome the blood-pancreas barrier while achieving lung-specific accumulation. Here, we report the first dual pancreas- and lung-targeting therapeutic strategy mediated by a phenolic propanediamine moiety for the treatment of acute pancreatitis. Using the proposed dual-targeting ligand, an anti-inflammatory compound Rhein has been tailored to preferentially accumulate in the pancreas and lungs with rapid distribution kinetics, excellent tissue-penetrating properties and minimum toxicity. Accordingly, the drug-ligand conjugate remarkably downregulated the proinflammatory cytokines in the target organs thus effectively inhibiting local pancreatic and systemic inflammation in rats. The dual-specific targeting therapeutic strategy may help pave the way for targeted drug delivery to treat complicated inflammatory diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

Temperature Controller System for Gas Gun Targets

NASA Astrophysics Data System (ADS)

Bucholtz, S. M.; Gehr, R. J.; Rupp, T. D.; Sheffield, S. A.; Robbins, D. L.

2006-07-01

A temperature controller system capable of heating and cooling gas gun targets over the range -75°C to +120°C was designed and tested. The system uses cold nitrogen gas from a liquid nitrogen Dewar for cooling and compressed air for heating. Two gas flow heaters control the gas temperature for both heating and cooling. One heater controls the temperature of the target mounting plate and the other the temperature of a copper tubing coil surrounding the target. Each heater is separately adjustable, so the target material will achieve a uniform temperature throughout its volume. A magnetic gauge membrane with integrated thermocouples was developed to measure the internal temperature of the target. Using this system, multiple magnetic gauge shock experiments, including equation-of-state measurements and shock initiation of high explosives, can be performed over a range of initial temperatures. Successful heating and cooling tests were completed on Teflon samples.

Nanoparticles that communicate in vivo to amplify tumour targeting

NASA Astrophysics Data System (ADS)

von Maltzahn, Geoffrey; Park, Ji-Ho; Lin, Kevin Y.; Singh, Neetu; Schwöppe, Christian; Mesters, Rolf; Berdel, Wolfgang E.; Ruoslahti, Erkki; Sailor, Michael J.; Bhatia, Sangeeta N.

2011-07-01

Nanomedicines have enormous potential to improve the precision of cancer therapy, yet our ability to efficiently home these materials to regions of disease in vivo remains very limited. Inspired by the ability of communication to improve targeting in biological systems, such as inflammatory-cell recruitment to sites of disease, we construct systems where synthetic biological and nanotechnological components communicate to amplify disease targeting in vivo. These systems are composed of ‘signalling’ modules (nanoparticles or engineered proteins) that target tumours and then locally activate the coagulation cascade to broadcast tumour location to clot-targeted ‘receiving’ nanoparticles in circulation that carry a diagnostic or therapeutic cargo, thereby amplifying their delivery. We show that communicating nanoparticle systems can be composed of multiple types of signalling and receiving modules, can transmit information through multiple molecular pathways in coagulation, can operate autonomously and can target over 40 times higher doses of chemotherapeutics to tumours than non-communicating controls.

Antares Reference Telescopes System

NASA Astrophysics Data System (ADS)

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

1983-11-01

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

Targeted delivery of drugs for liver fibrosis.

PubMed

Li, Feng; Wang, Ji-yao

2009-05-01

Liver fibrosis and its end stage disease cirrhosis are a major cause of mortality and morbidity around the world. There is no effective pharmaceutical intervention for liver fibrosis at present. Many drugs that show potent antifibrotic activities in vitro often show only minor effects in vivo because of insufficient concentrations of drugs accumulating around the target cell and their adverse effects as a result of affecting other non-target cells. Hepatic stellate cells (HSC) play a critical role in the fibrogenesis of liver, so they are the target cells of antifibrotic therapy. Several kinds of targeted delivery system that could target the receptors expressed on HSC have been designed, and have shown an attractive targeted potential in vivo. After being carried by these delivery systems, many agents showed a powerful antifibrotic effect in animal models of liver fibrosis. These targeted delivery systems provide a new pathway for the therapy of liver fibrosis. The characteristics of theses targeted carriers are reviewed in this paper.

Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus

PubMed Central

Guan, Jing; Wang, Wanying

2017-01-01

ABSTRACT CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCCmec). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5′ tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCCmec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive trinucleotide pairings between a selected target and the 5′ tag of crRNA can block targeting. These findings add to our understanding of the molecular mechanisms of the type III-A CRISPR-Cas system and provide a novel strategy for the exploitation of engineered CRISPR immunity against integrated MGEs in bacteria for clinical and industrial applications. PMID:29152580

Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus.

PubMed

Guan, Jing; Wang, Wanying; Sun, Baolin

2017-01-01

CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCC mec ). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5' tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCC mec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive trinucleotide pairings between a selected target and the 5' tag of crRNA can block targeting. These findings add to our understanding of the molecular mechanisms of the type III-A CRISPR-Cas system and provide a novel strategy for the exploitation of engineered CRISPR immunity against integrated MGEs in bacteria for clinical and industrial applications.

Meta-Analysis of PECS with Individuals with ASD: Investigation of Targeted versus Non-Targeted Outcomes, Participant Characteristics, and Implementation Phase

ERIC Educational Resources Information Center

Ganz, Jennifer B.; Davis, John L.; Lund, Emily M.; Goodwyn, Fara D.; Simpson, Richard L.

2012-01-01

The Picture Exchange Communication System (PECS) is a widely used picture/icon aided augmentative communication system designed for learners with autism and other developmental disorders. This meta-analysis analyzes the extant empirical literature for PECS relative to targeted (functional communication) and non-targeted concomitant outcomes…

Autonomous grain combine control system

DOEpatents

Hoskinson, Reed L.; Kenney, Kevin L.; Lucas, James R.; Prickel, Marvin A.

2013-06-25

A system for controlling a grain combine having a rotor/cylinder, a sieve, a fan, a concave, a feeder, a header, an engine, and a control system. The feeder of the grain combine is engaged and the header is lowered. A separator loss target, engine load target, and a sieve loss target are selected. Grain is harvested with the lowered header passing the grain through the engaged feeder. Separator loss, sieve loss, engine load and ground speed of the grain combine are continuously monitored during the harvesting. If the monitored separator loss exceeds the selected separator loss target, the speed of the rotor/cylinder, the concave setting, the engine load target, or a combination thereof is adjusted. If the monitored sieve loss exceeds the selected sieve loss target, the speed of the fan, the size of the sieve openings, or the engine load target is adjusted.

The 3D laser radar vision processor system

NASA Astrophysics Data System (ADS)

Sebok, T. M.

1990-10-01

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

The 3D laser radar vision processor system

NASA Technical Reports Server (NTRS)

Sebok, T. M.

1990-01-01

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

Video-Camera-Based Position-Measuring System

NASA Technical Reports Server (NTRS)

Lane, John; Immer, Christopher; Brink, Jeffrey; Youngquist, Robert

2005-01-01

A prototype optoelectronic system measures the three-dimensional relative coordinates of objects of interest or of targets affixed to objects of interest in a workspace. The system includes a charge-coupled-device video camera mounted in a known position and orientation in the workspace, a frame grabber, and a personal computer running image-data-processing software. Relative to conventional optical surveying equipment, this system can be built and operated at much lower cost; however, it is less accurate. It is also much easier to operate than are conventional instrumentation systems. In addition, there is no need to establish a coordinate system through cooperative action by a team of surveyors. The system operates in real time at around 30 frames per second (limited mostly by the frame rate of the camera). It continuously tracks targets as long as they remain in the field of the camera. In this respect, it emulates more expensive, elaborate laser tracking equipment that costs of the order of 100 times as much. Unlike laser tracking equipment, this system does not pose a hazard of laser exposure. Images acquired by the camera are digitized and processed to extract all valid targets in the field of view. The three-dimensional coordinates (x, y, and z) of each target are computed from the pixel coordinates of the targets in the images to accuracy of the order of millimeters over distances of the orders of meters. The system was originally intended specifically for real-time position measurement of payload transfers from payload canisters into the payload bay of the Space Shuttle Orbiters (see Figure 1). The system may be easily adapted to other applications that involve similar coordinate-measuring requirements. Examples of such applications include manufacturing, construction, preliminary approximate land surveying, and aerial surveying. For some applications with rectangular symmetry, it is feasible and desirable to attach a target composed of black and white squares to an object of interest (see Figure 2). For other situations, where circular symmetry is more desirable, circular targets also can be created. Such a target can readily be generated and modified by use of commercially available software and printed by use of a standard office printer. All three relative coordinates (x, y, and z) of each target can be determined by processing the video image of the target. Because of the unique design of corresponding image-processing filters and targets, the vision-based position- measurement system is extremely robust and tolerant of widely varying fields of view, lighting conditions, and varying background imagery.

Test Operations Procedure (TOP) 03-2-827 Test Procedures for Video Target Scoring Using Calibration Lights

DTIC Science & Technology

2016-04-04

Final 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE Test Operations Procedure (TOP) 03-2-827 Test Procedures for Video Target Scoring Using...ABSTRACT This Test Operations Procedure (TOP) describes typical equipment and procedures to setup and operate a Video Target Scoring System (VTSS) to...lights. 15. SUBJECT TERMS Video Target Scoring System, VTSS, witness screens, camera, target screen, light pole 16. SECURITY

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.

Measurements of elastic and inelastic scattering cross-sections using monoenergetic Kα radiation

NASA Astrophysics Data System (ADS)

Rao, Donepudi V.; Seltzer, S. M.; Hubbell, John H.; Cesareo, Roberto; Brunetti, Antonio; Gigante, Giovanni E.

2000-12-01

Elastic and inelastic scattering cross-sections for low, medium and high Z atoms are measured in vacuum using an x- ray tube with a secondary targets as an excitation source. Monoenergetic K(alpha) radiation emitted from the secondary target is used to excite the sample. Monoenergetic radiation emitted from the secondary target is used to excite the sample. Monoenergetic radiation is also produced using two secondary targets coupled to an x-ray tube and the radiation from the second target of the system is used to excite the sample. Elastic and inelastic scattering of K(alpha) X-ray line energies of the secondary target by the sample are recorded with Hp Ge and Si(Li) detectors. Using this system the degree of monochromaticity of the secondary emission and the geometrical effects of the measuring system is estimated. The efficiency is large because the secondary target acts as a converter. Experimental results based on this system will be presented and compared with theoretical estimates. The importance of the dat and the potential use of the system for few applications in the field of medicine and archaeometry will also be presented.

Beacon Collision Avoidance System (BCAS) Alternative Concepts for Determining Target Positions

DOT National Transportation Integrated Search

1978-09-01

The (Litchford) Beacon-based Collision Avoidance System concept requires the computation of target range and bearing relative to the BCAS aircraft. Techniques for determining target range and bearing under four different assumptions about the ground ...

Performance of target detection algorithm in compressive sensing miniature ultraspectral imaging compressed sensing system

NASA Astrophysics Data System (ADS)

Gedalin, Daniel; Oiknine, Yaniv; August, Isaac; Blumberg, Dan G.; Rotman, Stanley R.; Stern, Adrian

2017-04-01

Compressive sensing theory was proposed to deal with the high quantity of measurements demanded by traditional hyperspectral systems. Recently, a compressive spectral imaging technique dubbed compressive sensing miniature ultraspectral imaging (CS-MUSI) was presented. This system uses a voltage controlled liquid crystal device to create multiplexed hyperspectral cubes. We evaluate the utility of the data captured using the CS-MUSI system for the task of target detection. Specifically, we compare the performance of the matched filter target detection algorithm in traditional hyperspectral systems and in CS-MUSI multiplexed hyperspectral cubes. We found that the target detection algorithm performs similarly in both cases, despite the fact that the CS-MUSI data is up to an order of magnitude less than that in conventional hyperspectral cubes. Moreover, the target detection is approximately an order of magnitude faster in CS-MUSI data.

An ultra-high field strength MR image-guided robotic needle delivery system for in-bore small animal interventions.

PubMed

Gravett, Matthew; Cepek, Jeremy; Fenster, Aaron

2017-11-01

The purpose of this study was to develop and validate an image-guided robotic needle delivery system for accurate and repeatable needle targeting procedures in mouse brains inside the 12 cm inner diameter gradient coil insert of a 9.4 T MR scanner. Many preclinical research techniques require the use of accurate needle deliveries to soft tissues, including brain tissue. Soft tissues are optimally visualized in MR images, which offer high-soft tissue contrast, as well as a range of unique imaging techniques, including functional, spectroscopy and thermal imaging, however, there are currently no solutions for delivering needles to small animal brains inside the bore of an ultra-high field MR scanner. This paper describes the mechatronic design, evaluation of MR compatibility, registration technique, mechanical calibration, the quantitative validation of the in-bore image-guided needle targeting accuracy and repeatability, and demonstrated the system's ability to deliver needles in situ. Our six degree-of-freedom, MR compatible, mechatronic system was designed to fit inside the bore of a 9.4 T MR scanner and is actuated using a combination of piezoelectric and hydraulic mechanisms. The MR compatibility and targeting accuracy of the needle delivery system are evaluated to ensure that the system is precisely calibrated to perform the needle targeting procedures. A semi-automated image registration is performed to link the robot coordinates to the MR coordinate system. Soft tissue targets can be accurately localized in MR images, followed by automatic alignment of the needle trajectory to the target. Intra-procedure visualization of the needle target location and the needle were confirmed through MR images after needle insertion. The effects of geometric distortions and signal noise were found to be below threshold that would have an impact on the accuracy of the system. The system was found to have negligible effect on the MR image signal noise and geometric distortion. The system was mechanically calibrated and the mean image-guided needle targeting and needle trajectory accuracies were quantified in an image-guided tissue mimicking phantom experiment to be 178 ± 54 μm and 0.27 ± 0.65°, respectively. An MR image-guided system for in-bore needle deliveries to soft tissue targets in small animal models has been developed. The results of the needle targeting accuracy experiments in phantoms indicate that this system has the potential to deliver needles to the smallest soft tissue structures relevant in preclinical studies, at a wide variety of needle trajectories. Future work in the form of a fully-automated needle driver with precise depth control would benefit this system in terms of its applicability to a wider range of animal models and organ targets. © 2017 American Association of Physicists in Medicine.

Radiological Protection and Nuclear Engineering Studies in Multi-MW Target Systems

NASA Astrophysics Data System (ADS)

Luis, Raul Fernandes

Several innovative projects involving nuclear technology have emerged around the world in recent years, for applications such as spallation neutron sources, accelerator-driven systems for the transmutation of nuclear waste and radioactive ion beam (RIB) production. While the available neutron Wuxes from nuclear reactors did not increase substantially in intensity over the past three decades, the intensities of neutron sources produced in spallation targets have increased steadily, and should continue to do so during the 21st century. Innovative projects like ESS, MYRRHA and EURISOL lie at the forefront of the ongoing pursuit for increasingly bright neutron sources; driven by proton beams with energies up to 2 GeV and intensities up to several mA, the construction of their proposed facilities involves complex Nuclear Technology and Radiological Protection design studies executed by multidisciplinary teams of scientists and engineers from diUerent branches of Science. The intense neutron Wuxes foreseen for those facilities can be used in several scientiVc research Velds, such as Nuclear Physics and Astrophysics, Medicine and Materials Science. In this work, the target systems of two facilitites for the production of RIBs using the Isotope Separation On-Line (ISOL) method were studied in detail: ISOLDE, operating at CERN since 1967, and EURISOL, the next-generation ISOL facility to be built in Europe. For the EURISOL multi-MW target station, a detailed study of Radiological Protection was carried out using the Monte Carlo code FLUKA. Simulations were done to assess neutron Wuences, Vssion rates, ambient dose equivalent rates during operation and after shutdown and the production of radioactive nuclei in the targets and surrounding materials. DiUerent materials were discussed for diUerent components of the target system, aiming at improving its neutronics performance while keeping the residual activities resulting from material activation as low as possible. The second goal of this work was to perform an optimisation study for the ISOLDE neutron converter and Vssion target system. The target system was simulated using FLUKA and the cross section codes TALYS and ABRABLA, with the objective of maximising the performance of the system for the production of pure beams of neutron-rich isotopes, suppressing the contaminations by undesired neutron-deficient isobars. Two alternative target systems were proposed in the optimisation studies; the simplest of the two, with some modiVcations, was built as a prototype and tested at ISOLDE. The experimental results clearly show that it is possible, with simple changes in the layouts of the target systems, to produce purer beams of neutron-rich isotopes around the doubly magic nuclei 78Ni and 132Sn. A study of Radiological Protection was also performed, comparing the performances of the prototype target system and the standard ISOLDE target system. None

A smart telerobotic system driven by monocular vision

NASA Technical Reports Server (NTRS)

Defigueiredo, R. J. P.; Maccato, A.; Wlczek, P.; Denney, B.; Scheerer, J.

1994-01-01

A robotic system that accepts autonomously generated motion and control commands is described. The system provides images from the monocular vision of a camera mounted on a robot's end effector, eliminating the need for traditional guidance targets that must be predetermined and specifically identified. The telerobotic vision system presents different views of the targeted object relative to the camera, based on a single camera image and knowledge of the target's solid geometry.

Hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation system for cancer gene therapy

PubMed Central

Javan, Bita; Shahbazi, Majid

2017-01-01

Transcriptional targeting is the best approach for specific gene therapy. Hypoxia is a common feature of the tumour microenvironment. Therefore, targeting gene expression in hypoxic cells by placing transgene under the control of a hypoxia-responsive promoter can be a good strategy for cancer-specific gene therapy. The hypoxia-inducible gene expression system has been investigated more in suicide gene therapy and it can also be of great help in knocking down cancer gene therapy with siRNAs. However, this system needs to be optimised to have maximum efficacy with minimum side effects in normal tissues. The combination of tissue-/tumour-specific promoters with HRE core sequences has been found to enhance the specificity and efficacy of this system. In this review, hypoxia-inducible gene expression system as well as gene therapy strategies targeting tumour hypoxia will be discussed. This review will also focus on hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation systems developed for cancer-specific gene therapy. PMID:28798809

Automation of the targeting and reflective alignment concept

NASA Technical Reports Server (NTRS)

Redfield, Robin C.

1992-01-01

The automated alignment system, described herein, employs a reflective, passive (requiring no power) target and includes a PC-based imaging system and one camera mounted on a six degree of freedom robot manipulator. The system detects and corrects for manipulator misalignment in three translational and three rotational directions by employing the Targeting and Reflective Alignment Concept (TRAC), which simplifies alignment by decoupling translational and rotational alignment control. The concept uses information on the camera and the target's relative position based on video feedback from the camera. These relative positions are converted into alignment errors and minimized by motions of the robot. The system is robust to exogenous lighting by virtue of a subtraction algorithm which enables the camera to only see the target. These capabilities are realized with relatively minimal complexity and expense.

TU-A-201-01: Introduction to In-Room Imaging System Characteristics

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

Chang, J.

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

The Research Progress of Targeted Drug Delivery Systems

NASA Astrophysics Data System (ADS)

Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

2017-06-01

Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

ROGER a potential orbital space debris removal system

NASA Astrophysics Data System (ADS)

Starke, Juergen; Bischof, Bernd; Foth, W.-O.; -J., J.; Günther

The previous activities in the field of On Orbit Servicing studied in the 1990's included in partic-ular the capability of vehicles in GEO to capture and support satellites (mainly communication satellites) to enable repair and continuation of operations, and finally the controlled transfer the target into a permanent graveyard orbit. The specific capture tools for these applications were mostly based on robotic systems to capture and fix the target under specific dynamic constraints (e.g. slowly tumbling target) without damage, and to allow the stabilization, re-orientation and potential repair of the target and subsequent release or transport to the final disposal orbit. Due to the drastically increasing number of debris particularly in the Low Earth Orbits (SSO) the active debris removal is now necessary to counteract to the predicted debris production cascade (Kessler Syndrome), which means the pollution of the total sphere in low earth orbit and not only the SSO area. In most of the debris congresses it was recommended to start removal with the still integrated systems as soon as possible. In the case of large debris objects, the soft capture system can be replaced by a simpler and robust system able to operate from a safe distance to the target and flexible enough to capture and hold different types of targets such as deactivated and/or defective satellites, upper stages and big fragments. These nominally non -cooperative targets might be partially destroyed by the capture process, but the production of additional debris shall be avoided. A major argument for the commercial applications is a multi-target mission potential, which is possible at GEO because the transfer propellant requirement to the disposal orbit and the return to the orbit of the next potential target is relative low (orbits with similar inclination and altitude). The proposed ROGER system is designed as a spacecraft with rendezvous capabilities including inspection in the vicinity of the target and stabilization and transportation features for the combined configuration. The capture system is a deployable and closable net. The net is ejected from the mother spacecraft at a safe distance to prevent any collision with the target. After transport to the disposal orbit the net will be cut and the spacecraft will return to the operational orbit of the next target. An initial down-scaled demonstration is planned for the net capture system on a parabolic flight in autumn 2010. Further representative demonstrations including, for example, one in LEO are under discussion. The capture system can be used operationally also in other orbits e.g. LEO, but the propellant requirements for transport of the target into a direct controlled re-entry orbit and the subsequent return of the mother spacecraft to a new target orbit will be very high. This could impact the multi mission capability of the system. The potential applications are under discussion with different customers including satellite operators, insurance companies and international organisations. juergen.starke@astrium.eads.net Tel.: +49-421-539-4573

Unsupervised learning in persistent sensing for target recognition by wireless ad hoc networks of ground-based sensors

NASA Astrophysics Data System (ADS)

Hortos, William S.

2008-04-01

In previous work by the author, effective persistent and pervasive sensing for recognition and tracking of battlefield targets were seen to be achieved, using intelligent algorithms implemented by distributed mobile agents over a composite system of unmanned aerial vehicles (UAVs) for persistence and a wireless network of unattended ground sensors for pervasive coverage of the mission environment. While simulated performance results for the supervised algorithms of the composite system are shown to provide satisfactory target recognition over relatively brief periods of system operation, this performance can degrade by as much as 50% as target dynamics in the environment evolve beyond the period of system operation in which the training data are representative. To overcome this limitation, this paper applies the distributed approach using mobile agents to the network of ground-based wireless sensors alone, without the UAV subsystem, to provide persistent as well as pervasive sensing for target recognition and tracking. The supervised algorithms used in the earlier work are supplanted by unsupervised routines, including competitive-learning neural networks (CLNNs) and new versions of support vector machines (SVMs) for characterization of an unknown target environment. To capture the same physical phenomena from battlefield targets as the composite system, the suite of ground-based sensors can be expanded to include imaging and video capabilities. The spatial density of deployed sensor nodes is increased to allow more precise ground-based location and tracking of detected targets by active nodes. The "swarm" mobile agents enabling WSN intelligence are organized in a three processing stages: detection, recognition and sustained tracking of ground targets. Features formed from the compressed sensor data are down-selected according to an information-theoretic algorithm that reduces redundancy within the feature set, reducing the dimension of samples used in the target recognition and tracking routines. Target tracking is based on simplified versions of Kalman filtration. Accuracy of recognition and tracking of implemented versions of the proposed suite of unsupervised algorithms is somewhat degraded from the ideal. Target recognition and tracking by supervised routines and by unsupervised SVM and CLNN routines in the ground-based WSN is evaluated in simulations using published system values and sensor data from vehicular targets in ground-surveillance scenarios. Results are compared with previously published performance for the system of the ground-based sensor network (GSN) and UAV swarm.

The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells.

PubMed

Lee, Ciaran M; Cradick, Thomas J; Bao, Gang

2016-03-01

The clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system from Streptococcus pyogenes (Spy) has been successfully adapted for RNA-guided genome editing in a wide range of organisms. However, numerous reports have indicated that Spy CRISPR-Cas9 systems may have significant off-target cleavage of genomic DNA sequences differing from the intended on-target site. Here, we report the performance of the Neisseria meningitidis (Nme) CRISPR-Cas9 system that requires a longer protospacer-adjacent motif for site-specific cleavage, and present a comparison between the Spy and Nme CRISPR-Cas9 systems targeting the same protospacer sequence. The results with the native crRNA and tracrRNA as well as a chimeric single guide RNA for the Nme CRISPR-Cas9 system were also compared. Our results suggest that, compared with the Spy system, the Nme CRISPR-Cas9 system has similar or lower on-target cleavage activity but a reduced overall off-target effect on a genomic level when sites containing three or fewer mismatches are considered. Thus, the Nme CRISPR-Cas9 system may represent a safer alternative for precision genome engineering applications.

The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells

PubMed Central

Lee, Ciaran M; Cradick, Thomas J; Bao, Gang

2016-01-01

The clustered regularly-interspaced short palindromic repeats (CRISPR)—CRISPR-associated (Cas) system from Streptococcus pyogenes (Spy) has been successfully adapted for RNA-guided genome editing in a wide range of organisms. However, numerous reports have indicated that Spy CRISPR-Cas9 systems may have significant off-target cleavage of genomic DNA sequences differing from the intended on-target site. Here, we report the performance of the Neisseria meningitidis (Nme) CRISPR-Cas9 system that requires a longer protospacer-adjacent motif for site-specific cleavage, and present a comparison between the Spy and Nme CRISPR-Cas9 systems targeting the same protospacer sequence. The results with the native crRNA and tracrRNA as well as a chimeric single guide RNA for the Nme CRISPR-Cas9 system were also compared. Our results suggest that, compared with the Spy system, the Nme CRISPR-Cas9 system has similar or lower on-target cleavage activity but a reduced overall off-target effect on a genomic level when sites containing three or fewer mismatches are considered. Thus, the Nme CRISPR-Cas9 system may represent a safer alternative for precision genome engineering applications. PMID:26782639

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

PubMed

Reagan, Ian J; Brumbelow, Matthew L

2017-02-01

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

Measurement of the target current by inductive probe during laser interaction on terawatt laser system PALS.

PubMed

Cikhardt, J; Krása, J; De Marco, M; Pfeifer, M; Velyhan, A; Krouský, E; Cikhardtová, B; Klír, D; Rezáč, K; Ullschmied, J; Skála, J; Kubeš, P; Kravárik, J

2014-10-01

Measurements of the return-current flowing through a solid target irradiated with the sub-nanosecond kJ-class Prague Asterix Laser System is reported. A new inductive target probe was developed which allows us measuring the target current derivative in a kA/ns range. The dependences of the target current on the laser pulse energy for cooper, graphite, and polyethylene targets are reported. The experiment shows that the target current is proportional to the deposited laser energy and is strongly affected by the shot-to-shot fluctuations. The corresponding maximum target charge exceeded a value of 10 μC. A return-current dependence of the electromagnetic pulse produced by the laser-target interaction is presented.

Advances in Orion's On-Orbit Guidance and Targeting System Architecture

NASA Technical Reports Server (NTRS)

Scarritt, Sara K.; Fill, Thomas; Robinson, Shane

2015-01-01

NASA's manned spaceflight programs have a rich history of advancing onboard guidance and targeting technology. In order to support future missions, the guidance and targeting architecture for the Orion Multi-Purpose Crew Vehicle must be able to operate in complete autonomy, without any support from the ground. Orion's guidance and targeting system must be sufficiently flexible to easily adapt to a wide array of undecided future missions, yet also not cause an undue computational burden on the flight computer. This presents a unique design challenge from the perspective of both algorithm development and system architecture construction. The present work shows how Orion's guidance and targeting system addresses these challenges. On the algorithm side, the system advances the state-of-the-art by: (1) steering burns with a simple closed-loop guidance strategy based on Shuttle heritage, and (2) planning maneuvers with a cutting-edge two-level targeting routine. These algorithms are then placed into an architecture designed to leverage the advantages of each and ensure that they function in concert with one another. The resulting system is characterized by modularity and simplicity. As such, it is adaptable to the on-orbit phases of any future mission that Orion may attempt.

Global Positioning System Synchronized Active Light Autonomous Docking System

NASA Technical Reports Server (NTRS)

Howard, Richard T. (Inventor); Book, Michael L. (Inventor); Bryan, Thomas C. (Inventor); Bell, Joseph L. (Inventor)

1996-01-01

A Global Positioning System Synchronized Active Light Autonomous Docking System (GPSSALADS) for automatically docking a chase vehicle with a target vehicle comprising at least one active light emitting target which is operatively attached to the target vehicle. The target includes a three-dimensional array of concomitantly flashing lights which flash at a controlled common frequency. The GPSSALADS further comprises a visual tracking sensor operatively attached to the chase vehicle for detecting and tracking the target vehicle. Its performance is synchronized with the flash frequency of the lights by a synchronization means which is comprised of first and second internal clocks operatively connected to the active light target and visual tracking sensor, respectively, for providing timing control signals thereto, respectively. The synchronization means further includes first and second Global Positioning System receivers operatively connected to the first and second internal clocks, respectively, for repeatedly providing simultaneous synchronization pulses to the internal clocks, respectively. In addition, the GPSSALADS includes a docking process controller means which is operatively attached to the chase vehicle and is responsive to the visual tracking sensor for producing commands for the guidance and propulsion system of the chase vehicle.

Global Positioning System Synchronized Active Light Autonomous Docking System

NASA Technical Reports Server (NTRS)

Howard, Richard (Inventor)

1994-01-01

A Global Positioning System Synchronized Active Light Autonomous Docking System (GPSSALADS) for automatically docking a chase vehicle with a target vehicle comprises at least one active light emitting target which is operatively attached to the target vehicle. The target includes a three-dimensional array of concomitantly flashing lights which flash at a controlled common frequency. The GPSSALADS further comprises a visual tracking sensor operatively attached to the chase vehicle for detecting and tracking the target vehicle. Its performance is synchronized with the flash frequency of the lights by a synchronization means which is comprised of first and second internal clocks operatively connected to the active light target and visual tracking sensor, respectively, for providing timing control signals thereto, respectively. The synchronization means further includes first and second Global Positioning System receivers operatively connected to the first and second internal clocks, respectively, for repeatedly providing simultaneous synchronization pulses to the internal clocks, respectively. In addition, the GPSSALADS includes a docking process controller means which is operatively attached to the chase vehicle and is responsive to the visual tracking sensor for producing commands for the guidance and propulsion system of the chase vehicle.

Finding a Target with an Accessible Global Positioning System

ERIC Educational Resources Information Center

Ponchillia, Paul E.; MacKenzie, Nancy; Long, Richard G.; Denton-Smith, Pamela; Hicks, Thomas L.; Miley, Priscilla

2007-01-01

This article presents two target-location experiments. In the first experiment, 19 participants located a 25-foot chalk circle 93% of the time with a Global Positioning System (GPS) compared to 12% of the time without it. In a single-subject follow-up experiment, the participant came within 1 foot of the target on all GPS trials. Target-location…

Digital-Electronic/Optical Apparatus Would Recognize Targets

NASA Technical Reports Server (NTRS)

Scholl, Marija S.

1994-01-01

Proposed automatic target-recognition apparatus consists mostly of digital-electronic/optical cross-correlator that processes infrared images of targets. Infrared images of unknown targets correlated quickly with images of known targets. Apparatus incorporates some features of correlator described in "Prototype Optical Correlator for Robotic Vision System" (NPO-18451), and some of correlator described in "Compact Optical Correlator" (NPO-18473). Useful in robotic system; to recognize and track infrared-emitting, moving objects as variously shaped hot workpieces on conveyor belt.

Highly efficient targeted mutagenesis in one-cell mouse embryos mediated by the TALEN and CRISPR/Cas systems.

PubMed

Yasue, Akihiro; Mitsui, Silvia Naomi; Watanabe, Takahito; Sakuma, Tetsushi; Oyadomari, Seiichi; Yamamoto, Takashi; Noji, Sumihare; Mito, Taro; Tanaka, Eiji

2014-07-16

Since the establishment of embryonic stem (ES) cell lines, the combined use of gene targeting with homologous recombination has aided in elucidating the functions of various genes. However, the ES cell technique is inefficient and time-consuming. Recently, two new gene-targeting technologies have been developed: the transcription activator-like effector nuclease (TALEN) system, and the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) system. In addition to aiding researchers in solving conventional problems, these technologies can be used to induce site-specific mutations in various species for which ES cells have not been established. Here, by targeting the Fgf10 gene through RNA microinjection in one-cell mouse embryos with the TALEN and CRISPR/Cas systems, we produced the known limb-defect phenotypes of Fgf10-deficient embryos at the F0 generation. Compared to the TALEN system, the CRISPR/Cas system induced the limb-defect phenotypes with a strikingly higher efficiency. Our results demonstrate that although both gene-targeting technologies are useful, the CRISPR/Cas system more effectively elicits single-step biallelic mutations in mice.

Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

PubMed

Fang, J; Cai, C; Wang, Q; Lin, P; Zhao, Z; Cheng, F

2017-03-01

Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

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.

Fe₃O₄ Nanoparticles in Targeted Drug/Gene Delivery Systems.

PubMed

Shen, Lazhen; Li, Bei; Qiao, Yongsheng

2018-02-23

Fe₃O₄ nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe₃O₄ NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe₃O₄ NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe₃O₄ NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe₃O₄ NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe₃O₄ NPs targeting drug/gene delivery systems.

Atmospheric effects on active illumination

NASA Astrophysics Data System (ADS)

Shaw, Scot E. J.; Kansky, Jan E.

2005-08-01

For some beam-control applications, we can rely on the cooperation of the target when gathering information about the target location and the state of the atmosphere between the target and the beam-control system. The typical example is a cooperative point-source beacon on the target. Light from such a beacon allows the beam-control system to track the target accurately, and, if higher-order adaptive optics is to be employed, to make wave-front measurements and apply appropriate corrections with a deformable mirror. In many applications, including directed-energy weapons, the target is not cooperative. In the absence of a cooperative beacon, we must find other ways to collect the relevant information. This can be accomplished with an active-illumination system. Typically, this means shining one or more lasers at the target and observing the reflected light. In this paper, we qualitatively explore a number of difficulties inherent to active illumination, and suggest some possible mitigation techniques.

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.

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.

Airborne net-centric multi-INT sensor control, display, fusion, and exploitation systems

NASA Astrophysics Data System (ADS)

Linne von Berg, Dale C.; Lee, John N.; Kruer, Melvin R.; Duncan, Michael D.; Olchowski, Fred M.; Allman, Eric; Howard, Grant

2004-08-01

The NRL Optical Sciences Division has initiated a multi-year effort to develop and demonstrate an airborne net-centric suite of multi-intelligence (multi-INT) sensors and exploitation systems for real-time target detection and targeting product dissemination. The goal of this Net-centric Multi-Intelligence Fusion Targeting Initiative (NCMIFTI) is to develop an airborne real-time intelligence gathering and targeting system that can be used to detect concealed, camouflaged, and mobile targets. The multi-INT sensor suite will include high-resolution visible/infrared (EO/IR) dual-band cameras, hyperspectral imaging (HSI) sensors in the visible-to-near infrared, short-wave and long-wave infrared (VNIR/SWIR/LWIR) bands, Synthetic Aperture Radar (SAR), electronics intelligence sensors (ELINT), and off-board networked sensors. Other sensors are also being considered for inclusion in the suite to address unique target detection needs. Integrating a suite of multi-INT sensors on a single platform should optimize real-time fusion of the on-board sensor streams, thereby improving the detection probability and reducing the false alarms that occur in reconnaissance systems that use single-sensor types on separate platforms, or that use independent target detection algorithms on multiple sensors. In addition to the integration and fusion of the multi-INT sensors, the effort is establishing an open-systems net-centric architecture that will provide a modular "plug and play" capability for additional sensors and system components and provide distributed connectivity to multiple sites for remote system control and exploitation.

Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review

PubMed Central

Rosenblat, Christian; McIntyre, Roger S.; Alves, Gilberto S.; Fountoulakis, Konstantinos N.; Carvalho, André F.

2015-01-01

Major depressive disorder (MDD) is a leading cause of disability worldwide. Current first line therapies target modulation of the monoamine system. A large variety of agents are currently available that effectively alter monoamine levels; however, approximately one third of MDD patients remain treatment refractory after adequate trials of multiple monoamine based therapies. Therefore, patients with treatment-resistant depression (TRD) may require modulation of pathways outside of the classic monoamine system. The purpose of this review was thus to discuss novel targets for TRD, to describe their potential mechanisms of action, the available clinical evidence for these targets, the limitations of available evidence as well as future research directions. Several alternate pathways involved in the patho-etiology of TRD have been uncovered including the following: inflammatory pathways, the oxidative stress pathway, the hypothalamic-pituitary-adrenal (HPA) axis, the metabolic and bioenergetics system, neurotrophic pathways, the glutamate system, the opioid system and the cholinergic system. For each of these systems, several targets have been assessed in preclinical and clinical models. Preclinical models strongly implicate these pathways in the patho-etiology of MDD. Clinical trials for TRD have been conducted for several novel targets; however, most of the trials discussed are small and several are uncontrolled. Therefore, further clinical trials are required to assess the true efficacy of these targets for TRD. As well, several promising novel agents have been clinically tested in MDD populations, but have yet to be assessed specifically for TRD. Thus, their applicability to TRD remains unknown. PMID:26467412

The development and progress of XeCl Excimer laser system

NASA Astrophysics Data System (ADS)

Zhang, Yongsheng; Ma, Lianying; Wang, Dahui; Zhao, Xueqing; Zhu, Yongxiang; Hu, Yun; Qian, Hang; Shao, Bibo; Yi, Aiping; Liu, Jingru

2015-05-01

A large angularly multiplexed XeCl Excimer laser system is under development at the Northwest Institute of Nuclear Technology (NINT). It is designed to explore the technical issues of uniform and controllable target illumination. Short wavelength, uniform and controllable target illumination is the fundamental requirement of high energy density physics research using large laser facility. With broadband, extended light source and multi-beam overlapping techniques, rare gas halide Excimer laser facility will provide uniform target illumination theoretically. Angular multiplexing and image relay techniques are briefly reviewed and some of the limitations are examined to put it more practical. The system consists of a commercial oscillator front end, three gas discharge amplifiers, two electron beam pumped amplifiers and the optics required to relay, encode and decode the laser beam. An 18 lens array targeting optics direct and focus the laser in the vacuum target chamber. The system is operational and currently undergoing tests. The total 18 beams output energy is more than 100J and the pulse width is 7ns (FWHM), the intensities on the target will exceed 1013W/cm2. The aberration of off-axis imaging optics at main amplifier should be minimized to improve the final image quality at the target. Automatic computer controlled alignment of the whole system is vital to efficiency and stability of the laser system, an array of automatic alignment model is under test and will be incorporated in the system soon.

Perception and motor activity: reality is always virtual

NASA Astrophysics Data System (ADS)

Bridgeman, Bruce

1999-05-01

We differentiate a cognitive branch of the visual system from a sensorimotor branch with the Roelofs, effect, a perception that a target's position is biased in the direction opposite the offset of a surrounding frame. Previous research left the possibility that accurate motor responses to a perceptually mislocated target might be mediated by oculomotor fixation of the target. Subjects performed judging and jabbing tasks to probe cognitive and motor system representations respectively while engaging in a saccadic task that prevented fixation of the target. Three experiments with an oculomotor distractor task evaluated judging and jabbing responses to the target. Three experiments did not show a Roelofs effect in spite of the prevention of fixation on the target. Motor response did not show a Roelofs effect in spite of the prevention of fixation on the target. Further, a decision about which of two targets to jab does not result in cognitive-system information affect motor response. The Roelofs effect was presented, however, in judging trials that also involved the saccadic task.

Label-Free Raman Microspectral Analysis for Comparison of Cellular Uptake and Distribution between Non-Targeted and EGFR-Targeted Biodegradable Polymeric Nanoparticles

PubMed Central

Chernenko, Tatyana; Buyukozturk, Fulden; Miljkovic, Milos; Carrier, Rebecca; Diem, Max; Amiji, Mansoor

2013-01-01

Active targeted delivery of nanoparticle-encapsulated agents to tumor cells in vivo is expected to enhance therapeutic effect with significantly less non-specific toxicity. Active targeting is based on surface modification of nanoparticles with ligands that bind with extracellular targets and enhance payload delivery in the cells. In this study, we have used label-free Raman micro-spectral analysis and kinetic modeling to study cellular interactions and intracellular delivery of C6-ceramide using a non-targeted and an epidermal growth factor receptor (EGFR) targeted biodegradable polymeric nano-delivery systems, in EGFR-expressing human ovarian adenocarcinoma (SKOV3) cells. The results show that EGFR peptide-modified nanoparticles were rapidly internalized in SKOV3 cells leading to significant intracellular accumulation as compared to non-specific uptake by the non-targeted nanoparticles. Raman micro-spectral analysis enables visualization and quantification of the carrier system, drug-load, and responses of the biological systems interrogated, without exogenous staining and labeling procedures. PMID:24298430

Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR–Cas system

PubMed Central

Elmore, Joshua R.; Sheppard, Nolan F.; Ramia, Nancy; Deighan, Trace; Li, Hong; Terns, Rebecca M.; Terns, Michael P.

2016-01-01

CRISPR–Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM. PMID:26848045

An automated flow system incorporating in-line acid dissolution of bismuth metal from a cyclotron irradiated target assembly for use in the isolation of astatine-211

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

O’Hara, Matthew J.; Krzysko, Anthony J.; Niver, Cynthia M.

Astatine-211 (211At) is a promising cyclotron-produced radionuclide being investigated for use in targeted alpha therapy of blood borne and metastatic cancers, as well as treatment of tumor remnants after surgical resections. The isolation of trace quantities of 211At, produced within several grams of a Bi metal cyclotron target, involves a complex, multi-step procedure: (1) Bi metal dissolution in strong HNO3, (2) distillation of the HNO3 to yield Bi salts containing 211At, (3) dissolution of the salts in strong HCl, (4) solvent extraction of 211At from bismuth salts with diisopropyl ether (DIPE), and (5) back-extraction of 211At from DIPE into NaOH,more » leading to a purified 211At product. Step (1) has been addressed first to begin the process of automating the onerous 211At isolation process. A computer-controlled Bi target dissolution system has been designed. The system performs in-line dissolution of Bi metal from the target assembly using an enclosed target dissolution block, routing the resulting solubilized 211At/Bi mixture to the subsequent process step. The primary parameters involved in Bi metal solubilization (HNO3 concentration and influent flow rate) were optimized prior to evaluation of the system performance on replicate cyclotron irradiated targets. The results indicate that the system performs reproducibly, having nearly quantitative release of 211At from irradiated targets, with cumulative 211At recoveries that follow a sigmoidal function. The predictable nature of the 211At release profile allows the user to tune the system to meet target processing requirements.« less

75 FR 69005 - Flumioxazin; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-10

... reproduction studies indicated an effect on the nervous systems. Based on the lack of evidence of... flumioxazin does not directly impact the nervous system or directly target the immune system. The Agency does... to indicate that flumioxazin targets the nervous system or the immune system. Further, EPA has...

Optoelectronic Sensor System for Guidance in Docking

NASA Technical Reports Server (NTRS)

Howard, Richard T.; Bryan, Thomas C.; Book, Michael L.; Jackson, John L.

2004-01-01

The Video Guidance Sensor (VGS) system is an optoelectronic sensor that provides automated guidance between two vehicles. In the original intended application, the two vehicles would be spacecraft docking together, but the basic principles of design and operation of the sensor are applicable to aircraft, robots, vehicles, or other objects that may be required to be aligned for docking, assembly, resupply, or precise separation. The system includes a sensor head containing a monochrome charge-coupled- device video camera and pulsed laser diodes mounted on the tracking vehicle, and passive reflective targets on the tracked vehicle. The lasers illuminate the targets, and the resulting video images of the targets are digitized. Then, from the positions of the digitized target images and known geometric relationships among the targets, the relative position and orientation of the vehicles are computed. As described thus far, the VGS system is based on the same principles as those of the system described in "Improved Video Sensor System for Guidance in Docking" (MFS-31150), NASA Tech Briefs, Vol. 21, No. 4 (April 1997), page 9a. However, the two systems differ in the details of design and operation. The VGS system is designed to operate with the target completely visible within a relative-azimuth range of +/-10.5deg and a relative-elevation range of +/-8deg. The VGS acquires and tracks the target within that field of view at any distance from 1.0 to 110 m and at any relative roll, pitch, and/or yaw angle within +/-10deg. The VGS produces sets of distance and relative-orientation data at a repetition rate of 5 Hz. The software of this system also accommodates the simultaneous operation of two sensors for redundancy

Target discrimination strategies in optics detection

NASA Astrophysics Data System (ADS)

Sjöqvist, Lars; Allard, Lars; Henriksson, Markus; Jonsson, Per; Pettersson, Magnus

2013-10-01

Detection and localisation of optical assemblies used for weapon guidance or sniper rifle scopes has attracted interest for security and military applications. Typically a laser system is used to interrogate a scene of interest and the retro-reflected radiation is detected. Different system approaches for area coverage can be realised ranging from flood illumination to step-and-stare or continuous scanning schemes. Independently of the chosen approach target discrimination is a crucial issue, particularly if a complex scene such as in an urban environment and autonomous operation is considered. In this work target discrimination strategies in optics detection are discussed. Typical parameters affecting the reflected laser radiation from the target are the wavelength, polarisation properties, temporal effects and the range resolution. Knowledge about the target characteristics is important to predict the target discrimination capability. Two different systems were used to investigate polarisation properties and range resolution information from targets including e.g. road signs, optical reflexes, rifle sights and optical references. The experimental results and implications on target discrimination will be discussed. If autonomous operation is required target discrimination becomes critical in order to reduce the number of false alarms.

Requirement of the CroRS Two-Component System for Resistance to Cell Wall-Targeting Antimicrobials in Enterococcus faecium.

PubMed

Kellogg, Stephanie L; Little, Jaime L; Hoff, Jessica S; Kristich, Christopher J

2017-05-01

Enterococci are serious opportunistic pathogens that are resistant to many cell wall-targeting antibiotics. The CroRS two-component signaling system responds to antibiotic-mediated cell wall stress and is critical for resistance to cell wall-targeting antibiotics in Enterococcus faecalis Here, we identify and characterize an orthologous two-component system found in Enterococcus faecium that is functionally equivalent to the CroRS system of E. faecalis Deletion of croRS in E. faecium resulted in marked susceptibility to cell wall-targeting agents including cephalosporins and bacitracin, as well as moderate susceptibility to ampicillin and vancomycin. As in E. faecalis , exposure to bacitracin and vancomycin stimulates signaling through the CroRS system in E. faecium Moreover, the CroRS system is critical in E. faecium for enhanced beta-lactam resistance mediated by overexpression of Pbp5. Expression of a Pbp5 variant that confers enhanced beta-lactam resistance cannot overcome the requirement for CroRS function. Thus, the CroRS system is a conserved signaling system that responds to cell wall stress to promote intrinsic resistance to important cell wall-targeting antibiotics in clinically relevant enterococci. Copyright © 2017 American Society for Microbiology.

Requirement of the CroRS Two-Component System for Resistance to Cell Wall-Targeting Antimicrobials in Enterococcus faecium

PubMed Central

Kellogg, Stephanie L.; Little, Jaime L.; Hoff, Jessica S.

2017-01-01

ABSTRACT Enterococci are serious opportunistic pathogens that are resistant to many cell wall-targeting antibiotics. The CroRS two-component signaling system responds to antibiotic-mediated cell wall stress and is critical for resistance to cell wall-targeting antibiotics in Enterococcus faecalis. Here, we identify and characterize an orthologous two-component system found in Enterococcus faecium that is functionally equivalent to the CroRS system of E. faecalis. Deletion of croRS in E. faecium resulted in marked susceptibility to cell wall-targeting agents including cephalosporins and bacitracin, as well as moderate susceptibility to ampicillin and vancomycin. As in E. faecalis, exposure to bacitracin and vancomycin stimulates signaling through the CroRS system in E. faecium. Moreover, the CroRS system is critical in E. faecium for enhanced beta-lactam resistance mediated by overexpression of Pbp5. Expression of a Pbp5 variant that confers enhanced beta-lactam resistance cannot overcome the requirement for CroRS function. Thus, the CroRS system is a conserved signaling system that responds to cell wall stress to promote intrinsic resistance to important cell wall-targeting antibiotics in clinically relevant enterococci. PMID:28223383

Point target detection utilizing super-resolution strategy for infrared scanning oversampling system

NASA Astrophysics Data System (ADS)

Wang, Longguang; Lin, Zaiping; Deng, Xinpu; An, Wei

2017-11-01

To improve the resolution of remote sensing infrared images, infrared scanning oversampling system is employed with information amount quadrupled, which contributes to the target detection. Generally the image data from double-line detector of infrared scanning oversampling system is shuffled to a whole oversampled image to be post-processed, whereas the aliasing between neighboring pixels leads to image degradation with a great impact on target detection. This paper formulates a point target detection method utilizing super-resolution (SR) strategy concerning infrared scanning oversampling system, with an accelerated SR strategy proposed to realize fast de-aliasing of the oversampled image and an adaptive MRF-based regularization designed to achieve the preserving and aggregation of target energy. Extensive experiments demonstrate the superior detection performance, robustness and efficiency of the proposed method compared with other state-of-the-art approaches.

Development of beryllium-based neutron target system with three-layer structure for accelerator-based neutron source for boron neutron capture therapy.

PubMed

Kumada, Hiroaki; Kurihara, Toshikazu; Yoshioka, Masakazu; Kobayashi, Hitoshi; Matsumoto, Hiroshi; Sugano, Tomei; Sakurai, Hideyuki; Sakae, Takeji; Matsumura, Akira

2015-12-01

The iBNCT project team with University of Tsukuba is developing an accelerator-based neutron source. Regarding neutron target material, our project has applied beryllium. To deal with large heat load and blistering of the target system, we developed a three-layer structure for the target system that includes a blistering mitigation material between the beryllium used as the neutron generator and the copper heat sink. The three materials were bonded through diffusion bonding using a hot isostatic pressing method. Based on several verifications, our project chose palladium as the intermediate layer. A prototype of the neutron target system was produced. We will verify that sufficient neutrons for BNCT treatment are generated by the device in the near future. Copyright © 2015 Elsevier Ltd. All rights reserved.

Real-Time Two-Dimensional Magnetic Particle Imaging for Electromagnetic Navigation in Targeted Drug Delivery.

PubMed

Le, Tuan-Anh; Zhang, Xingming; Hoshiar, Ali Kafash; Yoon, Jungwon

2017-09-07

Magnetic nanoparticles (MNPs) are effective drug carriers. By using electromagnetic actuated systems, MNPs can be controlled noninvasively in a vascular network for targeted drug delivery (TDD). Although drugs can reach their target location through capturing schemes of MNPs by permanent magnets, drugs delivered to non-target regions can affect healthy tissues and cause undesirable side effects. Real-time monitoring of MNPs can improve the targeting efficiency of TDD systems. In this paper, a two-dimensional (2D) real-time monitoring scheme has been developed for an MNP guidance system. Resovist particles 45 to 65 nm in diameter (5 nm core) can be monitored in real-time (update rate = 2 Hz) in 2D. The proposed 2D monitoring system allows dynamic tracking of MNPs during TDD and renders magnetic particle imaging-based navigation more feasible.

Real-Time Two-Dimensional Magnetic Particle Imaging for Electromagnetic Navigation in Targeted Drug Delivery

PubMed Central

Le, Tuan-Anh; Zhang, Xingming; Hoshiar, Ali Kafash; Yoon, Jungwon

2017-01-01

Magnetic nanoparticles (MNPs) are effective drug carriers. By using electromagnetic actuated systems, MNPs can be controlled noninvasively in a vascular network for targeted drug delivery (TDD). Although drugs can reach their target location through capturing schemes of MNPs by permanent magnets, drugs delivered to non-target regions can affect healthy tissues and cause undesirable side effects. Real-time monitoring of MNPs can improve the targeting efficiency of TDD systems. In this paper, a two-dimensional (2D) real-time monitoring scheme has been developed for an MNP guidance system. Resovist particles 45 to 65 nm in diameter (5 nm core) can be monitored in real-time (update rate = 2 Hz) in 2D. The proposed 2D monitoring system allows dynamic tracking of MNPs during TDD and renders magnetic particle imaging-based navigation more feasible. PMID:28880220

Acoustic Suppression Systems and Related Methods

NASA Technical Reports Server (NTRS)

Kolaini, Ali R. (Inventor); Kern, Dennis L. (Inventor)

2013-01-01

An acoustic suppression system for absorbing and/or scattering acoustic energy comprising a plurality of acoustic targets in a containment is described, the acoustic targets configured to have resonance frequencies allowing the targets to be excited by incoming acoustic waves, the resonance frequencies being adjustable to suppress acoustic energy in a set frequency range. Methods for fabricating and implementing the acoustic suppression system are also provided.

High-resolution remotely sensed small target detection by imitating fly visual perception mechanism.

PubMed

Huang, Fengchen; Xu, Lizhong; Li, Min; Tang, Min

2012-01-01

The difficulty and limitation of small target detection methods for high-resolution remote sensing data have been a recent research hot spot. Inspired by the information capture and processing theory of fly visual system, this paper endeavors to construct a characterized model of information perception and make use of the advantages of fast and accurate small target detection under complex varied nature environment. The proposed model forms a theoretical basis of small target detection for high-resolution remote sensing data. After the comparison of prevailing simulation mechanism behind fly visual systems, we propose a fly-imitated visual system method of information processing for high-resolution remote sensing data. A small target detector and corresponding detection algorithm are designed by simulating the mechanism of information acquisition, compression, and fusion of fly visual system and the function of pool cell and the character of nonlinear self-adaption. Experiments verify the feasibility and rationality of the proposed small target detection model and fly-imitated visual perception method.

System considerations for detection and tracking of small targets using passive sensors

NASA Astrophysics Data System (ADS)

DeBell, David A.

1991-08-01

Passive sensors provide only a few discriminants to assist in threat assessment of small targets. Tracking of the small targets provides additional discriminants. This paper discusses the system considerations for tracking small targets using passive sensors, in particular EO sensors. Tracking helps establish good versus bad detections. Discussed are the requirements to be placed on the sensor system's accuracy, with respect to knowledge of the sightline direction. The detection of weak targets sets a requirement for two levels of tracking in order to reduce processor throughput. A system characteristic is the need to track all detections. For low thresholds, this can mean a heavy track burden. Therefore, thresholds must be adaptive in order not to saturate the processors. Second-level tracks must develop a range estimate in order to assess threat. Sensor platform maneuvers are required if the targets are moving. The need for accurate pointing, good stability, and a good update rate will be shown quantitatively, relating to track accuracy and track association.

Temperature Controller System for Gas Gun Targets

NASA Astrophysics Data System (ADS)

Bucholtz, Scott; Sheffield, Stephen

2005-07-01

A temperature controller system capable of heating and cooling gas gun targets over the range -75 C to +200 C was designed and tested. The system uses cold nitrogen gas from a liquid nitrogen Dewar for cooling and compressed air for heating. Two gas flow heaters control the gas temperature for both heating and cooling. One heater controls the temperature of the target mounting plate and the other the temperature of a copper tubing coil surrounding the target. Each heater is separately adjustable, so the target material will achieve a uniform temperature throughout its volume. A magnetic gauge with integrated thermocouples was developed to measure the internal temperature of the target. Using this system shock experiments, including equation-of-state measurements and shock initiation of high explosives, can be performed over a range of initial temperatures. Successful tests were completed on Teflon samples. This work was supported by the NNSA Enhanced Surveillance Campaign through contract DE-ACO4-01AL66850.

Systems Architectures for a Tactical Naval Command and Control System

DTIC Science & Technology

2009-03-01

Supplement TST Time-sensitive Targeting TTP Tactics, Techniques, and Procedures WTP Weapons-target pairing xix GLOSSARY Analysis...target pairings ( WTPs ) and are presented to OTC [a]. 24. OTC conducts risk assessment of engagement options [a]. 25. OTC orders confirmed surface...engagement options are generated through weapon- target pairings ( WTPs ) and are presented to OTC [a]. 24. OTC conducts risk assessment of engagement

In vivo potency revisited - Keep the target in sight.

PubMed

Gabrielsson, Johan; Peletier, Lambertus A; Hjorth, Stephan

2018-04-01

Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure. The analysis presented in this paper compares potency measures derived from three model situations. Model A represents the closed in vitro system, defining target binding of a ligand when total target and ligand concentrations remain static and constant. Model B describes an open in vivo system with ligand input and clearance (Cl (L) ), adding in parallel to the turnover (k syn , k deg ) of the target. Model C further adds to the open in vivo system in Model B also the elimination of the target-ligand complex (k e(RL) ) via a first-order process. We formulate corresponding equations of the equilibrium (steady-state) relationships between target and ligand, and complex and ligand for each of the three model systems and graphically illustrate the resulting simulations. These equilibrium relationships demonstrate the relative impact of target and target-ligand complex turnover, and are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. A new potency expression, labeled L 50 , is then derived. L 50 is the ligand concentration at half-maximal target and complex concentrations and is an amalgamation of target turnover, target-ligand binding and complex elimination parameters estimated from concentration-time data. L 50 is then compared to the dissociation constant K d (target-ligand binding affinity), the conventional Black & Leff potency estimate EC 50 , and the derived Michaelis-Menten parameter K m (target-ligand binding and complex removal) across a set of literature data. It is evident from a comparison between parameters derived from in vitro vs. in vivo experiments that L 50 can be either numerically greater or smaller than the K d (or K m ) parameter, primarily depending on the ratio of k deg -to-k e(RL) . Contrasting the limit values of target R and target-ligand complex RL for ligand concentrations approaching infinity demonstrates that the outcome of the three models differs to a great extent. Based on the analysis we propose that a better understanding of in vivo pharmacological potency requires simultaneous assessment of the impact of its underlying determinants in the open system setting. We propose that L 50 will be a useful parameter guiding predictions of the effective concentration range, for translational purposes, and assessment of in vivo target occupancy/suppression by ligand, since it also encompasses target turnover - in turn also subject to influence by pathophysiology and drug treatment. Different compounds may have similar binding affinity for a target in vitro (same K d ), but vastly different potencies in vivo. L 50 points to what parameters need to be taken into account, and particularly that closed-system (in vitro) parameters should not be first choice when ranking compounds in vivo (open system). Copyright © 2017 Elsevier Inc. All rights reserved.

The application of carbon nanotubes in target drug delivery systems for cancer therapies

NASA Astrophysics Data System (ADS)

Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

2011-10-01

Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

The CRISPR/Cas9 system produces specific and homozygous targeted gene editing in rice in one generation.

PubMed

Zhang, Hui; Zhang, Jinshan; Wei, Pengliang; Zhang, Botao; Gou, Feng; Feng, Zhengyan; Mao, Yanfei; Yang, Lan; Zhang, Heng; Xu, Nanfei; Zhu, Jian-Kang

2014-08-01

The CRISPR/Cas9 system has been demonstrated to efficiently induce targeted gene editing in a variety of organisms including plants. Recent work showed that CRISPR/Cas9-induced gene mutations in Arabidopsis were mostly somatic mutations in the early generation, although some mutations could be stably inherited in later generations. However, it remains unclear whether this system will work similarly in crops such as rice. In this study, we tested in two rice subspecies 11 target genes for their amenability to CRISPR/Cas9-induced editing and determined the patterns, specificity and heritability of the gene modifications. Analysis of the genotypes and frequency of edited genes in the first generation of transformed plants (T0) showed that the CRISPR/Cas9 system was highly efficient in rice, with target genes edited in nearly half of the transformed embryogenic cells before their first cell division. Homozygotes of edited target genes were readily found in T0 plants. The gene mutations were passed to the next generation (T1) following classic Mendelian law, without any detectable new mutation or reversion. Even with extensive searches including whole genome resequencing, we could not find any evidence of large-scale off-targeting in rice for any of the many targets tested in this study. By specifically sequencing the putative off-target sites of a large number of T0 plants, low-frequency mutations were found in only one off-target site where the sequence had 1-bp difference from the intended target. Overall, the data in this study point to the CRISPR/Cas9 system being a powerful tool in crop genome engineering. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Simultaneous targeting of prostate stem cell antigen and prostate-specific membrane antigen improves the killing of prostate cancer cells using a novel modular T cell-retargeting system.

PubMed

Arndt, Claudia; Feldmann, Anja; Koristka, Stefanie; Cartellieri, Marc; Dimmel, Maria; Ehninger, Armin; Ehninger, Gerhard; Bachmann, Michael

2014-09-01

Recently, we described a novel modular platform technology in which T cell-recruitment and tumor-targeting domains of conventional bispecific antibodies are split to independent components, a universal effector module (EM) and replaceable monospecific/monovalent target modules (TMs) that form highly efficient T cell-retargeting complexes. Theoretically, our unique strategy should allow us to simultaneously retarget T cells to different tumor antigens by combining the EM with two or more different monovalent/monospecific TMs or even with bivalent/bispecific TMs, thereby overcoming limitations of a monospecific treatment such as the selection of target-negative tumor escape variants. In order to advance our recently introduced prostate stem cell antigen (PSCA)-specific modular system for a dual-targeting of prostate cancer cells, two additional TMs were constructed: a monovalent/monospecific TM directed against the prostate-specific membrane antigen (PSMA) and a bivalent/bispecific TM (bsTM) with specificity for PSMA and PSCA. The functionality of the novel dual-targeting strategies was analyzed by performing T cell activation and chromium release assays. Similar to the PSCA-specific modular system, the novel PSMA-specific modular system mediates an efficient target-dependent and -specific tumor cell lysis at low E:T ratios and picomolar Ab concentrations. Moreover, by combination of the EM with either the bispecific TM directed to PSMA and PSCA or both monospecifc TMs directed to either PSCA or PSMA, dual-specific targeting complexes were formed which allowed us to kill potential escape variants expressing only one or the other target antigen. Overall, the novel modular system represents a promising tool for multiple tumor targeting. © 2014 Wiley Periodicals, Inc.

Radar for tracer particles

NASA Astrophysics Data System (ADS)

Ott, Felix; Herminghaus, Stephan; Huang, Kai

2017-05-01

We introduce a radar system capable of tracking a 5 mm spherical target continuously in three dimensions. The 10 GHz (X-band) radar system has a transmission power of 1 W and operates in the near field of the horn antennae. By comparing the phase shift of the electromagnetic wave traveling through the free space with an IQ-mixer, we obtain the relative movement of the target with respect to the antennae. From the azimuth and inclination angles of the receiving antennae obtained in the calibration, we reconstruct the target trajectory in a three-dimensional Cartesian system. Finally, we test the tracking algorithm with target moving in circular as well as in pendulum motions and discuss the capability of the radar system.

Targeted treatment in primary care for low back pain: the treatment system and clinical training programmes used in the IMPaCT Back study (ISRCTN 55174281)

PubMed Central

Sowden, Gail; Hill, Jonathan C; Konstantinou, Kika; Khanna, Meenee; Main, Chris J; Salmon, Paula; Somerville, Simon; Wathall, Simon; Foster, Nadine E

2012-01-01

Background. The IMPaCT Back study (IMplementation to improve Patient Care through Targeted treatment for Back pain) is a quality improvement study which aims to investigate the effects of introducing and supporting a subgrouping for targeted treatment system for patients with low back pain (LBP) in primary care. This paper details the subgrouping for targeted treatment system and the clinical training and mentoring programmes aimed at equipping clinicians to deliver it. The subgrouping and targeted treatment system. This system differs from ‘one-size fits all’ usual practice as it suggests that first contact health care practitioners should systematically allocate LBP patients to one of the three subgroups according to key modifiable prognostic indicators for chronicity. Patients in each subgroup (those at low, medium or high risk of chronicity) are then managed according to a targeted treatment system of increasing complexity. The subgrouping tools. Subgrouping tools help guide clinical decision-making about treatment and onward referral. Two subgrouping tools have been used in the IMPaCT Back study, a 9-item version used by participating physiotherapists and a 6-item version used by GPs. The targeted treatments. The targeted treatments include a minimal intervention delivered by GPs (for those patients at low risk of poor outcome) or referral to primary care physiotherapists who can apply physiotherapy approaches to addressing pain and disability (for those at medium risk) and additional cognitive-behavioural approaches to help address psychological and social obstacles to recovery (for those at high risk). The training packages. Building on previous interventions for other pilot studies and randomized trials, we have developed and delivered clinical training and support programmes for GPs and physiotherapists. Discussion. This paper describes in detail the IMPaCT Back study’s subgrouping for targeted treatment system and the training and mentoring packages aimed at equipping clinicians to deliver it, within the IMPaCT Back study. Study registration. ISRCTN55174281. PMID:21708984

Stateless and stateful implementations of faithful execution

DOEpatents

Pierson, Lyndon G; Witzke, Edward L; Tarman, Thomas D; Robertson, Perry J; Eldridge, John M; Campbell, Philip L

2014-12-16

A faithful execution system includes system memory, a target processor, and protection engine. The system memory stores a ciphertext including value fields and integrity fields. The value fields each include an encrypted executable instruction and the integrity fields each include an encrypted integrity value for determining whether a corresponding one of the value fields has been modified. The target processor executes plaintext instructions decoded from the ciphertext while the protection engine is coupled between the system memory and the target processor. The protection engine includes logic to retrieve the ciphertext from the system memory, decrypt the value fields into the plaintext instructions, perform an integrity check based on the integrity fields to determine whether any of the corresponding value fields have been modified, and provide the plaintext instructions to the target processor for execution.

TU-A-201-02: Treatment Site-Specific Considerations for Clinical IGRT

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

Wijesooriya, K.

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

TU-A-201-00: Image Guidance Technologies and Management Strategies

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

NONE

2016-06-15

Recent years have seen a widespread proliferation of available in-room image guidance systems for radiation therapy target localization with many centers having multiple in-room options. In this session, available imaging systems for in-room IGRT will be reviewed highlighting the main differences in workflow efficiency, targeting accuracy and image quality as it relates to target visualization. Decision-making strategies for integrating these tools into clinical image guidance protocols that are tailored to specific disease sites like H&N, lung, pelvis, and spine SBRT will be discussed. Learning Objectives: Major system characteristics of a wide range of available in-room imaging systems for IGRT. Advantagesmore » / disadvantages of different systems for site-specific IGRT considerations. Concepts of targeting accuracy and time efficiency in designing clinical imaging protocols.« less

Swept Frequency Laser Metrology System

NASA Technical Reports Server (NTRS)

Zhao, Feng (Inventor)

2010-01-01

A swept frequency laser ranging system having sub-micron accuracy that employs multiple common-path heterodyne interferometers, one coupled to a calibrated delay-line for use as an absolute reference for the ranging system. An exemplary embodiment uses two laser heterodyne interferometers to create two laser beams at two different frequencies to measure distance and motions of target(s). Heterodyne fringes generated from reflections off a reference fiducial X(sub R) and measurement (or target) fiducial X(sub M) are reflected back and are then detected by photodiodes. The measured phase changes Delta phi(sub R) and Delta phi (sub m) resulting from the laser frequency swept gives target position. The reference delay-line is the only absolute reference needed in the metrology system and this provides an ultra-stable reference and simple/economical system.

TIL system with nonlinear phase conjugation

NASA Astrophysics Data System (ADS)

Khizhnyak, Anatoliy; Markov, Vladimir

2007-09-01

Efficient laser beam delivery on a distant target remains a key problem for practical implementation of tactical laser systems. Since the conventional target-in-the-loop (TIL) concept is generally not effective in such operational environments, new solutions are needed. In this report we discuss an innovative approach for effective compensation of laser beam aberrations in TIL systems. It is based on a recently devised technique that combines optical phase conjugation (OPC) with a TIL system for effective hot-spot formation. The proposed method should enable delivery of enhanced density laser energy to a target within a finite number of iteration cycles. Using the model based on an analogy between the TIL system and laser resonator, pointing of the laser beam on the target is performed at the image plane, resulting in reduced hot-spot formation time.

An innovative pre-targeting strategy for tumor cell specific imaging and therapy

NASA Astrophysics Data System (ADS)

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-08-01

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments. Electronic supplementary information (ESI) available: Experimental details, peptide structures, molecular weights, and additional data. See DOI: 10.1039/c5nr03862f

Clinical evaluation of a mobile digital specimen radiography system for intraoperative specimen verification.

PubMed

Wang, Yingbing; Ebuoma, Lilian; Saksena, Mansi; Liu, Bob; Specht, Michelle; Rafferty, Elizabeth

2014-08-01

Use of mobile digital specimen radiography systems expedites intraoperative verification of excised breast specimens. The purpose of this study was to evaluate the performance of a such a system for verifying targets. A retrospective review included 100 consecutive pairs of breast specimen radiographs. Specimens were imaged in the operating room with a mobile digital specimen radiography system and then with a conventional digital mammography system in the radiology department. Two expert reviewers independently scored each image for image quality on a 3-point scale and confidence in target visualization on a 5-point scale. A target was considered confidently verified only if both reviewers declared the target to be confidently detected. The 100 specimens contained a total of 174 targets, including 85 clips (49%), 53 calcifications (30%), 35 masses (20%), and one architectural distortion (1%). Although a significantly higher percentage of mobile digital specimen radiographs were considered poor quality by at least one reviewer (25%) compared with conventional digital mammograms (1%), 169 targets (97%), were confidently verified with mobile specimen radiography; 172 targets (98%) were verified with conventional digital mammography. Three faint masses were not confidently verified with mobile specimen radiography, and conventional digital mammography was needed for confirmation. One faint mass and one architectural distortion were not confidently verified with either method. Mobile digital specimen radiography allows high diagnostic confidence for verification of target excision in breast specimens across target types, despite lower image quality. Substituting this modality for conventional digital mammography can eliminate delays associated with specimen transport, potentially decreasing surgical duration and increasing operating room throughput.

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting.

PubMed

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D

2017-04-07

Bacterial CRISPR-Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR-Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR-Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification.

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting

PubMed Central

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D.

2017-01-01

Bacterial CRISPR–Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR–Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR–Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification. PMID:28387220

Forming Uniform Deuterium-Ice Layers in Cryogenic Targets: Experiences Using the OMEGA Cryogenic Target Handling System

NASA Astrophysics Data System (ADS)

Harding, D. R.; Wittman, M. D.; Elasky, L.; Iwan, L. S.; Lund, L.

2001-10-01

The OMEGA Cryogenic Target Handling System (OCTHS) allows variable-thickness ice layers (nominal 100-μm) to be formed inside OMEGA-size (1-mm-diam., 3-μm-wall) plastic shells. The OCTHS design provides the most straightforward thermal environment for layering targets: permeation filled spherical targets are in a spherical isothermal environment. The layered target can be rotated 360^o to acquire multiple views of the ice layer. However, the capability of providing cryogenic targets for implosion experiments imposes constraints that do not exist in test systems dedicated to ice-layering studies. Most affected is the ability to characterize the target: space constraints and the need for multiple sets of windows limit the viewing access to f/5 optics, which affects the image quality. With these features, the OCTS provides the most relevant test system, to date, for layering targets and quantifying the overall ice roughness. No single layering protocol provides repeatable ice smoothness. All techniques require extensive operator interaction, and the layering process is lengthy. Typical ice rms smoothness varied from 5 to 10 μm for all targets studied. Characterizing the ice layer from different views shows a ~30% variation in the ice rms smoothness and a greater difference in the power spectra, depending on the view axis. This work was supported by the U.S. DOE Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460.

New production systems at ISOLDE

NASA Astrophysics Data System (ADS)

Hagebø, E.; Hoff, P.; Jonsson, O. C.; Kugler, E.; Omtvedt, J. P.; Ravn, H. L.; Steffensen, K.

1992-08-01

New target systems for the ISOLDE on-line mass separator facility are presented. Targets of carbides, metal/graphite mixtures, foils of refractory metals, molten metals and oxides have been tested. Beams of high intensity of neutron-rich isotopes of a large number of elements are obtained from a uranium carbide target with a hot plasma-discharge ion source. A target of ZrO 2 has been shown to provide high intensity beams of neutron-deficient isotopes of Mn, Cu, Zn, Ga, Ge, As, Se, Br, Kr and Rb, while a SiC target with a hot plasma ion source gives intense beams of radioactive isotopes of a number of light elements. All these systems are rather chemically unselective. Chemically selective performance has been obtained for several systems, i.e.: the production of neutron-deficient Au from ( 3He, pχn) reactions on a Pt/graphite target with a hot plasma ion source; the production of neutron-deficient Lu and LuF + and Hf and HfF 3+ from a Ta-foil target with a hot plasma ion source under CF 4 addition; the production of neutron-deficient Sr as SrF + and Y as YF 2+ form a Nb-foil target with a W surface ionizer under CF 4 addition; the production of neutron-deficient Se as COSe + from a ZrO 2 target with a hot plasma ion source under O 2 addition; and the production of radioactive F from a SiC target with a hot plasma ion source operating in Al vapour.

Delivery of drugs to intracellular organelles using drug delivery systems: Analysis of research trends and targeting efficiencies.

PubMed

Maity, Amit Ranjan; Stepensky, David

2015-12-30

Targeting of drug delivery systems (DDSs) to specific intracellular organelles (i.e., subcellular targeting) has been investigated in numerous publications, but targeting efficiency of these systems is seldom reported. We searched scientific publications in the subcellular DDS targeting field and analyzed targeting efficiency and major formulation parameters that affect it. We identified 77 scientific publications that matched the search criteria. In the majority of these studies nanoparticle-based DDSs were applied, while liposomes, quantum dots and conjugates were used less frequently. The nucleus was the most common intracellular target, followed by mitochondrion, endoplasmic reticulum and Golgi apparatus. In 65% of the publications, DDSs surface was decorated with specific targeting residues, but the efficiency of this surface decoration was not analyzed in predominant majority of the studies. Moreover, only 23% of the analyzed publications contained quantitative data on DDSs subcellular targeting efficiency, while the majority of publications reported qualitative results only. From the analysis of publications in the subcellular targeting field, it appears that insufficient efforts are devoted to quantitative analysis of the major formulation parameters and of the DDSs' intracellular fate. Based on these findings, we provide recommendations for future studies in the field of organelle-specific drug delivery and targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

Study on portable optical 3D coordinate measuring system

NASA Astrophysics Data System (ADS)

Ren, Tongqun; Zhu, Jigui; Guo, Yinbiao

2009-05-01

A portable optical 3D coordinate measuring system based on digital Close Range Photogrammetry (CRP) technology and binocular stereo vision theory is researched. Three ultra-red LED with high stability is set on a hand-hold target to provide measuring feature and establish target coordinate system. Ray intersection based field directional calibrating is done for the intersectant binocular measurement system composed of two cameras by a reference ruler. The hand-hold target controlled by Bluetooth wireless communication is free moved to implement contact measurement. The position of ceramic contact ball is pre-calibrated accurately. The coordinates of target feature points are obtained by binocular stereo vision model from the stereo images pair taken by cameras. Combining radius compensation for contact ball and residual error correction, object point can be resolved by transfer of axes using target coordinate system as intermediary. This system is suitable for on-field large-scale measurement because of its excellent portability, high precision, wide measuring volume, great adaptability and satisfying automatization. It is tested that the measuring precision is near to +/-0.1mm/m.

Method for controlling a vehicle with two or more independently steered wheels

DOEpatents

Reister, David B.; Unseren, Michael A.

1995-01-01

A method (10) for independently controlling each steerable drive wheel (W.sub.i) of a vehicle with two or more such wheels (W.sub.i). An instantaneous center of rotation target (ICR) and a tangential velocity target (v.sup.G) are inputs to a wheel target system (30) which sends the velocity target (v.sub.i.sup.G) and a steering angle target (.theta..sub.i.sup.G) for each drive wheel (W.sub.i) to a pseudovelocity target system (32). The pseudovelocity target system (32) determines a pseudovelocity target (v.sub.P.sup.G) which is compared to a current pseudovelocity (v.sub.P.sup.m) to determine a pseudovelocity error (.epsilon.). The steering angle targets (.theta..sup.G) and the steering angles (.theta..sup.m) are inputs to a steering angle control system (34) which outputs to the steering angle encoders (36), which measure the steering angles (.theta..sup.m). The pseudovelocity error (.epsilon.), the rate of change of the pseudovelocity error ( ), and the wheel slip between each pair of drive wheels (W.sub.i) are used to calculate intermediate control variables which, along with the steering angle targets (.theta..sup.G) are used to calculate the torque to be applied at each wheel (W.sub.i). The current distance traveled for each wheel (W.sub.i) is then calculated. The current wheel velocities (v.sup.m) and steering angle targets (.theta..sup.G) are used to calculate the cumulative and instantaneous wheel slip (e, ) and the current pseudovelocity (v.sub.P.sup.m).

Role of quality of service metrics in visual target acquisition and tracking in resource constrained environments

NASA Astrophysics Data System (ADS)

Anderson, Monica; David, Phillip

2007-04-01

Implementation of an intelligent, automated target acquisition and tracking systems alleviates the need for operators to monitor video continuously. This system could identify situations that fatigued operators could easily miss. If an automated acquisition and tracking system plans motions to maximize a coverage metric, how does the performance of that system change when the user intervenes and manually moves the camera? How can the operator give input to the system about what is important and understand how that relates to the overall task balance between surveillance and coverage? In this paper, we address these issues by introducing a new formulation of the average linear uncovered length (ALUL) metric, specially designed for use in surveilling urban environments. This metric coordinates the often competing goals of acquiring new targets and tracking existing targets. In addition, it provides current system performance feedback to system users in terms of the system's theoretical maximum and minimum performance. We show the successful integration of the algorithm via simulation.

Warden’s Five-Ring System Theory: Legitimate Wartime Military Targeting or an Increased Potential to Violate the Law and Norms of Expected Behavior?

DTIC Science & Technology

2000-04-01

the five-ring system theory that dramatically improves the warfighters ability to systematically identify wartime targets. However, for all of its...acclaim, little has been written about Warden’s five-ring system theory . Even less has been written about the legal and moral implications of using Warden’s theory to identify wartime targets.

Airborne Laser Systems Testing and Analysis (essals et analyse des systemes laser embarques)

DTIC Science & Technology

2010-04-01

of Surface/ Paints Reflection Properties (PILASTER targets); • PILASTER Sensors Testing and Calibration; • LOAS Laser System Testing; and • Test...PILASTER targets candidate paints and materials), a Laser Scatter-meter (LSM) was built. To briefly summarise the fundamental concepts involved...Green Painted Target. 7.6.3 Laser Beam Misalignment with Respect to the Beam-Expander Support For measuring the beam misalignment, the beam expander

Image change detection systems, methods, and articles of manufacture

DOEpatents

Jones, James L.; Lassahn, Gordon D.; Lancaster, Gregory D.

2010-01-05

Aspects of the invention relate to image change detection systems, methods, and articles of manufacture. According to one aspect, a method of identifying differences between a plurality of images is described. The method includes loading a source image and a target image into memory of a computer, constructing source and target edge images from the source and target images to enable processing of multiband images, displaying the source and target images on a display device of the computer, aligning the source and target edge images, switching displaying of the source image and the target image on the display device, to enable identification of differences between the source image and the target image.

Enhanced blood-brain barrier transport of vinpocetine by oral delivery of mixed micelles in combination with a message guider.

PubMed

Ding, Jiaojiao; Sun, Yujiao; Li, Jinfeng; Wang, Huimin; Mao, Shirui

2017-07-01

The blood-brain barrier represents an insurmountable obstacle for the therapy of central nervous system related diseases. Polymeric micelles have many desirable properties for brain targeting by oral delivery, but the stability and targeting efficiency needs to be improved. In this study, it was demonstrated that binary micelle system can compensate the drawbacks of mono system by preparing mixed micelles in combination with PEG-based copolymers. Here, we explored a brain targeting drug delivery system via facile approaches using P123 based mixed micelles in combination with a message guider from traditional Chinese medicine, borneol, for oral delivery. With higher drug-loading, improved stability, prolonged in vitro release profile, increased bioavailability and enhanced brain targeting effect was achieved after peroral delivery of the mixed micelles. More importantly, without extra structure modification for active targeting, it was demonstrated for the first time that oral delivery of vinpocetine loaded mixed micelles together with borneol is an effective way to increase drug concentration in the brain and the targeting efficiency is borneol dose dependent. Such a "simple but effective" modality may shed light on the potential use of polymeric micelles in combination with a message drug to achieve drug brain targeting or other targeting sites via oral delivery.

Application of the marine Ex-Bz transient system for delineating near shore resistive targets

NASA Astrophysics Data System (ADS)

Levi, Eldad; Goldman, Mark

2017-09-01

Under certain conditions, multidimensional coastal effect significantly enhances relative target response of the broadside transient marine Ex-Bz system. The effect is caused by a redistribution of the induced currents between the resistive target and the sea bottom compared to that existing in a 1-D geometry. As a result, the effect strongly depends on specific geoelectric conditions in the near-shore environment. The first study of the effect in the Mediterranean coast of central Israel was addressing shallow groundwater problem under specific geoelectric, hydrogeological and geomorphological conditions. Under different conditions (e.g. deep targets and sharp near-shore bathymetry), the influence of the effect on target response might be significantly different. More general analysis carried out in this study comprises various geoelectric scenarios that include both shallow and deep resistive targets at different distances from the shore line as well as various geometries of the target and the near-shore bathymetry. The study includes three major exploration aspects of the system, namely signal detectability, lateral and vertical resolution. Taking into account poor lateral resolution of the classical frequency domain CSEM and the limited application in shallow sea, the described broadside transient Ex-Bz system might represent a desired alternative for delineating shallow and deep resistive targets in transition zone.

Dolphin hearing during echolocation: evoked potential responses in an Atlantic bottlenose dolphin (Tursiops truncatus).

PubMed

Li, Songhai; Nachtigall, Paul E; Breese, Marlee

2011-06-15

Auditory evoked potential (AEP) responses were recorded during echolocation in an Atlantic bottlenose dolphin (Tursiops truncatus) trained to accept suction-cup EEG electrodes and detect targets by echolocation. AEP recording was triggered by the echolocation clicks of the animal. Three targets with target strengths of -34, -28 and -22 dB were used at a target distance of 2 to 6.5 m for each target. The results demonstrated that the AEP appeared to both outgoing echolocation clicks and echoes during echolocation, with AEP complexes consisting of alternative positive and negative waves. The echo-related AEP amplitudes were obviously lower than the outgoing click-related AEP amplitudes for all the targets at the investigated target distances. However, for targets with target strengths of -22 and -28 dB, the peak-to-peak amplitudes of the echo-related AEPs were dependent on the target distances. The echo-related AEP response amplitudes increased at further target distances, demonstrating an overcompensation of echo attenuation with target distance in the echo-perception system of the dolphin biosonar. Measurement and analysis of outgoing click intensities showed that the click levels increased with target distance (R) by a factor of approximately 10 to 17.5 logR depending on target strength. The results demonstrated that a dual-component biosonar control system formed by intensity compensation behavior in both the transmission and receiving phases of a biosonar cycle exists synchronously in the dolphin biosonar system.

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.

Deciphering the pharmacological mechanism of the Chinese formula Huanglian-Jie-Du decoction in the treatment of ischemic stroke using a systems biology-based strategy

PubMed Central

Zhang, Yan-qiong; Wang, Song-song; Zhu, Wei-liang; Ma, Yan; Zhang, Fang-bo; Liang, Ri-xin; Xu, Hai-yu; Yang, Hong-jun

2015-01-01

Aim: Huanglian-Jie-Du decoction (HLJDD) is an important multiherb remedy in TCM, which is recently demonstrated to be effective to treat ischemic stroke. Here, we aimed to investigate the pharmacological mechanisms of HLJDD in the treatment of ischemic stroke using systems biology approaches. Methods: Putative targets of HLJDD were predicted using MetaDrug. An interaction network of putative HLJDD targets and known therapeutic targets for the treatment of ischemic stroke was then constructed, and candidate HLJDD targets were identified by calculating topological features, including 'Degree', 'Node-betweenness', 'Closeness', and 'K-coreness'. The binding efficiencies of the candidate HLJDD targets with the corresponding compositive compounds were further validated by a molecular docking simulation. Results: A total of 809 putative targets were obtained for 168 compositive compounds in HLJDD. Additionally, 39 putative targets were common to all four herbs of HLJDD. Next, 49 major nodes were identified as candidate HLJDD targets due to their network topological importance. The enrichment analysis based on the Gene Ontology (GO) annotation system and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway demonstrated that candidate HLJDD targets were more frequently involved in G-protein-coupled receptor signaling pathways, neuroactive ligand-receptor interactions and gap junctions, which all played important roles in the progression of ischemic stroke. Finally, the molecular docking simulation showed that 170 pairs of chemical components and candidate HLJDD targets had strong binding efficiencies. Conclusion: This study has developed for the first time a comprehensive systems approach integrating drug target prediction, network analysis and molecular docking simulation to reveal the relationships between the herbs contained in HLJDD and their putative targets and ischemic stroke-related pathways. PMID:25937634

Stereo Electro-optical Tracking System (SETS)

NASA Astrophysics Data System (ADS)

Koenig, E. W.

1984-09-01

The SETS is a remote, non-contacting, high-accuracy tracking system for the measurement of deflection of models in the National Transonic Facility at Langley Research Center. The system consists of four electronically scanned image dissector trackers which locate the position of Light Emitting Diodes embedded in the wing or body of aircraft models. Target location data is recorded on magnetic tape for later 3-D processing. Up to 63 targets per model may be tracked at typical rates of 1280 targets per second and to precision of 0.02mm at the target under the cold (-193 C) environment of the NTF tunnel.

An analytical approach of thermodynamic behavior in a gas target system on a medical cyclotron.

PubMed

Jahangiri, Pouyan; Zacchia, Nicholas A; Buckley, Ken; Bénard, François; Schaffer, Paul; Martinez, D Mark; Hoehr, Cornelia

2016-01-01

An analytical model has been developed to study the thermo-mechanical behavior of gas targets used to produce medical isotopes, assuming that the system reaches steady-state. It is based on an integral analysis of the mass and energy balance of the gas-target system, the ideal gas law, and the deformation of the foil. The heat transfer coefficients for different target bodies and gases have been calculated. Excellent agreement is observed between experiments performed at TRIUMF's 13 MeV cyclotron and the model. Copyright © 2015 Elsevier Ltd. All rights reserved.

Board of Regents of the Nevada System of Higher Education, on behalf of the University of Nevada, Reno

DOEpatents

Adams, Jesse D.; Sulchek, Todd A.; Feigin, Stuart C.

2017-07-11

A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

PubMed

Hur, Eun-Mi; Lee, Byoung Dae

2014-12-01

Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

Cetuximab-conjugated nanodiamonds drug delivery system for enhanced targeting therapy and 3D Raman imaging.

PubMed

Li, Dandan; Chen, Xin; Wang, Hong; Liu, Jie; Zheng, Meiling; Fu, Yang; Yu, Yuan; Zhi, Jinfang

2017-12-01

In this study, a multicomponent nanodiamonds (NDs)-based targeting drug delivery system, cetuximab-NDs-cisplatin bioconjugate, combining both specific targeting and enhanced therapeutic efficacy capabilities, is developed and characterized. The specific targeting ability of cetuximab-NDs-cisplatin system on human liver hepatocellular carcinoma (HepG2) cells is evaluated through epidermal growth factor receptor (EGFR) blocking experiments, since EGFR is over-expressed on HepG2 cell membrane. Besides, cytotoxic evaluation confirms that cetuximab-NDs-cisplatin system could significantly inhibit the growth of HepG2 cells, and the therapeutic activity of this system is proven to be better than that of both nonspecific NDs-cisplatin conjugate and specific EGF-NDs-cisplatin conjugate. Furthermore, a 3-dimensional (3D) Raman imaging technique is utilized to visualize the targeting efficacy and enhanced internalization of cetuximab-NDs-cisplatin system in HepG2 cells, using the NDs existing in the bioconjugate as Raman probes, based on the characteristic Raman signal of NDs at 1332 cm -1 . These advantageous properties of cetuximab-NDs-cisplatin system propose a prospective imaging and treatment tool for further diagnostic and therapeutic purposes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Systemic p53 gene therapy of cancer with immunolipoplexes targeted by anti-transferrin receptor scFv.

PubMed Central

Xu, L.; Tang, W. H.; Huang, C. C.; Alexander, W.; Xiang, L. M.; Pirollo, K. F.; Rait, A.; Chang, E. H.

2001-01-01

BACKGROUND: A long-standing goal in genetic therapy for cancer is a systemic gene delivery system that selectively targets tumor cells, including metastases. Here we describe a novel cationic immunolipoplex system that shows high in vivo gene transfer efficiency and anti- tumor efficacy when used for systemic p53 gene therapy of cancer. MATERIALS AND METHODS: A cationic immunolipoplex incorporating a biosynthetically lipid-tagged, anti-transferrin receptor single-chain antibody (TfRscFv), was designed to target tumor cells both in vitro and in vivo. A human breast cancer metastasis model was employed to evaluate the in vivo efficacy of systemically administered, TfRscFv-immunolipoplex-mediated, p53 gene therapy in combination with docetaxel. RESULTS: The TfRscFv-targeting cationic immunolipoplex had a size of 60-100 nm, showed enhanced tumor cell binding, and improved targeted gene delivery and transfection efficiencies, both in vitro and in vivo. The p53 tumor suppressor gene was not only systemically delivered by the immunolipoplex to human tumor xenografts in nude mice but also functionally expressed. In the nude mouse breast cancer metastasis model, the combination of the p53 gene delivered by the systemic administration of the TfRscFv-immunolipoplex and docetaxel resulted in significantly improved efficacy with prolonged survival. CONCLUSIONS: This is the first report using scFv-targeting immunolipoplexes for systemic gene therapy. The TfRscFv has a number of advantages over the transferrin (Tf) molecule itself: (1) scFv has a much smaller size than Tf producing a smaller immunolipoplex giving better penetration into solid tumors; (2) unlike Tf, the scFv is a recombinant protein, not a blood product; (3) large scale production and strict quality control of the recombinant scFv, as well as scFv-immunolipoplex, are feasible. The sensitization of tumors to chemotherapy by this tumor-targeted and efficient p53 gene delivery method could lower the effective dose of the drug, correspondingly lessening the severe side effects, while decreasing the possibility of recurrence. Moreover, this approach is applicable to both primary and recurrent tumors, and more significantly, metastatic disease. The TfRscFv-targeting of cationic immunolipoplexes is a promising method of tumor targeted gene delivery that can be used for systemic gene therapy of cancer with the potential to critically impact the clinical management of cancer. PMID:11713371

Fe3O4 Nanoparticles in Targeted Drug/Gene Delivery Systems

PubMed Central

Shen, Lazhen; Li, Bei; Qiao, Yongsheng

2018-01-01

Fe3O4 nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe3O4 NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe3O4 NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe3O4 NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe3O4 NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe3O4 NPs targeting drug/gene delivery systems. PMID:29473914

Focused ultrasound: concept for automated transcutaneous control of hemorrhage in austere settings.

PubMed

Kucewicz, John C; Bailey, Michael R; Kaczkowski, Peter J; Carter, Stephen J

2009-04-01

High intensity focused ultrasound (HIFU) is being developed for a range of clinical applications. Of particular interest to NASA and the military is the use of HIFU for traumatic injuries because HIFU has the unique ability to transcutaneously stop bleeding. Automation of this technology would make possible its use in remote, austere settings by personnel not specialized in medical ultrasound. Here a system to automatically detect and target bleeding is tested and reported. The system uses Doppler ultrasound images from a clinical ultrasound scanner for bleeding detection and hardware for HIFU therapy. The system was tested using a moving string to simulate blood flow and targeting was visualized by Schlieren imaging to show the focusing of the HIFU acoustic waves. When instructed by the operator, a Doppler ultrasound image is acquired and processed to detect and localize the moving string, and the focus of the HIFU array is electronically adjusted to target the string. Precise and accurate targeting was verified in the Schlieren images. An automated system to detect and target simulated bleeding has been built and tested. The system could be combined with existing algorithms to detect, target, and treat clinical bleeding.

Autonomous target recognition using remotely sensed surface vibration measurements

NASA Astrophysics Data System (ADS)

Geurts, James; Ruck, Dennis W.; Rogers, Steven K.; Oxley, Mark E.; Barr, Dallas N.

1993-09-01

The remotely measured surface vibration signatures of tactical military ground vehicles are investigated for use in target classification and identification friend or foe (IFF) systems. The use of remote surface vibration sensing by a laser radar reduces the effects of partial occlusion, concealment, and camouflage experienced by automatic target recognition systems using traditional imagery in a tactical battlefield environment. Linear Predictive Coding (LPC) efficiently represents the vibration signatures and nearest neighbor classifiers exploit the LPC feature set using a variety of distortion metrics. Nearest neighbor classifiers achieve an 88 percent classification rate in an eight class problem, representing a classification performance increase of thirty percent from previous efforts. A novel confidence figure of merit is implemented to attain a 100 percent classification rate with less than 60 percent rejection. The high classification rates are achieved on a target set which would pose significant problems to traditional image-based recognition systems. The targets are presented to the sensor in a variety of aspects and engine speeds at a range of 1 kilometer. The classification rates achieved demonstrate the benefits of using remote vibration measurement in a ground IFF system. The signature modeling and classification system can also be used to identify rotary and fixed-wing targets.

Cas9-mediated targeting of viral RNA in eukaryotic cells.

PubMed

Price, Aryn A; Sampson, Timothy R; Ratner, Hannah K; Grakoui, Arash; Weiss, David S

2015-05-12

Clustered, regularly interspaced, short palindromic repeats-CRISPR associated (CRISPR-Cas) systems are prokaryotic RNA-directed endonuclease machineries that act as an adaptive immune system against foreign genetic elements. Using small CRISPR RNAs that provide specificity, Cas proteins recognize and degrade nucleic acids. Our previous work demonstrated that the Cas9 endonuclease from Francisella novicida (FnCas9) is capable of targeting endogenous bacterial RNA. Here, we show that FnCas9 can be directed by an engineered RNA-targeting guide RNA to target and inhibit a human +ssRNA virus, hepatitis C virus, within eukaryotic cells. This work reveals a versatile and portable RNA-targeting system that can effectively function in eukaryotic cells and be programmed as an antiviral defense.

Debris-free soft x-ray source with gas-puff target

NASA Astrophysics Data System (ADS)

Ni, Qiliang; Chen, Bo; Gong, Yan; Cao, Jianlin; Lin, Jingquan; Lee, Hongyan

2001-12-01

We have been developing a debris-free laser plasma light source with a gas-puff target system whose nozzle is driven by a piezoelectric crystal membrane. The gas-puff target system can utilize gases such as CO2, O2 or some gas mixture according to different experiments. Therefore, in comparison with soft X-ray source using a metal target, after continuously several-hour laser interaction with gas from the gas-puff target system, no evidences show that the light source can produce debris. The debris-free soft X-ray source is prepared for soft X-ray projection lithography research at State Key Laboratory of Applied Optics. Strong emission from CO2, O2 and Kr plasma is observed.

Cas9-mediated targeting of viral RNA in eukaryotic cells

PubMed Central

Price, Aryn A.; Sampson, Timothy R.; Ratner, Hannah K.; Grakoui, Arash; Weiss, David S.

2015-01-01

Clustered, regularly interspaced, short palindromic repeats–CRISPR associated (CRISPR-Cas) systems are prokaryotic RNA-directed endonuclease machineries that act as an adaptive immune system against foreign genetic elements. Using small CRISPR RNAs that provide specificity, Cas proteins recognize and degrade nucleic acids. Our previous work demonstrated that the Cas9 endonuclease from Francisella novicida (FnCas9) is capable of targeting endogenous bacterial RNA. Here, we show that FnCas9 can be directed by an engineered RNA-targeting guide RNA to target and inhibit a human +ssRNA virus, hepatitis C virus, within eukaryotic cells. This work reveals a versatile and portable RNA-targeting system that can effectively function in eukaryotic cells and be programmed as an antiviral defense. PMID:25918406

Nike Facility Diagnostics and Data Acquisition System

NASA Astrophysics Data System (ADS)

Chan, Yung; Aglitskiy, Yefim; Karasik, Max; Kehne, David; Obenschain, Steve; Oh, Jaechul; Serlin, Victor; Weaver, Jim

2013-10-01

The Nike laser-target facility is a 56-beam krypton fluoride system that can deliver 2 to 3 kJ of laser energy at 248 nm onto targets inside a two meter diameter vacuum chamber. Nike is used to study physics and technology issues related to laser direct-drive ICF fusion, including hydrodynamic and laser-plasma instabilities, material behavior at extreme pressures, and optical and x-ray diagnostics for laser-heated targets. A suite of laser and target diagnostics are fielded on the Nike facility, including high-speed, high-resolution x-ray and visible imaging cameras, spectrometers and photo-detectors. A centrally-controlled, distributed computerized data acquisition system provides robust data management and near real-time analysis feedback capability during target shots. Work supported by DOE/NNSA.

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.

Three-dimensional microscope tracking system using the astigmatic lens method and a profile sensor

NASA Astrophysics Data System (ADS)

Kibata, Hiroki; Ishii, Katsuhiro

2018-03-01

We developed a three-dimensional microscope tracking system using the astigmatic lens method and a profile sensor, which provides three-dimensional position detection over a wide range at the rate of 3.2 kHz. First, we confirmed the range of target detection of the developed system, where the range of target detection was shown to be ± 90 µm in the horizontal plane and ± 9 µm in the vertical plane for a 10× objective lens. Next, we attempted to track a motion-controlled target. The developed system kept the target at the center of the field of view and in focus up to a target speed of 50 µm/s for a 20× objective lens. Finally, we tracked a freely moving target. We successfully demonstrated the tracking of a 10-µm-diameter polystyrene bead suspended in water for 40 min. The target was kept in the range of approximately 4.9 µm around the center of the field of view. In addition, the vertical direction was maintained in the range of ± 0.84 µm, which was sufficiently within the depth of focus.

The Nike Laser Facility and its Capabilities

NASA Astrophysics Data System (ADS)

Serlin, V.; Aglitskiy, Y.; Chan, L. Y.; Karasik, M.; Kehne, D. M.; Oh, J.; Obenschain, S. P.; Weaver, J. L.

2013-10-01

The Nike laser is a 56-beam krypton fluoride (KrF) system that provides 3 to 4 kJ of laser energy on target. The laser uses induced spatial incoherence to achieve highly uniform focal distributions. 44 beams are overlapped onto target with peak intensities up to 1016 W/cm2. The effective time-averaged illumination nonuniformity is < 0 . 2 %. Nike produces highly uniform ablation pressures on target allowing well-controlled experiments at pressures up to 20 Mbar. The other 12 laser beams are used to generate diagnostic x-rays radiographing the primary laser-illuminated target. The facility includes a front end that generates the desired temporal and spatial laser profiles, two electron-beam pumped KrF amplifiers, a computer-controlled optical system, and a vacuum target chamber for experiments. Nike is used to study the physics and technology issues of direct-drive laser fusion, such as, hydrodynamic and laser-plasma instabilities, studies of the response of materials to extreme pressures, and generation of X rays from laser-heated targets. Nike features a computer-controlled data acquisition system, high-speed, high-resolution x-ray and visible imaging systems, x-ray and visible spectrometers, and cryogenic target capability. Work supported by DOE/NNSA.

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

Performance Evaluation Of The Antares Reference Telescope System

NASA Astrophysics Data System (ADS)

Parker, J. R.; Woodfin, G. L.; Viswanathan, V. K.

1985-11-01

The Antares Reference Telescope System is a complicated electro-optical-mechanical system whose main purpose is to enable positioning of targets used in the Antares Laser System to within 10 μm of a selected nominal position. To date, it has been used successfully to position targets ranging in size from 300 μm to 2 mm. The system consists of two electro-optical systems positioned in a nearly orthogonal manner. This "cross telescope" configuration facilitates accurate positioning in three planes. The results obtained so far in resolution and positioning of targets using this system are discussed. It is shown that a resolution of 200 1p/mm and a positioning precision of 25 μm can be obtained.

Performance evaluation of the Antares reference telescope system

NASA Astrophysics Data System (ADS)

Parker, J. R.; Woodfin, G. L.; Viswanathan, V. K.

The Antares Reference Telescope System is a complicated electro-optical-mechanical system whose main purpose is to enable positioning of targets used in the Antares Laser System to within 10 microns of a selected nominal position. To date, it has been used successfully to position targets ranging in size from 300 microns to 2 mm. The system consists of two electro-optical systems positioned in a nearly orthogonal manner. This cross telescope configuration facilitates accurate positioning in three planes. The results obtained so far in resolution and positioning of targets using this system are discussed. It is shown that a resolution of 200 lp/mm and a positioning precision of 25 microns can be obtained.

Study on a novel laser target detection system based on software radio technique

NASA Astrophysics Data System (ADS)

Song, Song; Deng, Jia-hao; Wang, Xue-tian; Gao, Zhen; Sun, Ji; Sun, Zhi-hui

2008-12-01

This paper presents that software radio technique is applied to laser target detection system with the pseudo-random code modulation. Based on the theory of software radio, the basic framework of the system, hardware platform, and the implementation of the software system are detailed. Also, the block diagram of the system, DSP circuit, block diagram of the pseudo-random code generator, and soft flow diagram of signal processing are designed. Experimental results have shown that the application of software radio technique provides a novel method to realize the modularization, miniaturization and intelligence of the laser target detection system, and the upgrade and improvement of the system will become simpler, more convenient, and cheaper.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Fincher, S.; Polsgrove, T.; Chapman, J.; Philips, A.

2002-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Structural, thermal and radiation-management design details are presented. Propellant storage and supply options are also discussed and a propulsion system mass estimate is given.

Magnetic confinement system using charged ammonia targets

DOEpatents

Porter, Gary D.; Bogdanoff, Anatoly

1979-01-01

A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

Guidance system for laser targets

DOEpatents

Porter, Gary D.; Bogdanoff, Anatoly

1978-01-01

A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

An algorithm for automatic target recognition using passive radar and an EKF for estimating aircraft orientation

NASA Astrophysics Data System (ADS)

Ehrman, Lisa M.

2005-07-01

Rather than emitting pulses, passive radar systems rely on "illuminators of opportunity," such as TV and FM radio, to illuminate potential targets. These systems are attractive since they allow receivers to operate without emitting energy, rendering them covert. Until recently, most of the research regarding passive radar has focused on detecting and tracking targets. This dissertation focuses on extending the capabilities of passive radar systems to include automatic target recognition. The target recognition algorithm described in this dissertation uses the radar cross section (RCS) of potential targets, collected over a short period of time, as the key information for target recognition. To make the simulated RCS as accurate as possible, the received signal model accounts for aircraft position and orientation, propagation losses, and antenna gain patterns. An extended Kalman filter (EKF) estimates the target's orientation (and uncertainty in the estimate) from velocity measurements obtained from the passive radar tracker. Coupling the aircraft orientation and state with the known antenna locations permits computation of the incident and observed azimuth and elevation angles. The Fast Illinois Solver Code (FISC) simulates the RCS of potential target classes as a function of these angles. Thus, the approximated incident and observed angles allow the appropriate RCS to be extracted from a database of FISC results. Using this process, the RCS of each aircraft in the target class is simulated as though each is executing the same maneuver as the target detected by the system. Two additional scaling processes are required to transform the RCS into a power profile (magnitude only) simulating the signal in the receiver. First, the RCS is scaled by the Advanced Refractive Effects Prediction System (AREPS) code to account for propagation losses that occur as functions of altitude and range. Then, the Numerical Electromagnetic Code (NEC2) computes the antenna gain pattern, further scaling the RCS. A Rician likelihood model compares the scaled RCS of the illuminated aircraft with those of the potential targets. To improve the robustness of the result, the algorithm jointly optimizes over feasible orientation profiles and target types via dynamic programming.

Performance Measurement and Target-Setting in California's Safety Net Health Systems.

PubMed

Hemmat, Shirin; Schillinger, Dean; Lyles, Courtney; Ackerman, Sara; Gourley, Gato; Vittinghoff, Eric; Handley, Margaret; Sarkar, Urmimala

Health policies encourage implementing quality measurement with performance targets. The 2010-2015 California Medicaid waiver mandated quality measurement and reporting. In 2013, California safety net hospitals participating in the waiver set a voluntary performance target (the 90th percentile for Medicare preferred provider organization plans) for mammography screening and cholesterol control in diabetes. They did not reach the target, and the difference-in-differences analysis suggested that there was no difference for mammography ( P = .39) and low-density lipoprotein control ( P = .11) performance compared to measures for which no statewide quality improvement initiative existed. California's Medicaid waiver was associated with improved performance on a number of metrics, but this performance was not attributable to target setting on specific health conditions. Performance may have improved because of secular trends or systems improvements related to waiver funding. Relying on condition-specific targets to measure performance may underestimate improvements and disadvantage certain health systems. Achieving ambitious targets likely requires sustained fiscal, management, and workforce investments.

Sequential Axon-derived Signals Couple Target Survival and Layer Specificity in the Drosophila Visual System

PubMed Central

Pecot, Matthew Y.; Chen, Yi; Akin, Orkun; Chen, Zhenqing; Tsui, C.Y. Kimberly; Zipursky, S. Lawrence

2015-01-01

SUMMARY Neural circuit formation relies on interactions between axons and cells within the target field. While it is well established that target-derived signals act on axons to regulate circuit assembly, the extent to which axon-derived signals control circuit formation is not known. In the Drosophila visual system, anterograde signals numerically match R1–R6 photoreceptors with their targets by controlling target proliferation and neuronal differentiation. Here we demonstrate that additional axon-derived signals selectively couple target survival with layer-specificity. We show that Jelly belly (Jeb) produced by R1–R6 axons interacts with its receptor, anaplastic lymphoma kinase (Alk), on budding dendrites to control survival of L3 neurons, one of three postsynaptic targets. L3 axons then produce Netrin, which regulates the layer-specific targeting of another neuron within the same circuit. We propose that a cascade of axon-derived signals, regulating diverse cellular processes, provides a strategy for coordinating circuit assembly across different regions of the nervous system. PMID:24742459

Method and infrastructure for cycle-reproducible simulation on large scale digital circuits on a coordinated set of field-programmable gate arrays (FPGAs)

DOEpatents

Asaad, Sameh W; Bellofatto, Ralph E; Brezzo, Bernard; Haymes, Charles L; Kapur, Mohit; Parker, Benjamin D; Roewer, Thomas; Tierno, Jose A

2014-01-28

A plurality of target field programmable gate arrays are interconnected in accordance with a connection topology and map portions of a target system. A control module is coupled to the plurality of target field programmable gate arrays. A balanced clock distribution network is configured to distribute a reference clock signal, and a balanced reset distribution network is coupled to the control module and configured to distribute a reset signal to the plurality of target field programmable gate arrays. The control module and the balanced reset distribution network are cooperatively configured to initiate and control a simulation of the target system with the plurality of target field programmable gate arrays. A plurality of local clock control state machines reside in the target field programmable gate arrays. The local clock state machines are configured to generate a set of synchronized free-running and stoppable clocks to maintain cycle-accurate and cycle-reproducible execution of the simulation of the target system. A method is also provided.

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

PubMed

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

2018-05-01

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

Study of a stereo electro-optical tracker system for the measurement of model deformations at the national transonic facility

NASA Technical Reports Server (NTRS)

Hertel, R. J.

1979-01-01

An electro-optical method to measure the aeroelastic deformations of wind tunnel models is examined. The multitarget tracking performance of one of the two electronic cameras comprising the stereo pair is modeled and measured. The properties of the targets at the model, the camera optics, target illumination, number of targets, acquisition time, target velocities, and tracker performance are considered. The electronic camera system is shown to be capable of locating, measuring, and following the positions of 5 to 50 targets attached to the model at measuring rates up to 5000 targets per second.

Development of Bone Targeting Drugs.

PubMed

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

2017-06-23

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

Development of Bone Targeting Drugs

PubMed Central

Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2017-01-01

The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

Mo99 Production Plant Layout

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

Woloshun, Keith Albert; Dale, Gregory E.; Naranjo, Angela Carol

The NorthStar Medical Technologies 99Mo production facility configuration is envisioned to be 8 accelerator pairs irradiating 7 100Mo targets (one spare accelerator pair undergoing maintenance while the other 7 pairs are irradiating targets). The required shielding in every direction for the accelerators is initially estimated to be 10 feet of concrete. With the accelerator pairs on one (ground) level and spaced with the required shielding between adjacent pairs, the only practical path for target insertion and removal while minimizing floor space is vertical. The current scheme then requires a target vertical lift of nominally 10 feet through a shield stack.more » It is envisioned that the lift will be directly into a hot cell where an activated target can be removed from its holder and a new target attached and lowered. The hot cell is on a rail system so that a single hot cell can service all active target locations, as well as deliver the ready targets to the separations lab. On this rail system, coupled to the hot cell, will be a helium recovery and clean-up system. All helium coolant equipment is located on the upper level near to the target removal point.« less

Conceptual studies for a mercury target circuit

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

Sigg, B.

1996-06-01

For the now favored target design of the European Spallation Source project, i.e. the version using mercury as target material, a basic concept of the primary system has been worked out. It does not include a detailed design of the various components of the target circuit, but tries to outline a feasible solution for the system. Besides the removal of the thermal power of about 3MW produced in the target by the proton beam, the primary system has to satisfy a number of other requirements related to processing, safety, and operation. The basic proposal uses an electromagnetic pump and amore » mercury-water intermediate heat excanger, but other alternatives are also being discussed. Basic safety requirements, i.e. protection against radiation and toxic mercury vapours, are satisfied by a design using an air-tight primary system containment, double-walled tubes in the intermediate heat exchanger, a fail-safe system for decay heat removal, and a remote handling facility for the active part of the system. Much engineering work has still to be done, because many details of the design of the mercury and gas processing systems remain to be clarified, the thermal-hydraulic components need further optimisation, the system for control and instrumentation is only known in outline and a through safety analysis will be required.« less

Multibeam Altimeter Navigation Update Using Faceted Shape Model

NASA Technical Reports Server (NTRS)

Bayard, David S.; Brugarolas, Paul; Broschart, Steve

2008-01-01

A method of incorporating information, acquired by a multibeam laser or radar altimeter system, pertaining to the distance and direction between the system and a nearby target body, into an estimate of the state of a vehicle upon which the system is mounted, involves the use of a faceted model to represent the shape of the target body. Fundamentally, what one seeks to measure is the distance from the vehicle to the target body.

Bolts from Orion: Destroying Mobile Surface-to-Air Missile Systems with Lethal Autonomous Aircraft

DTIC Science & Technology

2016-07-01

era SAMs that had been upgraded by Ukrainian contractors . During the operation, Russian aircraft’s 10 electronic countermeasures could not...main SEAD asset is the F-16 CJ equipped with the HARM targeting system ( HTS ). The HTS can autonomously locate and identify threat radars and pass...targeting information to the HARMs before launch. The HTS can also provide targeting 13 information to global positioning system (GPS) guided

Enhancement of tracking performance in electro-optical system based on servo control algorithm

NASA Astrophysics Data System (ADS)

Choi, WooJin; Kim, SungSu; Jung, DaeYoon; Seo, HyoungKyu

2017-10-01

Modern electro-optical surveillance and reconnaissance systems require tracking capability to get exact images of target or to accurately direct the line of sight to target which is moving or still. This leads to the tracking system composed of image based tracking algorithm and servo control algorithm. In this study, we focus on the servo control function to minimize the overshoot in the tracking motion and do not miss the target. The scheme is to limit acceleration and velocity parameters in the tracking controller, depending on the target state information in the image. We implement the proposed techniques by creating a system model of DIRCM and simulate the same environment, validate the performance on the actual equipment.

MIT modular x-ray source systems for the study of plasma diagnostics

NASA Astrophysics Data System (ADS)

Coleman, J. W.; Wenzel, K. W.; Petrasso, R. D.; Lo, D. H.; Li, C. K.; Lierzer, J. R.; Wei, T.

1992-10-01

Two new x-ray source systems are now on line at our facility. Each provides an e-beam to 25 kV. Targets are interchangeable between machines, and four x-ray detectors may be used simultaneously with a target. The gridded e-gun of the RACEHORSE system gives a 0.5-1.0-cm pulsable spot on target. The nongridded e-gun of the SCORPION system provides a 0.3-mm or smaller dc microspot on target. RACEHORSE is being used to study and characterize type-II diamond photoconductors for use in diagnosing plasmas, while SCORPION is being used to develop a slitless spectrograph using photographic film. Source design details and some RACEHORSE results are presented.

Analysis of Photogrammetry Data from ISIM Mockup, June 1, 2007

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.

Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma

PubMed Central

Li, Min; Zhang, Weiyue; Wang, Birong; Gao, Yang; Song, Zifang; Zheng, Qi Chang

2016-01-01

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC. PMID:27920520

Test target for characterizing 3D resolution of optical coherence tomography

NASA Astrophysics Data System (ADS)

Hu, Zhixiong; Hao, Bingtao; Liu, Wenli; Hong, Baoyu; Li, Jiao

2014-12-01

Optical coherence tomography (OCT) is a non-invasive 3D imaging technology which has been applied or investigated in many diagnostic fields including ophthalmology, dermatology, dentistry, cardiovasology, endoscopy, brain imaging and so on. Optical resolution is an important characteristic that can describe the quality and utility of an image acquiring system. We employ 3D printing technology to design and fabricate a test target for characterizing 3D resolution of optical coherence tomography. The test target which mimics USAF 1951 test chart was produced with photopolymer. By measuring the 3D test target, axial resolution as well as lateral resolution of a spectral domain OCT system was evaluated. For comparison, conventional microscope and surface profiler were employed to characterize the 3D test targets. The results demonstrate that the 3D resolution test targets have the potential of qualitatively and quantitatively validating the performance of OCT systems.

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.

Automated multiple target detection and tracking in UAV videos

NASA Astrophysics Data System (ADS)

Mao, Hongwei; Yang, Chenhui; Abousleman, Glen P.; Si, Jennie

2010-04-01

In this paper, a novel system is presented to detect and track multiple targets in Unmanned Air Vehicles (UAV) video sequences. Since the output of the system is based on target motion, we first segment foreground moving areas from the background in each video frame using background subtraction. To stabilize the video, a multi-point-descriptor-based image registration method is performed where a projective model is employed to describe the global transformation between frames. For each detected foreground blob, an object model is used to describe its appearance and motion information. Rather than immediately classifying the detected objects as targets, we track them for a certain period of time and only those with qualified motion patterns are labeled as targets. In the subsequent tracking process, a Kalman filter is assigned to each tracked target to dynamically estimate its position in each frame. Blobs detected at a later time are used as observations to update the state of the tracked targets to which they are associated. The proposed overlap-rate-based data association method considers the splitting and merging of the observations, and therefore is able to maintain tracks more consistently. Experimental results demonstrate that the system performs well on real-world UAV video sequences. Moreover, careful consideration given to each component in the system has made the proposed system feasible for real-time applications.

An intelligent re-shieldable targeting system for enhanced tumor accumulation.

PubMed

Hu, Zhenpeng; Ma, Jinlong; Fu, Fei; Cui, Chen; Li, Xiaomin; Wang, Xinyu; Wang, Wei; Wan, Yeda; Yuan, Zhi

2017-12-28

Programmed ligand targeting strategy promotes the blood circulation stability of nanoparticles by shielding the ligand. However, the irreversible shielding causes the deshielded nanoparticles to be easily recognized and cleared by the reticuloendothelial system (RES), impeding their further retention in the tumor. Here, we for the first time prove the superiority of the intelligent re-shieldable targeting system that is based on the pH-responsive self-assembly/disassembly of gold nanoparticles. The system can enhance the stability of gold nanoparticles in the blood circulation (2.6-fold at 24h), reduce uptake by the RES (35% lower) and improve tumor accumulation (41% higher by analysis of gold content in tumor) effectively compared with the conventional irreversible system. Furthermore, preliminary study indicates that the system could be applied as computed tomography contrast agent in tumor imaging. The in vivo validity of the intelligent re-shieldable targeting system provides inspiration for the design of nanomaterials for cancer diagnosis and treatment. Copyright © 2017. Published by Elsevier B.V.

Aptamer-conjugated nanobubbles for targeted ultrasound molecular imaging.

PubMed

Wang, Chung-Hsin; Huang, Yu-Fen; Yeh, Chih-Kuang

2011-06-07

Targeted ultrasound contrast agents can be prepared by some specific bioconjugation techniques. The biotin-avidin complex is an extremely useful noncovalent binding system, but the system might induce immunogenic side effects in human bodies. Previous proposed covalently conjugated systems suffered from low conjugation efficiency and complex procedures. In this study, we propose a covalently conjugated nanobubble coupling with nucleic acid ligands, aptamers, for providing a higher specific affinity for ultrasound targeting studies. The sgc8c aptamer was linked with nanobubbles through thiol-maleimide coupling chemistry for specific targeting to CCRF-CEM cells. Further improvements to reduce the required time and avoid the degradation of nanobubbles during conjugation procedures were also made. Several investigations were used to discuss the performance and consistency of the prepared nanobubbles, such as size distribution, conjugation efficiency analysis, and flow cytometry assay. Further, we applied our conjugated nanobubbles to ex vivo ultrasound targeted imaging and compared the resulting images with optical images. The results indicated the availability of aptamer-conjugated nanobubbles in targeted ultrasound imaging and the practicability of using a highly sensitive ultrasound system in noninvasive biological research.

A real-time tracking system of infrared dim and small target based on FPGA and DSP

NASA Astrophysics Data System (ADS)

Rong, Sheng-hui; Zhou, Hui-xin; Qin, Han-lin; Wang, Bing-jian; Qian, Kun

2014-11-01

A core technology in the infrared warning system is the detection tracking of dim and small targets with complicated background. Consequently, running the detection algorithm on the hardware platform has highly practical value in the military field. In this paper, a real-time detection tracking system of infrared dim and small target which is used FPGA (Field Programmable Gate Array) and DSP (Digital Signal Processor) as the core was designed and the corresponding detection tracking algorithm and the signal flow is elaborated. At the first stage, the FPGA obtain the infrared image sequence from the sensor, then it suppresses background clutter by mathematical morphology method and enhances the target intensity by Laplacian of Gaussian operator. At the second stage, the DSP obtain both the original image and the filtered image form the FPGA via the video port. Then it segments the target from the filtered image by an adaptive threshold segmentation method and gets rid of false target by pipeline filter. Experimental results show that our system can achieve higher detection rate and lower false alarm rate.

Targeted nitric oxide delivery by supramolecular nanofibers for the prevention of restenosis after arterial injury

DOE PAGES

Bahnson, Edward S. M.; Kassam, Hussein A.; Moyer, Tyson J.; ...

2016-01-21

Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. Here we sought to develop and evaluate a systemically delivered nanostructure targeted to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues. As a result, structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescentmore » detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl [SNO])-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation. This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects. In conclusion, we successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases« less

High affinity ligands from in vitro selection: Complex targets

PubMed Central

Morris, Kevin N.; Jensen, Kirk B.; Julin, Carol M.; Weil, Michael; Gold, Larry

1998-01-01

Human red blood cell membranes were used as a model system to determine if the systematic evolution of ligands by exponential enrichment (SELEX) methodology, an in vitro protocol for isolating high-affinity oligonucleotides that bind specifically to virtually any single protein, could be used with a complex mixture of potential targets. Ligands to multiple targets were generated simultaneously during the selection process, and the binding affinities of these ligands for their targets are comparable to those found in similar experiments against pure targets. A secondary selection scheme, deconvolution-SELEX, facilitates rapid isolation of the ligands to targets of special interest within the mixture. SELEX provides high-affinity compounds for multiple targets in a mixture and might allow a means for dissecting complex biological systems. PMID:9501188

48 CFR 16.403-1 - Fixed-price incentive (firm target) contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... (firm target) contracts. 16.403-1 Section 16.403-1 Federal Acquisition Regulations System FEDERAL... Fixed-price incentive (firm target) contracts. (a) Description. A fixed-price incentive (firm target) contract specifies a target cost, a target profit, a price ceiling (but not a profit ceiling or floor), and...

48 CFR 16.403-1 - Fixed-price incentive (firm target) contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

... (firm target) contracts. 16.403-1 Section 16.403-1 Federal Acquisition Regulations System FEDERAL... Fixed-price incentive (firm target) contracts. (a) Description. A fixed-price incentive (firm target) contract specifies a target cost, a target profit, a price ceiling (but not a profit ceiling or floor), and...

Non-viral and viral delivery systems for CRISPR-Cas9 technology in the biomedical field.

PubMed

He, Zhi-Yao; Men, Ke; Qin, Zhou; Yang, Yang; Xu, Ting; Wei, Yu-Quan

2017-05-01

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR-Cas9) system provides a novel genome editing technology that can precisely target a genomic site to disrupt or repair a specific gene. Some CRISPR-Cas9 systems from different bacteria or artificial variants have been discovered or constructed by biologists, and Cas9 nucleases and single guide RNAs (sgRNA) are the major components of the CRISPR-Cas9 system. These Cas9 systems have been extensively applied for identifying therapeutic targets, identifying gene functions, generating animal models, and developing gene therapies. Moreover, CRISPR-Cas9 systems have been used to partially or completely alleviate disease symptoms by mutating or correcting related genes. However, the efficient transfer of CRISPR-Cas9 system into cells and target organs remains a challenge that affects the robust and precise genome editing activity. The current review focuses on delivery systems for Cas9 mRNA, Cas9 protein, or vectors encoding the Cas9 gene and corresponding sgRNA. Non-viral delivery of Cas9 appears to help Cas9 maintain its on-target effect and reduce off-target effects, and viral vectors for sgRNA and donor template can improve the efficacy of genome editing and homology-directed repair. Safe, efficient, and producible delivery systems will promote the application of CRISPR-Cas9 technology in human gene therapy.

Tether deployment monitoring system, phase 2

NASA Technical Reports Server (NTRS)

1989-01-01

An operational Tether Deployment Monitoring System (TEDEMS) was constructed that would show system functionality in a terrestrial environment. The principle function of the TEDEMS system is the launching and attachment of reflective targets onto the tether during its deployment. These targets would be tracked with a radar antenna that was pointed towards the targets by a positioning system. A spring powered launcher for the targets was designed and fabricated. An instrumentation platform and launcher were also developed. These modules are relatively heavy and will influence tether deployment scenarios, unless they are released with a velocity and trajectory closely matching that of the tether. Owing to the tracking range limitations encountered during field trails of the Radar system, final TEDEMS system integration was not completed. The major module not finished was the system control computer. The lack of this device prevented any subsystem testing or field trials to be conducted. Other items only partially complete were the instrumentation platform launcher and modules and the radar target launcher. The work completed and the tests performed suggest that the proposed system continues to be a feasible approach to tether monitoring, although additional effort is still necessary to increase the range at which modules can be detected. The equipment completed and tested, to the extent stated, is available to NASA for use on any future program that requires tether tracking capability.

Cryogenic target system for hydrogen layering

DOE PAGES

Parham, T.; Kozioziemski, B.; Atkinson, D.; ...

2015-11-24

Here, a cryogenic target positioning system was designed and installed on the National Ignition Facility (NIF) target chamber. This instrument incorporates the ability to fill, form, and characterize the NIF targets with hydrogen isotopes needed for ignition experiments inside the NIF target bay then transport and position them in the target chamber. This effort brought to fruition years of research in growing and metrologizing high-quality hydrogen fuel layers and landed it in an especially demanding operations environment in the NIF facility. D-T (deuterium-tritium) layers for NIF ignition experiments have extremely tight specifications and must be grown in a very highlymore » constrained environment: a NIF ignition target inside a cryogenic target positioner inside the NIF target bay. Exquisite control of temperature, pressure, contaminant level, and thermal uniformity are necessary throughout seed formation and layer growth to create an essentially-groove-free single crystal layer.« less

A new airborne laser rangefinder dynamic target simulator for non-stationary environment

NASA Astrophysics Data System (ADS)

Ma, Pengge; Pang, Dongdong; Yi, Yang

2017-11-01

For the non-stationary environment simulation in laser range finder product testing, a new dynamic target simulation system is studied. First of all, the three-pulsed laser ranging principle, laser target signal composition and mathematical representation are introduced. Then, the actual nonstationary working environment of laser range finder is analyzed, and points out that the real sunshine background light clutter and target shielding effect in laser echo become the main influencing factors. After that, the dynamic laser target signal simulation method is given. Eventlly, the implementation of automatic test system based on arbitrary waveform generator is described. Practical application shows that the new echo signal automatic test system can simulate the real laser ranging environment of laser range finder, and is suitable for performance test of products.

Consensus pursuit of heterogeneous multi-agent systems under a directed acyclic graph

NASA Astrophysics Data System (ADS)

Yan, Jing; Guan, Xin-Ping; Luo, Xiao-Yuan

2011-04-01

This paper is concerned with the cooperative target pursuit problem by multiple agents based on directed acyclic graph. The target appears at a random location and moves only when sensed by the agents, and agents will pursue the target once they detect its existence. Since the ability of each agent may be different, we consider the heterogeneous multi-agent systems. According to the topology of the multi-agent systems, a novel consensus-based control law is proposed, where the target and agents are modeled as a leader and followers, respectively. Based on Mason's rule and signal flow graph analysis, the convergence conditions are provided to show that the agents can catch the target in a finite time. Finally, simulation studies are provided to verify the effectiveness of the proposed approach.

A real-time optical tracking and measurement processing system for flying targets.

PubMed

Guo, Pengyu; Ding, Shaowen; Zhang, Hongliang; Zhang, Xiaohu

2014-01-01

Optical tracking and measurement for flying targets is unlike the close range photography under a controllable observation environment, which brings extreme conditions like diverse target changes as a result of high maneuver ability and long cruising range. This paper first designed and realized a distributed image interpretation and measurement processing system to achieve resource centralized management, multisite simultaneous interpretation and adaptive estimation algorithm selection; then proposed a real-time interpretation method which contains automatic foreground detection, online target tracking, multiple features location, and human guidance. An experiment is carried out at performance and efficiency evaluation of the method by semisynthetic video. The system can be used in the field of aerospace tests like target analysis including dynamic parameter, transient states, and optical physics characteristics, with security control.

A Real-Time Optical Tracking and Measurement Processing System for Flying Targets

PubMed Central

Guo, Pengyu; Ding, Shaowen; Zhang, Hongliang; Zhang, Xiaohu

2014-01-01

Optical tracking and measurement for flying targets is unlike the close range photography under a controllable observation environment, which brings extreme conditions like diverse target changes as a result of high maneuver ability and long cruising range. This paper first designed and realized a distributed image interpretation and measurement processing system to achieve resource centralized management, multisite simultaneous interpretation and adaptive estimation algorithm selection; then proposed a real-time interpretation method which contains automatic foreground detection, online target tracking, multiple features location, and human guidance. An experiment is carried out at performance and efficiency evaluation of the method by semisynthetic video. The system can be used in the field of aerospace tests like target analysis including dynamic parameter, transient states, and optical physics characteristics, with security control. PMID:24987748

A hemispherical imaging and tracking (HIT) system

NASA Astrophysics Data System (ADS)

Gilbert, John A.; Fair, Sara B.; Caldwell, Scott E.; Gronner, Sally J.

1992-05-01

A hemispherical imaging and tracking (HIT) system is described which is used for an interceptor designed to acquire, select, home, and hit-to-kill reentry vehicle targets from intercontinental ballistic missiles. The system provides a sizable field of view, over which a target may be tracked and yields a unique and distinctive optical signal when the system is 'on target'. The system has an infinite depth of focus and no moving parts are required for imaging within a hemisphere. Critical alignment of the HIT system is based on the comparison of signals captured through different points on an annular window. Assuming that the perturbations are radially symmetric, errors may be eliminated during the subtraction.

Functional Requirements of a Target Description System for Vulnerability Analysis

DTIC Science & Technology

1979-11-01

called GIFT .1,2 Together the COMGEOM description model and GIFT codes make up the BRL’s target description system. The significance of a target...and modifying target descriptions are described. 1 Lawrence W. Bain, Jr. and Mathew J. Reisinger, "The GIFT Code User Manual; Volume 1...34The GIFT Code User Manual; Volume II, The Output Options," unpublished draft of BRL report. II. UNDERLYING PHILOSOPHY The BRL has a computer

Remote liquid target loading system for LANL two-stage gas gun

NASA Astrophysics Data System (ADS)

Gibson, L. L.; Bartram, B.; Dattelbaum, D. M.; Sheffield, S. A.; Stahl, D. B.

2009-06-01

A Remote Liquid Loading System (RLLS) was designed to load high hazard liquid materials into targets for gas-gun driven impact experiments. These high hazard liquids tend to react with confining materials in a short period of time, degrading target assemblies and potentially building up pressure through the evolution of gas in the reactions. Therefore, the ability to load a gas gun target in place immediately prior to firing the gun, provides the most stable and reliable target fielding approach. We present the design and evaluation of a RLLS built for the LANL two-stage gas gun. Targets for the gun are made of PMMA and assembled to form a liquid containment cell with a volume of approximately 25 cc. The compatibility of materials was a major consideration in the design of the system, particularly for its use with highly concentrated hydrogen peroxide. Teflon and 304-stainless steel were the two most compatible materials with the materials to be tested. Teflon valves and tubing, as well as stainless steel tubing, were used to handle the liquid, along with a stainless steel reservoir. Preliminary testing was done to ensure proper flow rate and safety. The system has been used to successfully load 97.5 percent hydrogen peroxide into a target cell just prior to a successful multiple magnetic gauge experiment. TV cameras on the target verified the bubble-free filling operation.

IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

PubMed

Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

2017-11-01

The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Quantum illumination for enhanced detection of Rayleigh-fading targets

NASA Astrophysics Data System (ADS)

Zhuang, Quntao; Zhang, Zheshen; Shapiro, Jeffrey H.

2017-08-01

Quantum illumination (QI) is an entanglement-enhanced sensing system whose performance advantage over a comparable classical system survives its usage in an entanglement-breaking scenario plagued by loss and noise. In particular, QI's error-probability exponent for discriminating between equally likely hypotheses of target absence or presence is 6 dB higher than that of the optimum classical system using the same transmitted power. This performance advantage, however, presumes that the target return, when present, has known amplitude and phase, a situation that seldom occurs in light detection and ranging (lidar) applications. At lidar wavelengths, most target surfaces are sufficiently rough that their returns are speckled, i.e., they have Rayleigh-distributed amplitudes and uniformly distributed phases. QI's optical parametric amplifier receiver—which affords a 3 dB better-than-classical error-probability exponent for a return with known amplitude and phase—fails to offer any performance gain for Rayleigh-fading targets. We show that the sum-frequency generation receiver [Zhuang et al., Phys. Rev. Lett. 118, 040801 (2017), 10.1103/PhysRevLett.118.040801]—whose error-probability exponent for a nonfading target achieves QI's full 6 dB advantage over optimum classical operation—outperforms the classical system for Rayleigh-fading targets. In this case, QI's advantage is subexponential: its error probability is lower than the classical system's by a factor of 1 /ln(M κ ¯NS/NB) , when M κ ¯NS/NB≫1 , with M ≫1 being the QI transmitter's time-bandwidth product, NS≪1 its brightness, κ ¯ the target return's average intensity, and NB the background light's brightness.

Real-time visual target tracking: two implementations of velocity-based smooth pursuit

NASA Astrophysics Data System (ADS)

Etienne-Cummings, Ralph; Longo, Paul; Van der Spiegel, Jan; Mueller, Paul

1995-06-01

Two systems for velocity-based visual target tracking are presented. The first two computational layers of both implementations are composed of VLSI photoreceptors (logarithmic compression) and edge detection (difference-of-Gaussians) arrays that mimic the outer-plexiform layer of mammalian retinas. The subsequent processing layers for measuring the target velocity and to realize smooth pursuit tracking are implemented in software and at the focal plane in the two versions, respectively. One implentation uses a hybrid of a PC and a silicon retina (39 X 38 pixels) operating at 333 frames/second. The software implementation of a real-time optical flow measurement algorithm is used to determine the target velocity, and a closed-loop control system zeroes the relative velocity of the target and retina. The second implementation is a single VLSI chip, which contains a linear array of photoreceptors, edge detectors and motion detectors at the focal plane. The closed-loop control system is also included on chip. This chip realizes all the computational properties of the hybrid system. The effects of background motion, target occlusion, and disappearance are studied as a function of retinal size and spatial distribution of the measured motion vectors (i.e. foveal/peripheral and diverging/converging measurement schemes). The hybrid system, which tested successfully, tracks targets moving as fast as 3 m/s at 1.3 meters from the camera and it can compensate for external arbitrary movements in its mounting platform. The single chip version, whose circuits tested successfully, can handle targets moving at 10 m/s.

SU-F-J-45: Sparing Normal Tissue with Ultra-High Dose Rate in Radiation Therapy

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

Feng, Y

Purpose: To spare normal tissue by reducing the location uncertainty of a moving target, we proposed an ultra-high dose rate system and evaluated. Methods: High energy electrons generated with a linear accelerator were injected into a storage ring to be accumulated. The number of the electrons in the ring was determined based on the prescribed radiation dose. The dose was delivered within a millisecond, when an online imaging system found that the target was in the position that was consistent with that in a treatment plan. In such a short time period, the displacement of the target was negligible. Themore » margin added to the clinical target volume (CTV) could be reduced that was evaluated by comparing of volumes between CTV and ITV in 14 cases of lung stereotactic body radiation therapy (SBRT) treatments. A design of the ultra-high dose rate system was evaluated based clinical needs and the recent developments of low energy (a few MeV) electron storage ring. Results: This design of ultra-high dose rate system was feasible based on the techniques currently available. The reduction of a target volume was significant by reducing the margin that accounted the motion of the target. ∼50% volume reduction of the internal target volume (ITV) could be achieved in lung SBRT treatments. Conclusion: With this innovation of ultra-high dose rate system, the margin of target is able to be significantly reduced. It will reduce treatment time of gating and allow precisely specified gating window to improve the accuracy of dose delivering.« less

Image-guided ex-vivo targeting accuracy using a laparoscopic tissue localization system

NASA Astrophysics Data System (ADS)

Bieszczad, Jerry; Friets, Eric; Knaus, Darin; Rauth, Thomas; Herline, Alan; Miga, Michael; Galloway, Robert; Kynor, David

2007-03-01

In image-guided surgery, discrete fiducials are used to determine a spatial registration between the location of surgical tools in the operating theater and the location of targeted subsurface lesions and critical anatomic features depicted in preoperative tomographic image data. However, the lack of readily localized anatomic landmarks has greatly hindered the use of image-guided surgery in minimally invasive abdominal procedures. To address these needs, we have previously described a laser-based system for localization of internal surface anatomy using conventional laparoscopes. During a procedure, this system generates a digitized, three-dimensional representation of visible anatomic surfaces in the abdominal cavity. This paper presents the results of an experiment utilizing an ex-vivo bovine liver to assess subsurface targeting accuracy achieved using our system. During the experiment, several radiopaque targets were inserted into the liver parenchyma. The location of each target was recorded using an optically-tracked insertion probe. The liver surface was digitized using our system, and registered with the liver surface extracted from post-procedure CT images. This surface-based registration was then used to transform the position of the inserted targets into the CT image volume. The target registration error (TRE) achieved using our surface-based registration (given a suitable registration algorithm initialization) was 2.4 mm +/- 1.0 mm. A comparable TRE (2.6 mm +/- 1.7 mm) was obtained using a registration based on traditional fiducial markers placed on the surface of the same liver. These results indicate the potential of fiducial-free, surface-to-surface registration for image-guided lesion targeting in minimally invasive abdominal surgery.

Laser-ranging scanning system to observe topographical deformations of volcanoes.

PubMed

Aoki, T; Takabe, M; Mizutani, K; Itabe, T

1997-02-20

We have developed a laser-ranging system to observe the topographical structure of volcanoes. This system can be used to measure the distance to a target by a laser and shows the three-dimensional topographical structure of a volcano with an accuracy of 30 cm. This accuracy is greater than that of a typical laser-ranging system that uses a corner-cube reflector as a target because the reflected light jitters as a result of inclination and unevenness of the target ground surface. However, this laser-ranging system is useful for detecting deformations of topographical features in which placement of a reflector is difficult, such as in volcanic regions.

Results from the Maine 1992 foliage penetration experiment

NASA Astrophysics Data System (ADS)

Toups, Michael F.; Ayasli, Serpil

1993-11-01

In order to investigate the detection of targets which are hidden by foliage, an experiment was designed which utilized a forest region located near Portage, Maine. The experiment was designed to address four issues. First, the properties of the backscatter or clutter which competes with the desired target were investigated. Second, the foliage induced attenuation that is experienced by the radar energy traversing the foliage were measured. Third, the ability of a synthetic aperture radar system to focus on a target obscured by foliage was investigated. Fourth, target signatures of foliage obscured and unobscured targets were measured. The forest region was investigated using two different airborne synthetic aperture radar (SAR) systems. A UHF wide-band SAR operated by SRI International was used as well as a L-, C-, and X-band SAR installed on a P-3 aircraft operated by the U.S. Navy. The SRI system was used to collect data over 16 square kilometers with repeat passes for verification of system performance. The P-3 system was used to collect over 50 square kilometers of data at three different depression angles with several repeat passes.

Multifunctional Nucleus-targeting Nanoparticles with Ultra-high Gene Transfection Efficiency for In Vivo Gene Therapy

PubMed Central

Li, Ling; Li, Xia; Wu, Yuzhe; Song, Linjiang; Yang, Xi; He, Tao; Wang, Ning; Yang, Suleixin; Zeng, Yan; Wu, Qinjie; Qian, Zhiyong; Wei, Yuquan; Gong, Changyang

2017-01-01

Cancer stem cell-like cells (CSCL) are responsible for tumor recurrence associated with conventional therapy (e.g. surgery, radiation, and chemotherapy). Here, we developed a novel multifunctional nucleus-targeting nanoparticle-based gene delivery system which is capable of targeting and eradicating CSCL. These nanoparticles can facilitate efficient endosomal escape and spontaneously penetrate into nucleus without additional nuclear localization signal. They also induced extremely high gene transfection efficiency (>95%) even in culture medium containing 30% serum, which significantly surpassed that of some commercial transfection reagents, such as Lipofectamine 2000 and Lipofectamine 3000 etc. Especially, when loaded with the TRAIL gene, this system mediated remarkable depletion of CSCL. Upon systemic administration, the nanoparticles accumulated in tumor sites while sparing the non-cancer tissues and significantly inhibited the growth of tumors with no evident systemic toxicity. Taken together, our results suggest that these novel multifunctional, nucleus-targeting nanoparticles are a very promising in vivo gene delivery system capable of targeting CSCL and represent a new treatment candidate for improving the survival of cancer patients. PMID:28529641

A magnetic resonance image-guided breast needle intervention robot system: overview and design considerations.

PubMed

Park, Samuel Byeongjun; Kim, Jung-Gun; Lim, Ki-Woong; Yoon, Chae-Hyun; Kim, Dong-Jun; Kang, Han-Sung; Jo, Yung-Ho

2017-08-01

We developed an image-guided intervention robot system that can be operated in a magnetic resonance (MR) imaging gantry. The system incorporates a bendable needle intervention robot for breast cancer patients that overcomes the space limitations of the MR gantry. Most breast coil designs for breast MR imaging have side openings to allow manual localization. However, for many intervention procedures, the patient must be removed from the gantry. A robotic manipulation system with integrated image guidance software was developed. Our robotic manipulator was designed to be slim, so as to fit between the patient's side and the MR gantry wall. Only non-magnetic materials were used, and an electromagnetic shield was employed for cables and circuits. The image guidance software was built using open source libraries. In situ feasibility tests were performed in a 3-T MR system. One target point in the breast phantom was chosen by the clinician for each experiment, and our robot moved the needle close to the target point. Without image-guided feedback control, the needle end could not hit the target point (distance = 5 mm) in the first experiment. Using our robotic system, the needle hits the target lesion of the breast phantom at a distance of 2.3 mm from the same target point using image-guided feedback. The second experiment was performed using other target points, and the distance between the final needle end point and the target point was 0.8 mm. We successfully developed an MR-guided needle intervention robot for breast cancer patients. Further research will allow the expansion of these interventions.

A picosecond beam-timing system for the OMEGA laser

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

Donaldson, W. R.; Katz, J.; Huff, R.

Here, a timing system is demonstrated for the OMEGA Laser System that guarantees all 60 beams will arrive on target simultaneously with a root mean square variability of 4 ps. The system relies on placing a scattering sphere at the target position to couple the UV light from each beam into a single photodetector.

A picosecond beam-timing system for the OMEGA laser

DOE PAGES

Donaldson, W. R.; Katz, J.; Huff, R.; ...

2016-05-27

Here, a timing system is demonstrated for the OMEGA Laser System that guarantees all 60 beams will arrive on target simultaneously with a root mean square variability of 4 ps. The system relies on placing a scattering sphere at the target position to couple the UV light from each beam into a single photodetector.

A picosecond beam-timing system for the OMEGA laser

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

Donaldson, W. R.; Katz, J.; Huff, R.

A timing system is demonstrated for the OMEGA Laser System that guarantees all 60 beams will arrive on target simultaneously with a root mean square variability of 4 ps. The system relies on placing a scattering sphere at the target position to couple the ultraviolet light from each beam into a single photodetector.

Research on target information optics communications transmission characteristic and performance in multi-screens testing system

NASA Astrophysics Data System (ADS)

Li, Hanshan

2016-04-01

To enhance the stability and reliability of multi-screens testing system, this paper studies multi-screens target optical information transmission link properties and performance in long-distance, sets up the discrete multi-tone modulation transmission model based on geometric model of laser multi-screens testing system and visible light information communication principle; analyzes the electro-optic and photoelectric conversion function of sender and receiver in target optical information communication system; researches target information transmission performance and transfer function of the generalized visible-light communication channel; found optical information communication transmission link light intensity space distribution model and distribution function; derives the SNR model of information transmission communication system. Through the calculation and experiment analysis, the results show that the transmission error rate increases with the increment of transmission rate in a certain channel modulation depth; when selecting the appropriate transmission rate, the bit error rate reach 0.01.

Glioblastoma Multiforme and Lipid Nanocapsules: A Review.

PubMed

Aparicio-Blanco, Juan; Torres-Suárez, Ana-Isabel

2015-08-01

Epidemiological data on central nervous system disorders call for a focus on the major hindrance to brain drug delivery, blood-central nervous system barriers. Otherwise, there is little chance of improving the short-term survival of patients with diseases such as glioblastoma multiforme, which is one of the brain disorders associated with many years of life lost. Targetable nanocarriers for treating malignant gliomas are a unique way to overcome low chemotherapeutic levels at target sites devoid of systemic toxicity. This review describes the currently available targetable nanocarriers, focusing particularly on one of the newest nanocarriers, lipid nanocapsules. All of the strategies that are likely to be exploited by lipid nanocapsules to bypass blood-central nervous system barriers, including the most recent targeting approaches (mesenchymal cells), and novel administration routes (convection enhanced delivery) are discussed, together with their most remarkable achievements in glioma-implanted animal models. Although these systems are promising, much research remains to be done in this field.

Method and system for providing autonomous control of a platform

NASA Technical Reports Server (NTRS)

Seelinger, Michael J. (Inventor); Yoder, John-David (Inventor)

2012-01-01

The present application provides a system for enabling instrument placement from distances on the order of five meters, for example, and increases accuracy of the instrument placement relative to visually-specified targets. The system provides precision control of a mobile base of a rover and onboard manipulators (e.g., robotic arms) relative to a visually-specified target using one or more sets of cameras. The system automatically compensates for wheel slippage and kinematic inaccuracy ensuring accurate placement (on the order of 2 mm, for example) of the instrument relative to the target. The system provides the ability for autonomous instrument placement by controlling both the base of the rover and the onboard manipulator using a single set of cameras. To extend the distance from which the placement can be completed to nearly five meters, target information may be transferred from navigation cameras (used for long-range) to front hazard cameras (used for positioning the manipulator).

Geodemographics as a tool for targeting neighbourhoods in public health campaigns

NASA Astrophysics Data System (ADS)

Petersen, Jakob; Gibin, Maurizio; Longley, Paul; Mateos, Pablo; Atkinson, Philip; Ashby, David

2011-06-01

Geodemographics offers the prospects of integrating, modelling and mapping health care needs and other health indicators that are useful for targeting neighbourhoods in public health campaigns. Yet reports about this application domain has to date been sporadic. The purpose of this paper is to examine the potential of a bespoke geodemographic system for neighbourhood targeting in an inner city public health authority, Southwark Primary Care Trust, London. This system, the London Output Area Classification (LOAC), is compared to six other geodemographic systems from both governmental and commercial sources. The paper proposes two new indicators for assessing the performance of geodemographic systems for neighbourhood targeting based on local hospital demand data. The paper also analyses and discusses the utility of age- and sex standardisation of geodemographic profiles of health care demand.

Evaluation of the Performance of the Distributed Phased-MIMO Sonar.

PubMed

Pan, Xiang; Jiang, Jingning; Wang, Nan

2017-01-11

A broadband signal model is proposed for a distributed multiple-input multiple-output (MIMO) sonar system consisting of two transmitters and a receiving linear array. Transmitters are widely separated to illuminate the different aspects of an extended target of interest. The beamforming technique is utilized at the reception ends for enhancement of weak target echoes. A MIMO detector is designed with the estimated target position parameters within the general likelihood rate test (GLRT) framework. For the high signal-to-noise ratio case, the detection performance of the MIMO system is better than that of the phased-array system in the numerical simulations and the tank experiments. The robustness of the distributed phased-MIMO sonar system is further demonstrated in localization of a target in at-lake experiments.

Evaluation of the Performance of the Distributed Phased-MIMO Sonar

PubMed Central

Pan, Xiang; Jiang, Jingning; Wang, Nan

2017-01-01

A broadband signal model is proposed for a distributed multiple-input multiple-output (MIMO) sonar system consisting of two transmitters and a receiving linear array. Transmitters are widely separated to illuminate the different aspects of an extended target of interest. The beamforming technique is utilized at the reception ends for enhancement of weak target echoes. A MIMO detector is designed with the estimated target position parameters within the general likelihood rate test (GLRT) framework. For the high signal-to-noise ratio case, the detection performance of the MIMO system is better than that of the phased-array system in the numerical simulations and the tank experiments. The robustness of the distributed phased-MIMO sonar system is further demonstrated in localization of a target in at-lake experiments. PMID:28085071

MIT modular x-ray source systems for the study of plasma diagnostics

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

Coleman, J.W.; Wenzel, K.W.; Petrasso, R.D.

1992-10-01

Two new x-ray source systems are now on line at our facility. Each provides an {ital e}-beam to 25 kV. Targets are interchangeable between machines, and four x-ray detectors may be used simultaneously with a target. The gridded {ital e}-gun of the RACEHORSE system gives a 0.5--1.0-cm pulsable spot on target. The nongridded {ital e}-gun of the SCORPION system provides a 0.3-mm or smaller dc microspot on target. RACEHORSE is being used to study and characterize type-II diamond photoconductors for use in diagnosing plasmas, while SCORPION is being used to develop a slitless spectrograph using photographic film. Source design detailsmore » and some RACEHORSE results are presented.« less

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

The vascular endothelium in diabetes--a therapeutic target?

PubMed

Mather, Kieren J

2013-03-01

Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function. We review the available literature presenting studies in humans, evaluating the effects of metabolically targeted and vascular targeted therapies on insulin action and systemic metabolism. Therapies that improve systemic insulin resistance exert strong concurrent effects to improve vascular function and vascular insulin action. RAS-acting agents and statins have widely recognized beneficial effects on vascular function but have not uniformly produced the hoped-for metabolic benefits. These observations support the notion that systemic metabolic benefits can arise from therapies targeted at the endothelium, but improving vascular insulin action does not result from all treatments that improve endothelium-dependent vasodilation. A better understanding of the mechanisms of insulin's actions in the vascular wall will advance our understanding of the specificity of these responses, and allow us to better target the vasculature for metabolic benefits.

Nanoparticles for targeted delivery of therapeutics and small interfering RNAs in hepatocellular carcinoma

PubMed Central

Varshosaz, Jaleh; Farzan, Maryam

2015-01-01

Hepatocellular carcinoma (HCC) is the 5th most common malignancy which is responsible for more than half million annual mortalities; also, it is the third leading cause of cancer related death. Unfavorable systemic side-effects of chemotherapeutic agents and susceptibility to the degradation of small interfering RNAs (siRNAs), which can knock down a specific gene involved in the disease, have hampered their clinical application. So, it could be beneficial to develop an efficient carrier for the stabilization and specific delivery of drugs and siRNA to cells. Targeted nanoparticles have gained considerable attention as an efficient drug and gene delivery system, which is due to their capability in achieving the highest accumulation of cytotoxic agents in tumor tissue, modifiable drug pharmacokinetic- and bio-distribution, improved effectiveness of treatment, and limited side-effects. Recent studies have shed more light on the advantages of novel drug loaded carrier systems vs free drugs. Most of the animal studies have reported improvement in treatment efficacy and survival rate using novel carrier systems. Targeted delivery may be achieved passively or actively. In passive targeting, no ligand as homing device is used, while targeting is achieved by incorporating the therapeutic agent into a macromolecule or nanoparticle that passively reaches the target organ. However, in active targeting, the therapeutic agent or carrier system is conjugated to a tissue or cell-specific receptor which is over-expressed in a special malignancy using a ligand called a homing device. This review covers a broad spectrum of targeted nanoparticles as therapeutic and non-viral siRNA delivery systems, which are developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and their characteristics and opportunities for the clinical applications of drugs and therapeutic siRNA are discussed in this article. Asialoglycoprotein receptors, low-density lipoprotein, ganglioside GM1 cell surface ligand, epidermal growth factor receptor receptors, monoclonal antibodies, retinoic acid receptors, integrin receptors targeted by Arg-Gly-Asp peptide, folate, and transferrin receptors are the most widely studied cell surface receptors which are used for the site specific delivery of drugs and siRNA-based therapeutics in HCC and discussed in detail in this article. PMID:26576089

Integrative FourD omics approach profiles the target network of the carbon storage regulatory system

PubMed Central

Sowa, Steven W.; Gelderman, Grant; Leistra, Abigail N.; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A.; Romeo, Tony; Baldea, Michael

2017-01-01

Abstract Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. PMID:28126921

Targeted mutagenesis in cotton (Gossypium hirsutum L.) using the CRISPR/Cas9 system

PubMed Central

Chen, Xiugui; Lu, Xuke; Shu, Na; Wang, Shuai; Wang, Junjuan; Wang, Delong; Guo, Lixue; Ye, Wuwei

2017-01-01

The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has been widely used for genome editing in various plants because of its simplicity, high efficiency and design flexibility. However, to our knowledge, there is no report on the application of CRISPR/Cas9-mediated targeted mutagenesis in cotton. Here, we report the genome editing and targeted mutagenesis in upland cotton (Gossypium hirsutum L., hereafter cotton) using the CRISPR/Cas9 system. We designed two guide RNAs to target distinct sites of the cotton Cloroplastos alterados 1 (GhCLA1) and vacuolar H+-pyrophosphatase (GhVP) genes. Mutations in these two genes were detected in cotton protoplasts. Most of the mutations were nucleotide substitutions, with one nucleotide insertion and one substitution found in GhCLA1 and one deletion found in GhVP in cotton protoplasts. Subsequently, the two vectors were transformed into cotton shoot apexes through Agrobacterium-mediated transformation, resulting in efficient target gene editing. Most of the mutations were nucleotide deletions, and the mutation efficiencies were 47.6–81.8% in transgenic cotton plants. Evaluation using restriction-enzyme-PCR assay and sequence analysis detected no off-target mutations. Our results indicated that the CRISPR/Cas9 system was an efficient and specific tool for targeted mutagenesis of the cotton genome. PMID:28287154

Targeted mutagenesis in cotton (Gossypium hirsutum L.) using the CRISPR/Cas9 system.

PubMed

Chen, Xiugui; Lu, Xuke; Shu, Na; Wang, Shuai; Wang, Junjuan; Wang, Delong; Guo, Lixue; Ye, Wuwei

2017-03-13

The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has been widely used for genome editing in various plants because of its simplicity, high efficiency and design flexibility. However, to our knowledge, there is no report on the application of CRISPR/Cas9-mediated targeted mutagenesis in cotton. Here, we report the genome editing and targeted mutagenesis in upland cotton (Gossypium hirsutum L., hereafter cotton) using the CRISPR/Cas9 system. We designed two guide RNAs to target distinct sites of the cotton Cloroplastos alterados 1 (GhCLA1) and vacuolar H + -pyrophosphatase (GhVP) genes. Mutations in these two genes were detected in cotton protoplasts. Most of the mutations were nucleotide substitutions, with one nucleotide insertion and one substitution found in GhCLA1 and one deletion found in GhVP in cotton protoplasts. Subsequently, the two vectors were transformed into cotton shoot apexes through Agrobacterium-mediated transformation, resulting in efficient target gene editing. Most of the mutations were nucleotide deletions, and the mutation efficiencies were 47.6-81.8% in transgenic cotton plants. Evaluation using restriction-enzyme-PCR assay and sequence analysis detected no off-target mutations. Our results indicated that the CRISPR/Cas9 system was an efficient and specific tool for targeted mutagenesis of the cotton genome.

Binaural segregation in multisource reverberant environments.

PubMed

Roman, Nicoleta; Srinivasan, Soundararajan; Wang, DeLiang

2006-12-01

In a natural environment, speech signals are degraded by both reverberation and concurrent noise sources. While human listening is robust under these conditions using only two ears, current two-microphone algorithms perform poorly. The psychological process of figure-ground segregation suggests that the target signal is perceived as a foreground while the remaining stimuli are perceived as a background. Accordingly, the goal is to estimate an ideal time-frequency (T-F) binary mask, which selects the target if it is stronger than the interference in a local T-F unit. In this paper, a binaural segregation system that extracts the reverberant target signal from multisource reverberant mixtures by utilizing only the location information of target source is proposed. The proposed system combines target cancellation through adaptive filtering and a binary decision rule to estimate the ideal T-F binary mask. The main observation in this work is that the target attenuation in a T-F unit resulting from adaptive filtering is correlated with the relative strength of target to mixture. A comprehensive evaluation shows that the proposed system results in large SNR gains. In addition, comparisons using SNR as well as automatic speech recognition measures show that this system outperforms standard two-microphone beamforming approaches and a recent binaural processor.

The p38α mitogen-activated protein kinase as a central nervous system drug discovery target

PubMed Central

Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

2008-01-01

Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38α mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38α MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38α MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38α MAPK in neurodegenerative disorders. PMID:19090985

Integration of bio-inspired, control-based visual and olfactory data for the detection of an elusive target

NASA Astrophysics Data System (ADS)

Duong, Tuan A.; Duong, Nghi; Le, Duong

2017-01-01

In this paper, we present an integration technique using a bio-inspired, control-based visual and olfactory receptor system to search for elusive targets in practical environments where the targets cannot be seen obviously by either sensory data. Bio-inspired Visual System is based on a modeling of extended visual pathway which consists of saccadic eye movements and visual pathway (vertebrate retina, lateral geniculate nucleus and visual cortex) to enable powerful target detections of noisy, partial, incomplete visual data. Olfactory receptor algorithm, namely spatial invariant independent component analysis, that was developed based on data of old factory receptor-electronic nose (enose) of Caltech, is adopted to enable the odorant target detection in an unknown environment. The integration of two systems is a vital approach and sets up a cornerstone for effective and low-cost of miniaturized UAVs or fly robots for future DOD and NASA missions, as well as for security systems in Internet of Things environments.

The p38alpha mitogen-activated protein kinase as a central nervous system drug discovery target.

PubMed

Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

2008-12-03

Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38alpha mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38alpha MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38alpha MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38alpha MAPK in neurodegenerative disorders.

DrugECs: An Ensemble System with Feature Subspaces for Accurate Drug-Target Interaction Prediction

PubMed Central

Jiang, Jinjian; Wang, Nian; Zhang, Jun

2017-01-01

Background Drug-target interaction is key in drug discovery, especially in the design of new lead compound. However, the work to find a new lead compound for a specific target is complicated and hard, and it always leads to many mistakes. Therefore computational techniques are commonly adopted in drug design, which can save time and costs to a significant extent. Results To address the issue, a new prediction system is proposed in this work to identify drug-target interaction. First, drug-target pairs are encoded with a fragment technique and the software “PaDEL-Descriptor.” The fragment technique is for encoding target proteins, which divides each protein sequence into several fragments in order and encodes each fragment with several physiochemical properties of amino acids. The software “PaDEL-Descriptor” creates encoding vectors for drug molecules. Second, the dataset of drug-target pairs is resampled and several overlapped subsets are obtained, which are then input into kNN (k-Nearest Neighbor) classifier to build an ensemble system. Conclusion Experimental results on the drug-target dataset showed that our method performs better and runs faster than the state-of-the-art predictors. PMID:28744468

A Dynamic Navigation Model for Unmanned Aircraft Systems and an Application to Autonomous Front-On Environmental Sensing and Photography Using Low-Cost Sensor Systems.

PubMed

Cooper, Andrew James; Redman, Chelsea Anne; Stoneham, David Mark; Gonzalez, Luis Felipe; Etse, Victor Kwesi

2015-08-28

This paper presents an unmanned aircraft system (UAS) that uses a probabilistic model for autonomous front-on environmental sensing or photography of a target. The system is based on low-cost and readily-available sensor systems in dynamic environments and with the general intent of improving the capabilities of dynamic waypoint-based navigation systems for a low-cost UAS. The behavioural dynamics of target movement for the design of a Kalman filter and Markov model-based prediction algorithm are included. Geometrical concepts and the Haversine formula are applied to the maximum likelihood case in order to make a prediction regarding a future state of a target, thus delivering a new waypoint for autonomous navigation. The results of the application to aerial filming with low-cost UAS are presented, achieving the desired goal of maintained front-on perspective without significant constraint to the route or pace of target movement.

Applying Standard Interfaces to a Process-Control Language

NASA Technical Reports Server (NTRS)

Berthold, Richard T.

2005-01-01

A method of applying open-operating-system standard interfaces to the NASA User Interface Language (UIL) has been devised. UIL is a computing language that can be used in monitoring and controlling automated processes: for example, the Timeliner computer program, written in UIL, is a general-purpose software system for monitoring and controlling sequences of automated tasks in a target system. In providing the major elements of connectivity between UIL and the target system, the present method offers advantages over the prior method. Most notably, unlike in the prior method, the software description of the target system can be made independent of the applicable compiler software and need not be linked to the applicable executable compiler image. Also unlike in the prior method, it is not necessary to recompile the source code and relink the source code to a new executable compiler image. Abstraction of the description of the target system to a data file can be defined easily, with intuitive syntax, and knowledge of the source-code language is not needed for the definition.

Neural Network Target Identification System for False Alarm Reduction

NASA Technical Reports Server (NTRS)

Ye, David; Edens, Weston; Lu, Thomas T.; Chao, Tien-Hsin

2009-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feed forward back propagation neural network (NN) is then trained to classify each feature vector and remove false positives. This paper discusses the test of the system performance and parameter optimizations process which adapts the system to various targets and datasets. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar image dataset.

A Dynamic Navigation Model for Unmanned Aircraft Systems and an Application to Autonomous Front-On Environmental Sensing and Photography Using Low-Cost Sensor Systems

PubMed Central

Cooper, Andrew James; Redman, Chelsea Anne; Stoneham, David Mark; Gonzalez, Luis Felipe; Etse, Victor Kwesi

2015-01-01

This paper presents an unmanned aircraft system (UAS) that uses a probabilistic model for autonomous front-on environmental sensing or photography of a target. The system is based on low-cost and readily-available sensor systems in dynamic environments and with the general intent of improving the capabilities of dynamic waypoint-based navigation systems for a low-cost UAS. The behavioural dynamics of target movement for the design of a Kalman filter and Markov model-based prediction algorithm are included. Geometrical concepts and the Haversine formula are applied to the maximum likelihood case in order to make a prediction regarding a future state of a target, thus delivering a new waypoint for autonomous navigation. The results of the application to aerial filming with low-cost UAS are presented, achieving the desired goal of maintained front-on perspective without significant constraint to the route or pace of target movement. PMID:26343680

A Fast MEANSHIFT Algorithm-Based Target Tracking System

PubMed Central

Sun, Jian

2012-01-01

Tracking moving targets in complex scenes using an active video camera is a challenging task. Tracking accuracy and efficiency are two key yet generally incompatible aspects of a Target Tracking System (TTS). A compromise scheme will be studied in this paper. A fast mean-shift-based Target Tracking scheme is designed and realized, which is robust to partial occlusion and changes in object appearance. The physical simulation shows that the image signal processing speed is >50 frame/s. PMID:22969397

Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

PubMed

Basu, P P; Aloysius, M M; Shah, N J; Brown, R S

2014-04-01

Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. © 2014 John Wiley & Sons Ltd.

Nanocarrier-mediated drugs targeting cancer stem cells: an emerging delivery approach.

PubMed

Malhi, Sarandeep; Gu, Xiaochen

2015-07-01

Cancer stem cells (CSCs) play an important role in the development of drug resistance, metastasis and recurrence. Current conventional therapies do not commonly target CSCs. Nanocarrier-based delivery systems targeting cancer cells have entered a new era of treatment, where specific targeting to CSCs may offer superior outcomes to efficient cancer therapies. This review discusses the involvement of CSCs in tumor progression and relevant mechanisms associated with CSCs resistance to conventional chemo- and radio-therapies. It highlights CSCs-targeted strategies that are either under evaluation or could be explored in the near future, with a focus on various nanocarrier-based delivery systems of drugs and nucleic acids to CSCs. Novel nanocarriers targeting CSCs are presented in a cancer-specific way to provide a current perspective on anti-CSCs therapeutics. The field of CSCs-targeted therapeutics is still emerging with a few small molecules and macromolecules currently proving efficacy in clinical trials. However considering the complexities of CSCs and existing delivery difficulties in conventional anticancer therapies, CSC-specific delivery systems would face tremendous technical and clinical challenges. Nanocarrier-based approaches have demonstrated significant potential in specific drug delivery and targeting; their success in CSCs-targeted drug delivery would not only significantly enhance anticancer treatment but also address current difficulties associated with cancer resistance, metastasis and recurrence.

Through-the-Wall Localization of a Moving Target by Two Independent Ultra Wideband (UWB) Radar Systems

PubMed Central

Kocur, Dušan; Švecová, Mária; Rovňáková, Jana

2013-01-01

In the case of through-the-wall localization of moving targets by ultra wideband (UWB) radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered. PMID:24021968

Through-the-wall localization of a moving target by two independent ultra wideband (UWB) radar systems.

PubMed

Kocur, Dušan; Svecová, Mária; Rovňáková, Jana

2013-09-09

In the case of through-the-wall localization of moving targets by ultra wideband (UWB) radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered.

A system for the real-time display of radar and video images of targets

NASA Technical Reports Server (NTRS)

Allen, W. W.; Burnside, W. D.

1990-01-01

Described here is a software and hardware system for the real-time display of radar and video images for use in a measurement range. The main purpose is to give the reader a clear idea of the software and hardware design and its functions. This system is designed around a Tektronix XD88-30 graphics workstation, used to display radar images superimposed on video images of the actual target. The system's purpose is to provide a platform for tha analysis and documentation of radar images and their associated targets in a menu-driven, user oriented environment.

An Accurate Non-Cooperative Method for Measuring Textureless Spherical Target Based on Calibrated Lasers.

PubMed

Wang, Fei; Dong, Hang; Chen, Yanan; Zheng, Nanning

2016-12-09

Strong demands for accurate non-cooperative target measurement have been arising recently for the tasks of assembling and capturing. Spherical objects are one of the most common targets in these applications. However, the performance of the traditional vision-based reconstruction method was limited for practical use when handling poorly-textured targets. In this paper, we propose a novel multi-sensor fusion system for measuring and reconstructing textureless non-cooperative spherical targets. Our system consists of four simple lasers and a visual camera. This paper presents a complete framework of estimating the geometric parameters of textureless spherical targets: (1) an approach to calibrate the extrinsic parameters between a camera and simple lasers; and (2) a method to reconstruct the 3D position of the laser spots on the target surface and achieve the refined results via an optimized scheme. The experiment results show that our proposed calibration method can obtain a fine calibration result, which is comparable to the state-of-the-art LRF-based methods, and our calibrated system can estimate the geometric parameters with high accuracy in real time.

Universalism under siege? Exploring the association between targeting, child benefits and child poverty across 26 countries.

PubMed

Van Lancker, Wim; Van Mechelen, Natascha

2015-03-01

The long-standing wisdom that universally designed benefits outperform targeted benefits in terms of poverty reduction has come under siege. Recent empirical studies tend to find that targeting is not necessarily associated anymore with lower levels of poverty reduction. In this study, we investigate for a broad set of European countries (1) the relationship between child benefits and child poverty reduction; (2) whether a universal or targeted approach is more effective in reducing child poverty; and (3) the causal mechanisms explaining the link between (1) and (2). In doing so, we take into account the general characteristics of the child benefit system, the size of the redistributive budget and the generosity of benefit levels. In contrast to previous studies, we construct an indicator of targeting that captures the design instead of the outcomes of child benefit systems. We find that targeting towards lower incomes is associated with higher levels of child poverty reduction, conditional on the direction of targeting and the characteristics of the benefit system. Copyright © 2014 Elsevier Inc. All rights reserved.

An Accurate Non-Cooperative Method for Measuring Textureless Spherical Target Based on Calibrated Lasers

PubMed Central

Wang, Fei; Dong, Hang; Chen, Yanan; Zheng, Nanning

2016-01-01

Strong demands for accurate non-cooperative target measurement have been arising recently for the tasks of assembling and capturing. Spherical objects are one of the most common targets in these applications. However, the performance of the traditional vision-based reconstruction method was limited for practical use when handling poorly-textured targets. In this paper, we propose a novel multi-sensor fusion system for measuring and reconstructing textureless non-cooperative spherical targets. Our system consists of four simple lasers and a visual camera. This paper presents a complete framework of estimating the geometric parameters of textureless spherical targets: (1) an approach to calibrate the extrinsic parameters between a camera and simple lasers; and (2) a method to reconstruct the 3D position of the laser spots on the target surface and achieve the refined results via an optimized scheme. The experiment results show that our proposed calibration method can obtain a fine calibration result, which is comparable to the state-of-the-art LRF-based methods, and our calibrated system can estimate the geometric parameters with high accuracy in real time. PMID:27941705

Development of germ-line-specific CRISPR-Cas9 systems to improve the production of heritable gene modifications in Arabidopsis

PubMed Central

Mao, Yanfei; Zhang, Zhengjing; Feng, Zhengyan; Wei, Pengliang; Zhang, Hui; Botella, José Ramón; Zhu, Jian-Kang

2017-01-01

Summary The Streptococcus-derived CRISPR/Cas9 system is being widely used to perform targeted gene modifications in plants. This customized endonuclease system has two components, the single-guide RNA (sgRNA) for target DNA recognition and the CRISPR-associated protein 9 (Cas9) for DNA cleavage. Ubiquitously expressed CRISPR/Cas9 systems (UC) generate targeted gene modifications with high efficiency but only those produced in reproductive cells are transmitted to the next generation. We report the design and characterization of a germ-line-specific Cas9 system (GSC) for Arabidopsis gene modification in male gametocytes, constructed using a SPOROCYTELESS (SPL) genomic expression cassette. Four loci in two endogenous genes were targeted by both systems for comparative analysis. Mutations generated by the GSC system were rare in T1 plants but were abundant (30%) in the T2 generation. The vast majority (70%) of the T2 mutant population generated using the UC system were chimeras while the newly developed GSC system produced only 29% chimeras, with 70% of the T2 mutants being heterozygous. Analysis of two loci in the T2 population showed that the abundance of heritable gene mutations was 37% higher in the GSC system compared to the UC system and the level of polymorphism of the mutations was also dramatically increased with the GSC system. Two additional systems based on germ-line-specific promoters (pDD45-GT and pLAT52-GT) were also tested, and one of them was capable of generating heritable homozygous T1 mutant plants. Our results suggest that future application of the described GSC system will facilitate the screening for targeted gene modifications, especially lethal mutations in the T2 population. PMID:26360626

Clinical evidence for cervical myelopathy due to Chiari malformation and spinal stenosis in a non-randomized group of patients with the diagnosis of fibromyalgia.

PubMed

Heffez, Dan S; Ross, Ruth E; Shade-Zeldow, Yvonne; Kostas, Konstantinos; Shah, Sagar; Gottschalk, Robert; Elias, Dean A; Shepard, Alan; Leurgans, Sue E; Moore, Charity G

2004-10-01

While patients with fibromyalgia report symptoms consistent with cervical myelopathy, a detailed neurological evaluation is not routine. We sought to determine if patients with fibromyalgia manifest objective neurological signs of cervical myelopathy. Two hundred and seventy patients, 18 years and older, who carried the diagnosis of fibromyalgia but who had no previously recognized neurological disease underwent detailed clinical neurological and neuroradiological evaluation for the prevalence of objective evidence of cervical myelopathy and radiological evidence of cerebellar tonsillar herniation (Chiari 1 malformation) or cervical spinal canal stenosis. Patients were primarily women (87%), of mean age 44 years, who had been symptomatic for 8 years (standard deviation, 6.3 years). The predominant complaints were neck/back pain (95%), fatigue (95%), exertional fatigue (96%), cognitive impairment (92%), instability of gait (85%), grip weakness (83%), paresthesiae (80%), dizziness (71%) and numbness (69%). Eighty-eight percent of patients reported worsening symptoms with neck extension. The neurological examination was consistent with cervical myelopathy: upper thoracic spinothalamic sensory level (83%), hyperreflexia (64%), inversion of the radial periosteal reflex (57%), positive Romberg sign (28%), ankle clonus (25%), positive Hoffman sign (26%), impaired tandem walk (23%), dysmetria (15%) and dysdiadochokinesia (13%). MRI and contrast-enhanced CT imaging of the cervical spine revealed stenosis. The mean antero-posterior (AP) spinal canal diameter at C2/3, C3/4, C4/5, C5/6, C6/7 and C7/T1 was 13.5 mm, 11.8 mm, 11.5 mm, 10.4 mm, 11.3 mm and 14.5 mm respectively, (CT images). In 46% of patients, the AP spinal diameter at C5/6 measured 10 mm, or less, with the neck positioned in mild extension, i.e., clinically significant spinal canal stenosis. MRI of the brain revealed tonsillar ectopia >5 mm in 20% of patients (mean=7.1+/-1.8 mm), i.e., Chiari 1 malformation. CONCLUSION. Our findings indicate that some patients who carry the diagnosis of fibromyalgia have both signs and symptoms consistent with cervical myelopathy, most likely resulting from spinal cord compression. We recommend detailed neurological evaluation of patients with fibromyalgia in order to exclude cervical myelopathy, a potentially treatable condition.

Development of Water Target for Radioisotope Production

NASA Astrophysics Data System (ADS)

Tripp, Nathan

2011-10-01

Ongoing studies of plant physiology at TUNL require a supply of nitrogen-13 for use as a radiotracer. Production of nitrogen-13 using a water target and a proton beam follows the nuclear reaction 16-O(p,a)13-N. Unfortunately the irradiation of trace amounts of oxygen-18 within a natural water target produces fluorine-18 by the reaction 18-O(p, n)18-F. The presence of this second radioisotope reduces the efficacy of nitrogen-13 as a radiotracer. Designing a natural water target for nitrogen-13 production at TUNL required the design of several new systems to address the problems inherent in nitrogen-13 production. A heat exchanger cools the target water after irradiation within the target cell. The resulting improved thermal regulation of the target water prevents the system from overheating and minimizes the effect of the cavitations occurring within the target. Alumina pellets within a scrubbing unit remove the fluorine-18 contamination from the irradiated water. The modular design of the water target apparatus makes the system highly adaptable, allowing for easy reuse and adaptation of the different components into future projects. The newly designed and constructed water target should meet the current and future needs of TUNL researchers in the production of nitrogen-13. This TUNL REU project was funded in part by a grant from the National Science Foundation (NSF) NSF-PHY-08-51813.

Infrared moving small target detection based on saliency extraction and image sparse representation

NASA Astrophysics Data System (ADS)

Zhang, Xiaomin; Ren, Kan; Gao, Jin; Li, Chaowei; Gu, Guohua; Wan, Minjie

2016-10-01

Moving small target detection in infrared image is a crucial technique of infrared search and tracking system. This paper present a novel small target detection technique based on frequency-domain saliency extraction and image sparse representation. First, we exploit the features of Fourier spectrum image and magnitude spectrum of Fourier transform to make a rough extract of saliency regions and use a threshold segmentation system to classify the regions which look salient from the background, which gives us a binary image as result. Second, a new patch-image model and over-complete dictionary were introduced to the detection system, then the infrared small target detection was converted into a problem solving and optimization process of patch-image information reconstruction based on sparse representation. More specifically, the test image and binary image can be decomposed into some image patches follow certain rules. We select the target potential area according to the binary patch-image which contains salient region information, then exploit the over-complete infrared small target dictionary to reconstruct the test image blocks which may contain targets. The coefficients of target image patch satisfy sparse features. Finally, for image sequence, Euclidean distance was used to reduce false alarm ratio and increase the detection accuracy of moving small targets in infrared images due to the target position correlation between frames.

Multi-Stage System for Automatic Target Recognition

NASA Technical Reports Server (NTRS)

Chao, Tien-Hsin; Lu, Thomas T.; Ye, David; Edens, Weston; Johnson, Oliver

2010-01-01

A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an artificial neural network classifier. The multi-stage system allows tuning the detection sensitivity and the identification specificity individually in each stage. It is easier to achieve optimized ATR operation based on its specific goal. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar and video image datasets.

Laser range profiling for small target recognition

NASA Astrophysics Data System (ADS)

Steinvall, Ove; Tulldahl, Michael

2016-05-01

The detection and classification of small surface and airborne targets at long ranges is a growing need for naval security. Long range ID or ID at closer range of small targets has its limitations in imaging due to the demand on very high transverse sensor resolution. It is therefore motivated to look for 1D laser techniques for target ID. These include vibrometry, and laser range profiling. Vibrometry can give good results but is also sensitive to certain vibrating parts on the target being in the field of view. Laser range profiling is attractive because the maximum range can be substantial, especially for a small laser beam width. A range profiler can also be used in a scanning mode to detect targets within a certain sector. The same laser can also be used for active imaging when the target comes closer and is angular resolved. The present paper will show both experimental and simulated results for laser range profiling of small boats out to 6-7 km range and a UAV mockup at close range (1.3 km). We obtained good results with the profiling system both for target detection and recognition. Comparison of experimental and simulated range waveforms based on CAD models of the target support the idea of having a profiling system as a first recognition sensor and thus narrowing the search space for the automatic target recognition based on imaging at close ranges. The naval experiments took place in the Baltic Sea with many other active and passive EO sensors beside the profiling system. Discussion of data fusion between laser profiling and imaging systems will be given. The UAV experiments were made from the rooftop laboratory at FOI.

Magnetic nanoparticles for targeted therapeutic gene delivery and magnetic-inducing heating on hepatoma

NASA Astrophysics Data System (ADS)

Yuan, Chenyan; An, Yanli; Zhang, Jia; Li, Hongbo; Zhang, Hao; Wang, Ling; Zhang, Dongsheng

2014-08-01

Gene therapy holds great promise for treating cancers, but their clinical applications are being hampered due to uncontrolled gene delivery and expression. To develop a targeted, safe and efficient tumor therapy system, we constructed a tissue-specific suicide gene delivery system by using magnetic nanoparticles (MNPs) as carriers for the combination of gene therapy and hyperthermia on hepatoma. The suicide gene was hepatoma-targeted and hypoxia-enhanced, and the MNPs possessed the ability to elevate temperature to the effective range for tumor hyperthermia as imposed on an alternating magnetic field (AMF). The tumoricidal effects of targeted gene therapy associated with hyperthermia were evaluated in vitro and in vivo. The experiment demonstrated that hyperthermia combined with a targeted gene therapy system proffer an effective tool for tumor therapy with high selectivity and the synergistic effect of hepatoma suppression.

Cantilevered probe detector with piezoelectric element

DOEpatents

Adams, Jesse D; Sulchek, Todd A; Feigin, Stuart C

2014-04-29

A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

Cantilevered probe detector with piezoelectric element

DOEpatents

Adams, Jesse D; Sulchek, Todd A; Feigin, Stuart C

2013-04-30

A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

Cantilevered probe detector with piezoelectric element

DOEpatents

Adams, Jesse D [Reno, NV; Sulchek, Todd A [Oakland, CA; Feigin, Stuart C [Reno, NV

2012-07-10

A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

Cantilevered probe detector with piezoelectric element

DOEpatents

Adams, Jesse D.; Sulchek, Todd A.; Feigin, Stuart C.

2010-04-06

A disclosed chemical detection system for detecting a target material, such as an explosive material, can include a cantilevered probe, a probe heater coupled to the cantilevered probe, and a piezoelectric element disposed on the cantilevered probe. The piezoelectric element can be configured as a detector and/or an actuator. Detection can include, for example, detecting a movement of the cantilevered probe or a property of the cantilevered probe. The movement or a change in the property of the cantilevered probe can occur, for example, by adsorption of the target material, desorption of the target material, reaction of the target material and/or phase change of the target material. Examples of detectable movements and properties include temperature shifts, impedance shifts, and resonant frequency shifts of the cantilevered probe. The overall chemical detection system can be incorporated, for example, into a handheld explosive material detection system.

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.

Monitoring System for the Gold Target by Radiation Detectors in Hadron Experimental Facility at J-PARC

NASA Astrophysics Data System (ADS)

Muto, Ryotaro; Agari, Keizo; Aoki, Kazuya; Bessho, Kotaro; Hagiwara, Masayuki; Hirose, Erina; Ieiri, Masaharu; Iwasaki, Ruri; Katoh, Yohji; Kitagawa, Jun-ichi; Minakawa, Michifumi; Morino, Yuhei; Saito, Kiwamu; Sato, Yoshinori; Sawada, Shin'ya; Shirakabe, Yoshihisa; Suzuki, Yoshihiro; Takahashi, Hitoshi; Tanaka, Kazuhiro; Toyoda, Akihisa; Watanabe, Hiroaki; Yamanoi, Yutaka

2017-09-01

At the Hadron Experimental Facility in J-PARC, we inject a 30-GeV proton beam into a gold target to produce secondary particle beams required for various particle and nuclear physics experiments. The gold target is placed in a hermetic chamber, and helium gas is circulated in the chamber to monitor the soundness of the target. The radioactivity in helium gas is continuously monitored by gamma-ray detectors such as a germanium detector and a NaI(Tl) detector. Beam operations with those target-monitoring systems were successfully performed from April to June and October to December 2015, and from May to June 2016. In this paper, the details of the helium gas circulation system and gamma-ray detectors and the analysis results of the obtained gamma-ray spectra are reported.

Tracking target objects orbiting earth using satellite-based telescopes

DOEpatents

De Vries, Willem H; Olivier, Scot S; Pertica, Alexander J

2014-10-14

A system for tracking objects that are in earth orbit via a constellation or network of satellites having imaging devices is provided. An object tracking system includes a ground controller and, for each satellite in the constellation, an onboard controller. The ground controller receives ephemeris information for a target object and directs that ephemeris information be transmitted to the satellites. Each onboard controller receives ephemeris information for a target object, collects images of the target object based on the expected location of the target object at an expected time, identifies actual locations of the target object from the collected images, and identifies a next expected location at a next expected time based on the identified actual locations of the target object. The onboard controller processes the collected image to identify the actual location of the target object and transmits the actual location information to the ground controller.

An innovative pre-targeting strategy for tumor cell specific imaging and therapy.

PubMed

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-09-21

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the "biotin-avidin" interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.

Single-Molecule View of Small RNA-Guided Target Search and Recognition.

PubMed

Globyte, Viktorija; Kim, Sung Hyun; Joo, Chirlmin

2018-05-20

Most everyday processes in life involve a necessity for an entity to locate its target. On a cellular level, many proteins have to find their target to perform their function. From gene-expression regulation to DNA repair to host defense, numerous nucleic acid-interacting proteins use distinct target search mechanisms. Several proteins achieve that with the help of short RNA strands known as guides. This review focuses on single-molecule advances studying the target search and recognition mechanism of Argonaute and CRISPR (clustered regularly interspaced short palindromic repeats) systems. We discuss different steps involved in search and recognition, from the initial complex prearrangement into the target-search competent state to the final proofreading steps. We focus on target search mechanisms that range from weak interactions, to one- and three-dimensional diffusion, to conformational proofreading. We compare the mechanisms of Argonaute and CRISPR with a well-studied target search system, RecA.

Design and engineering of a target for x-ray Thomson scattering measurements on matter at extreme densities and gigabar pressures

DOE PAGES

Boehm, K. -J.; Hash, N.; Barker, D.; ...

2016-06-24

Reconciling the experimental and system requirements during the development of a new target system is one of the most challenging tasks in the design and engineering of targets used in the National Ignition Facility. Targets for the GigaBar 3 campaign were meant to allow the detection of extremely weak Thomson scattering from matter at extreme densities in the face of very bright backlighter and laser entry hole plasma emissions. The problem was to shield the detector sufficiently while maintaining beamline and view clearances, and observing target mass restrictions. A new construction process, based on a rapid prototype frame structure, wasmore » used to develop this target. As a result, details of the design process for these targets are described, and lessons from this development for production and target assembly teams are discussed.« less

Image reconstruction of dynamic infrared single-pixel imaging system

NASA Astrophysics Data System (ADS)

Tong, Qi; Jiang, Yilin; Wang, Haiyan; Guo, Limin

2018-03-01

Single-pixel imaging technique has recently received much attention. Most of the current single-pixel imaging is aimed at relatively static targets or the imaging system is fixed, which is limited by the number of measurements received through the single detector. In this paper, we proposed a novel dynamic compressive imaging method to solve the imaging problem, where exists imaging system motion behavior, for the infrared (IR) rosette scanning system. The relationship between adjacent target images and scene is analyzed under different system movement scenarios. These relationships are used to build dynamic compressive imaging models. Simulation results demonstrate that the proposed method can improve the reconstruction quality of IR image and enhance the contrast between the target and the background in the presence of system movement.

Experimental evaluation of the performance of pulsed two-color laser-ranging systems

NASA Technical Reports Server (NTRS)

Im, Kwaifong E.; Gardner, Chester S.; Abshire, James B.; Mcgarry, Jan F.

1987-01-01

Two-color laser-ranging systems can be used to estimate the atmospheric delay by measuring the difference in propagation times between two optical pulses transmitted at different wavelengths. This paper describes horizontal-path ranging experiments that were conducted using flat diffuse targets and cube-corner reflector arrays. Measurements of the timing accuracy of the cross-correlation estimator, atmospheric delay, received pulse shapes, and signal power spectra are presented. The results are in general agreement with theory and indicate that target speckle can be the dominant noise source when the target is small and is located far from the ranging system or when the target consists of a small number of cube-corner reflectors.

Excluded Facility Financial Status and Options for Payment System Modification

PubMed Central

Schneider, John E.; Cromwell, Jerry; McGuire, Thomas P.

1993-01-01

Psychiatric, rehabilitation, long-term care, and children's facilities have remained under the reimbursement system established under the Tax Equity and Fiscal Responsibility Act (TEFRA) of 1982 (Public Law 97-248). The number of TEFRA facilities and discharges has been increasing while their average profit rates have been steadily declining. Modifying TEFRA would require either rebasing the target amount or adjusting cost sharing for facilities exceeding their cost target. Based on our simulations of alternative payment systems, we recommend rebasing facilities' target amounts using a 50/50 blend of own costs and national average costs. Cost sharing above the target amount could be increased to include more government sharing of losses. PMID:10135345

An Improved Vision-based Algorithm for Unmanned Aerial Vehicles Autonomous Landing

NASA Astrophysics Data System (ADS)

Zhao, Yunji; Pei, Hailong

In vision-based autonomous landing system of UAV, the efficiency of target detecting and tracking will directly affect the control system. The improved algorithm of SURF(Speed Up Robust Features) will resolve the problem which is the inefficiency of the SURF algorithm in the autonomous landing system. The improved algorithm is composed of three steps: first, detect the region of the target using the Camshift; second, detect the feature points in the region of the above acquired using the SURF algorithm; third, do the matching between the template target and the region of target in frame. The results of experiment and theoretical analysis testify the efficiency of the algorithm.

Quantitative and Systems Pharmacology. 1. In Silico Prediction of Drug-Target Interactions of Natural Products Enables New Targeted Cancer Therapy.

PubMed

Fang, Jiansong; Wu, Zengrui; Cai, Chuipu; Wang, Qi; Tang, Yun; Cheng, Feixiong

2017-11-27

Natural products with diverse chemical scaffolds have been recognized as an invaluable source of compounds in drug discovery and development. However, systematic identification of drug targets for natural products at the human proteome level via various experimental assays is highly expensive and time-consuming. In this study, we proposed a systems pharmacology infrastructure to predict new drug targets and anticancer indications of natural products. Specifically, we reconstructed a global drug-target network with 7,314 interactions connecting 751 targets and 2,388 natural products and built predictive network models via a balanced substructure-drug-target network-based inference approach. A high area under receiver operating characteristic curve of 0.96 was yielded for predicting new targets of natural products during cross-validation. The newly predicted targets of natural products (e.g., resveratrol, genistein, and kaempferol) with high scores were validated by various literature studies. We further built the statistical network models for identification of new anticancer indications of natural products through integration of both experimentally validated and computationally predicted drug-target interactions of natural products with known cancer proteins. We showed that the significantly predicted anticancer indications of multiple natural products (e.g., naringenin, disulfiram, and metformin) with new mechanism-of-action were validated by various published experimental evidence. In summary, this study offers powerful computational systems pharmacology approaches and tools for the development of novel targeted cancer therapies by exploiting the polypharmacology of natural products.

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.

Active tensor magnetic gradiometer system final report for Project MM–1514

USGS Publications Warehouse

Smith, David V.; Phillips, Jeffrey D.; Hutton, S. Raymond

2014-01-01

An interactive computer simulation program, based on physical models of system sensors, platform geometry, Earth environment, and spheroidal magnetically-permeable targets, was developed to generate synthetic magnetic field data from a conceptual tensor magnetic gradiometer system equipped with an active primary field generator. The system sensors emulate the prototype tensor magnetic gradiometer system (TMGS) developed under a separate contract for unexploded ordnance (UXO) detection and classification. Time-series data from different simulation scenarios were analyzed to recover physical dimensions of the target source. Helbig-Euler simulations were run with rectangular and rod-like source bodies to determine whether such a system could separate the induced component of the magnetization from the remanent component for each target. This report concludes with an engineering assessment of a practical system design.

Development of three-dimensional tracking system using astigmatic lens method for microscopes

NASA Astrophysics Data System (ADS)

Kibata, Hiroki; Ishii, Katsuhiro

2017-07-01

We have developed a three-dimensional tracking system for microscopes. Using the astigmatic lens method and a CMOS image sensor, we realize a rapid detection of a target position in a wide range. We demonstrate a target tracking using the developed system.

Feasibility Test of a Pulse Modulated Pressurization System for a High Altitude Supersonic Target Vehicle Propulsion System.

DTIC Science & Technology

1976-11-01

pressure switch . The system was tested for stability of operation and accuracy of pressure control, using a High Altitude Supersonic Target (HAST...stable and accurate to approximately the deadband of the pressure switch used, 2 psi. (Author)

A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

PubMed

Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

2018-01-19

The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes). Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng . In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the practical strategic utility of TCOA to incorporate prior drug information into potential drug-target forecasts. Thus applicably, our method paves a novel and efficient way to identify the drug targets for leading the phenotype transitions of underlying biological networks.

Laser-Directed Ranging System Implementing Single Camera System for Telerobotics Applications

NASA Technical Reports Server (NTRS)

Wells, Dennis L. (Inventor); Li, Larry C. (Inventor); Cox, Brian J. (Inventor)

1995-01-01

The invention relates generally to systems for determining the range of an object from a reference point and, in one embodiment, to laser-directed ranging systems useful in telerobotics applications. Digital processing techniques are employed which minimize the complexity and cost of the hardware and software for processing range calculations, thereby enhancing the commercial attractiveness of the system for use in relatively low-cost robotic systems. The system includes a video camera for generating images of the target, image digitizing circuitry, and an associated frame grabber circuit. The circuit first captures one of the pairs of stereo video images of the target, and then captures a second video image of the target as it is partly illuminated by the light beam, suitably generated by a laser. The two video images, taken sufficiently close together in time to minimize camera and scene motion, are converted to digital images and then compared. Common pixels are eliminated, leaving only a digital image of the laser-illuminated spot on the target. Mw centroid of the laser illuminated spot is dm obtained and compared with a predetermined reference point, predetermined by design or calibration, which represents the coordinate at the focal plane of the laser illumination at infinite range. Preferably, the laser and camera are mounted on a servo-driven platform which can be oriented to direct the camera and the laser toward the target. In one embodiment the platform is positioned in response to movement of the operator's head. Position and orientation sensors are used to monitor head movement. The disparity between the digital image of the laser spot and the reference point is calculated for determining range to the target. Commercial applications for the system relate to active range-determination systems, such as those used with robotic systems in which it is necessary to determine the, range to a workpiece or object to be grasped or acted upon by a robot arm end-effector in response to commands generated by an operator. In one embodiment, the system provides a real-time image of the target for the operator as the robot approaches the object. The system is also adapted for use in virtual reality systems in which a remote object or workpiece is to be acted upon by a remote robot arm or other mechanism controlled by an operator.

To be targeted: is the magic bullet concept a viable option for synthetic nucleic acid therapeutics?

PubMed

Ogris, Manfred; Wagner, Ernst

2011-07-01

Nucleic acids offer the possibility of tailor-made, individualized treatments for genetic disorders, infectious diseases, and cancer. As an alternative to viral vectors, synthetic delivery systems have a potentially improved safety profile, but often lack sufficient efficiency especially when applied in vivo. Receptor targeting of synthetic vectors can improve the specificity of the vector and increase the efficiency of nucleic acid delivery to the target site. This review covers recent concepts for targeted DNA and RNA delivery to organs like liver and lung, and also to solid cancers. Syntheses and applications of delivery systems targeted with proteins, peptides, and small molecules as ligands coupled to polymeric or lipidic nucleic acid carriers are reviewed. Therapeutic concepts for treatment of genetic and infectious diseases are explained. Systemic treatment regimens of metastasized malignancies in combination with chemotherapy and radiation have already been successfully applied in preclinical studies. In addition, a first clinical study in the human application of a targeted synthetic carrier has been performed.

Improving Robotic Assembly of Planar High Energy Density Targets

NASA Astrophysics Data System (ADS)

Dudt, D.; Carlson, L.; Alexander, N.; Boehm, K.

2016-10-01

Increased quantities of planar assemblies for high energy density targets are needed with higher shot rates being implemented at facilities such as the National Ignition Facility and the Matter in Extreme Conditions station of the Linac Coherent Light Source. To meet this growing demand, robotics are used to reduce assembly time. This project studies how machine vision and force feedback systems can be used to improve the quantity and quality of planar target assemblies. Vision-guided robotics can identify and locate parts, reducing laborious manual loading of parts into precision pallets and associated teaching of locations. On-board automated inspection can measure part pickup offsets to correct part drop-off placement into target assemblies. Force feedback systems can detect pickup locations and apply consistent force to produce more uniform glue bond thickness, thus improving the performance of the targets. System designs and performance evaluations will be presented. Work supported in part by the US DOE under the Science Undergraduate Laboratory Internships Program (SULI) and ICF Target Fabrication DE-NA0001808.

Department of Defense Chemical and Biological Defense Program. FY2004-2006 Performance Plan

DTIC Science & Technology

2005-03-01

Agents (NTAs) Compare the direct effects of PAF on smooth muscle, hematic constituents, and lung to determine role in toxicity. Continue to identify...Range Biometric Target ID System Explore technologies for a long range biometric target identification system. Air Containment Monitoring System...Continue development of systems for contained air monitoring for chemical agents.Long Range Biometric Air Containment Monitoring System Continued

A versatile targeting system with lentiviral vectors bearing the biotin-adaptor peptide

PubMed Central

Morizono, Kouki; Xie, Yiming; Helguera, Gustavo; Daniels, Tracy R.; Lane, Timothy F.; Penichet, Manuel L.; Chen, Irvin S. Y.

2010-01-01

Background Targeted gene transduction in vivo is the ultimate preferred method for gene delivery. We previously developed targeting lentiviral vectors that specifically recognize cell surface molecules with conjugated antibodies and mediate targeted gene transduction both in vitro and in vivo. Although effective in some experimental settings, the conjugation of virus with antibodies is mediated by the interaction between protein A and the Fc region of antibodies, which is not as stable as covalent conjugation. We have now developed a more stable conjugation strategy utilizing the interaction between avidin and biotin. Methods We inserted the biotin-adaptor-peptide, which was biotinylated by secretory biotin ligase at specific sites, into our targeting envelope proteins, enabling conjugation of the pseudotyped virus with avidin, streptavidin or neutravidin. Results When conjugated with avidin-antibody fusion proteins or the complex of avidin and biotinylated targeting molecules, the vectors could mediate specific transduction to targeted cells recognized by the targeting molecules. When conjugated with streptavidin-coated magnetic beads, transduction by the vectors was targeted to the locations of magnets. Conclusions This targeting vector system can be used for broad applications of targeted gene transduction using biotinylated targeting molecules or targeting molecules fused with avidin. PMID:19455593

Fibrin-binding, peptide amphiphile micelles for targeting glioblastoma☆

PubMed Central

Chung, Eun Ji; Cheng, Yu; Morshed, Ramin; Nord, Kathryn; Han, Yu; Wegscheid, Michelle L.; Auffinger, Brenda; Wainwright, Derek A.; Lesniak, Maciej S.; Tirrell, Matthew V.

2013-01-01

Glioblastoma-targeted drug delivery systems facilitate efficient delivery of chemotherapeutic agents to malignant gliomas, while minimizing systemic toxicity and side effects. Taking advantage of the fibrin deposition that is characteristic of tumors, we constructed spherical, Cy7-labeled, targeting micelles to glioblastoma through the addition of the fibrin-binding pentapeptide, cysteine–arginine–glutamic acid–lysine–alanine, or CREKA. Conjugation of the CREKA peptide to Cy7-micelles increased the average particle size and zeta potential. Upon intravenous administration to GL261 glioma bearing mice, Cy7-micelles passively accumulated at the brain tumor site via the enhanced permeability and retention (EPR) effect, and Cy7-CREKA-micelles displayed enhanced tumor homing via active targeting as early as 1 h after administration, as confirmed via in vivo and ex vivo imaging and immunohistochemistry. Biodistribution of micelles showed an accumulation within the liver and kidneys, leading to micelle elimination via renal clearance and the reticuloendothelial system (RES). Histological evaluation showed no signs of cytotoxicity or tissue damage, confirming the safety and utility of this nanoparticle system for delivery to glioblastoma. Our findings offer strong evidence for the glioblastoma-targeting potential of CREKA-micelles and provide the foundation for CREKA-mediated, targeted therapy of glioma. PMID:24211079

Steering a virtual blowfly: simulation of visual pursuit.

PubMed

Boeddeker, Norbert; Egelhaaf, Martin

2003-09-22

The behavioural repertoire of male flies includes visually guided chasing after moving targets. The visuomotor control system for these pursuits belongs to the fastest found in the animal kingdom. We simulated a virtual fly, to test whether or not experimentally established hypotheses on the underlying control system are sufficient to explain chasing behaviour. Two operating instructions for steering the chasing virtual fly were derived from behavioural experiments: (i) the retinal size of the target controls the fly's forward speed and, thus, indirectly its distance to the target; and (ii) a smooth pursuit system uses the retinal position of the target to regulate the fly's flight direction. Low-pass filters implement neuronal processing time. Treating the virtual fly as a point mass, its kinematics are modelled in consideration of the effects of translatory inertia and air friction. Despite its simplicity, the model shows behaviour similar to that of real flies. Depending on its starting position and orientation as well as on target size and speed, the virtual fly either catches the target or follows it indefinitely without capture. These two behavioural modes of the virtual fly emerge from the control system for flight steering without implementation of an explicit decision maker.

MAGID-II: a next-generation magnetic unattended ground sensor (UGS)

NASA Astrophysics Data System (ADS)

Walter, Paul A.; Mauriello, Fred; Huber, Philip

2012-06-01

A next generation magnetic sensor is being developed at L-3 Communications, Communication Systems East to enhance the ability of Army and Marine Corps unattended ground sensor (UGS) systems to detect and track targets on the battlefield. This paper describes a magnetic sensor that provides superior detection range for both armed personnel and vehicle targets, at a reduced size, weight, and level of power consumption (SWAP) over currently available magnetic sensors. The design integrates the proven technology of a flux gate magnetometer combined with advanced digital signal processing algorithms to provide the warfighter with a rapidly deployable, extremely low false-alarm-rate sensor. This new sensor improves on currently available magnetic UGS systems by providing not only target detection and direction information, but also a magnetic disturbance readout, indicating the size of the target. The sensor integrates with Government Off-the-Shelf (GOTS) systems such as the United States Army's Battlefield Anti-Intrusion System (BAIS) and the United States Marine Corps Tactical Remote Sensor System (TRSS). The system has undergone testing by the US Marine Corps, as well as extensive company testing. Results from these field tests are given.

Research on key technologies of LADAR echo signal simulator

NASA Astrophysics Data System (ADS)

Xu, Rui; Shi, Rui; Ye, Jiansen; Wang, Xin; Li, Zhuo

2015-10-01

LADAR echo signal simulator is one of the most significant components of hardware-in-the-loop (HWIL) simulation systems for LADAR, which is designed to simulate the LADAR return signal in laboratory conditions. The device can provide the laser echo signal of target and background for imaging LADAR systems to test whether it is of good performance. Some key technologies are investigated in this paper. Firstly, the 3D model of typical target is built, and transformed to the data of the target echo signal based on ranging equation and targets reflection characteristics. Then, system model and time series model of LADAR echo signal simulator are established. Some influential factors which could induce fixed delay error and random delay error on the simulated return signals are analyzed. In the simulation system, the signal propagating delay of circuits and the response time of pulsed lasers are belong to fixed delay error. The counting error of digital delay generator, the jitter of system clock and the desynchronized between trigger signal and clock signal are a part of random delay error. Furthermore, these system insertion delays are analyzed quantitatively, and the noisy data are obtained. The target echo signals are got by superimposing of the noisy data and the pure target echo signal. In order to overcome these disadvantageous factors, a method of adjusting the timing diagram of the simulation system is proposed. Finally, the simulated echo signals are processed by using a detection algorithm to complete the 3D model reconstruction of object. The simulation results reveal that the range resolution can be better than 8 cm.

[Drug delivery systems using nano-sized drug carriers].

PubMed

Nakayama, Masamichi; Okano, Teruo

2005-07-01

Nanotechnology has attracted great attention all over the world in recent several years and has led to the establishment of the novel technical field of "nanomedicine" through collaboration with advanced medical technology. Particularly, site-specific drug targeting using particle drug carrier systems has made substantial progress and been actively developed. This review explains the essential factors (size and chemical character) of drug carriers to allow long circulation in the bloodstream avoiding the reticuloendothelial system, and shows the present status and future perspective of several types of nano-carrier systems (water-soluble polymer, liposome and polymeric micelle). We also introduce the novel concept of multi-targeting system (combination of two or more targeting methodologies) for ideal drug therapies.

Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

PubMed Central

Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

2016-01-01

Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

Dendritic cell targeted chitosan nanoparticles for nasal DNA immunization against SARS CoV nucleocapsid protein.

PubMed

Raghuwanshi, Dharmendra; Mishra, Vivek; Das, Dipankar; Kaur, Kamaljit; Suresh, Mavanur R

2012-04-02

This work investigates the formulation and in vivo efficacy of dendritic cell (DC) targeted plasmid DNA loaded biotinylated chitosan nanoparticles for nasal immunization against nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus (SARS-CoV) as antigen. The induction of antigen-specific mucosal and systemic immune response at the site of virus entry is a major challenge for vaccine design. Here, we designed a strategy for noninvasive receptor mediated gene delivery to nasal resident DCs. The pDNA loaded biotinylated chitosan nanoparticles were prepared using a complex coacervation process and characterized for size, shape, surface charge, plasmid DNA loading and protection against nuclease digestion. The pDNA loaded biotinylated chitosan nanoparticles were targeted with bifunctional fusion protein (bfFp) vector for achieving DC selective targeting. The bfFp is a recombinant fusion protein consisting of truncated core-streptavidin fused with anti-DEC-205 single chain antibody (scFv). The core-streptavidin arm of fusion protein binds with biotinylated nanoparticles, while anti-DEC-205 scFv imparts targeting specificity to DC DEC-205 receptor. We demonstrate that intranasal administration of bfFp targeted formulations along with anti-CD40 DC maturation stimuli enhanced magnitude of mucosal IgA as well as systemic IgG against N protein. The strategy led to the detection of augmented levels of N protein specific systemic IgG and nasal IgA antibodies. However, following intranasal delivery of naked pDNA no mucosal and systemic immune responses were detected. A parallel comparison of targeted formulations using intramuscular and intranasal routes showed that the intramuscular route is superior for induction of systemic IgG responses compared with the intranasal route. Our results suggest that targeted pDNA delivery through a noninvasive intranasal route can be a strategy for designing low-dose vaccines.

ManPortable and UGV LIVAR: advances in sensor suite integration bring improvements to target observation and identification for the electronic battlefield

NASA Astrophysics Data System (ADS)

Lynam, Jeff R.

2001-09-01

A more highly integrated, electro-optical sensor suite using Laser Illuminated Viewing and Ranging (LIVAR) techniques is being developed under the Army Advanced Concept Technology- II (ACT-II) program for enhanced manportable target surveillance and identification. The ManPortable LIVAR system currently in development employs a wide-array of sensor technologies that provides the foot-bound soldier and UGV significant advantages and capabilities in lightweight, fieldable, target location, ranging and imaging systems. The unit incorporates a wide field-of-view, 5DEG x 3DEG, uncooled LWIR passive sensor for primary target location. Laser range finding and active illumination is done with a triggered, flash-lamp pumped, eyesafe micro-laser operating in the 1.5 micron region, and is used in conjunction with a range-gated, electron-bombarded CCD digital camera to then image the target objective in a more- narrow, 0.3$DEG, field-of-view. Target range determination is acquired using the integrated LRF and a target position is calculated using data from other onboard devices providing GPS coordinates, tilt, bank and corrected magnetic azimuth. Range gate timing and coordinated receiver optics focus control allow for target imaging operations to be optimized. The onboard control electronics provide power efficient, system operations for extended field use periods from the internal, rechargeable battery packs. Image data storage, transmission, and processing performance capabilities are also being incorporated to provide the best all-around support, for the electronic battlefield, in this type of system. The paper will describe flash laser illumination technology, EBCCD camera technology with flash laser detection system, and image resolution improvement through frame averaging.

STS-1 operational flight profile. Volume 5: Descent, cycle 3. Appendix C: Monte Carlo dispersion analysis

NASA Technical Reports Server (NTRS)

1980-01-01

The results of three nonlinear the Monte Carlo dispersion analyses for the Space Transportation System 1 Flight (STS-1) Orbiter Descent Operational Flight Profile, Cycle 3 are presented. Fifty randomly selected simulation for the end of mission (EOM) descent, the abort once around (AOA) descent targeted line are steep target line, and the AOA descent targeted to the shallow target line are analyzed. These analyses compare the flight environment with system and operational constraints on the flight environment and in some cases use simplified system models as an aid in assessing the STS-1 descent flight profile. In addition, descent flight envelops are provided as a data base for use by system specialists to determine the flight readiness for STS-1. The results of these dispersion analyses supersede results of the dispersion analysis previously documented.

Developing a Telescope Simulator Towards a Global Autonomous Robotic Telescope Network

NASA Astrophysics Data System (ADS)

Giakoumidis, N.; Ioannou, Z.; Dong, H.; Mavridis, N.

2013-05-01

A robotic telescope network is a system that integrates a number of telescopes to observe a variety of astronomical targets without being operated by a human. This system autonomously selects and observes targets in accordance to an optimized target. It dynamically allocates telescope resources depending on the observation requests, specifications of the telescopes, target visibility, meteorological conditions, daylight, location restrictions and availability and many other factors. In this paper, we introduce a telescope simulator, which can control a telescope to a desired position in order to observe a specific object. The system includes a Client Module, a Server Module, and a Dynamic Scheduler module. We make use and integrate a number of open source software to simulate the movement of a robotic telescope, the telescope characteristics, the observational data and weather conditions in order to test and optimize our system.

Radiation effects in IFMIF Li target diagnostic systems

NASA Astrophysics Data System (ADS)

Molla, J.; Vila, R.; Shikama, T.; Horiike, H.; Simakov, S.; Ciotti, M.; Ibarra, A.

2009-04-01

Diagnostics for the lithium target will be crucial for the operation of IFMIF. Several parameters as the lithium temperature, target thickness or wave pattern must be monitored during operation. Radiation effects may produce malfunctioning in any of these diagnostics due to the exposure to high radiation fields. The main diagnostic systems proposed for the operation of IFMIF are reviewed in this paper from the point of view of radiation damage. The main tools for the assessment of the performance of these diagnostics are the neutronics calculations by using specialised codes and the information accumulated during the last decades on the radiation effects in functional materials, components and diagnostics for ITER. This analysis allows to conclude that the design of some of the diagnostic systems must be revised to assure the high availability required for the target system.

Analysis of A Drug Target-based Classification System using Molecular Descriptors.

PubMed

Lu, Jing; Zhang, Pin; Bi, Yi; Luo, Xiaomin

2016-01-01

Drug-target interaction is an important topic in drug discovery and drug repositioning. KEGG database offers a drug annotation and classification using a target-based classification system. In this study, we gave an investigation on five target-based classes: (I) G protein-coupled receptors; (II) Nuclear receptors; (III) Ion channels; (IV) Enzymes; (V) Pathogens, using molecular descriptors to represent each drug compound. Two popular feature selection methods, maximum relevance minimum redundancy and incremental feature selection, were adopted to extract the important descriptors. Meanwhile, an optimal prediction model based on nearest neighbor algorithm was constructed, which got the best result in identifying drug target-based classes. Finally, some key descriptors were discussed to uncover their important roles in the identification of drug-target classes.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Chapman, J.; Fincher, S.; Philips, A.; Polsgrove, T.

2003-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Basic operation of an MTF propulsion system is introduced. Structural, thermal, radiation-management and electrical design details are presented. The propellant storage and supply system design is also presented. A propulsion system mass estimate and associated performance figures are given. The advantages of helium-3 as a fusion fuel for an advanced MTF system are discussed.

BODY SENSING SYSTEM

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor)

2005-01-01

System and method for performing one or more relevant measurements at a target site in an animal body, using a probe. One or more of a group of selected internal measurements is performed at the target site, is optionally combined with one or more selected external measurements, and is optionally combined with one or more selected heuristic information items, in order to reduce to a relatively small number the probable medical conditions associated with the target site. One or more of the internal measurements is optionally used to navigate the probe to the target site. Neural net information processing is performed to provide a reduced set of probable medical conditions associated with the target site.

Laser driven ion accelerator

DOEpatents

Tajima, Toshiki

2006-04-18

A system and method of accelerating ions in an accelerator to optimize the energy produced by a light source. Several parameters may be controlled in constructing a target used in the accelerator system to adjust performance of the accelerator system. These parameters include the material, thickness, geometry and surface of the target.

Computational design of high efficiency release targets for use at ISOL facilities

NASA Astrophysics Data System (ADS)

Liu, Y.; Alton, G. D.; Middleton, J. W.

1999-06-01

This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated vitreous carbon fiber (RVCF) or carbon-bonded-carbon-fiber (CBCF) to form highly permeable composite target matrices. Computational studies which simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected targets and thermal analyses of temperature distributions within a prototype target/heat-sink system subjected to primary ion beam irradiation will be presented in this report.

High-efficiency-release targets for use at ISOL facilities: computational design

NASA Astrophysics Data System (ADS)

Liu, Y.; Alton, G. D.

1999-12-01

This report describes efforts made at the Oak Ridge National Laboratory to design high-efficiency-release targets that simultaneously incorporate the short diffusion lengths, high permeabilities, controllable temperatures, and heat-removal properties required for the generation of useful radioactive ion beam (RIB) intensities for nuclear physics and astrophysics research using the isotope separation on-line (ISOL) technique. Short diffusion lengths are achieved either by using thin fibrous target materials or by coating thin layers of selected target material onto low-density carbon fibers such as reticulated-vitreous-carbon fiber (RVCF) or carbon-bonded-carbon fiber (CBCF) to form highly permeable composite target matrices. Computational studies that simulate the generation and removal of primary beam deposited heat from target materials have been conducted to optimize the design of target/heat-sink systems for generating RIBs. The results derived from diffusion release-rate simulation studies for selected targets and thermal analyses of temperature distributions within a prototype target/heat-sink system subjected to primary ion beam irradiation are presented in this report.

Advanced surface-enhanced Raman gene probe systems and methods thereof

DOEpatents

Vo-Dinh, Tuan

2001-01-01

The subject invention is a series of methods and systems for using the Surface-Enhanced Raman (SER)-labeled Gene Probe for hybridization, detection and identification of SER-labeled hybridized target oligonucleotide material comprising the steps of immobilizing SER-labeled hybridized target oligonucleotide material on a support means, wherein the SER-labeled hybridized target oligonucleotide material comprise a SER label attached either to a target oligonucleotide of unknown sequence or to a gene probe of known sequence complementary to the target oligonucleotide sequence, the SER label is unique for the target oligonucleotide strands of a particular sequence wherein the SER-labeled oligonucleotide is hybridized to its complementary oligonucleotide strand, then the support means having the SER-labeled hybridized target oligonucleotide material adsorbed thereon is SERS activated with a SERS activating means, then the support means is analyzed.

Off-target Effects in CRISPR/Cas9-mediated Genome Engineering

PubMed Central

Zhang, Xiao-Hui; Tee, Louis Y; Wang, Xiao-Gang; Huang, Qun-Shan; Yang, Shi-Hua

2015-01-01

CRISPR/Cas9 is a versatile genome-editing technology that is widely used for studying the functionality of genetic elements, creating genetically modified organisms as well as preclinical research of genetic disorders. However, the high frequency of off-target activity (≥50%)—RGEN (RNA-guided endonuclease)-induced mutations at sites other than the intended on-target site—is one major concern, especially for therapeutic and clinical applications. Here, we review the basic mechanisms underlying off-target cutting in the CRISPR/Cas9 system, methods for detecting off-target mutations, and strategies for minimizing off-target cleavage. The improvement off-target specificity in the CRISPR/Cas9 system will provide solid genotype–phenotype correlations, and thus enable faithful interpretation of genome-editing data, which will certainly facilitate the basic and clinical application of this technology. PMID:26575098

A novel 9 × 9 map-based solvent selection strategy for targeted counter-current chromatography isolation of natural products.

PubMed

Liang, Junling; Meng, Jie; Wu, Dingfang; Guo, Mengzhe; Wu, Shihua

2015-06-26

Counter-current chromatography (CCC) is an efficient liquid-liquid chromatography technique for separation and purification of complex mixtures like natural products extracts and synthetic chemicals. However, CCC is still a challenging process requiring some special technical knowledge especially in the selection of appropriated solvent systems. In this work, we introduced a new 9 × 9 map-based solvent selection strategy for CCC isolation of targets, which permit more than 60 hexane-ethyl acetate-methanol-water (HEMWat) solvent systems as the start candidates for the selection of solvent systems. Among these solvent systems, there are clear linear correlations between partition coefficient (K) and the system numbers. Thus, an appropriate CCC solvent system (i.e., sweet spot for K = 1) may be hit by measurement of k values of the target only in two random solvent systems. Besides this, surprisingly, we found that through two sweet spots, we could get a line ("Sweet line") where there are infinite sweet solvent systems being suitable for CCC separation. In these sweet solvent systems, the target has the same partition coefficient (K) but different solubilities. Thus, the better sweet solvent system with higher sample solubility can be obtained for high capacity CCC preparation. Furthermore, we found that there is a zone ("Sweet zone") where all solvent systems have their own sweet partition coefficients values for the target in range of 0.4 < K< 2.5 or extended range of 0.25 < K < 16. All results were validated by using 14 pure GUESSmix mimic natural products as standards and further confirmed by isolation of several targets including honokiol and magnolol from the extracts of Magnolia officinalis Rehd. Et Wils and tanshinone IIA from Salvia miltiorrhiza Bunge. In practice, it is much easier to get a suitable solvent system only by making a simple screening two to four HEMWat two-phase solvent systems to obtain the sweet line or sweet zone without special knowledge or comprehensive standards as references. This is an important advancement for solvent system selection and also will be very useful for isolation of current natural products including Traditional Chinese Medicines. Copyright © 2015 Elsevier B.V. All rights reserved.

A rail system for circular synthetic aperture sonar imaging and acoustic target strength measurements: design/operation/preliminary results.

PubMed

Kennedy, J L; Marston, T M; Lee, K; Lopes, J L; Lim, R

2014-01-01

A 22 m diameter circular rail, outfitted with a mobile sonar tower trolley, was designed, fabricated, instrumented with underwater acoustic transducers, and assembled on a 1.5 m thick sand layer at the bottom of a large freshwater pool to carry out sonar design and target scattering response studies. The mobile sonar tower translates along the rail via a drive motor controlled by customized LabVIEW software. The rail system is modular and assembly consists of separately deploying eight circular arc sections, measuring a nominal center radius of 11 m and 8.64 m arc length each, and having divers connect them together in the underwater environment. The system enables full scale measurements on targets of interest with 0.1° angular resolution over a complete 360° aperture, without disrupting target setup, and affording a level of control over target environment conditions and noise sources unachievable in standard field measurements. In recent use, the mobile cart carrying an instrumented sonar tower was translated along the rail in 720 equal position increments and acoustic backscatter data were acquired at each position. In addition, this system can accommodate both broadband monostatic and bistatic scattering measurements on targets of interest, allowing capture of target signature phenomena under diverse configurations to address current scientific and technical issues encountered in mine countermeasure and unexploded ordnance applications. In the work discussed here, the circular rail apparatus is used for acoustic backscatter testing, but this system also has the capacity to facilitate the acquisition of magnetic and optical sensor data from targets of interest. A brief description of the system design and operation will be presented along with preliminary processed results for data acquired from acoustic measurements conducted at the Naval Surface Warfare Center, Panama City Division Test Pond Facility. [Work Supported by the U.S. Office of Naval Research and The Strategic Environmental Research and Development Program.].

The application and research of the multi-receiving telescopes technology in laser ranging to space targets

NASA Astrophysics Data System (ADS)

Wu, Zhibo; Zhang, Haifeng; Zhang, Zhongping; Deng, Huarong; Li, Pu; Meng, Wendong; Cheng, Zhien; Shen, Lurun; Tang, Zhenhong

2014-11-01

Laser ranging technology can directly measure the distance between space targets and ground stations with the highest measurement precision and will play an irreplaceable role in orbit check and calibrating microwave measurement system. The precise orbit determination and accurate catalogue of space targets can also be realized by laser ranging with multi-stations. Among space targets, most of ones are inactive targets and space debris, which should be paid the great attentions for the safety of active spacecrafts. Because of laser diffuse reflection from the surface of targets, laser ranging to space debris has the characteristics of wide coverage and weak strength of laser echoes, even though the powerful laser system is applied. In order to increase the receiving ability of laser echoes, the large aperture telescope should be adopted. As well known, some disadvantages for one set of large aperture telescope, technical development difficulty and system running and maintenance complexity, will limit its flexible applications. The multi-receiving telescopes technology in laser ranging to space targets is put forward to realize the equivalent receiving ability produced by one larger aperture telescope by way of using multi-receiving telescopes, with the advantages of flexibility and maintenance. The theoretical analysis of the feasibility and key technologies of multi-receiving telescopes technology in laser ranging to space targets are presented in this paper. The experimental measurement system based on the 60cm SLR system and 1.56m astronomical telescopes with a distance of about 50m is established to provide the platform for researching on the multi-receiving telescopes technology. The laser ranging experiments to satellites equipped with retro-reflectors are successfully performed by using the above experimental system and verify the technical feasibility to increase the ability of echo detection. And the multi-receiving telescopes technology will become a novel effective way to improve the detection ability of laser ranging to space debris.

A rail system for circular synthetic aperture sonar imaging and acoustic target strength measurements: Design/operation/preliminary results

NASA Astrophysics Data System (ADS)

Kennedy, J. L.; Marston, T. M.; Lee, K.; Lopes, J. L.; Lim, R.

2014-01-01

A 22 m diameter circular rail, outfitted with a mobile sonar tower trolley, was designed, fabricated, instrumented with underwater acoustic transducers, and assembled on a 1.5 m thick sand layer at the bottom of a large freshwater pool to carry out sonar design and target scattering response studies. The mobile sonar tower translates along the rail via a drive motor controlled by customized LabVIEW software. The rail system is modular and assembly consists of separately deploying eight circular arc sections, measuring a nominal center radius of 11 m and 8.64 m arc length each, and having divers connect them together in the underwater environment. The system enables full scale measurements on targets of interest with 0.1° angular resolution over a complete 360° aperture, without disrupting target setup, and affording a level of control over target environment conditions and noise sources unachievable in standard field measurements. In recent use, the mobile cart carrying an instrumented sonar tower was translated along the rail in 720 equal position increments and acoustic backscatter data were acquired at each position. In addition, this system can accommodate both broadband monostatic and bistatic scattering measurements on targets of interest, allowing capture of target signature phenomena under diverse configurations to address current scientific and technical issues encountered in mine countermeasure and unexploded ordnance applications. In the work discussed here, the circular rail apparatus is used for acoustic backscatter testing, but this system also has the capacity to facilitate the acquisition of magnetic and optical sensor data from targets of interest. A brief description of the system design and operation will be presented along with preliminary processed results for data acquired from acoustic measurements conducted at the Naval Surface Warfare Center, Panama City Division Test Pond Facility. [Work Supported by the U.S. Office of Naval Research and The Strategic Environmental Research and Development Program.

Analysis on Target Detection and Classification in LTE Based Passive Forward Scattering Radar.

PubMed

Raja Abdullah, Raja Syamsul Azmir; Abdul Aziz, Noor Hafizah; Abdul Rashid, Nur Emileen; Ahmad Salah, Asem; Hashim, Fazirulhisyam

2016-09-29

The passive bistatic radar (PBR) system can utilize the illuminator of opportunity to enhance radar capability. By utilizing the forward scattering technique and procedure into the specific mode of PBR can provide an improvement in target detection and classification. The system is known as passive Forward Scattering Radar (FSR). The passive FSR system can exploit the peculiar advantage of the enhancement in forward scatter radar cross section (FSRCS) for target detection. Thus, the aim of this paper is to show the feasibility of passive FSR for moving target detection and classification by experimental analysis and results. The signal source is coming from the latest technology of 4G Long-Term Evolution (LTE) base station. A detailed explanation on the passive FSR receiver circuit, the detection scheme and the classification algorithm are given. In addition, the proposed passive FSR circuit employs the self-mixing technique at the receiver; hence the synchronization signal from the transmitter is not required. The experimental results confirm the passive FSR system's capability for ground target detection and classification. Furthermore, this paper illustrates the first classification result in the passive FSR system. The great potential in the passive FSR system provides a new research area in passive radar that can be used for diverse remote monitoring applications.

Smart Stylet: The development and use of a bedside external ventricular drain image-guidance system

PubMed Central

Patil, Vaibhav; Gupta, Rajiv; Estépar, Raúl San José; Lacson, Ronilda; Cheung, Arnold; Wong, Judith M.; Popp, A. John; Golby, Alexandra; Ogilvy, Christopher; Vosburgh, Kirby G.

2015-01-01

Background Placement accuracy of ventriculostomy catheters is reported in a wide and variable range. Development of an efficient image-guidance system may improve physician performance and patient safety. Objective We evaluate the prototype of Smart Stylet, a new electromagnetic image-guidance system for use during bedside ventriculostomy. Methods Accuracy of the Smart Stylet system was assessed. System operators were evaluated for their ability to successfully target the ipsilateral frontal horn in a phantom model. Results Target registration error across 15 intracranial targets ranged from 1.3 – 4.6 mm (mean 3.1 mm). Using Smart Stylet guidance, a test operator successfully passed a ventriculostomy catheter to a shifted ipsilateral frontal horn 20/20 (100%) times from the frontal approach in a skull phantom. Without Smart Stylet guidance, the operator was successful 4/10 (40 %) from the right frontal approach and 6/10 (60 %) from the left frontal approach. In a separate experiment, resident operators were successful 2/4 (50%) when targeting the shifted ipsilateral frontal horn with Smart Stylet guidance and 0/4 (0 %) without image-guidance using a skull phantom. Conclusions Smart Stylet may improve the ability to successfully target the ventricles during frontal ventriculostomy. PMID:25662506

[Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum].

PubMed

Sun, Yi-Yi; Ll, Tong-Hui; Tang, Chen-Kang; Zhu, Zi-Ping; Chi, Qun; Hou, Shi-Xiang

2005-06-01

To study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity. BCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system. D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection. The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.

Artificial Virus Delivers CRISPR-Cas9 System for Genome Editing of Cells in Mice.

PubMed

Li, Ling; Song, Linjiang; Liu, Xiaowei; Yang, Xi; Li, Xia; He, Tao; Wang, Ning; Yang, Suleixin; Yu, Chuan; Yin, Tao; Wen, Yanzhu; He, Zhiyao; Wei, Xiawei; Su, Weijun; Wu, Qinjie; Yao, Shaohua; Gong, Changyang; Wei, Yuquan

2017-01-24

CRISPR-Cas9 has emerged as a versatile genome-editing platform. However, due to the large size of the commonly used CRISPR-Cas9 system, its effective delivery has been a challenge and limits its utility for basic research and therapeutic applications. Herein, a multifunctional nucleus-targeting "core-shell" artificial virus (RRPHC) was constructed for the delivery of CRISPR-Cas9 system. The artificial virus could efficiently load with the CRISPR-Cas9 system, accelerate the endosomal escape, and promote the penetration into the nucleus without additional nuclear-localization signal, thus enabling targeted gene disruption. Notably, the artificial virus is more efficient than SuperFect, Lipofectamine 2000, and Lipofectamine 3000. When loaded with a CRISPR-Cas9 plasmid, it induced higher targeted gene disruption efficacy than that of Lipofectamine 3000. Furthermore, the artificial virus effectively targets the ovarian cancer via dual-receptor-mediated endocytosis and had minimum side effects. When loaded with the Cas9-hMTH1 system targeting MTH1 gene, RRPHC showed effective disruption of MTH1 in vivo. This strategy could be adapted for delivering CRISPR-Cas9 plasmid or other functional nucleic acids in vivo.

Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

PubMed

Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

2015-11-01

Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Intelligent person identification system using stereo camera-based height and stride estimation

NASA Astrophysics Data System (ADS)

Ko, Jung-Hwan; Jang, Jae-Hun; Kim, Eun-Soo

2005-05-01

In this paper, a stereo camera-based intelligent person identification system is suggested. In the proposed method, face area of the moving target person is extracted from the left image of the input steros image pair by using a threshold value of YCbCr color model and by carrying out correlation between the face area segmented from this threshold value of YCbCr color model and the right input image, the location coordinates of the target face can be acquired, and then these values are used to control the pan/tilt system through the modified PID-based recursive controller. Also, by using the geometric parameters between the target face and the stereo camera system, the vertical distance between the target and stereo camera system can be calculated through a triangulation method. Using this calculated vertical distance and the angles of the pan and tilt, the target's real position data in the world space can be acquired and from them its height and stride values can be finally extracted. Some experiments with video images for 16 moving persons show that a person could be identified with these extracted height and stride parameters.

A free-jet Hg target operating in a high magnetic field intersecting a high-power proton beam

NASA Astrophysics Data System (ADS)

Graves, Van; Spampinato, Philip; Gabriel, Tony; Kirk, Harold; Simos, Nicholas; Tsang, Thomas; McDonald, Kirk; Peter Titus; Fabich, Adrian; Haseroth, Helmut; Lettry, Jacques

2006-06-01

A proof-of-principal experiment to investigate the interaction of a proton beam, high magnetic field, and high-Z target is planned to take place at CERN in early 2007. This experiment is part of the Muon Collider Collaboration, with participants from Brookhaven National Laboratory, Princeton University, Massachusetts Institute Of Technology, European Organization for Nuclear Research-CERN, Rutherford Appleton Laboratory, and Oak Ridge National Laboratory. An unconstrained mercury jet target system that interacts with a high power (1 MW) proton beam in a high magnetic field (15 T) is being designed. The Hg jet diameter is 1-cm with a velocity up to 20 m/s. A laser optical diagnostic system will be incorporated into the target design to permit observation of the dispersal of the jet resulting from interaction with a 24 GeV proton beam with up to 20×1012 ppp. The target system includes instruments for sensing mercury vapor, temperature, flow rate, and sump tank level, and the means to position the jet relative to the magnetic axis of a solenoid and the proton beam. The design considerations for the system include all issues dealing with safely handling approximately 23 l of Hg, transporting the target system and the mercury to CERN, decommissioning the experiment, and returning the mildly activated equipment and Hg to the US.

A free-jet Hg target operating in a high magnetic field intersecting a high-power proton beam

NASA Astrophysics Data System (ADS)

Van Graves; Spampinato, Philip; Gabriel, Tony; Kirk, Harold; Simos, Nicholas; Tsang, Thomas; McDonald, Kirk; Peter Titus; Fabich, Adrian; Haseroth, Helmut; Lettry, Jacques

2006-06-01

A proof-of-principal experiment to investigate the interaction of a proton beam, high magnetic field, and high- Z target is planned to take place at CERN in early 2007. This experiment is part of the Muon Collider Collaboration, with participants from Brookhaven National Laboratory, Princeton University, Massachusetts Institute Of Technology, European Organization for Nuclear Research-CERN, Rutherford Appleton Laboratory, and Oak Ridge National Laboratory. An unconstrained mercury jet target system that interacts with a high power (1 MW) proton beam in a high magnetic field (15 T) is being designed. The Hg jet diameter is 1-cm with a velocity up to 20 m/s. A laser optical diagnostic system will be incorporated into the target design to permit observation of the dispersal of the jet resulting from interaction with a 24 GeV proton beam with up to 20×10 12 ppp. The target system includes instruments for sensing mercury vapor, temperature, flow rate, and sump tank level, and the means to position the jet relative to the magnetic axis of a solenoid and the proton beam. The design considerations for the system include all issues dealing with safely handling approximately 23 l of Hg, transporting the target system and the mercury to CERN, decommissioning the experiment, and returning the mildly activated equipment and Hg to the US.

Performance Analysis for Joint Target Parameter Estimation in UMTS-Based Passive Multistatic Radar with Antenna Arrays Using Modified Cramér-Rao Lower Bounds.

PubMed

Shi, Chenguang; Wang, Fei; Salous, Sana; Zhou, Jianjiang

2017-10-18

In this study, the modified Cramér-Rao lower bounds (MCRLBs) on the joint estimation of target position and velocity is investigated for a universal mobile telecommunication system (UMTS)-based passive multistatic radar system with antenna arrays. First, we analyze the log-likelihood redfunction of the received signal for a complex Gaussian extended target. Then, due to the non-deterministic transmitted data symbols, the analytically closed-form expressions of the MCRLBs on the Cartesian coordinates of target position and velocity are derived for a multistatic radar system with N t UMTS-based transmit station of L t antenna elements and N r receive stations of L r antenna elements. With the aid of numerical simulations, it is shown that increasing the number of receiving elements in each receive station can reduce the estimation errors. In addition, it is demonstrated that the MCRLB is not only a function of signal-to-noise ratio (SNR), the number of receiving antenna elements and the properties of the transmitted UMTS signals, but also a function of the relative geometric configuration between the target and the multistatic radar system.The analytical expressions for MCRLB will open up a new dimension for passive multistatic radar system by aiding the optimal placement of receive stations to improve the target parameter estimation performance.

Performance Analysis for Joint Target Parameter Estimation in UMTS-Based Passive Multistatic Radar with Antenna Arrays Using Modified Cramér-Rao Lower Bounds

PubMed Central

Wang, Fei; Salous, Sana; Zhou, Jianjiang

2017-01-01

In this study, the modified Cramér-Rao lower bounds (MCRLBs) on the joint estimation of target position and velocity is investigated for a universal mobile telecommunication system (UMTS)-based passive multistatic radar system with antenna arrays. First, we analyze the log-likelihood redfunction of the received signal for a complex Gaussian extended target. Then, due to the non-deterministic transmitted data symbols, the analytically closed-form expressions of the MCRLBs on the Cartesian coordinates of target position and velocity are derived for a multistatic radar system with Nt UMTS-based transmit station of Lt antenna elements and Nr receive stations of Lr antenna elements. With the aid of numerical simulations, it is shown that increasing the number of receiving elements in each receive station can reduce the estimation errors. In addition, it is demonstrated that the MCRLB is not only a function of signal-to-noise ratio (SNR), the number of receiving antenna elements and the properties of the transmitted UMTS signals, but also a function of the relative geometric configuration between the target and the multistatic radar system.The analytical expressions for MCRLB will open up a new dimension for passive multistatic radar system by aiding the optimal placement of receive stations to improve the target parameter estimation performance. PMID:29057805

Circulating and disseminated tumor cells: diagnostic tools and therapeutic targets in motion

PubMed Central

Lin, Peter P.; Gires, Olivier

2017-01-01

Enumeration of circulating tumor cells (CTCs) in peripheral blood with the gold standard CellSearchTM has proven prognostic value for tumor recurrence and progression of metastatic disease. Therefore, the further molecular characterization of isolated CTCs might have clinical relevance as liquid biopsy for therapeutic decision-making and to monitor disease progression. The direct analysis of systemic cancer appears particularly important in view of the known disparity in expression of therapeutic targets as well as epithelial-to-mesenchymal transition (EMT)-based heterogeneity between primary and systemic tumor cells, which all substantially complicate monitoring and therapeutic targeting at present. Since CTCs are the potential precursor cells of metastasis, their in-depth molecular profiling should also provide a useful resource for target discovery. The present review will discuss the use of systemically spread cancer cells as liquid biopsy and focus on potential target antigens. PMID:27683128

An underwater ranging system based on photoacoustic effect occurring on target surface

NASA Astrophysics Data System (ADS)

Ni, Kai; Hu, Kai; Li, Xinghui; Wang, Lidai; Zhou, Qian; Wang, Xiaohao

2016-11-01

In this paper, an underwater ranging system based on photoacoustic effect occurring on target surface is proposed. In this proposal, laser pulse generated by blue-green laser is directly incident on target surface, where the photoacoustic effect occurs and a sound source is formed. And then the sound wave which is also called photoacoustic signal is received by the ultrasonic receiver after passing through water. According to the time delay between transmitting laser and receiving photoacoustic signal, and sound velocity in water, the distance between the target and the ultrasonic receiver can be calculated. Differing from underwater range finding by only laser, this approach can avoid backscattering of laser beam, so easier to implement. Experimental system according to this principle has been constructed to verify the feasibility of this technology. The experimental results showed that a ranging accuracy of 1 mm can be effectively achieved when the target is close to the ultrasonic receiver.

Optimization of a Multi-Stage ATR System for Small Target Identification

NASA Technical Reports Server (NTRS)

Lin, Tsung-Han; Lu, Thomas; Braun, Henry; Edens, Western; Zhang, Yuhan; Chao, Tien- Hsin; Assad, Christopher; Huntsberger, Terrance

2010-01-01

An Automated Target Recognition system (ATR) was developed to locate and target small object in images and videos. The data is preprocessed and sent to a grayscale optical correlator (GOC) filter to identify possible regionsof- interest (ROIs). Next, features are extracted from ROIs based on Principal Component Analysis (PCA) and sent to neural network (NN) to be classified. The features are analyzed by the NN classifier indicating if each ROI contains the desired target or not. The ATR system was found useful in identifying small boats in open sea. However, due to "noisy background," such as weather conditions, background buildings, or water wakes, some false targets are mis-classified. Feedforward backpropagation and Radial Basis neural networks are optimized for generalization of representative features to reduce false-alarm rate. The neural networks are compared for their performance in classification accuracy, classifying time, and training time.

Integrative FourD omics approach profiles the target network of the carbon storage regulatory system.

PubMed

Sowa, Steven W; Gelderman, Grant; Leistra, Abigail N; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A; Romeo, Tony; Baldea, Michael; Contreras, Lydia M

2017-02-28

Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Directed area search using socio-biological vision algorithms and cognitive Bayesian reasoning

NASA Astrophysics Data System (ADS)

Medasani, S.; Owechko, Y.; Allen, D.; Lu, T. C.; Khosla, D.

2010-04-01

Volitional search systems that assist the analyst by searching for specific targets or objects such as vehicles, factories, airports, etc in wide area overhead imagery need to overcome multiple problems present in current manual and automatic approaches. These problems include finding targets hidden in terabytes of information, relatively few pixels on targets, long intervals between interesting regions, time consuming analysis requiring many analysts, no a priori representative examples or templates of interest, detecting multiple classes of objects, and the need for very high detection rates and very low false alarm rates. This paper describes a conceptual analyst-centric framework that utilizes existing technology modules to search and locate occurrences of targets of interest (e.g., buildings, mobile targets of military significance, factories, nuclear plants, etc.), from video imagery of large areas. Our framework takes simple queries from the analyst and finds the queried targets with relatively minimum interaction from the analyst. It uses a hybrid approach that combines biologically inspired bottom up attention, socio-biologically inspired object recognition for volitionally recognizing targets, and hierarchical Bayesian networks for modeling and representing the domain knowledge. This approach has the benefits of high accuracy, low false alarm rate and can handle both low-level visual information and high-level domain knowledge in a single framework. Such a system would be of immense help for search and rescue efforts, intelligence gathering, change detection systems, and other surveillance systems.

Dual-cyclical nucleic acid strand-displacement polymerization based signal amplification system for highly sensitive determination of p53 gene.

PubMed

Xu, Jianguo; Wu, Zai-Sheng; Li, Hongling; Wang, Zhenmeng; Le, Jingqing; Zheng, Tingting; Jia, Lee

2016-12-15

In the present study, we proposed a novel dual-cyclical nucleic acid strand-displacement polymerization (dual-CNDP) based signal amplification system for highly sensitive determination of tumor suppressor genes. The system primarily consisted of a signaling hairpin probe (SHP), a label-free hairpin probe (LHP) and an initiating primer (IP). The presence of target DNA was able to induce one CNDP through continuous process of ligation, polymerization and nicking, leading to extensively accumulation of two nicked triggers (NT1 and NT2). Intriguingly, the NT1 could directly hybridize SHP, while the NT2 could act as the target analog to induce another CNDP. The resulting dual-CNDP contributed the striking signal amplification, and only a very weak blank noise existed since the ligation template of target was not involved. In this case, the target could be detected in a wide linear range (5 orders of magnitude), and a low detection limit (78 fM) was obtained, which is superior to most of the existing fluorescent methods. Moreover, the dual-CNDP sensing system provided a high selectivity towards target DNA against mismatched target and was successfully applied to analysis of target gene extracted from cancer cells or in human serum-contained samples, indicating its great potential for practical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

Light localization with low-contrast targets in a patient implanted with a suprachoroidal-transretinal stimulation retinal prosthesis.

PubMed

Endo, Takao; Fujikado, Takashi; Hirota, Masakazu; Kanda, Hiroyuki; Morimoto, Takeshi; Nishida, Kohji

2018-04-20

To evaluate the improvement in targeted reaching movements toward targets of various contrasts in a patient implanted with a suprachoroidal-transretinal stimulation (STS) retinal prosthesis. An STS retinal prosthesis was implanted in the right eye of a 42-year-old man with advanced Stargardt disease (visual acuity: right eye, light perception; left eye, hand motion). In localization tests during the 1-year follow-up period, the patient attempted to touch the center of a white square target (visual angle, 10°; contrast, 96, 85, or 74%) displayed at a random position on a monitor. The distance between the touched point and the center of the target (the absolute deviation) was averaged over 20 trials with the STS system on or off. With the left eye occluded, the absolute deviation was not consistently lower with the system on than off for high-contrast (96%) targets, but was consistently lower with the system on for low-contrast (74%) targets. With both eyes open, the absolute deviation was consistently lower with the system on than off for 85%-contrast targets. With the system on and 96%-contrast targets, we detected a shorter response time while covering the right eye, which was being implanted with the STS, compared to covering the left eye (2.41 ± 2.52 vs 8.45 ± 3.78 s, p < 0.01). Performance of a reaching movement improved in a patient with an STS retinal prosthesis implanted in an eye with residual natural vision. Patients with a retinal prosthesis may be able to improve their visual performance by using both artificial vision and their residual natural vision. Beginning date of the trial: Feb. 20, 2014 Date of registration: Jan. 4, 2014 Trial registration number: UMIN000012754 Registration site: UMIN Clinical Trials Registry (UMIN-CTR) http://www.umin.ac.jp/ctr/index.htm.

[CT-guided intervention by means of a laser marking and targeting aid].

PubMed

Klöppel, R; Wilke, W; Weisse, T; Steinecke, R

1997-08-01

The present study evaluates the use of a laser guidance system for CT-guided intervention. 94 cases of diagnostic biopsies and lumbar sympathectomies (54 cases with laser guidance system and 40 without) were compared. Using the laser guidance system, the number of control scans decreased by 30 to 50%, and necessary corrections of needle location were reduced by a maximum of 30%. The average target deviation of the needle decreased to less than 5 mm in 50% of cases. The laser guidance system is strongly recommended in CT-guided interventions for quality assurance and higher efficiency. The advantage is especially marked if the target area is small.

Bacteriophage-Derived Vectors for Targeted Cancer Gene Therapy

PubMed Central

Pranjol, Md Zahidul Islam; Hajitou, Amin

2015-01-01

Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration. PMID:25606974

Bacteriophage-derived vectors for targeted cancer gene therapy.

PubMed

Pranjol, Md Zahidul Islam; Hajitou, Amin

2015-01-19

Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration.

The Effects of Target and Missile Characteristics on Theoretical Minimum Miss Distance for a Beam-Rider Guidance System in the Presence of Noise

NASA Technical Reports Server (NTRS)

Stewart, Elwood C.; Druding, Frank; Nishiura, Togo

1959-01-01

A study has been made to determine the relative importance of those factors which place an inherent limitation on the minimum obtainable miss distance for a beam-rider navigation system operating in the presence of glint noise and target evasive maneuver. Target and missile motions are assumed to be coplanar. The factors considered are the missile natural frequencies and damping ratios, missile steady-state acceleration capabilities, target evasive maneuver characteristics, and angular scintillation noise characteristics.

Quantum dot tailored to single wall carbon nanotubes: a multifunctional hybrid nanoconstruct for cellular imaging and targeted photothermal therapy.

PubMed

Nair, Lakshmi V; Nagaoka, Yutaka; Maekawa, Toru; Sakthikumar, D; Jayasree, Ramapurath S

2014-07-23

Hybrid nanomaterial based on quantum dots and SWCNTs is used for cellular imaging and photothermal therapy. Furthermore, the ligand conjugated hybrid system (FaQd@CNT) enables selective targeting in cancer cells. The imaging capability of quantum dots and the therapeutic potential of SWCNT are available in a single system with cancer targeting property. Heat generated by the system is found to be high enough to destroy cancer cells. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The chance of Sweden's public health targets making a difference.

PubMed

Lager, Anton; Guldbrandsson, Karin; Fossum, Bjöörn

2007-03-01

There is a trend in health policy towards more focus on determinants and societal interventions and less on individuals. The Swedish public health targets are in line with this trend. The value of public health targets lies in their ability to function as a tool in governing with targets. This paper examines the possibility of the Swedish targets functioning as such a tool. Document analyses were performed to examine three prerequisites of governing with targets: (1) the influence of the administration in the target setting process, (2) the explicitness of targets and (3) the follow-up system. The material consisted of the documents from the committee drafting the targets, the written opinions on the drafts, and the governmental bill with the adopted public health targets. The administration influenced the target setting process. Further, the government invests in a follow-up system that makes indicators on health determinants visible. However, although there existed explicit targets earlier in the process, the final targets in the bill are not explicit enough. The Swedish public health targets are not explicit enough to function in governing with targets. The reasons for this were political rather than technical. This suggests that policy makers focusing health determinants should not put time and resources in technical target formulating. Instead they could make indicators visible, thereby drawing attention to trends that are political by nature.

An enhanced chemiluminescence resonance energy transfer system based on target recycling G-guadruplexes/hemin DNAzyme catalysis and its application in ultrasensitive detection of DNA.

PubMed

Chen, Jia; Huang, Yong; Vdovenko, Marina; Sakharov, Ivan Yu; Su, Guifa; Zhao, Shulin

2015-06-01

An enhanced chemiluminescence resonance energy transfer (CRET) system based on target recycling G-guadruplexes/hemin DNAzyme catalysis was developed for ultrasensitive detection of DNA. CRET system consists of luminol as chemiluminescent donor, and fluorescein isothiocyanate (FITC) as acceptor. The sensitive detection was achieved by using the system consisted of G-riched DNA, blocker DNA, and the Nb.BbvCI biocatalyst. Upon addition of target DNA to the system, target DNA hybridizes with the quasi-circular DNA structure, and forms a DNA duplex. The formation of DNA duplex triggers selective enzymatic cleavage of quasi-circular DNA by Nb.BbvCI, resulting in the release of target DNA and two G-riched DNAzyme segments. Released target DNA then hybridizes with another quasi-circular DNA structure to initiate the cleavage of the quasi-circular DNA structure. Eventually, each target DNA can go through many cycles, resulting in the digestion of many quasi-circular DNA structures, generating many G-riched DNAzyme segments. G-riched DNAzyme segment products assemble with hemin to form stable hemin/G-quadruplexes that exhibit peroxidase-like activity which can catalyze the oxidation of luminol by H2O2 to produce CL signals. In the presence of FITC, CL of luminol can excite FITC molecules, and thus produced CRET between the luminol and FITC. This unique analysis strategy gives a detection limit down to 80 fM, which is at least four orders of magnitude lower than that of unamplified DNA detection methods. Copyright © 2015 Elsevier B.V. All rights reserved.

Ultrasound-guided three-dimensional needle steering in biological tissue with curved surfaces

PubMed Central

Abayazid, Momen; Moreira, Pedro; Shahriari, Navid; Patil, Sachin; Alterovitz, Ron; Misra, Sarthak

2015-01-01

In this paper, we present a system capable of automatically steering a bevel-tipped flexible needle under ultrasound guidance toward a physical target while avoiding a physical obstacle embedded in gelatin phantoms and biological tissue with curved surfaces. An ultrasound pre-operative scan is performed for three-dimensional (3D) target localization and shape reconstruction. A controller based on implicit force control is developed to align the transducer with curved surfaces to assure the maximum contact area, and thus obtain an image of sufficient quality. We experimentally investigate the effect of needle insertion system parameters such as insertion speed, needle diameter and bevel angle on target motion to adjust the parameters that minimize the target motion during insertion. A fast sampling-based path planner is used to compute and periodically update a feasible path to the target that avoids obstacles. We present experimental results for target reconstruction and needle insertion procedures in gelatin-based phantoms and biological tissue. Mean targeting errors of 1.46 ± 0.37 mm, 1.29 ± 0.29 mm and 1.82 ± 0.58 mm are obtained for phantoms with inclined, curved and combined (inclined and curved) surfaces, respectively, for insertion distance of 86–103 mm. The achieved targeting errors suggest that our approach is sufficient for targeting lesions of 3 mm radius that can be detected using clinical ultrasound imaging systems. PMID:25455165

Extended Fitts' model of pointing time in eye-gaze input system - Incorporating effects of target shape and movement direction into modeling.

PubMed

Murata, Atsuo; Fukunaga, Daichi

2018-04-01

This study attempted to investigate the effects of the target shape and the movement direction on the pointing time using an eye-gaze input system and extend Fitts' model so that these factors are incorporated into the model and the predictive power of Fitts' model is enhanced. The target shape, the target size, the movement distance, and the direction of target presentation were set as within-subject experimental variables. The target shape included: a circle, and rectangles with an aspect ratio of 1:1, 1:2, 1:3, and 1:4. The movement direction included eight directions: upper, lower, left, right, upper left, upper right, lower left, and lower right. On the basis of the data for identifying the effects of the target shape and the movement direction on the pointing time, an attempt was made to develop a generalized and extended Fitts' model that took into account the movement direction and the target shape. As a result, the generalized and extended model was found to fit better to the experimental data, and be more effective for predicting the pointing time for a variety of human-computer interaction (HCI) task using an eye-gaze input system. Copyright © 2017. Published by Elsevier Ltd.

Mesoporous silica nanoparticle-based intelligent drug delivery system for bienzyme-responsive tumour targeting and controlled release.

PubMed

Zhang, Yang; Xu, Juan

2018-01-01

This paper proposes a novel type of multifunctional envelope-type mesoporous silica nanoparticle (MSN) to achieve cancer cell targeting and drug-controlled release. In this system, MSNs were first modified by active targeting moiety hyaluronic acid (HA) for breast cancer cell targeting and hyaluronidases (Hyal)-induced intracellular drug release. Then gelatin, a proteinaceous biopolymer, was grafted onto the MSNs to form a capping layer via glutaraldehyde-mediated cross-linking. To shield against unspecific uptake of cells and prolong circulation time, the nanoparticles were further decorated with poly(ethylene glycol) polymers (PEG) to obtain MSN@HA-gelatin-PEG (MHGP). Doxorubicin (DOX), as a model drug, was loaded into PEMSN to assess the breast cancer cell targeting and drug release behaviours. In vitro study revealed that PEG chains protect the targeting ligand and shield against normal cells. After reaching the breast cancer cells, MMP-2 overpressed by cells hydrolyses gelatin layer to deshield PEG and switch on the function of HA. As a result, DOX-loaded MHGP was selectively trapped by cancer cells through HA receptor-mediated endocytosis and subsequently release DOX due to Hyal-catalysed degradation of HA. This system presents successful bienzyme-responsive targeting drug delivery in an optimal fashion and provides potential applications for targeted cancer therapy.

A dual-targeting liposome conjugated with transferrin and arginine-glycine-aspartic acid peptide for glioma-targeting therapy.

PubMed

Qin, Li; Wang, Cheng-Zheng; Fan, Hui-Jie; Zhang, Chong-Jian; Zhang, Heng-Wei; Lv, Min-Hao; Cui, Shu-DE

2014-11-01

The treatment of a brain glioma remains one of the most difficult challenges in oncology. In the present study a delivery system was developed for targeted drug delivery across the blood-brain barrier (BBB) to the brain cancer cells. A cyclic arginine-glycine-aspartic acid (RGD) peptide and transferrin (TF) were utilized as targeting ligands. Cyclic RGD peptides are specific targeting ligands of cancer cells and TFs are ligands that specifically target the BBB and cancer cells. Liposome (LP) was used to conjugate the cyclic RGD and TFs to establish the brain glioma cascade delivery system (RGD/TF-LP). The LPs were prepared by the thin film hydration method and physicochemical characterization was conducted. In vitro cell uptake and three-dimensional tumor spheroid penetration studies demonstrated that the system could target endothelial and tumor cells, as well as penetrate the tumor cells to reach the core of the tumor spheroids. The results of the in vivo imaging further demonstrated that the RGD/TF-LP provided the highest brain distribution. As a result, the paclitaxel-loaded RGD/TF-LP presents the best antiproliferative activity against C6 cells and tumor spheroids. In conclusion, the RGD/TF-LP may precisely target brain glioma, which may be valuable for glioma imaging and therapy.

Folate-containing reduction-sensitive lipid-polymer hybrid nanoparticles for targeted delivery of doxorubicin.

PubMed

Wu, Bo; Yu, Ping; Cui, Can; Wu, Ming; Zhang, Yang; Liu, Lei; Wang, Cai-Xia; Zhuo, Ren-Xi; Huang, Shi-Wen

2015-04-01

The development and evaluation of folate-targeted and reduction-triggered biodegradable nanoparticles are introduced to the research on targeted delivery of doxorubicin (DOX). This type of folate-targeted lipid-polymer hybrid nanoparticles (FLPNPs) is comprised of a poly(D,L-lactide-co-glycolide) (PLGA) core, a soybean lecithin monolayer, a monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16) reduction-sensitive shell, and a folic acid-targeted ligand. FLPNPs exhibited high size stability but fast disassembly in a simulated cancer cell reductive environment. The experiments on the release process in vitro revealed that as a reduction-sensitive drug delivery system, FLPNPs released DOX faster in the presence of 10 mM dithiothreitol (DTT). Results from flow cytometry, confocal image and in vitro cytotoxicity assays revealed that FLPNPs further enhanced cell uptake and generated higher cytotoxicity against human epidermoid carcinoma in the oral cavity than non-targeted redox-sensitive and targeted redox-insensitive controls. Furthermore, in vivo animal experiments demonstrated that systemic administration of DOX-loaded FLPNPs remarkably reduced tumor growth. Experiments on biodistribution of DOX-loaded FLPNPs showed that an increasing amount of DOX accumulated in the tumor. Therefore, FLPNPs formulations have proved to be a stable, controllable and targeted anticancer drug delivery system.

Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

PubMed

Gdowski, Andrew S; Ranjan, Amalendu; Sarker, Marjana R; Vishwanatha, Jamboor K

2017-09-01

The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

Systems and methods for imaging using radiation from laser produced plasmas

DOEpatents

Renard-Le Galloudec, Nathalie; Cowan, Thomas E.; Sentoku, Yasuhiko; Rassuchine, Jennifer

2009-06-30

In particular embodiments, the present disclosure provides systems and methods for imaging a subject using radiation emitted from a laser produced plasma generating by irradiating a target with a laser. In particular examples, the target includes at least one radiation enhancing component, such as a fluor, cap, or wire. In further examples, the target has a metal layer and an internal surface defining an internal apex, the internal apex of less than about 15 .mu.m, such as less than about 1 .mu.m. The targets may take a variety of shapes, including cones, pyramids, and hemispheres. Certain aspects of the present disclosure provide improved imaging of a subject, such as improved medical images of a radiation dose than typical conventional methods and systems.

Multi-channel, passive, short-range anti-aircraft defence system

NASA Astrophysics Data System (ADS)

Gapiński, Daniel; Krzysztofik, Izabela; Koruba, Zbigniew

2018-01-01

The paper presents a novel method for tracking several air targets simultaneously. The developed concept concerns a multi-channel, passive, short-range anti-aircraft defence system based on the programmed selection of air targets and an algorithm of simultaneous synchronisation of several modified optical scanning seekers. The above system is supposed to facilitate simultaneous firing of several self-guided infrared rocket missiles at many different air targets. From the available information, it appears that, currently, there are no passive self-guided seekers that fulfil such tasks. This paper contains theoretical discussions and simulations of simultaneous detection and tracking of many air targets by mutually integrated seekers of several rocket missiles. The results of computer simulation research have been presented in a graphical form.

Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

PubMed Central

Azizi, Ali; Kumar, Ashok; Diaz-Mitoma, Francisco; Mestecky, Jiri

2010-01-01

The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M) cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells. PMID:21085599

Feasible and technical aspects of transcatheter arterial chemoembolization for non-resectable hepatocellular carcinoma using a 3.5-French catheter system.

PubMed

Yagyu, Yukinobu; Tsurusaki, Masakatsu; Kamiyama, Kazutoshi; Kitagaki, Hajime; Murakami, Takamichi

2014-12-01

To evaluate the feasibility and technical aspects of transcatheter arterial chemoembolization (TACE) for non-resectable hepatocellular carcinoma (HCC) using a 3.5-French (Fr) catheter system. This study included 328 consecutive cases of HCC among 232 patients who underwent TACE procedures using both a 3.5-Fr catheter system and a microcatheter fitted to a 3.5-Fr system between April 2009 and November 2011. We assessed the ability to reach the catheter into the proper hepatic artery (PHA), main hepatic branch, segmental artery, and subsegmental or sub-subsegmental artery. The feasibility was rated according to the following factors: (1) the number of arteries that could be used to reach the target artery/total number of procedures using the 3.5-Fr system, (2) the rate of successful completion of the procedures without changing over to the 4-Fr system and (3) the reasons for changing over the 4-Fr system. TACE of the PHA (27 sessions), RHA/LHA (103 sessions), segmental (31 sessions), or subsegmental/sub-subsegmental arteries (162 sessions) was performed. The rate of successfully reaching the target artery using the 3.5-Fr system was 93% (306/328 sessions). We were unable to reach the target artery in 22 sessions, including 11/8/3 procedures targeting the sub-subsegmental artery, subsegmental artery, and RHA/LHA, respectively. We changed over to the 4-Fr system in six sessions; therefore, the rate of successful completion of the procedures without changing over to the 4-Fr system was 98% (322/328 sessions). TACE of the target artery can be successfully performed using the 3.5-Fr system in most patients with HCC.

Dual responsive PNIPAM-chitosan targeted magnetic nanopolymers for targeted drug delivery

NASA Astrophysics Data System (ADS)

Yadavalli, Tejabhiram; Ramasamy, Shivaraman; Chandrasekaran, Gopalakrishnan; Michael, Isaac; Therese, Helen Annal; Chennakesavulu, Ramasamy

2015-04-01

A dual stimuli sensitive magnetic hyperthermia based drug delivery system has been developed for targeted cancer treatment. Thermosensitive amine terminated poly-N-isopropylacrylamide complexed with pH sensitive chitosan nanoparticles was prepared as the drug carrier. Folic acid and fluorescein were tagged to the nanopolymer complex via N-hydroxysuccinimide and ethyl-3-(3-dimethylaminopropyl)carbodiimide reaction to form a fluorescent and cancer targeting magnetic carrier system. The formation of the polymer complex was confirmed using infrared spectroscopy. Gadolinium doped nickel ferrite nanoparticles prepared by a hydrothermal method were encapsulated in the polymer complex to form a magnetic drug carrier system. The proton relaxation studies on the magnetic carrier system revealed a 200% increase in the T1 proton relaxation rate. These magnetic carriers were loaded with curcumin using solvent evaporation method with a drug loading efficiency of 86%. Drug loaded nanoparticles were tested for their targeting and anticancer properties on four cancer cell lines with the help of MTT assay. The results indicated apoptosis of cancer cell lines within 3 h of incubation.

Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting.

PubMed

Nakayama, Masamichi; Akimoto, Jun; Okano, Teruo

2014-08-01

Since the 1990s, nanoscale drug carriers have played a pivotal role in cancer chemotherapy, acting through passive drug delivery mechanisms and subsequent pharmaceutical action at tumor tissues with reduction of adverse effects. Polymeric micelles, as supramolecular assemblies of amphiphilic polymers, have been considerably developed as promising drug carrier candidates, and a number of clinical studies of anticancer drug-loaded polymeric micelle carriers for cancer chemotherapy applications are now in progress. However, these systems still face several issues; at present, the simultaneous control of target-selective delivery and release of incorporated drugs remains difficult. To resolve these points, the introduction of stimuli-responsive mechanisms to drug carrier systems is believed to be a promising approach to provide better solutions for future tumor drug targeting strategies. As possible trigger signals, biological acidic pH, light, heating/cooling and ultrasound actively play significant roles in signal-triggering drug release and carrier interaction with target cells. This review article summarizes several molecular designs for stimuli-responsive polymeric micelles in response to variation of pH, light and temperature and discusses their potentials as next-generation tumor drug targeting systems.

Biodiscovery of aluminum binding peptides

NASA Astrophysics Data System (ADS)

Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Hurley, Margaret M.; Stratis-Cullum, Dimitra

2013-05-01

Cell surface peptide display systems are large and diverse libraries of peptides (7-15 amino acids) which are presented by a display scaffold hosted by a phage (virus), bacteria, or yeast cell. This allows the selfsustaining peptide libraries to be rapidly screened for high affinity binders to a given target of interest, and those binders quickly identified. Peptide display systems have traditionally been utilized in conjunction with organic-based targets, such as protein toxins or carbon nanotubes. However, this technology has been expanded for use with inorganic targets, such as metals, for biofabrication, hybrid material assembly and corrosion prevention. While most current peptide display systems employ viruses to host the display scaffold, we have recently shown that a bacterial host, Escherichia coli, displaying peptides in the ubiquitous, membrane protein scaffold eCPX can also provide specific peptide binders to an organic target. We have, for the first time, extended the use of this bacterial peptide display system for the biodiscovery of aluminum binding 15mer peptides. We will present the process of biopanning with macroscopic inorganic targets, binder enrichment, and binder isolation and discovery.

On the performance of infrared sensors in earth observations

NASA Technical Reports Server (NTRS)

Johnson, L. F.

1972-01-01

The performance of infrared sensing systems is dependent upon the radiative properties of targets in addition to constraints imposed by system components. The unclassified state-of-the-art of infrared system performance figures is reviewed to indicate the relevance to system performance of target radiative properties. A theory of rough surface scattering is developed which allows the formulation of the reflective characteristics of extended targets. The thermal radiation emission from extended targets is formulated on the basis of internal radiation characteristics of natural materials and the transmissive scattering effects at the surface. Finally, the total radiative characteristics may be expressed as functions of material properties and incident and received directions, although the expressions are extremely complex functions and do not account for the effects of shadowing or multiple scattering. It is believed that the theory may be extended to include these effects and to incorporate the local radii of curvature of the surface.

Visual search for motion-form conjunctions: is form discriminated within the motion system?

PubMed

von Mühlenen, A; Müller, H J

2001-06-01

Motion-form conjunction search can be more efficient when the target is moving (a moving 45 degrees tilted line among moving vertical and stationary 45 degrees tilted lines) rather than stationary. This asymmetry may be due to aspects of form being discriminated within a motion system representing only moving items, whereas discrimination of stationary items relies on a static form system (J. Driver & P. McLeod, 1992). Alternatively, it may be due to search exploiting differential motion velocity and direction signals generated by the moving-target and distractor lines. To decide between these alternatives, 4 experiments systematically varied the motion-signal information conveyed by the moving target and distractors while keeping their form difference salient. Moving-target search was found to be facilitated only when differential motion-signal information was available. Thus, there is no need to assume that form is discriminated within the motion system.

Use of an inertial navigation system for accurate track recovery and coastal oceanographic measurements

NASA Technical Reports Server (NTRS)

Oliver, B. M.; Gower, J. F. R.

1977-01-01

A data acquisition system using a Litton LTN-51 inertial navigation unit (INU) was tested and used for aircraft track recovery and for location and tracking from the air of targets at sea. The characteristic position drift of the INU is compensated for by sighting landmarks of accurately known position at discrete time intervals using a visual sighting system in the transparent nose of the Beechcraft 18 aircraft used. For an aircraft altitude of about 300 m, theoretical and experimental tests indicate that calculated aircraft and/or target positions obtained from the interpolated INU drift curve will be accurate to within 10 m for landmarks spaced approximately every 15 minutes in time. For applications in coastal oceanography, such as surface current mapping by tracking artificial targets, the system allows a broad area to be covered without use of high altitude photography and its attendant needs for large targets and clear weather.

Nanoliposome is a Promising Carrier of Protein and Peptide Biomolecule for the Treatment of Cancer.

PubMed

Kumar Giri, Tapan; Giri, Ayan; Kumar Barman, Tapan; Maity, Subhasis

2016-01-01

Nano-liposomes are the newly developed delivery systems for cancer therapy that are finding a position particularly suitable as peptide and protein carriers. These are three-layered self-assembled structures with nanoparticulate carrier systems. The overall pharmacological properties of commonly used protein and peptide in cancer therapy can be improved by the incorporation of protein and peptide into the nano-liposome. The surface modifications can be made liposomes to make compatible with targeting ligands has made these nanocarriers for targeted delivery. This review discusses the method of preparation and characterization of liposome based protein peptide delivery for the treatment of cancer. This review also explores latest work intended for targeted treatment of cancer by nano-liposomal protein and peptide delivery system. This type of delivery is targeting protein and peptide to tumor site by avoiding the reticuloendothelial system. Methods of nano-liposome delivery containing protein and peptide are also highlighted.

Determining the Specificity of Cascade Binding, Interference, and Primed Adaptation In Vivo in the Escherichia coli Type I-E CRISPR-Cas System.

PubMed

Cooper, Lauren A; Stringer, Anne M; Wade, Joseph T

2018-04-17

In clustered regularly interspaced short palindromic repeat (CRISPR)-Cas (CRISPR-associated) immunity systems, short CRISPR RNAs (crRNAs) are bound by Cas proteins, and these complexes target invading nucleic acid molecules for degradation in a process known as interference. In type I CRISPR-Cas systems, the Cas protein complex that binds DNA is known as Cascade. Association of Cascade with target DNA can also lead to acquisition of new immunity elements in a process known as primed adaptation. Here, we assess the specificity determinants for Cascade-DNA interaction, interference, and primed adaptation in vivo , for the type I-E system of Escherichia coli Remarkably, as few as 5 bp of crRNA-DNA are sufficient for association of Cascade with a DNA target. Consequently, a single crRNA promotes Cascade association with numerous off-target sites, and the endogenous E. coli crRNAs direct Cascade binding to >100 chromosomal sites. In contrast to the low specificity of Cascade-DNA interactions, >18 bp are required for both interference and primed adaptation. Hence, Cascade binding to suboptimal, off-target sites is inert. Our data support a model in which the initial Cascade association with DNA targets requires only limited sequence complementarity at the crRNA 5' end whereas recruitment and/or activation of the Cas3 nuclease, a prerequisite for interference and primed adaptation, requires extensive base pairing. IMPORTANCE Many bacterial and archaeal species encode CRISPR-Cas immunity systems that protect against invasion by foreign DNA. In the Escherichia coli CRISPR-Cas system, a protein complex, Cascade, binds 61-nucleotide (nt) CRISPR RNAs (crRNAs). The Cascade complex is directed to invading DNA molecules through base pairing between the crRNA and target DNA. This leads to recruitment of the Cas3 nuclease, which destroys the invading DNA molecule and promotes acquisition of new immunity elements. We made the first in vivo measurements of Cascade binding to DNA targets. Thus, we show that Cascade binding to DNA is highly promiscuous; endogenous E. coli crRNAs can direct Cascade binding to >100 chromosomal locations. In contrast, we show that targeted degradation and acquisition of new immunity elements require highly specific association of Cascade with DNA, limiting CRISPR-Cas function to the appropriate targets. Copyright © 2018 Cooper et al.

Ground target geolocation based on digital elevation model for airborne wide-area reconnaissance system

NASA Astrophysics Data System (ADS)

Qiao, Chuan; Ding, Yalin; Xu, Yongsen; Xiu, Jihong

2018-01-01

To obtain the geographical position of the ground target accurately, a geolocation algorithm based on the digital elevation model (DEM) is developed for an airborne wide-area reconnaissance system. According to the platform position and attitude information measured by the airborne position and orientation system and the gimbal angles information from the encoder, the line-of-sight pointing vector in the Earth-centered Earth-fixed coordinate frame is solved by the homogeneous coordinate transformation. The target longitude and latitude can be solved with the elliptical Earth model and the global DEM. The influences of the systematic error and measurement error on ground target geolocation calculation accuracy are analyzed by the Monte Carlo method. The simulation results show that this algorithm can improve the geolocation accuracy of ground target in rough terrain area obviously. The geolocation accuracy of moving ground target can be improved by moving average filtering (MAF). The validity of the geolocation algorithm is verified by the flight test in which the plane flies at a geodetic height of 15,000 m and the outer gimbal angle is <47°. The geolocation root mean square error of the target trajectory is <45 and <7 m after MAF.

[Research and application of microcontroller system for target controlled infusion].

PubMed

Cheng, Yuke; Dou, Jianhong; Zhang, Xingan; Wang, Ruosong

2005-08-01

This paper presents a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extending power and easy manipulation. It has been used in the clinical anesthesia.

A holographic system that records front-surface detail of a scene moving at high velocity

NASA Technical Reports Server (NTRS)

Kurtz, R. L.; Loh, H. Y.

1972-01-01

A holographic technique that uses an elliptical orientation for the holographic arrangement is discussed. It is shown that the degree of image degradation is not only a function of exposure time but also of the system used. The form of the functional system dependence is given, as well as the results of several systems tested, which verify this dependence. It is further demonstrated that the important parameter is the total motion of the target. Using the experimentally determined resolution of front-surface detail from a target with a velocity of 17,546 centimeters per second, an upper limit on target velocity for resolution of front-surface detail for a given system can be predicted.

Recent Advances in Aptamers Targeting Immune System.

PubMed

Hu, Piao-Ping

2017-02-01

The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

[Advances of tumor targeting peptides drug delivery system with pH-sensitive activities].

PubMed

Ma, Yin-yun; Li, Li; Huang, Hai-feng; Gou, San-hu; Ni, Jing-man

2016-05-01

The pH-sensitive peptides drug delivery systems, which target to acidic extracellular environment of tumor tissue, have many advantages in drug delivery. They exhibit a high specificity to tumor and low cytotoxicity, which significantly increase the efficacy of traditional anti-cancer drugs. In recent years the systems have received a great attention. The pH-sensitive peptides drug delivery systems can be divided into five types according to the difference in pH-responsive mechanism,type of peptides and carrier materials. This paper summarizes the recent progresses in the field with a focus on the five types of pH-sensitive peptides in drug delivery systems. This may provide a guideline to design and application of tumor targeting drugs.

Assessing the performance of a motion tracking system based on optical joint transform correlation

NASA Astrophysics Data System (ADS)

Elbouz, M.; Alfalou, A.; Brosseau, C.; Ben Haj Yahia, N.; Alam, M. S.

2015-08-01

We present an optimized system specially designed for the tracking and recognition of moving subjects in a confined environment (such as an elderly remaining at home). In the first step of our study, we use a VanderLugt correlator (VLC) with an adapted pre-processing treatment of the input plane and a postprocessing of the correlation plane via a nonlinear function allowing us to make a robust decision. The second step is based on an optical joint transform correlation (JTC)-based system (NZ-NL-correlation JTC) for achieving improved detection and tracking of moving persons in a confined space. The proposed system has been found to have significantly superior discrimination and robustness capabilities allowing to detect an unknown target in an input scene and to determine the target's trajectory when this target is in motion. This system offers robust tracking performance of a moving target in several scenarios, such as rotational variation of input faces. Test results obtained using various real life video sequences show that the proposed system is particularly suitable for real-time detection and tracking of moving objects.

JANUS: A Compilation System for Balancing Parallelism and Performance in OpenVX

NASA Astrophysics Data System (ADS)

Omidian, Hossein; Lemieux, Guy G. F.

2018-04-01

Embedded systems typically do not have enough on-chip memory for entire an image buffer. Programming systems like OpenCV operate on entire image frames at each step, making them use excessive memory bandwidth and power. In contrast, the paradigm used by OpenVX is much more efficient; it uses image tiling, and the compilation system is allowed to analyze and optimize the operation sequence, specified as a compute graph, before doing any pixel processing. In this work, we are building a compilation system for OpenVX that can analyze and optimize the compute graph to take advantage of parallel resources in many-core systems or FPGAs. Using a database of prewritten OpenVX kernels, it automatically adjusts the image tile size as well as using kernel duplication and coalescing to meet a defined area (resource) target, or to meet a specified throughput target. This allows a single compute graph to target implementations with a wide range of performance needs or capabilities, e.g. from handheld to datacenter, that use minimal resources and power to reach the performance target.

Choice reaching with a LEGO arm robot (CoRLEGO): The motor system guides visual attention to movement-relevant information

PubMed Central

Strauss, Soeren; Woodgate, Philip J.W.; Sami, Saber A.; Heinke, Dietmar

2015-01-01

We present an extension of a neurobiologically inspired robotics model, termed CoRLEGO (Choice reaching with a LEGO arm robot). CoRLEGO models experimental evidence from choice reaching tasks (CRT). In a CRT participants are asked to rapidly reach and touch an item presented on the screen. These experiments show that non-target items can divert the reaching movement away from the ideal trajectory to the target item. This is seen as evidence attentional selection of reaching targets can leak into the motor system. Using competitive target selection and topological representations of motor parameters (dynamic neural fields) CoRLEGO is able to mimic this leakage effect. Furthermore if the reaching target is determined by its colour oddity (i.e. a green square among red squares or vice versa), the reaching trajectories become straighter with repetitions of the target colour (colour streaks). This colour priming effect can also be modelled with CoRLEGO. The paper also presents an extension of CoRLEGO. This extension mimics findings that transcranial direct current stimulation (tDCS) over the motor cortex modulates the colour priming effect (Woodgate et al., 2015). The results with the new CoRLEGO suggest that feedback connections from the motor system to the brain’s attentional system (parietal cortex) guide visual attention to extract movement-relevant information (i.e. colour) from visual stimuli. This paper adds to growing evidence that there is a close interaction between the motor system and the attention system. This evidence contradicts the traditional conceptualization of the motor system as the endpoint of a serial chain of processing stages. At the end of the paper we discuss CoRLEGO’s predictions and also lessons for neurobiologically inspired robotics emerging from this work. PMID:26667353

A new type of gene-disruption cassette with a rescue gene for Pichia pastoris.

PubMed

Shibui, Tatsuro; Hara, Hiroyoshi

2017-09-01

Pichia pastoris has been used for the production of many recombinant proteins, and many useful mutant strains have been created. However, the efficiency of mutant isolation by gene-targeting is usually low and the procedure is difficult for those inexperienced in yeast genetics. In order to overcome these issues, we developed a new gene-disruption system with a rescue gene using an inducible Cre/mutant-loxP system. With only short homology regions, the gene-disruption cassette of the system replaces its target-gene locus containing a mutation with a compensatory rescue gene. As the cassette contains the AOX1 promoter-driven Cre gene, when targeted strains are grown on media containing methanol, the DNA fragment, i.e., the marker, rescue and Cre genes, between the mutant-loxP sequences in the cassette is excised, leaving only the remaining mutant-loxP sequence in the genome, and consequently a target gene-disrupted mutant can be isolated. The system was initially validated on ADE2 gene disruption, where the disruption can easily be detected by color-change of the colonies. Then, the system was applied for knocking-out URA3 and OCH1 genes, reported to be difficult to accomplish by conventional gene-targeting methods. All three gene-disruption cassettes with their rescue genes replaced their target genes, and the Cre/mutant-loxP system worked well to successfully isolate their knock-out mutants. This study identified a new gene-disruption system that could be used to effectively and strategically knock out genes of interest, especially whose deletion is detrimental to growth, without using special strains, e.g., deficient in nonhomologous end-joining, in P. pastoris. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1201-1208, 2017. © 2017 American Institute of Chemical Engineers.

Dual systemic tumor targeting with ligand-directed phage and Grp78 promoter induces tumor regression.

PubMed

Kia, Azadeh; Przystal, Justyna M; Nianiaris, Nastasia; Mazarakis, Nicholas D; Mintz, Paul J; Hajitou, Amin

2012-12-01

The tumor-specific Grp78 promoter is overexpressed in aggressive tumors. Cancer patients would benefit greatly from application of this promoter in gene therapy and molecular imaging; however, clinical benefit is limited by lack of strategies to target the systemic delivery of Grp78-driven transgenes to tumors. This study aims to assess the systemic efficacy of Grp78-guided expression of therapeutic and imaging transgenes relative to the standard cytomegalovirus (CMV) promoter. Combination of ligand and Grp78 transcriptional targeting into a single vector would facilitate systemic applications of the Grp78 promoter. We generated a dual tumor-targeted phage containing the arginine-glycine-aspartic acid tumor homing ligand and Grp78 promoter. Next, we combined flow cytometry, Western blot analysis, bioluminescence imaging of luciferase, and HSVtk/ganciclovir gene therapy and compared efficacy to conventional phage carrying the CMV promoter in vitro and in vivo in subcutaneous models of rat and human glioblastoma. We show that double-targeted phage provides persistent transgene expression in vitro and in tumors in vivo after systemic administration compared with conventional phage. Next, we showed significant tumor killing in vivo using the HSVtk/ganciclovir gene therapy and found a systemic antitumor effect of Grp78-driven HSVtk against therapy-resistant tumors. Finally, we uncovered a novel mechanism of Grp78 promoter activation whereby HSVtk/ganciclovir therapy upregulates Grp78 and transgene expression via the conserved unfolded protein response signaling cascade. These data validate the potential of Grp78 promoter in systemic cancer gene therapy and report the efficacy of a dual tumor targeting phage that may prove useful for translation into gene therapy and molecular imaging applications.

Fuzzy Neural Network-Based Interacting Multiple Model for Multi-Node Target Tracking Algorithm

PubMed Central

Sun, Baoliang; Jiang, Chunlan; Li, Ming

2016-01-01

An interacting multiple model for multi-node target tracking algorithm was proposed based on a fuzzy neural network (FNN) to solve the multi-node target tracking problem of wireless sensor networks (WSNs). Measured error variance was adaptively adjusted during the multiple model interacting output stage using the difference between the theoretical and estimated values of the measured error covariance matrix. The FNN fusion system was established during multi-node fusion to integrate with the target state estimated data from different nodes and consequently obtain network target state estimation. The feasibility of the algorithm was verified based on a network of nine detection nodes. Experimental results indicated that the proposed algorithm could trace the maneuvering target effectively under sensor failure and unknown system measurement errors. The proposed algorithm exhibited great practicability in the multi-node target tracking of WSNs. PMID:27809271

Penalty dynamic programming algorithm for dim targets detection in sensor systems.

PubMed

Huang, Dayu; Xue, Anke; Guo, Yunfei

2012-01-01

In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations.

Interferometric Quasi-Autocollimator

NASA Technical Reports Server (NTRS)

Turner, Matthew D. (Inventor); Gundlach, Jens H. (Inventor); Schlamminger, Stephan (Inventor); Hagedorn, Charles A. (Inventor)

2014-01-01

Systems and method are disclosed for measuring small angular deflections of a target using weak value amplification. A system includes a beam source, a beam splitter, a target reflecting surface, a photodetector, and a processor. The beam source generates an input beam that is split into first and second beams by the beam splitter. The first and second beams are propagated to the target reflecting surface, at least partially superimposed at the target reflecting surface, and incident to the target reflecting surface normal to the target reflecting surface. The first beam is reflected an additional even number of times during propagation to the photodetector. The second beam is reflected an additional odd number of times during propagation to the photodetector. The first and second beams interfere at the photodetector so as to produce interference patterns. The interference patterns are interpreted to measure angular deflections of the target reflecting surface.

Multiple target drug cocktail design for attacking the core network markers of four cancers using ligand-based and structure-based virtual screening methods

PubMed Central

2015-01-01

Background Computer-aided drug design has a long history of being applied to discover new molecules to treat various cancers, but it has always been focused on single targets. The development of systems biology has let scientists reveal more hidden mechanisms of cancers, but attempts to apply systems biology to cancer therapies remain at preliminary stages. Our lab has successfully developed various systems biology models for several cancers. Based on these achievements, we present the first attempt to combine multiple-target therapy with systems biology. Methods In our previous study, we identified 28 significant proteins--i.e., common core network markers--of four types of cancers as house-keeping proteins of these cancers. In this study, we ranked these proteins by summing their carcinogenesis relevance values (CRVs) across the four cancers, and then performed docking and pharmacophore modeling to do virtual screening on the NCI database for anti-cancer drugs. We also performed pathway analysis on these proteins using Panther and MetaCore to reveal more mechanisms of these cancer house-keeping proteins. Results We designed several approaches to discover targets for multiple-target cocktail therapies. In the first one, we identified the top 20 drugs for each of the 28 cancer house-keeping proteins, and analyzed the docking pose to further understand the interaction mechanisms of these drugs. After screening for duplicates, we found that 13 of these drugs could target 11 proteins simultaneously. In the second approach, we chose the top 5 proteins with the highest summed CRVs and used them as the drug targets. We built a pharmacophore and applied it to do virtual screening against the Life-Chemical library for anti-cancer drugs. Based on these results, wet-lab bio-scientists could freely investigate combinations of these drugs for multiple-target therapy for cancers, in contrast to the traditional single target therapy. Conclusions Combination of systems biology with computer-aided drug design could help us develop novel drug cocktails with multiple targets. We believe this will enhance the efficiency of therapeutic practice and lead to new directions for cancer therapy. PMID:26680552

Current trends in the use of liposomes for tumor targeting

PubMed Central

Deshpande, Pranali P; Biswas, Swati; Torchilin, Vladimir P

2013-01-01

The use of liposomes for drug delivery began early in the history of pharmaceutical nanocarriers. These nanosized, lipid bilayered vesicles have become popular as drug delivery systems owing to their efficiency, biocompatibility, nonimmunogenicity, enhanced solubility of chemotherapeutic agents and their ability to encapsulate a wide array of drugs. Passive and ligand-mediated active targeting promote tumor specificity with diminished adverse off-target effects. The current field of liposomes focuses on both clinical and diagnostic applications. Recent efforts have concentrated on the development of multifunctional liposomes that target cells and cellular organelles with a single delivery system. This review discusses the recent advances in liposome research in tumor targeting. PMID:23914966

Theoretical analysis of the electrical aspects of the basic electro-impulse problem in aircraft de-icing applications

NASA Technical Reports Server (NTRS)

Henderson, R. A.; Schrag, R. L.

1986-01-01

A summary of modeling the electrical system aspects of a coil and metal target configuration resembling a practical electro-impulse deicing (EIDI) installation, and a simple circuit for providing energy to the coil, was presented. The model was developed in sufficient theoretical detail to allow the generation of computer algorithms for the current in the coil, the magnetic induction on both surfaces of the target, the force between the coil and target, and the impulse delivered to the target. These algorithms were applied to a specific prototype EIDI test system for which the current, magnetic fields near the target surfaces, and impulse were previously measured.

Polarization effects on hard target calibration of lidar systems

NASA Technical Reports Server (NTRS)

Kavaya, Michael J.

1987-01-01

The theory of hard target calibration of lidar backscatter data, including laboratory measurements of the pertinent target reflectance parameters, is extended to include the effects of polarization of the transmitted and received laser radiation. The bidirectional reflectance-distribution function model of reflectance is expanded to a 4 x 4 matrix allowing Mueller matrix and Stokes vector calculus to be employed. Target reflectance parameters for calibration of lidar backscatter data are derived for various lidar system polarization configurations from integrating sphere and monostatic reflectometer measurements. It is found that correct modeling of polarization effects is mandatory for accurate calibration of hard target reflectance parameters and, therefore, for accurate calibration of lidar backscatter data.

Multiple operating system rotation environment moving target defense

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

Evans, Nathaniel; Thompson, Michael

Systems and methods for providing a multiple operating system rotation environment ("MORE") moving target defense ("MTD") computing system are described. The MORE-MTD system provides enhanced computer system security through a rotation of multiple operating systems. The MORE-MTD system increases attacker uncertainty, increases the cost of attacking the system, reduces the likelihood of an attacker locating a vulnerability, and reduces the exposure time of any located vulnerability. The MORE-MTD environment is effectuated by rotation of the operating systems at a given interval. The rotating operating systems create a consistently changing attack surface for remote attackers.

Quantitative targeting maps based on experimental investigations for a branched tube model in magnetic drug targeting

NASA Astrophysics Data System (ADS)

Gitter, K.; Odenbach, S.

2011-12-01

Magnetic drug targeting (MDT), because of its high targeting efficiency, is a promising approach for tumour treatment. Unwanted side effects are considerably reduced, since the nanoparticles are concentrated within the target region due to the influence of a magnetic field. Nevertheless, understanding the transport phenomena of nanoparticles in an artery system is still challenging. This work presents experimental results for a branched tube model. Quantitative results describe, for example, the net amount of nanoparticles that are targeted towards the chosen region due to the influence of a magnetic field. As a result of measurements, novel drug targeting maps, combining, e.g. the magnetic volume force, the position of the magnet and the net amount of targeted nanoparticles, are presented. The targeting maps are valuable for evaluation and comparison of setups and are also helpful for the design and the optimisation of a magnet system with an appropriate strength and distribution of the field gradient. The maps indicate the danger of accretion within the tube and also show the promising result of magnetic drug targeting that up to 97% of the nanoparticles were successfully targeted.

Interacting with target tracking algorithms in a gaze-enhanced motion video analysis system

NASA Astrophysics Data System (ADS)

Hild, Jutta; Krüger, Wolfgang; Heinze, Norbert; Peinsipp-Byma, Elisabeth; Beyerer, Jürgen

2016-05-01

Motion video analysis is a challenging task, particularly if real-time analysis is required. It is therefore an important issue how to provide suitable assistance for the human operator. Given that the use of customized video analysis systems is more and more established, one supporting measure is to provide system functions which perform subtasks of the analysis. Recent progress in the development of automated image exploitation algorithms allow, e.g., real-time moving target tracking. Another supporting measure is to provide a user interface which strives to reduce the perceptual, cognitive and motor load of the human operator for example by incorporating the operator's visual focus of attention. A gaze-enhanced user interface is able to help here. This work extends prior work on automated target recognition, segmentation, and tracking algorithms as well as about the benefits of a gaze-enhanced user interface for interaction with moving targets. We also propose a prototypical system design aiming to combine both the qualities of the human observer's perception and the automated algorithms in order to improve the overall performance of a real-time video analysis system. In this contribution, we address two novel issues analyzing gaze-based interaction with target tracking algorithms. The first issue extends the gaze-based triggering of a target tracking process, e.g., investigating how to best relaunch in the case of track loss. The second issue addresses the initialization of tracking algorithms without motion segmentation where the operator has to provide the system with the object's image region in order to start the tracking algorithm.

Targeting Extracellular Matrix Glycoproteins in Metastases for Tumor-Initiating Cell Therapy

DTIC Science & Technology

2016-04-01

effects of OPN-targeting system carrying a hedgehog pathway inhibitor (month 3-12) (not completed)  What was accomplished under these goals? Major...Preparation of prostaspheres 4 • objective 2: Evaluate the therapeutic effects of OPN-targeting system carrying a hedgehog pathway inhibitor...encapsulate a hedgehog pathway inhibitor cyclopamine (CP), and the data are as follows: Average diameter (nm) PDI Zeta potential (mV) Blank LN, no OPN

Remote Sensing Operational Capabilities

DTIC Science & Technology

1999-10-01

systems. In each of the cases orbital and sensor characteristics were modeled , as was the possible impact of weather over target areas. In each of the...collect the desired information quickly, it is imperative that the satellite be capable of accessing the target area frequently. • Flexibility and...be capable of accessing the target area frequently. 66 • Flexibility and speed in tasking: the system should be capable of collecting data with a

Fibrin-binding, peptide amphiphile micelles for targeting glioblastoma.

PubMed

Chung, Eun Ji; Cheng, Yu; Morshed, Ramin; Nord, Kathryn; Han, Yu; Wegscheid, Michelle L; Auffinger, Brenda; Wainwright, Derek A; Lesniak, Maciej S; Tirrell, Matthew V

2014-01-01

Glioblastoma-targeted drug delivery systems facilitate efficient delivery of chemotherapeutic agents to malignant gliomas, while minimizing systemic toxicity and side effects. Taking advantage of the fibrin deposition that is characteristic of tumors, we constructed spherical, Cy7-labeled, targeting micelles to glioblastoma through the addition of the fibrin-binding pentapeptide, cysteine-arginine-glutamic acid-lysine-alanine, or CREKA. Conjugation of the CREKA peptide to Cy7-micelles increased the average particle size and zeta potential. Upon intravenous administration to GL261 glioma bearing mice, Cy7-micelles passively accumulated at the brain tumor site via the enhanced permeability and retention (EPR) effect, and Cy7-CREKA-micelles displayed enhanced tumor homing via active targeting as early as 1 h after administration, as confirmed via in vivo and ex vivo imaging and immunohistochemistry. Biodistribution of micelles showed an accumulation within the liver and kidneys, leading to micelle elimination via renal clearance and the reticuloendothelial system (RES). Histological evaluation showed no signs of cytotoxicity or tissue damage, confirming the safety and utility of this nanoparticle system for delivery to glioblastoma. Our findings offer strong evidence for the glioblastoma-targeting potential of CREKA-micelles and provide the foundation for CREKA-mediated, targeted therapy of glioma. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chromosomal targeting by CRISPR-Cas systems can contribute to genome plasticity in bacteria

PubMed Central

Dy, Ron L; Pitman, Andrew R; Fineran, Peter C

2013-01-01

The clustered regularly interspaced short palindromic repeats (CRISPR) and their associated (Cas) proteins form adaptive immune systems in bacteria to combat phage and other foreign genetic elements. Typically, short spacer sequences are acquired from the invader DNA and incorporated into CRISPR arrays in the bacterial genome. Small RNAs are generated that contain these spacer sequences and enable sequence-specific destruction of the foreign nucleic acids. Occasionally, spacers are acquired from the chromosome, which instead leads to targeting of the host genome. Chromosomal targeting is highly toxic to the bacterium, providing a strong selective pressure for a variety of evolutionary routes that enable host cell survival. Mutations that inactivate the CRISPR-Cas functionality, such as within the cas genes, CRISPR repeat, protospacer adjacent motifs (PAM), and target sequence, mediate escape from toxicity. This self-targeting might provide some explanation for the incomplete distribution of CRISPR-Cas systems in less than half of sequenced bacterial genomes. More importantly, self-genome targeting can cause large-scale genomic alterations, including remodeling or deletion of pathogenicity islands and other non-mobile chromosomal regions. While control of horizontal gene transfer is perceived as their main function, our recent work illuminates an alternative role of CRISPR-Cas systems in causing host genomic changes and influencing bacterial evolution. PMID:24251073

shRNA target prediction informed by comprehensive enquiry (SPICE): a supporting system for high-throughput screening of shRNA library.

PubMed

Kamatuka, Kenta; Hattori, Masahiro; Sugiyama, Tomoyasu

2016-12-01

RNA interference (RNAi) screening is extensively used in the field of reverse genetics. RNAi libraries constructed using random oligonucleotides have made this technology affordable. However, the new methodology requires exploration of the RNAi target gene information after screening because the RNAi library includes non-natural sequences that are not found in genes. Here, we developed a web-based tool to support RNAi screening. The system performs short hairpin RNA (shRNA) target prediction that is informed by comprehensive enquiry (SPICE). SPICE automates several tasks that are laborious but indispensable to evaluate the shRNAs obtained by RNAi screening. SPICE has four main functions: (i) sequence identification of shRNA in the input sequence (the sequence might be obtained by sequencing clones in the RNAi library), (ii) searching the target genes in the database, (iii) demonstrating biological information obtained from the database, and (iv) preparation of search result files that can be utilized in a local personal computer (PC). Using this system, we demonstrated that genes targeted by random oligonucleotide-derived shRNAs were not different from those targeted by organism-specific shRNA. The system facilitates RNAi screening, which requires sequence analysis after screening. The SPICE web application is available at http://www.spice.sugysun.org/.

Designing oral vaccines targeting intestinal dendritic cells.

PubMed

Devriendt, Bert; De Geest, Bruno G; Cox, Eric

2011-04-01

Most pathogens colonize and invade the host at mucosal surfaces, such as the lung and the intestine. To combat intestinal pathogens the induction of local adaptive immune responses is required, which is mainly achieved through oral vaccination. However, most vaccines are ineffective when given orally owing to the hostile environment in the gastrointestinal tract. The encapsulation of antigens in biodegradable microparticulate delivery systems enhances their immunogenicity; however, the uptake of these delivery systems by intestinal immune cells is rather poor. Surface decoration of the particulates with targeting ligands could increase the uptake and mediate the selective targeting of the vaccine to intestinal antigen-presenting cells, including dendritic cells. In this review, current knowledge on dendritic cell subsets is discussed, along with progress in the development of selective antigen targeting to these cells, in addition to focusing on data obtained in mice and, where possible, the pig, as a non-rodent animal model for humans. Moreover, the potential use and benefits of Fcγ receptor-mediated targeting of antigen delivery systems are highlighted. In conclusion, dendritic cell targeting ligands grafted on antigen carrier systems should preferably bind to a conserved endocytotic receptor, facilitating the design of a multispecies vaccine platform, which could elicit robust protective immune responses against enteric pathogens.

Anti-ship missile tracking with a chirped amplitude modulation ladar

NASA Astrophysics Data System (ADS)

Redman, Brian C.; Stann, Barry L.; Ruff, William C.; Giza, Mark M.; Aliberti, Keith; Lawler, William B.

2004-09-01

Shipboard infrared search and track (IRST) systems can detect sea-skimming anti-ship missiles at long ranges. Since IRST systems cannot measure range and velocity, they have difficulty distinguishing missiles from slowly moving false targets and clutter. ARL is developing a ladar based on its patented chirped amplitude modulation (AM) technique to provide unambiguous range and velocity measurements of targets handed over to it by the IRST. Using the ladar's range and velocity data, false alarms and clutter objects will be distinguished from valid targets. If the target is valid, it's angular location, range, and velocity, will be used to update the target track until remediation has been effected. By using an array receiver, ARL's ladar can also provide 3D imagery of potential threats in support of force protection. The ladar development program will be accomplished in two phases. In Phase I, currently in progress, ARL is designing and building a breadboard ladar test system for proof-of-principle static platform field tests. In Phase II, ARL will build a brassboard ladar test system that will meet operational goals in shipboard testing against realistic targets. The principles of operation for the chirped AM ladar for range and velocity measurements, the ladar performance model, and the top-level design for the Phase I breadboard are presented in this paper.

CT-Guided Interventions Using a Free-Hand, Optical Tracking System: Initial Clinical Experience

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

Schubert, Tilman, E-mail: TSchubert@uhbs.ch; Jacob, Augustinus L.; Pansini, Michele

2013-08-01

PurposeThe present study was designed to evaluate the geometrical accuracy and clinical applicability of a new, free-hand, CT-guided, optical navigation system.MethodsFifteen procedures in 14 consecutive patients were retrospectively analyzed. The navigation system was applied for interventional procedures on small target lesions, in cases with long needle paths, narrow access windows, or when an out-of-plane access was expected. Mean lesion volume was 27.9 ml, and mean distance to target measured was 107.5 mm. Eleven of 15 needle trajectories were planned as out-of-plane approaches regarding the axial CT plane.ResultsNinety-one percent of the biopsies were diagnostic. All therapeutic interventions were technically successful. Targetingmore » precision was high with a mean distance of the needle tip from planned target of 1.98 mm. Mean intervention time was 1:12 h. A statistically significant correlation between angular needle deviation and intervention time (p = 0.007), respiratory movement of the target (p = 0.008), and body mass index (p = 0.02) was detected. None of the evaluated parameters correlated significantly with the distance from the needle tip to the planned target.ConclusionsThe application of a navigation system for complex CT-guided procedures provided safe and effective targeting within a reasonable intervention time in our series.« less

Target Recognition Using Neural Networks for Model Deformation Measurements

NASA Technical Reports Server (NTRS)

Ross, Richard W.; Hibler, David L.

1999-01-01

Optical measurements provide a non-invasive method for measuring deformation of wind tunnel models. Model deformation systems use targets mounted or painted on the surface of the model to identify known positions, and photogrammetric methods are used to calculate 3-D positions of the targets on the model from digital 2-D images. Under ideal conditions, the reflective targets are placed against a dark background and provide high-contrast images, aiding in target recognition. However, glints of light reflecting from the model surface, or reduced contrast caused by light source or model smoothness constraints, can compromise accurate target determination using current algorithmic methods. This paper describes a technique using a neural network and image processing technologies which increases the reliability of target recognition systems. Unlike algorithmic methods, the neural network can be trained to identify the characteristic patterns that distinguish targets from other objects of similar size and appearance and can adapt to changes in lighting and environmental conditions.

Molecular Composition Analysis of Distant Targets

NASA Technical Reports Server (NTRS)

Hughes, Gary B.; Lubin, Philip

2017-01-01

This document is the Final Report for NASA Innovative Advanced Concepts (NIAC) Phase I Grant 15-NIAC16A-0145, titled Molecular Composition Analysis of Distant Targets. The research was focused on developing a system concept for probing the molecular composition of cold solar system targets, such as Asteroids, Comets, Planets and Moons from a distant vantage, for example from a spacecraft that is orbiting the target (Hughes et al., 2015). The orbiting spacecraft is equipped with a high-power laser, which is run by electricity from photovoltaic panels. The laser is directed at a spot on the target. Materials on the surface of the target are heated by the laser beam, and begin to melt and then evaporate, forming a plume of asteroid molecules in front of the heated spot. The heated spot glows, producing blackbody illumination that is visible from the spacecraft, via a path through the evaporated plume. As the blackbody radiation from the heated spot passes through the plume of evaporated material, molecules in the plume absorb radiation in a manner that is specific to the rotational and vibrational characteristics of the specific molecules. A spectrometer aboard the spacecraft is used to observe absorption lines in the blackbody signal. The pattern of absorption can be used to estimate the molecular composition of materials in the plume, which originated on the target. Focusing on a single spot produces a borehole, and shallow subsurface profiling of the targets bulk composition is possible. At the beginning of the Phase I research, the estimated Technology Readiness Level (TRL) of the system was TRL-1. During the Phase I research, an end-to-end theoretical model of the sensor system was developed from first principles. The model includes laser energy and optical propagation, target heating, melting and evaporation of target material, plume density, thermal radiation from the heated spot, molecular cross section of likely asteroid materials, and estimation of the absorption profile at a distant spectrometer. Results obtained by executing simulations based on the model provide compelling evidence that the concept of remote laser evaporative molecular absorption spectroscopy is feasible. In this document, technical details of the model are presented, and results of simulations are described that indicate the utility of the proposed sensor system. Additionally, an asteroid rendezvous mission is analyzed, with a survey of system requirements to accomplish molecular composition analysis of the asteroid. Based on positive theoretical results obtained during Phase I, the estimated TRL of the system is now TRL-2. This document also describes potential future research and experimentation that could push the system to TRL-4 within 2 years. Steps required for construction of a laboratory prototype are described. An experiment to test predictions of the theory is described, based on the laboratory prototype setup.

Multi-agent autonomous system

NASA Technical Reports Server (NTRS)

Fink, Wolfgang (Inventor); Dohm, James (Inventor); Tarbell, Mark A. (Inventor)

2010-01-01

A multi-agent autonomous system for exploration of hazardous or inaccessible locations. The multi-agent autonomous system includes simple surface-based agents or craft controlled by an airborne tracking and command system. The airborne tracking and command system includes an instrument suite used to image an operational area and any craft deployed within the operational area. The image data is used to identify the craft, targets for exploration, and obstacles in the operational area. The tracking and command system determines paths for the surface-based craft using the identified targets and obstacles and commands the craft using simple movement commands to move through the operational area to the targets while avoiding the obstacles. Each craft includes its own instrument suite to collect information about the operational area that is transmitted back to the tracking and command system. The tracking and command system may be further coupled to a satellite system to provide additional image information about the operational area and provide operational and location commands to the tracking and command system.

Researchers use Modified CRISPR Systems to Modulate Gene Expression on a Genomic Scale

Cancer.gov

Cancer Target Discovery and Development Network (CTD2) researchers at the University of California, San Francisco, developed a CRISPR system that can regulate both gene repression and activation with fewer off-target effects.

Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex.

PubMed

Guo, Tai Wei; Bartesaghi, Alberto; Yang, Hui; Falconieri, Veronica; Rao, Prashant; Merk, Alan; Eng, Edward T; Raczkowski, Ashleigh M; Fox, Tara; Earl, Lesley A; Patel, Dinshaw J; Subramaniam, Sriram

2017-10-05

Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition. Published by Elsevier Inc.

Design, construction and performance evaluation of the target tissue thickness measurement system in intraoperative radiotherapy for breast cancer

NASA Astrophysics Data System (ADS)

Yazdani, Mohammad Reza; Setayeshi, Saeed; Arabalibeik, Hossein; Akbari, Mohammad Esmaeil

2017-05-01

Intraoperative electron radiation therapy (IOERT), which uses electron beams for irradiating the target directly during the surgery, has the advantage of delivering a homogeneous dose to a controlled layer of tissue. Since the dose falls off quickly below the target thickness, the underlying normal tissues are spared. In selecting the appropriate electron energy, the accuracy of the target tissue thickness measurement is critical. In contrast to other procedures applied in IOERT, the routine measurement method is considered to be completely traditional and approximate. In this work, a novel mechanism is proposed for measuring the target tissue thickness with an acceptable level of accuracy. An electronic system has been designed and manufactured with the capability of measuring the tissue thickness based on the recorded electron density under the target. The results indicated the possibility of thickness measurement with a maximum error of 2 mm for 91.35% of data. Aside from system limitation in estimating the thickness of 5 mm phantom, for 88.94% of data, maximum error is 1 mm.

Optical system design of solar-blind UV target simulator with long focal length

NASA Astrophysics Data System (ADS)

Chen, Yu; Huo, Furong; Zheng, Liqin

2014-11-01

Ultraviolet (UV) radiation of 200nm-300nm waveband from the sun is absorbed by atmosphere, which is often referred to the solar-blind region of the solar spectrum. Solar-blind characteristics of this waveband have important application value, especially in military fields. The application of solar-blind waveband has developed very rapidly, which is receiving more and more attention. Sometimes, to test the performance of a UV optical system, a standard solar-blind UV target simulator is needed as the UV light source. In this paper, an optical system of a solar-blind UV target simulator is designed with waveband 240nm-280nm. To simulate a far UV target, the focal length of this UV optical system needs to be long. Besides, different field of view (FOV) of the system should meet aplanatic condition. The optional materials are very few for UV optical systems, in which only CaF2 and JGS1 are commonly used. Various aberrations are difficult to be corrected. To save production cost and enhance the precision of fabrication and test, aspheric surfaces and binary elements are not adopted in the system. Moreover, doublet or triplet cannot be used in UV optical system considering possible cracking for different thermal expansion coefficients of different materials. After optimization, the system is composed of 4 lenses with focal length 500mm. MTF curves of different FOV coincide together. The maximum RMS radius of the optimized system has almost the same size as Airy disk, which proves the good image quality after system optimization. The aplanatic condition is met very well in this system. In the spot diagram, root mean square (RMS) radius changes from 3 microns to 3.6 microns, which has similar size with Airy disk and meets aplanatic condition very well. This optical system of solar-blind UV target simulator also has relatively loose tolerance data, which can prove the system is designed in an optimal state.

Development of germ-line-specific CRISPR-Cas9 systems to improve the production of heritable gene modifications in Arabidopsis.

PubMed

Mao, Yanfei; Zhang, Zhengjing; Feng, Zhengyan; Wei, Pengliang; Zhang, Hui; Botella, José Ramón; Zhu, Jian-Kang

2016-02-01

The Streptococcus-derived CRISPR/Cas9 system is being widely used to perform targeted gene modifications in plants. This customized endonuclease system has two components, the single-guide RNA (sgRNA) for target DNA recognition and the CRISPR-associated protein 9 (Cas9) for DNA cleavage. Ubiquitously expressed CRISPR/Cas9 systems (UC) generate targeted gene modifications with high efficiency but only those produced in reproductive cells are transmitted to the next generation. We report the design and characterization of a germ-line-specific Cas9 system (GSC) for Arabidopsis gene modification in male gametocytes, constructed using a SPOROCYTELESS (SPL) genomic expression cassette. Four loci in two endogenous genes were targeted by both systems for comparative analysis. Mutations generated by the GSC system were rare in T1 plants but were abundant (30%) in the T2 generation. The vast majority (70%) of the T2 mutant population generated using the UC system were chimeras while the newly developed GSC system produced only 29% chimeras, with 70% of the T2 mutants being heterozygous. Analysis of two loci in the T2 population showed that the abundance of heritable gene mutations was 37% higher in the GSC system compared to the UC system and the level of polymorphism of the mutations was also dramatically increased with the GSC system. Two additional systems based on germ-line-specific promoters (pDD45-GT and pLAT52-GT) were also tested, and one of them was capable of generating heritable homozygous T1 mutant plants. Our results suggest that future application of the described GSC system will facilitate the screening for targeted gene modifications, especially lethal mutations in the T2 population. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Repurposing endogenous type I CRISPR-Cas systems for programmable gene repression

PubMed Central

Luo, Michelle L.; Mullis, Adam S.; Leenay, Ryan T.; Beisel, Chase L.

2015-01-01

CRISPR-Cas systems have shown tremendous promise as heterologous tools for genome editing and transcriptional regulation. Because these RNA-directed immune systems are found in most prokaryotes, an opportunity exists to harness the endogenous systems as convenient tools in these organisms. Here, we report that the Type I-E CRISPR-Cas system in Escherichia coli can be co-opted for programmable transcriptional repression. We found that deletion of the signature cas3 gene converted this immune system into a programmable gene regulator capable of reversible gene silencing of heterologous and endogenous genes. Targeting promoter regions yielded the strongest repression, whereas targeting coding regions showed consistent strand bias. Furthermore, multi-targeting CRISPR arrays could generate complex phenotypes. This strategy offers a simple approach to convert many endogenous Type I systems into transcriptional regulators, thereby expanding the available toolkit for CRISPR-mediated genetic control while creating new opportunities for genome-wide screens and pathway engineering. PMID:25326321

The development of a multi-target compiler-writing system for flight software development

NASA Technical Reports Server (NTRS)

Feyock, S.; Donegan, M. K.

1977-01-01

A wide variety of systems designed to assist the user in the task of writing compilers has been developed. A survey of these systems reveals that none is entirely appropriate to the purposes of the MUST project, which involves the compilation of one or at most a small set of higher-order languages to a wide variety of target machines offering little or no software support. This requirement dictates that any compiler writing system employed must provide maximal support in the areas of semantics specification and code generation, the areas in which existing compiler writing systems as well as theoretical underpinnings are weakest. This paper describes an ongoing research and development effort to create a compiler writing system which will overcome these difficulties, thus providing a software system which makes possible the fast, trouble-free creation of reliable compilers for a wide variety of target computers.

Network-based drug discovery by integrating systems biology and computational technologies

PubMed Central

Leung, Elaine L.; Cao, Zhi-Wei; Jiang, Zhi-Hong; Zhou, Hua

2013-01-01

Network-based intervention has been a trend of curing systemic diseases, but it relies on regimen optimization and valid multi-target actions of the drugs. The complex multi-component nature of medicinal herbs may serve as valuable resources for network-based multi-target drug discovery due to its potential treatment effects by synergy. Recently, robustness of multiple systems biology platforms shows powerful to uncover molecular mechanisms and connections between the drugs and their targeting dynamic network. However, optimization methods of drug combination are insufficient, owning to lacking of tighter integration across multiple ‘-omics’ databases. The newly developed algorithm- or network-based computational models can tightly integrate ‘-omics’ databases and optimize combinational regimens of drug development, which encourage using medicinal herbs to develop into new wave of network-based multi-target drugs. However, challenges on further integration across the databases of medicinal herbs with multiple system biology platforms for multi-target drug optimization remain to the uncertain reliability of individual data sets, width and depth and degree of standardization of herbal medicine. Standardization of the methodology and terminology of multiple system biology and herbal database would facilitate the integration. Enhance public accessible databases and the number of research using system biology platform on herbal medicine would be helpful. Further integration across various ‘-omics’ platforms and computational tools would accelerate development of network-based drug discovery and network medicine. PMID:22877768

An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

PubMed

Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

2017-04-01

Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

HIV-1 Proteins, Tat and gp120, Target the Developing Dopamine System

PubMed Central

Fitting, Sylvia; Booze, Rosemarie M.; Mactutus, Charles F.

2015-01-01

In 2014, 3.2 million children (< 15 years of age) were estimated to be living with HIV and AIDS worldwide, with the 240,000 newly infected children in the past year, i.e., another child infected approximately every two minutes [1]. The primary mode of HIV infection is through mother-to-child transmission (MTCT), occurring either in utero, intrapartum, or during breastfeeding. The effects of HIV-1 on the central nervous system (CNS) are putatively accepted to be mediated, in part, via viral proteins, such as Tat and gp120. The current review focuses on the targets of HIV-1 proteins during the development of the dopamine (DA) system, which appears to be specifically susceptible in HIV-1-infected children. Collectively, the data suggest that the DA system is a clinically relevant target in chronic HIV-1 infection, is one of the major targets in pediatric HIV-1 CNS infection, and may be specifically susceptible during development. The present review discusses the development of the DA system, follows the possible targets of the HIV-1 proteins during the development of the DA system, and suggests potential therapeutic approaches. By coupling our growing understanding of the development of the CNS with the pronounced age-related differences in disease progression, new light may be shed on the neurological and neurocognitive deficits that follow HIV-1 infection. PMID:25613135

The eyes of LITENING

NASA Astrophysics Data System (ADS)

Moser, Eric K.

2016-05-01

LITENING is an airborne system-of-systems providing long-range imaging, targeting, situational awareness, target tracking, weapon guidance, and damage assessment, incorporating a laser designator and laser range finders, as well as non-thermal and thermal imaging systems, with multi-sensor boresight. Robust operation is at a premium, and subsystems are partitioned to modular, swappable line-replaceable-units (LRUs) and shop-replaceable-units (SRUs). This presentation will explore design concepts for sensing, data storage, and presentation of imagery associated with the LITENING targeting pod. The "eyes" of LITENING are the electro-optic sensors. Since the initial LITENING II introduction to the US market in the late 90s, as the program has evolved and matured, a series of spiral functional improvements and sensor upgrades have been incorporated. These include laser-illuminated imaging, and more recently, color sensing. While aircraft displays are outside of the LITENING system, updates to the available viewing modules have also driven change, and resulted in increasingly effective ways of utilizing the targeting system. One of the latest LITENING spiral upgrades adds a new capability to display and capture visible-band color imagery, using new sensors. This is an augmentation to the system's existing capabilities, which operate over a growing set of visible and invisible colors, infrared bands, and laser line wavelengths. A COTS visible-band camera solution using a CMOS sensor has been adapted to meet the particular needs associated with the airborne targeting use case.

Mobile Aerial Tracking and Imaging System (MATRIS) for Aeronautical Research

NASA Technical Reports Server (NTRS)

Banks, Daniel W.; Blanchard, R. C.; Miller, G. M.

2004-01-01

A mobile, rapidly deployable ground-based system to track and image targets of aeronautical interest has been developed. Targets include reentering reusable launch vehicles (RLVs) as well as atmospheric and transatmospheric vehicles. The optics were designed to image targets in the visible and infrared wavelengths. To minimize acquisition cost and development time, the system uses commercially available hardware and software where possible. The conception and initial funding of this system originated with a study of ground-based imaging of global aerothermal characteristics of RLV configurations. During that study NASA teamed with the Missile Defense Agency/Innovative Science and Technology Experimentation Facility (MDA/ISTEF) to test techniques and analysis on two Space Shuttle flights.

The design and application of a multi-band IR imager

NASA Astrophysics Data System (ADS)

Li, Lijuan

2018-02-01

Multi-band IR imaging system has many applications in security, national defense, petroleum and gas industry, etc. So the relevant technologies are getting more and more attention in rent years. As we know, when used in missile warning and missile seeker systems, multi-band IR imaging technology has the advantage of high target recognition capability and low false alarm rate if suitable spectral bands are selected. Compared with traditional single band IR imager, multi-band IR imager can make use of spectral features in addition to space and time domain features to discriminate target from background clutters and decoys. So, one of the key work is to select the right spectral bands in which the feature difference between target and false target is evident and is well utilized. Multi-band IR imager is a useful instrument to collect multi-band IR images of target, backgrounds and decoys for spectral band selection study at low cost and with adjustable parameters and property compared with commercial imaging spectrometer. In this paper, a multi-band IR imaging system is developed which is suitable to collect 4 spectral band images of various scenes at every turn and can be expanded to other short-wave and mid-wave IR spectral bands combination by changing filter groups. The multi-band IR imaging system consists of a broad band optical system, a cryogenic InSb large array detector, a spinning filter wheel and electronic processing system. The multi-band IR imaging system's performance is tested in real data collection experiments.

Simultaneous quantification of tumor uptake for targeted and non-targeted liposomes and their encapsulated contents by ICP-MS

PubMed Central

Cheng, Zhiliang; Zaki, Ajlan Al; Hui, James Z; Tsourkas, Andrew

2012-01-01

Liposomes are intensively being developed for biomedical applications including drug and gene delivery. However, targeted liposomal delivery in cancer treatment is a very complicated multi-step process. Unfavorable liposome biodistribution upon intravenous administration and membrane destabilization in blood circulation could result in only a very small fraction of cargo reaching the tumors. It would therefore be desirable to develop new quantitative strategies to track liposomal delivery systems to improve the therapeutic index and decrease systemic toxicity. Here, we developed a simple and non-radiative method to quantify the tumor uptake of targeted and non-targeted control liposomes as well as their encapsulated contents simultaneously. Specifically, four different chelated lanthanide metals were encapsulated or surface-conjugated onto tumor-targeted and non-targeted liposomes, respectively. The two liposome formulations were then injected into tumor-bearing mice simultaneously and their tumor delivery was determined quantitatively via inductively coupled plasma-mass spectroscopy (ICP-MS), allowing for direct comparisons. Tumor uptake of the liposomes themselves and their encapsulated contents were consistent with targeted and non-targeted liposome formulations that were injected individually. PMID:22882145

Biodistribution and Pharmacokinetics of EGFR-Targeted Thiolated Gelatin Nanoparticles Following Systemic Administration in Pancreatic Tumor-Bearing Mice

PubMed Central

Xu, Jing; Gattacceca, Florence; Amiji, Mansoor

2013-01-01

The objective of this study was to evaluate qualitative and quantitative biodistribution of epidermal growth factor receptor (EGFR)-targeted thiolated type B gelatin nanoparticles in vivo in a subcutaneous human pancreatic adenocarcinoma (Panc-1) bearing female SCID Beige mice. EGFR-targeted nanoparticles showed preferential and sustained accumulation in the tumor mass, especially at early time points. Higher blood concentrations and higher tumor accumulations were observed with PEG-modified and EGFR-targeted nanoparticles during the study (AUClast: 17.38 and 19.56 %ID/mL*h in blood, 187 and 322 %ID/g*h in tumor for PEG-modified and EGFR-targeted nanoparticles, respectively), as compared to control, unmodified particles (AUClast: 10.71 %ID/mL*h in blood and 138 %ID/g*h in tumor). EGFR-targeted nanoparticles displayed almost twice tumor targeting efficiency than either PEG-modified or the unmodified nanoparticles, highlighting the efficacy of the active targeting strategy. In conclusion, this study shows that EGFR-targeted and PEG-modified nanoparticles were suitable vehicles for specific systemic delivery in subcutaneous Panc-1 tumor xenograft models. PMID:23544877

Biodistribution and pharmacokinetics of EGFR-targeted thiolated gelatin nanoparticles following systemic administration in pancreatic tumor-bearing mice.

PubMed

Xu, Jing; Gattacceca, Florence; Amiji, Mansoor

2013-05-06

The objective of this study was to evaluate qualitative and quantitative biodistribution of epidermal growth factor receptor (EGFR)-targeted thiolated type B gelatin nanoparticles in vivo in subcutaneous human pancreatic adenocarcinoma (Panc-1) bearing female SCID Beige mice. EGFR-targeted nanoparticles showed preferential and sustained accumulation in the tumor mass, especially at early time points. Higher blood concentrations and higher tumor accumulations were observed with PEG-modified and EGFR-targeted nanoparticles during the study (AUClast: 17.38 and 19.56%ID/mL·h in blood, 187 and 322%ID/g·h in tumor for PEG-modified and EGFR-targeted nanoparticles, respectively), as compared to control, unmodified particles (AUClast: 10.71%ID/mL·h in blood and 138%ID/g·h in tumor). EGFR-targeted nanoparticles displayed almost twice tumor targeting efficiency than either PEG-modified or the unmodified nanoparticles, highlighting the efficacy of the active targeting strategy. In conclusion, this study shows that EGFR-targeted and PEG-modified nanoparticles were suitable vehicles for specific systemic delivery in subcutaneous Panc-1 tumor xenograft models.

Overview of Target Fabrication in Support of Sandia National Laboratories

NASA Astrophysics Data System (ADS)

Schroen, Diana; Breden, Eric; Florio, Joseph; Grine-Jones, Suzi; Holt, Randy; Krych, Wojtek; Metzler, James; Russell, Chris; Stolp, Justin; Streit, Jonathan; Youngblood, Kelly

2004-11-01

Sandia National Laboratories has succeeded in making its pulsed power driver, the Z machine, a valuable testbed for a great variety of experiments. These experiments include ICF, weapon physics, Equation of State and astrophysics. There are four main target types: Dynamic Hohlraum, Double Pinch, Fast Igniter and EOS. The target sizes are comparable to projected NIF sizes. For example, capsules up to 5 mm have been fielded. This talk will focus on the assembly challenges and the use of foams to create these targets. For many targets, diagnostics and capsules are embedded in the foams, and foam dopants have been added. It is the 14 mg/cc foam target with an embedded capsule (containing deuterium) that has reproducibly produced thermonuclear neutrons. For all target types, the characterization and documentation has had to develop to ensure understanding of target performance. To achieve the required resolution we are using a Nikon automated microscope and a custom OMEGA/NIF target assembly system. Our drive for quality has lead us develop a management system that been registered to ISO 9001.

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

Code of Federal Regulations, 2010 CFR

2010-10-01

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

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

Code of Federal Regulations, 2011 CFR

2011-10-01

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

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

Code of Federal Regulations, 2011 CFR

2011-10-01

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

Systems-level mechanisms of action of Panax ginseng: a network pharmacological approach.

PubMed

Park, Sa-Yoon; Park, Ji-Hun; Kim, Hyo-Su; Lee, Choong-Yeol; Lee, Hae-Jeung; Kang, Ki Sung; Kim, Chang-Eop

2018-01-01

Panax ginseng has been used since ancient times based on the traditional Asian medicine theory and clinical experiences, and currently, is one of the most popular herbs in the world. To date, most of the studies concerning P. ginseng have focused on specific mechanisms of action of individual constituents. However, in spite of many studies on the molecular mechanisms of P. ginseng , it still remains unclear how multiple active ingredients of P. ginseng interact with multiple targets simultaneously, giving the multidimensional effects on various conditions and diseases. In order to decipher the systems-level mechanism of multiple ingredients of P. ginseng , a novel approach is needed beyond conventional reductive analysis. We aim to review the systems-level mechanism of P. ginseng by adopting novel analytical framework-network pharmacology. Here, we constructed a compound-target network of P. ginseng using experimentally validated and machine learning-based prediction results. The targets of the network were analyzed in terms of related biological process, pathways, and diseases. The majority of targets were found to be related with primary metabolic process, signal transduction, nitrogen compound metabolic process, blood circulation, immune system process, cell-cell signaling, biosynthetic process, and neurological system process. In pathway enrichment analysis of targets, mainly the terms related with neural activity showed significant enrichment and formed a cluster. Finally, relative degrees analysis for the target-disease association of P. ginseng revealed several categories of related diseases, including respiratory, psychiatric, and cardiovascular diseases.

Programmable Removal of Bacterial Strains by Use of Genome-Targeting CRISPR-Cas Systems

PubMed Central

Gomaa, Ahmed A.; Klumpe, Heidi E.; Luo, Michelle L.; Selle, Kurt; Barrangou, Rodolphe; Beisel, Chase L.

2014-01-01

ABSTRACT CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems in bacteria and archaea employ CRISPR RNAs to specifically recognize the complementary DNA of foreign invaders, leading to sequence-specific cleavage or degradation of the target DNA. Recent work has shown that the accidental or intentional targeting of the bacterial genome is cytotoxic and can lead to cell death. Here, we have demonstrated that genome targeting with CRISPR-Cas systems can be employed for the sequence-specific and titratable removal of individual bacterial strains and species. Using the type I-E CRISPR-Cas system in Escherichia coli as a model, we found that this effect could be elicited using native or imported systems and was similarly potent regardless of the genomic location, strand, or transcriptional activity of the target sequence. Furthermore, the specificity of targeting with CRISPR RNAs could readily distinguish between even highly similar strains in pure or mixed cultures. Finally, varying the collection of delivered CRISPR RNAs could quantitatively control the relative number of individual strains within a mixed culture. Critically, the observed selectivity and programmability of bacterial removal would be virtually impossible with traditional antibiotics, bacteriophages, selectable markers, or tailored growth conditions. Once delivery challenges are addressed, we envision that this approach could offer a novel means to quantitatively control the composition of environmental and industrial microbial consortia and may open new avenues for the development of “smart” antibiotics that circumvent multidrug resistance and differentiate between pathogenic and beneficial microorganisms. PMID:24473129

CRISPR-based screening of genomic island excision events in bacteria.

PubMed

Selle, Kurt; Klaenhammer, Todd R; Barrangou, Rodolphe

2015-06-30

Genomic analysis of Streptococcus thermophilus revealed that mobile genetic elements (MGEs) likely contributed to gene acquisition and loss during evolutionary adaptation to milk. Clustered regularly interspaced short palindromic repeats-CRISPR-associated genes (CRISPR-Cas), the adaptive immune system in bacteria, limits genetic diversity by targeting MGEs including bacteriophages, transposons, and plasmids. CRISPR-Cas systems are widespread in streptococci, suggesting that the interplay between CRISPR-Cas systems and MGEs is one of the driving forces governing genome homeostasis in this genus. To investigate the genetic outcomes resulting from CRISPR-Cas targeting of integrated MGEs, in silico prediction revealed four genomic islands without essential genes in lengths from 8 to 102 kbp, totaling 7% of the genome. In this study, the endogenous CRISPR3 type II system was programmed to target the four islands independently through plasmid-based expression of engineered CRISPR arrays. Targeting lacZ within the largest 102-kbp genomic island was lethal to wild-type cells and resulted in a reduction of up to 2.5-log in the surviving population. Genotyping of Lac(-) survivors revealed variable deletion events between the flanking insertion-sequence elements, all resulting in elimination of the Lac-encoding island. Chimeric insertion sequence footprints were observed at the deletion junctions after targeting all of the four genomic islands, suggesting a common mechanism of deletion via recombination between flanking insertion sequences. These results established that self-targeting CRISPR-Cas systems may direct significant evolution of bacterial genomes on a population level, influencing genome homeostasis and remodeling.

Contribution of self-motion perception to acoustic target localization.

PubMed

Pettorossi, V E; Brosch, M; Panichi, R; Botti, F; Grassi, S; Troiani, D

2005-05-01

The findings of this study suggest that acoustic spatial perception during head movement is achieved by the vestibular system, which is responsible for the correct dynamic of acoustic target pursuit. The ability to localize sounds in space during whole-body rotation relies on the auditory localization system, which recognizes the position of sound in a head-related frame, and on the sensory systems, namely the vestibular system, which perceive head and body movement. The aim of this study was to analyse the contribution of head motion cues to the spatial representation of acoustic targets in humans. Healthy subjects standing on a rotating platform in the dark were asked to pursue with a laser pointer an acoustic target which was horizontally rotated while the body was kept stationary or maintained stationary while the whole body was rotated. The contribution of head motion to the spatial acoustic representation could be inferred by comparing the gains and phases of the pursuit in the two experimental conditions when the frequency was varied. During acoustic target rotation there was a reduction in the gain and an increase in the phase lag, while during whole-body rotations the gain tended to increase and the phase remained constant. The different contributions of the vestibular and acoustic systems were confirmed by analysing the acoustic pursuit during asymmetric body rotation. In this particular condition, in which self-motion perception gradually diminished, an increasing delay in target pursuit was observed.

A Parallel Finite Set Statistical Simulator for Multi-Target Detection and Tracking

NASA Astrophysics Data System (ADS)

Hussein, I.; MacMillan, R.

2014-09-01

Finite Set Statistics (FISST) is a powerful Bayesian inference tool for the joint detection, classification and tracking of multi-target environments. FISST is capable of handling phenomena such as clutter, misdetections, and target birth and decay. Implicit within the approach are solutions to the data association and target label-tracking problems. Finally, FISST provides generalized information measures that can be used for sensor allocation across different types of tasks such as: searching for new targets, and classification and tracking of known targets. These FISST capabilities have been demonstrated on several small-scale illustrative examples. However, for implementation in a large-scale system as in the Space Situational Awareness problem, these capabilities require a lot of computational power. In this paper, we implement FISST in a parallel environment for the joint detection and tracking of multi-target systems. In this implementation, false alarms and misdetections will be modeled. Target birth and decay will not be modeled in the present paper. We will demonstrate the success of the method for as many targets as we possibly can in a desktop parallel environment. Performance measures will include: number of targets in the simulation, certainty of detected target tracks, computational time as a function of clutter returns and number of targets, among other factors.

Calculation of Lung Cancer Volume of Target Based on Thorax Computed Tomography Images using Active Contour Segmentation Method for Treatment Planning System

NASA Astrophysics Data System (ADS)

Patra Yosandha, Fiet; Adi, Kusworo; Edi Widodo, Catur

2017-06-01

In this research, calculation process of the lung cancer volume of target based on computed tomography (CT) thorax images was done. Volume of the target calculation was done in purpose to treatment planning system in radiotherapy. The calculation of the target volume consists of gross tumor volume (GTV), clinical target volume (CTV), planning target volume (PTV) and organs at risk (OAR). The calculation of the target volume was done by adding the target area on each slices and then multiply the result with the slice thickness. Calculations of area using of digital image processing techniques with active contour segmentation method. This segmentation for contouring to obtain the target volume. The calculation of volume produced on each of the targets is 577.2 cm3 for GTV, 769.9 cm3 for CTV, 877.8 cm3 for PTV, 618.7 cm3 for OAR 1, 1,162 cm3 for OAR 2 right, and 1,597 cm3 for OAR 2 left. These values indicate that the image processing techniques developed can be implemented to calculate the lung cancer target volume based on CT thorax images. This research expected to help doctors and medical physicists in determining and contouring the target volume quickly and precisely.

Photogrammetric system and method used in the characterization of a structure

NASA Technical Reports Server (NTRS)

Watson, Kent A. (Inventor); Connell, John W. (Inventor); Pappa, Richard S. (Inventor); Belvin, W. Keith (Inventor); Dorrington, Adrian A. (Inventor); Jones, Thomas W. (Inventor); Danehy, Paul M. (Inventor)

2010-01-01

A photogrammetric system uses an array of spaced-apart targets coupled to a structure. Each target exhibits fluorescence when exposed to a broad beam of illumination. A photogrammetric imaging system located remotely with respect to the structure detects and processes the fluorescence (but not the illumination wavelength) to measure the shape of a structure.

[The research on a pocket microcontroller system for target controlled infusion].

PubMed

Cheng, Yu-Ke; Zhang, Xin-An; Zhang, Yan-Wu; Wu, Qun-Ling; Dou, Jian-Hong; Wang, Rou-Shong

2005-05-01

This paper present a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extended function and easy operation. It has been now used in the clinical anesthesia.

Toward Optimal Target Placement for Neural Prosthetic Devices

PubMed Central

Cunningham, John P.; Yu, Byron M.; Gilja, Vikash; Ryu, Stephen I.; Shenoy, Krishna V.

2008-01-01

Neural prosthetic systems have been designed to estimate continuous reach trajectories (motor prostheses) and to predict discrete reach targets (communication prostheses). In the latter case, reach targets are typically decoded from neural spiking activity during an instructed delay period before the reach begins. Such systems use targets placed in radially symmetric geometries independent of the tuning properties of the neurons available. Here we seek to automate the target placement process and increase decode accuracy in communication prostheses by selecting target locations based on the neural population at hand. Motor prostheses that incorporate intended target information could also benefit from this consideration. We present an optimal target placement algorithm that approximately maximizes decode accuracy with respect to target locations. In simulated neural spiking data fit from two monkeys, the optimal target placement algorithm yielded statistically significant improvements up to 8 and 9% for two and sixteen targets, respectively. For four and eight targets, gains were more modest, as the target layouts found by the algorithm closely resembled the canonical layouts. We trained a monkey in this paradigm and tested the algorithm with experimental neural data to confirm some of the results found in simulation. In all, the algorithm can serve not only to create new target layouts that outperform canonical layouts, but it can also confirm or help select among multiple canonical layouts. The optimal target placement algorithm developed here is the first algorithm of its kind, and it should both improve decode accuracy and help automate target placement for neural prostheses. PMID:18829845

Targeting the Thioredoxin System for Cancer Therapy.

PubMed

Zhang, Junmin; Li, Xinming; Han, Xiao; Liu, Ruijuan; Fang, Jianguo

2017-09-01

Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-molecule TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sinusoidal Siemens star spatial frequency response measurement errors due to misidentified target centers

DOE PAGES

Birch, Gabriel Carisle; Griffin, John Clark

2015-07-23

Numerous methods are available to measure the spatial frequency response (SFR) of an optical system. A recent change to the ISO 12233 photography resolution standard includes a sinusoidal Siemens star test target. We take the sinusoidal Siemens star proposed by the ISO 12233 standard, measure system SFR, and perform an analysis of errors induced by incorrectly identifying the center of a test target. We show a closed-form solution for the radial profile intensity measurement given an incorrectly determined center and describe how this error reduces the measured SFR of the system. As a result, using the closed-form solution, we proposemore » a two-step process by which test target centers are corrected and the measured SFR is restored to the nominal, correctly centered values.« less

Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

PubMed

Masood, Farha

2016-03-01

A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Composite Wavelet Filters for Enhanced Automated Target Recognition

NASA Technical Reports Server (NTRS)

Chiang, Jeffrey N.; Zhang, Yuhan; Lu, Thomas T.; Chao, Tien-Hsin

2012-01-01

Automated Target Recognition (ATR) systems aim to automate target detection, recognition, and tracking. The current project applies a JPL ATR system to low-resolution sonar and camera videos taken from unmanned vehicles. These sonar images are inherently noisy and difficult to interpret, and pictures taken underwater are unreliable due to murkiness and inconsistent lighting. The ATR system breaks target recognition into three stages: 1) Videos of both sonar and camera footage are broken into frames and preprocessed to enhance images and detect Regions of Interest (ROIs). 2) Features are extracted from these ROIs in preparation for classification. 3) ROIs are classified as true or false positives using a standard Neural Network based on the extracted features. Several preprocessing, feature extraction, and training methods are tested and discussed in this paper.

35-GHz radar sensor for automotive collision avoidance

NASA Astrophysics Data System (ADS)

Zhang, Jun

1999-07-01

This paper describes the development of a radar sensor system used for automotive collision avoidance. Because the heavy truck may have great larger radar cross section than a motorcyclist has, the radar receiver may have a large dynamic range. And multi-targets at different speed may confuse the echo spectrum causing the ambiguity between range and speed of target. To get more information about target and background and to adapt to the large dynamic range and multi-targets, a frequency modulated and pseudo- random binary sequences phase modulated continuous wave radar system is described. The analysis of this double- modulation system is given. A high-speed signal processing and data processing component are used to process and combine the data and information from echo at different direction and at every moment.

Systems biology-embedded target validation: improving efficacy in drug discovery.

PubMed

Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

2014-01-01

The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.

A new liposome-based gene delivery system targeting lung epithelial cells using endothelin antagonist.

PubMed

Allon, Nahum; Saxena, Ashima; Chambers, Carolyn; Doctor, Bhupendra P

2012-06-10

We formulated a new gene delivery system based on targeted liposomes. The efficacy of the delivery system was demonstrated in in vitro and in vivo models. The targeting moiety consists of a high-affinity 7-amino-acid peptide, covalently and evenly conjugated to the liposome surface. The targeting peptide acts as an endothelin antagonist, and accelerates liposome binding and internalization. It is devoid of other biological activity. Liposomes with high phosphatidyl serine (PS) were specially formulated to help their fusion with the endosomal membrane at low pH and enable release of the liposome payload into the cytoplasm. A DNA payload, pre-compressed by protamine, was encapsulated into the liposomes, which directed the plasmid into the cell's nucleus. Upon exposure to epithelial cells, binding of the liposomes occurred within 5-10 min, followed by facilitated internalization of the complex. Endosomal escape was complete within 30 min, followed by DNA accumulation in the nucleus 2h post-transfection. A549 lung epithelial cells transfected with plasmid encoding for GFP encapsulated in targeted liposomes expressed significantly more protein than those transfected with plasmid complexed with Lipofectamine. The intra-tracheal instillation of plasmid encoding for GFP encapsulated in targeted liposomes into rat lungs resulted in the expression of GFP in bronchioles and alveoli within 5 days. These results suggest that this delivery system has great potential in targeting genes to lungs. Copyright © 2011 Elsevier B.V. All rights reserved.

Temporal correlation measurements of pulsed dual CO2 lidar returns. [for atmospheric pollution detection

NASA Technical Reports Server (NTRS)

Menyuk, N.; Killinger, D. K.

1981-01-01

A pulsed dual-laser direct-detection differential-absorption lidar DIAL system, operating near 10.6 microns, is used to measure the temporal correlation and statistical properties of backscattered returns from specular and diffuse topographic targets. Results show that atmospheric-turbulence fluctuations can effectively be frozen for pulse separation times on the order of 1-3 msec or less. The diffuse target returns, however, yielded a much lower correlation than that obtained with the specular targets; this being due to uncorrelated system noise effects and different statistics for the two types of target returns.

Real-time wideband cylindrical holographic surveillance system

DOEpatents

Sheen, David M.; McMakin, Douglas L.; Hall, Thomas E.; Severtsen, Ronald H.

1999-01-01

A wideband holographic cylindrical surveillance system including a transceiver for generating a plurality of electromagnetic waves; antenna for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; the transceiver also receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; a computer for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and a display for displaying the processed information to determine nature of the target. The computer has instructions to apply Fast Fourier Transforms and obtain a three dimensional cylindrical image.

System, Apparatus, and Method for Active Debris Removal

NASA Technical Reports Server (NTRS)

Hickey, Christopher J. (Inventor); Spehar, Peter T. (Inventor); Griffith, Sr., Anthony D. (Inventor); Kohli, Rajiv (Inventor); Burns, Susan H. (Inventor); Gruber, David J. (Inventor); Lee, David E. (Inventor); Robinson, Travis M. (Inventor); Damico, Stephen J. (Inventor); Smith, Jason T. (Inventor)

2017-01-01

Systems, apparatuses, and methods for removal of orbital debris are provided. In one embodiment, an apparatus includes a spacecraft control unit configured to guide and navigate the apparatus to a target. The apparatus also includes a dynamic object characterization unit configured to characterize movement, and a capture feature, of the target. The apparatus further includes a capture and release unit configured to capture a target and deorbit or release the target. The collection of these apparatuses is then employed as multiple, independent and individually operated vehicles launched from a single launch vehicle for the purpose of disposing of multiple debris objects.

Real-time holographic surveillance system

DOEpatents

Collins, H. Dale; McMakin, Douglas L.; Hall, Thomas E.; Gribble, R. Parks

1995-01-01

A holographic surveillance system including means for generating electromagnetic waves; means for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; means for receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; means for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and means for displaying the processed information to determine nature of the target. The means for processing the electrical signals includes means for converting analog signals to digital signals followed by a computer means to apply a backward wave algorithm.

Real-time wideband holographic surveillance system

DOEpatents

Sheen, David M.; Collins, H. Dale; Hall, Thomas E.; McMakin, Douglas L.; Gribble, R. Parks; Severtsen, Ronald H.; Prince, James M.; Reid, Larry D.

1996-01-01

A wideband holographic surveillance system including a transceiver for generating a plurality of electromagnetic waves; antenna for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; the transceiver also receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; a computer for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and a display for displaying the processed information to determine nature of the target. The computer has instructions to apply a three dimensional backward wave algorithm.

Real-time wideband holographic surveillance system

DOEpatents

Sheen, D.M.; Collins, H.D.; Hall, T.E.; McMakin, D.L.; Gribble, R.P.; Severtsen, R.H.; Prince, J.M.; Reid, L.D.

1996-09-17

A wideband holographic surveillance system including a transceiver for generating a plurality of electromagnetic waves; antenna for transmitting the electromagnetic waves toward a target at a plurality of predetermined positions in space; the transceiver also receiving and converting electromagnetic waves reflected from the target to electrical signals at a plurality of predetermined positions in space; a computer for processing the electrical signals to obtain signals corresponding to a holographic reconstruction of the target; and a display for displaying the processed information to determine nature of the target. The computer has instructions to apply a three dimensional backward wave algorithm. 28 figs.

Linear and angular retroreflecting interferometric alignment target

DOEpatents

Maxey, L. Curtis

2001-01-01

The present invention provides a method and apparatus for measuring both the linear displacement and angular displacement of an object using a linear interferometer system and an optical target comprising a lens, a reflective surface and a retroreflector. The lens, reflecting surface and retroreflector are specifically aligned and fixed in optical connection with one another, creating a single optical target which moves as a unit that provides multi-axis displacement information for the object with which it is associated. This displacement information is useful in many applications including machine tool control systems and laser tracker systems, among others.

Neural network based system for equipment surveillance

DOEpatents

Vilim, Richard B.; Gross, Kenneth C.; Wegerich, Stephan W.

1998-01-01

A method and system for performing surveillance of transient signals of an industrial device to ascertain the operating state. The method and system involves the steps of reading into a memory training data, determining neural network weighting values until achieving target outputs close to the neural network output. If the target outputs are inadequate, wavelet parameters are determined to yield neural network outputs close to the desired set of target outputs and then providing signals characteristic of an industrial process and comparing the neural network output to the industrial process signals to evaluate the operating state of the industrial process.

Neural network based system for equipment surveillance

DOEpatents

Vilim, R.B.; Gross, K.C.; Wegerich, S.W.

1998-04-28

A method and system are disclosed for performing surveillance of transient signals of an industrial device to ascertain the operating state. The method and system involves the steps of reading into a memory training data, determining neural network weighting values until achieving target outputs close to the neural network output. If the target outputs are inadequate, wavelet parameters are determined to yield neural network outputs close to the desired set of target outputs and then providing signals characteristic of an industrial process and comparing the neural network output to the industrial process signals to evaluate the operating state of the industrial process. 33 figs.

A combined impedance-PD approach for controlling a dual-arm space manipulator in the capture of a non-cooperative target

NASA Astrophysics Data System (ADS)

Stolfi, A.; Gasbarri, P.; Sabatini, M.

2017-10-01

In the near future robotic systems will be playing an increasingly important role in space applications such as repairing, refueling, re-orbiting spacecraft and cleaning up the increasing amount of space debris. Space Manipulator Systems (SMSs) are robotic systems made of a platform (which has its own actuators such as thrusters and reaction wheels) equipped with one or more deployable arms. The present paper focuses on the issue of maintaining a stable first contact between the arms terminal parts (i.e. the end-effectors) and a target satellite, before the actual grasp is performed. The selected approach is a modified version of the Impedance Control algorithm, in which the end-effector is controlled in order to make it behave like a mass-spring-damper system regardless of the reaction motion of the base, so to absorb the impact energy. The usual approach consists in considering a point mass target and one-dimensional contact dynamics; however, the contact between the chaser and the target could generate a perturbation on the attitude of the target. On account of this, in the present work a more realistic scenario, consisting in a 2D rigid target and a relevant 2D contact dynamics, is considered. A two-arm configuration of the SMS is modelled and its effectiveness analyzed. The performance of the proposed control architecture is evaluated by means of a co-simulation involving the MSC Adams multibody code (for describing the dynamics of the space robot and target) together with Simulink (for the determination of the control actions). The co-simulation is a particularly useful tool to implement robust control applied to detailed dynamic systems. Several numerical results complete the work.

Aiming for the Insulin-like Growth Factor-1 system in breast cancer therapeutics.

PubMed

Christopoulos, Panagiotis F; Corthay, Alexandre; Koutsilieris, Michael

2018-02-01

Despite the major discoveries occurred in oncology the recent years, breast malignancies remain one of the most common causes of cancer-related deaths for women in developed countries. Development of HER2-targeting drugs has been considered a breakthrough in anti-cancer approaches and alluded to the potential of targeting growth factors in breast cancer (BrCa) therapeutics. More than twenty-five years have passed since the Insulin-like Growth Factor-1 (IGF-1) system was initially recognized as a potential target candidate in BrCa therapy. To date, a growing body of studies have implicated the IGF-1 signaling with the BrCa biology. Despite the promising experimental evidence, the impression from clinical trials is rather disappointing. Several reasons may account for this and the last word regarding the efficacy of this system as a target candidate in BrCa therapeutics is probably not written yet. Herein, we provide the theoretical basis, as well as, a comprehensive overview of the current literature, regarding the different strategies targeting the various components of the IGF-1/IGF-1R axis in several pathophysiological aspects of BrCa, including the tumor micro-environment and cancer stemness. In addition, we review the rationale for targeting the IGF-1 system in the different BrCa molecular subtypes and in treatment resistant breast tumors with a focus on both the molecular mechanisms and on the clinical perspectives of such approaches in specific population subgroups. We also discuss the future challenges, as well as, the development of novel molecules and strategies targeting the system and suggest potential improvements in the field. Copyright © 2017 Elsevier Ltd. All rights reserved.

SU-G-JeP3-09: Tumor Location Prediction Using Natural Respiratory Volume for Respiratory Gated Radiation Therapy (RGRT): System Verification Study

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

Kim, M; Jung, J; Yoon, D

Purpose: Respiratory gated radiation therapy (RGRT) gives accurate results when a patient’s breathing is stable and regular. Thus, the patient should be fully aware during respiratory pattern training before undergoing the RGRT treatment. In order to bypass the process of respiratory pattern training, we propose a target location prediction system for RGRT that uses only natural respiratory volume, and confirm its application. Methods: In order to verify the proposed target location prediction system, an in-house phantom set was used. This set involves a chest phantom including target, external markers, and motion generator. Natural respiratory volume signals were generated using themore » random function in MATLAB code. In the chest phantom, the target takes a linear motion based on the respiratory signal. After a four-dimensional computed tomography (4DCT) scan of the in-house phantom, the motion trajectory was derived as a linear equation. The accuracy of the linear equation was compared with that of the motion algorithm used by the operating motion generator. In addition, we attempted target location prediction using random respiratory volume values. Results: The correspondence rate of the linear equation derived from the 4DCT images with the motion algorithm of the motion generator was 99.41%. In addition, the average error rate of target location prediction was 1.23% for 26 cases. Conclusion: We confirmed the applicability of our proposed target location prediction system for RGRT using natural respiratory volume. If additional clinical studies can be conducted, a more accurate prediction system can be realized without requiring respiratory pattern training.« less

Mechanism of tissue-selective drug action in the cardiovascular system.

PubMed

Barrett, Terrance D; Triggle, David J; Walker, Michael J A; Maurice, Donald H

2005-04-01

Analysis of the human genome project tells us that there may be as few as 3000 genes that are likely to be good drug targets. Although the number of targets is still very large, these data have been interpreted by some to mean that the pharmaceutical industry may someday run out of novel drug targets. Despite the doom and gloom of such analysis, there is considerable reason for optimism. Drugs may exhibit selectivity of action beyond that predicted by target expression alone. Drugs that act at a single molecular target may have very different pharmacology and, as a result, different therapeutic uses. Three well-characterized model systems are highlighted to illustrate this point. The first model system is exemplified by nifedipine and verapamil, both of which act on L-type calcium channels. Both drugs are used to treat hypertension, but only verapamil can be used to produce atrioventricular block in patients with atrial fibrillation. The second model system describes the therapeutic exploitation of unusual conditions that occur in the ischemic myocardium to produce drugs that are more effective for suppressing ischemia-induced arrhythmias. The third model system discusses the mechanisms through which phosphodiesterase-5 (PDE5) inhibitors act selectively to facilitate penile erection while having little effect in the non-penile vasculature that also expresses PDE5.

Development of Commercial Thermo-sensitive Genic Male Sterile Rice Accelerates Hybrid Rice Breeding Using the CRISPR/Cas9-mediated TMS5 Editing System.

PubMed

Zhou, Hai; He, Ming; Li, Jing; Chen, Liang; Huang, Zhifeng; Zheng, Shaoyan; Zhu, Liya; Ni, Erdong; Jiang, Dagang; Zhao, Bingran; Zhuang, Chuxiong

2016-11-22

Hybrid rice breeding offers an important strategy to improve rice production, in which the cultivation of a male sterile line is the key to the success of cross-breeding. CRISPR/Cas9 systems have been widely used in target-site genome editing, whereas their application for crop genetic improvement has been rarely reported. Here, using the CRISPR/Cas9 system, we induced specific mutations in TMS5, which is the most widely applied thermo-sensitive genic male sterility (TGMS) gene in China, and developed new "transgene clean" TGMS lines. We designed 10 target sites in the coding region of TMS5 for targeted mutagenesis using the CRISPR/Cas9 system and assessed the potential rates of on- and off-target effects. Finally, we established the most efficient construct, the TMS5ab construct, for breeding potentially applicable "transgene clean" TGMS lines. We also discussed factors that affect the editing efficiency according to the characteristics of different target sequences. Notably, using the TMS5ab construct, we developed 11 new "transgene clean" TGMS lines with potential applications in hybrid breeding within only one year in both rice subspecies. The application of our system not only significantly accelerates the breeding of sterile lines but also facilitates the exploitation of heterosis.

Needle Steering in 3-D Via Rapid Replanning

PubMed Central

Patil, Sachin; Burgner, Jessica; Webster, Robert J.; Alterovitz, Ron

2014-01-01

Steerable needles have the potential to improve the effectiveness of needle-based clinical procedures such as biopsy and drug delivery by improving targeting accuracy and reaching previously inaccessible targets that are behind sensitive or impenetrable anatomical regions. We present a new needle steering system capable of automatically reaching targets in 3-D environments while avoiding obstacles and compensating for real-world uncertainties. Given a specification of anatomical obstacles and a clinical target (e.g., from preoperative medical images), our system plans and controls needle motion in a closed-loop fashion under sensory feedback to optimize a clinical metric. We unify planning and control using a new fast algorithm that continuously replans the needle motion. Our rapid replanning approach is enabled by an efficient sampling-based rapidly exploring random tree (RRT) planner that achieves orders-of-magnitude reduction in computation time compared with prior 3-D approaches by incorporating variable curvature kinematics and a novel distance metric for planning. Our system uses an electromagnetic tracking system to sense the state of the needle tip during the procedure. We experimentally evaluate our needle steering system using tissue phantoms and animal tissue ex vivo. We demonstrate that our rapid replanning strategy successfully guides the needle around obstacles to desired 3-D targets with an average error of less than 3 mm. PMID:25435829

Analysis on Target Detection and Classification in LTE Based Passive Forward Scattering Radar

PubMed Central

Raja Abdullah, Raja Syamsul Azmir; Abdul Aziz, Noor Hafizah; Abdul Rashid, Nur Emileen; Ahmad Salah, Asem; Hashim, Fazirulhisyam

2016-01-01

The passive bistatic radar (PBR) system can utilize the illuminator of opportunity to enhance radar capability. By utilizing the forward scattering technique and procedure into the specific mode of PBR can provide an improvement in target detection and classification. The system is known as passive Forward Scattering Radar (FSR). The passive FSR system can exploit the peculiar advantage of the enhancement in forward scatter radar cross section (FSRCS) for target detection. Thus, the aim of this paper is to show the feasibility of passive FSR for moving target detection and classification by experimental analysis and results. The signal source is coming from the latest technology of 4G Long-Term Evolution (LTE) base station. A detailed explanation on the passive FSR receiver circuit, the detection scheme and the classification algorithm are given. In addition, the proposed passive FSR circuit employs the self-mixing technique at the receiver; hence the synchronization signal from the transmitter is not required. The experimental results confirm the passive FSR system’s capability for ground target detection and classification. Furthermore, this paper illustrates the first classification result in the passive FSR system. The great potential in the passive FSR system provides a new research area in passive radar that can be used for diverse remote monitoring applications. PMID:27690051

Network Randomization and Dynamic Defense for Critical Infrastructure Systems

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

Chavez, Adrian R.; Martin, Mitchell Tyler; Hamlet, Jason

2015-04-01

Critical Infrastructure control systems continue to foster predictable communication paths, static configurations, and unpatched systems that allow easy access to our nation's most critical assets. This makes them attractive targets for cyber intrusion. We seek to address these attack vectors by automatically randomizing network settings, randomizing applications on the end devices themselves, and dynamically defending these systems against active attacks. Applying these protective measures will convert control systems into moving targets that proactively defend themselves against attack. Sandia National Laboratories has led this effort by gathering operational and technical requirements from Tennessee Valley Authority (TVA) and performing research and developmentmore » to create a proof-of-concept solution. Our proof-of-concept has been tested in a laboratory environment with over 300 nodes. The vision of this project is to enhance control system security by converting existing control systems into moving targets and building these security measures into future systems while meeting the unique constraints that control systems face.« less

Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems

PubMed Central

Kydd, Janel; Jadia, Rahul; Velpurisiva, Praveena; Gad, Aniket; Paliwal, Shailee; Rai, Prakash

2017-01-01

Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’), the tumor microenvironment (‘tissue targeting’) or the individual cancer cells (‘cellular targeting’). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines. PMID:29036899

Light-emitting diode-based multiwavelength diffuse optical tomography system guided by ultrasound

PubMed Central

Yuan, Guangqian; Alqasemi, Umar; Chen, Aaron; Yang, Yi; Zhu, Quing

2014-01-01

Abstract. Laser diodes are widely used in diffuse optical tomography (DOT) systems but are typically expensive and fragile, while light-emitting diodes (LEDs) are cheaper and are also available in the near-infrared (NIR) range with adequate output power for imaging deeply seated targets. In this study, we introduce a new low-cost DOT system using LEDs of four wavelengths in the NIR spectrum as light sources. The LEDs were modulated at 20 kHz to avoid ambient light. The LEDs were distributed on a hand-held probe and a printed circuit board was mounted at the back of the probe to separately provide switching and driving current to each LED. Ten optical fibers were used to couple the reflected light to 10 parallel photomultiplier tube detectors. A commercial ultrasound system provided simultaneous images of target location and size to guide the image reconstruction. A frequency-domain (FD) laser-diode-based system with ultrasound guidance was also used to compare the results obtained from those of the LED-based system. Results of absorbers embedded in intralipid and inhomogeneous tissue phantoms have demonstrated that the LED-based system provides a comparable quantification accuracy of targets to the FD system and has the potential to image deep targets such as breast lesions. PMID:25473884