Deploying Solid Targets in Dense Plasma Focus Devices for Improved Neutron Yields

NASA Astrophysics Data System (ADS)

Podpaly, Y. A.; Chapman, S.; Povilus, A.; Falabella, S.; Link, A.; Shaw, B. H.; Cooper, C. M.; Higginson, D.; Holod, I.; Sipe, N.; Gall, B.; Schmidt, A. E.

2017-10-01

We report on recent progress in using solid targets in dense plasma focus (DPF) devices. DPFs have been observed to generate energetic ion beams during the pinch phase; these beams interact with the dense plasma in the pinch region as well as the background gas and are believed to be the primary neutron generation mechanism for a D2 gas fill. Targets can be placed in the beam path to enhance neutron yield and to shorten the neutron pulse if desired. In this work, we measure yields from placing titanium deuteride foils, deuterated polyethylene, and non-deuterated control targets in deuterium filled DPFs at both megajoule and kilojoule scales. Furthermore, we have deployed beryllium targets in a helium gas-filled, kilojoule scale DPF for use as a potential AmBe radiological source replacement. Neutron yield, neutron time of flight, and optical images are used to diagnose the effectiveness of target deployments relative to particle-in-cell simulation predictions. A discussion of target holder engineering for material compatibility and damage control will be shown as well. Prepared by LLNL under Contract DE-AC52-07NA27344. Supported by the Office of Defense Nuclear Nonproliferation Research and Development within U.S. DOE's National Nuclear Security Administration and the LLNL Institutional Computing Grand Challenge program.

Indoor detection of passive targets recast as an inverse scattering problem

NASA Astrophysics Data System (ADS)

Gottardi, G.; Moriyama, T.

2017-10-01

The wireless local area networks represent an alternative to custom sensors and dedicated surveillance systems for target indoor detection. The availability of the channel state information has opened the exploitation of the spatial and frequency diversity given by the orthogonal frequency division multiplexing. Such a fine-grained information can be used to solve the detection problem as an inverse scattering problem. The goal of the detection is to reconstruct the properties of the investigation domain, namely to estimate if the domain is empty or occupied by targets, starting from the measurement of the electromagnetic perturbation of the wireless channel. An innovative inversion strategy exploiting both the frequency and the spatial diversity of the channel state information is proposed. The target-dependent features are identified combining the Kruskal-Wallis test and the principal component analysis. The experimental validation points out the detection performance of the proposed method when applied to an existing wireless link of a WiFi architecture deployed in a real indoor scenario. False detection rates lower than 2 [%] have been obtained.

Perceptual load vs. dilution: the roles of attentional focus, stimulus category, and target predictability.

PubMed

Chen, Zhe; Cave, Kyle R

2013-01-01

Many studies have shown that increasing the number of neutral stimuli in a display decreases distractor interference. This result has been interpreted within two different frameworks; a perceptual load account, based on a reduction in spare resources, and a dilution account, based on a degradation in distractor representation and/or an increase in crosstalk between the distractor and the neutral stimuli that contain visually similar features. In four experiments, we systematically manipulated the extent of attentional focus, stimulus category, and preknowledge of the target to examine how these factors would interact with the display set size to influence the degree of distractor processing. Display set size did not affect the degree of distractor processing in all situations. Increasing the number of neutral items decreased distractor processing only when a task induced a broad attentional focus that included the neutral stimuli, when the neutral stimuli were in the same category as the target and distractor, and when the preknowledge of the target was insufficient to guide attention to the target efficiently. These results suggest that the effect of neutral stimuli on the degree of distractor processing is more complex than previously assumed. They provide new insight into the competitive interactions between bottom-up and top-down processes that govern the efficiency of visual selective attention.

Speckle pattern sequential extraction metric for estimating the focus spot size on a remote diffuse target.

PubMed

Yu, Zhan; Li, Yuanyang; Liu, Lisheng; Guo, Jin; Wang, Tingfeng; Yang, Guoqing

2017-11-10

The speckle pattern (line by line) sequential extraction (SPSE) metric is proposed by the one-dimensional speckle intensity level crossing theory. Through the sequential extraction of received speckle information, the speckle metrics for estimating the variation of focusing spot size on a remote diffuse target are obtained. Based on the simulation, we will give some discussions about the SPSE metric range of application under the theoretical conditions, and the aperture size will affect the metric performance of the observation system. The results of the analyses are verified by the experiment. This method is applied to the detection of relative static target (speckled jitter frequency is less than the CCD sampling frequency). The SPSE metric can determine the variation of the focusing spot size over a long distance, moreover, the metric will estimate the spot size under some conditions. Therefore, the monitoring and the feedback of far-field spot will be implemented laser focusing system applications and help the system to optimize the focusing performance.

Perceptual load vs. dilution: the roles of attentional focus, stimulus category, and target predictability

PubMed Central

Chen, Zhe; Cave, Kyle R.

2013-01-01

Many studies have shown that increasing the number of neutral stimuli in a display decreases distractor interference. This result has been interpreted within two different frameworks; a perceptual load account, based on a reduction in spare resources, and a dilution account, based on a degradation in distractor representation and/or an increase in crosstalk between the distractor and the neutral stimuli that contain visually similar features. In four experiments, we systematically manipulated the extent of attentional focus, stimulus category, and preknowledge of the target to examine how these factors would interact with the display set size to influence the degree of distractor processing. Display set size did not affect the degree of distractor processing in all situations. Increasing the number of neutral items decreased distractor processing only when a task induced a broad attentional focus that included the neutral stimuli, when the neutral stimuli were in the same category as the target and distractor, and when the preknowledge of the target was insufficient to guide attention to the target efficiently. These results suggest that the effect of neutral stimuli on the degree of distractor processing is more complex than previously assumed. They provide new insight into the competitive interactions between bottom-up and top-down processes that govern the efficiency of visual selective attention. PMID:23761777

Analyzing Interpersonal Problem Solving in Terms of Solution Focused Approach and Humor Styles of University Student

ERIC Educational Resources Information Center

Koc, Hayri; Arslan, Coskun

2017-01-01

In this study university students interpersonal problem solving approaches were investigated in terms of solution focused approach and humor styles. The participants were 773 (542 female and 231 male, between 17-33 years old) university students. To determine the university students' problem solving approaches "Interpersonal Problem Solving…

Interaction of the high energy deuterons with the graphite target in the plasma focus devices based on Lee model

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

Akel, M., E-mail: pscientific2@aec.org.sy; Alsheikh Salo, S.; Ismael, Sh.

2014-07-15

Numerical experiments are systematically carried out using the Lee model code extended to compute the ion beams on various plasma focus devices operated with Deuterium gas. The deuteron beam properties of the plasma focus are studied for low and high energy plasma focus device. The energy spectral distribution for deuteron ions ejected from the pinch plasma is calculated and the ion numbers with energy around 1 MeV is then determined. The deuteron–graphite target interaction is studied for different conditions. The yield of the reaction {sup 12}C(d,n){sup 13}N and the induced radioactivity for one and multi shots plasma focus devices in themore » graphite solid target is investigated. Our results present the optimized high energy repetitive plasma focus devices as an alternative to accelerators for the production of {sup 13}N short lived radioisotopes. However, technical challenges await solutions on two fronts: (a) operation of plasma focus machines at high rep rates for a sufficient period of time (b) design of durable targets that can take the thermal load.« less

Can ill-structured problems reveal beliefs about medical knowledge and knowing? A focus-group approach

PubMed Central

Roex, Ann; Clarebout, Geraldine; Dory, Valerie; Degryse, Jan

2009-01-01

Background Epistemological beliefs (EB) are an individual's cognitions about knowledge and knowing. In several non-medical domains, EB have been found to contribute to the way individuals reason when faced with ill-structured problems (i.e. problems with no clear-cut, right or wrong solutions). Such problems are very common in medical practice. Determining whether EB are also influential in reasoning processes with regard to medical issues to which there is no straightforward answer, could have implications for medical education. This study focused on 2 research questions: 1. Can ill-structured problems be used to elicit general practice trainees' and trainers' EB? and 2. What are the views of general practice trainees and trainers about knowledge and how do they justify knowing? Methods 2 focus groups of trainees (n = 18) were convened on 3 occasions during their 1st year of postgraduate GP training. 2 groups of GP trainers (n = 11) met on one occasion. Based on the methodology of the Reflective Judgement Interview (RJI), participants were asked to comment on 11 ill-structured problems. The sessions were audio taped and transcribed and an adapted version of the RJI scoring rules was used to assess the trainees' reasoning about ill-structured problems. Results Participants made a number of statements illustrating their EB and their importance in clinical reasoning. The level of EB varied widely form one meeting to another and depending on the problem addressed. Overall, the EB expressed by trainees did not differ from those of trainers except on a particular ill-structured problem regarding shoulder pain. Conclusion The use of focus groups has entailed some difficulties in the interpretation of the results, but a number of preliminary conclusions can be drawn. Ill-structured medical problems can be used to elicit EB. Most trainees and trainers displayed pre-reflective and quasi-reflective EB. The way trainees and doctors view and justify knowledge are likely to be

Target discovery focused approaches to overcome bottlenecks in the exploitation of antimycobacterial natural products.

PubMed

Baptista, Rafael; Bhowmick, Sumana; Nash, Robert J; Baillie, Les; Mur, Luis Aj

2018-04-01

Tuberculosis is a major global health hazard. The search for new antimycobacterials has focused on such as screening combinational chemistry libraries or designing chemicals to target predefined pockets of essential bacterial proteins. The relative ineffectiveness of these has led to a reappraisal of natural products for new antimycobacterial drug leads. However, progress has been limited, we suggest through a failure in many cases to define the drug target and optimize the hits using this information. We highlight methods of target discovery needed to develop a drug into a candidate for clinical trials. We incorporate these into suggested analysis pipelines which could inform the research strategies to accelerate the development of new drug leads from natural products.

Preliminary Study on the Role of Alternative Educational Pathways in Promoting the Use of Problem-Focused Coping Strategies

ERIC Educational Resources Information Center

Shankland, Rebecca; Franca, Lionel Riou; Genolini, Christophe M.; Guelfi, Julien-Daniel; Ionescu, Serban

2009-01-01

Coping styles are generally considered to be environmentally driven. Up to now, research has mainly focused on family influences. However, some studies underline the effect of educational settings on the development of problem-focused coping strategies. Consistently with previous reports on the enhancement of autonomy and problem-solving in…

Enabling university teaching for Canadian academics with multiple sclerosis through problem-focused coping.

PubMed

Crooks, Valorie A; Stone, Sharon Dale; Owen, Michelle

2011-02-01

Research shows that sustained employment contributes to a higher quality of life for those with multiple sclerosis (MS). Occupational therapists can work to create therapeutic interventions that assist people with MS with maintaining employment. To detail the problem-focused coping strategies that academics with MS employ to enable them to teach in universities. Semi-structured interviews were conducted with 45 Canadian academics with MS. Thematic analysis was used to generate findings. While there is flexibility in research and service work tasks, teaching tasks are the most seemingly inflexible. This necessitated the development of problem-focused coping strategies to enable teaching. Three categories of strategies were employed: (1) organizational; (2) before/after teaching; and (3) during teaching. This brief report is intended to serve as a resource for occupational therapists and others wanting to gain a better understanding of the types of therapeutic interventions useful to those teaching in universities.

Efficient proton acceleration and focusing by an ultraintense laser interacting with a parabolic double concave target with an extended rear

NASA Astrophysics Data System (ADS)

Bake, Muhammad Ali; Xie, Bai-Song; Aimidula, Aimierding; Wang, Hong-Yu

2013-07-01

A new scheme for acceleration and focusing of protons via an improved parabolic double concave target irradiated by an ultraintense laser pulse is proposed. When an intense laser pulse illuminates a concave target, the hot electrons are concentrated on the focal region of the rear cavity and they form a strong space-charge-separation field, which accelerates the protons. For a simple concave target, the proton energy spectrum becomes very broad outside the rear cavity because of transverse divergence of the electromagnetic fields. However, particle-in-cell simulations show that, when the concave target has an extended rear, the hot electrons along the wall surface induce a transverse focusing sheath field, resulting in a clear enhancement of proton focusing, which makes the lower proton energy spread, while, leads to a little reduction of the proton bunch peak energy.

Data and methodological problems in establishing state gasoline-conservation targets

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

Greene, D.L.; Walton, G.H.

The Emergency Energy Conservation Act of 1979 gives the President the authority to set gasoline-conservation targets for states in the event of a supply shortage. This paper examines data and methodological problems associated with setting state gasoline-conservation targets. The target-setting method currently used is examined and found to have some flaws. Ways of correcting these deficiencies through the use of Box-Jenkins time-series analysis are investigated. A successful estimation of Box-Jenkins models for all states included the estimation of the magnitude of the supply shortages of 1979 in each state and a preliminary estimation of state short-run price elasticities, which weremore » found to vary about a median value of -0.16. The time-series models identified were very simple in structure and lent support to the simple consumption growth model assumed by the current target method. The authors conclude that the flaws in the current method can be remedied either by replacing the current procedures with time-series models or by using the models in conjunction with minor modifications of the current method.« less

Pediatric Sarcomas Are Targetable by MR-Guided High Intensity Focused Ultrasound (MR-HIFU): Anatomical Distribution and Radiological Characteristics.

PubMed

Shim, Jenny; Staruch, Robert M; Koral, Korgun; Xie, Xian-Jin; Chopra, Rajiv; Laetsch, Theodore W

2016-10-01

Despite intensive therapy, children with metastatic and recurrent sarcoma or neuroblastoma have a poor prognosis. Magnetic resonance guided high intensity focused ultrasound (MR-HIFU) is a noninvasive technique allowing the delivery of targeted ultrasound energy under MR imaging guidance. MR-HIFU may be used to ablate tumors without ionizing radiation or target chemotherapy using hyperthermia. Here, we evaluated the anatomic locations of tumors to assess the technical feasibility of MR-HIFU therapy for children with solid tumors. Patients with sarcoma or neuroblastoma with available cross-sectional imaging were studied. Tumors were classified based on the location and surrounding structures within the ultrasound beam path as (i) not targetable, (ii) completely or partially targetable with the currently available MR-HIFU system, and (iii) potentially targetable if a respiratory motion compensation technique was used. Of the 121 patients with sarcoma and 61 patients with neuroblastoma, 64% and 25% of primary tumors were targetable at diagnosis, respectively. Less than 20% of metastases at diagnosis or relapse were targetable for both sarcoma and neuroblastoma. Most targetable lesions were located in extremities or in the pelvis. Respiratory motion compensation may increase the percentage of targetable tumors by 4% for sarcomas and 10% for neuroblastoma. Many pediatric sarcomas are localized at diagnosis and are targetable by current MR-HIFU technology. Some children with neuroblastoma have bony tumors targetable by MR-HIFU at relapse, but few newly diagnosed children with neuroblastoma have tumors amenable to MR-HIFU therapy. Clinical trials of MR-HIFU should focus on patients with anatomically targetable tumors. © 2016 Wiley Periodicals, Inc.

Correlative Raman spectroscopy and focused ion beam for targeted phase boundary analysis of titania polymorphs.

PubMed

Mangum, John S; Chan, Lisa H; Schmidt, Ute; Garten, Lauren M; Ginley, David S; Gorman, Brian P

2018-05-01

Site-specific preparation of specimens using focused ion beam instruments for transmission electron microscopy is at the forefront of targeting regions of interest for nanoscale characterization. Typical methods of pinpointing desired features include electron backscatter diffraction for differentiating crystal structures and energy-dispersive X-Ray spectroscopy for probing compositional variations. Yet there are situations, notably in the titanium dioxide system, where these techniques can fail. Differentiating between the brookite and anatase polymorphs of titania is either excessively laborious or impossible with the aforementioned techniques. However, due to differences in bonding structure, Raman spectroscopy serves as an ideal candidate for polymorph differentiation. In this work, a correlative approach utilizing Raman spectroscopy for targeted focused ion beam specimen preparation was employed. Dark field imaging and diffraction in the transmission electron microscope confirmed the region of interest located via Raman spectroscopy and demonstrated the validity of this new method. Correlative Raman spectroscopy, scanning electron microscopy, and focused ion beam is shown to be a promising new technique for identifying site-specific preparation of nanoscale specimens in cases where conventional approaches do not suffice. Copyright © 2018 Elsevier B.V. All rights reserved.

Correlative Raman spectroscopy and focused ion beam for targeted phase boundary analysis of titania polymorphs

DOE PAGES

Mangum, John S.; Chan, Lisa H.; Schmidt, Ute; ...

2018-02-23

Site-specific preparation of specimens using focused ion beam instruments for transmission electron microscopy is at the forefront of targeting regions of interest for nanoscale characterization. Typical methods of pinpointing desired features include electron backscatter diffraction for differentiating crystal structures and energy-dispersive X-Ray spectroscopy for probing compositional variations. Yet there are situations, notably in the titanium dioxide system, where these techniques can fail. Differentiating between the brookite and anatase polymorphs of titania is either excessively laborious or impossible with the aforementioned techniques. However, due to differences in bonding structure, Raman spectroscopy serves as an ideal candidate for polymorph differentiation. In thismore » work, a correlative approach utilizing Raman spectroscopy for targeted focused ion beam specimen preparation was employed. Dark field imaging and diffraction in the transmission electron microscope confirmed the region of interest located via Raman spectroscopy and demonstrated the validity of this new method. Correlative Raman spectroscopy, scanning electron microscopy, and focused ion beam is shown to be a promising new technique for identifying site-specific preparation of nanoscale specimens in cases where conventional approaches do not suffice.« less

Correlative Raman spectroscopy and focused ion beam for targeted phase boundary analysis of titania polymorphs

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

Mangum, John S.; Chan, Lisa H.; Schmidt, Ute

Site-specific preparation of specimens using focused ion beam instruments for transmission electron microscopy is at the forefront of targeting regions of interest for nanoscale characterization. Typical methods of pinpointing desired features include electron backscatter diffraction for differentiating crystal structures and energy-dispersive X-Ray spectroscopy for probing compositional variations. Yet there are situations, notably in the titanium dioxide system, where these techniques can fail. Differentiating between the brookite and anatase polymorphs of titania is either excessively laborious or impossible with the aforementioned techniques. However, due to differences in bonding structure, Raman spectroscopy serves as an ideal candidate for polymorph differentiation. In thismore » work, a correlative approach utilizing Raman spectroscopy for targeted focused ion beam specimen preparation was employed. Dark field imaging and diffraction in the transmission electron microscope confirmed the region of interest located via Raman spectroscopy and demonstrated the validity of this new method. Correlative Raman spectroscopy, scanning electron microscopy, and focused ion beam is shown to be a promising new technique for identifying site-specific preparation of nanoscale specimens in cases where conventional approaches do not suffice.« less

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood-brain barrier opening.

PubMed

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel; Konofagou, Elisa E

2017-04-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood-brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood-brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo.

Noninvasive and Targeted Drug Delivery to the Brain Using Focused Ultrasound

PubMed Central

2013-01-01

Brain diseases are notoriously difficult to treat due to the presence of the blood-brain barrier (BBB). Here, we review the development of focused ultrasound (FUS) as a noninvasive method for BBB disruption, aiding in drug delivery to the brain. FUS can be applied through the skull to a targeted region in the brain. When combined with microbubbles, FUS causes localized and reversible disruption of the BBB. The cellular mechanisms of BBB disruption are presented. Several therapeutic agents have been delivered to the brain resulting in significant improvements in pathology in models of glioblastoma and Alzheimer’s disease. The requirements for clinical translation of FUS will be discussed. PMID:23379618

Self-focusing therapeutic gene delivery with intelligent gene vector swarms: intra-swarm signalling through receptor transgene expression in targeted cells.

PubMed

Tolmachov, Oleg E

2015-01-01

Gene delivery in vivo that is tightly focused on the intended target cells is essential to maximize the benefits of gene therapy and to reduce unwanted side-effects. Cell surface markers are immediately available for probing by therapeutic gene vectors and are often used to direct gene transfer with these vectors to specific target cell populations. However, it is not unusual for the choice of available extra-cellular markers to be too scarce to provide a reliable definition of the desired therapeutically relevant set of target cells. Therefore, interrogation of intra-cellular determinants of cell-specificity, such as tissue-specific transcription factors, can be vital in order to provide detailed cell-guiding information to gene vector particles. An important improvement in cell-specific gene delivery can be achieved through auto-buildup in vector homing efficiency using intelligent 'self-focusing' of swarms of vector particles on target cells. Vector self-focusing was previously suggested to rely on the release of diffusible chemo-attractants after a successful target-specific hit by 'scout' vector particles. I hypothesize that intelligent self-focusing behaviour of swarms of cell-targeted therapeutic gene vectors can be accomplished without the employment of difficult-to-use diffusible chemo-attractants, instead relying on the intra-swarm signalling through cells expressing a non-diffusible extra-cellular receptor for the gene vectors. In the proposed model, cell-guiding information is gathered by the 'scout' gene vector particles, which: (1) attach to a variety of cells via a weakly binding (low affinity) receptor; (2) successfully facilitate gene transfer into these cells; (3) query intra-cellular determinants of cell-specificity with their transgene expression control elements and (4) direct the cell-specific biosynthesis of a vector-encoded strongly binding (high affinity) cell-surface receptor. Free members of the vector swarm loaded with therapeutic cargo

Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening

PubMed Central

Sierra, Carlos; Acosta, Camilo; Chen, Cherry; Wu, Shih-Ying; Karakatsani, Maria E; Bernal, Manuel

2016-01-01

Focused ultrasound in conjunction with lipid microbubbles has fully demonstrated its ability to induce non-invasive, transient, and reversible blood–brain barrier opening. This study was aimed at testing the feasibility of our lipid-coated microbubbles as a vector for targeted drug delivery in the treatment of central nervous system diseases. These microbubbles were labeled with the fluorophore 5-dodecanoylaminfluorescein. Focused ultrasound targeted mouse brains in vivo in the presence of these microbubbles for trans-blood–brain barrier delivery of 5-dodecanoylaminfluorescein. This new approach, compared to previously studies of our group, where fluorescently labeled dextrans and microbubbles were co-administered, represents an appreciable improvement in safety outcome and targeted drug delivery. This novel technique allows the delivery of 5-dodecanoylaminfluorescein at the region of interest unlike the alternative of systemic exposure. 5-dodecanoylaminfluorescein delivery was assessed by ex vivo fluorescence imaging and by in vivo transcranial passive cavitation detection. Stable and inertial cavitation doses were quantified. The cavitation dose thresholds for estimating, a priori, successful targeted drug delivery were, for the first time, identified with inertial cavitation were concluded to be necessary for successful delivery. The findings presented herein indicate the feasibility and safety of the proposed microbubble-based targeted drug delivery and that, if successful, can be predicted by cavitation detection in vivo. PMID:27278929

Semiclassical limit of the focusing NLS: Whitham equations and the Riemann-Hilbert Problem approach

NASA Astrophysics Data System (ADS)

Tovbis, Alexander; El, Gennady A.

2016-10-01

The main goal of this paper is to put together: a) the Whitham theory applicable to slowly modulated N-phase nonlinear wave solutions to the focusing nonlinear Schrödinger (fNLS) equation, and b) the Riemann-Hilbert Problem approach to particular solutions of the fNLS in the semiclassical (small dispersion) limit that develop slowly modulated N-phase nonlinear wave in the process of evolution. Both approaches have their own merits and limitations. Understanding of the interrelations between them could prove beneficial for a broad range of problems involving the semiclassical fNLS.

Focusing on the golden ball metaheuristic: an extended study on a wider set of problems.

PubMed

Osaba, E; Diaz, F; Carballedo, R; Onieva, E; Perallos, A

2014-01-01

Nowadays, the development of new metaheuristics for solving optimization problems is a topic of interest in the scientific community. In the literature, a large number of techniques of this kind can be found. Anyway, there are many recently proposed techniques, such as the artificial bee colony and imperialist competitive algorithm. This paper is focused on one recently published technique, the one called Golden Ball (GB). The GB is a multiple-population metaheuristic based on soccer concepts. Although it was designed to solve combinatorial optimization problems, until now, it has only been tested with two simple routing problems: the traveling salesman problem and the capacitated vehicle routing problem. In this paper, the GB is applied to four different combinatorial optimization problems. Two of them are routing problems, which are more complex than the previously used ones: the asymmetric traveling salesman problem and the vehicle routing problem with backhauls. Additionally, one constraint satisfaction problem (the n-queen problem) and one combinatorial design problem (the one-dimensional bin packing problem) have also been used. The outcomes obtained by GB are compared with the ones got by two different genetic algorithms and two distributed genetic algorithms. Additionally, two statistical tests are conducted to compare these results.

Focusing on the Golden Ball Metaheuristic: An Extended Study on a Wider Set of Problems

PubMed Central

Osaba, E.; Diaz, F.; Carballedo, R.; Onieva, E.; Perallos, A.

2014-01-01

Nowadays, the development of new metaheuristics for solving optimization problems is a topic of interest in the scientific community. In the literature, a large number of techniques of this kind can be found. Anyway, there are many recently proposed techniques, such as the artificial bee colony and imperialist competitive algorithm. This paper is focused on one recently published technique, the one called Golden Ball (GB). The GB is a multiple-population metaheuristic based on soccer concepts. Although it was designed to solve combinatorial optimization problems, until now, it has only been tested with two simple routing problems: the traveling salesman problem and the capacitated vehicle routing problem. In this paper, the GB is applied to four different combinatorial optimization problems. Two of them are routing problems, which are more complex than the previously used ones: the asymmetric traveling salesman problem and the vehicle routing problem with backhauls. Additionally, one constraint satisfaction problem (the n-queen problem) and one combinatorial design problem (the one-dimensional bin packing problem) have also been used. The outcomes obtained by GB are compared with the ones got by two different genetic algorithms and two distributed genetic algorithms. Additionally, two statistical tests are conducted to compare these results. PMID:25165742

How do Dutch GPs address work-related problems? A focus group study.

PubMed

de Kock, Cornelis A; Lucassen, Peter L B J; Spinnewijn, Laura; Knottnerus, J André; Buijs, Peter C; Steenbeek, Romy; Lagro-Janssen, Antoine L M

2016-09-01

In the Netherlands, there is a lack of knowledge about general practitioners' (GPs) perception of their role regarding patients' occupation and work related problems (WRP). As work and health are closely related, and patients expect help from their GPs in this area, a better understanding is needed of GPs' motivation to address WRP. To explore GPs' opinions on their role in the area of work and health. This is a qualitative study using three focus groups with Dutch GPs from the catchment area of a hospital in the Southeast of the Netherlands. The group was heterogeneous in characteristics such as sex, age, and practice setting. Three focus groups were convened with 18 GPs. The moderator used an interview guide. Two researchers analysed verbatim transcripts using constant comparative analysis. We distinguished three items: (a) work context in a GP's integrated consultation style; (b) counselling about sick leave; (c) cooperation with occupational physicians (OPs). The participants are willing to address the topic and counsel about sick leave. They consider WRP in patients with medically unexplained symptoms (MUS) challenging. They tend to advise these patients to continue working as they think this will ultimately benefit them. The participating GPs seemed well aware of the relation between work and health but need more knowledge, communication skills and better cooperation with occupational physicians to manage work-related problems. [Box: see text].

Linking science to policy: the role of international collaboration and problem-focused integrative reviews.

PubMed

Babor, Thomas F

2015-07-01

This paper traces the modern history of alcohol and drug policy research through a series of four monographs that were written collaboratively by international groups of career scientists. The books promoted the view, supported by a considerable amount of evidence, that alcohol and drug problems can be reduced, if not prevented, through organized policy action by governments and public health organizations. The books used a problem-focused integrative approach to align research more effectively with public policy. A common thread that runs throughout the monographs is the influence of Professor Griffith Edwards. © 2015 Society for the Study of Addiction.

Cooperative Robots to Observe Moving Targets: Review.

PubMed

Khan, Asif; Rinner, Bernhard; Cavallaro, Andrea

2018-01-01

The deployment of multiple robots for achieving a common goal helps to improve the performance, efficiency, and/or robustness in a variety of tasks. In particular, the observation of moving targets is an important multirobot application that still exhibits numerous open challenges, including the effective coordination of the robots. This paper reviews control techniques for cooperative mobile robots monitoring multiple targets. The simultaneous movement of robots and targets makes this problem particularly interesting, and our review systematically addresses this cooperative multirobot problem for the first time. We classify and critically discuss the control techniques: cooperative multirobot observation of multiple moving targets, cooperative search, acquisition, and track, cooperative tracking, and multirobot pursuit evasion. We also identify the five major elements that characterize this problem, namely, the coordination method, the environment, the target, the robot and its sensor(s). These elements are used to systematically analyze the control techniques. The majority of the studied work is based on simulation and laboratory studies, which may not accurately reflect real-world operational conditions. Importantly, while our systematic analysis is focused on multitarget observation, our proposed classification is useful also for related multirobot applications.

Metric Calibration of a Focused Plenoptic Camera Based on a 3d Calibration Target

NASA Astrophysics Data System (ADS)

Zeller, N.; Noury, C. A.; Quint, F.; Teulière, C.; Stilla, U.; Dhome, M.

2016-06-01

In this paper we present a new calibration approach for focused plenoptic cameras. We derive a new mathematical projection model of a focused plenoptic camera which considers lateral as well as depth distortion. Therefore, we derive a new depth distortion model directly from the theory of depth estimation in a focused plenoptic camera. In total the model consists of five intrinsic parameters, the parameters for radial and tangential distortion in the image plane and two new depth distortion parameters. In the proposed calibration we perform a complete bundle adjustment based on a 3D calibration target. The residual of our optimization approach is three dimensional, where the depth residual is defined by a scaled version of the inverse virtual depth difference and thus conforms well to the measured data. Our method is evaluated based on different camera setups and shows good accuracy. For a better characterization of our approach we evaluate the accuracy of virtual image points projected back to 3D space.

Guiding and focusing of fast electron beams produced by ultra-intense laser pulse using a double cone funnel target

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

Zhang, Wen-shuai; Cai, Hong-bo, E-mail: Cai-hongbo@iapcm.ac.cn; HEDPS, Center for Applied Physics and Technology, Peking University, Beijing 100871

A novel double cone funnel target design aiming at efficiently guiding and focusing fast electron beams produced in high intensity (>10{sup 19 }W/cm{sup 2}) laser-solid interactions is investigated via two-dimensional particle-in-cell simulations. The forward-going fast electron beams are shown to be directed and focused to a smaller size in comparison with the incident laser spot size. This plasma funnel attached on the cone target guides and focuses electrons in a manner akin to the control of liquid by a plastic funnel. Such device has the potential to add substantial design flexibility and prevent inefficiencies for important applications such as fast ignition.more » Two reasons account for the collimation of fast electron beams. First, the sheath electric fields and quasistatic magnetic fields inside the vacuum gap of the double cone provide confinement of the fast electrons in the laser-plasma interaction region. Second, the interface magnetic fields inside the beam collimator further guide and focus the fast electrons during the transport. The application of this technique to cone-guided fast ignition is considered, and it is shown that it can enhance the laser energy deposition in the compressed fuel plasma by a factor of 2 in comparison with the single cone target case.« less

Metaphor and analogy in everyday problem solving.

PubMed

Keefer, Lucas A; Landau, Mark J

2016-11-01

Early accounts of problem solving focused on the ways people represent information directly related to target problems and possible solutions. Subsequent theory and research point to the role of peripheral influences such as heuristics and bodily states. We discuss how metaphor and analogy similarly influence stages of everyday problem solving: Both processes mentally map features of a target problem onto the structure of a relatively more familiar concept. When individuals apply this structure, they use a well-known concept as a framework for reasoning about real world problems and candidate solutions. Early studies found that analogy use helped people gain insight into novel problems. More recent research on metaphor goes further to show that activating mappings has subtle, sometimes surprising effects on judgment and reasoning in everyday problem solving. These findings highlight situations in which mappings can help or hinder efforts to solve problems. WIREs Cogn Sci 2016, 7:394-405. doi: 10.1002/wcs.1407 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

Perceptions of Problem Behavior in Adolescents' Families: Perceiver, Target, and Family Effects

ERIC Educational Resources Information Center

Manders, Willeke A.; Janssens, Jan M. A. M.; Cook, William L.; Oud, Johan H. L.; De Bruyn, Eric E. J.; Scholte, Ron H. J.

2009-01-01

Considerable research has focused on the reliability and validity of informant reports of family behavior, especially maternal reports of adolescent problem behavior. None of these studies, however, has based their orientation on a theoretical model of interpersonal perception. In this study we used the social relations model (SRM) to examine…

Influence of distance between focusing lens and target surface on laser-induced Cu plasma temperature

NASA Astrophysics Data System (ADS)

Wang, Ying; Chen, Anmin; Wang, Qiuyun; Sui, Laizhi; Ke, Da; Cao, Sheng; Li, Suyu; Jiang, Yuanfei; Jin, Mingxing

2018-03-01

In this study, the influence of distance between the focusing lens and target surface on the plasma temperature of copper induced by a Nd:YAG laser was investigated in the atmosphere. The plasma temperature was calculated by using the Cu (I) lines (510.55 nm, 515.32 nm, and 521.82 nm). The Cu (I) lines were recorded under different lens-to-sample distances and laser pulse energies (15.8 mJ, 27.0 mJ, 43.4 mJ, 59.2 mJ, and 76.8 mJ). The results indicated that the plasma temperature depended strongly on the distance between the focusing lens and target surface. With the increase in the distance, the plasma temperature firstly rose, and then dropped. This could be attributed to the interaction between the tailing of the nanosecond laser pulse and the front portion of the plasma plume, the plasma shielding effect, and the expanding of the plasma. In addition, there was an interesting phenomenon that the plasma temperature and the emission intensity were not completely consistent with the change of the lens-to-sample distance. It is hoped that our research will provide a deeper insight into the underlying physical processes.

Regulatory Focus Affects Physician Risk Tolerance

PubMed Central

Veazie, Peter J.; McIntosh, Scott; Chapman, Benjamin P.; Dolan, James G.

2014-01-01

Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention – regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (P=0.01). The Cohen’s d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (P=0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor. PMID:25431799

Potential immunologic targets for treating fibrosis in systemic sclerosis: a review focused on leukocytes and cytokines.

PubMed

Hasegawa, Minoru; Takehara, Kazuhiko

2012-12-01

Systemic sclerosis (SSc) is a connective tissue disease characterized by tissue fibrosis. Although the pathogenesis remains unclear, a variety of cells contribute to the fibrotic process via interactions with each other and production of various cytokines. Recent literature related to the immunologic pathogenesis and future strategies for treating the fibrosis of SSc are discussed and, especially, this literature-based review that includes the authors' perspective, focused on leukocytes and cytokines. A PubMed search for articles published between January 2005 and January 2012 was conducted using the following keywords: systemic sclerosis, leukocyte, cytokine, growth factor, and chemokine. The reference lists of identified articles were searched for further articles. Targeting profibrogenic cytokines, including transforming growth factor-β, is still a very active area of research in SSc and most cellular studies have focused on the roles of fibroblasts in SSc. However, a growing number of recent studies indicate a role for B cells in the development of SSc and other autoimmune diseases such as systemic lupus erythematosus. Therefore, B-cell-targeted therapies, including currently available monoclonal antibodies against CD19, CD20, CD22, and B-cell-activating factor, belonging to the tumor necrosis factor family represent possible treatment options. Furthermore, the modulation of T-cell costimulatory molecules such as a recombinant fusion protein of cytotoxic T-lymphocyte antigen-4 may be as effective in SSc as it is in treating other autoimmune diseases. Approaches to antagonize interleukin (IL)-1, IL-6, or IL-17A signaling may also be attractive. This review describes recent advances in the treatment of fibrosis in SSc patients focused on immunologic strategies, such as leukocyte- or cytokine-targeted therapies. Copyright © 2012 Elsevier Inc. All rights reserved.

Automatic Focusing for a 675 GHz Imaging Radar with Target Standoff Distances from 14 to 34 Meters

NASA Technical Reports Server (NTRS)

Tang, Adrian; Cooper, Ken B.; Dengler, Robert J.; Llombart, Nuria; Siegel, Peter H.

2013-01-01

This paper dicusses the issue of limited focal depth for high-resolution imaging radar operating over a wide range of standoff distances. We describe a technique for automatically focusing a THz imaging radar system using translational optics combined with range estimation based on a reduced chirp bandwidth setting. The demonstarted focusing algorithm estimates the correct focal depth for desired targets in the field of view at unknown standoffs and in the presence of clutter to provide good imagery at 14 to 30 meters of standoff.

Central Limit Theorems for the Shrinking Target Problem

NASA Astrophysics Data System (ADS)

Haydn, Nicolai; Nicol, Matthew; Vaienti, Sandro; Zhang, Licheng

2013-12-01

Suppose B i := B( p, r i ) are nested balls of radius r i about a point p in a dynamical system ( T, X, μ). The question of whether T i x∈ B i infinitely often (i.o.) for μ a.e. x is often called the shrinking target problem. In many dynamical settings it has been shown that if diverges then there is a quantitative rate of entry and for μ a.e. x∈ X. This is a self-norming type of strong law of large numbers. We establish self-norming central limit theorems (CLT) of the form (in distribution) for a variety of hyperbolic and non-uniformly hyperbolic dynamical systems, the normalization constants are . Dynamical systems to which our results apply include smooth expanding maps of the interval, Rychlik type maps, Gibbs-Markov maps, rational maps and, in higher dimensions, piecewise expanding maps. For such central limit theorems the main difficulty is to prove that the non-stationary variance has a limit in probability.

Assessment Instrument for Problem-focused Coping. Reliability test of APC. Part 1.

PubMed

Tollén, A; Ahlström, G

1998-01-01

A new self-report instrument, the Assessment Instrument of Problem-focused Coping (APC) developed from qualitative interviews, is described. This instrument provides knowledge of the patients' own competence in coping with activities of daily living (ADL), the patients' own assessment of what they experience as problems, and the extent to which they are satisfied with their ADL. The purpose of the study was to test the reliability of the instrument with regard to intra-rater reliability and internal consistency. The study group comprised 40 patients with muscular weakness and other symptoms relating to the postpolio syndrome. The result showed an acceptable internal consistency (alpha 0.70), which confirms the construct validity of the instrument. The test-retest showed that the stability over a period of time varied from low to high for a total of 28 items. At the same time, it is evident that the instrument does not achieve the aim of being a good evaluation instrument, because the stability over a period of time was unsatisfactory. The test-retest should be repeated with a larger test group in future research projects.

The Case for Problem Solving in Second Language Learning. CLCS Occasional Paper No. 33.

ERIC Educational Resources Information Center

Bourke, James Mannes

A study undertaken in Ireland investigated the effectiveness of a second language teaching strategy that focused on grammatical problem-solving. In this approach, the problems are located within the target language system, and the problem-solving involves induction of grammatical rules and use of those rules. Learners are confronted with instances…

Wave energy focusing to subsurface poroelastic formations to promote oil mobilization

NASA Astrophysics Data System (ADS)

Karve, Pranav M.; Kallivokas, Loukas F.

2015-07-01

We discuss an inverse source formulation aimed at focusing wave energy produced by ground surface sources to target subsurface poroelastic formations. The intent of the focusing is to facilitate or enhance the mobility of oil entrapped within the target formation. The underlying forward wave propagation problem is cast in two spatial dimensions for a heterogeneous poroelastic target embedded within a heterogeneous elastic semi-infinite host. The semi-infiniteness of the elastic host is simulated by augmenting the (finite) computational domain with a buffer of perfectly matched layers. The inverse source algorithm is based on a systematic framework of partial-differential-equation-constrained optimization. It is demonstrated, via numerical experiments, that the algorithm is capable of converging to the spatial and temporal characteristics of surface loads that maximize energy delivery to the target formation. Consequently, the methodology is well-suited for designing field implementations that could meet a desired oil mobility threshold. Even though the methodology, and the results presented herein are in two dimensions, extensions to three dimensions are straightforward.

[Genome-editing: focus on the off-target effects].

PubMed

He, Xiubin; Gu, Feng

2017-10-25

Breakthroughs of genome-editing in recent years have paved the way to develop new therapeutic strategies. These genome-editing tools mainly include Zinc-finger nucleases (ZFNs), Transcription activator-like effector nucleases (TALENs), and clustered regulatory interspaced short palindromic repeat (CRISPR)/Cas-based RNA-guided DNA endonucleases. However, off-target effects are still the major issue in genome editing, and limit the application in gene therapy. Here, we summarized the cause and compared different detection methods of off-targets.

Non-erotic thoughts, attentional focus, and sexual problems in a community sample.

PubMed

Nelson, Andrea L; Purdon, Christine

2011-04-01

According to Barlow's model of sexual dysfunction, anxiety in sexual situations leads to attentional focus on sexual performance at the expense of erotic cues, which compromises sexual arousal. This negative experience will enhance anxiety in future sexual situations, and non-erotic thoughts (NETs) relevant to performance will receive attentional priority. Previous research with student samples (Purdon & Holdaway, 2006; Purdon & Watson, 2010) has found that people experience many types of NETs in addition to performance-relevant thoughts, and that, consistent with Barlow's model, the frequency of and anxiety evoked by these thoughts is positively associated with sexual problems. Extending this previous work, the current study found that, in a community sample of women (N = 81) and men (N = 72) in long-term relationships, women were more likely to report body image concerns and external consequences of the sexual activity, while men were more likely to report performance-related concerns. Equally likely among men and women were thoughts about emotional consequences of the sexual activity. Regardless of thought content, experiencing more frequent NETs was associated with more sexual problems in both women and men. Moreover, as per Barlow's model, greater negative affect in anticipation of and during sexual activity predicted greater frequency of NETs and greater anxiety in response to NETs was associated with greater difficulty dismissing the thoughts. However, greater difficulty in refocusing on erotic thoughts during sexual activity uniquely predicted more sexual problems above the frequency and dismissability of NETs. Together, these data support the cognitive interference mechanism implicated by Barlow's causal model of sexual dysfunction and have implications for the treatment of sexual problems.

Testing implications of varying targets for Bordetella pertussis: comparison of the FilmArray Respiratory Panel and the Focus B. pertussis PCR assay

PubMed Central

Jerris, Robert C; Williams, Sally R; MacDonald, Heather J; Ingebrigtsen, Danielle R; Westblade, Lars F; Rogers, Beverly B

2015-01-01

Background The FilmArray Respiratory Panel (RP) detects multiple pathogens, including Bordetella pertussis. The multiplex PCR system is appropriate for a core laboratory or point of care due to ease of use. The purpose of this study is to compare the analytical sensitivity of the FilmArray RP, which targets the promoter region of the B. pertussis toxin gene, with the Focus real-time PCR assay, which targets the insertion sequence IS481. Methods Seventy-one specimens from patients aged 1 month to 18 years, which had tested positive for B. pertussis using the Focus assay, were analysed using the FilmArray RP. Results Forty-six specimens were positive for B. pertussis by both the Focus and the FilmArray RP assays. Twenty-five specimens were negative for B. pertussis using the FilmArray RP assay, but positive using the Focus assay. Conclusions The FilmArray RP assays will detect approximately 1/3 less cases of B. pertussis than the Focus assay. PMID:25742911

Comparing an Emotion- and a Behavior-Focused Parenting Program as Part of a Multsystemic Intervention for Child Conduct Problems.

PubMed

Duncombe, Melissa E; Havighurst, Sophie S; Kehoe, Christiane E; Holland, Kerry A; Frankling, Emma J; Stargatt, Robyn

2016-01-01

This study evaluated the effectiveness of a multisystemic early intervention that included a comparison of an emotion- and behavior-focused parenting program for children with emerging conduct problems. The processes that moderated positive child outcomes were also explored. A repeated measures cluster randomized group design methodology was employed with three conditions (Tuning in to Kids, Positive Parenting Program, and waitlist control) and two periods (preintervention and 6-month follow-up). The sample consisted of 320 predominantly Caucasian 4- to 9-year-old children who were screened for disruptive behavior problems. Three outcome measures of child conduct problems were evaluated using a parent (Eyberg Child Behavior Inventory) and teacher (Strengths and Difficulties Questionnaire) rating scale and a structured child interview (Home Interview With Child). Six moderators were assessed using family demographic information and a parent-rated measure of psychological well-being (Depression Anxiety and Stress Scales short form). The results indicated that the multisystemic intervention was effective compared to a control group and that, despite different theoretical orientations, the emotion- and behavior-focused parenting programs were equally effective in reducing child conduct problems. Child age and parent psychological well-being moderated intervention response. This effectiveness trial supports the use of either emotion- or behavior-focused parenting programs in a multisystemic early intervention and provides greater choice for practitioners in the selection of specific programs.

Pathways and therapeutic targets in melanoma

PubMed Central

Shtivelman, Emma; Davies, Michael A.; Hwu, Patrick; Yang, James; Lotem, Michal; Oren, Moshe; Flaherty, Keith T.; Fisher, David E.

2014-01-01

This review aims to summarize the current knowledge of molecular pathways and their clinical relevance in melanoma. Metastatic melanoma was a grim diagnosis, but in recent years tremendous advances have been made in treatments. Chemotherapy provided little benefit in these patients, but development of targeted and new immune approaches made radical changes in prognosis. This would not have happened without remarkable advances in understanding the biology of disease and tremendous progress in the genomic (and other “omics”) scale analyses of tumors. The big problems facing the field are no longer focused exclusively on the development of new treatment modalities, though this is a very busy area of clinical research. The focus shifted now to understanding and overcoming resistance to targeted therapies, and understanding the underlying causes of the heterogeneous responses to immune therapy. PMID:24743024

Polynomial algorithms for the Maximal Pairing Problem: efficient phylogenetic targeting on arbitrary trees

PubMed Central

2010-01-01

Background The Maximal Pairing Problem (MPP) is the prototype of a class of combinatorial optimization problems that are of considerable interest in bioinformatics: Given an arbitrary phylogenetic tree T and weights ωxy for the paths between any two pairs of leaves (x, y), what is the collection of edge-disjoint paths between pairs of leaves that maximizes the total weight? Special cases of the MPP for binary trees and equal weights have been described previously; algorithms to solve the general MPP are still missing, however. Results We describe a relatively simple dynamic programming algorithm for the special case of binary trees. We then show that the general case of multifurcating trees can be treated by interleaving solutions to certain auxiliary Maximum Weighted Matching problems with an extension of this dynamic programming approach, resulting in an overall polynomial-time solution of complexity (n4 log n) w.r.t. the number n of leaves. The source code of a C implementation can be obtained under the GNU Public License from http://www.bioinf.uni-leipzig.de/Software/Targeting. For binary trees, we furthermore discuss several constrained variants of the MPP as well as a partition function approach to the probabilistic version of the MPP. Conclusions The algorithms introduced here make it possible to solve the MPP also for large trees with high-degree vertices. This has practical relevance in the field of comparative phylogenetics and, for example, in the context of phylogenetic targeting, i.e., data collection with resource limitations. PMID:20525185

A simple solution to the problem of effective utilisation of the target material for pulsed laser deposition of thin films

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

Kuzanyan, A S; Kuzanyan, A A; Petrosyan, V A

The factors determining the efficiency of the target material utilisation for pulsed laser deposition of films are considered. The target volume is calculated, which is evaporated in the ablation process by the focused laser radiation having a rectangular form. The new device is suggested and developed for obtaining thin films by the method of laser deposition, which is specific in the employment of a simple optical system mounted outside a deposition chamber that comprises two lenses and the diaphragm and focuses the laser beam onto a target in the form of a sector-like spot. Thin films of CuO and YBaCuOmore » were deposited with this device. Several deposition cycles revealed that the target material is consumed uniformly from the entire surface of the target. A maximal spread of the target thickness was not greater than ±2% both prior to deposition and after it. The device designed provides a high coefficient of the target material utilisation efficiency. (laser deposition of thin films)« less

Combining on-chip synthesis of a focused combinatorial library with computational target prediction reveals imidazopyridine GPCR ligands.

PubMed

Reutlinger, Michael; Rodrigues, Tiago; Schneider, Petra; Schneider, Gisbert

2014-01-07

Using the example of the Ugi three-component reaction we report a fast and efficient microfluidic-assisted entry into the imidazopyridine scaffold, where building block prioritization was coupled to a new computational method for predicting ligand-target associations. We identified an innovative GPCR-modulating combinatorial chemotype featuring ligand-efficient adenosine A1/2B and adrenergic α1A/B receptor antagonists. Our results suggest the tight integration of microfluidics-assisted synthesis with computer-based target prediction as a viable approach to rapidly generate bioactivity-focused combinatorial compound libraries with high success rates. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Designing divertor targets for uniform power load

NASA Astrophysics Data System (ADS)

Dekeyser, W.; Reiter, D.; Baelmans, M.

2015-08-01

Divertor design for next step fusion reactors heavily relies on 2D edge plasma modeling with codes as e.g. B2-EIRENE. While these codes are typically used in a design-by-analysis approach, in previous work we have shown that divertor design can alternatively be posed as a mathematical optimization problem, and solved very efficiently using adjoint methods adapted from computational aerodynamics. This approach has been applied successfully to divertor target shape design for more uniform power load. In this paper, the concept is further extended to include all contributions to the target power load, with particular focus on radiation. In a simplified test problem, we show the potential benefits of fully including the radiation load in the design cycle as compared to only assessing this load in a post-processing step.

What are the health needs, familial and social problems of Thai migrants in a local community in Australia? A focus group study.

PubMed

Vatcharavongvan, Pasitpon; Hepworth, Julie; Lim, Joanne; Marley, John

2014-02-01

This study explored the health needs, familial and social problems of Thai migrants in a local community in Brisbane, Australia. Five focus groups with Thai migrants were conducted. The qualitative data were examined using thematic content analysis that is specifically designed for focus group analysis. Four themes were identified: (1) positive experiences in Australia, (2) physical health problems, (3) mental health problems, and (4) familial and social health problems. This study revealed key health needs related to chronic disease and mental health, major barriers to health service use, such as language skills, and facilitating factors, such as the Thai Temple. We concluded that because the health needs, familial and social problems of Thai migrants were complex and culture bound, the development of health and community services for Thai migrants needs to take account of the ways in which Thai culture both negatively impacts health and offer positive solutions to problems.

Cancer-linked targets modulated by curcumin

PubMed Central

Hasima, Noor; Aggarwal, Bharat B

2012-01-01

In spite of major advances in oncology, the World Health Organization predicts that cancer incidence will double within the next two decades. Although it is well understood that cancer is a hyperproliferative disorder mediated through dysregulation of multiple cell signaling pathways, most cancer drug development remains focused on modulation of specific targets, mostly one at a time, with agents referred to as “targeted therapies,” “smart drugs,” or “magic bullets.” How many cancer targets there are is not known, and how many targets must be attacked to control cancer growth is not well understood. Although more than 90% of cancer-linked deaths are due to metastasis of the tumor to vital organs, most drug targeting is focused on killing the primary tumor. Besides lacking specificity, the targeted drugs induce toxicity and side effects that sometimes are greater problems than the disease itself. Furthermore, the cost of some of these drugs is so high that most people cannot afford them. The present report describes the potential anticancer properties of curcumin, a component of the Indian spice turmeric (Curcuma longa), known for its safety and low cost. Curcumin can selectively modulate multiple cell signaling pathways linked to inflammation and to survival, growth, invasion, angiogenesis, and metastasis of cancer cells. More clinical trials of curcumin are needed to prove its usefulness in the cancer setting. PMID:23301199

Interactive Computer Based Assessment Tasks: How Problem-Solving Process Data Can Inform Instruction

ERIC Educational Resources Information Center

Zoanetti, Nathan

2010-01-01

This article presents key steps in the design and analysis of a computer based problem-solving assessment featuring interactive tasks. The purpose of the assessment is to support targeted instruction for students by diagnosing strengths and weaknesses at different stages of problem-solving. The first focus of this article is the task piloting…

Technology transfer from NASA to targeted industries, volume 1

NASA Technical Reports Server (NTRS)

Mccain, Wayne; Schroer, Bernard J.; Souder, William E.; Spann, Mary S.; Watters, Harry; Ziemke, M. Carl

1993-01-01

This report summarizes the University of Alabama in Huntsville (UAH) technology transfer to three target industries with focus on the apparel manufacturing industry in Alabama. Also included in this report are an analysis of the 1992 problem statements submitted by Alabama firms, the results of the survey of 1987-88 NASA Tech Brief requests, the results of the followup to Alabama submitted problem statements, and the development of the model describing the MSFC technology transfer process.

Target Coverage in Wireless Sensor Networks with Probabilistic Sensors

PubMed Central

Shan, Anxing; Xu, Xianghua; Cheng, Zongmao

2016-01-01

Sensing coverage is a fundamental problem in wireless sensor networks (WSNs), which has attracted considerable attention. Conventional research on this topic focuses on the 0/1 coverage model, which is only a coarse approximation to the practical sensing model. In this paper, we study the target coverage problem, where the objective is to find the least number of sensor nodes in randomly-deployed WSNs based on the probabilistic sensing model. We analyze the joint detection probability of target with multiple sensors. Based on the theoretical analysis of the detection probability, we formulate the minimum ϵ-detection coverage problem. We prove that the minimum ϵ-detection coverage problem is NP-hard and present an approximation algorithm called the Probabilistic Sensor Coverage Algorithm (PSCA) with provable approximation ratios. To evaluate our design, we analyze the performance of PSCA theoretically and also perform extensive simulations to demonstrate the effectiveness of our proposed algorithm. PMID:27618902

Improving problem solving in primary school students: The effect of a training programme focusing on metacognition and working memory.

PubMed

Cornoldi, Cesare; Carretti, Barbara; Drusi, Silvia; Tencati, Chiara

2015-09-01

Despite doubts voiced on their efficacy, a series of studies has been carried out on the capacity of training programmes to improve academic and reasoning skills by focusing on underlying cognitive abilities and working memory in particular. No systematic efforts have been made, however, to test training programmes that involve both general and specific underlying abilities. If effective, these programmes could help to increase students' motivation and competence. This study examined the feasibility of improving problem-solving skills in school children by means of a training programme that addresses general and specific abilities involved in problem solving, focusing on metacognition and working memory. The project involved a sample of 135 primary school children attending eight classes in the third, fourth, and fifth grades (age range 8-10 years). The classes were assigned to two groups, one attending the training programme in the first 3 months of the study (Training Group 1) and the other serving as a waiting-list control group (Training Group 2). In the second phase of the study, the role of the two groups was reversed, with Training Group 2 attending the training instead of Training Group 1. The training programme led to improvements in both metacognitive and working memory tasks, with positive-related effects on the ability to solve problems. The gains seen in Training Group 1 were also maintained at the second post-test (after 3 months). Specific activities focusing on metacognition and working memory may contribute to modifying arithmetical problem-solving performance in primary school children. © 2015 The British Psychological Society.

The Replication Focus Targeting Sequence (RFTS) Domain Is a DNA-competitive Inhibitor of Dnmt1

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

Syeda, Farisa; Fagan, Rebecca L.; Wean, Matthew

Dnmt1 (DNA methyltransferase 1) is the principal enzyme responsible for maintenance of cytosine methylation at CpG dinucleotides in the mammalian genome. The N-terminal replication focus targeting sequence (RFTS) domain of Dnmt1 has been implicated in subcellular localization, protein association, and catalytic function. However, progress in understanding its function has been limited by the lack of assays for and a structure of this domain. Here, we show that the naked DNA- and polynucleosome-binding activities of Dnmt1 are inhibited by the RFTS domain, which functions by virtue of binding the catalytic domain to the exclusion of DNA. Kinetic analysis with a fluorogenicmore » DNA substrate established the RFTS domain as a 600-fold inhibitor of Dnmt1 enzymatic activity. The crystal structure of the RFTS domain reveals a novel fold and supports a mechanism in which an RFTS-targeted Dnmt1-binding protein, such as Uhrf1, may activate Dnmt1 for DNA binding.« less

Robust Targeting for the Smartphone Video Guidance Sensor

NASA Technical Reports Server (NTRS)

Carter, Christopher

2017-01-01

The Smartphone Video Guidance Sensor (SVGS) is a miniature, self-contained autonomous rendezvous and docking sensor developed using a commercial off the shelf Android-based smartphone. It aims to provide a miniaturized solution for rendezvous and docking, enabling small satellites to conduct proximity operations and formation flying while minimizing interference with a primary payload. Previously, the sensor was limited by a slow (2 Hz) refresh rate and its use of retro-reflectors, both of which contributed to a limited operating environment. To advance the technology readiness level, a modified approach was developed, combining a multi-colored LED target with a focused target-detection algorithm. Alone, the use of an LED system was determined to be much more reliable, though slower, than the retro-reflector system. The focused target-detection system was developed in response to this problem to mitigate the speed reduction of using color. However, it also improved the reliability. In combination these two methods have been demonstrated to dramatically increase sensor speed and allow the sensor to select the target even with significant noise interfering with the sensor, providing millimeter level accuracy at a range of two meters with a 1U target.

Robust Targeting for the Smartphone Video Guidance Sensor

NASA Technical Reports Server (NTRS)

Carter, C.

2017-01-01

The Smartphone Video Guidance Sensor (SVGS) is a miniature, self-contained autonomous rendezvous and docking sensor developed using a commercial off the shelf Android-based smartphone. It aims to provide a miniaturized solution for rendezvous and docking, enabling small satellites to conduct proximity operations and formation flying while minimizing interference with a primary payload. Previously, the sensor was limited by a slow (2 Hz) refresh rate and its use of retro-reflectors, both of which contributed to a limited operating environment. To advance the technology readiness level, a modified approach was developed, combining a multi-colored LED target with a focused target-detection algorithm. Alone, the use of an LED system was determined to be much more reliable, though slower, than the retro-reflector system. The focused target-detection system was developed in response to this problem to mitigate the speed reduction of using color. However it also improved the reliability. In combination these two methods have been demonstrated to dramatically increase sensor speed and allow the sensor to select the target even with significant noise interfering with the sensor, providing millimeter level precision at a range of two meters with a 1U target.

The Developmental Trajectories of Attention Focusing, Attentional and Behavioral Persistence, and Externalizing Problems during School-Age Years

ERIC Educational Resources Information Center

Zhou, Qing; Hofer, Claire; Eisenberg, Nancy; Reiser, Mark; Spinrad, Tracy L.; Fabes, Richard A.

2007-01-01

The developmental trajectories of attention focusing (by parents' and teachers' reports) and attentional and behavioral persistence (observed during a laboratory task)--2 indexes of effortful control--and externalizing problems from ages 5 to 10 years were examined for 356 children combined from a pair of 3-wave (2 years apart) longitudinal…

SU-F-T-211: Evaluation of a Dual Focusing Magnet System for the Treatment of Small Proton Targets

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

Nguyen, TT; McAuley, GA; Heczko, S

Purpose: To investigate magnetic focusing for small volume proton targets using a doublet combination of quadrupole rare earth permanent magnet Halbach cylinder assemblies Methods: Monte Carlo computer simulations were performed using the Geant4 toolkit to compare dose depositions of proton beams transported through two focusing magnets or in their absence. Proton beams with energies of 127 MeV and initial diameters of 5, 8 and 10 mm were delivered through two identical focusing magnets similar to those currently in experimental use at Loma Linda University Medical Center. Analogous experiments used optimized configurations based on the simulation results. Dose was measured bymore » a diode detector and Gafchromic EBT3 film and compared to simulation data. Based on results from the experimental data, an additional set of simulations was performed with an initial beam diameter of 18 mm and a two differing length magnets (40mm & 68mm). Results: Experimental data matched well with Monte Carlo simulations. However, under conditions necessary to produce circular beam spots at target depth, magnetically focused beams using two identical 40 mm length magnets did not meet all of our performance criteria of circular beam spots, improved peak to entrance (P/E) dose ratios and dose delivery efficiencies. The simulations using the longer 68 mm 2nd magnet yielded better results with 34% better P/E dose ratio and 20–50% better dose delivery efficiencies when compared to unfocused 10 mm beams. Conclusion: While magnetic focusing using two magnets with identical focusing power did not yield desired results, ongoing Monte Carlo simulations suggest that increasing the length of the 2nd magnet to 68 mm could improve P/E dose ratios and dose efficiencies. Future work includes additional experimental validation of the longer 2nd magnet setup as well as experiments with triplet magnet systems. This project was sponsored with funding from the Department of Defense (DOD# W81XWH-BAA-10

Drug-targeting methodologies with applications: A review

PubMed Central

Kleinstreuer, Clement; Feng, Yu; Childress, Emily

2014-01-01

Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850

Problem-solving skills in high school biology: The effectiveness of the IMMEX problem-solving assessment software

NASA Astrophysics Data System (ADS)

Palacio-Cayetano, Joycelin

with the ability to fill in knowledge gaps by accessing the appropriate resources; (2) targeted search strategy coupled with high level of analytical and integration skills; and (3) focused search strategy coupled with superior discrimination, analytical, and integration skills. The strategies of students who were successful and unsuccessful solving IMMEX problems were consistent with those of expert and novice problem solvers identified in the literature on problem-solving.

Knowledge focus via software agents

NASA Astrophysics Data System (ADS)

Henager, Donald E.

2001-09-01

The essence of military Command and Control (C2) is making knowledge intensive decisions in a limited amount of time using uncertain, incorrect, or outdated information. It is essential to provide tools to decision-makers that provide: * Management of friendly forces by treating the "friendly resources as a system". * Rapid assessment of effects of military actions againt the "enemy as a system". * Assessment of how an enemy should, can, and could react to friendly military activities. Software agents in the form of mission agents, target agents, maintenance agents, and logistics agents can meet this information challenge. The role of each agent is to know all the details about its assigned mission, target, maintenance, or logistics entity. The Mission Agent would fight for mission resources based on the mission priority and analyze the effect that a proposed mission's results would have on the enemy. The Target Agent (TA) communicates with other targets to determine its role in the system of targets. A system of TAs would be able to inform a planner or analyst of the status of a system of targets, the effect of that status, adn the effect of attacks on that system. The system of TAs would also be able to analyze possible enemy reactions to attack by determining ways to minimize the effect of attack, such as rerouting traffic or using deception. The Maintenance Agent would scheudle maintenance events and notify the maintenance unit. The Logistics Agent would manage shipment and delivery of supplies to maintain appropriate levels of weapons, fuel and spare parts. The central idea underlying this case of software agents is knowledge focus. Software agents are createad automatically to focus their attention on individual real-world entities (e.g., missions, targets) and view the world from that entities perspective. The agent autonomously monitors the entity, identifies problems/opportunities, formulates solutions, and informs the decision-maker. The agent must be

Research on Life Science and Life Support Engineering Problems of Manned Deep Space Exploration Mission

NASA Astrophysics Data System (ADS)

Qi, Bin; Guo, Linli; Zhang, Zhixian

2016-07-01

Space life science and life support engineering are prominent problems in manned deep space exploration mission. Some typical problems are discussed in this paper, including long-term life support problem, physiological effect and defense of varying extraterrestrial environment. The causes of these problems are developed for these problems. To solve these problems, research on space life science and space medical-engineering should be conducted. In the aspect of space life science, the study of space gravity biology should focus on character of physiological effect in long term zero gravity, co-regulation of physiological systems, impact on stem cells in space, etc. The study of space radiation biology should focus on target effect and non-target effect of radiation, carcinogenicity of radiation, spread of radiation damage in life system, etc. The study of basic biology of space life support system should focus on theoretical basis and simulating mode of constructing the life support system, filtration and combination of species, regulation and optimization method of life support system, etc. In the aspect of space medical-engineering, the study of bio-regenerative life support technology should focus on plants cultivation technology, animal-protein production technology, waste treatment technology, etc. The study of varying gravity defense technology should focus on biological and medical measures to defend varying gravity effect, generation and evaluation of artificial gravity, etc. The study of extraterrestrial environment defense technology should focus on risk evaluation of radiation, monitoring and defending of radiation, compound prevention and removal technology of dust, etc. At last, a case of manned lunar base is analyzed, in which the effective schemes of life support system, defense of varying gravity, defense of extraterrestrial environment are advanced respectively. The points in this paper can be used as references for intensive study on key

Quality Assessment of Medical Apps that Target Medication-Related Problems.

PubMed

Loy, John Shiguang; Ali, Eskinder Eshetu; Yap, Kevin Yi-Lwern

2016-10-01

The advent of smartphones has enabled a plethora of medical apps for disease management. As of 2012, there are 40,000 health care-related mobile apps available in the market. Since most of these medical apps do not go through any stringent quality assessment, there is a risk of consumers being misinformed or misled by unreliable information. In this regard, apps that target medication-related problems (MRPs) are not an exception. There is little information on what constitutes quality in apps that target MRPs and how good the existing apps are. To develop a quality assessment tool for evaluating apps that target MRPs and assess the quality of such apps available in the major mobile app stores (iTunes and Google Play). The top 100 free and paid apps in the medical categories of iTunes and Google Play stores (total of 400 apps) were screened for inclusion in the final analysis. English language apps that targeted MRPs were downloaded on test devices to evaluate their quality. Apps intended for clinicians, patients, or both were eligible for evaluation. The quality assessment tool consisted of 4 sections (appropriateness, reliability, usability, privacy), which determined the overall quality of the apps. Apps that fulfilled the inclusion criteria were classified based on the presence of any 1 or more of the 5 features considered important for apps targeting MRPs (monitoring, interaction checker, dose calculator, medication information, medication record). Descriptive statistics and Mann-Whitney tests were used for analysis. Final analysis was based on 59 apps that fulfilled the study inclusion criteria. Apps with interaction checker (66.9%) and monitoring features (54.8%) had the highest and lowest overall qualities. Paid apps generally scored higher for usability than free apps (P = 0.006) but lower for privacy (P = 0.003). Half of the interaction checker apps were unable to detect interactions with herbal medications. Blood pressure and heart rate monitoring apps

Localized Harmonic Motion Imaging for Focused Ultrasound Surgery Targeting

PubMed Central

Curiel, Laura; Hynynen, Kullervo

2011-01-01

Recently, an in vivo real-time ultrasound-based monitoring technique that uses localized harmonic motion (LHM) to detect changes in tissues during focused ultrasound surgery (FUS) has been proposed to control the exposure. This technique can potentially be used as well for targeting imaging. In the present study we evaluated the potential of using LHM to detect changes in stiffness and the feasibility of using it for imaging purposes in phantoms and in vivo tumor detection. A single-element FUS transducer (80 mm focal length, 100 mm diameter, 1.485 MHz) was used for inducing a localized harmonic motion and a separate ultrasound diagnostic transducer excited by a pulser/receiver (5 kHz PRF, 5 MHz) was used to track motion. The motion was estimated using cross-correlation techniques on the acquired RF signal. Silicon phantom studies were performed in order to determine the size of inclusion that was possible to detect using this technique. Inclusions were discerned from the surroundings as a reduction on LHM amplitude and it was possible to depict inclusions as small as 4 mm. The amplitude of the induced LHM was always lower at the inclusions as compared with the one obtained at the surroundings. Ten New Zealand rabbits had VX2 tumors implanted on their thighs and LHM was induced and measured at the tumor region. Tumors (as small as 10 mm in length and 4 mm in width) were discerned from the surroundings as a reduction on LHM amplitude. PMID:21683514

Adaptive ISAR Imaging of Maneuvering Targets Based on a Modified Fourier Transform.

PubMed

Wang, Binbin; Xu, Shiyou; Wu, Wenzhen; Hu, Pengjiang; Chen, Zengping

2018-04-27

Focusing on the inverse synthetic aperture radar (ISAR) imaging of maneuvering targets, this paper presents a new imaging method which works well when the target's maneuvering is not too severe. After translational motion compensation, we describe the equivalent rotation of maneuvering targets by two variables-the relative chirp rate of the linear frequency modulated (LFM) signal and the Doppler focus shift. The first variable indicates the target's motion status, and the second one represents the possible residual error of the translational motion compensation. With them, a modified Fourier transform matrix is constructed and then used for cross-range compression. Consequently, the imaging of maneuvering is converted into a two-dimensional parameter optimization problem in which a stable and clear ISAR image is guaranteed. A gradient descent optimization scheme is employed to obtain the accurate relative chirp rate and Doppler focus shift. Moreover, we designed an efficient and robust initialization process for the gradient descent method, thus, the well-focused ISAR images of maneuvering targets can be achieved adaptively. Human intervention is not needed, and it is quite convenient for practical ISAR imaging systems. Compared to precedent imaging methods, the new method achieves better imaging quality under reasonable computational cost. Simulation results are provided to validate the effectiveness and advantages of the proposed method.

Conceptual Versus Algorithmic Problem-solving: Focusing on Problems Dealing with Conservation of Matter in Chemistry

NASA Astrophysics Data System (ADS)

Salta, Katerina; Tzougraki, Chryssa

2011-08-01

The students' performance in various types of problems dealing with the conservation of matter during chemical reactions has been investigated at different levels of schooling. The participants were 499 ninth grade (ages 14, 15 years) and 624 eleventh grade (ages 16, 17 years) Greek students. Data was collected using a written questionnaire concerning basic chemical concepts. Results of statistical factor and correlation analysis confirmed the classification of the problems used in three types: "algorithmic-type", "particulate-type", and "conceptual-type". All the students had a far better performance in "particulate-type" problems than in the others. Although students' ability in solving "algorithmic-type" problem increases as their school experience in chemistry progresses, their ability in solving "conceptual-type" problems decreases. Students' achievement in chemistry was measured by a Chemical Concepts Test (CCT) containing 57 questions of various forms. High-achievement students scored higher both on "algorithmic-type" and "particulate-type" problems than low achievers with the greatest difference observed in solving "algorithmic-type" problems. It is concluded that competence in "particulate-type" and "algorithmic-type" problem solving may be independent of competence in solving "conceptual-type" ones. Furthermore, it was found that students' misconceptions concerning chemical reactions and equivalence between mass and energy are impediments to their problem solving abilities. Finally, based on the findings, few suggestions concerning teaching practices are discussed.

Chasing Ghosts in Space Radiobiology Research: The Lost Focus on Non-Targeted Effects

NASA Astrophysics Data System (ADS)

Cucinotta, Francis; Saganti, Premkumar; Cacao, Eliedonna

2016-07-01

The doses and dose-rates of astronaut exposures to galactic cosmic rays (GCR) are accurately known, and lead to particle hits per cell nucleus from high charge and energy (HZE) particles of much less than one hit per cell per week. A large number of experiments have shown that additivity of biological effects is a valid assumption for space radiation exposures, while experiments at higher doses and dose-rates than occur in space continue to be a focus of the majority of space radiobiology research. Furthermore HZE particle exposures with mono-energetic particles manifest themselves as a mixed-radiation field due to the contributions of delta-rays and the random impact parameter of a particles track core to DNA and non-DNA targets in cells and tissues. The mixed-field manifestation of mono-energetic HZE particle exposures is well known from theoretical studies of microdosimetry and track structure. Additional mixed-field effects occur for single species experiments due to nuclear fragmentation in particle accelerator beam-lines and biological samples along with energy straggling. In contrast to these well known aspects of space radiobiology there are many open questions on the contribution of non-targeted effects to low dose and dose-rate exposures. Non-targeted effects (NTEs) include bystander effects and genomic instability, and have been shown to be the most important outstanding question for reducing uncertainties in space radiation cancer risk assessment. The dose-rate and radiation quality dependence of NTE's has not been established, while there is an over-arching need to develop 21st century experimental models of human cancer risk. We review possible mechanisms of NTE's and how new experiments to address these issues could be designed.

Potential and problems in ultrasound-responsive drug delivery systems

PubMed Central

Zhao, Ying-Zheng; Du, Li-Na; Lu, Cui-Tao; Jin, Yi-Guang; Ge, Shu-Ping

2013-01-01

Ultrasound is an important local stimulus for triggering drug release at the target tissue. Ultrasound-responsive drug delivery systems (URDDS) have become an important research focus in targeted therapy. URDDS include many different formulations, such as microbubbles, nanobubbles, nanodroplets, liposomes, emulsions, and micelles. Drugs that can be loaded into URDDS include small molecules, biomacromolecules, and inorganic substances. Fields of clinical application include anticancer therapy, treatment of ischemic myocardium, induction of an immune response, cartilage tissue engineering, transdermal drug delivery, treatment of Huntington’s disease, thrombolysis, and disruption of the blood–brain barrier. This review focuses on recent advances in URDDS, and discusses their formulations, clinical application, and problems, as well as a perspective on their potential use in the future. PMID:23637531

Targeted disruption of the blood brain barrier with focused ultrasound: association with cavitation activity

NASA Astrophysics Data System (ADS)

McDannold, N.; Vykhodtseva, N.; Hynynen, K.

2006-02-01

Acoustic emission was monitored during focused ultrasound exposures in conjunction with an ultrasound contrast agent (Optison®) in order to determine if cavitation activity is associated with the induction of blood-brain barrier disruption (BBBD). Thirty-four locations were sonicated (frequency: 260 kHz) at targets 10 mm deep in rabbit brain (N = 9). The sonications were applied at peak pressure amplitudes ranging from 0.11 to 0.57 MPa (burst length: 10 ms; repetition frequency of 1 Hz; duration: 20 s). Acoustic emission was recorded with a focused passive cavitation detector. This emission was recorded at each location during sonications with and without Optison®. Detectable wideband acoustic emission was observed only at 0.40 and 0.57 MPa. BBBD was observed in contrast MRI after sonication at 0.29-0.57 MPa. The appearance of small regions of extravasated erythrocytes appeared to be associated with this wideband emission signal. The results thus suggest that BBBD resulting from focused ultrasound pulses in the presence of Optison® can occur without indicators for inertial cavitation in vivo, wideband emission and extravasation. If inertial cavitation is not responsible for the BBBD, other ultrasound/microbubble interactions are likely the source. A significant increase in the emission signal due to Optison® at the second and third harmonics of the ultrasound driving frequency was found to correlate with BBBD and might be useful as an online method to indicate when the disruption occurs.

Thinking in Italian: Problem-Solving Activities for the Italian Classroom.

ERIC Educational Resources Information Center

Danesi, Marcel

1985-01-01

Looks at devices that stimulate intralinguistic thinking patterns, that is, patterns that can only be induced by the structures and forms of the target language without any dependency upon native-language patterns. Focuses on problem-solving activities that help the learner develop modes of thought that can be solved "Italian." (SED)

The solution of target assignment problem in command and control decision-making behaviour simulation

NASA Astrophysics Data System (ADS)

Li, Ni; Huai, Wenqing; Wang, Shaodan

2017-08-01

C2 (command and control) has been understood to be a critical military component to meet an increasing demand for rapid information gathering and real-time decision-making in a dynamically changing battlefield environment. In this article, to improve a C2 behaviour model's reusability and interoperability, a behaviour modelling framework was proposed to specify a C2 model's internal modules and a set of interoperability interfaces based on the C-BML (coalition battle management language). WTA (weapon target assignment) is a typical C2 autonomous decision-making behaviour modelling problem. Different from most WTA problem descriptions, here sensors were considered to be available resources of detection and the relationship constraints between weapons and sensors were also taken into account, which brought it much closer to actual application. A modified differential evolution (MDE) algorithm was developed to solve this high-dimension optimisation problem and obtained an optimal assignment plan with high efficiency. In case study, we built a simulation system to validate the proposed C2 modelling framework and interoperability interface specification. Also, a new optimisation solution was used to solve the WTA problem efficiently and successfully.

Nanomedicine strategies for targeting skin inflammation.

PubMed

Abdel-Mottaleb, Mona Ma; Try, Celine; Pellequer, Yann; Lamprecht, Alf

2014-08-01

Topical treatment of skin diseases is an attractive strategy as it receives high acceptance from patients, resulting in higher compliance and therapeutic outcomes. Recently, the use of variable nanocarriers for dermal application has been widely explored, as they offer several advantages compared with conventional topical preparations, including higher skin penetration, controlled and targeted drug delivery and the achievement of higher therapeutic effects. This article will focus on skin inflammation or dermatitis as it is one of the most common skin problems, describing the different types and causes of dermatitis, as well as the typical treatment regimens. The potential use of nanocarriers for targeting skin inflammation and the achievement of higher therapeutic effects using nanotechnology will be explored.

Problem-focused coping and self-efficacy as correlates of quality of life and severity of fibromyalgia in primary fibromyalgia patients.

PubMed

Alok, Ragini; Das, Siddharth Kumar; Agarwal, Girdhar Gopal; Tiwari, Sarvada Chand; Salwahan, Latika; Srivastava, Ragini

2014-09-01

Patients with fibromyalgia syndrome (FMS) often experience problems such as poor quality of life (QoL), loss of self-efficacy (SE), inappropriate coping behavior, and chronic widespread pain along with other symptoms. Recent studies have indicated that sense of SE and effective coping strategies (CSs) are the crux on which the management of chronic pain and enrichment of QoL of FMS patients depend. Realizing the importance of this subject for the rehabilitation of the people with FMS, this study aimed at analyzing the correlation between severity of FMS, and QoL, SE, and CSs among the patients of FMS. One hundred patients with fibromyalgia (FM) and 100 control subjects were studied. Fibromyalgia Impact Questionnaire-Revised, Quality of Life Scale, Arthritis Self-efficacy Scale, and COPE Scales for CSs were administered to both the groups. Significantly lower SE, poor QoL, and less use of CSs were reported by FM patients (P < 0.01) vis-à-vis healthy people. Problem-focused coping (r = 0.27, P < 0.01) and SE (r = 0.20, P < 0.05) were found to be significantly and positively associated with QoL. Components of Fibromyalgia Impact Questionnaire-Revised, namely, pain, function, and symptoms, were found to be significantly and negatively associated with problem-focused coping (P < 0.05), SE (P < 0.01), and QoL (P < 0.01). This study confirms that problem-focused CSs and SE are important correlates of QoL and severity of FM in Indian as well as other populations.

Solution-focused intervention for sick listed employees with psychological problems or muscle skeletal pain: a randomised controlled trial [ISRCTN39140363

PubMed Central

Nystuen, Pal; Hagen, Kare B

2006-01-01

Background Long-term sick leave has been of concern to politicians and decision-makers in Norway for several years. In the current study we assess the efficacy of a solution-focused follow-up for sick-listed employees. Methods Employees on long-term sick leave due to psychological problems or muscle skeletal pain (n = 703) were invited to participate in the project. Following self-recruitment, 103 were randomly allocated to receive solution-focused follow-up (n = 53) or "treatment as usual" (n = 50). The intervention was integrated within the regular follow up of six social security offices and organised as eight weekly solution focused work sessions. Effectiveness was measured by rate of return to work and health related quality of life (SF-36). Results Intention to treat analysis showed no significant differences between the two groups for any of the outcome measures. Secondary analysis, comparing those who attended at least 50% of the sessions with the control group revealed a significant difference in favour of the active intervention group in the SF-36 subscale of mental health (Effect Size 0.56, p = 0.05). When comparing the subgroup of participants with psychological problems there was a significant difference in mental health in favour of the intervention group (Effect Size 0.71, p = 0.041). Conclusion A voluntary solution-focused intervention offered by social-security offices is no more effective than regular follow up for employees on long-term sick leave due to psychological problems or muscle skeletal pain. PMID:16542443

Planning paths to multiple targets: memory involvement and planning heuristics in spatial problem solving.

PubMed

Wiener, J M; Ehbauer, N N; Mallot, H A

2009-09-01

For large numbers of targets, path planning is a complex and computationally expensive task. Humans, however, usually solve such tasks quickly and efficiently. We present experiments studying human path planning performance and the cognitive processes and heuristics involved. Twenty-five places were arranged on a regular grid in a large room. Participants were repeatedly asked to solve traveling salesman problems (TSP), i.e., to find the shortest closed loop connecting a start location with multiple target locations. In Experiment 1, we tested whether humans employed the nearest neighbor (NN) strategy when solving the TSP. Results showed that subjects outperform the NN-strategy, suggesting that it is not sufficient to explain human route planning behavior. As a second possible strategy we tested a hierarchical planning heuristic in Experiment 2, demonstrating that participants first plan a coarse route on the region level that is refined during navigation. To test for the relevance of spatial working memory (SWM) and spatial long-term memory (LTM) for planning performance and the planning heuristics applied, we varied the memory demands between conditions in Experiment 2. In one condition the target locations were directly marked, such that no memory was required; a second condition required participants to memorize the target locations during path planning (SWM); in a third condition, additionally, the locations of targets had to retrieved from LTM (SWM and LTM). Results showed that navigation performance decreased with increasing memory demands while the dependence on the hierarchical planning heuristic increased.

Confidence level estimation in multi-target classification problems

NASA Astrophysics Data System (ADS)

Chang, Shi; Isaacs, Jason; Fu, Bo; Shin, Jaejeong; Zhu, Pingping; Ferrari, Silvia

2018-04-01

This paper presents an approach for estimating the confidence level in automatic multi-target classification performed by an imaging sensor on an unmanned vehicle. An automatic target recognition algorithm comprised of a deep convolutional neural network in series with a support vector machine classifier detects and classifies targets based on the image matrix. The joint posterior probability mass function of target class, features, and classification estimates is learned from labeled data, and recursively updated as additional images become available. Based on the learned joint probability mass function, the approach presented in this paper predicts the expected confidence level of future target classifications, prior to obtaining new images. The proposed approach is tested with a set of simulated sonar image data. The numerical results show that the estimated confidence level provides a close approximation to the actual confidence level value determined a posteriori, i.e. after the new image is obtained by the on-board sensor. Therefore, the expected confidence level function presented in this paper can be used to adaptively plan the path of the unmanned vehicle so as to optimize the expected confidence levels and ensure that all targets are classified with satisfactory confidence after the path is executed.

A controlled trial of trauma-focused therapy versus problem-solving in Islamic children affected by civil conflict and disaster in Aceh, Indonesia.

PubMed

Dawson, Katie; Joscelyne, Amy; Meijer, Catherine; Steel, Zachary; Silove, Derrick; Bryant, Richard A

2018-03-01

To evaluate the relative efficacies of trauma-focused cognitive behavior therapy and problem-solving therapy in treating post-traumatic stress disorder in children affected by civil conflict in Aceh, Indonesia. A controlled trial of children with post-traumatic stress disorder ( N = 64) randomized children to either five individual weekly sessions of trauma-focused cognitive behavior therapy or problem-solving therapy provided by lay-counselors who were provided with brief training. Children were assessed by blind independent assessors at pretreatment, posttreatment and 3-month follow-up on post-traumatic stress disorder, depression and anger, as well as caregiver ratings of the child's post-traumatic stress disorder levels. Intent-to-treat analyses indicated no significant linear time × treatment condition interaction effects for post-traumatic stress disorder at follow-up ( t(129.05) = -0.55, p = 0.58), indicating the two conditions did not differ. Across both conditions, there were significant reductions in post-traumatic stress disorder on self-reported ( t(131.26) = -9.26, p < 0.001) and caregiver-reported ( t(170.65) = 3.53, p = 0.001) measures and anger ( t(127.66) = -7.14, p < 0.001). Across both conditions, there was a large effect size for self-reported post-traumatic stress disorder (cognitive behavior therapy: 3.73, 95% confidence interval = [2.75, 3.97]; problem-solving: 2.68, 95% confidence interval = [2.07, 3.29]). These findings suggest that trauma-focused cognitive behavior therapy and problem-solving approaches are comparably successful in reducing post-traumatic stress disorder and anger in treating mental health in children in a post-conflict setting. This pattern may reflect the benefits of non-specific therapy effects or gains associated with trauma-focused or problem-solving approaches.

Effects of a Target-Task Problem-Solving Model on Senior Secondary School Students' Performance in Physics

ERIC Educational Resources Information Center

Olaniyan, A. O.; Omosewo, E. O.

2015-01-01

The study investigated the Effects of a Target-Task Problem-Solving Model on Senior Secondary School Students' Performance in Physics. The research design was a quasi-experimental, non-randomized, non-equivalent pretest, post-test using a control group. The study was conducted in two schools purposively selected and involved a total of 120 Senior…

The Universities and Environmental Quality--Commitment to Problem Focused Education. A Report to The President's Environmental Quality Council.

ERIC Educational Resources Information Center

Steinhart, John S.; Cherniack, Stacie

This report is based on a study of a few of the multidisciplinary enviromental programs in over 30 universities. The study was undertaken to discover what kind of programs have been tried, which ones have been successful, and how the federal government might encourage effective interdisciplinary problem-focused programs. The report reviews the…

Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets.

PubMed

Chen, Cherry C; Sheeran, Paul S; Wu, Shih-Ying; Olumolade, Oluyemi O; Dayton, Paul A; Konofagou, Elisa E

2013-12-28

Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. © 2013.

A Review of Technology-Based Youth and Family-Focused Interventions

PubMed Central

Prinz, Ronald J.

2017-01-01

In the past 10 years, mental and behavioral health has seen a proliferation of technology-based interventions in the form of online and other computer-delivered programs. This paper focuses on technology-based treatment and preventive interventions aimed at benefitting children and adolescents via either involving the parents and families, or only the youth. The review considered only technology-based interventions that had at least one published study with a randomized controlled trial design. Questions being addressed included: (1) What are the technology-based interventions in the mental/behavioral health area that have been systematically evaluated in published studies? (2) What are the common and unique characteristics of these interventions and their application with respect to sample characteristics, target problems, and technology characteristics (platforms, structures, elements, and communication formats)? and (3) Which intervention approaches and strategies have accrued the greatest evidence? The review identified 30 technology-based psychosocial interventions for children and families, 19 of which were parent or family-focused (32 studies) and 11 of which were youth-focused (in 13 studies). For the parent/family-focused interventions, greatest promise was found in those that addressed either youth behavioral problems or depressive/anxious symptoms, as well as more general bolstering of parenting efficacy. The youth-focused interventions showed some promise in reducing depressive/ anxious symptoms. Advantages and disadvantages of the technology-based approaches were considered, and areas for future research and development were discussed. PMID:27787701

A Review of Technology-Based Youth and Family-Focused Interventions.

PubMed

MacDonell, Kathleen Watson; Prinz, Ronald J

2017-06-01

In the past 10 years, mental and behavioral health has seen a proliferation of technology-based interventions in the form of online and other computer-delivered programs. This paper focuses on technology-based treatment and preventive interventions aimed at benefitting children and adolescents via either involving the parents and families, or only the youth. The review considered only technology-based interventions that had at least one published study with a randomized controlled trial design. Questions being addressed included: (1) What are the technology-based interventions in the mental/behavioral health area that have been systematically evaluated in published studies? (2) What are the common and unique characteristics of these interventions and their application with respect to sample characteristics, target problems, and technology characteristics (platforms, structures, elements, and communication formats)? and (3) Which intervention approaches and strategies have accrued the greatest evidence? The review identified 30 technology-based psychosocial interventions for children and families, 19 of which were parent or family-focused (32 studies) and 11 of which were youth-focused (in 13 studies). For the parent/family-focused interventions, greatest promise was found in those that addressed either youth behavioral problems or depressive/anxious symptoms, as well as more general bolstering of parenting efficacy. The youth-focused interventions showed some promise in reducing depressive/anxious symptoms. Advantages and disadvantages of the technology-based approaches were considered, and areas for future research and development were discussed.

Self-focused and other-focused resiliency: Plausible mechanisms linking early family adversity to health problems in college women.

PubMed

Coleman, Sulamunn R M; Zawadzki, Matthew J; Heron, Kristin E; Vartanian, Lenny R; Smyth, Joshua M

2016-01-01

This study examined whether self-focused and other-focused resiliency help explain how early family adversity relates to perceived stress, subjective health, and health behaviors in college women. Female students (N = 795) participated between October 2009 and May 2010. Participants completed self-report measures of early family adversity, self-focused (self-esteem, personal growth initiative) and other-focused (perceived social support, gratitude) resiliency, stress, subjective health, and health behaviors. Using structural equation modeling, self-focused resiliency associated with less stress, better subjective health, more sleep, less smoking, and less weekend alcohol consumption. Other-focused resiliency associated with more exercise, greater stress, and more weekend alcohol consumption. Early family adversity was indirectly related to all health outcomes, except smoking, via self-focused and other-focused resiliency. Self-focused and other-focused resiliency represent plausible mechanisms through which early family adversity relates to stress and health in college women. This highlights areas for future research in disease prevention and management.

Effect of "Focus on Form" versus "Focus on Forms" Pragmatic Instruction on Development of Pragmatic Comprehension and Production

ERIC Educational Resources Information Center

Rafieyan, Vahid

2016-01-01

To develop target language pragmatic competence, language learners' attention must be directed toward not only linguistic but also pragmatic aspect of the target language expressions (Schmidt, 2001). Thus, some sorts of pragmatic awareness-raising instruction, using either explicit "Focus on Forms" or implicit "Focus on Form"…

Definition and use of Solution-focused Sustainability Assessment: A novel approach to generate, explore and decide on sustainable solutions for wicked problems.

PubMed

Zijp, Michiel C; Posthuma, Leo; Wintersen, Arjen; Devilee, Jeroen; Swartjes, Frank A

2016-05-01

This paper introduces Solution-focused Sustainability Assessment (SfSA), provides practical guidance formatted as a versatile process framework, and illustrates its utility for solving a wicked environmental management problem. Society faces complex and increasingly wicked environmental problems for which sustainable solutions are sought. Wicked problems are multi-faceted, and deriving of a management solution requires an approach that is participative, iterative, innovative, and transparent in its definition of sustainability and translation to sustainability metrics. We suggest to add the use of a solution-focused approach. The SfSA framework is collated from elements from risk assessment, risk governance, adaptive management and sustainability assessment frameworks, expanded with the 'solution-focused' paradigm as recently proposed in the context of risk assessment. The main innovation of this approach is the broad exploration of solutions upfront in assessment projects. The case study concerns the sustainable management of slightly contaminated sediments continuously formed in ditches in rural, agricultural areas. This problem is wicked, as disposal of contaminated sediment on adjacent land is potentially hazardous to humans, ecosystems and agricultural products. Non-removal would however reduce drainage capacity followed by increased risks of flooding, while contaminated sediment removal followed by offsite treatment implies high budget costs and soil subsidence. Application of the steps in the SfSA-framework served in solving this problem. Important elements were early exploration of a wide 'solution-space', stakeholder involvement from the onset of the assessment, clear agreements on the risk and sustainability metrics of the problem and on the interpretation and decision procedures, and adaptive management. Application of the key elements of the SfSA approach eventually resulted in adoption of a novel sediment management policy. The stakeholder

Focused ultrasound facilitated thermo-chemotherapy for targeted retinoblastoma treatment: a modeling study.

PubMed

Wang, Shutao; Mahesh, Sankaranarayana P; Liu, Ji; Geist, Craig; Zderic, Vesna

2012-07-01

Retinoblastoma is the most common type of intraocular tumors in children. Currently, with early detection and improved systemic chemo-adjuvant therapies, treatment paradigm has shifted from survival to globe salvation/vision preservation. The objective of our work has been to explore the possible application of focused ultrasound (FUS) for targeted drug delivery in the posterior pole retinoblastoma. Specifically, theoretical models were implemented to evaluate the feasibility of using FUS to generate localized hyperthermia in retinal tumor areas, for potential triggering the chemotherapeutic agent deployment from heat-sensitive drug carriers. In-vitro experiments were conducted in tissue-mimicking phantoms with embedded excised rabbit eyes to validate the reliability of the modeling results. After confirming the reliability of our model, various FUS transducer parameters were investigated to induce maximal hyperthermia coverage in the tumor, while sparing adjacent eye structures (e.g. the lens). The evaluated FUS parameters included operating frequency, total acoustic power, geometric dimensions, transducer f-number, standoff distance, as well as different pulsing scenarios. Our modeling results suggest that the most suitable ultrasound frequency for this type of treatments was in the range of 2-3.5 MHz depending on the size of retinoblastoma. Appropriate transducer f-number (close to 1) and standoff distance could be selected to minimize the risks of over-heating undesired regions. With the total acoustic power of 0.4 W, 56.3% of the tumor was heated to hyperthermic temperature range (39-44 °C) while the temperature in lens was maintained below 41 °C. In conclusion, FUS-induced hyperthermia for targeted drug delivery may be a viable option in treatments of juxta-foveal or posterior pole retinoblastomas. Future in-vivo studies will allow us to determine the effectiveness and safety of the proposed approach. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of a Multifocused Prevention Program on Preschool Children's Competencies and Behavior Problems

ERIC Educational Resources Information Center

Stefan, Catrinel A.; Miclea, Mircea

2013-01-01

This study was designed to assess the effectiveness of a multifocused (child-, teacher- and parent-focused) prevention program for Romanian preschoolers, targeting social--emotional competence development, as well as reduction of behavior problems. Fourteen classrooms were randomly assigned to the intervention and control conditions. Subsequent…

The Pitt Innovation Challenge (PInCh): Driving Innovation in Translational Research Through an Incentive-Based, Problem-Focused Competition

PubMed Central

Fitzpatrick, Nicole Edgar; Maier, John; Yasko, Laurel; Mathias, David; Qua, Kacy; Wagner, Erika; Miller, Elizabeth; Reis, Steven E.

2017-01-01

Problem Translational research aims to move scientific discoveries across the biomedical spectrum from the laboratory to humans, and to ultimately transform clinical practice and public health policies. Despite efforts to accelerate translational research through national initiatives, several major hurdles remain. Approach The authors created the Pitt Innovation Challenge (PInCh) as an incentive-based, problem-focused approach to solving identified clinical or public health problems at the University of Pittsburgh Clinical and Translational Science Institute in spring 2014. With input from a broad range of stakeholders, PInCh leadership arrived at the challenge question: How do we empower individuals to take control of their own health outcomes? The authors developed the PInCh’s three-round proposal submission and review process as well as an online contest management tool to support the process. Outcomes Ninety-two teams submitted videos proposals in round one. Proposals included mobile applications (29, 32%), other information technology (19, 21%), and community program (22, 24%) solutions. Ten teams advanced to the final round, where three were awarded $100,000 to implement their solution over twelve months. In a six-month follow-up survey, 6/11 (55%) team leaders stated the PInCh helped to facilitate connections outside their normal sphere of collaborators. Next Steps Additional educational training sessions related to problem-focused research will be developed. The PInCh will be expanded to engage investment and industry communities to facilitate the translation of solutions to clinical practice via commercialization pathways. External organizations and other universities will be engaged to use the PInCh as a mechanism to fuel innovation in their spaces. PMID:27508341

Targeting chronic inflammation in cerebral aneurysms: focusing on NF-kappaB as a putative target of medical therapy.

PubMed

Aoki, Tomohiro; Nishimura, M

2010-03-01

Cerebral aneurysms (CAs) are the main cause of life-threatening subarachnoid hemorrhage. Given its prevalence and endpoint, CA treatment is a public health issue. Effective medical treatment of CAs is lacking because the detailed mechanisms of CA formation are incompletely understood. The aim of this contribution is to review recent articles about CA formation, to suggest the underlying mechanisms of CA formation, and to discuss potential therapeutic targets for treatment. Articles were collected by an internet search of PubMed using the keywords 'intracranial' or 'cerebral aneurysm'. A review of articles about the pathogenesis of CA formation focusing on inflammation. Recent articles demonstrate that inflammation-related-molecule induction and inflammatory cell infiltration in CA walls and the close relationship between inflammatory responses and CA formation. From studies in experimental models, chronic inflammation triggered primarily by NF-kappaB activation in endothelial cells and subsequent macrophage infiltration have critical roles in CA formation. Inhibition of inflammation-related molecules in CA walls results in the decreased incidence of CA formation. Agents with anti-inflammatory activity (particularly anti- NF-kappaB effects) have potential as therapeutic drugs for CAs.

An ecological momentary assessment of comparison target as a moderator of the effects of appearance-focused social comparisons.

PubMed

Leahey, Tricia M; Crowther, Janis H

2008-09-01

This research examined whether comparison target moderates the effects of naturally occurring appearance-focused social comparisons on women's affect, appearance esteem, and dieting thoughts. During daily activities, body-satisfied (BS) women and body-dissatisfied (BD) women recorded their comparison targets and reactions to comparison information. For BS women, upward comparisons with peers were associated with more positive affect (PA) and appearance esteem and less guilt than upward comparisons with media images and downward comparisons with peers were associated with less PA than downward comparisons with media images. For BD women, upward comparisons with peers were associated with more appearance esteem and diet thoughts than upward comparisons with media images and downward comparisons with peers were associated with less PA, appearance esteem, and diet thoughts and more guilt than downward comparisons with media images.

Cardiotoxicity of the new cancer therapeutics- mechanisms of, and approaches to, the problem

PubMed Central

Force, Thomas; Kerkelä, Risto

2009-01-01

Cardiotoxicity of some targeted therapeutics, including monoclonal antibodies and small molecule inhibitors, is a reality. Herein we will examine why it occurs, focusing on molecular mechanisms to better understand the issue. We will also examine how big the problem is and, more importantly, how big it may become in the future. We will review models for detecting cardiotoxicity in the pre-clinical phase. We will also focus on two key areas that drive cardiotoxicity- multi-targeting and the inherent lack of selectivity of ATP-competitive antagonists. Finally, we will examine the issue of reversibility and discuss possible approaches to keeping patients on therapy. PMID:18617014

Families OverComing under Stress (FOCUS) for Early Childhood: Building Resilience for Young Children in High Stress Families

ERIC Educational Resources Information Center

Mogil, Catherine; Paley, Blair; Doud, Tricia; Havens, Linda; Moore-Tyson, Jessica; Beardslee, William R.; Lester, Patricia

2010-01-01

Parental distress and trauma affects the entire family, including the youngest children. Families OverComing Under Stress (FOCUS) is a targeted prevention program for high-risk families that aims to enhance family cohesion, support the parent-child relationship, and build emotional regulation, communication, and problem-solving skills across the…

An ex vivo feasibility experimental study on targeted cell surgery by high intensity focused ultrasound

NASA Astrophysics Data System (ADS)

Wang, Zhi Biao; Wu, Junru; Fang, Liao Qiong; Wang, Hua; Li, Fa Qi; Tian, Yun Bo; Gong, Xiao Bo; Zhang, Hong; Zhang, Lian; Feng, Ruo

2012-10-01

High intensity focused ultrasound (HIFU) has become a new noninvasive surgical modality in medicine. A portion of tissue seated inside a patient's body may experience coagulative necrosis after a few seconds of insonification by high intensity focused ultrasound (US) generated by an extracorporeal focusing US transducer. The region of tissue affected by coagulative necrosis (CN) usually has an ellipsoidal shape when the thermal effect due to US absorption plays the dominant role. Its long and short axes are parallel and perpendicular to the US propagation direction respectively. It was shown by ex vivo experiments that the dimension of the short and long axes of the tissue which experiences CN can be as small as 50 μm and 250 μm respectively after one second exposure of US pulse (the spatial and pulse average acoustic power is on the order of tens of Watts and the local acoustic spatial and temporal pulse averaged intensity is on the order of 3 × 104 W/cm2) generated by a 1.6 MHz HIFU transducer of 12 cm diameter and 11 cm geometric focal length (f-number = 0.92). The numbers of cells which suffered CN were estimated to be on the order of 40. This result suggests that HIFU is able to interact with tens of cells at/near its focal zone while keeping the neighboring cells minimally affected, and thus the targeted cell surgery may be achievable.

Emerging therapeutic targets in metastatic progression: a focus on breast cancer

PubMed Central

Li, Zhuo; Kang, Yibin

2016-01-01

Metastasis is the underlying cause of death for the majority of breast cancer patients. Despite significant advances in recent years in basic research and clinical development, therapies that specifically target metastatic breast cancer remain inadequate, and represents the single greatest obstacle to reducing mortality of late-stage breast cancer. Recent efforts have leveraged genomic analysis of breast cancer and molecular dissection of tumor-stromal cross-talk to uncover a number of promising candidates for targeted treatment of metastatic breast cancer. Rational combinations of therapeutic agents targeting tumor-intrinsic properties and microenvironmental components provide a promising strategy to develop precision treatments with higher specificity and less toxicity. In this review, we discuss the emerging therapeutic targets in breast cancer metastasis, from tumor-intrinsic pathways to those that involve the host tissue components, including the immune system. PMID:27000769

Trans-cranial opening of the blood-brain barrier in targeted regions using a stereotaxic brain atlas and focused ultrasound energy.

PubMed

Bing, Chenchen; Ladouceur-Wodzak, Michelle; Wanner, Clinton R; Shelton, John M; Richardson, James A; Chopra, Rajiv

2014-01-01

The blood-brain barrier (BBB) protects the brain by preventing the entry of large molecules; this poses a major obstacle for the delivery of drugs to the brain. A novel technique using focused ultrasound (FUS) energy combined with microbubble contrast agents has been widely used for non-invasive trans-cranial BBB opening. Traditionally, FUS research is conducted with magnetic resonance imaging (MRI) guidance, which is expensive and poses physical limitations due to the magnetic field. A system that could allow researchers to test brain therapies without MR intervention could facilitate and accelerate translational research. In this study, we present a novel FUS system that uses a custom-built FUS generator mounted on a motorized stereotaxic apparatus with embedded brain atlas to locally open the BBB in rodents. The system was initially characterized using a tissue-mimicking phantom. Rodent studies were also performed to evaluate whether non-invasive, localized BBB opening could be achieved using brain atlas-based targeting. Brains were exposed to pulsed focused ultrasound energy at 1.06 MHz in rats and 3.23 MHz in mice, with the focal pressure estimated to be 0.5-0.6 MPa through the skull. BBB opening was confirmed in gross tissue sections by the presence of Evans blue leakage in the exposed region of the brain and by histological assessment. The targeting accuracy of the stereotaxic system was better than 0.5 mm in the tissue-mimicking phantom. Reproducible localized BBB opening was verified with Evans blue dye leakage in 32/33 rats and had a targeting accuracy of ±0.3 mm. The use of higher frequency exposures in mice enabled a similar precision of localized BBB opening as was observed with the low frequency in the rat model. With this dedicated small-animal motorized stereotaxic-FUS system, we achieved accurate targeting of focused ultrasound exposures in the brain for non-invasive opening of the BBB. This system can be used as an alternative to MR

An Improved Aerial Target Localization Method with a Single Vector Sensor

PubMed Central

Zhao, Anbang; Bi, Xuejie; Hui, Juan; Zeng, Caigao; Ma, Lin

2017-01-01

This paper focuses on the problems encountered in the actual data processing with the use of the existing aerial target localization methods, analyzes the causes of the problems, and proposes an improved algorithm. Through the processing of the sea experiment data, it is found that the existing algorithms have higher requirements for the accuracy of the angle estimation. The improved algorithm reduces the requirements of the angle estimation accuracy and obtains the robust estimation results. The closest distance matching estimation algorithm and the horizontal distance estimation compensation algorithm are proposed. The smoothing effect of the data after being post-processed by using the forward and backward two-direction double-filtering method has been improved, thus the initial stage data can be filtered, so that the filtering results retain more useful information. In this paper, the aerial target height measurement methods are studied, the estimation results of the aerial target are given, so as to realize the three-dimensional localization of the aerial target and increase the understanding of the underwater platform to the aerial target, so that the underwater platform has better mobility and concealment. PMID:29135956

Problem-Solving Test: Targeted Gene Disruption

ERIC Educational Resources Information Center

Szeberenyi, Jozsef

2008-01-01

Mutational inactivation of a specific gene is the most powerful technique to analyze the biological function of the gene. This approach has been used for a long time in viruses, bacteria, yeast, and fruit fly, but looked quite hopeless in more complex organisms. Targeted inactivation of specific genes (also known as knock-out mutation) in mice is…

Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem

PubMed Central

Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar

2016-01-01

Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design. PMID:27958331

Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem.

PubMed

Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar

2016-12-13

Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design.

Group Training in Interpersonal Problem-Solving Skills for Workplace Adaptation of Adolescents and Adults with Asperger Syndrome: A Preliminary Study

ERIC Educational Resources Information Center

Bonete, Saray; Calero, María Dolores; Fernández-Parra, Antonio

2015-01-01

Adults with Asperger syndrome show persistent difficulties in social situations which psychosocial treatments may address. Despite the multiple studies focusing on social skills interventions, only some have focused specifically on problem-solving skills and have not targeted workplace adaptation training in the adult population. This study…

Are Your Students Problem Performers or Problem Solvers?

ERIC Educational Resources Information Center

Barlow, Angela T.; Duncan, Matthew; Lischka, Alyson E.; Hartland, Kristin S.; Willingham, J. Christopher

2017-01-01

When presented with a problem in mathematics class, students often function as problem performers rather than problem solvers (Rigelman 2007). That is, rather than understanding the problem, students focus on using an operation to complete it. Students' tendencies to act as problem performers can prevent them from suggesting problem-solving…

About an Optimal Visiting Problem

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

Bagagiolo, Fabio, E-mail: bagagiol@science.unitn.it; Benetton, Michela

In this paper we are concerned with the optimal control problem consisting in minimizing the time for reaching (visiting) a fixed number of target sets, in particular more than one target. Such a problem is of course reminiscent of the famous 'Traveling Salesman Problem' and brings all its computational difficulties. Our aim is to apply the dynamic programming technique in order to characterize the value function of the problem as the unique viscosity solution of a suitable Hamilton-Jacobi equation. We introduce some 'external' variables, one per target, which keep in memory whether the corresponding target is already visited or not,more » and we transform the visiting problem in a suitable Mayer problem. This fact allows us to overcome the lacking of the Dynamic Programming Principle for the originary problem. The external variables evolve with a hysteresis law and the Hamilton-Jacobi equation turns out to be discontinuous.« less

Sensory-motor problems in Autism

PubMed Central

Whyatt, Caroline; Craig, Cathy

2013-01-01

Despite being largely characterized as a social and cognitive disorder, strong evidence indicates the presence of significant sensory-motor problems in Autism Spectrum Disorder (ASD). This paper outlines our progression from initial, broad assessment using the Movement Assessment Battery for Children (M-ABC2) to subsequent targeted kinematic assessment. In particular, pronounced ASD impairment seen in the broad categories of manual dexterity and ball skills was found to be routed in specific difficulties on isolated tasks, which were translated into focused experimental assessment. Kinematic results from both subsequent studies highlight impaired use of perception-action coupling to guide, adapt and tailor movement to task demands, resulting in inflexible and rigid motor profiles. In particular difficulties with the use of temporal adaption are shown, with “hyperdexterity” witnessed in ballistic movement profiles, often at the cost of spatial accuracy and task performance. By linearly progressing from the use of a standardized assessment tool to targeted kinematic assessment, clear and defined links are drawn between measureable difficulties and underlying sensory-motor assessment. Results are specifically viewed in-light of perception-action coupling and its role in early infant development suggesting that rather than being “secondary” level impairment, sensory-motor problems may be fundamental in the progression of ASD. This logical and systematic process thus allows a further understanding into the potential root of observable motor problems in ASD; a vital step if underlying motor problems are to be considered a fundamental aspect of autism and allow a route of non-invasive preliminary diagnosis. PMID:23882194

Goals and everyday problem solving: examining the link between age-related goals and problem-solving strategy use.

PubMed

Hoppmann, Christiane A; Coats, Abby Heckman; Blanchard-Fields, Fredda

2008-07-01

Qualitative interviews on family and financial problems from 332 adolescents, young, middle-aged, and older adults, demonstrated that developmentally relevant goals predicted problem-solving strategy use over and above problem domain. Four focal goals concerned autonomy, generativity, maintaining good relationships with others, and changing another person. We examined both self- and other-focused problem-solving strategies. Autonomy goals were associated with self-focused instrumental problem solving and generative goals were related to other-focused instrumental problem solving in family and financial problems. Goals of changing another person were related to other-focused instrumental problem solving in the family domain only. The match between goals and strategies, an indicator of problem-solving adaptiveness, showed that young individuals displayed the greatest match between autonomy goals and self-focused problem solving, whereas older adults showed a greater match between generative goals and other-focused problem solving. Findings speak to the importance of considering goals in investigations of age-related differences in everyday problem solving.

The Pitt Innovation Challenge (PInCh): Driving Innovation in Translational Research Through an Incentive-Based, Problem-Focused Competition.

PubMed

Fitzpatrick, Nicole Edgar; Maier, John; Yasko, Laurel; Mathias, David; Qua, Kacy; Wagner, Erika; Miller, Elizabeth; Reis, Steven E

2017-05-01

Translational research aims to move scientific discoveries across the biomedical spectrum from the laboratory to humans, and to ultimately transform clinical practice and public health policies. Despite efforts to accelerate translational research through national initiatives, several major hurdles remain. The authors created the Pitt Innovation Challenge (PInCh) as an incentive-based, problem-focused approach to solving identified clinical or public health problems at the University of Pittsburgh Clinical and Translational Science Institute in spring 2014. With input from a broad range of stakeholders, PInCh leadership arrived at the challenge question: How do we empower individuals to take control of their own health outcomes? The authors developed the PInCh's three-round proposal submission and review process as well as an online contest management tool to support the process. Ninety-two teams submitted video proposals in round one. Proposals included mobile applications (29; 32%), other information technology (19; 21%), and community program (22; 24%) solutions. Ten teams advanced to the final round, where three were awarded $100,000 to implement their solution over 12 months. In a 6-month follow-up survey, 6/11 (55%) team leaders stated the PInCh helped to facilitate connections outside their normal sphere of collaborators. Additional educational training sessions related to problem-focused research will be developed. The PInCh will be expanded to engage investment and industry communities to facilitate the translation of solutions to clinical practice via commercialization pathways. External organizations and other universities will be engaged to use the PInCh as a mechanism to fuel innovation in their spaces.

Targeted therapy in severe asthma today: focus on immunoglobulin E.

PubMed

Pelaia, Girolamo; Canonica, Giorgio Walter; Matucci, Andrea; Paolini, Rossella; Triggiani, Massimo; Paggiaro, Pierluigi

2017-01-01

Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard "one size fits all" approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes current knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma.

Targeted therapy in severe asthma today: focus on immunoglobulin E

PubMed Central

Pelaia, Girolamo; Canonica, Giorgio Walter; Matucci, Andrea; Paolini, Rossella; Triggiani, Massimo; Paggiaro, Pierluigi

2017-01-01

Asthma is a complex chronic inflammatory disease of multifactorial etiology. International guidelines increasingly recognize that a standard “one size fits all” approach is no longer an effective approach to achieve optimal treatment outcomes, and a number of disease phenotypes have been proposed for asthma, which has the potential to guide treatment decisions. Among the many asthma phenotypes, allergic asthma represents the widest and most easily recognized asthma phenotype, present in up to two-thirds of adults with asthma. Immunoglobulin E (IgE) production is the primary and key cause of allergic asthma leading to persistent symptoms, exacerbations and a poor quality of life. Therefore, limiting IgE activity upstream could stop the entire allergic inflammation cascade in IgE-mediated allergic asthma. The anti-IgE treatment omalizumab has an accepted place in the management of severe asthma (Global Initiative for Asthma [GINA] step 5) and represents the first (and, currently, only) targeted therapy with a specific target in severe allergic asthma. This review summarizes current knowledge of the mechanisms and pathogenesis of severe asthma, examines the actual role of IgE in asthma and the biological rationale for targeting IgE in allergic asthma and reviews the data for the efficacy and safety of omalizumab in the treatment of severe asthma. Current knowledge of the role of IgE in asthma, extensive clinical trial data and a decade of use in clinical practice has established omalizumab as a safe and effective targeted therapy for the treatment of patients with severe persistent IgE-mediated allergic asthma. PMID:28721017

Promoting interdomain analogical transfer: When creating a problem helps to solve a problem.

PubMed

Minervino, Ricardo A; Olguín, Valeria; Trench, Máximo

2017-02-01

Research on analogical thinking has devised several ways of promoting an abstract encoding of base analogs, thus rendering them more retrievable during later encounters with similar situations lacking surface similarities. Recent studies have begun to explore ways of facilitating transfer at retrieval time, which could facilitate the retrieval of distant analogs learned within contexts that were not specially directed to emphasize their abstract structure. Such studies demonstrate that comparing a target problem to an analogous problem helps students retrieve base analogs that lack surface similarities. To devise more portable ways of enhancing analogical transfer, Experiment 1 replicated Kurtz and Loewenstein's (Memory & Cognition, 35, 334-341, 2007) target-comparison procedure with an additional condition in which participants compared the target to a nonanalogous problem before attempting to reach its solution. Although comparing two analogous targets outperformed the standard transfer condition in promoting analogical transfer, comparing nonanalogous problems did not yield a transfer advantage. Based on prior studies that showed that the activity of creating analogous problems during their initial encoding elicits a more abstract representation of base analogs, in Experiment 2 we assessed whether constructing a second analogous target problem at retrieval time helps participants retrieve superficially dissimilar base analogs. As predicted, target invention increased the retrieval of distant sources. In both experiments we found an association between the quality of the generated schemas and the probability of retrieving a distant base analog from memory.

PROGRESS AND PROBLEMS IN THE APPLICATION OF FOCUSED ULTRASOUND FOR BLOOD-BRAIN BARRIER DISRUPTION

PubMed Central

Vykhodtseva, Natalia; McDannold, Nathan; Hynynen, Kullervo

2008-01-01

Advances in neuroscience have resulted in the development of new diagnostic and therapeutic agents for potential use in the central nervous system (CNS). However, the ability to deliver the majority of these agents to the brain is limited by the blood–brain barrier (BBB), a specialized structure of the blood vessel wall that hampers transport and diffusion from the blood to the brain. Many CNS disorders could be treated with drugs, enzymes, genes, or large-molecule biotechnological products such as recombinant proteins, if they could cross the BBB. This article reviews the problems of the BBB presence in treating the vast majority of CNS diseases and the efforts to circumvent the BBB through the design of new drugs and the development of more sophisticated delivery methods. Recent advances in the development of noninvasive, targeted drug delivery by MRI-guided ultrasound-induced BBB disruption are also summarized. PMID:18511095

Phospholipid Capped Mesoporous Nanoparticles for Targeted High Intensity Focused Ultrasound Ablation.

PubMed

Yildirim, Adem; Chattaraj, Rajarshi; Blum, Nicholas T; Shi, Dennis; Kumar, Kaushlendra; Goodwin, Andrew P

2017-09-01

The mechanical effects of cavitation can be effective for therapy but difficult to control, thus potentially leading to off-target side effects in patients. While administration of ultrasound active agents such as fluorocarbon microbubbles and nanodroplets can locally enhance the effects of high intensity focused ultrasound (HIFU), it has been challenging to prepare ultrasound active agents that are small and stable enough to accumulate in tumors and internalize into cancer cells. Here, this paper reports the synthesis of 100 nm nanoparticle ultrasound agents based on phospholipid-coated, mesoporous, hydrophobically functionalized silica nanoparticles that can internalize into cancer cells and remain acoustically active. The ultrasound agents produce bubbles when subjected to short HIFU pulses (≈6 µs) with peak negative pressure as low as ≈7 MPa and at particle concentrations down to 12.5 µg mL -1 (7 × 10 9 particles mL -1 ). Importantly, ultrasound agents are effectively uptaken by cancer cells without cytotoxic effects, but HIFU insonation causes destruction of the cells by the acoustically generated bubbles, as demonstrated by (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase assays and flow cytometry. Finally, it is showed that the HIFU dose required to effectively eliminate cancer cells in the presence of ultrasound agents causes only a small temperature increase of ≈3.5 °C. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Robotic Automation of In Vivo Two-Photon Targeted Whole-Cell Patch-Clamp Electrophysiology.

PubMed

Annecchino, Luca A; Morris, Alexander R; Copeland, Caroline S; Agabi, Oshiorenoya E; Chadderton, Paul; Schultz, Simon R

2017-08-30

Whole-cell patch-clamp electrophysiological recording is a powerful technique for studying cellular function. While in vivo patch-clamp recording has recently benefited from automation, it is normally performed "blind," meaning that throughput for sampling some genetically or morphologically defined cell types is unacceptably low. One solution to this problem is to use two-photon microscopy to target fluorescently labeled neurons. Combining this with robotic automation is difficult, however, as micropipette penetration induces tissue deformation, moving target cells from their initial location. Here we describe a platform for automated two-photon targeted patch-clamp recording, which solves this problem by making use of a closed loop visual servo algorithm. Our system keeps the target cell in focus while iteratively adjusting the pipette approach trajectory to compensate for tissue motion. We demonstrate platform validation with patch-clamp recordings from a variety of cells in the mouse neocortex and cerebellum. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Children's Problems with Focus and Cohesion in Revising.

ERIC Educational Resources Information Center

Champagne, Mireille; And Others

A study was conducted to determine whether children in revising their writing to accommodate new information would make corresponding textual changes to preserve appropriate focus and cohesion. The subjects, 48 children each from grades three, six, and nine, were presented with a task that involved descriptions of pictures with incongruent…

Effectiveness of an Attachment-Focused Manualized Intervention for Parents of Teens at Risk for Aggressive Behaviour: The Connect Program

ERIC Educational Resources Information Center

Moretti, Marlene M.; Obsuth, Ingrid

2009-01-01

Aggressive, violent and antisocial behaviour in children and adolescents is a growing concern across the globe. Targeting parent-teen relationships is critical in reducing problem behaviour. "Connect" is a manualized ten-week program for parents or alternative caregivers of at-risk teens that focuses on the building blocks of secure attachment:…

Targeted drug delivery for cancer therapy: the other side of antibodies

PubMed Central

2012-01-01

Therapeutic monoclonal antibody (TMA) based therapies for cancer have advanced significantly over the past two decades both in their molecular sophistication and clinical efficacy. Initial development efforts focused mainly on humanizing the antibody protein to overcome problems of immunogenicity and on expanding of the target antigen repertoire. In parallel to naked TMAs, antibody-drug conjugates (ADCs) have been developed for targeted delivery of potent anti-cancer drugs with the aim of bypassing the morbidity common to conventional chemotherapy. This paper first presents a review of TMAs and ADCs approved for clinical use by the FDA and those in development, focusing on hematological malignancies. Despite advances in these areas, both TMAs and ADCs still carry limitations and we highlight the more important ones including cancer cell specificity, conjugation chemistry, tumor penetration, product heterogeneity and manufacturing issues. In view of the recognized importance of targeted drug delivery strategies for cancer therapy, we discuss the advantages of alternative drug carriers and where these should be applied, focusing on peptide-drug conjugates (PDCs), particularly those discovered through combinatorial peptide libraries. By defining the advantages and disadvantages of naked TMAs, ADCs and PDCs it should be possible to develop a more rational approach to the application of targeted drug delivery strategies in different situations and ultimately, to a broader basket of more effective therapies for cancer patients. PMID:23140144

Increase in velocimeter depth of focus through astigmatism

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

Erskine, D.J.

1996-05-01

Frequently, velocimeter targets are illuminated by a laser beam passing through a hole in a mirror. This mirror is responsible for diverting returning light from a target lens to a velocity interferometer system for any reflector (VISAR). This mirror is often a significant distance from the target lens. Consequently, at certain target focus positions the returning light is strongly vignetted by the hole, causing a loss of signal. We find that we can prevent loss of signal and greatly increase the useful depth of focus by attaching a cylindrical lens to the target lens. {copyright} {ital 1996 American Institute ofmore » Physics.}« less

A decade of research on health content in the media: the focus on health challenges and sociocultural context and attendant informational and ideological problems.

PubMed

Kline, Kimberly N

2006-01-01

There is a burgeoning interest in the health and illness content of popular media in the domains of advertising, journalism, and entertainment. This article reviews the past 10 years of this research, describing the relationship between the health topics addressed in the research, the shifting focus of concerns about the media, and, ultimately, the variation in problems for health promotion. I suggest that research attending to topics related to bodily health challenges focused on whether popular media accurately or appropriately represented health challenges. The implication was that there is some consensus about more right or wrong, complete or incomplete ways of representing an issue; the problem was that the media are generally wrong. Alternatively, research addressing topics related to sociocultural context issues focused on how certain interests are privileged in the media. The implication was that competing groups are making claims on the system, but the problem was that popular media marginalizes certain interests. In short, popular media is not likely to facilitate understandings helpful to individuals coping with health challenges and is likely to perpetuate social and political power differentials with regard to health-related issues. I conclude by offering some possibilities for future health media content research.

Real-time adaptive methods for treatment of mobile organs by MRI-controlled high-intensity focused ultrasound.

PubMed

de Senneville, Baudouin Denis; Mougenot, Charles; Moonen, Chrit T W

2007-02-01

Focused ultrasound (US) is a unique and noninvasive technique for local deposition of thermal energy deep inside the body. MRI guidance offers the additional benefits of excellent target visualization and continuous temperature mapping. However, treating a moving target poses severe problems because 1) motion-related thermometry artifacts must be corrected, 2) the US focal point must be relocated according to the target displacement. In this paper a complete MRI-compatible, high-intensity focused US (HIFU) system is described together with adaptive methods that allow continuous MR thermometry and therapeutic US with real-time tracking of a moving target, online motion correction of the thermometry maps, and regional temperature control based on the proportional, integral, and derivative method. The hardware is based on a 256-element phased-array transducer with rapid electronic displacement of the focal point. The exact location of the target during US firing is anticipated using automatic analysis of periodic motions. The methods were tested with moving phantoms undergoing either rigid body or elastic periodical motions. The results show accurate tracking of the focal point. Focal and regional temperature control is demonstrated with a performance similar to that obtained with stationary phantoms. Copyright (c) 2007 Wiley-Liss, Inc.

Cross-wind profiling based on the scattered wave scintillation in a telescope focus.

PubMed

Banakh, V A; Marakasov, D A; Vorontsov, M A

2007-11-20

The problem of wind profile reconstruction from scintillation of an optical wave scattered off a rough surface in a telescope focus plane is considered. Both the expression for the spatiotemporal correlation function and the algorithm of cross-wind velocity and direction profiles reconstruction based on the spatiotemporal spectrum of intensity of an optical wave scattered by a diffuse target in a turbulent atmosphere are presented. Computer simulations performed under conditions of weak optical turbulence show wind profiles reconstruction by the developed algorithm.

Focused ion beam source method and apparatus

DOEpatents

Pellin, Michael J.; Lykke, Keith R.; Lill, Thorsten B.

2000-01-01

A focused ion beam having a cross section of submicron diameter, a high ion current, and a narrow energy range is generated from a target comprised of particle source material by laser ablation. The method involves directing a laser beam having a cross section of critical diameter onto the target, producing a cloud of laser ablated particles having unique characteristics, and extracting and focusing a charged particle beam from the laser ablated cloud. The method is especially suited for producing focused ion beams for semiconductor device analysis and modification.

Dam break problem for the focusing nonlinear Schrödinger equation and the generation of rogue waves

NASA Astrophysics Data System (ADS)

El, G. A.; Khamis, E. G.; Tovbis, A.

2016-09-01

We propose a novel, analytically tractable, scenario of the rogue wave formation in the framework of the small-dispersion focusing nonlinear Schrödinger (NLS) equation with the initial condition in the form of a rectangular barrier (a ‘box’). We use the Whitham modulation theory combined with the nonlinear steepest descent for the semi-classical inverse scattering transform, to describe the evolution and interaction of two counter-propagating nonlinear wave trains—the dispersive dam break flows—generated in the NLS box problem. We show that the interaction dynamics results in the emergence of modulated large-amplitude quasi-periodic breather lattices whose amplitude profiles are closely approximated by the Akhmediev and Peregrine breathers within certain space-time domain. Our semi-classical analytical results are shown to be in excellent agreement with the results of direct numerical simulations of the small-dispersion focusing NLS equation.

Application of reduced order modeling techniques to problems in heat conduction, isoelectric focusing and differential algebraic equations

NASA Astrophysics Data System (ADS)

Mathai, Pramod P.

This thesis focuses on applying and augmenting 'Reduced Order Modeling' (ROM) techniques to large scale problems. ROM refers to the set of mathematical techniques that are used to reduce the computational expense of conventional modeling techniques, like finite element and finite difference methods, while minimizing the loss of accuracy that typically accompanies such a reduction. The first problem that we address pertains to the prediction of the level of heat dissipation in electronic and MEMS devices. With the ever decreasing feature sizes in electronic devices, and the accompanied rise in Joule heating, the electronics industry has, since the 1990s, identified a clear need for computationally cheap heat transfer modeling techniques that can be incorporated along with the electronic design process. We demonstrate how one can create reduced order models for simulating heat conduction in individual components that constitute an idealized electronic device. The reduced order models are created using Krylov Subspace Techniques (KST). We introduce a novel 'plug and play' approach, based on the small gain theorem in control theory, to interconnect these component reduced order models (according to the device architecture) to reliably and cheaply replicate whole device behavior. The final aim is to have this technique available commercially as a computationally cheap and reliable option that enables a designer to optimize for heat dissipation among competing VLSI architectures. Another place where model reduction is crucial to better design is Isoelectric Focusing (IEF) - the second problem in this thesis - which is a popular technique that is used to separate minute amounts of proteins from the other constituents that are present in a typical biological tissue sample. Fundamental questions about how to design IEF experiments still remain because of the high dimensional and highly nonlinear nature of the differential equations that describe the IEF process as well as

Design a 10 kJ IS Mather Type Plasma Focus for Solid Target Activation to Produce Short-Lived Radioisotopes 12C(d,n)13N

NASA Astrophysics Data System (ADS)

Sadat Kiai, S. M.; Adlparvar, S.; Sheibani, S.; Elahi, M.; Safarien, A.; Farhangi, S.; Zirak, A. R.; Alhooie, S.; Mortazavi, B. N.; Khalaj, M. M.; Khanchi, A. R.; Dabirzadeh, A. A.; Kashani, A.; Zahedi, F.

2010-10-01

A 10 kJ (15 kV, 88 μF) IS (Iranian Sun) Mather type plasma focus device has been studied to determine the activity of a compound exogenous carbon solid target through 12C(d,n)13N nuclear reaction. The produced 13N is a short-lived radioisotope with a half-life of 9.97 min and threshold energy of 0.28 MeV. The results indicate that energetic deuterons impinging on the solid target can produce yield of = 6.7 × 10-5 with an activity of A = 6.8 × 104 Bq for one plasma focus shut and A ν = 4 × 105 Bq for 6 shut per mint when the projectile maximum deuterons energy is E max = 3 MeV.

Frnakenstein: multiple target inverse RNA folding.

PubMed

Lyngsø, Rune B; Anderson, James W J; Sizikova, Elena; Badugu, Amarendra; Hyland, Tomas; Hein, Jotun

2012-10-09

RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures when the target structures are

Frnakenstein: multiple target inverse RNA folding

PubMed Central

2012-01-01

Background RNA secondary structure prediction, or folding, is a classic problem in bioinformatics: given a sequence of nucleotides, the aim is to predict the base pairs formed in its three dimensional conformation. The inverse problem of designing a sequence folding into a particular target structure has only more recently received notable interest. With a growing appreciation and understanding of the functional and structural properties of RNA motifs, and a growing interest in utilising biomolecules in nano-scale designs, the interest in the inverse RNA folding problem is bound to increase. However, whereas the RNA folding problem from an algorithmic viewpoint has an elegant and efficient solution, the inverse RNA folding problem appears to be hard. Results In this paper we present a genetic algorithm approach to solve the inverse folding problem. The main aims of the development was to address the hitherto mostly ignored extension of solving the inverse folding problem, the multi-target inverse folding problem, while simultaneously designing a method with superior performance when measured on the quality of designed sequences. The genetic algorithm has been implemented as a Python program called Frnakenstein. It was benchmarked against four existing methods and several data sets totalling 769 real and predicted single structure targets, and on 292 two structure targets. It performed as well as or better at finding sequences which folded in silico into the target structure than all existing methods, without the heavy bias towards CG base pairs that was observed for all other top performing methods. On the two structure targets it also performed well, generating a perfect design for about 80% of the targets. Conclusions Our method illustrates that successful designs for the inverse RNA folding problem does not necessarily have to rely on heavy biases in base pair and unpaired base distributions. The design problem seems to become more difficult on larger structures

On Connected Target k-Coverage in Heterogeneous Wireless Sensor Networks.

PubMed

Yu, Jiguo; Chen, Ying; Ma, Liran; Huang, Baogui; Cheng, Xiuzhen

2016-01-15

Coverage and connectivity are two important performance evaluation indices for wireless sensor networks (WSNs). In this paper, we focus on the connected target k-coverage (CTC k) problem in heterogeneous wireless sensor networks (HWSNs). A centralized connected target k-coverage algorithm (CCTC k) and a distributed connected target k-coverage algorithm (DCTC k) are proposed so as to generate connected cover sets for energy-efficient connectivity and coverage maintenance. To be specific, our proposed algorithms aim at achieving minimum connected target k-coverage, where each target in the monitored region is covered by at least k active sensor nodes. In addition, these two algorithms strive to minimize the total number of active sensor nodes and guarantee that each sensor node is connected to a sink, such that the sensed data can be forwarded to the sink. Our theoretical analysis and simulation results show that our proposed algorithms outperform a state-of-art connected k-coverage protocol for HWSNs.

Testing boundary conditions for the conjunction fallacy: effects of response mode, conceptual focus, and problem type.

PubMed

Wedell, Douglas H; Moro, Rodrigo

2008-04-01

Two experiments used within-subject designs to examine how conjunction errors depend on the use of (1) choice versus estimation tasks, (2) probability versus frequency language, and (3) conjunctions of two likely events versus conjunctions of likely and unlikely events. All problems included a three-option format verified to minimize misinterpretation of the base event. In both experiments, conjunction errors were reduced when likely events were conjoined. Conjunction errors were also reduced for estimations compared with choices, with this reduction greater for likely conjuncts, an interaction effect. Shifting conceptual focus from probabilities to frequencies did not affect conjunction error rates. Analyses of numerical estimates for a subset of the problems provided support for the use of three general models by participants for generating estimates. Strikingly, the order in which the two tasks were carried out did not affect the pattern of results, supporting the idea that the mode of responding strongly determines the mode of thinking about conjunctions and hence the occurrence of the conjunction fallacy. These findings were evaluated in terms of implications for rationality of human judgment and reasoning.

Oscillating fluid lens in coherent retinal projection displays for extending depth of focus

NASA Astrophysics Data System (ADS)

von Waldkirch, extending depth of focus M.; Lukowicz, P.; Troster, G.

2005-09-01

See-through head-mounted displays, which allow to overlay virtual information over the user's real view, suffer normally from a limited depth of focus (DOF). To overcome this problem we discuss in this paper the use of a fast oscillating, variable-focus lens in a retinal projection display. The evaluation is based on a schematic eye model and on the partial coherence simulation tool SPLAT which allows us to calculate the projected retinal images of a text target. Objective image quality criteria demonstrate that the use of an oscillating lens is promising provided that partially coherent illumination light is used. In this case, psychometric measurements reveal that the depth of focus for reading text can be extended by a factor of up to 2.2. For fully coherent and incoherent illumination, however, the retinal images suffer from structural and contrast degradation effects, respectively.

FOREWORD: Focus on Combinatorial Materials Science Focus on Combinatorial Materials Science

NASA Astrophysics Data System (ADS)

Chikyo, Toyohiro

2011-10-01

About 15 years have passed since the introduction of modern combinatorial synthesis and high-throughput techniques for the development of novel inorganic materials; however, similar methods existed before. The most famous was reported in 1970 by Hanak who prepared composition-spread films of metal alloys by sputtering mixed-material targets. Although this method was innovative, it was rarely used because of the large amount of data to be processed. This problem is solved in the modern combinatorial material research, which is strongly related to computer data analysis and robotics. This field is still at the developing stage and may be enriched by new methods. Nevertheless, given the progress in measurement equipment and procedures, we believe the combinatorial approach will become a major and standard tool of materials screening and development. The first article of this journal, published in 2000, was titled 'Combinatorial solid state materials science and technology', and this focus issue aims to reintroduce this topic to the Science and Technology of Advanced Materials audience. It covers recent progress in combinatorial materials research describing new results in catalysis, phosphors, polymers and metal alloys for shape memory materials. Sophisticated high-throughput characterization schemes and innovative synthesis tools are also presented, such as spray deposition using nanoparticles or ion plating. On a technical note, data handling systems are introduced to familiarize researchers with the combinatorial methodology. We hope that through this focus issue a wide audience of materials scientists can learn about recent and future trends in combinatorial materials science and high-throughput experimentation.

Inertial Confinement fusion targets

NASA Technical Reports Server (NTRS)

Hendricks, C. D.

1982-01-01

Inertial confinement fusion (ICF) targets are made as simple flat discs, as hollow shells or as complicated multilayer structures. Many techniques were devised for producing the targets. Glass and metal shells are made by using drop and bubble techniques. Solid hydrogen shells are also produced by adapting old methods to the solution of modern problems. Some of these techniques, problems, and solutions are discussed. In addition, the applications of many of the techniques to fabrication of ICF targets is presented.

Workplace victimization: aggression from the target's perspective.

PubMed

Aquino, Karl; Thau, Stefan

2009-01-01

This article reviews research on workplace victimization, which we define as acts of aggression perpetrated by one or more members of an organization that cause psychological, emotional, or physical harm to their intended target. We compare several types of victimizing behaviors that have been introduced into the organizational psychology literature to illustrate differences and similarities among them. We then review studies looking at who is likely to become a victim of aggression. Predictors include personality, demographic, behavioral, structural, and organizational variables. We also review research on coping strategies for victimization, which include problem-focused and emotion-focused strategies. We conclude with a summary of challenges for victimization research. These include addressing the proliferation of constructs and terms into the literature, attempting to clarify inconclusive findings, and using theory to guide the selection of study variables.

Preliminary ex vivo feasibility study on targeted cell surgery by high intensity focused ultrasound (HIFU).

PubMed

Wang, Zhi Biao; Wu, Junru; Fang, Liao Qiong; Wang, Hua; Li, Fa Qi; Tian, Yun Bo; Gong, Xiao Bo; Zhang, Hong; Zhang, Lian; Feng, Ruo

2011-04-01

High intensity focused ultrasound (HIFU) has become a new noninvasive surgical modality in medicine. A portion of tissue seated inside a patient's body may experience coagulative necrosis after a few seconds of insonification by high intensity focused ultrasound (US) generated by an extracorporeal focusing US transducer. The region of tissue affected by coagulative necrosis (CN) usually has an ellipsoidal shape when the thermal effect due to US absorption plays the dominant role. Its long and short axes are parallel and perpendicular to the US propagation direction respectively. It was shown by numerical computations using a nonlinear Gaussian beams model to describe the sound field in a focal zone and ex vivo experiments that the dimension of the short and long axes of the tissue which experiences CN can be as small as 50μm and 250μm respectively after one second exposure of US pulse (the spatial and pulse average acoustic power is on the order of tens of Watts and the local acoustic spatial and temporal pulse averaged intensity is on the order of 3×10(4)W/cm(2)) generated by a 1.6MHz HIFU transducer of 12cm diameter and 11cm geometric focal length (f-number=0.92). The concept of thermal dose of cumulative equivalent minutes was used to describe the possible tissue coagulative necrosis generated by HIFU. The numbers of cells which suffered CN were estimated to be on the order of 40. This result suggests that HIFU is able to interact with tens of cells at/near its focal zone while keeping the neighboring cells minimally affected, and thus the targeted cell surgery may be achievable. Copyright © 2010 Elsevier B.V. All rights reserved.

The Association between Attention Problems and Internalizing and Externalizing Problems: The Mediating Role of Peer Problems

ERIC Educational Resources Information Center

Yip, Vania T.; Ang, Rebecca P.; Ooi, Yoon Phaik; Fung, Daniel S. S.; Mehrotra, Kala; Sung, Min; Lim, Choon Guan

2013-01-01

Background: The high prevalence of attention problems in children warrants concern, as it is a risk factor for internalizing and externalizing problems. There lies a need to understand possible factors that may mediate this link so that interventions may be targeted to alleviate these mediators and interrupt the link between attention problems and…

How calorie-focused thinking about obesity and related diseases may mislead and harm public health. An alternative.

PubMed

Lucan, Sean C; DiNicolantonio, James J

2015-03-01

Prevailing thinking about obesity and related diseases holds that quantifying calories should be a principal concern and target for intervention. Part of this thinking is that consumed calories - regardless of their sources - are equivalent; i.e. 'a calorie is a calorie'. The present commentary discusses various problems with the idea that 'a calorie is a calorie' and with a primarily quantitative focus on food calories. Instead, the authors argue for a greater qualitative focus on the sources of calories consumed (i.e. a greater focus on types of foods) and on the metabolic changes that result from consuming foods of different types. In particular, the authors consider how calorie-focused thinking is inherently biased against high-fat foods, many of which may be protective against obesity and related diseases, and supportive of starchy and sugary replacements, which are likely detrimental. Shifting the focus to qualitative food distinctions, a central argument of the paper is that obesity and related diseases are problems due largely to food-induced physiology (e.g. neurohormonal pathways) not addressable through arithmetic dieting (i.e. calorie counting). The paper considers potential harms of public health initiatives framed around calorie balance sheets - targeting 'calories in' and/or 'calories out' - that reinforce messages of overeating and inactivity as underlying causes, rather than intermediate effects, of obesity. Finally, the paper concludes that public health should work primarily to support the consumption of whole foods that help protect against obesity-promoting energy imbalance and metabolic dysfunction and not continue to promote calorie-directed messages that may create and blame victims and possibly exacerbate epidemics of obesity and related diseases.

MRI-guided targeted blood-brain barrier disruption with focused ultrasound: histological findings in rabbits.

PubMed

McDannold, Nathan; Vykhodtseva, Natalia; Raymond, Scott; Jolesz, Ferenc A; Hynynen, Kullervo

2005-11-01

Focused ultrasound offers a method to disrupt the blood-brain barrier (BBB) noninvasively and reversibly at targeted locations. The purpose of this study was to test the safety of this method by searching for ischemia and apoptosis in areas with BBB disruption induced by pulsed ultrasound in the presence of preformed gas bubbles and by looking for delayed effects up to one month after sonication. Pulsed ultrasound exposures (sonications) were performed in the brains of 24 rabbits under monitoring by magnetic resonance imaging (MRI) (ultrasound: frequency = 1.63 MHz, burst length = 100 ms, PRF = 1 Hz, duration = 20 s, pressure amplitude 0.7 to 1.0 MPa). Before sonication, an ultrasound contrast agent (Optison, GE Healthcare, Milwaukee, WI, USA) was injected IV. BBB disruption was confirmed with contrast-enhanced MR images. Whole brain histologic examination was performed using haematoxylin and eosin staining for general histology, vanadium acid fuchsin-toluidine blue staining for ischemic neurons and TUNEL staining for apoptosis. The main effects observed were tiny regions of extravasated red blood cells scattered around the sonicated locations, indicating affected capillaries. Despite these vasculature effects, only a few cells in some of the sonicated areas showed evidence for apoptosis or ischemia. No ischemic or apoptotic regions were detected that would indicate a compromised blood supply was induced by the sonications. No delayed effects were observed either by MRI or histology up to 4 wk after sonication. Ultrasound-induced BBB disruption is possible without inducing substantial vascular damage that would result in ischemic or apoptotic death to neurons. These findings indicate that this method is safe for targeted drug delivery, at least when compared with the currently available invasive methods.

Glycosylated Triterpenoids as Endosomal Escape Enhancers in Targeted Tumor Therapies

PubMed Central

Fuchs, Hendrik; Niesler, Nicole; Trautner, Alexandra; Sama, Simko; Jerz, Gerold; Panjideh, Hossein; Weng, Alexander

2017-01-01

Protein-based targeted toxins play an increasingly important role in targeted tumor therapies. In spite of their high intrinsic toxicity, their efficacy in animal models is low. A major reason for this is the limited entry of the toxin into the cytosol of the target cell, which is required to mediate the fatal effect. Target receptor bound and internalized toxins are mostly either recycled back to the cell surface or lysosomally degraded. This might explain why no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date although more than 500 targeted toxins have been developed within the last decades. To overcome the problem of insufficient endosomal escape, a number of strategies that make use of diverse chemicals, cell-penetrating or fusogenic peptides, and light-induced techniques were designed to weaken the membrane integrity of endosomes. This review focuses on glycosylated triterpenoids as endosomal escape enhancers and throws light on their structure, the mechanism of action, and on their efficacy in cell culture and animal models. Obstacles, challenges, opportunities, and future prospects are discussed. PMID:28536357

Towards large scale multi-target tracking

NASA Astrophysics Data System (ADS)

Vo, Ba-Ngu; Vo, Ba-Tuong; Reuter, Stephan; Lam, Quang; Dietmayer, Klaus

2014-06-01

Multi-target tracking is intrinsically an NP-hard problem and the complexity of multi-target tracking solutions usually do not scale gracefully with problem size. Multi-target tracking for on-line applications involving a large number of targets is extremely challenging. This article demonstrates the capability of the random finite set approach to provide large scale multi-target tracking algorithms. In particular it is shown that an approximate filter known as the labeled multi-Bernoulli filter can simultaneously track one thousand five hundred targets in clutter on a standard laptop computer.

A Tikhonov Regularization Scheme for Focus Rotations with Focused Ultrasound Phased Arrays

PubMed Central

Hughes, Alec; Hynynen, Kullervo

2016-01-01

Phased arrays have a wide range of applications in focused ultrasound therapy. By using an array of individually-driven transducer elements, it is possible to steer a focus through space electronically and compensate for acoustically heterogeneous media with phase delays. In this paper, the concept of focusing an ultrasound phased array is expanded to include a method to control the orientation of the focus using a Tikhonov regularization scheme. It is then shown that the Tikhonov regularization parameter used to solve the ill-posed focus rotation problem plays an important role in the balance between quality focusing and array efficiency. Finally, the technique is applied to the synthesis of multiple foci, showing that this method allows for multiple independent spatial rotations. PMID:27913323

A Tikhonov Regularization Scheme for Focus Rotations With Focused Ultrasound-Phased Arrays.

PubMed

Hughes, Alec; Hynynen, Kullervo

2016-12-01

Phased arrays have a wide range of applications in focused ultrasound therapy. By using an array of individually driven transducer elements, it is possible to steer a focus through space electronically and compensate for acoustically heterogeneous media with phase delays. In this paper, the concept of focusing an ultrasound-phased array is expanded to include a method to control the orientation of the focus using a Tikhonov regularization scheme. It is then shown that the Tikhonov regularization parameter used to solve the ill-posed focus rotation problem plays an important role in the balance between quality focusing and array efficiency. Finally, the technique is applied to the synthesis of multiple foci, showing that this method allows for multiple independent spatial rotations.

Target Fishing for Chemical Compounds using Target-Ligand Activity data and Ranking based Methods

PubMed Central

Wale, Nikil; Karypis, George

2009-01-01

In recent years the development of computational techniques that identify all the likely targets for a given chemical compound, also termed as the problem of Target Fishing, has been an active area of research. Identification of likely targets of a chemical compound helps to understand problems such as toxicity, lack of efficacy in humans, and poor physical properties associated with that compound in the early stages of drug discovery. In this paper we present a set of techniques whose goal is to rank or prioritize targets in the context of a given chemical compound such that most targets that this compound may show activity against appear higher in the ranked list. These methods are based on our extensions to the SVM and Ranking Perceptron algorithms for this problem. Our extensive experimental study shows that the methods developed in this work outperform previous approaches by 2% to 60% under different evaluation criterions. PMID:19764745

Maritally distressed women with alcohol problems: the impact of a short-term alcohol-focused intervention on drinking behaviour and marital satisfaction.

PubMed

Kelly, A B; Halford, W K; Young, R M

2000-10-01

To evaluate the efficacy of a short-term alcohol-focused intervention for maritally distressed women, and to explore changes in relationship functioning. Participants were assigned randomly to an alcohol-focused treatment or to a waiting-list control group. The waiting-list control group began the intervention at 1-month follow-up. The intervention took place at a research and training centre offering outpatient psychology services to the community. A sample of 32 women with alcohol and marital problems were recruited through the media. Participants reported protracted alcohol problems, moderate to severe impact of alcohol on social and occupational functioning, and moderate to severe marital distress. Measures of average alcohol consumption, marital distress, relational efficacy and depression were administered at pre- and post-therapy, and at 1, 6 and 12-month follow-up. The intervention involved six 1-hour sessions, consisting of clinical assessment, motivational interviewing, cognitive-behavioural strategies and relapse prevention. At 1-month follow-up, the intervention was associated with statistically significant improvements in alcohol consumption, marital satisfaction, relational efficacy and depression, and these effects were sustained at 12-month follow-up. At 1-month follow-up the intervention was associated with decreased alcohol consumption and depression, and increased marital satisfaction and relational efficacy, with evidence of maintained effects at 12-month follow-up. However, it is unlikely that reduced problem drinking and improved confidence in resolving problems were the only factors producing low marital quality in these couples. Further research is needed to identify those individuals who might benefit from marital interventions.

Transformational and derivational strategies in analogical problem solving.

PubMed

Schelhorn, Sven-Eric; Griego, Jacqueline; Schmid, Ute

2007-03-01

Analogical problem solving is mostly described as transfer of a source solution to a target problem based on the structural correspondences (mapping) between source and target. Derivational analogy (Carbonell, Machine learning: an artificial intelligence approach Los Altos. Morgan Kaufmann, 1986) proposes an alternative view: a target problem is solved by replaying a remembered problem-solving episode. Thus, the experience with the source problem is used to guide the search for the target solution by applying the same solution technique rather than by transferring the complete solution. We report an empirical study using the path finding problems presented in Novick and Hmelo (J Exp Psychol Learn Mem Cogn 20:1296-1321, 1994) as material. We show that both transformational and derivational analogy are problem-solving strategies realized by human problem solvers. Which strategy is evoked in a given problem-solving context depends on the constraints guiding object-to-object mapping between source and target problem. Specifically, if constraints facilitating mapping are available, subjects are more likely to employ a transformational strategy, otherwise they are more likely to use a derivational strategy.

Reducing Behavior Problems among Students with Autism Spectrum Disorder: Coaching Teachers in a Mixed-Reality Setting

ERIC Educational Resources Information Center

Pas, Elise T.; Johnson, Stacy R.; Larson, Kristine E.; Brandenburg, Linda; Church, Robin; Bradshaw, Catherine P.

2016-01-01

Most approaches aiming to reduce behavior problems among youth with Autism Spectrum Disorder (ASD) focus on individual students; however, school personnel also need professional development to better support students. This study targeted teachers' skill development to promote positive outcomes for students with ASD. The sample included 19 teachers…

Social Orientation: Problem Behavior and Motivations Toward Interpersonal Problem Solving Among High Risk Adolescents

PubMed Central

Kuperminc, Gabriel P.; Allen, Joseph P.

2006-01-01

A model of problematic adolescent behavior that expands current theories of social skill deficits in delinquent behavior to consider both social skills and orientation toward the use of adaptive skills was examined in an ethnically and socioeconomically diverse sample of 113 male and female adolescents. Adolescents were selected on the basis of moderate to serious risk for difficulties in social adaptation in order to focus on the population of youth most likely to be targeted by prevention efforts. Structural equation modeling was used to examine cross-sectional data using multiple informants (adolescents, peers, and parents) and multiple methods (performance test and self-report). Adolescent social orientation, as reflected in perceived problem solving effectiveness, identification with adult prosocial values, and self-efficacy expectations, exhibited a direct association to delinquent behavior and an indirect association to drug involvement mediated by demonstrated success in using problem solving skills. Results suggest that the utility of social skill theories of adolescent problem behaviors for informing preventive and remedial interventions can be enhanced by expanding them to consider adolescents’ orientation toward using the skills they may already possess. PMID:16929380

Services to Multi-Problem Youth. Georgia Department of Human Resources Program and Funding Report, Vol. 2, No. 1, January 15, 1976.

ERIC Educational Resources Information Center

Schiffman, Jan; Washington, Blanche

This report focuses on a problem area which is being addressed by a consortium of agencies, and is designed to enrich the options of planners and program personnel in terms of both innovative concepts and potential resources required for program support. This report relates to the target population of "multi-problem" youth for whom no existing…

A degeneration of two-phase solutions of the focusing nonlinear Schrödinger equation via Riemann-Hilbert problems

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

Bertola, Marco, E-mail: Marco.Bertola@concordia.ca; Centre de Recherches Mathématiques, Université de Montréal, Montréal, Québec H3C 3J7; SISSA/ISAS, via Bonomea 265, Trieste

2015-06-15

Two-phase solutions of focusing NLS equation are classically constructed out of an appropriate Riemann surface of genus two and expressed in terms of the corresponding theta-function. We show here that in a certain limiting regime, such solutions reduce to some elementary ones called “Solitons on unstable condensate.” This degeneration turns out to be conveniently studied by means of basic tools from the theory of Riemann-Hilbert problems. In particular, no acquaintance with Riemann surfaces and theta-function is required for such analysis.

Effect of different external attention of focus instruction on learning of golf putting skill.

PubMed

Shafizadeh, Mohsen; McMorris, Terry; Sproule, John

2011-10-01

The effect of different sources of external attentional focus on learning a motor skill was assessed in the present study. 30 students (12 men, 18 women) participated voluntarily and were divided, according to type of external focus, into target, club swing, and target-club swing groups. The task was a golf putting skill. The target focus group attended to the target (hole), the club swing focus group attended to the execution of the club's swing, and the target-club swing focus group attended to both. All participants performed 50 trials of the putting skill in the acquisition phase and 10 trials in the 24-hr. delayed retention phase. The dependent variable was the error in the putting skill measured as the distance from the hole to the ball after each strike. Results showed the target-club swing focus group had better scores in the acquisition and retention phases than the other groups. It was concluded that external focus instruction helped the learners to integrate target cue with action cue and is more effective in skill learning than other external-focus instructions. These results support the claims of ecological psychology theorists concerning the effects of external focus of attention.

Increase in velocimeter depth of focus through astigmatism. Revision 1

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

Erskine, D.J.

1995-09-26

Frequently, velocimeter targets are illuminated by a laser beam passing through a hole in a mirror. This mirror is responsible for diverting returning light from a target lens to a velocity interferometer system for any reflector (VISAR). This mirror is often a significant distance from the target lens. Consequently, at certain target focus positions the returning light is strongly vignetted by the hole, causing a loss of signal. The authors find that they can prevent loss of signal and greatly increase the useful depth of focus by attaching a cylindrical lens to the target lens.

Self-Focused and Other-Focused Resiliency: Plausible Mechanisms Linking Early Family Adversity to Health Problems in College Women

ERIC Educational Resources Information Center

Coleman, Sulamunn R. M.; Zawadzki, Matthew J.; Heron, Kristin E.; Vartanian, Lenny R.; Smyth, Joshua M.

2016-01-01

Objectives: This study examined whether self-focused and other-focused resiliency help explain how early family adversity relates to perceived stress, subjective health, and health behaviors in college women. Participants: Female students (N = 795) participated between October 2009 and May 2010. Methods: Participants completed self-report measures…

The Holistic Targeting (HOT) Methodology as the Means to Improve Information Operations (IO) Target Development and Prioritization

DTIC Science & Technology

2008-09-01

software facilitate targeting problem understanding and the network analysis tool, Palantir , as an efficient and tailored semi-automated means to...the use of compendium software facilitate targeting problem understanding and the network analysis tool, Palantir , as an efficient and tailored semi...OBJECTIVES USING COMPENDIUM SOFTWARE .....63 E. HOT TARGET PRIORITIZATION AND DEVELOPMENT USING PALANTIR SOFTWARE .................................69 1

Trajectory Optimization for Missions to Small Bodies with a Focus on Scientific Merit.

PubMed

Englander, Jacob A; Vavrina, Matthew A; Lim, Lucy F; McFadden, Lucy A; Rhoden, Alyssa R; Noll, Keith S

2017-01-01

Trajectory design for missions to small bodies is tightly coupled both with the selection of targets for a mission and with the choice of spacecraft power, propulsion, and other hardware. Traditional methods of trajectory optimization have focused on finding the optimal trajectory for an a priori selection of destinations and spacecraft parameters. Recent research has expanded the field of trajectory optimization to multidisciplinary systems optimization that includes spacecraft parameters. The logical next step is to extend the optimization process to include target selection based not only on engineering figures of merit but also scientific value. This paper presents a new technique to solve the multidisciplinary mission optimization problem for small-bodies missions, including classical trajectory design, the choice of spacecraft power and propulsion systems, and also the scientific value of the targets. This technique, when combined with modern parallel computers, enables a holistic view of the small body mission design process that previously required iteration among several different design processes.

Work-supportive family, family-supportive supervision, use of organizational benefits, and problem-focused coping: implications for work-family conflict and employee well-being.

PubMed

Lapierre, Laurent M; Allen, Tammy D

2006-04-01

Employees (n = 230) from multiple organizations and industries were involved in a study assessing how work-family conflict avoidance methods stemming from the family domain (emotional sustenance and instrumental assistance from the family), the work domain (family-supportive supervision, use of telework and flextime), and the individual (use of problem-focused coping) independently relate to different dimensions of work-family conflict and to employees' affective and physical well-being. Results suggest that support from one's family and one's supervisor and the use of problem-focused coping seem most promising in terms of avoiding work-family conflict and/or decreased well-being. Benefits associated with the use of flextime, however, are relatively less evident, and using telework may potentially increase the extent to which family time demands interfere with work responsibilities. (c) 2006 APA, all rights reserved.

Predicting problem behaviors with multiple expectancies: expanding expectancy-value theory.

PubMed

Borders, Ashley; Earleywine, Mitchell; Huey, Stanley J

2004-01-01

Expectancy-value theory emphasizes the importance of outcome expectancies for behavioral decisions, but most tests of the theory focus on a single behavior and a single expectancy. However, the matching law suggests that individuals consider expected outcomes for both the target behavior and alternative behaviors when making decisions. In this study, we expanded expectancy-value theory to evaluate the contributions of two competing expectancies to adolescent behavior problems. One hundred twenty-one high school students completed measures of behavior problems, expectancies for both acting out and academic effort, and perceived academic competence. Students' self-reported behavior problems covaried mostly with perceived competence and academic expectancies and only nominally with problem behavior expectancies. We suggest that behavior problems may result from students perceiving a lack of valued or feasible alternative behaviors, such as studying. We discuss implications for interventions and suggest that future research continue to investigate the contribution of alternative expectancies to behavioral decisions.

Problem? "No Problem!" Solving Technical Contradictions

ERIC Educational Resources Information Center

Kutz, K. Scott; Stefan, Victor

2007-01-01

TRIZ (pronounced TREES), the Russian acronym for the theory of inventive problem solving, enables a person to focus his attention on finding genuine, potential solutions in contrast to searching for ideas that "may" work through a happenstance way. It is a patent database-backed methodology that helps to reduce time spent on the problem,…

An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver.

PubMed

Petrusca, Lorena; Viallon, Magalie; Breguet, Romain; Terraz, Sylvain; Manasseh, Gibran; Auboiroux, Vincent; Goget, Thomas; Baboi, Loredana; Gross, Patrick; Sekins, K Michael; Becker, Christoph D; Salomir, Rares

2014-01-16

Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. At the end of the procedure, no ultrasound indication of the marker's presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. Experimental validation of this new ballistic marker method was performed for

NICMOS Focus and HST Breathing

NASA Astrophysics Data System (ADS)

Suchkov, A.; Hershey, J.

1998-09-01

The program 7608 monitored on a biweekly basis NICMOS camera foci from June 9, 1997, through February 18, 1998. Each of the biweekly observations included 17 measurements of focus position (focus sweeps), individually for each of the three cameras. The measurements for camera 1 and camera 3 foci covered one or two HST orbital periods. Comparison of these measurements with the predictions of the three OTA focus breathing models has shown the following. (1). Focus variations seen in NICMOS focus sweeps correlate well with the OTA focus thermal breathing as predicted by breathing models (“4- temperature”, “full-temperature”, and “attitude” models). Thus they can be attributed mostly to the HST orbital temperature variation. (2). The amount of breathing (breathing amplitude) has been found to be on average larger in the first orbit after a telescope slew to a new target. This is explained as being due to additional thermal perturbations caused by the change in the HST attitude as the telescope repoints to a new target. (3). In the first orbit, the amount of focus change predicted by the 4-temperature model is about the same as that seen in the focus sweeps data (breathing scale factor ~1). However the full-temperature model predicts a two times smaller breathing amplitude (breathing scale factor ~1.7). This suggests that the light shield temperatures are more responsive to the attitude change than temperatures from the other temperature sensors. The results of this study may help to better understand the HST thermal cycles and to improve the models describing the impact of those on both the OTA and NICMOS focus.

Self-organizing team formation for target observation

NASA Astrophysics Data System (ADS)

Bowyer, Richard S.; Bogner, Robert E.

2001-08-01

Target observation is a problem where the application of multiple sensors can improve the probability of detection and observation of the target. Team formation is one method by which seemingly unsophisticated heterogeneous sensors may be organized to achieve a coordinated observation system. The sensors, which we shall refer to as agents, are situated in an area of interest with the goal of observing a moving target. We apply a team approach to this problem, which combines the strengths of individual agents into a cohesive entity - the team. In autonomous systems, the mechanisms that underlie the formation of a team are of interest. Teams may be formed by various mechanisms, which include an externally imposed grouping of agents, or an internally, self-organized (SO) grouping of agents. Internally motivated mechanisms are particularly challenging, but offer the benefit of being unsupervised, an important quality for groups of autonomous cooperating machines. This is the focus of our research. By studying natural systems such as colonies of ants, we obtain insight into these mechanisms of self organization. We propose that the team is an expression of a distributed agent-self, and that a particular realization of the agent-self exists, whilst the environmental conditions are conducive to that existence. We describe an algorithms for agent team formation that is inspired by the self-organizing behavior of ants, and describe simulation results for team formation amongst a lattice of networked sensors.

Change in interpersonal problems after cognitive agoraphobia and schema-focused therapy versus psychodynamic treatment as usual of inpatients with agoraphobia and Cluster C personality disorders.

PubMed

Gude, Tore; Hoffart, Asle

2008-04-01

The aim was to study whether patients with panic disorder with agoraphobia and co-occurring Cluster C traits would respond differently regarding change in interpersonal problems as part of their personality functioning when receiving two different treatment modalities. Two cohorts of patients were followed through three months' in-patient treatment programs and assessed at follow-up one year after end of treatment. The one cohort comprised 18 patients treated with "treatment as usual" according to psychodynamic principles, the second comprised 24 patients treated in a cognitive agoraphobia and schema-focused therapy program. Patients in the cognitive condition showed greater improvement in interpersonal problems than patients in the treatment as usual condition. Although this quasi-experimental study has serious limitations, the results may indicate that agoraphobic patients with Cluster C traits should be treated in cognitive agoraphobia and schema-focused programs rather than in psychodynamic treatment as usual programs in order to reduce their level of interpersonal problems.

Targeted violence against law enforcement officers.

PubMed

Schouten, Ronald; Brennan, Douglas V

2016-09-01

As highly visible representatives and guardians of society, law enforcement officers (LEOs) are very public figures. Injury or death in the line of duty, whether due to accidents or intentional acts of violence, is an occupational hazard for LEOs. Targeted assaults on police officers, referred to as ambushes in previous literature, are a particularly perplexing problem with significant implications for society at large. In the summer of 2016, the latest in a series of high-profile acts of violence aimed at police occurred, leading to increased examination of the acts themselves and their causes. This article examines recent trends in assaults on LEOs, focusing on predatory rather than reactive attacks, and applies a threat assessment model to a case of targeted violence against police. We use State of Washington v. Christopher Monfort (2015), a prosecution for arson, assault with intent to murder, and murder, as a case example, to examine how the threat assessment model, and the concepts of affective versus predatory violence help in understanding targeted violence against LEOs, assessing its risk, and managing it. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Focusing educational initiatives

NASA Technical Reports Server (NTRS)

Parks, George K.

1990-01-01

The United States will soon be facing a critical shortage of aerospace scientists and engineers. To address this problem, Space Grant Colleges can assist in focusing interest in existing educational initiatives and in creating new educational opportunities, particularly for women and underrepresented minorities.

The research and application of visual saliency and adaptive support vector machine in target tracking field.

PubMed

Chen, Yuantao; Xu, Weihong; Kuang, Fangjun; Gao, Shangbing

2013-01-01

The efficient target tracking algorithm researches have become current research focus of intelligent robots. The main problems of target tracking process in mobile robot face environmental uncertainty. They are very difficult to estimate the target states, illumination change, target shape changes, complex backgrounds, and other factors and all affect the occlusion in tracking robustness. To further improve the target tracking's accuracy and reliability, we present a novel target tracking algorithm to use visual saliency and adaptive support vector machine (ASVM). Furthermore, the paper's algorithm has been based on the mixture saliency of image features. These features include color, brightness, and sport feature. The execution process used visual saliency features and those common characteristics have been expressed as the target's saliency. Numerous experiments demonstrate the effectiveness and timeliness of the proposed target tracking algorithm in video sequences where the target objects undergo large changes in pose, scale, and illumination.

Problem-Oriented Learning in Geography Education: Construction of Motivating Problems

ERIC Educational Resources Information Center

Weiss, Günther

2017-01-01

This article reports on the possibilities and challenges of starting problem-oriented learning in geography lessons. The article focuses on the features of motivating problems, because one of the essential functions of the problem to start with is to animate learners to solve it. The analysis of various introductions to problem-oriented learning…

A cortical-spinal prosthesis for targeted limb movement in paralyzed primate avatars

PubMed Central

Shanechi, Maryam M.; Hu, Rollin C.; Williams, Ziv M.

2014-01-01

Motor paralysis is among the most disabling aspects of injury to the central nervous system. Here we develop and test a target-based cortical-spinal neural prosthesis that employs neural activity recorded from pre-motor neurons to control limb movements in functionally paralyzed primate avatars. Given the complexity by which muscle contractions are naturally controlled, we approach the problem of eliciting goal-directed limb movement in paralyzed animals by focusing on the intended targets of movement rather than their intermediate trajectories. We then match this information in real-time with spinal cord and muscle stimulation parameters that produce free planar limb movements to those intended target locations. We demonstrate that both the decoded activities of pre-motor populations and their adaptive responses can be used, after brief training, to effectively direct an avatar’s limb to distinct targets variably displayed on a screen. These findings advance the future possibility of reconstituting targeted limb movement in paralyzed subjects. PMID:24549394

Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention.

PubMed

Musiat, Peter; Conrod, Patricia; Treasure, Janet; Tylee, Andre; Williams, Chris; Schmidt, Ulrike

2014-01-01

A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders. To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students. Students were recruited online (n=1047, age: M=21.8, SD=4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n=519) or a control intervention (n=528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes. Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p=.018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating. This study suggests that a transdiagnostic web

Automatic Focus Adjustment of a Microscope

NASA Technical Reports Server (NTRS)

Huntsberger, Terrance

2005-01-01

AUTOFOCUS is a computer program for use in a control system that automatically adjusts the position of an instrument arm that carries a microscope equipped with an electronic camera. In the original intended application of AUTOFOCUS, the imaging microscope would be carried by an exploratory robotic vehicle on a remote planet, but AUTOFOCUS could also be adapted to similar applications on Earth. Initially control software other than AUTOFOCUS brings the microscope to a position above a target to be imaged. Then the instrument arm is moved to lower the microscope toward the target: nominally, the target is approached from a starting distance of 3 cm in 10 steps of 3 mm each. After each step, the image in the camera is subjected to a wavelet transform, which is used to evaluate the texture in the image at multiple scales to determine whether and by how much the microscope is approaching focus. A focus measure is derived from the transform and used to guide the arm to bring the microscope to the focal height. When the analysis reveals that the microscope is in focus, image data are recorded and transmitted.

A metabolic network approach for the identification and prioritization of antimicrobial drug targets

PubMed Central

Chavali, Arvind K.; D’Auria, Kevin M.; Hewlett, Erik L.; Pearson, Richard D.; Papin, Jason A.

2012-01-01

For many infectious diseases, novel treatment options are needed to address problems with cost, toxicity and resistance to current drugs. Systems biology tools can be used to gain valuable insight into pathogenic processes and aid in expediting drug discovery. In the past decade, constraint-based modeling of genome-scale metabolic networks has become widely used. Focusing on pathogen metabolic networks, we review in silico strategies to identify effective drug targets, and we highlight recent successes as well as limitations associated with such computational analyses. We further discuss how accounting for the host environment and even targeting the host may offer new therapeutic options. These systems-level approaches are beginning to provide novel avenues for drug targeting against infectious agents. PMID:22300758

Therapeutic targeting of epithelial plasticity programs – Focus on the epithelial-mesenchymal transition

PubMed Central

Malek, Reem; Wang, Hailun; Taparra, Kekoa; Tran, Phuoc T.

2017-01-01

Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer. In this review we organized our discussion on pathways and agents that can be used to target the EMT in cancer into three groups: (1) extracellular inducers of EMT; (2) the transcription factors that orchestrate the EMT transcriptome; and, (3) the downstream effectors of EMT. We highlight only briefly specific canonical pathways known to be involved in EMT such as the signal transduction pathways TGFβ, EFGR and Axl-Gas6. We emphasize in more detail pathways that are we believe are emerging novel pathways and therapeutic targets such as epigenetic therapies, glycosylation pathways and immunotherapy. The heterogeneity of tumors and the dynamic nature of epithelial plasticity in cancer cells make it likely that targeting only one EMT related process will be unsuccessful or only transiently successful. We suggest with greater understanding of epithelial plasticity regulation such as with the EMT, a more systematic targeting of multiple EMT regulatory networks will be the best path forward to improve cancer outcomes. PMID:28214899

Interactive object recognition assistance: an approach to recognition starting from target objects

NASA Astrophysics Data System (ADS)

Geisler, Juergen; Littfass, Michael

1999-07-01

Recognition of target objects in remotely sensed imagery required detailed knowledge about the target object domain as well as about mapping properties of the sensing system. The art of object recognition is to combine both worlds appropriately and to provide models of target appearance with respect to sensor characteristics. Common approaches to support interactive object recognition are either driven from the sensor point of view and address the problem of displaying images in a manner adequate to the sensing system. Or they focus on target objects and provide exhaustive encyclopedic information about this domain. Our paper discusses an approach to assist interactive object recognition based on knowledge about target objects and taking into account the significance of object features with respect to characteristics of the sensed imagery, e.g. spatial and spectral resolution. An `interactive recognition assistant' takes the image analyst through the interpretation process by indicating step-by-step the respectively most significant features of objects in an actual set of candidates. The significance of object features is expressed by pregenerated trees of significance, and by the dynamic computation of decision relevance for every feature at each step of the recognition process. In the context of this approach we discuss the question of modeling and storing the multisensorial/multispectral appearances of target objects and object classes as well as the problem of an adequate dynamic human-machine-interface that takes into account various mental models of human image interpretation.

A Random Variable Approach to Nuclear Targeting and Survivability

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

Undem, Halvor A.

We demonstrate a common mathematical formalism for analyzing problems in nuclear survivability and targeting. This formalism, beginning with a random variable approach, can be used to interpret past efforts in nuclear-effects analysis, including targeting analysis. It can also be used to analyze new problems brought about by the post Cold War Era, such as the potential effects of yield degradation in a permanently untested nuclear stockpile. In particular, we illustrate the formalism through four natural case studies or illustrative problems, linking these to actual past data, modeling, and simulation, and suggesting future uses. In the first problem, we illustrate themore » case of a deterministically modeled weapon used against a deterministically responding target. Classic "Cookie Cutter" damage functions result. In the second problem, we illustrate, with actual target test data, the case of a deterministically modeled weapon used against a statistically responding target. This case matches many of the results of current nuclear targeting modeling and simulation tools, including the result of distance damage functions as complementary cumulative lognormal functions in the range variable. In the third problem, we illustrate the case of a statistically behaving weapon used against a deterministically responding target. In particular, we show the dependence of target damage on weapon yield for an untested nuclear stockpile experiencing yield degradation. Finally, and using actual unclassified weapon test data, we illustrate in the fourth problem the case of a statistically behaving weapon used against a statistically responding target.« less

Gamma-ray generation in the interaction of two tightly focused laser pulses with a low-density target composed of electrons

NASA Astrophysics Data System (ADS)

Jirka, M.; Klimo, O.; Weber, S.; Bulanov, Sergei V.; Esirkepov, Timur Zh.; Korn, G.

2015-05-01

With the continuing development of laser systems, new important and so-far unexplored fields of research related to interaction of ultra-intense laser beams with matter are opening. At intensities of the order of 1022 W=cm2, electrons may be accelerated in the electromagnetic field of the laser wave and achieve such a high energy that they can enter the regime affected by the radiation reaction. Due to the non-linear Thomson and Compton scattering the accelerated electrons emit photons. The interaction of emitted photons with the laser field may result in effective generation of electron-positron pairs by means of the Breit-Wheeler process. In this work we study the influence of laser pulse polarization on gamma-ray generation during interaction of two colliding and tightly focused laser pulses with a low density target composed of electrons. This paper focuses on evolution of electron trajectories and key parameters χe (probability of photon emission) and χγ(probability of pair generation) in the laser field. These interactions are studied using 2D PIC simulations. It is shown that in the case of circularly polarized and tightly focused laser beams, electrons are not following circular trajectories at the magnetic node of the standing wave established in the focus, which leads to lowering the radiation emission efficiency.

Decision tools in health care: focus on the problem, not the solution.

PubMed

Liu, Joseph; Wyatt, Jeremy C; Altman, Douglas G

2006-01-20

Systematic reviews or randomised-controlled trials usually help to establish the effectiveness of drugs and other health technologies, but are rarely sufficient by themselves to ensure actual clinical use of the technology. The process from innovation to routine clinical use is complex. Numerous computerised decision support systems (DSS) have been developed, but many fail to be taken up into actual use. Some developers construct technologically advanced systems with little relevance to the real world. Others did not determine whether a clinical need exists. With NHS investing 5 billion pounds sterling in computer systems, also occurring in other countries, there is an urgent need to shift from a technology-driven approach to one that identifies and employs the most cost-effective method to manage knowledge, regardless of the technology. The generic term, 'decision tool' (DT), is therefore suggested to demonstrate that these aids, which seem different technically, are conceptually the same from a clinical viewpoint. Many computerised DSSs failed for various reasons, for example, they were not based on best available knowledge; there was insufficient emphasis on their need for high quality clinical data; their development was technology-led; or evaluation methods were misapplied. We argue that DSSs and other computer-based, paper-based and even mechanical decision aids are members of a wider family of decision tools. A DT is an active knowledge resource that uses patient data to generate case specific advice, which supports decision making about individual patients by health professionals, the patients themselves or others concerned about them. The identification of DTs as a consistent and important category of health technology should encourage the sharing of lessons between DT developers and users and reduce the frequency of decision tool projects focusing only on technology. The focus of evaluation should become more clinical, with the impact of computer

Effectiveness of a pragmatic school-based universal intervention targeting student resilience protective factors in reducing mental health problems in adolescents.

PubMed

Dray, Julia; Bowman, Jenny; Campbell, Elizabeth; Freund, Megan; Hodder, Rebecca; Wolfenden, Luke; Richards, Jody; Leane, Catherine; Green, Sue; Lecathelinais, Christophe; Oldmeadow, Christopher; Attia, John; Gillham, Karen; Wiggers, John

2017-06-01

Worldwide, 10-20% of adolescents experience mental health problems. Strategies aimed at strengthening resilience protective factors provide a potential approach for reducing mental health problems in adolescents. This study evaluated the effectiveness of a universal, school-based intervention targeting resilience protective factors in reducing mental health problems in adolescents. A cluster randomised controlled trial was conducted in 20 intervention and 12 control secondary schools located in socio-economically disadvantaged areas of NSW, Australia. Data were collected from 3115 students at baseline (Grade 7, 2011), of whom 2149 provided data at follow up (Grade 10, 2014; enrolments in Grades 7 to 10 typically aged 12-16 years; 50% male; 69.0% retention). There were no significant differences between groups at follow-up for three mental health outcomes: total SDQ, internalising problems, and prosocial behaviour. A small statistically significant difference in favour of the control group was found for externalising problems. Findings highlight the continued difficulties in developing effective, school-based prevention programs for mental health problems in adolescents. ANZCTR (Ref no: ACTRN12611000606987). Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Does Prevention Pay? Costs and Potential Cost-savings of School Interventions Targeting Children with Mental Health Problems.

PubMed

Wellander, Lisa; Wells, Michael B; Feldman, Inna

2016-06-01

In Sweden, the local government is responsible for funding schools in their district. One funding initiative is for schools to provide students with mental health problems with additional support via extra teachers, personal assistants, and special education classes. There are evidence-based preventive interventions delivered in schools, which have been shown to decrease the levels of students' mental health problems. However, little is known about how much the local government currently spends on students' mental health support and if evidence-based interventions could be financially beneficial. The aim of this study was to estimate the costs of providing additional support for students' mental health problems and the potential cost-offsets, defined as reduced school-based additional support, if two evidence-based school interventions targeting children's mental health problems were implemented in routine practice. This study uses data on the additional support students with mental health problems received in schools. Data was collected from one school district for students aged 6 to 16 years. We modeled two Swedish school interventions, Comet for Teachers and Social and Emotional Training (SET), which both had evidence of reducing mental health problems. We used a cost-offset analysis framework, assuming both interventions were fully implemented throughout the whole school district. Based on the published studies, the expected effects and the costs of the interventions were calculated. We defined the cost-offsets as the amount of predicted averted additional support for students with ongoing mental health problems who might no longer require receiving services such as one-on-one time with an extra teacher, a personal assistant, or to be placed in a special education classroom. A cost-offset analysis, from a payer's perspective (the local government responsible for school financing), was conducted comparing the costs of both interventions with the potential cost

Inquiry and Problem Solving.

ERIC Educational Resources Information Center

Thorson, Annette, Ed.

1999-01-01

This issue of ENC Focus focuses on the topic of inquiry and problem solving. Featured articles include: (1) "Inquiry in the Everyday World of Schools" (Ronald D. Anderson); (2) "In the Cascade Reservoir Restoration Project Students Tackle Real-World Problems" (Clint Kennedy with Advanced Biology Students from Cascade High…

[Target volume margins for lung cancer: internal target volume/clinical target volume].

PubMed

Jouin, A; Pourel, N

2013-10-01

The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. Copyright © 2013. Published by Elsevier SAS.

Focusing analytes from 50 μL into 500 pL: On-chip focusing from large sample volumes using isotachophoresis.

PubMed

van Kooten, Xander F; Truman-Rosentsvit, Marianna; Kaigala, Govind V; Bercovici, Moran

2017-09-05

The use of on-chip isotachophoresis assays for diagnostic applications is often limited by the small volumes of standard microfluidic channels. Overcoming this limitation is particularly important for detection of 'discrete' biological targets (such as bacteria) at low concentrations, where the volume of processed liquid in a standard microchannel might not contain any targets. We present a novel microfluidic chip that enables ITP focusing of target analytes from initial sample volumes of 50 μL into a concentrated zone with a volume of 500 pL, corresponding to a 100,000-fold increase in mean concentration, and a 300,000-fold increase in peak concentration. We present design considerations for limiting sample dispersion in such large-volume focusing (LVF) chips and discuss the trade-off between assay time and Joule heating, which ultimately governs the scalability of LVF designs. Finally, we demonstrate a 100-fold improvement of ITP focusing performance in the LVF chip as compared to conventional microchannels, and apply this enhancement to achieve highly sensitive detection of both molecular targets (DNA, down to 10 fM) and whole bacteria (down to 100 cfu/mL).

Representations in Problem Solving: A Case Study with Optimization Problems

ERIC Educational Resources Information Center

Villegas, Jose L.; Castro, Enrique; Gutierrez, Jose

2009-01-01

Introduction: Representations play an essential role in mathematical thinking. They favor the understanding of mathematical concepts and stimulate the development of flexible and versatile thinking in problem solving. Here our focus is on their use in optimization problems, a type of problem considered important in mathematics teaching and…

An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver

PubMed Central

2014-01-01

Background Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. Methods The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. Results At the end of the procedure, no ultrasound indication of the marker’s presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. Conclusions Experimental validation of this

CRISPR-FOCUS: A web server for designing focused CRISPR screening experiments.

PubMed

Cao, Qingyi; Ma, Jian; Chen, Chen-Hao; Xu, Han; Chen, Zhi; Li, Wei; Liu, X Shirley

2017-01-01

The recently developed CRISPR screen technology, based on the CRISPR/Cas9 genome editing system, enables genome-wide interrogation of gene functions in an efficient and cost-effective manner. Although many computational algorithms and web servers have been developed to design single-guide RNAs (sgRNAs) with high specificity and efficiency, algorithms specifically designed for conducting CRISPR screens are still lacking. Here we present CRISPR-FOCUS, a web-based platform to search and prioritize sgRNAs for CRISPR screen experiments. With official gene symbols or RefSeq IDs as the only mandatory input, CRISPR-FOCUS filters and prioritizes sgRNAs based on multiple criteria, including efficiency, specificity, sequence conservation, isoform structure, as well as genomic variations including Single Nucleotide Polymorphisms and cancer somatic mutations. CRISPR-FOCUS also provides pre-defined positive and negative control sgRNAs, as well as other necessary sequences in the construct (e.g., U6 promoters to drive sgRNA transcription and RNA scaffolds of the CRISPR/Cas9). These features allow users to synthesize oligonucleotides directly based on the output of CRISPR-FOCUS. Overall, CRISPR-FOCUS provides a rational and high-throughput approach for sgRNA library design that enables users to efficiently conduct a focused screen experiment targeting up to thousands of genes. (CRISPR-FOCUS is freely available at http://cistrome.org/crispr-focus/).

Evaluation and control of miRNA-like off-target repression for RNA interference.

PubMed

Seok, Heeyoung; Lee, Haejeong; Jang, Eun-Sook; Chi, Sung Wook

2018-03-01

RNA interference (RNAi) has been widely adopted to repress specific gene expression and is easily achieved by designing small interfering RNAs (siRNAs) with perfect sequence complementarity to the intended target mRNAs. Although siRNAs direct Argonaute (Ago), a core component of the RNA-induced silencing complex (RISC), to recognize and silence target mRNAs, they also inevitably function as microRNAs (miRNAs) and suppress hundreds of off-targets. Such miRNA-like off-target repression is potentially detrimental, resulting in unwanted toxicity and phenotypes. Despite early recognition of the severity of miRNA-like off-target repression, this effect has often been overlooked because of difficulties in recognizing and avoiding off-targets. However, recent advances in genome-wide methods and knowledge of Ago-miRNA target interactions have set the stage for properly evaluating and controlling miRNA-like off-target repression. Here, we describe the intrinsic problems of miRNA-like off-target effects caused by canonical and noncanonical interactions. We particularly focus on various genome-wide approaches and chemical modifications for the evaluation and prevention of off-target repression to facilitate the use of RNAi with secured specificity.

Liposomes and nanotechnology in drug development: focus on ocular targets

PubMed Central

Honda, Miki; Asai, Tomohiro; Oku, Naoto; Araki, Yoshihiko; Tanaka, Minoru; Ebihara, Nobuyuki

2013-01-01

Poor drug delivery to lesions in patients’ eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood–retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases. PMID:23439842

Can Targeted Intervention Mitigate Early Emotional and Behavioral Problems?: Generating Robust Evidence within Randomized Controlled Trials

PubMed Central

Doyle, Orla; McGlanaghy, Edel; O’Farrelly, Christine; Tremblay, Richard E.

2016-01-01

This study examined the impact of a targeted Irish early intervention program on children’s emotional and behavioral development using multiple methods to test the robustness of the results. Data on 164 Preparing for Life participants who were randomly assigned into an intervention group, involving home visits from pregnancy onwards, or a control group, was used to test the impact of the intervention on Child Behavior Checklist scores at 24-months. Using inverse probability weighting to account for differential attrition, permutation testing to address small sample size, and quantile regression to characterize the distributional impact of the intervention, we found that the few treatment effects were largely concentrated among boys most at risk of developing emotional and behavioral problems. The average treatment effect identified a 13% reduction in the likelihood of falling into the borderline clinical threshold for Total Problems. The interaction and subgroup analysis found that this main effect was driven by boys. The distributional analysis identified a 10-point reduction in the Externalizing Problems score for boys at the 90th percentile. No effects were observed for girls or for the continuous measures of Total, Internalizing, and Externalizing problems. These findings suggest that the impact of this prenatally commencing home visiting program may be limited to boys experiencing the most difficulties. Further adoption of the statistical methods applied here may help to improve the internal validity of randomized controlled trials and contribute to the field of evaluation science more generally. Trial Registration: ISRCTN Registry ISRCTN04631728 PMID:27253184

Effectiveness and cost-effectiveness of an educational intervention for practice teams to deliver problem focused therapy for insomnia: rationale and design of a pilot cluster randomised trial

PubMed Central

Siriwardena, A Niroshan; Apekey, Tanefa; Tilling, Michelle; Harrison, Andrew; Dyas, Jane V; Middleton, Hugh C; Ørner, Roderick; Sach, Tracey; Dewey, Michael; Qureshi, Zubair M

2009-01-01

Background Sleep problems are common, affecting over a third of adults in the United Kingdom and leading to reduced productivity and impaired health-related quality of life. Many of those whose lives are affected seek medical help from primary care. Drug treatment is ineffective long term. Psychological methods for managing sleep problems, including cognitive behavioural therapy for insomnia (CBTi) have been shown to be effective and cost effective but have not been widely implemented or evaluated in a general practice setting where they are most likely to be needed and most appropriately delivered. This paper outlines the protocol for a pilot study designed to evaluate the effectiveness and cost-effectiveness of an educational intervention for general practitioners, primary care nurses and other members of the primary care team to deliver problem focused therapy to adult patients presenting with sleep problems due to lifestyle causes, pain or mild to moderate depression or anxiety. Methods and design This will be a pilot cluster randomised controlled trial of a complex intervention. General practices will be randomised to an educational intervention for problem focused therapy which includes a consultation approach comprising careful assessment (using assessment of secondary causes, sleep diaries and severity) and use of modified CBTi for insomnia in the consultation compared with usual care (general advice on sleep hygiene and pharmacotherapy with hypnotic drugs). Clinicians randomised to the intervention will receive an educational intervention (2 × 2 hours) to implement a complex intervention of problem focused therapy. Clinicians randomised to the control group will receive reinforcement of usual care with sleep hygiene advice. Outcomes will be assessed via self-completion questionnaires and telephone interviews of patients and staff as well as clinical records for interventions and prescribing. Discussion Previous studies in adults have shown that

Heart disease education and prevention program targeting immigrant Latinos: using focus group responses to develop effective interventions.

PubMed

Moreno, C; Alvarado, M; Balcazar, H; Lane, C; Newman, E; Ortiz, G; Forrest, M

1997-12-01

Although research has provided considerable knowledge concerning the positive effects of behavioral change on morbidity and mortality from heart disease and related risk factors, some segments of the population have not benefited equitably from this information. In April 1995, the National Heart, Lung, and Blood Institute (NHLBI) conducted seven focus groups to determine knowledge and attitudes about heart disease and associated risk factors, identify media usage and preferences, and assess publications usage and preferences among Spanish-speaking Latino immigrants residing in the Washington, D.C., metropolitan area. This information was gathered to assist in the development of key messages and strategies for the NHLBI Latino Community Cardiovascular Disease Prevention and Outreach Initiative, Salud para su Corazón--a heart disease prevention and education campaign. Findings from these focus groups indicate that Latinos may not benefit from heart disease prevention messages developed for the general population because of language and cultural differences. The researchers concluded that health education and disease prevention programs targeting the Latino community should develop educational materials and interventions that address language preferences and cultural values. Furthermore, to be effective, these programs should show people how to make positive behavioral changes based on their current circumstances, while remaining sensitive to the fact that Latino immigrants face major life adjustments and many are still greatly influenced by their country of origin.

Infrared variation reduction by simultaneous background suppression and target contrast enhancement for deep convolutional neural network-based automatic target recognition

NASA Astrophysics Data System (ADS)

Kim, Sungho

2017-06-01

Automatic target recognition (ATR) is a traditionally challenging problem in military applications because of the wide range of infrared (IR) image variations and the limited number of training images. IR variations are caused by various three-dimensional target poses, noncooperative weather conditions (fog and rain), and difficult target acquisition environments. Recently, deep convolutional neural network-based approaches for RGB images (RGB-CNN) showed breakthrough performance in computer vision problems, such as object detection and classification. The direct use of RGB-CNN to the IR ATR problem fails to work because of the IR database problems (limited database size and IR image variations). An IR variation-reduced deep CNN (IVR-CNN) to cope with the problems is presented. The problem of limited IR database size is solved by a commercial thermal simulator (OKTAL-SE). The second problem of IR variations is mitigated by the proposed shifted ramp function-based intensity transformation. This can suppress the background and enhance the target contrast simultaneously. The experimental results on the synthesized IR images generated by the thermal simulator (OKTAL-SE) validated the feasibility of IVR-CNN for military ATR applications.

Problems Implementing Problem-Based Learning by a Private Malaysian University

ERIC Educational Resources Information Center

Tik, Chan Chang

2014-01-01

In this case study the focus is on lecturers' readiness in the design of PBL problems and to facilitate students' learning. This paper also looks into students' readiness in terms of acquiring metacognitive skills and collaborating in group to solve PBL problems. Problems encountered by both lecturers and students are discussed in the context of…

Focus is key: Panic-focused interpretations are associated with symptomatic improvement in panic-focused psychodynamic psychotherapy.

PubMed

Keefe, John R; Solomonov, Nili; Derubeis, Robert J; Phillips, Alexander C; Busch, Fredric N; Barber, Jacques P; Chambless, Dianne L; Milrod, Barbara L

2018-04-18

This study examines whether, in panic-focused psychodynamic psychotherapy (PFPP), interpretations of conflicts that underlie anxiety (panic-focused or PF-interpretations) are specifically associated with subsequent panic disorder (PD) symptom improvement, over and above the provision of non-symptom-focused interpretations. Technique use in Sessions 2 and 10 of a 24-session PFPP protocol was assessed for the 65 patients with complete outcome data randomized to PFPP in a two-site trial of psychotherapies for PD. Sessions were rated in 15-min segments for therapists' use of PF-interpretations, non-PF-interpretations, and PF-clarifications. Robust regressions were conducted to examine the relationship between these interventions and symptom change subsequent to the sampled session. Interpersonal problems were examined as a moderator of the relationship of PF-interpretations to symptom change. At Session 10, but not at Session 2, patients who received a higher degree of PF-interpretations experienced greater subsequent improvement in panic symptoms. Non-PF-interpretations were not predictive. Patients with more interpersonal distress benefitted particularly from the use of PF-interpretations at Session 10. By the middle phase of PFPP, panic-focused interpretations may drive subsequent improvements in panic symptoms, especially among patients with higher interpersonal distress. Interpretations of conflict absent a panic focus may not be especially helpful.

Targeted Prevention of Common Mental Health Disorders in University Students: Randomised Controlled Trial of a Transdiagnostic Trait-Focused Web-Based Intervention

PubMed Central

Musiat, Peter; Conrod, Patricia; Treasure, Janet; Tylee, Andre; Williams, Chris; Schmidt, Ulrike

2014-01-01

Background A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders. Aims To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students. Method Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes. Results Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered

Inverse photoelectron spectrometer with magnetically focused electron gun

NASA Technical Reports Server (NTRS)

Krainsky, Isay L.

1991-01-01

An inverse photoelectron spectrometer is described which is based on the design of a magnetically focused low energy electron gun. The magnetic lens extends its field over a relatively large segment of the electron trajectory, which could provide a better focusing effect on a high-current-density low-velocity electron beam, providing the magnetic field in the vicinity of the target is reduced sufficiently to preserve the collinearity of the beam. In order to prove the concept, ray tracing is conducted using the Herrmannsfeldt program for solving electron trajectories in electrostatic and magnetostatic focusing systems. The program allows the calculation of the angles of the electron trajectories with the z axis, at the target location. The results of the ray-tracing procedure conducted for this gun are discussed. Some of the advantages of the magnetic focusing are also discussed.

Target detection and localization in shallow water: an experimental demonstration of the acoustic barrier problem at the laboratory scale.

PubMed

Marandet, Christian; Roux, Philippe; Nicolas, Barbara; Mars, Jérôme

2011-01-01

This study demonstrates experimentally at the laboratory scale the detection and localization of a wavelength-sized target in a shallow ultrasonic waveguide between two source-receiver arrays at 3 MHz. In the framework of the acoustic barrier problem, at the 1/1000 scale, the waveguide represents a 1.1-km-long, 52-m-deep ocean acoustic channel in the kilohertz frequency range. The two coplanar arrays record in the time-domain the transfer matrix of the waveguide between each pair of source-receiver transducers. Invoking the reciprocity principle, a time-domain double-beamforming algorithm is simultaneously performed on the source and receiver arrays. This array processing projects the multireverberated acoustic echoes into an equivalent set of eigenrays, which are defined by their launch and arrival angles. Comparison is made between the intensity of each eigenray without and with a target for detection in the waveguide. Localization is performed through tomography inversion of the acoustic impedance of the target, using all of the eigenrays extracted from double beamforming. The use of the diffraction-based sensitivity kernel for each eigenray provides both the localization and the signature of the target. Experimental results are shown in the presence of surface waves, and methodological issues are discussed for detection and localization.

Targetting Teenagers.

ERIC Educational Resources Information Center

Bernard van Leer Foundation Newsletter, 1995

1995-01-01

This theme issue of the Bernard van Leer Foundation newsletter focuses on the problem of teenage pregnancy and teenage parenthood in developing and developed nations, and examines the problems that teenage mothers face in different societies. It explores societal norms and values related to teenage parenting; the effects of teenage parents on…

Conceptual versus Algorithmic Problem-Solving: Focusing on Problems Dealing with Conservation of Matter in Chemistry

ERIC Educational Resources Information Center

Salta, Katerina; Tzougraki, Chryssa

2011-01-01

The students' performance in various types of problems dealing with the conservation of matter during chemical reactions has been investigated at different levels of schooling. The participants were 499 ninth grade (ages 14, 15 years) and 624 eleventh grade (ages 16, 17 years) Greek students. Data was collected using a written questionnaire…

Simulation of laser radar tooling ball measurements: focus dependence

NASA Astrophysics Data System (ADS)

Smith, Daniel G.; Slotwinski, Anthony; Hedges, Thomas

2015-10-01

The Nikon Metrology Laser Radar system focuses a beam from a fiber to a target object and receives the light scattered from the target through the same fiber. The system can, among other things, make highly accurate measurements of the position of a tooling ball by locating the angular position of peak signal quality, which is related to the fiber coupling efficiency. This article explores the relationship between fiber coupling efficiency and focus condition.

Statistical Use of Argonaute Expression and RISC Assembly in microRNA Target Identification

PubMed Central

Stanhope, Stephen A.; Sengupta, Srikumar; den Boon, Johan; Ahlquist, Paul; Newton, Michael A.

2009-01-01

MicroRNAs (miRNAs) posttranscriptionally regulate targeted messenger RNAs (mRNAs) by inducing cleavage or otherwise repressing their translation. We address the problem of detecting m/miRNA targeting relationships in homo sapiens from microarray data by developing statistical models that are motivated by the biological mechanisms used by miRNAs. The focus of our modeling is the construction, activity, and mediation of RNA-induced silencing complexes (RISCs) competent for targeted mRNA cleavage. We demonstrate that regression models accommodating RISC abundance and controlling for other mediating factors fit the expression profiles of known target pairs substantially better than models based on m/miRNA expressions alone, and lead to verifications of computational target pair predictions that are more sensitive than those based on marginal expression levels. Because our models are fully independent of exogenous results from sequence-based computational methods, they are appropriate for use as either a primary or secondary source of information regarding m/miRNA target pair relationships, especially in conjunction with high-throughput expression studies. PMID:19779550

Statistical use of argonaute expression and RISC assembly in microRNA target identification.

PubMed

Stanhope, Stephen A; Sengupta, Srikumar; den Boon, Johan; Ahlquist, Paul; Newton, Michael A

2009-09-01

MicroRNAs (miRNAs) posttranscriptionally regulate targeted messenger RNAs (mRNAs) by inducing cleavage or otherwise repressing their translation. We address the problem of detecting m/miRNA targeting relationships in homo sapiens from microarray data by developing statistical models that are motivated by the biological mechanisms used by miRNAs. The focus of our modeling is the construction, activity, and mediation of RNA-induced silencing complexes (RISCs) competent for targeted mRNA cleavage. We demonstrate that regression models accommodating RISC abundance and controlling for other mediating factors fit the expression profiles of known target pairs substantially better than models based on m/miRNA expressions alone, and lead to verifications of computational target pair predictions that are more sensitive than those based on marginal expression levels. Because our models are fully independent of exogenous results from sequence-based computational methods, they are appropriate for use as either a primary or secondary source of information regarding m/miRNA target pair relationships, especially in conjunction with high-throughput expression studies.

Modeling dynamic plasmas driven by ultraintense nano-focused x-ray laser pulses in solid iron targets

NASA Astrophysics Data System (ADS)

Royle, Ryan; Sentoku, Yasuhiko; Mancini, Roberto

2017-10-01

The hard x-ray free electron laser has proven to be a valuable tool for high energy density (HED) physics as it is able to produce well-characterized samples of HED matter at exactly solid density and homogeneous temperatures. However, if the x-ray pulses are focused to sub-micron spot sizes, where peak intensities can exceed 1020 W/cm2, the plasmas driven by sources of non-thermal photoelectrons and Auger electrons can be highly dynamic and so cannot be modeled by atomic kinetics or fluid codes. We apply the 2D/3D particle-in-cell code, PICLS-which has been extended with numerous physics models to enable the simulation of XFEL-driven plasmas-to the modeling of such dynamic plasmas driven by nano-focused XFEL pulses in solid iron targets. In the case of the smallest focal spot investigated of just 100 nm in diameter, keV plasmas induce strong radial E-fields that accelerate keV ions radially as well as sheath fields that accelerate surface ions to hundreds of keV. The heated spot, which is initially larger than the laser spot due to the kinetic nature of the fast Auger electrons, expands as ion and electron waves propagate radially, leaving a low density region along the laser axis. This research was supported by the US DOE-OFES under Grant No. DE-SC0008827, the DOE-NNSA under Grant No. DE-NA0002075, and the JSPS KAKENHI under Grant No. JP15K21767.

Pharmacological Targeting Of Neuronal Kv7.2/3 Channels: A Focus On Chemotypes And Receptor Sites.

PubMed

Miceli, Francesco; Soldovieri, Maria Virginia; Ambrosino, Paolo; Manocchio, Laura; Medoro, Alessandro; Mosca, Ilaria; Taglialatela, Maurizio

2017-10-12

The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing a characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for development of new drugs for neuronal, cardiac and metabolic diseases. In the present manuscript, we focus on describing the pharmacological relevance and the potential therapeutic applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing particular emphasis on the different modulator chemotypes, and highlighting their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities. The present work is based on an in-depth search of the currently available scientific literature, and on our own experience and knowledge in the field of neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full pharmacological potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy. An astonishing heterogeneity in the molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct compound classes. In the present work we have attempted to show the current status and growing potential of the Kv7 pharmacology field. We anticipate a bright future for the field, and we express our hopes that the efforts herein reviewed will result in an improved treatment of hyperexcitability (or any other) diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Design of a bioactive small molecule that targets r(AUUCU) repeats in spinocerebellar ataxia 10.

PubMed

Yang, Wang-Yong; Gao, Rui; Southern, Mark; Sarkar, Partha S; Disney, Matthew D

2016-06-01

RNA is an important target for chemical probes of function and lead therapeutics; however, it is difficult to target with small molecules. One approach to tackle this problem is to identify compounds that target RNA structures and utilize them to multivalently target RNA. Here we show that small molecules can be identified to selectively bind RNA base pairs by probing a library of RNA-focused small molecules. A small molecule that selectively binds AU base pairs informed design of a dimeric compound (2AU-2) that targets the pathogenic RNA, expanded r(AUUCU) repeats, that causes spinocerebellar ataxia type 10 (SCA10) in patient-derived cells. Indeed, 2AU-2 (50 nM) ameliorates various aspects of SCA10 pathology including improvement of mitochondrial dysfunction, reduced activation of caspase 3, and reduction of nuclear foci. These studies provide a first-in-class chemical probe to study SCA10 RNA toxicity and potentially define broadly applicable compounds targeting RNA AU base pairs in cells.

B cell Variable genes have evolved their codon usage to focus the targeted patterns of somatic mutation on the complementarity determining regions

PubMed Central

Saini, Jasmine; Hershberg, Uri

2015-01-01

The exceptional ability of B cells to diversify through somatic mutation and improve affinity of the repertoire towards the antigens is the cornerstone of adaptive immunity. Somatic mutation is not evenly distributed and exhibits certain micro-sequence specificities. We show here that the combination of somatic mutation targeting and the codon usage in human B cell receptor (BCR) Variable (V) genes create expected patterns of mutation and post mutation changes that are focused on their complementarity determining regions (CDR). T cell V genes are also skewed in targeting mutations but to a lesser extent and are lacking the codon usage bias observed in BCRs. This suggests that the observed skew in T cell receptors is due to their amino acid usage, which is similar to that of BCRs. The mutation targeting and the codon bias allow B cell CDRs to diversify by specifically accumulating nonconservative changes. We counted the distribution of mutations to CDR in 4 different human datasets. In all four cases we found that the number of actual mutations in the CDR correlated significantly with the V gene mutation biases to the CDR predicted by our models. Finally, it appears that the mutation bias in V genes indeed relates to their long-term survival in actual human repertoires. We observed that resting repertoires of B cells overexpressed V genes that were especially biased towards focused mutation and change in the CDR. This bias in V gene usage was somewhat relaxed at the height of the immune response to a vaccine, presumably because of the need for a wider diversity in a primary response. However, older patients did not retain this flexibility and were biased towards using only highly skewed V genes at all stages of their response. PMID:25660968

B cell variable genes have evolved their codon usage to focus the targeted patterns of somatic mutation on the complementarity determining regions.

PubMed

Saini, Jasmine; Hershberg, Uri

2015-05-01

The exceptional ability of B cells to diversify through somatic mutation and improve affinity of the repertoire toward the antigens is the cornerstone of adaptive immunity. Somatic mutation is not evenly distributed and exhibits certain micro-sequence specificities. We show here that the combination of somatic mutation targeting and the codon usage in human B cell receptor (BCR) Variable (V) genes create expected patterns of mutation and post mutation changes that are focused on their complementarity determining regions (CDR). T cell V genes are also skewed in targeting mutations but to a lesser extent and are lacking the codon usage bias observed in BCRs. This suggests that the observed skew in T cell receptors is due to their amino acid usage, which is similar to that of BCRs. The mutation targeting and the codon bias allow B cell CDRs to diversify by specifically accumulating nonconservative changes. We counted the distribution of mutations to CDR in 4 different human datasets. In all four cases we found that the number of actual mutations in the CDR correlated significantly with the V gene mutation biases to the CDR predicted by our models. Finally, it appears that the mutation bias in V genes indeed relates to their long-term survival in actual human repertoires. We observed that resting repertoires of B cells overexpressed V genes that were especially biased toward focused mutation and change in the CDR. This bias in V gene usage was somewhat relaxed at the height of the immune response to a vaccine, presumably because of the need for a wider diversity in a primary response. However, older patients did not retain this flexibility and were biased toward using only highly skewed V genes at all stages of their response. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nanoparticle-blood interactions: the implications on solid tumour targeting.

PubMed

Lazarovits, James; Chen, Yih Yang; Sykes, Edward A; Chan, Warren C W

2015-02-18

Nanoparticles are suitable platforms for cancer targeting and diagnostic applications. Typically, less than 10% of all systemically administered nanoparticles accumulate in the tumour. Here we explore the interactions of blood components with nanoparticles and describe how these interactions influence solid tumour targeting. In the blood, serum proteins adsorb onto nanoparticles to form a protein corona in a manner dependent on nanoparticle physicochemical properties. These serum proteins can block nanoparticle tumour targeting ligands from binding to tumour cell receptors. Additionally, serum proteins can also encourage nanoparticle uptake by macrophages, which decreases nanoparticle availability in the blood and limits tumour accumulation. The formation of this protein corona will also increase the nanoparticle hydrodynamic size or induce aggregation, which makes nanoparticles too large to enter into the tumour through pores of the leaky vessels, and prevents their deep penetration into tumours for cell targeting. Recent studies have focused on developing new chemical strategies to reduce or eliminate serum protein adsorption, and rescue the targeting potential of nanoparticles to tumour cells. An in-depth and complete understanding of nanoparticle-blood interactions is key to designing nanoparticles with optimal physicochemical properties with high tumour accumulation. The purpose of this review article is to describe how the protein corona alters the targeting of nanoparticles to solid tumours and explains current solutions to solve this problem.

Peptide vaccines and peptidomimetics targeting HER and VEGF proteins may offer a potentially new paradigm in cancer immunotherapy

PubMed Central

Kaumaya, Pravin TP; Foy, Kevin Chu

2013-01-01

The ErbB family (HER-1, HER-2, HER-3 and HER-4) of receptor tyrosine kinases has been the focus of cancer immunotherapeutic strategies while antiangiogenic therapies have focused on VEGF and its receptors VEGFR-1 and VEGFR-2. Agents targeting receptor tyrosine kinases in oncology include therapeutic antibodies to receptor tyrosine kinase ligands or the receptors themselves, and small-molecule inhibitors. Many of the US FDA-approved therapies targeting HER-2 and VEGF exhibit unacceptable toxicities, and show problems of efficacy, development of resistance and unacceptable safety profiles that continue to hamper their clinical progress. The combination of dif ferent peptide vaccines and peptidomimetics targeting specific molecular pathways that are dysregulated in tumors may potentiate anticancer immune responses, bypass immune tolerance and circumvent resistance mechanisms. The focus of this review is to discuss efforts in our laboratory spanning two decades of rationally developing peptide vaccines and therapeutics for breast cancer. This review highlights the prospective benefit of a new, untapped category of therapies biologically targeted to EGF receptor (HER-1), HER-2 and VEGF with potential peptide ‘blockbusters‘ that could lay the foundation of a new paradigm in cancer immunotherapy by creating clinical breakthroughs for safe and efficacious cancer cures. PMID:22894670

Child welfare caseworkers as service brokers for youth in foster care: findings from project focus.

PubMed

Dorsey, Shannon; Kerns, Suzanne E U; Trupin, Eric W; Conover, Kate L; Berliner, Lucy

2012-02-01

Youth in the foster care system have substantially higher rates of mental health needs compared to the general population, yet they rarely receive targeted, evidence-based practices (EBPs). Increasingly emerging in the literature on mental health services is the importance of "brokers" or "gateway providers" of services. For youth in foster care, child welfare caseworkers often play this role. This study examines caseworker-level outcomes of Project Focus, a caseworker training and consultation model designed to improve emotional and behavioral outcomes for youth in foster care through increased linkages with EBPs. Project Focus was tested through a small, randomized trial involving four child welfare offices. Caseworkers in the Project Focus intervention group demonstrated an increased awareness of EBPs and a trend toward increased ability to identify appropriate EBP referrals for particular mental health problems but did not have significantly different rates of actual referral to EBPs. Dose of consultation was associated with general awareness of EBPs. Implications for practice and outcomes for youth are discussed.

Targeting von Willebrand Factor in Ischaemic Stroke: Focus on Clinical Evidence.

PubMed

Buchtele, Nina; Schwameis, Michael; Gilbert, James C; Schörgenhofer, Christian; Jilma, Bernd

2018-06-01

Despite great efforts in stroke research, disability and recurrence rates in ischaemic stroke remain unacceptably high. To address this issue, one potential target for novel therapeutics is the glycoprotein von Willebrand factor (vWF), which increases in thrombogenicity especially under high shear rates as it bridges between vascular sub-endothelial collagen and platelets. The rationale for vWF as a potential target in stroke comes from four bodies of evidence. (1) Animal models which recapitulate the pathogenesis of stroke and validate the concept of targeting vWF for stroke prevention and the use of the vWF cleavage enzyme ADAMTS13 in acute stroke treatment. (2) Extensive epidemiologic data establishing the prognostic role of vWF in the clinical setting showing that high vWF levels are associated with an increased risk of first stroke, stroke recurrence or stroke-associated mortality. As such, vWF levels may be a suitable marker for further risk stratification to potentially fine-tune current risk prediction models which are mainly based on clinical and imaging data. (3) Genetic studies showing an association between vWF levels and stroke risk on genomic levels. Finally, (4) studies of patients with primary disorders of excess or deficiency of function in the vWF axis (e.g. thrombotic thrombocytopenic purpura and von Willebrand disease, respectively) which demonstrate the crucial role of vWF in atherothrombosis. Therapeutic inhibition of VWF by novel agents appears particularly promising for secondary prevention of stroke recurrence in specific sub-groups of patients such as those suffering from large artery atherosclerosis, as designated according to the TOAST classification. Schattauer GmbH Stuttgart.

Alignment and focus of mirrored facets of a heliosat

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

Yellowhair, Julius E; Ho, Clifford Kuofei; Diver, Richard B

2013-11-12

Various technologies pertaining to aligning and focusing mirrored facets of a heliostat are described herein. Updating alignment and/or focus of mirrored facets is undertaken through generation of a theoretical image, wherein the theoretical image is indicative of a reflection of the target via the mirrored facets when the mirrored facets are properly aligned. This theoretical image includes reference points that are overlaid on an image of the target as reflected by the mirrored facets of the heliostat. A technician adjusts alignment/focus of a mirrored facet by causing reflected reference markings to become aligned with the reference points in the theoreticalmore » image.« less

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;…

Shape-from-focus by tensor voting.

PubMed

Hariharan, R; Rajagopalan, A N

2012-07-01

In this correspondence, we address the task of recovering shape-from-focus (SFF) as a perceptual organization problem in 3-D. Using tensor voting, depth hypotheses from different focus operators are validated based on their likelihood to be part of a coherent 3-D surface, thereby exploiting scene geometry and focus information to generate reliable depth estimates. The proposed method is fast and yields significantly better results compared with existing SFF methods.

Implementation of modified team-based learning within a problem based learning medical curriculum: a focus group study.

PubMed

Burgess, Annette; Roberts, Chris; Ayton, Tom; Mellis, Craig

2018-04-10

While Problem Based Learning (PBL) has long been established internationally, Team-based learning (TBL) is a relatively new pedagogy in medical curricula. Both PBL and TBL are designed to facilitate a learner-centred approach, where students, in interactive small groups, use peer-assisted learning to solve authentic, professionally relevant problems. Differences, however, exist between PBL and TBL in terms of preparation requirements, group numbers, learning strategies, and class structure. Although there are many similarities and some differences between PBL and TBL, both rely on constructivist learning theory to engage and motivate students in their learning. The aim of our study was to qualitatively explore students' perceptions of having their usual PBL classes run in TBL format. In 2014, two iterations in a hybrid PBL curriculum were converted to TBL format, with two PBL groups of 10 students each, being combined to form one TBL class of 20, split into four groups of five students. At the completion of two TBL sessions, all students were invited to attend one of two focus groups, with 14 attending. Thematic analysis was used to code and categorise the data into themes, with constructivist theory used as a conceptual framework to identify recurrent themes. Four key themes emerged; guided learning, problem solving, collaborative learning, and critical reflection. Although structured, students were attracted to the active and collaborative approach of TBL. They perceived the key advantages of TBL to include the smaller group size, the preparatory Readiness Assurance Testing process, facilitation by a clinician, an emphasis on basic science concepts, and immediate feedback. The competitiveness of TBL was seen as a spur to learning. These elements motivated students to prepare, promoted peer assisted teaching and learning, and focussed team discussion. An important advantage of PBL over TBL, was the opportunity for adequate clinical reasoning within the problem

Game theory-based visual tracking approach focusing on color and texture features.

PubMed

Jin, Zefenfen; Hou, Zhiqiang; Yu, Wangsheng; Chen, Chuanhua; Wang, Xin

2017-07-20

It is difficult for a single-feature tracking algorithm to achieve strong robustness under a complex environment. To solve this problem, we proposed a multifeature fusion tracking algorithm that is based on game theory. By focusing on color and texture features as two gamers, this algorithm accomplishes tracking by using a mean shift iterative formula to search for the Nash equilibrium of the game. The contribution of different features is always keeping the state of optical balance, so that the algorithm can fully take advantage of feature fusion. According to the experiment results, this algorithm proves to possess good performance, especially under the condition of scene variation, target occlusion, and similar interference.

Two-phase framework for near-optimal multi-target Lambert rendezvous

NASA Astrophysics Data System (ADS)

Bang, Jun; Ahn, Jaemyung

2018-03-01

This paper proposes a two-phase framework to obtain a near-optimal solution of multi-target Lambert rendezvous problem. The objective of the problem is to determine the minimum-cost rendezvous sequence and trajectories to visit a given set of targets within a maximum mission duration. The first phase solves a series of single-target rendezvous problems for all departure-arrival object pairs to generate the elementary solutions, which provides candidate rendezvous trajectories. The second phase formulates a variant of traveling salesman problem (TSP) using the elementary solutions prepared in the first phase and determines the final rendezvous sequence and trajectories of the multi-target rendezvous problem. The validity of the proposed optimization framework is demonstrated through an asteroid exploration case study.

From problem solving to problem definition: scrutinizing the complex nature of clinical practice.

PubMed

Cristancho, Sayra; Lingard, Lorelei; Regehr, Glenn

2017-02-01

In medical education, we have tended to present problems as being singular, stable, and solvable. Problem solving has, therefore, drawn much of medical education researchers' attention. This focus has been important but it is limited in terms of preparing clinicians to deal with the complexity of the 21st century healthcare system in which they will provide team-based care for patients with complex medical illness. In this paper, we use the Soft Systems Engineering principles to introduce the idea that in complex, team-based situations, problems usually involve divergent views and evolve with multiple solution iterations. As such we need to shift the conversation from (1) problem solving to problem definition, and (2) from a problem definition derived exclusively at the level of the individual to a definition derived at the level of the situation in which the problem is manifested. Embracing such a focus on problem definition will enable us to advocate for novel educational practices that will equip trainees to effectively manage the problems they will encounter in complex, team-based healthcare.

Teachers-Problems-Teachers' Problems: What is Considered as a Problem, among the Main Teacher Activities, by Hungarian Teachers

ERIC Educational Resources Information Center

Mrazik, Julianna

2009-01-01

This paper is about a research focusing on recent problems of Hungarian teachers. The aim of the study is to reveal the real troubles of Hungarian pedagogues, on the basis of their answers to a questionnaire, the nature of these problems and how they affect the role of the teacher. Supposedly, the nucleus of the problems of the teachers is…

New pediatric vision screener employing polarization-modulated, retinal-birefringence-scanning-based strabismus detection and bull's eye focus detection with an improved target system: opto-mechanical design and operation

NASA Astrophysics Data System (ADS)

Irsch, Kristina; Gramatikov, Boris I.; Wu, Yi-Kai; Guyton, David L.

2014-06-01

Amblyopia ("lazy eye") is a major public health problem, caused by misalignment of the eyes (strabismus) or defocus. If detected early in childhood, there is an excellent response to therapy, yet most children are detected too late to be treated effectively. Commercially available vision screening devices that test for amblyopia's primary causes can detect strabismus only indirectly and inaccurately via assessment of the positions of external light reflections from the cornea, but they cannot detect the anatomical feature of the eyes where fixation actually occurs (the fovea). Our laboratory has been developing technology to detect true foveal fixation, by exploiting the birefringence of the uniquely arranged Henle fibers delineating the fovea using retinal birefringence scanning (RBS), and we recently described a polarization-modulated approach to RBS that enables entirely direct and reliable detection of true foveal fixation, with greatly enhanced signal-to-noise ratio and essentially independent of corneal birefringence (a confounding variable with all polarization-sensitive ophthalmic technology). Here, we describe the design and operation of a new pediatric vision screener that employs polarization-modulated, RBS-based strabismus detection and bull's eye focus detection with an improved target system, and demonstrate the feasibility of this new approach.

New pediatric vision screener employing polarization-modulated, retinal-birefringence-scanning-based strabismus detection and bull's eye focus detection with an improved target system: opto-mechanical design and operation.

PubMed

Irsch, Kristina; Gramatikov, Boris I; Wu, Yi-Kai; Guyton, David L

2014-06-01

Amblyopia ("lazy eye") is a major public health problem, caused by misalignment of the eyes (strabismus) or defocus. If detected early in childhood, there is an excellent response to therapy, yet most children are detected too late to be treated effectively. Commercially available vision screening devices that test for amblyopia's primary causes can detect strabismus only indirectly and inaccurately via assessment of the positions of external light reflections from the cornea, but they cannot detect the anatomical feature of the eyes where fixation actually occurs (the fovea). Our laboratory has been developing technology to detect true foveal fixation, by exploiting the birefringence of the uniquely arranged Henle fibers delineating the fovea using retinal birefringence scanning (RBS), and we recently described a polarization-modulated approach to RBS that enables entirely direct and reliable detection of true foveal fixation, with greatly enhanced signal-to-noise ratio and essentially independent of corneal birefringence (a confounding variable with all polarization-sensitive ophthalmic technology). Here, we describe the design and operation of a new pediatric vision screener that employs polarization-modulated, RBS-based strabismus detection and bull's eye focus detection with an improved target system, and demonstrate the feasibility of this new approach.

Distributed and grid computing projects with research focus in human health.

PubMed

Diomidous, Marianna; Zikos, Dimitrios

2012-01-01

Distributed systems and grid computing systems are used to connect several computers to obtain a higher level of performance, in order to solve a problem. During the last decade, projects use the World Wide Web to aggregate individuals' CPU power for research purposes. This paper presents the existing active large scale distributed and grid computing projects with research focus in human health. There have been found and presented 11 active projects with more than 2000 Processing Units (PUs) each. The research focus for most of them is molecular biology and, specifically on understanding or predicting protein structure through simulation, comparing proteins, genomic analysis for disease provoking genes and drug design. Though not in all cases explicitly stated, common target diseases include research to find cure against HIV, dengue, Duchene dystrophy, Parkinson's disease, various types of cancer and influenza. Other diseases include malaria, anthrax, Alzheimer's disease. The need for national initiatives and European Collaboration for larger scale projects is stressed, to raise the awareness of citizens to participate in order to create a culture of internet volunteering altruism.

Stimuli-responsive Smart Liposomes in Cancer Targeting.

PubMed

Jain, Ankit; Jain, Sanjay K

2018-02-08

Liposomes are vesicular carriers which possess aqueous core entrapped within the lipid bilayer. These are carriers of choice because of biocompatible and biodegradable features in addition to flexibility of surface modifications at surface and lipid compositions of lipid bilayers. Liposomes have been reported well for cancer treatment using both passive and active targeting approaches however tumor microenvironment is still the biggest hurdle for safe and effective delivery of anticancer agents. To overcome this problem, stimuli-responsive smart liposomes have emerged as promising cargoes pioneered to anomalous tumor milieu in response to pH, temperature, and enzymes etc. as internal triggers, and magnetic field, ultrasound, and redox potential as external guides for enhancement of drug delivery to tumors. This review focuses on all such stimuli-responsive approaches using fabrication potentiality of liposomes in combination to various ligands, linkers, and PEGylation etc. Scientists engaged in cancer targeting approaches can get benefited greatly with this knowledgeable assemblage of advances in liposomal nanovectors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Informing pedagogy through the brain-targeted teaching model.

PubMed

Hardiman, Mariale

2012-01-01

Improving teaching to foster creative thinking and problem-solving for students of all ages will require two essential changes in current educational practice. First, to allow more time for deeper engagement with material, it is critical to reduce the vast number of topics often required in many courses. Second, and perhaps more challenging, is the alignment of pedagogy with recent research on cognition and learning. With a growing focus on the use of research to inform teaching practices, educators need a pedagogical framework that helps them interpret and apply research findings. This article describes the Brain-Targeted Teaching Model, a scheme that relates six distinct aspects of instruction to research from the neuro- and cognitive sciences.

Vocabulary Intervention for Children with Down Syndrome: Parent Training Using Focused Stimulation.

ERIC Educational Resources Information Center

Girolametto, Luigi; Weitzman, Elaine; Clements-Baartman, Jill

1998-01-01

This study explored effects of training six mothers to use focused stimulation to teach specific target words to their toddlers with Down syndrome. Following treatment, trained mothers used the focused stimulation technique more often than mothers in the control group. Concomitantly, their children used target words more often, as reported by…

Focusing on the Environment to Improve Youth Participation: Experiences and Perspectives of Occupational Therapists.

PubMed

Anaby, Dana; Law, Mary; Teplicky, Rachel; Turner, Laura

2015-10-23

The environment plays a key role in supporting children's participation and can serve as a focus of intervention. This study aimed to elicit the perceptions and experiences of occupational therapists who had applied the PREP approach--Pathways and Resources for Engagement and Participation. PREP is a novel 12-week intervention for youth with physical disabilities, aimed at improving participation in leisure community-based activities by modifying aspects of the environment. Using a qualitative post-intervention only design, 12 therapists took part in individual semi-structured interviews, in which the therapists reflected on their experience using PREP to enable participation. A thematic analysis was conducted. Four themes emerged from the data; two of which were informative in nature, describing elements of the PREP intervention that target multi-layered composition of the environment and use strategies that involve leveraging resources and problem solving. The two remaining themes were reflective in nature, illustrating a new take on the Occupational Therapy role and re-positioning the concept of participation in therapy practices. Results emphasize aspects of the environment that can serve as effective targets of intervention, guided by the PREP approach. Findings can broaden the scope and focus of occupational therapy practice by redefining views on participation and the environment.

A randomized wait-list controlled analysis of the implementation integrity of team-initiated problem solving processes.

PubMed

Newton, J Stephen; Horner, Robert H; Algozzine, Bob; Todd, Anne W; Algozzine, Kate

2012-08-01

Members of Positive Behavior Interventions and Supports (PBIS) teams from 34 elementary schools participated in a Team-Initiated Problem Solving (TIPS) Workshop and follow-up technical assistance. Within the context of a randomized wait-list controlled trial, team members who were the first recipients of the TIPS intervention demonstrated greater implementation integrity in using the problem-solving processes during their team meetings than did members of PBIS Teams in the Wait-List Control group. The success of TIPS at improving implementation integrity of the problem-solving processes is encouraging and suggests the value of conducting additional research focused on determining whether there is a functional relation between use of these problem-solving processes and actual resolution of targeted student academic and social problems. Copyright © 2012 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Focused and shifting attention in children with heavy prenatal alcohol exposure.

PubMed

Mattson, Sarah N; Calarco, Katherine E; Lang, Aimée R

2006-05-01

Attention deficits are a hallmark of the teratogenic effects of alcohol. However, characterization of these deficits remains inconclusive. Children with heavy prenatal alcohol exposure and nonexposed controls were evaluated using a paradigm consisting of three conditions: visual focus, auditory focus, and auditory-visual shift of attention. For the focus conditions, participants responded manually to visual or auditory targets. For the shift condition, participants alternated responses between visual targets and auditory targets. For the visual focus condition, alcohol-exposed children had lower accuracy and slower reaction time for all intertarget intervals (ITIs), while on the auditory focus condition, alcohol-exposed children were less accurate but displayed slower reaction time only on the longest ITI. Finally, for the shift condition, the alcohol-exposed group was accurate but had slowed reaction times. These results indicate that children with heavy prenatal alcohol exposure have pervasive deficits in visual focused attention and deficits in maintaining auditory attention over time. However, no deficits were noted in the ability to disengage and reengage attention when required to shift attention between visual and auditory stimuli, although reaction times to shift were slower. Copyright (c) 2006 APA, all rights reserved.

Drug targets for resistant malaria: Historic to future perspectives.

PubMed

Kumar, Sahil; Bhardwaj, T R; Prasad, D N; Singh, Rajesh K

2018-05-11

New antimalarial targets are the prime need for the discovery of potent drug candidates. In order to fulfill this objective, antimalarial drug researches are focusing on promising targets in order to develop new drug candidates. Basic metabolism and biochemical process in the malaria parasite, i.e. Plasmodium falciparum can play an indispensable role in the identification of these targets. But, the emergence of resistance to antimalarial drugs is an escalating comprehensive problem with the progress of antimalarial drug development. The development of resistance has highlighted the need for the search of novel antimalarial molecules. The pharmaceutical industries are committed to new drug development due to the global recognition of this life threatening resistance to the currently available antimalarial therapy. The recent developments in the understanding of parasite biology are exhilarating this resistance issue which is further being ignited by malaria genome project. With this background of information, this review was aimed to highlights and provides useful information on various present and promising treatment approaches for resistant malaria, new progresses, pursued by some innovative targets that have been explored till date. This review also discusses modern and futuristic multiple approaches to antimalarial drug discovery and development with pictorial presentations highlighting the various targets, that could be exploited for generating promising new drugs in the future for drug resistant malaria. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

An Examination of Special Focus Facility Nursing Homes

ERIC Educational Resources Information Center

Castle, Nicholas G.; Engberg, John

2010-01-01

Purpose: Nursing facilities that are determined to have a greater number of quality problems, more serious problems than average, and a demonstrated pattern of quality problems are included in the Special Focus Facility (SFF) initiative. The purpose of this research was to provide descriptive information on these SFFs and to examine the quality…

Efforts Aimed To Reduce Attrition in Antimalarial Drug Discovery: A Systematic Evaluation of the Current Antimalarial Targets Portfolio.

PubMed

Chaparro, María Jesús; Calderón, Félix; Castañeda, Pablo; Fernández-Alvaro, Elena; Gabarró, Raquel; Gamo, Francisco Javier; Gómez-Lorenzo, María G; Martín, Julio; Fernández, Esther

2018-04-13

Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (artemisinin combination therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits. Optimization efforts on several chemical series have been successful, and clinical candidates have been identified. In addition, recent advances in genetics and proteomics have led to the target deconvolution of phenotypic clinical candidates. New mechanisms of action will also be critical to overcome resistance and reduce attrition. Therefore, a complementary strategy focused on identifying well-validated targets to start hit identification programs is essential to reinforce the clinical pipeline. Leveraging published data, we have assessed the status quo of the current antimalarial target portfolio with a focus on the blood stage clinical disease. From an extensive list of reported Plasmodium targets, we have defined triage criteria. These criteria consider genetic, pharmacological, and chemical validation, as well as tractability/doability, and safety implications. These criteria have provided a quantitative score that has led us to prioritize those targets with the highest probability to deliver successful and differentiated new drugs.

Familial risk and sibling mentalization: Links with preschoolers' internalizing problems.

PubMed

Rodrigues, Michelle; Binnoon-Erez, Noam; Prime, Heather; Perlman, Michal; Jenkins, Jennifer M

2017-09-01

The current study explored whether older sibling mentalization moderated the relationship between familial risk for internalizing symptoms and the development of future internalizing problems in the younger siblings, referred to as target children. Data were collected on 397 older siblings at Time 1 (T1) when target children were newborn and their older siblings were on average 2.61 years old (SD = .75). Target children were on average 1.60 years old at Time 2 (T2). Internalizing problems were assessed via mother and partner reports. Familial risk was operationalized as the average of all older siblings' level of internalizing problems. Older sibling mentalization, indexed by internal state talk and reasoning, was observed and coded during a sibling pretend-play interaction at T2. Results revealed a significant interaction between familial risk of internalizing problems and older siblings' mentalizing abilities, showing that familial risk was related to target children's internalizing problems in the absence of sibling mentalization. Familial risk was not associated with target children's internalizing problems when siblings demonstrated mentalizing abilities. Findings support the need to consider sibling mentalization as a protective factor for children's internalizing problems. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Design and Fabrication of Double-Focused Ultrasound Transducers to Achieve Tight Focusing.

PubMed

Jang, Jihun; Chang, Jin Ho

2016-08-06

Beauty treatment for skin requires a high-intensity focused ultrasound (HIFU) transducer to generate coagulative necrosis in a small focal volume (e.g., 1 mm³) placed at a shallow depth (3-4.5 mm from the skin surface). For this, it is desirable to make the F-number as small as possible under the largest possible aperture in order to generate ultrasound energy high enough to induce tissue coagulation in such a small focal volume. However, satisfying both conditions at the same time is demanding. To meet the requirements, this paper, therefore, proposes a double-focusing technique, in which the aperture of an ultrasound transducer is spherically shaped for initial focusing and an acoustic lens is used to finally focus ultrasound on a target depth of treatment; it is possible to achieve the F-number of unity or less while keeping the aperture of a transducer as large as possible. In accordance with the proposed method, we designed and fabricated a 7-MHz double-focused ultrasound transducer. The experimental results demonstrated that the fabricated double-focused transducer had a focal length of 10.2 mm reduced from an initial focal length of 15.2 mm and, thus, the F-number changed from 1.52 to 1.02. Based on the results, we concluded that the proposed double-focusing method is suitable to decrease F-number while maintaining a large aperture size.

A Max-Flow Based Algorithm for Connected Target Coverage with Probabilistic Sensors

PubMed Central

Shan, Anxing; Xu, Xianghua; Cheng, Zongmao; Wang, Wensheng

2017-01-01

Coverage is a fundamental issue in the research field of wireless sensor networks (WSNs). Connected target coverage discusses the sensor placement to guarantee the needs of both coverage and connectivity. Existing works largely leverage on the Boolean disk model, which is only a coarse approximation to the practical sensing model. In this paper, we focus on the connected target coverage issue based on the probabilistic sensing model, which can characterize the quality of coverage more accurately. In the probabilistic sensing model, sensors are only be able to detect a target with certain probability. We study the collaborative detection probability of target under multiple sensors. Armed with the analysis of collaborative detection probability, we further formulate the minimum ϵ-connected target coverage problem, aiming to minimize the number of sensors satisfying the requirements of both coverage and connectivity. We map it into a flow graph and present an approximation algorithm called the minimum vertices maximum flow algorithm (MVMFA) with provable time complex and approximation ratios. To evaluate our design, we analyze the performance of MVMFA theoretically and also conduct extensive simulation studies to demonstrate the effectiveness of our proposed algorithm. PMID:28587084

A Max-Flow Based Algorithm for Connected Target Coverage with Probabilistic Sensors.

PubMed

Shan, Anxing; Xu, Xianghua; Cheng, Zongmao; Wang, Wensheng

2017-05-25

Coverage is a fundamental issue in the research field of wireless sensor networks (WSNs). Connected target coverage discusses the sensor placement to guarantee the needs of both coverage and connectivity. Existing works largely leverage on the Boolean disk model, which is only a coarse approximation to the practical sensing model. In this paper, we focus on the connected target coverage issue based on the probabilistic sensing model, which can characterize the quality of coverage more accurately. In the probabilistic sensing model, sensors are only be able to detect a target with certain probability. We study the collaborative detection probability of target under multiple sensors. Armed with the analysis of collaborative detection probability, we further formulate the minimum ϵ -connected target coverage problem, aiming to minimize the number of sensors satisfying the requirements of both coverage and connectivity. We map it into a flow graph and present an approximation algorithm called the minimum vertices maximum flow algorithm (MVMFA) with provable time complex and approximation ratios. To evaluate our design, we analyze the performance of MVMFA theoretically and also conduct extensive simulation studies to demonstrate the effectiveness of our proposed algorithm.

Deregulated MicroRNAs in Biliary Tract Cancer: Functional Targets and Potential Biomarkers

PubMed Central

Beyreis, Marlena; Wagner, Andrej; Pichler, Martin; Neureiter, Daniel

2016-01-01

Biliary tract cancer (BTC) is still a fatal disease with very poor prognosis. The lack of reliable biomarkers for early diagnosis and of effective therapeutic targets is a major demanding problem in diagnosis and management of BTC. Due to the clinically silent and asymptomatic characteristics of the tumor, most patients are diagnosed at an already advanced stage allowing only for a palliative therapeutic approach. MicroRNAs are small noncoding RNAs well known to regulate various cellular functions and pathologic events including the formation and progression of cancer. Over the last years, several studies have shed light on the role of microRNAs in BTC, making them potentially attractive therapeutic targets and candidates as biomarkers. In this review, we will focus on the role of oncogenic and tumor suppressor microRNAs and their direct targets in BTC. Furthermore, we summarize and discuss data that evaluate the diagnostic power of deregulated microRNAs as possible future biomarkers for BTC. PMID:27957497

Adding tsetse control to medical activities contributes to decreasing transmission of sleeping sickness in the Mandoul focus (Chad).

PubMed

Mahamat, Mahamat Hissene; Peka, Mallaye; Rayaisse, Jean-Baptiste; Rock, Kat S; Toko, Mahamat Abdelrahim; Darnas, Justin; Brahim, Guihini Mollo; Alkatib, Ali Bachar; Yoni, Wilfrid; Tirados, Inaki; Courtin, Fabrice; Brand, Samuel P C; Nersy, Cyrus; Alfaroukh, Idriss Oumar; Torr, Steve J; Lehane, Mike J; Solano, Philippe

2017-07-01

Gambian sleeping sickness or HAT (human African trypanosomiasis) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by riverine species of tsetse. A global programme aims to eliminate the disease as a public health problem by 2020 and stop transmission by 2030. In the South of Chad, the Mandoul area is a persistent focus of Gambian sleeping sickness where around 100 HAT cases were still diagnosed and treated annually until 2013. Pre-2014, control of HAT relied solely on case detection and treatment, which lead to a gradual decrease in the number of cases of HAT due to annual screening of the population. Because of the persistence of transmission and detection of new cases, we assessed whether the addition of vector control to case detection and treatment could further reduce transmission and consequently, reduce annual incidence of HAT in Mandoul. In particular, we investigated the impact of deploying 'tiny targets' which attract and kill tsetse. Before tsetse control commenced, a census of the human population was conducted and their settlements mapped. A pre-intervention survey of tsetse distribution and abundance was implemented in November 2013 and 2600 targets were deployed in the riverine habitats of tsetse in early 2014, 2015 and 2016. Impact on tsetse and on the incidence of sleeping sickness was assessed through nine tsetse monitoring surveys and four medical surveys of the human population in 2014 and 2015. Mathematical modelling was used to assess the relative impact of tsetse control on incidence compared to active and passive screening. The census indicated that a population of 38674 inhabitants lived in the vicinity of the Mandoul focus. Within this focus in November 2013, the vector is Glossina fuscipes fuscipes and the mean catch of tsetse from traps was 0.7 flies/trap/day (range, 0-26). The catch of tsetse from 44 sentinel biconical traps declined after target deployment with only five tsetse being caught in nine

Morphological and structural effects on tungsten targets produced by fusion plasma pulses from a table top plasma focus

NASA Astrophysics Data System (ADS)

Inestrosa-Izurieta, M. J.; Ramos-Moore, E.; Soto, L.

2015-09-01

A table top plasma focus device operating at hundreds of joules was used to simulate an equivalent damage factor than the obtained on the divertor in tokamak experiments. Using the ejected plasma produced after the pinch disruptions, the effects on tungsten targets from 50 cumulative plasma shocks with power fluxes per shot between 2.6 and 9200 kW cm-2 and with a duration time in the order of tens of nanoseconds (damage factor in the order of 100-103 (W cm-2)s1/2) were studied. Morphological analysis shows an increasing appearance of cracked surfaces with holes, fissures and defects, suggesting a potential progression of stress effects and a fast heat load that melts the surface, ending in thermal contractions that recrystallize the surface of the target. A structural analysis demonstrates a compressive stress development and suggests that part of the energy is released in the melting of the surface in case of a plasma shock with a power flux of 9.2 MW cm-2, 75 ns duration pulse, 2.5   ×   103 (W cm-2)s1/2 damage factor. How to increase the damage factor by one order of magnitude up to the expected value from type I ELMs on the ITER divertor, i.e. 104 (W cm-2)s1/2 is discussed.

Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

PubMed

Arrue, Lily; Ratjen, Lars

2017-12-07

The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ethical research as the target of animal extremism: an international problem.

PubMed

Conn, P Michael; Rantin, F T

2010-02-01

Animal extremism has been increasing worldwide; frequently researchers are the targets of actions by groups with extreme animal rights agendas. Sometimes this targeting is violent and may involve assaults on family members or destruction of property. In this article, we summarize recent events and suggest steps that researchers can take to educate the public on the value of animal research both for people and animals.

Focusers of obliquely incident laser radiation

NASA Astrophysics Data System (ADS)

Goncharskiy, A. V.; Danilov, V. A.; Popov, V. V.; Prokhorov, A. M.; Sisakyan, I. N.; Sayfer, V. A.; Stepanov, V. V.

1984-08-01

Focusing obliquely incident laser radiation along a given line in space with a given intensity distribution is treated as a problem of synthesizing a mirror surface. The intricate shape of such a surface, characterized by a function z= z (u,v) in the approximation of geometrical optics, is determined from the equation phi (u,v,z) - phi O(u,v,z)=O, which expresses that the incident field and the reflected field have identical eikonals. Further calculations are facilitated by replacing continuous mirror with a more easily manufactured piecewise continuous one. The problem is solved for the simple case of a plane incident wave with a typical iconal phi O(u,v,z)= -z cos0 at a large angle to a focus mirror in the z-plane region. Mirrors constructed on the basis of the theoretical solution were tested in an experiment with a CO2 laser. A light beam with Gaussian intensity distribution was, upon incidence at a 45 deg angle, focused into a circle or into an ellipse with uniform intensity distribution. Improvements in amplitudinal masking and selective tanning technology should reduce energy losses at the surface which results in efficient laser focusing mirrors.

Multi-Agent Cooperative Target Search

PubMed Central

Hu, Jinwen; Xie, Lihua; Xu, Jun; Xu, Zhao

2014-01-01

This paper addresses a vision-based cooperative search for multiple mobile ground targets by a group of unmanned aerial vehicles (UAVs) with limited sensing and communication capabilities. The airborne camera on each UAV has a limited field of view and its target discriminability varies as a function of altitude. First, by dividing the whole surveillance region into cells, a probability map can be formed for each UAV indicating the probability of target existence within each cell. Then, we propose a distributed probability map updating model which includes the fusion of measurement information, information sharing among neighboring agents, information decay and transmission due to environmental changes such as the target movement. Furthermore, we formulate the target search problem as a multi-agent cooperative coverage control problem by optimizing the collective coverage area and the detection performance. The proposed map updating model and the cooperative control scheme are distributed, i.e., assuming that each agent only communicates with its neighbors within its communication range. Finally, the effectiveness of the proposed algorithms is illustrated by simulation. PMID:24865884

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.

Group training in interpersonal problem-solving skills for workplace adaptation of adolescents and adults with Asperger syndrome: a preliminary study.

PubMed

Bonete, Saray; Calero, María Dolores; Fernández-Parra, Antonio

2015-05-01

Adults with Asperger syndrome show persistent difficulties in social situations which psychosocial treatments may address. Despite the multiple studies focusing on social skills interventions, only some have focused specifically on problem-solving skills and have not targeted workplace adaptation training in the adult population. This study describes preliminary data from a group format manual-based intervention, the Interpersonal Problem-Solving for Workplace Adaptation Programme, aimed at improving the cognitive and metacognitive process of social problem-solving skills focusing on typical social situations in the workplace based on mediation as the main strategy. A total of 50 adults with Asperger syndrome received the programme and were compared with a control group of typical development. The feasibility and effectiveness of the treatment were explored. Participants were assessed at pre-treatment and post-treatment on a task of social problem-solving skills and two secondary measures of socialisation and work profile using self- and caregiver-report. Using a variety of methods, the results showed that scores were significantly higher at post-treatment in the social problem-solving task and socialisation skills based on reports by parents. Differences in comparison to the control group had decreased after treatment. The treatment was acceptable to families and subject adherence was high. The Interpersonal Problem-Solving for Workplace Adaptation Programme appears to be a feasible training programme. © The Author(s) 2014.

DOA Estimation for Underwater Wideband Weak Targets Based on Coherent Signal Subspace and Compressed Sensing

PubMed Central

2018-01-01

Direction of arrival (DOA) estimation is the basis for underwater target localization and tracking using towed line array sonar devices. A method of DOA estimation for underwater wideband weak targets based on coherent signal subspace (CSS) processing and compressed sensing (CS) theory is proposed. Under the CSS processing framework, wideband frequency focusing is accompanied by a two-sided correlation transformation, allowing the DOA of underwater wideband targets to be estimated based on the spatial sparsity of the targets and the compressed sensing reconstruction algorithm. Through analysis and processing of simulation data and marine trial data, it is shown that this method can accomplish the DOA estimation of underwater wideband weak targets. Results also show that this method can considerably improve the spatial spectrum of weak target signals, enhancing the ability to detect them. It can solve the problems of low directional resolution and unreliable weak-target detection in traditional beamforming technology. Compared with the conventional minimum variance distortionless response beamformers (MVDR), this method has many advantages, such as higher directional resolution, wider detection range, fewer required snapshots and more accurate detection for weak targets. PMID:29562642

DOA Estimation for Underwater Wideband Weak Targets Based on Coherent Signal Subspace and Compressed Sensing.

PubMed

Li, Jun; Lin, Qiu-Hua; Kang, Chun-Yu; Wang, Kai; Yang, Xiu-Ting

2018-03-18

Direction of arrival (DOA) estimation is the basis for underwater target localization and tracking using towed line array sonar devices. A method of DOA estimation for underwater wideband weak targets based on coherent signal subspace (CSS) processing and compressed sensing (CS) theory is proposed. Under the CSS processing framework, wideband frequency focusing is accompanied by a two-sided correlation transformation, allowing the DOA of underwater wideband targets to be estimated based on the spatial sparsity of the targets and the compressed sensing reconstruction algorithm. Through analysis and processing of simulation data and marine trial data, it is shown that this method can accomplish the DOA estimation of underwater wideband weak targets. Results also show that this method can considerably improve the spatial spectrum of weak target signals, enhancing the ability to detect them. It can solve the problems of low directional resolution and unreliable weak-target detection in traditional beamforming technology. Compared with the conventional minimum variance distortionless response beamformers (MVDR), this method has many advantages, such as higher directional resolution, wider detection range, fewer required snapshots and more accurate detection for weak targets.

Business Languages: Teaching Culture through a Regional Focus.

ERIC Educational Resources Information Center

Novack, Frances

One method used to examine a target culture is to focus on a single region of a target language country, approaching all the issues normally raised in a culture class through the perspective of that region. The coherence this adds to class activities and overall class structure, the manageability of topics, and the opportunity to work with a range…

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model.

PubMed

Huisman, Merel; Staruch, Robert M; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A; Burns, Dennis K; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160-300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson's trichrome and toluidine blue staining. All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

PubMed Central

Huisman, Merel; Staruch, Robert M.; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A.; Burns, Dennis K.; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Purpose Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Methods Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160–300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson’s trichrome and toluidine blue staining. Results All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Conclusion Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may

Evaluate depth of field limits of fixed focus lens arrangements in thermal infrared

NASA Astrophysics Data System (ADS)

Schuster, Norbert

2016-05-01

More and more modern thermal imaging systems use uncooled detectors. High volume applications work with detectors that have a reduced pixel count (typically between 200x150 and 640x480). This reduces the usefulness of modern image treatment procedures such as wave front coding. On the other hand, uncooled detectors demand lenses with fast fnumbers, near f/1.0, which reduces the expected Depth of Field (DoF). What are the limits on resolution if the target changes distance to the camera system? The desire to implement lens arrangements without a focusing mechanism demands a deeper quantification of the DoF problem. A new approach avoids the classic "accepted image blur circle" and quantifies the expected DoF by the Through Focus MTF of the lens. This function is defined for a certain spatial frequency that provides a straightforward relation to the pixel pitch of imaging device. A certain minimum MTF-level is necessary so that the complete thermal imaging system can realize its basic functions, such as recognition or detection of specified targets. Very often, this technical tradeoff is approved with a certain lens. But what is the impact of changing the lens for one with a different focal length? Narrow field lenses, which give more details of targets in longer distances, tighten the DoF problem. A first orientation is given by the hyperfocal distance. It depends in a square relation on the focal length and in a linear relation on the through focus MTF of the lens. The analysis of these relations shows the contradicting requirements between higher thermal and spatial resolution, faster f-number and desired DoF. Furthermore, the hyperfocal distance defines the DoF-borders. Their relation between is such as the first order imaging formulas. A calculation methodology will be presented to transfer DoF-results from an approved combination lens and camera to another lens in combination with the initial camera. Necessary input for this prediction is the accepted DoF of

Psychodynamic psychotherapy for complex trauma: targets, focus, applications, and outcomes

PubMed Central

Spermon, Deborah; Darlington, Yvonne; Gibney, Paul

2010-01-01

Complex trauma describes that category of severe, chronic interpersonal trauma usually originating in the formative years of a child. In the adult, this can result in global dissociative difficulties across areas of cognitive, affective, somatic, and behavioral functions. Targeting this field of traumatic pathology, this article reviews the contributions and developments within one broad approach: psychodynamic theory and practice. Brief descriptions of aspects of analytical, Jungian, relational, object relations, and attachment therapeutic approaches are given, along with understandings of pathology and the formulation of therapeutic goals. Major practices within client sessions are canvassed and the issues of researching treatment outcomes are discussed. PMID:22110335

Auditory and visual capture during focused visual attention.

PubMed

Koelewijn, Thomas; Bronkhorst, Adelbert; Theeuwes, Jan

2009-10-01

It is well known that auditory and visual onsets presented at a particular location can capture a person's visual attention. However, the question of whether such attentional capture disappears when attention is focused endogenously beforehand has not yet been answered. Moreover, previous studies have not differentiated between capture by onsets presented at a nontarget (invalid) location and possible performance benefits occurring when the target location is (validly) cued. In this study, the authors modulated the degree of attentional focus by presenting endogenous cues with varying reliability and by displaying placeholders indicating the precise areas where the target stimuli could occur. By using not only valid and invalid exogenous cues but also neutral cues that provide temporal but no spatial information, they found performance benefits as well as costs when attention is not strongly focused. The benefits disappear when the attentional focus is increased. These results indicate that there is bottom-up capture of visual attention by irrelevant auditory and visual stimuli that cannot be suppressed by top-down attentional control. PsycINFO Database Record (c) 2009 APA, all rights reserved.

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.

Doubly-focused echos from spheres unfold into a hyperbolic umbilic diffraction catastrophe

NASA Astrophysics Data System (ADS)

Dzikowicz, Ben; Marston, Philip L.

2003-04-01

An underwater spherical target resides in an Airy field formed by reflection off a curved surface representing the sea floor or sea surface. In prior work [B. Dzikowicz and P. L. Marston, J. Acoust. Soc Am. 110, 2778 (2001)] direct returns of a tone burst from the surface reflection focused toward the target were shown to have a dependence on the target position described by an Airy function. The return echo can also be focused again by the surface onto the source and receive transducer. This gives the square of an Airy function for the case of a point target. With a finite sized target (as in the experiment) this goes over to a hyperbolic umbilic catastrophe with symmetric arguments. The arguments of the hyperbolic umbilic function are derived from only the relative return times of a transient pulse. Experiment confirms the predicted merging of transient echoes in the time domain, as well as the hyperbolic umbilic diffraction integral amplitudes for a tone burst. This method would allow for the observation of a target at a greater distance in the presence of a focusing surface. [Research supported by ONR.

Problem-Framing: A perspective on environmental problem-solving

NASA Astrophysics Data System (ADS)

Bardwell, Lisa V.

1991-09-01

The specter of environmental calamity calls for the best efforts of an involved public. Ironically, the way people understand the issues all too often serves to discourage and frustrate rather than motivate them to action. This article draws from problem-solving perspectives offered by cognitive psychology and conflict management to examine a framework for thinking about environmental problems that promises to help rather than hinder efforts to address them. Problem-framing emphasizes focusing on the problem definition. Since how one defines a problem determines one's understanding of and approach to that problem, being able to redefine or reframe a problem and to explore the “problem space” can help broaden the range of alternatives and solutions examined. Problem-framing incorporates a cognitive perspective on how people respond to information. It explains why an emphasis on problem definition is not part of people's typical approach to problems. It recognizes the importance of structure and of having ways to organize that information on one's problem-solving effort. Finally, problem-framing draws on both cognitive psychology and conflict management for strategies to manage information and to create a problem-solving environment that not only encourages participation but can yield better approaches to our environmental problems.

Deployment Design of Wireless Sensor Network for Simple Multi-Point Surveillance of a Moving Target

PubMed Central

Tsukamoto, Kazuya; Ueda, Hirofumi; Tamura, Hitomi; Kawahara, Kenji; Oie, Yuji

2009-01-01

In this paper, we focus on the problem of tracking a moving target in a wireless sensor network (WSN), in which the capability of each sensor is relatively limited, to construct large-scale WSNs at a reasonable cost. We first propose two simple multi-point surveillance schemes for a moving target in a WSN and demonstrate that one of the schemes can achieve high tracking probability with low power consumption. In addition, we examine the relationship between tracking probability and sensor density through simulations, and then derive an approximate expression representing the relationship. As the results, we present guidelines for sensor density, tracking probability, and the number of monitoring sensors that satisfy a variety of application demands. PMID:22412326

Targeted Training: An Integrated Initiative.

ERIC Educational Resources Information Center

Valvasori, Joe

The Learning Enrichment Foundation (LEF) in Toronto, Ontario (Canada) offers 12 targeted training programs that have successfully helped "hard-to-serve" clients return to the workforce. Compared with traditional training, targeted training has a much narrower focus and adapts quickly to industry trends to meet employers' changing…

Reduction of Maintenance Error Through Focused Interventions

NASA Technical Reports Server (NTRS)

Kanki, Barbara G.; Walter, Diane; Rosekind, Mark R. (Technical Monitor)

1997-01-01

It is well known that a significant proportion of aviation accidents and incidents are tied to human error. In flight operations, research of operational errors has shown that so-called "pilot error" often involves a variety of human factors issues and not a simple lack of individual technical skills. In aircraft maintenance operations, there is similar concern that maintenance errors which may lead to incidents and accidents are related to a large variety of human factors issues. Although maintenance error data and research are limited, industry initiatives involving human factors training in maintenance have become increasingly accepted as one type of maintenance error intervention. Conscientious efforts have been made in re-inventing the "team" concept for maintenance operations and in tailoring programs to fit the needs of technical operations. Nevertheless, there remains a dual challenge: to develop human factors interventions which are directly supported by reliable human error data, and to integrate human factors concepts into the procedures and practices of everyday technical tasks. In this paper, we describe several varieties of human factors interventions and focus on two specific alternatives which target problems related to procedures and practices; namely, 1) structured on-the-job training and 2) procedure re-design. We hope to demonstrate that the key to leveraging the impact of these solutions comes from focused interventions; that is, interventions which are derived from a clear understanding of specific maintenance errors, their operational context and human factors components.

Depressive Symptoms and Conversational Self-Focus in Adolescents’ Friendships

PubMed Central

Schwartz-Mette, Rebecca A.; Rose, Amanda J.

2015-01-01

This multi-method, longitudinal study considered the interplay among depressive symptoms, aversive interpersonal behavior, and interpersonal rejection in early and middle adolescents’ friendships. In particular, the study examined a newly identified interpersonal process, conversational self-focus (i.e., the tendency to redirect conversations about problems to focus on the self). Traditional interpersonal theories of depression suggest that individuals with depressive symptoms engage in aversive behaviors (such as conversational self-focus) and are rejected by others. However, in the current study, not all adolescents with depressive symptoms engaged in conversational self-focus and were rejected by friends. Instead, conversational self-focus moderated prospective relations of depressive symptoms and later friendship problems such that only adolescents with depressive symptoms who engaged in conversational self-focus were rejected by friends. These findings are consistent with current conceptualizations of the development of psychopathology that highlight heterogeneity among youth who share similar symptoms and the possibility of multifinality of outcomes. PMID:25640911

Increase in velocimeter depth of focus through astigmatism

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

Erskine, D.J.

1995-11-01

Frequently, velocimeter targets are illuminated by a laser beam passing through a hole in a mirror. This mirror is responsible for diverting returning light from a target lens to a velocity interferometer system for any reflector. This mirror is often a significant distance from the target lens. Consequently, at certain target focus positions the returning light is strongly vignetted by the hole, causing a loss of signal. This note finds that the loss of signal can be prevented and that the useful depth can be greatly increased by attaching a cylindrical lens to the target lens. {copyright} {ital 1995} {italmore » American} {ital Institute} {ital of} {ital Physics}.« less

Target identification using Zernike moments and neural networks

NASA Astrophysics Data System (ADS)

Azimi-Sadjadi, Mahmood R.; Jamshidi, Arta A.; Nevis, Andrew J.

2001-10-01

The development of an underwater target identification algorithm capable of identifying various types of underwater targets, such as mines, under different environmental conditions pose many technical problems. Some of the contributing factors are: targets have diverse sizes, shapes and reflectivity properties. Target emplacement environment is variable; targets may be proud or partially buried. Environmental properties vary significantly from one location to another. Bottom features such as sand, rocks, corals, and vegetation can conceal a target whether it is partially buried or proud. Competing clutter with responses that closely resemble those of the targets may lead to false positives. All the problems mentioned above contribute to overly difficult and challenging conditions that could lead to unreliable algorithm performance with existing methods. In this paper, we developed and tested a shape-dependent feature extraction scheme that provides features invariant to rotation, size scaling and translation; properties that are extremely useful for any target classification problem. The developed schemes were tested on an electro-optical imagery data set collected under different environmental conditions with variable background, range and target types. The electro-optic data set was collected using a Laser Line Scan (LLS) sensor by the Coastal Systems Station (CSS), located in Panama City, Florida. The performance of the developed scheme and its robustness to distortion, rotation, scaling and translation was also studied.

Effect of controlled offset of focal position in cavitation-enhanced high-intensity focused ultrasound treatment

NASA Astrophysics Data System (ADS)

Goto, Kota; Takagi, Ryo; Miyashita, Takuya; Jimbo, Hayato; Yoshizawa, Shin; Umemura, Shin-ichiro

2015-07-01

High-intensity focused ultrasound (HIFU) is a noninvasive treatment for tumors such as cancer. In this method, ultrasound is generated outside the body and focused to the target tissue. Therefore, physical and mental stresses on the patient are minimal. A drawback of the HIFU treatment is a long treatment time for a large tumor due to the small therapeutic volume by a single exposure. Enhancing the heating effect of ultrasound by cavitation bubbles may solve this problem. However, this is rather difficult because cavitation clouds tend to be formed backward from the focal point while ultrasonic intensity for heating is centered at the focal point. In this study, the focal points of the trigger pulses to generate cavitation were offset forward from those of the heating ultrasound to match the cavitation clouds with the heating patterns. Results suggest that the controlled offset of focal points makes the thermal coagulation more predictable.

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.

The flexible focus: whether spatial attention is unitary or divided depends on observer goals.

PubMed

Jefferies, Lisa N; Enns, James T; Di Lollo, Vincent

2014-04-01

The distribution of visual attention has been the topic of much investigation, and various theories have posited that attention is allocated either as a single unitary focus or as multiple independent foci. In the present experiment, we demonstrate that attention can be flexibly deployed as either a unitary or a divided focus in the same experimental task, depending on the observer's goals. To assess the distribution of attention, we used a dual-stream Attentional Blink (AB) paradigm and 2 target pairs. One component of the AB, Lag-1 sparing, occurs only if the second target pair appears within the focus of attention. By varying whether the first-target-pair could be expected in a predictable location (always in-stream) or not (unpredictably in-stream or between-streams), observers were encouraged to deploy a divided or a unitary focus, respectively. When the second-target-pair appeared between the streams, Lag-1 sparing occurred for the Unpredictable group (consistent with a unitary focus) but not for the Predictable group (consistent with a divided focus). Thus, diametrically different outcomes occurred for physically identical displays, depending on the expectations of the observer about where spatial attention would be required.

Using Solution-Focused Intervention for Behavioral Problems in an Inclusive Classroom.

ERIC Educational Resources Information Center

Quigney, Theresa A.; Studer, Jeannine R.

1999-01-01

Solution-focused intervention deviates from using negative labels (angry, aggressive, or shy) to describe misbehaving students, and reframes behavior descriptions more positively. Four steps (goal setting, looking for exceptions, visualizing a new life story, and practicing the desired behaviors) are vital to facilitating positive behavior…

Sensor planning for moving targets

NASA Astrophysics Data System (ADS)

Musman, Scott A.; Lehner, Paul; Elsaesser, Chris

1994-10-01

Planning a search for moving ground targets is difficult for humans and computationally intractable. This paper describes a technique to solve such problems. The main idea is to combine probability of detection assessments with computational search heuristics to generate sensor plans which approximately maximize either the probability of detection or a user- specified knowledge function (e.g., determining the target's probable destination; locating the enemy tanks). In contrast to super computer-based moving target search planning, our technique has been implemented using workstation technology. The data structures generated by sensor planning can be used to evaluate sensor reports during plan execution. Our system revises its objective function with each sensor report, allowing the user to assess both the current situation as well as the expected value of future information. This capability is particularly useful in situations involving a high rate of sensor reporting, helping the user focus his attention on sensors reports most pertinent to current needs. Our planning approach is implemented in a three layer architecture. The layers are: mobility analysis, followed by sensor coverage analysis, and concluding with sensor plan analysis. It is possible using these layers to describe the physical, spatial, and temporal characteristics of a scenario in the first two layers, and customize the final analysis to specific intelligence objectives. The architecture also allows a user to customize operational parameters in each of the three major components of the system. As examples of these performance options, we briefly describe the mobility analysis and discuss issues affecting sensor plan analysis.

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors

PubMed Central

Tosi, Umberto; Marnell, Christopher S.; Chang, Raymond; Cho, William C.; Ting, Richard; Maachani, Uday B.; Souweidane, Mark M.

2017-01-01

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood–brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a “wait-and-see” approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents. PMID:28208698

Advances in Molecular Imaging of Locally Delivered Targeted Therapeutics for Central Nervous System Tumors.

PubMed

Tosi, Umberto; Marnell, Christopher S; Chang, Raymond; Cho, William C; Ting, Richard; Maachani, Uday B; Souweidane, Mark M

2017-02-08

Thanks to the recent advances in the development of chemotherapeutics, the morbidity and mortality of many cancers has decreased significantly. However, compared to oncology in general, the field of neuro-oncology has lagged behind. While new molecularly targeted chemotherapeutics have emerged, the impermeability of the blood-brain barrier (BBB) renders systemic delivery of these clinical agents suboptimal. To circumvent the BBB, novel routes of administration are being applied in the clinic, ranging from intra-arterial infusion and direct infusion into the target tissue (convection enhanced delivery (CED)) to the use of focused ultrasound to temporarily disrupt the BBB. However, the current system depends on a "wait-and-see" approach, whereby drug delivery is deemed successful only when a specific clinical outcome is observed. The shortcomings of this approach are evident, as a failed delivery that needs immediate refinement cannot be observed and corrected. In response to this problem, new theranostic agents, compounds with both imaging and therapeutic potential, are being developed, paving the way for improved and monitored delivery to central nervous system (CNS) malignancies. In this review, we focus on the advances and the challenges to improve early cancer detection, selection of targeted therapy, and evaluation of therapeutic efficacy, brought forth by the development of these new agents.

Risk-based targeting: A new approach in environmental protection

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

Fox, C.A.

1995-12-31

Risk-based targeting has recently emerged as an effective tool to help prioritize efforts to identify and manage geographic areas, chemicals, facilities, and agricultural activities that cause the most environmental degradation. This paper focuses on how the Environmental Protection Agency (EPA) has recently used risk-based targeting to identify and screen Federal, industrial, commercial and municipal facilities which contribute to probable human health (fish consumption advisories and contaminated fish tissue) and aquatic life (contaminated sediments) impacts. Preliminary results identified several hundred potential contributors of problem chemicals to probable impacts within the same river reach in 1991--93. Analysis by industry sector showed thatmore » the majority of the facilities identified were publicly owned treatment works (POTWs), in addition to industry organic and inorganic chemical manufacturers, petroleum refineries, and electric services, coatings, engravings, and allied services, among others. Both compliant and non-compliant potentially contributing facilities were identified to some extent in all EPA regions. Additional results identifying possible linkages of other pollutant sources to probable impacts, as well as estimation of potential exposure of these contaminants to minority and/or poverty populations are also presented. Out of these analyses, a number of short and long-term strategies are being developed that EPA may use to reduce loadings of problem contaminants to impacted waterbodies.« less

MRI-Guided Focused Ultrasound Surgery

PubMed Central

Jolesz, Ferenc A.

2014-01-01

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

Distinguishing dose, focus, and blur for lithography characterization and control

NASA Astrophysics Data System (ADS)

Ausschnitt, Christopher P.; Brunner, Timothy A.

2007-03-01

We derive a physical model to describe the dependence of pattern dimensions on dose, defocus and blur. The coefficients of our model are constants of a given lithographic process. Model inversion applied to dimensional measurements then determines effective dose, defocus and blur for wafers patterned with the same process. In practice, our approach entails the measurement of proximate grating targets of differing dose and focus sensitivity. In our embodiment, the measured attribute of one target is exclusively sensitive to dose, whereas the measured attributes of a second target are distinctly sensitive to defocus and blur. On step-and-scan exposure tools, z-blur is varied in a controlled manner by adjusting the across slit tilt of the image plane. The effects of z-blur and x,y-blur are shown to be equivalent. Furthermore, the exposure slit width is shown to determine the tilt response of the grating attributes. Thus, the response of the measured attributes can be characterized by a conventional focus-exposure matrix (FEM), over which the exposure tool settings are intentionally changed. The model coefficients are determined by a fit to the measured FEM response. The model then fully defines the response for wafers processed under "fixed" dose, focus and blur conditions. Model inversion applied to measurements from the same targets on all such wafers enables the simultaneous determination of effective dose and focus/tilt (DaFT) at each measurement site.

One-Step "Change" and "Compare" Word Problems: Focusing on Eye-Movements

ERIC Educational Resources Information Center

Moutsios-Rentzos, Andreas; Stamatis, Panagiotis J.

2015-01-01

Introduction. In this study, we focus on the relationship between the students' mathematical thinking and their non-mechanically identified eye-movements with the purpose to gain deeper understanding about the students' reasoning processes and to investigate the feasibility of incorporating eye-movement information in everyday pedagogy. Method.…

Achromatic illumination system for small targets

DOEpatents

Sigler, Robert D.

1979-01-01

A pair of light beams is directed to provide illumination that is substantially uniform from all directions on a small target by a system comprising a pair of corrector windows, a pair of planar reflecting surfaces, a pair of paraboloidal mirrors and a reflecting mirror cavity. The components are arranged so that each of the beams passes through a corrector and is reflected from the planar surface to the paraboloidal mirror, from which it is focused through a hole in the planar surface to the interior of the cavity. The surface of the interior portion of the cavity is shaped to reflect the focused beam three times before the focused reflected beam strikes the target.

Targeting Resources for Local Growth.

ERIC Educational Resources Information Center

Casto, James E.

2001-01-01

Focusing state and federal dollars on targeted areas, the Kentucky Appalachian Community Development Initiative helps communities in eastern Kentucky fund their own strategies for economic growth. In Hindman, the project focuses on creating the Kentucky School of Crafts, to train master artisans; supporting the Kentucky Appalachian Artisan Center;…

Toward a magic or imaginary bullet? Ligands for drug targeting to cancer cells: principles, hopes, and challenges

PubMed Central

Toporkiewicz, Monika; Meissner, Justyna; Matusewicz, Lucyna; Czogalla, Aleksander; Sikorski, Aleksander F

2015-01-01

There are many problems directly correlated with the systemic administration of drugs and how they reach their target site. Targeting promises to be a hopeful strategy as an improved means of drug delivery, with reduced toxicity and minimal adverse side effects. Targeting exploits the high affinity of cell-surface-targeted ligands, either directly or as carriers for a drug, for specific retention and uptake by the targeted diseased cells. One of the most important parameters which should be taken into consideration in the selection of an appropriate ligand for targeting is the binding affinity (KD). In this review we focus on the importance of binding affinities of monoclonal antibodies, antibody derivatives, peptides, aptamers, DARPins, and small targeting molecules in the process of selection of the most suitable ligand for targeting of nanoparticles. In order to provide a critical comparison between these various options, we have also assessed each technology format across a range of parameters such as molecular size, immunogenicity, costs of production, clinical profiles, and examples of the level of selectivity and toxicity of each. Wherever possible, we have also assessed how incorporating such a targeted approach compares with, or is superior to, original treatments. PMID:25733832

A game theory approach to target tracking in sensor networks.

PubMed

Gu, Dongbing

2011-02-01

In this paper, we investigate a moving-target tracking problem with sensor networks. Each sensor node has a sensor to observe the target and a processor to estimate the target position. It also has wireless communication capability but with limited range and can only communicate with neighbors. The moving target is assumed to be an intelligent agent, which is "smart" enough to escape from the detection by maximizing the estimation error. This adversary behavior makes the target tracking problem more difficult. We formulate this target estimation problem as a zero-sum game in this paper and use a minimax filter to estimate the target position. The minimax filter is a robust filter that minimizes the estimation error by considering the worst case noise. Furthermore, we develop a distributed version of the minimax filter for multiple sensor nodes. The distributed computation is implemented via modeling the information received from neighbors as measurements in the minimax filter. The simulation results show that the target tracking algorithm proposed in this paper provides a satisfactory result.

Strategies for addressing adherence problems in patients with serious and persistent mental illness: recommendations from the expert consensus guidelines.

PubMed

Velligan, Dawn I; Weiden, Peter J; Sajatovic, Martha; Scott, Jan; Carpenter, Daniel; Ross, Ruth; Docherty, John P

2010-09-01

Poor adherence to medication can have devastating consequences for patients with serious mental illness. The literature review and recommendations in this article are reprinted from The Expert Consensus Guideline Series: Adherence Problems in Patients with Serious and Persistent Mental Illness, published in 2009. The expert consensus survey (39 questions, 521 options) on adherence problems in schizophrenia and bipolar disorder was completed by 41 experts in 2008. This article first reviews the literature on interventions aimed at improving adherence. It then presents the experts' recommendations for targeting factors that can contribute to nonadherence and relates them to the literature. The following psychosocial/programmatic and pharmacologic interventions were rated first line for specific problems that can lead to nonadherence: ongoing symptom/ side-effect monitoring for persistent symptoms or side effects; services targeting logistic problems; medication monitoring/environmental supports (e.g., Cognitive Adaptation Training, assertive community treatment) for lack of routines or cognitive deficits; and adjusting the dose or switching to a different oral antipsychotic for persistent side effects (also high second-line for persistent symptoms). Among pharmacologic interventions, the experts gave high second-line ratings to switching to a long-acting antipsychotic when lack of insight, substance use, persistent symptoms, logistic problems, lack of routines, or lack of family/ social support interfere with adherence and to simplifying the treatment regimen when logistic problems, lack of routines, cognitive deficits, or lack of family/social support interfere with adherence. Psychosocial/programmatic interventions that received high second-line ratings in a number of situations included medication monitoring/environmental supports, patient psychoeducation, more frequent and/or longer visits if possible, cognitive behavioral therapy (CBT), family-focused therapy

UGS video target detection and discrimination

NASA Astrophysics Data System (ADS)

Roberts, G. Marlon; Fitzgerald, James; McCormack, Michael; Steadman, Robert; Vitale, Joseph D.

2007-04-01

This project focuses on developing electro-optic algorithms which rank images by their likelihood of containing vehicles and people. These algorithms have been applied to images obtained from Textron's Terrain Commander 2 (TC2) Unattended Ground Sensor system. The TC2 is a multi-sensor surveillance system used in military applications. It combines infrared, acoustic, seismic, magnetic, and electro-optic sensors to detect nearby targets. When targets are detected by the seismic and acoustic sensors, the system is triggered and images are taken in the visible and infrared spectrum. The original Terrain Commander system occasionally captured and transmitted an excessive number of images, sometimes triggered by undesirable targets such as swaying trees. This wasted communications bandwidth, increased power consumption, and resulted in a large amount of end-user time being spent evaluating unimportant images. The algorithms discussed here help alleviate these problems. These algorithms are currently optimized for infra-red images, which give the best visibility in a wide range of environments, but could be adapted to visible imagery as well. It is important that the algorithms be robust, with minimal dependency on user input. They should be effective when tracking varying numbers of targets of different sizes and orientations, despite the low resolutions of the images used. Most importantly, the algorithms must be appropriate for implementation on a low-power processor in real time. This would enable us to maintain frame rates of 2 Hz for effective surveillance operations. Throughout our project we have implemented several algorithms, and used an appropriate methodology to quantitatively compare their performance. They are discussed in this paper.

Conducting a team-based multi-sited focused ethnography in primary care.

PubMed

Bikker, A P; Atherton, H; Brant, H; Porqueddu, T; Campbell, J L; Gibson, A; McKinstry, B; Salisbury, C; Ziebland, S

2017-09-12

Focused ethnography is an applied and pragmatic form of ethnography that explores a specific social phenomenon as it occurs in everyday life. Based on the literature a problem-focused research question is formulated before the data collection. The data generation process targets key informants and situations so that relevant results on the pre-defined topic can be obtained within a relatively short time-span. As part of a theory based evaluation of alternative forms of consultation (such as video, phone and email) in primary care we used the focused ethnographic method in a multisite study in general practice across the UK. To date there is a gap in the literature on using focused ethnography in healthcare research.The aim of the paper is to build on the various methodological approaches in health services research by presenting the challenges and benefits we encountered whilst conducing a focused ethnography in British primary care. Our considerations are clustered under three headings: constructing a shared understanding, dividing the tasks within the team, and the functioning of the focused ethnographers within the broader multi-disciplinary team.As a result of using this approach we experienced several advantages, like the ability to collect focused data in several settings simultaneously within in a short time-span. Also, the sharing of experiences and interpretations between the researchers contributed to a more holistic understanding of the research topic. However, mechanisms need to be in place to facilitate and synthesise the observations, guide the analysis, and to ensure that all researchers feel engaged. Reflection, trust and flexibility among the team members were crucial to successfully adopt a team focused ethnographic approach. When used for policy focussed applied healthcare research a team-based multi-sited focused ethnography can uncover practices and understandings that would not be apparent through surveys or interviews alone. If conducted with

Targeting School Factors that Contribute to Youth Alienation: Focused School Counseling Programs

ERIC Educational Resources Information Center

Schulz, Lisa L.

2011-01-01

This article explores students at risk of academic non-completion. Schools and school counselors need to target the factors which put students at risk of academic non-completion to reduce the number of adolescents feeling a sense of alienation from school, from educators, and from learning. The construct of student alienation is examined based on…

Quo vadis radiotherapy? Technological advances and the rising problems in cancer management.

PubMed

Allen, Barry J; Bezak, Eva; Marcu, Loredana G

2013-01-01

Despite the latest technological advances in radiotherapy, cancer control is still challenging for several tumour sites. The survival rates for the most deadly cancers, such as ovarian and pancreatic, have not changed over the last decades. The solution to the problem lies in the change of focus: from local treatment to systemic therapy. The aim of this paper is to present the current status as well as the gaps in radiotherapy and, at the same time, to look into potential solutions to improve cancer control and survival. The currently available advanced radiotherapy treatment techniques have been analysed and their cost-effectiveness discussed. The problem of systemic disease management was specifically targeted. Clinical studies show limited benefit in cancer control from hadron therapy. However, targeted therapies together with molecular imaging could improve treatment outcome for several tumour sites while controlling the systemic disease. The advances in photon therapy continue to be competitive with the much more expensive hadron therapy. To justify the cost effectiveness of proton/heavy ion therapy, there is a need for phase III randomised clinical trials. Furthermore, the success of systemic disease management lies in the fusion between radiation oncology technology and microbiology.

Targeting Cardiac Fibroblasts to Treat Fibrosis of the Heart: Focus on HDACs

PubMed Central

Schuetze, Katherine B.; McKinsey, Timothy A.; Long, Carlin S.

2014-01-01

Cardiac fibrosis is implicated in numerous physiologic and pathologic conditions, including scar formation, heart failure and cardiac arrhythmias. However the specific cells and signaling pathways mediating this process are poorly understood. Lysine acetylation of nucleosomal histone tails is an important mechanism for the regulation of gene expression. Additionally, proteomic studies have revealed that thousands of proteins in all cellular compartments are subject to reversible lysine acetylation, and thus it is becoming clear that this post-translational modification will rival phosphorylation in terms of biological import. Acetyl groups are conjugated to lysine by histone acetyltransferases (HATs) and removed from lysine by histone deacetylases (HDACs). Recent studies have shown that pharmacologic agents that alter lysine acetylation by targeting HDACs have the remarkable ability to block pathological fibrosis. Here, we review the current understanding of cardiac fibroblasts and the fibrogenic process with respect to the roles of lysine acetylation in the control of disease-related cardiac fibrosis. Potential for small molecule HDAC inhibitors as antifibrotic therapeutics that target cardiac fibroblasts is highlighted. PMID:24631770

Quiet is the new loud: pausing and focus in child and adult Dutch.

PubMed

Romøren, Anna Sara H; Chen, Aoju

2015-03-01

In a number of languages, prosody is used to highlight new information (or focus). In Dutch, focus is marked by accentuation, whereby focal constituents are accented and post-focal constituents are de-accented. Even if pausing is not traditionally seen as a cue to focus in Dutch, several previous studies have pointed to a possible relationship between pausing and information structure. Considering that Dutch-speaking 4 to 5 year olds are not yet completely proficient in using accentuation for focus and that children generally pause more than adults, we asked whether pausing might be an available parameter for children to manipulate for focus. Sentences with varying focus structure were elicited from 10 Dutch-speaking 4 to 5 year olds and 9 Dutch-speaking adults by means of a picture-matching game. Comparing pause durations before focal and non-focal targets showed pre-target pauses to be significantly longer when the targets were focal than when they were not. Notably, the use of pausing was more robust in the children than in the adults, suggesting that children exploit pausing to mark focus more generally than adults do, at a stage where their mastery of the canonical cues to focus is still developing.

Optimization of Self-Directed Target Coverage in Wireless Multimedia Sensor Network

PubMed Central

Yang, Yang; Wang, Yufei; Pi, Dechang; Wang, Ruchuan

2014-01-01

Video and image sensors in wireless multimedia sensor networks (WMSNs) have directed view and limited sensing angle. So the methods to solve target coverage problem for traditional sensor networks, which use circle sensing model, are not suitable for WMSNs. Based on the FoV (field of view) sensing model and FoV disk model proposed, how expected multimedia sensor covers the target is defined by the deflection angle between target and the sensor's current orientation and the distance between target and the sensor. Then target coverage optimization algorithms based on expected coverage value are presented for single-sensor single-target, multisensor single-target, and single-sensor multitargets problems distinguishingly. Selecting the orientation that sensor rotated to cover every target falling in the FoV disk of that sensor for candidate orientations and using genetic algorithm to multisensor multitargets problem, which has NP-complete complexity, then result in the approximated minimum subset of sensors which covers all the targets in networks. Simulation results show the algorithm's performance and the effect of number of targets on the resulting subset. PMID:25136667

The molecular matching problem

NASA Technical Reports Server (NTRS)

Kincaid, Rex K.

1993-01-01

Molecular chemistry contains many difficult optimization problems that have begun to attract the attention of optimizers in the Operations Research community. Problems including protein folding, molecular conformation, molecular similarity, and molecular matching have been addressed. Minimum energy conformations for simple molecular structures such as water clusters, Lennard-Jones microclusters, and short polypeptides have dominated the literature to date. However, a variety of interesting problems exist and we focus here on a molecular structure matching (MSM) problem.

Antifungal Resistance, Metabolic Routes as Drug Targets, and New Antifungal Agents: An Overview about Endemic Dimorphic Fungi

PubMed Central

Parente-Rocha, Juliana Alves; Bailão, Alexandre Melo; Amaral, André Correa; Paccez, Juliano Domiraci; Borges, Clayton Luiz

2017-01-01

Diseases caused by fungi can occur in healthy people, but immunocompromised patients are the major risk group for invasive fungal infections. Cases of fungal resistance and the difficulty of treatment make fungal infections a public health problem. This review explores mechanisms used by fungi to promote fungal resistance, such as the mutation or overexpression of drug targets, efflux and degradation systems, and pleiotropic drug responses. Alternative novel drug targets have been investigated; these include metabolic routes used by fungi during infection, such as trehalose and amino acid metabolism and mitochondrial proteins. An overview of new antifungal agents, including nanostructured antifungals, as well as of repositioning approaches is discussed. Studies focusing on the development of vaccines against antifungal diseases have increased in recent years, as these strategies can be applied in combination with antifungal therapy to prevent posttreatment sequelae. Studies focused on the development of a pan-fungal vaccine and antifungal drugs can improve the treatment of immunocompromised patients and reduce treatment costs. PMID:28694566

Chemoprevention in gastrointestinal physiology and disease. Targeting the progression of cancer with natural products: a focus on gastrointestinal cancer.

PubMed

Khoogar, Roxane; Kim, Byung-Chang; Morris, Jay; Wargovich, Michael J

2016-05-01

The last decade has witnessed remarkable progress in the utilization of natural products for the prevention and treatment of human cancer. Many agents now in the pipeline for clinical trial testing have evolved from our understanding of how human nutritional patterns account for widespread differences in cancer risk. In this review, we have focused on many of these promising agents arguing that they may provide a new strategy for cancer control: natural products once thought to be only preventive in their mode of action now are being explored for efficacy in tandem with cancer therapeutics. Natural products may reduce off-target toxicity of therapeutics while making cancers more amenable to therapy. On the horizon is the use of certain natural products, in their own right, as mitigants of late-stage cancer, a new frontier for small-molecule natural product drug discovery. Copyright © 2016 the American Physiological Society.

Externally Delivered Focused Ultrasound for Renal Denervation.

PubMed

Neuzil, Petr; Ormiston, John; Brinton, Todd J; Starek, Zdenek; Esler, Murray; Dawood, Omar; Anderson, Thomas L; Gertner, Michael; Whitbourne, Rob; Schmieder, Roland E

2016-06-27

The aim of this study was to assess clinical safety and efficacy outcomes of renal denervation executed by an externally delivered, completely noninvasive focused therapeutic ultrasound device. Renal denervation has emerged as a potential treatment approach for resistant hypertension. Sixty-nine subjects received renal denervation with externally delivered focused ultrasound via the Kona Medical Surround Sound System. This approach was investigated across 3 consecutive studies to optimize targeting, tracking, and dosing. In the third study, treatments were performed in a completely noninvasive way using duplex ultrasound image guidance to target the therapy. Short- and long-term safety and efficacy were evaluated through use of clinical assessments, magnetic resonance imaging scans prior to and 3 and 24 weeks after renal denervation, and, in cases in which a targeting catheter was used to facilitate targeting, fluoroscopic angiography with contrast. All patients tolerated renal denervation using externally delivered focused ultrasound. Office blood pressure (BP) decreased by 24.6 ± 27.6/9.0 ± 15.0 mm Hg (from baseline BP of 180.0 ± 18.5/97.7 ± 13.7 mm Hg) in 69 patients after 6 months and 23.8 ± 24.1/10.3 ± 13.1 mm Hg in 64 patients with complete 1-year follow-up. The response rate (BP decrease >10 mm Hg) was 75% after 6 months and 77% after 1 year. The most common adverse event was post-treatment back pain, which was reported in 32 of 69 patients and resolved within 72 h in most cases. No intervention-related adverse events involving motor or sensory deficits were reported. Renal function was not altered, and vascular safety was established by magnetic resonance imaging (all patients), fluoroscopic angiography (n = 48), and optical coherence tomography (n = 5). Using externally delivered focused ultrasound and noninvasive duplex ultrasound, image-guided targeting was associated with substantial BP reduction without any major safety signals. Further

Comparison of Travel-Time and Amplitude Measurements for Deep-Focusing Time-Distance Helioseismology

NASA Astrophysics Data System (ADS)

Pourabdian, Majid; Fournier, Damien; Gizon, Laurent

2018-04-01

The purpose of deep-focusing time-distance helioseismology is to construct seismic measurements that have a high sensitivity to the physical conditions at a desired target point in the solar interior. With this technique, pairs of points on the solar surface are chosen such that acoustic ray paths intersect at this target (focus) point. Considering acoustic waves in a homogeneous medium, we compare travel-time and amplitude measurements extracted from the deep-focusing cross-covariance functions. Using a single-scattering approximation, we find that the spatial sensitivity of deep-focusing travel times to sound-speed perturbations is zero at the target location and maximum in a surrounding shell. This is unlike the deep-focusing amplitude measurements, which have maximum sensitivity at the target point. We compare the signal-to-noise ratio for travel-time and amplitude measurements for different types of sound-speed perturbations, under the assumption that noise is solely due to the random excitation of the waves. We find that, for highly localized perturbations in sound speed, the signal-to-noise ratio is higher for amplitude measurements than for travel-time measurements. We conclude that amplitude measurements are a useful complement to travel-time measurements in time-distance helioseismology.

Brain-inspired cheminformatics of drug-target brain interactome, synthesis, and assay of TVP1022 derivatives.

PubMed

Romero-Durán, Francisco J; Alonso, Nerea; Yañez, Matilde; Caamaño, Olga; García-Mera, Xerardo; González-Díaz, Humberto

2016-04-01

The use of Cheminformatics tools is gaining importance in the field of translational research from Medicinal Chemistry to Neuropharmacology. In particular, we need it for the analysis of chemical information on large datasets of bioactive compounds. These compounds form large multi-target complex networks (drug-target interactome network) resulting in a very challenging data analysis problem. Artificial Neural Network (ANN) algorithms may help us predict the interactions of drugs and targets in CNS interactome. In this work, we trained different ANN models able to predict a large number of drug-target interactions. These models predict a dataset of thousands of interactions of central nervous system (CNS) drugs characterized by > 30 different experimental measures in >400 different experimental protocols for >150 molecular and cellular targets present in 11 different organisms (including human). The model was able to classify cases of non-interacting vs. interacting drug-target pairs with satisfactory performance. A second aim focus on two main directions: the synthesis and assay of new derivatives of TVP1022 (S-analogues of rasagiline) and the comparison with other rasagiline derivatives recently reported. Finally, we used the best of our models to predict drug-target interactions for the best new synthesized compound against a large number of CNS protein targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

The testing effect and analogical problem-solving.

PubMed

Peterson, Daniel J; Wissman, Kathryn T

2018-06-25

Researchers generally agree that retrieval practice of previously learned material facilitates subsequent recall of same material, a phenomenon known as the testing effect. There is debate, however, about when such benefits transfer to related (though not identical) material. The current study examines the phenomenon of transfer in the domain of analogical problem-solving. In Experiments 1 and 2, learners were presented a source text describing a problem and solution to read which was subsequently either restudied or recalled. Following a short (Experiment 1) or long (Experiment 2) delay, learners were given a new target text and asked to solve a problem. The two texts shared a common structure such that the provided solution for the source text could be applied to solve the problem in the target text. In a combined analysis of both experiments, learners in the retrieval practice condition were more successful at solving the problem than those in the restudy condition. Experiment 3 explored the degree to which retrieval practice promotes cued versus spontaneous transfer by manipulating whether participants were provided with an explicit hint that the source and target texts were related. Results revealed no effect of retrieval practice.

Age-related physical and psychological vulnerability as pathways to problem gambling in older adults.

PubMed

Parke, Adrian; Griffiths, Mark; Pattinson, Julie; Keatley, David

2018-03-01

Background To inform clinical treatment and preventative efforts, there is an important need to understand the pathways to late-life gambling disorder. Aims This study assesses the association between age-related physical health, social networks, and problem gambling in adults aged over 65 years and assesses the mediating role of affective disorders in this association. Methods The sample comprised 595 older adults (mean age: 74.4 years, range: 65-94 years; 77.1% female) who were interviewed using a structured questionnaire to assess physical frailty, geriatric pain, loneliness, geriatric depression, geriatric anxiety, and problem gambling. Results Pathway analysis demonstrated associations between these variables and gambling problems, providing a good fit for the data, but that critically these relationships were mediated by both anxiety and depression symptoms. Conclusions This study indicates that late-life problem gambling may develop as vulnerable individuals gamble to escape anxiety and depression consequent to deteriorating physical well-being and social support. When individuals develop late-life problem gambling, it is recommended that the treatment primarily focuses upon targeting and replacing avoidant coping approaches.

Targeting the tumor microenvironment

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

Kenny, P.A.; Lee, G.Y.; Bissell, M.J.

2006-11-07

Despite some notable successes cancer remains, for the most part, a seemingly intractable problem. There is, however, a growing appreciation that targeting the tumor epithelium in isolation is not sufficient as there is an intricate mutually sustaining synergy between the tumor epithelial cells and their surrounding stroma. As the details of this dialogue emerge, new therapeutic targets have been proposed. The FDA has already approved drugs targeting microenvironmental components such as VEGF and aromatase and many more agents are in the pipeline. In this article, we describe some of the 'druggable' targets and processes within the tumor microenvironment and reviewmore » the approaches being taken to disrupt these interactions.« less

A graph-based approach to construct target-focused libraries for virtual screening.

PubMed

Naderi, Misagh; Alvin, Chris; Ding, Yun; Mukhopadhyay, Supratik; Brylinski, Michal

2016-01-01

Due to exorbitant costs of high-throughput screening, many drug discovery projects commonly employ inexpensive virtual screening to support experimental efforts. However, the vast majority of compounds in widely used screening libraries, such as the ZINC database, will have a very low probability to exhibit the desired bioactivity for a given protein. Although combinatorial chemistry methods can be used to augment existing compound libraries with novel drug-like compounds, the broad chemical space is often too large to be explored. Consequently, the trend in library design has shifted to produce screening collections specifically tailored to modulate the function of a particular target or a protein family. Assuming that organic compounds are composed of sets of rigid fragments connected by flexible linkers, a molecule can be decomposed into its building blocks tracking their atomic connectivity. On this account, we developed eSynth, an exhaustive graph-based search algorithm to computationally synthesize new compounds by reconnecting these building blocks following their connectivity patterns. We conducted a series of benchmarking calculations against the Directory of Useful Decoys, Enhanced database. First, in a self-benchmarking test, the correctness of the algorithm is validated with the objective to recover a molecule from its building blocks. Encouragingly, eSynth can efficiently rebuild more than 80 % of active molecules from their fragment components. Next, the capability to discover novel scaffolds is assessed in a cross-benchmarking test, where eSynth successfully reconstructed 40 % of the target molecules using fragments extracted from chemically distinct compounds. Despite an enormous chemical space to be explored, eSynth is computationally efficient; half of the molecules are rebuilt in less than a second, whereas 90 % take only about a minute to be generated. eSynth can successfully reconstruct chemically feasible molecules from molecular fragments

Safe Handling of Oral Antineoplastic Medications: Focus on Targeted Therapeutics in the Home Setting

PubMed Central

Cass, Yaakov; Connor, Thomas H.; Tabachnik, Alexander

2017-01-01

Introduction With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the potential to expose family members and caregivers to them either through direct contact with the drugs or indirectly by exposure to the parent compounds and/or their active metabolites in contaminated patient's waste. Methods A systematic literature review was performed and the known adverse health effect of 32 oral targeted therapeutics is summarized. In particular, the carcinogenicity, genotoxicity, and embryo-foetal toxicity, along with the route of excretion were evaluated. Results Carcinogenicity testing has not been performed on most of the oral targeted therapeutics and the genotoxicity data are mixed. However, the majority of these drugs exhibit adverse reproductive effects, some of which are severe. Currently available data does not permit the possibility of a health hazard from inappropriate handling of drugs and contaminated patients waste to be ignored, especially in a long-term home setting. Further research is needed to understand these issues. Conclusions With the expanding use of targeted therapies in the home setting, family members and caregivers, especially those of reproductive risk age, are, potentially at risk. Overall basic education and related precautions should be taken to protect family members and caregivers from indirect or direct exposure from these drugs. Further investigations and discussion on this subject is warranted. PMID:27009803

Project-Based Learning. Focus On

ERIC Educational Resources Information Center

Clarke, Suzanne

2009-01-01

Project-Based Learning (PBL) connects standards-based content to real-world scenarios through the use of projects to improve student achievement. By engaging students in authentic problems that do not have a predetermined solution, students learn both subject matter and critical 21st-century skills. This "Focus On" addresses what…

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

PubMed

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

2010-05-01

Focused ultrasound surgery (FUS) is a highly precise noninvasive procedure to ablate pathogenic tissue. FUS therapy is often combined with magnetic resonance (MR) imaging as MR imaging offers excellent target identification and allows for continuous monitoring of FUS induced temperature changes. As the dimensions of the ultrasound (US) focus are typically much smaller than the targeted volume, multiple sonications and focus repositioning are interleaved to scan the focus over the target volume. Focal scanning can be achieved electronically by using phased-array US transducers or mechanically by using dedicated mechanical actuators. In this study, the authors propose and evaluate the precision of a combined robotic FUS setup to overcome some of the limitations of the existing MRgFUS systems. Such systems are typically integrated into the patient table of the MR scanner and thus only provide an application of the US wave within a limited spatial range from below the patient. The fully MR-compatible robotic assistance system InnoMotion (InnoMedic GmbH, Herxheim, Germany) was originally designed for MR-guided interventions with needles. It offers five pneumatically driven degrees of freedom and can be moved over a wide range within the bore of the magnet. In this work, the robotic system was combined with a fixed-focus US transducer (frequency: 1.7 MHz; focal length: 68 mm, and numerical aperture: 0.44) that was integrated into a dedicated, in-house developed treatment unit for FUS application. A series of MR-guided focal scanning procedures was performed in a polyacrylamide-egg white gel phantom to assess the positioning accuracy of the combined FUS setup. In animal experiments with a 3-month-old domestic pig, the system's potential and suitability for MRgFUS was tested. In phantom experiments, a total targeting precision of about 3 mm was found, which is comparable to that of the existing MRgFUS systems. Focus positioning could be performed within a few seconds

Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

PubMed Central

Jo, Dong-Gyu; Park, Daeui; Chung, Hae Young

2014-01-01

During the past 5 decades, it has been widely promulgated that the chemicals in plants that are good for health act as direct scavengers of free radicals. Here we review evidence that favors a different hypothesis for the health benefits of plant consumption, namely, that some phytochemicals exert disease-preventive and therapeutic actions by engaging one or more adaptive cellular response pathways in cells. The evolutionary basis for the latter mechanism is grounded in the fact that plants produce natural antifeedant/noxious chemicals that discourage insects and other organisms from eating them. However, in the amounts typically consumed by humans, the phytochemicals activate one or more conserved adaptive cellular stress response pathways and thereby enhance the ability of cells to resist injury and disease. Examplesof such pathways include those involving the transcription factors nuclear factor erythroid 2-related factor 2, nuclear factor-κB, hypoxia-inducible factor 1α, peroxisome proliferator-activated receptor γ, and forkhead box subgroup O, as well as the production and action of trophic factors and hormones. Translational research to develop interventions that target these pathways may lead to new classes of therapeutic agents that act by stimulating adaptive stress response pathways to bolster endogenous defenses against tissue injury and disease. Because neurons are particularly sensitive to potentially noxious phytochemicals, we focus on the nervous system but also include findings from other cell types in which actions of phytochemicals on specific signal transduction pathways have been more thoroughly studied. PMID:24958636

Active echolocation beam focusing in the false killer whale, Pseudorca crassidens.

PubMed

Kloepper, Laura N; Nachtigall, Paul E; Donahue, Megan J; Breese, Marlee

2012-04-15

The odontocete sound production system is highly complex and produces intense, directional signals that are thought to be focused by the melon and the air sacs. Because odontocete echolocation signals are variable and the emitted click frequency greatly affects the echolocation beam shape, investigations of beam focusing must account for frequency-related beam changes. In this study we tested whether the echolocation beam of a false killer whale changed depending on target difficulty and distance while also accounting for frequency-related changes in the echolocation beam. The data indicate that the false killer whale changes its beam size according to target distance and difficulty, which may be a strategy of maximizing the energy of the target echo. We propose that the animal is using a strategy of changing the focal region according to target distance and that this strategy is under active control.

The influence of cueing on attentional focus in perceptual decision making.

PubMed

Yang, Cheng-Ta; Little, Daniel R; Hsu, Ching-Chun

2014-11-01

Selective attention has been known to play an important role in decision making. In the present study, we combined a cueing paradigm with a redundant-target detection task to examine how attention affects the decision process when detecting the redundant targets. Cue validity was manipulated in two experiments. The results showed that when the cue was 50 % valid in one experiment, the participants adopted a parallel self-terminating processing strategy, indicative of a diffuse attentional focus on both target locations. When the cue was 100 % valid in the second experiment, all of the participants switched to a serial self-terminating processing strategy, which in our study indicated focused attention to a single target location. This study demonstrates the flexibility of the decision mechanism and highlights the importance of top-down control in selecting a decision strategy.

Student Modeling Based on Problem Solving Times

ERIC Educational Resources Information Center

Pelánek, Radek; Jarušek, Petr

2015-01-01

Student modeling in intelligent tutoring systems is mostly concerned with modeling correctness of students' answers. As interactive problem solving activities become increasingly common in educational systems, it is useful to focus also on timing information associated with problem solving. We argue that the focus on timing is natural for certain…

[Problems of reforming pension schemes of the Georgian population].

PubMed

Gorgiladze, L Sh; Gerzmava, O Kh

2014-12-01

Decent level of pension provision for older people is one of the indispensable condition of any democratic society. Over time, the objectives pursued by the public pension system, have undergone many changes, but remains a constant problem preventing poverty of older citizens, and later, ensuring adequate standards of living of this, increasing the proportion of citizens. Certainly, the question of the relationship of the working population of premiums and pensions becomes essential economic and political importance. In the countries with transitive economy, which include Georgia, the most vulnerable because limited possibilities of pensioners fit into the new economic development. Georgia has not yet happened formation sufficiently clear approach to the reform of the existing system of social protection, which is characterized by extremely high paternalistic role of the state and very poorly marked public institutions. The system mainly focuses on targeted, efficient solution of problems of the crisis, however, this approach does not provide a long-term effect, because is not aimed at preventing repetition of crises on social protection perspective of each individual and the population as a whole. It is need creating highly focused on society's expectations of a multidisciplinary task of social protection, which should provide a comprehensive multifaceted assistance in solving problems throughout his life. In this context, social protection should be seen as a protection against social risks of loss or limitation of economic independence and social well-being. Forms and methods of organization of social protection of the elderly should be differentiated, affordable, high-grade, fully oriented to the prevention and resolution of the positive ways to separate the individual complex emergencies. Requires special consideration problem with the level of pensions, the solution of which depends not only on the economy but also on the new concept of pensions, which should

Improved Spatial Registration and Target Tracking Method for Sensors on Multiple Missiles.

PubMed

Lu, Xiaodong; Xie, Yuting; Zhou, Jun

2018-05-27

Inspired by the problem that the current spatial registration methods are unsuitable for three-dimensional (3-D) sensor on high-dynamic platform, this paper focuses on the estimation for the registration errors of cooperative missiles and motion states of maneuvering target. There are two types of errors being discussed: sensor measurement biases and attitude biases. Firstly, an improved Kalman Filter on Earth-Centered Earth-Fixed (ECEF-KF) coordinate algorithm is proposed to estimate the deviations mentioned above, from which the outcomes are furtherly compensated to the error terms. Secondly, the Pseudo Linear Kalman Filter (PLKF) and the nonlinear scheme the Unscented Kalman Filter (UKF) with modified inputs are employed for target tracking. The convergence of filtering results are monitored by a position-judgement logic, and a low-pass first order filter is selectively introduced before compensation to inhibit the jitter of estimations. In the simulation, the ECEF-KF enhancement is proven to improve the accuracy and robustness of the space alignment, while the conditional-compensation-based PLKF method is demonstrated to be the optimal performance in target tracking.

Identification of control targets in Boolean molecular network models via computational algebra.

PubMed

Murrugarra, David; Veliz-Cuba, Alan; Aguilar, Boris; Laubenbacher, Reinhard

2016-09-23

Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network. Supplementary data is available online and our code in Macaulay2 and Matlab are available via http://www.ms.uky.edu/~dmu228/ControlAlg . This paper presents a novel method for the identification of intervention targets in Boolean network models. The results in this paper show that the proposed methods are useful and efficient for moderately large networks.

School Leaders' Problem Framing: A Sense-Making Approach to Problem-Solving Processes of Beginning School Leaders

ERIC Educational Resources Information Center

Sleegers, Peter; Wassink, Hartger; van Veen, Klaas; Imants, Jeroen

2009-01-01

In addition to cognitive research on school leaders' problem solving, this study focuses on the situated and personal nature of problem framing by combining insights from cognitive research on problem solving and sense-making theory. The study reports the results of a case study of two school leaders solving problems in their daily context by…

Fast super-resolution estimation of DOA and DOD in bistatic MIMO Radar with off-grid targets

NASA Astrophysics Data System (ADS)

Zhang, Dong; Zhang, Yongshun; Zheng, Guimei; Feng, Cunqian; Tang, Jun

2018-05-01

In this paper, we focus on the problem of joint DOA and DOD estimation in Bistatic MIMO Radar using sparse reconstruction method. In traditional ways, we usually convert the 2D parameter estimation problem into 1D parameter estimation problem by Kronecker product which will enlarge the scale of the parameter estimation problem and bring more computational burden. Furthermore, it requires that the targets must fall on the predefined grids. In this paper, a 2D-off-grid model is built which can solve the grid mismatch problem of 2D parameters estimation. Then in order to solve the joint 2D sparse reconstruction problem directly and efficiently, three kinds of fast joint sparse matrix reconstruction methods are proposed which are Joint-2D-OMP algorithm, Joint-2D-SL0 algorithm and Joint-2D-SOONE algorithm. Simulation results demonstrate that our methods not only can improve the 2D parameter estimation accuracy but also reduce the computational complexity compared with the traditional Kronecker Compressed Sensing method.

Anger in Middle School: The Solving Problems Together Model

ERIC Educational Resources Information Center

Hall, Kimberly R.; Rushing, Jeri L.; Owens, Rachel B.

2009-01-01

Problem-focused interventions are considered to be one of the most effective group counseling strategies with adolescents. This article describes a problem-focused group counseling model, Solving Problems Together (SPT), with a small group of adolescent African American boys struggling with anger management. Adapted from the teaching philosophy of…

Graphing as a Problem-Solving Strategy.

ERIC Educational Resources Information Center

Cohen, Donald

1984-01-01

The focus is on how line graphs can be used to approximate solutions to rate problems and to suggest equations that offer exact algebraic solutions to the problem. Four problems requiring progressively greater graphing sophistication are presented plus four exercises. (MNS)

Common pitfalls in preclinical cancer target validation.

PubMed

Kaelin, William G

2017-07-01

An alarming number of papers from laboratories nominating new cancer drug targets contain findings that cannot be reproduced by others or are simply not robust enough to justify drug discovery efforts. This problem probably has many causes, including an underappreciation of the danger of being misled by off-target effects when using pharmacological or genetic perturbants in complex biological assays. This danger is particularly acute when, as is often the case in cancer pharmacology, the biological phenotype being measured is a 'down' readout (such as decreased proliferation, decreased viability or decreased tumour growth) that could simply reflect a nonspecific loss of cellular fitness. These problems are compounded by multiple hypothesis testing, such as when candidate targets emerge from high-throughput screens that interrogate multiple targets in parallel, and by a publication and promotion system that preferentially rewards positive findings. In this Perspective, I outline some of the common pitfalls in preclinical cancer target identification and some potential approaches to mitigate them.

Magnetic resonance-guided focused ultrasound surgery for treatment of painful osseous metastases

NASA Astrophysics Data System (ADS)

Hurwitz, Mark; Machtinger, Ronit; Fennessy, Fiona

2011-03-01

Magnetic resonance guided focused ultrasound surgery (MRgFUS) is an emerging technology that can non-invasively heat and ablate targeted tissue utilizing ultrasound energy. Use of MR imaging for treatment guidance provides several key advantages over more widely used ultrasound guidance for focused ultrasound ablation. MR allows for precise targeting, detailed beam path visualization, real time non-invasive temperature measurement, and treatment feedback to ensure therapeutic goals are achieved. In the realm of oncology, management of painful bone metastases is a common and daunting clinical problem. The Insightec ExAblate System has been shown in phase I/II trials for treatment of bone metastases to have an excellent safety profile and high rates of pain response. An international multi-center phase III trial for patients with painful bone metastases or multiple myeloma who are not candidates for radiation therapy is currently open. Patients are randomized 3:1 to MRgFUS or sham treatment with crossover to study treatment allowed for sham failures. The primary study endpoint is assessment of pain control over 3 months following treatment. In addition safety, quality of life, cost effectiveness analysis, and patient perceived clinical benefit are also being assessed. Details of the MRgFUS system, technical and clinical therapeutic parameters, use of real time non-invasive MR thermometry, and examples of patient treatments with use of MRgFUS to treat bone metastases will be discussed. New directions in use of MRgFUS including an update on development of a new mobile applicator and integration of MRgFUS in multimodality oncologic care will also be presented.

Adding tsetse control to medical activities contributes to decreasing transmission of sleeping sickness in the Mandoul focus (Chad)

PubMed Central

Mahamat, Mahamat Hissene; Peka, Mallaye; Rayaisse, Jean-Baptiste; Rock, Kat S.; Toko, Mahamat Abdelrahim; Darnas, Justin; Brahim, Guihini Mollo; Yoni, Wilfrid; Tirados, Inaki; Courtin, Fabrice; Brand, Samuel P. C.; Nersy, Cyrus; Alfaroukh, Idriss Oumar; Torr, Steve J.; Lehane, Mike J.; Solano, Philippe

2017-01-01

Background Gambian sleeping sickness or HAT (human African trypanosomiasis) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by riverine species of tsetse. A global programme aims to eliminate the disease as a public health problem by 2020 and stop transmission by 2030. In the South of Chad, the Mandoul area is a persistent focus of Gambian sleeping sickness where around 100 HAT cases were still diagnosed and treated annually until 2013. Pre-2014, control of HAT relied solely on case detection and treatment, which lead to a gradual decrease in the number of cases of HAT due to annual screening of the population. Methods Because of the persistence of transmission and detection of new cases, we assessed whether the addition of vector control to case detection and treatment could further reduce transmission and consequently, reduce annual incidence of HAT in Mandoul. In particular, we investigated the impact of deploying ‘tiny targets’ which attract and kill tsetse. Before tsetse control commenced, a census of the human population was conducted and their settlements mapped. A pre-intervention survey of tsetse distribution and abundance was implemented in November 2013 and 2600 targets were deployed in the riverine habitats of tsetse in early 2014, 2015 and 2016. Impact on tsetse and on the incidence of sleeping sickness was assessed through nine tsetse monitoring surveys and four medical surveys of the human population in 2014 and 2015. Mathematical modelling was used to assess the relative impact of tsetse control on incidence compared to active and passive screening. Findings The census indicated that a population of 38674 inhabitants lived in the vicinity of the Mandoul focus. Within this focus in November 2013, the vector is Glossina fuscipes fuscipes and the mean catch of tsetse from traps was 0.7 flies/trap/day (range, 0–26). The catch of tsetse from 44 sentinel biconical traps declined after target deployment with only

Current Interruption and Particle Beam Generation by a Plasma Focus.

DTIC Science & Technology

1982-11-30

Through collaboration with Dr. K. H. Schoenbach of Texas Tech University the plasma focus opening switch (PFOS) was revised to answer basic questions...results are consistent with the snowplow model. The final analysis of the plasma focus particle beam generation experiments was completed and a...strong correlation was found for the beam-target model as the mechanism for neutron production in the Illinois plasma focus device. (Author)

Recognizing visual focus of attention from head pose in natural meetings.

PubMed

Ba, Sileye O; Odobez, Jean-Marc

2009-02-01

We address the problem of recognizing the visual focus of attention (VFOA) of meeting participants based on their head pose. To this end, the head pose observations are modeled using a Gaussian mixture model (GMM) or a hidden Markov model (HMM) whose hidden states correspond to the VFOA. The novelties of this paper are threefold. First, contrary to previous studies on the topic, in our setup, the potential VFOA of a person is not restricted to other participants only. It includes environmental targets as well (a table and a projection screen), which increases the complexity of the task, with more VFOA targets spread in the pan as well as tilt gaze space. Second, we propose a geometric model to set the GMM or HMM parameters by exploiting results from cognitive science on saccadic eye motion, which allows the prediction of the head pose given a gaze target. Third, an unsupervised parameter adaptation step not using any labeled data is proposed, which accounts for the specific gazing behavior of each participant. Using a publicly available corpus of eight meetings featuring four persons, we analyze the above methods by evaluating, through objective performance measures, the recognition of the VFOA from head pose information obtained either using a magnetic sensor device or a vision-based tracking system. The results clearly show that in such complex but realistic situations, the VFOA recognition performance is highly dependent on how well the visual targets are separated for a given meeting participant. In addition, the results show that the use of a geometric model with unsupervised adaptation achieves better results than the use of training data to set the HMM parameters.

Application of liposomes in drug development — focus on gastroenterological targets

PubMed Central

Zhang, Jian-Xin; Wang, Kun; Mao, Zheng-Fa; Fan, Xin; Jiang, De-Li; Chen, Min; Cui, Lei; Sun, Kang; Dang, Sheng-Chun

2013-01-01

Over the past decade, liposomes became a focal point in developing drug delivery systems. New liposomes, with novel lipid molecules or conjugates, and new formulations opened possibilities for safely and efficiently treating many diseases including cancers. New types of liposomes can prolong circulation time or specifically deliver drugs to therapeutic targets. This article concentrates on current developments in liposome based drug delivery systems for treating diseases of the gastrointestinal tract. We will review different types and uses of liposomes in the development of therapeutics for gastrointestinal diseases including inflammatory bowel diseases and colorectal cancer. PMID:23630417

Control of treatment size in cavitation-enhanced high-intensity focused ultrasound using radio-frequency echo signals

NASA Astrophysics Data System (ADS)

Tomiyasu, Kentaro; Takagi, Ryo; Iwasaki, Ryosuke; Yoshizawa, Shin; Umemura, Shin-ichiro

2017-07-01

In high-intensity focused ultrasound (HIFU) treatment, controlling the ultrasound dose at each focal target spot is important because it is a problem that the length of the coagulated region in front of the focal point deviates owing to the differences in absorption in each focal target spot and attenuation in the intervening tissues. In this study, the detected changes in the power spectra of HIFU echoes were used by controlling the HIFU duration in the “trigger HIFU” sequence with the aim to increase coagulation size through the enhancement of the ultrasonic heating by the cavitation induced by the preceding extremely high intensity short “trigger” pulse. The result shows that this method can be used to detect boiling bubbles and the following generated cavitation bubbles at their early stage. By automatically stopping HIFU exposure immediately after detecting the bubbles, overheating was prevented and the deviation of the length of the coagulated region was reduced.

The Optimal Conditions for Form-Focused Instruction: Method, Target Complexity, and Types of Knowledge

ERIC Educational Resources Information Center

Kim, Jeong-eun

2012-01-01

This dissertation investigates optimal conditions for form-focused instruction (FFI) by considering effects of internal (i.e., timing and types of FFI) and external (i.e., complexity and familiarity) variables of FFI when it is offered within a primarily meaning-focused context of adult second language (L2) learning. Ninety-two Korean-speaking…

Tour of a Simple Trigonometry Problem

ERIC Educational Resources Information Center

Poon, Kin-Keung

2012-01-01

This article focuses on a simple trigonometric problem that generates a strange phenomenon when different methods are applied to tackling it. A series of problem-solving activities are discussed, so that students can be alerted that the precision of diagrams is important when solving geometric problems. In addition, the problem-solving plan was…

The effectiveness of return-to-work interventions that incorporate work-focused problem-solving skills for workers with sickness absences related to mental disorders: a systematic literature review

PubMed Central

Dewa, Carolyn S; Loong, Desmond; Bonato, Sarah; Joosen, Margot C W

2015-01-01

Objectives This paper reviews the current state of the published peer-reviewed literature related to return-to-work (RTW) interventions that incorporate work-related problem-solving skills for workers with sickness absences related to mental disorders. It addresses the question: What is the evidence for the effectiveness of these RTW interventions? Design Using a multiphase screening process, this systematic literature review was based on publically available peer-reviewed studies. Five electronic databases were searched: (1) Medline Current, (2) Medline In-process, (3) PsycINFO, (4) Econlit and (5) Web of Science. Setting The focus was on RTW interventions for workers with medically certified sickness absences related to mental disorders. Participants Workers with medically certified sickness absences related to mental disorders. Interventions RTW intervention included work-focused problem-solving skills. Primary and secondary outcome measures RTW rates and length of sickness absences. Results There were 4709 unique citations identified. Of these, eight articles representing a total of six studies were included in the review. In terms of bias avoidance, two of the six studies were rated as excellent, two as good and two as weak. Five studies were from the Netherlands; one was from Norway. There was variability among the studies with regard to RTW findings. Two of three studies reported significant differences in RTW rates between the intervention and control groups. One of six studies observed a significant difference in sickness absence duration between intervention and control groups. Conclusions There is limited evidence that combinations of interventions that include work-related problem-solving skills are effective in RTW outcomes. The evidence could be strengthened if future studies included more detailed examinations of intervention adherence and changes in problem-solving skills. Future studies should also examine the long-term effects of problem

Structural Problems in Teacher Training.

ERIC Educational Resources Information Center

Visalberghi, Aldo

1980-01-01

Focuses on educational problems in Italy, with particular regard to the effect of various pieces of educational legislation on these problems. Various solutions are proferred and suggestions are presented for integrating research, experimentation, and supplementary teacher training. (DB)

Design of the LBNF Beamline Target Station

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

Tariq, S.; Ammigan, K.; Anderson, K.

2016-10-01

The Long Baseline Neutrino Facility (LBNF) project will build a beamline located at Fermilab to create and aim an intense neutrino beam of appropriate energy range toward the DUNE detectors at the SURF facility in Lead, South Dakota. Neutrino production starts in the Target Station, which consists of a solid target, magnetic focusing horns, and the associated sub-systems and shielding infrastructure. Protons hit the target producing mesons which are then focused by the horns into a helium-filled decay pipe where they decay into muons and neutrinos. The target and horns are encased in actively cooled steel and concrete shielding inmore » a chamber called the target chase. The reference design chase is filled with air, but nitrogen and helium are being evaluated as alternatives. A replaceable beam window separates the decay pipe from the target chase. The facility is designed for initial operation at 1.2 MW, with the ability to upgrade to 2.4 MW, and is taking advantage of the experience gained by operating Fermilab’s NuMI facility. We discuss here the design status, associated challenges, and ongoing R&D and physics-driven component optimization of the Target Station.« less

Enantioselective Effects of Chiral Pesticides on their Primary Targets and Secondary Targets.

PubMed

Yang, Ye; Zhang, Jianyun; Yao, Yijun

2017-01-01

Enantioselectivity has been well recognized in the environmental fate and effects of chiral pesticides. Enantiospecific action of the optical enantiomers on the biological molecules establishes the mechanistic basis for the enantioselective toxicity of chiral pesticides to both target and non-target organisms. We undertook a structured search of bibliographic databases for research literature concerning the enantioselective effects of chiral pesticides, including insecticides, herbicides and fungicides, on biomolecules in various species by using some key words. The results of the relevant literatures were reviewed in the text and summarized in tables. Pesticides generally exert their activity on the target organisms via disrupting the primary target biomolecules. In non-target species, effects of pesticides on the secondary targets distinguished from the primary ones make great contribution to their toxicity. Recent investigations have provided convincing evidence of enantioselective toxicity of chiral pesticides to both target and non-target species which is recognized to result from their enantiospecific action on the primary or secondary targets in organisms. This review confirms that chiral pesticides have enantiospecific effects on both primary and secondary target biomolecules in organisms. Future studies regarding toxicological effects of chiral pesticides should focus on the relationship between the enantiomeric difference in the compound-biomolecules interaction and the enantioselectivity in their toxicity.

Handling target obscuration through Markov chain observations

NASA Astrophysics Data System (ADS)

Kouritzin, Michael A.; Wu, Biao

2008-04-01

Target Obscuration, including foliage or building obscuration of ground targets and landscape or horizon obscuration of airborne targets, plagues many real world filtering problems. In particular, ground moving target identification Doppler radar, mounted on a surveillance aircraft or unattended airborne vehicle, is used to detect motion consistent with targets of interest. However, these targets try to obscure themselves (at least partially) by, for example, traveling along the edge of a forest or around buildings. This has the effect of creating random blockages in the Doppler radar image that move dynamically and somewhat randomly through this image. Herein, we address tracking problems with target obscuration by building memory into the observations, eschewing the usual corrupted, distorted partial measurement assumptions of filtering in favor of dynamic Markov chain assumptions. In particular, we assume the observations are a Markov chain whose transition probabilities depend upon the signal. The state of the observation Markov chain attempts to depict the current obscuration and the Markov chain dynamics are used to handle the evolution of the partially obscured radar image. Modifications of the classical filtering equations that allow observation memory (in the form of a Markov chain) are given. We use particle filters to estimate the position of the moving targets. Moreover, positive proof-of-concept simulations are included.

Detecting targets hidden in random forests

NASA Astrophysics Data System (ADS)

Kouritzin, Michael A.; Luo, Dandan; Newton, Fraser; Wu, Biao

2009-05-01

Military tanks, cargo or troop carriers, missile carriers or rocket launchers often hide themselves from detection in the forests. This plagues the detection problem of locating these hidden targets. An electro-optic camera mounted on a surveillance aircraft or unmanned aerial vehicle is used to capture the images of the forests with possible hidden targets, e.g., rocket launchers. We consider random forests of longitudinal and latitudinal correlations. Specifically, foliage coverage is encoded with a binary representation (i.e., foliage or no foliage), and is correlated in adjacent regions. We address the detection problem of camouflaged targets hidden in random forests by building memory into the observations. In particular, we propose an efficient algorithm to generate random forests, ground, and camouflage of hidden targets with two dimensional correlations. The observations are a sequence of snapshots consisting of foliage-obscured ground or target. Theoretically, detection is possible because there are subtle differences in the correlations of the ground and camouflage of the rocket launcher. However, these differences are well beyond human perception. To detect the presence of hidden targets automatically, we develop a Markov representation for these sequences and modify the classical filtering equations to allow the Markov chain observation. Particle filters are used to estimate the position of the targets in combination with a novel random weighting technique. Furthermore, we give positive proof-of-concept simulations.

Complementary Approaches to Existing Target Based Drug Discovery for Identifying Novel Drug Targets.

PubMed

Vasaikar, Suhas; Bhatia, Pooja; Bhatia, Partap G; Chu Yaiw, Koon

2016-11-21

In the past decade, it was observed that the relationship between the emerging New Molecular Entities and the quantum of R&D investment has not been favorable. There might be numerous reasons but few studies stress the introduction of target based drug discovery approach as one of the factors. Although a number of drugs have been developed with an emphasis on a single protein target, yet identification of valid target is complex. The approach focuses on an in vitro single target, which overlooks the complexity of cell and makes process of validation drug targets uncertain. Thus, it is imperative to search for alternatives rather than looking at success stories of target-based drug discovery. It would be beneficial if the drugs were developed to target multiple components. New approaches like reverse engineering and translational research need to take into account both system and target-based approach. This review evaluates the strengths and limitations of known drug discovery approaches and proposes alternative approaches for increasing efficiency against treatment.

Issues in the Analysis of Focus Groups: Generalisability, Quantifiability, Treatment of Context and Quotations

ERIC Educational Resources Information Center

Vicsek, Lilla

2010-01-01

In this paper I discuss some concerns related to the analysis of focus groups: (a) the issue of generalisation; (b) the problems of using numbers and quantifying in the analysis; (c) how the concrete situation of the focus groups could be included in the analysis, and (d) what formats can be used when quoting from focus groups. Problems with…

Schizophrenia, narrative, and neurocognition: The utility of life-stories in understanding social problem-solving skills.

PubMed

Moe, Aubrey M; Breitborde, Nicholas J K; Bourassa, Kyle J; Gallagher, Colin J; Shakeel, Mohammed K; Docherty, Nancy M

2018-06-01

Schizophrenia researchers have focused on phenomenological aspects of the disorder to better understand its underlying nature. In particular, development of personal narratives-that is, the complexity with which people form, organize, and articulate their "life stories"-has recently been investigated in individuals with schizophrenia. However, less is known about how aspects of narrative relate to indicators of neurocognitive and social functioning. The objective of the present study was to investigate the association of linguistic complexity of life-story narratives to measures of cognitive and social problem-solving abilities among people with schizophrenia. Thirty-two individuals with a diagnosis of schizophrenia completed a research battery consisting of clinical interviews, a life-story narrative, neurocognitive testing, and a measure assessing multiple aspects of social problem solving. Narrative interviews were assessed for linguistic complexity using computerized technology. The results indicate differential relationships of linguistic complexity and neurocognition to domains of social problem-solving skills. More specifically, although neurocognition predicted how well one could both describe and enact a solution to a social problem, linguistic complexity alone was associated with accurately recognizing that a social problem had occurred. In addition, linguistic complexity appears to be a cognitive factor that is discernible from other broader measures of neurocognition. Linguistic complexity may be more relevant in understanding earlier steps of the social problem-solving process than more traditional, broad measures of cognition, and thus is relevant in conceptualizing treatment targets. These findings also support the relevance of developing narrative-focused psychotherapies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

A signature correlation study of ground target VHF/UHF ISAR imagery

NASA Astrophysics Data System (ADS)

Gatesman, Andrew J.; Beaudoin, Christopher J.; Giles, Robert H.; Kersey, William T.; Waldman, Jerry; Carter, Steve; Nixon, William E.

2003-09-01

VV and HH-polarized radar signatures of several ground targets were acquired in the VHF/UHF band (171-342 MHz) by using 1/35th scale models and an indoor radar range operating from 6 to 12 GHz. Data were processed into medianized radar cross sections as well as focused, ISAR imagery. Measurement validation was confirmed by comparing the radar cross section of a test object with a method of moments radar cross section prediction code. The signatures of several vehicles from three vehicle classes (tanks, trunks, and TELs) were measured and a signature cross-correlation study was performed. The VHF/UHF band is currently being exploited for its foliage penetration ability, however, the coarse image resolution which results from the relatively long radar wavelengths suggests a more challenging target recognition problem. One of the study's goals was to determine the amount of unique signature content in VHF/UHF ISAR imagery of military ground vehicles. Open-field signatures are compared with each other as well as with simplified shapes of similar size. Signatures were also acquired on one vehicle in a variety of configurations to determine the impact of monitor target variations on the signature content at these frequencies.

Superintendent Leadership: Focusing on District Culture

ERIC Educational Resources Information Center

Donnelly, Tanya A.; Adams, Jeffery S.; Smith, Dwayne E.

2012-01-01

This report describes a problem-based learning project focusing on superintendent leadership and stakeholder influence of school district culture. Current research findings suggest the importance of superintendent leadership in assessing, influencing, and enhancing school district culture. Multiple scholars wrote literature in the area of…

Puzzles, Pastimes, Problems.

ERIC Educational Resources Information Center

Eperson, D. B.

1985-01-01

Presents six mathematical problems (with answers) which focus on: (1) chess moves; (2) patterned numbers; (3) quadratics with rational roots; (4) number puzzles; (5) Euclidean geometry; and (6) Carrollian word puzzles. (JN)

Novel Antitubercular 6-Dialkylaminopyrimidine Carboxamides from Phenotypic Whole-Cell High Throughput Screening of a SoftFocus Library: Structure–Activity Relationship and Target Identification Studies

PubMed Central

2017-01-01

A BioFocus DPI SoftFocus library of ∼35 000 compounds was screened against Mycobacterium tuberculosis (Mtb) in order to identify novel hits with antitubercular activity. The hits were evaluated in biology triage assays to exclude compounds suggested to function via frequently encountered promiscuous mechanisms of action including inhibition of the QcrB subunit of the cytochrome bc1 complex, disruption of cell–wall homeostasis, and DNA damage. Among the hits that passed this screening cascade, a 6-dialkylaminopyrimidine carboxamide series was prioritized for hit to lead optimization. Compounds from this series were active against clinical Mtb strains, while no cross-resistance to conventional antituberculosis drugs was observed. This suggested a novel mechanism of action, which was confirmed by chemoproteomic analysis leading to the identification of BCG_3193 and BCG_3827 as putative targets of the series with unknown function. Initial structure–activity relationship studies have resulted in compounds with moderate to potent antitubercular activity and improved physicochemical properties. PMID:29148755

Vacuum aperture isolator for retroreflection from laser-irradiated target

DOEpatents

Benjamin, Robert F.; Mitchell, Kenneth B.

1980-01-01

The disclosure is directed to a vacuum aperture isolator for retroreflection of a laser-irradiated target. Within a vacuum chamber are disposed a beam focusing element, a disc having an aperture and a recollimating element. The edge of the focused beam impinges on the edge of the aperture to produce a plasma which refracts any retroreflected light from the laser's target.

Numerical Study on Focusing of Ultrasounds in Microbubble-enhanced HIFU

NASA Astrophysics Data System (ADS)

Matsumoto, Yoichiro; Okita, Kohei; Takagi, Shu

2011-11-01

The injection of microbubbles into the target tissue enhances tissue heating in High-Intensity Focused Ultrasound therapy, via inertial cavitation. The control of the inertial cavitation is required to achieve the efficient tissue ablation. Microbubbles between a transducer and a target disturb the ultrasound propagation depending on the conditions. A method to clear such microbubbles has been proposed by Kajiyama et al. [Physics Procedia 3 (2010) 305-314]. In the method, the irradiation of intense ultrasounds with a burst waveform fragmentize microbubbles in the pathways before the irradiation of ultrasounds for tissue heating. The vitro experiment using a gel containing microbubbles has showed that the method enables to heat the target correctly by controlling the microbubble distribution. Following the experiment, we simulate the focusing of ultrasounds through a mixture containing microbubbles with considering the size and number density distributions in space. The numerical simulation shows that the movement of the heating region from the transducer side to the target by controlling the microbubble distributions. The numerical results elucidate well the experimental ones.

Collis-Romberg Mathematical Problem Solving Profiles.

ERIC Educational Resources Information Center

Collis, K. F.; Romberg, T. A.

Problem solving has become a focus of mathematics programs in Australia in recent years, necessitating the assessment of students' problem-solving abilities. This manual provides a problem-solving assessment and teaching resource package containing four elements: (1) profiles assessment items; (2) profiles diagnostic forms for recording individual…

Evolutionary Multiobjective Design Targeting a Field Programmable Transistor Array

NASA Technical Reports Server (NTRS)

Aguirre, Arturo Hernandez; Zebulum, Ricardo S.; Coello, Carlos Coello

2004-01-01

This paper introduces the ISPAES algorithm for circuit design targeting a Field Programmable Transistor Array (FPTA). The use of evolutionary algorithms is common in circuit design problems, where a single fitness function drives the evolution process. Frequently, the design problem is subject to several goals or operating constraints, thus, designing a suitable fitness function catching all requirements becomes an issue. Such a problem is amenable for multi-objective optimization, however, evolutionary algorithms lack an inherent mechanism for constraint handling. This paper introduces ISPAES, an evolutionary optimization algorithm enhanced with a constraint handling technique. Several design problems targeting a FPTA show the potential of our approach.

[PAHO focuses on the problem of violence against women].

PubMed

Hartigan, P

1997-10-01

In Latin American and the Caribbean, a woman who is abused by her partner tends to deny the fact that she is the object of violence out of embarrassment, fear of revenge on the part of the assailant, or tacit consent on the part of the family and society at large. If she finally appeals to the justice or health care system, no one alleviates her circumstances, since both sectors operate independently and less efficiently than if intersectoral coordination existed. In June 1994 PAHO initiated a project in 16 countries involving the creation within the community of branches of the justice and health care systems, police, churches, non-government organizations, and community groups. These meet on a regular basis with the aim of launching a coordinated response to domestic violence. At the national level, the project fosters policies and legal norms that strengthen the institutional capacity to respond to the problem. Links with the media are also being promoted in order to combat social beliefs and attitudes that lead to women being abused in their own homes.

Optimization of Focused Ultrasound and Image Based Modeling in Image Guided Interventions

NASA Astrophysics Data System (ADS)

Almekkawy, Mohamed Khaled Ibrahim

Image-guided high intensity focused ultrasound (HIFU) is becoming increasingly accepted as a form of noninvasive ablative therapy for the treatment of prostate cancer, uterine fibroids and other tissue abnormalities. In principle, HIFU beams can be focused within small volumes which results in forming precise lesions within the target volume (e.g. tumor, atherosclerotic plaque) while sparing the intervening tissue. With this precision, HIFU offers the promise of noninvasive tumor therapy. The goal of this thesis is to develop an image-guidance mode with an interactive image-based computational modeling of tissue response to HIFU. This model could be used in treatment planning and post-treatment retrospective evaluation of treatment outcome(s). Within the context of treatment planning, the challenge of using HIFU to target tumors in organs partially obscured by the rib cage are addressed. Ribs distort HIFU beams in a manner that reduces the focusing gain at the target (tumor) and could cause a treatment-limiting collateral damage. We present a refocusing algorithms to efficiently steer higher power towards the target while limiting power deposition on the ribs, improving the safety and efficacy of tumor ablation. Our approach is based on an approximation of a non-convex to a convex optimization known as the semidefinite relaxation (SDR) technique. An important advantage of the SDR method over previously proposed optimization methods is the explicit control of the sidelobes in the focal plane. A finite-difference time domain (FDTD) heterogeneous propagation model of a 1-MHz concave phased array was used to model the acoustic propagation and temperature simulations in different tissues including ribs. The numerical methods developed for the refocusing problem are also used for retrospective analysis of targeting of atherosclerotic plaques using HIFU. Cases were simulated where seven adjacent HIFU shots (5000 W/cm2, 2 sec exposure time) were focused at the plaque

Nanocarriers for cancer-targeted drug delivery.

PubMed

Kumari, Preeti; Ghosh, Balaram; Biswas, Swati

2016-01-01

Nanoparticles as drug delivery system have received much attention in recent years, especially for cancer treatment. In addition to improving the pharmacokinetics of the loaded poorly soluble hydrophobic drugs by solubilizing them in the hydrophobic compartments, nanoparticles allowed cancer specific drug delivery by inherent passive targeting phenomena and adopted active targeting strategies. For this reason, nanoparticles-drug formulations are capable of enhancing the safety, pharmacokinetic profiles and bioavailability of the administered drugs leading to improved therapeutic efficacy compared to conventional therapy. The focus of this review is to provide an overview of various nanoparticle formulations in both research and clinical applications with a focus on various chemotherapeutic drug delivery systems for the treatment of cancer. The use of various nanoparticles, including liposomes, polymeric nanoparticles, dendrimers, magnetic and other inorganic nanoparticles for targeted drug delivery in cancer is detailed.

Distinct emotion regulation skills explain psychopathology and problems in social relationships following childhood emotional abuse and neglect.

PubMed

Berzenski, Sara R

2018-03-22

Efforts to differentiate between the developmental sequelae of childhood emotional abuse and childhood emotional neglect are critical to both research and practice efforts. As an oft-identified mechanism of the effects of child maltreatment on later adjustment, emotion dysregulation represents a key potential pathway. The present study explored a higher order factor model of specific emotion regulation skills, and the extent to which these skill sets would indicate distinct developmental pathways from unique emotional maltreatment experiences to multidomain adjustment. A sample of 500 ethnoracially diverse college students reported on their experiences. A two-factor model of emotion regulation skills based on subscales of the Difficulties in Emotion Regulation Scale was revealed. Significant indirect effects of childhood emotional abuse on psychopathology and problems in social relationships were found through response-focused difficulties in emotion regulation, whereas a significant indirect effect of childhood emotional neglect on problems in social relationships was found through antecedent-focused difficulties in emotion regulation. These results are consistent with theoretical models and empirical evidence suggesting differential effects of childhood emotional abuse and emotional neglect, and provide an important indication for developing targeted interventions focusing on specific higher order emotion dysregulation skill clusters.

Form-Focused Discovery Activities in English Classes

ERIC Educational Resources Information Center

Ogeyik, Muhlise Cosgun

2011-01-01

Form-focused discovery activities allow language learners to grasp various aspects of a target language by contributing implicit knowledge by using discovered explicit knowledge. Moreover, such activities can assist learners to perceive and discover the features of their language input. In foreign language teaching environments, they can be used…

[Feminists' approach to population problems: new paradigm or Utopia?].

PubMed

Kono, S

1997-05-01

The author first notes that, partly because of events occurring at the International Conference on Population and Development that took place in Cairo in 1994, a consensus has emerged that population programs based on a philosophy of empowering women and focusing on reproductive health are more likely to be effective than programs that focus on providing family planning services and achieving demographic targets. Some reservations about this consensus are then expressed. The author points out the difficulties inherent in widening the mandate of family planning programs in an era of diminished resources for international assistance, the past success of such programs in reducing fertility with limited resources, and the inherent contradictions in following a laissez-faire attitude toward reproduction in such regions as Sub-Saharan Africa, where economies and political systems are often in crisis, health services are minimal, and desired levels of fertility both way above current levels and far above the replacement level. While not challenging the value of the Cairo philosophy, the need to move from rhetoric to reality in the face of the world's current population problems is stressed.

Addressing the Immunogenicity of the Cargo and of the Targeting Antibodies with a Focus on Deimmunized Bacterial Toxins and on Antibody-Targeted Human Effector Proteins

PubMed Central

Grinberg, Yehudit; Benhar, Itai

2017-01-01

Third-generation immunotoxins are composed of a human, or humanized, targeting moiety, usually a monoclonal antibody or an antibody fragment, and a non-human effector molecule. Due to the non-human origin of the cytotoxic domain, these molecules stimulate potent anti-drug immune responses, which limit treatment options. Efforts are made to deimmunize such immunotoxins or to combine treatment with immunosuppression. An alternative approach is using the so-called “human cytotoxic fusion proteins”, in which antibodies are used to target human effector proteins. Here, we present three relevant approaches for reducing the immunogenicity of antibody-targeted protein therapeutics: (1) reducing the immunogenicity of the bacterial toxin, (2) fusing human cytokines to antibodies to generate immunocytokines and (3) addressing the immunogenicity of the targeting antibodies. PMID:28574434

Design of a new type synchronous focusing mechanism

NASA Astrophysics Data System (ADS)

Zhang, Jintao; Tan, Ruijun; Chen, Zhou; Zhang, Yongqi; Fu, Panlong; Qu, Yachen

2018-05-01

Aiming at the dual channel telescopic imaging system composed of infrared imaging system, low-light-level imaging system and image fusion module, In the fusion of low-light-level images and infrared images, it is obvious that using clear source images is easier to obtain high definition fused images. When the target is imaged at 15m to infinity, focusing is needed to ensure the imaging quality of the dual channel imaging system; therefore, a new type of synchronous focusing mechanism is designed. The synchronous focusing mechanism realizes the focusing function through the synchronous translational imaging devices, mainly including the structure of the screw rod nut, the shaft hole coordination structure and the spring steel ball eliminating clearance structure, etc. Starting from the synchronous focusing function of two imaging devices, the structure characteristics of the synchronous focusing mechanism are introduced in detail, and the focusing range is analyzed. The experimental results show that the synchronous focusing mechanism has the advantages of ingenious design, high focusing accuracy and stable and reliable operation.

Development of a Problem-Focused Behavioral Screener Linked to Evidence-Based Intervention

ERIC Educational Resources Information Center

Daniels, Brian; Volpe, Robert J.; Briesch, Amy M.; Fabiano, Gregory A.

2014-01-01

This study examines the factor structure, reliability and validity of a novel school-based screening instrument for academic and disruptive behavior problems commonly experienced by children and adolescents with attention deficit hyperactivity disorder (ADHD). Participants included 39 classroom teachers from two public school districts in the…

Case of Two Electrostatics Problems: Can Providing a Diagram Adversely Impact Introductory Physics Students' Problem Solving Performance?

ERIC Educational Resources Information Center

Maries, Alexandru; Singh, Chandralekha

2018-01-01

Drawing appropriate diagrams is a useful problem solving heuristic that can transform a problem into a representation that is easier to exploit for solving it. One major focus while helping introductory physics students learn effective problem solving is to help them understand that drawing diagrams can facilitate problem solution. We conducted an…

Reproductive autonomy, the non-identity problem, and the non-person problem.

PubMed

DiSilvestro, Russell

2009-01-01

The Non-Identity Problem is the problem of explaining the apparent wrongness of a decision that does not harm people, especially since some of the people affected by the decision would not exist at all were it not for the decision. One approach to this problem, in the context of reproductive decisions, is to focus on wronging, rather than harming, one's offspring. But a Non-Person Problem emerges for any view that claims (1) that only persons can be wronged and (2) that the person-making properties allow for there to be human non-persons. Consider an individual human organism that is prevented from ever possessing the person-making properties. On person-only accounts of the victims of wronging, this organism cannot be wronged by anyone. Hence even individuals whose decisions prevent it from ever possessing the person-making properties cannot wrong it. But this is counter-intuitive. We can think of examples where a human organism is wronged by precisely those decisions that prevent it from possessing the person-making properties. The best solution to this problem, in the case where the person-making property is rational self-governance in pursuit of a meaningful life, is to adjust the concept of a person so that it refers, not merely to those with the immediate capacity for rational self-governance in pursuit of a meaningful life, but also to those with a higher-order capacity for such self-governance. Any solution to the Non-Identity Problem that focuses on wronging rather than harming should incorporate this sort of solution to the Non-Person Problem.

Back-streaming ion emission and beam focusing on high power linear induction accelerator

NASA Astrophysics Data System (ADS)

Zhu, Jun; Chen, Nan; Yu, Haijun; Jiang, Xiaoguo; Wang, Yuan; Dai, Wenhua; Gao, Feng; Wang, Minhong; Li, Jin; Shi, Jinshui

2011-08-01

Ions released from target surfaces by impact of a high intensity and current electron beam can be accelerated and trapped in the beam potential, and further destroy the beam focus. By solving the 2D Poisson equation, we found that the charge neutralization factor of the ions to the beam under space charge limited condition is 1/3, which is large enough to disrupt the spot size. Therefore, the ion emission at the target in a single-pulse beam/target system must be source limited. Experimental results on the time-resolved beam profile measurement have also proven that. A new focus scheme is proposed in this paper to focus the beam to a small spot size with the existence of back-streaming ions. We found that the focal spot will move upstream as the charge neutralization factor increases. By comparing the theoretical and experimental focal length of the Dragon-I accelerator (20 MeV, 2.5 kA, 60 ns flattop), we found that the average neutralization factor is about 5% in the beam/target system.

Problem-Solving Software

NASA Technical Reports Server (NTRS)

1992-01-01

CBR Express software solves problems by adapting sorted solutions to new problems specified by a user. It is applicable to a wide range of situations. The technology was originally developed by Inference Corporation for Johnson Space Center's Advanced Software Development Workstation. The project focused on the reuse of software designs, and Inference used CBR as part of the ACCESS prototype software. The commercial CBR Express is used as a "help desk" for customer support, enabling reuse of existing information when necessary. It has been adopted by several companies, among them American Airlines, which uses it to solve reservation system software problems.

No arousal-biased competition in focused visuospatial attention.

PubMed

Ásgeirsson, Árni Gunnar; Nieuwenhuis, Sander

2017-11-01

Arousal sometimes enhances and sometimes impairs perception and memory. A recent theory attempts to reconcile these findings by proposing that arousal amplifies the competition between stimulus representations, strengthening already strong representations and weakening already weak representations. Here, we report a stringent test of this arousal-biased competition theory in the context of focused visuospatial attention. Participants were required to identify a briefly presented target in the context of multiple distractors, which varied in the degree to which they competed for representation with the target, as revealed by psychophysics. We manipulated arousal using emotionally arousing pictures (Experiment 1), alerting tones (Experiment 2) and white-noise stimulation (Experiment 3), and validated these manipulations with electroencephalography and pupillometry. In none of the experiments did we find evidence that arousal modulated the effect of distractor competition on the accuracy of target identification. Bayesian statistics revealed moderate to strong evidence against arousal-biased competition. Modeling of the psychophysical data based on Bundesen's (1990) theory of visual attention corroborated the conclusion that arousal does not bias competition in focused visuospatial attention. Copyright © 2017 Elsevier B.V. All rights reserved.

In Vivo Targeted, Responsive, and Synergistic Cancer Nanotheranostics by Magnetic Resonance Imaging-Guided Synergistic High-Intensity Focused Ultrasound Ablation and Chemotherapy.

PubMed

Tang, Hailin; Guo, Yuan; Peng, Li; Fang, Hui; Wang, Zhigang; Zheng, Yuanyi; Ran, Haitao; Chen, Yu

2018-05-09

As one of the most representative noninvasive therapeutic modalities, high-intensity focused ultrasound (HIFU) has shown great promise for cancer therapy, but its low therapeutic efficacy and biosafety significantly hinder further extensive clinical translation and application. In this work, we report on the construction of a multifunctional theranostic nanoplatform to synergistically enhance the HIFU-therapeutic efficacy based on nanomedicine. A targeted and temperature-responsive theranostic nanoplatform (PFH/DOX@PLGA/Fe 3 O 4 -FA) has been designed and fabricated for efficient ultrasound/magnetic resonance dual-modality imaging-guided HIFU/chemo synergistic therapy. Especially, the folate was conjugated onto the surface of the nanoplatform for achieving active targeting to hepatoma cells by receptor-ligand interaction, which facilitates accumulation of the nanoplatforms into the tumor site. The integrated superparamagnetic iron oxide nanoparticles could generate the contrast enhancement in T 2 -weighted magnetic resonance imaging. By virtue of the thermal effect as generated by HIFU, liquid-gas phase transition of perfluorohexane (PFH) in nanocomposites was induced to generate PFH microbubbles, which achieved the contrast-enhanced ultrasound imaging and significantly improved the HIFU ablation efficacy. The loaded anticancer drugs could be released from the nanocomposites in a controllable manner (both pH and HIFU responsiveness). These multifunctional nanocomposites have been demonstrated to efficiently suppress the tumor growth based on the enhanced and synergistic chemotherapy and HIFU ablation, providing an efficient theranostic nanoplatform for cancer treatment.

Student Target Marketing Strategies for Universities

ERIC Educational Resources Information Center

Lewison, Dale M.; Hawes, Jon M.

2007-01-01

As colleges and universities adopt marketing orientations to an ever-increasing extent, the relative merits of mass marketing and target marketing must also be explored. Researchers identify buyer types as potential students focused on quality, value or economy. On the other axis, learner types are described as those who focus on career,…

Neurosurgical Applications of High-Intensity Focused Ultrasound with Magnetic Resonance Thermometry.

PubMed

Colen, Rivka R; Sahnoune, Iman; Weinberg, Jeffrey S

2017-10-01

Magnetic resonance guided focused ultrasound surgery (MRgFUS) has potential noninvasive effects on targeted tissue. MRgFUS integrates MRI and focused ultrasound surgery (FUS) into a single platform. MRI enables visualization of the target tissue and monitors ultrasound-induced effects in near real-time during FUS treatment. MRgFUS may serve as an adjunct or replace invasive surgery and radiotherapy for specific conditions. Its thermal effects ablate tumors in locations involved in movement disorders and essential tremors. Its nonthermal effects increase blood-brain barrier permeability to enhance delivery of therapeutics and other molecules. Copyright © 2017 Elsevier Inc. All rights reserved.

Reducing Behavior Problems Among Students with Autism Spectrum Disorder: Coaching Teachers in a Mixed-Reality Setting.

PubMed

Pas, Elise T; Johnson, Stacy R; Larson, Kristine E; Brandenburg, Linda; Church, Robin; Bradshaw, Catherine P

2016-12-01

Most approaches aiming to reduce behavior problems among youth with Autism Spectrum Disorder (ASD) focus on individual students; however, school personnel also need professional development to better support students. This study targeted teachers' skill development to promote positive outcomes for students with ASD. The sample included 19 teachers in two non-public special education settings serving students with moderate to severe ASD. Participating teachers received professional development and coaching in classroom management, with guided practice in a mixed-reality simulator. Repeated-measures ANOVAs examining externally-conducted classroom observations revealed statistically significant improvements in teacher management and student behavior over time. Findings suggest that coaching and guided practice in a mixed-reality simulator is perceived as acceptable and may reduce behavior problems among students with ASD.

[Publication activity of the Russian medicine in focus of national science policy: estimating the feasibility of policy targets].

PubMed

Starodubov, V I; Kuznetsov, S L; Kurakova, N G; Tsvetkova, L A; Aref'ev, P G; Ivanov, A V; Eremchenko, O A

2013-01-01

A comprehensive review of National research policy papers issued over the past 6 years was carried out. A set of problems concerning the quality of predicted values of some bibliometric indicators reflecting the level of research performance and publication activity that were declared in governmental documents was discussed. Basic metrics of scientific performance that should be required to achieve the goals declared in the recent governmental policy papers including President's Executive Order No 599 of May 7, 2012 (increasing the share of Russian researchers' publications in the total number of publications in international scientific journals indexed in the Web of Science up to 2.44% in 2015). Taking into account the current structure of modern global science in which papers in biomedical subjects make up for approximately one third of the total world scientific output, it becomes obvious how difficult is the governmental task set up to the researchers--to double the number of journal publications indexed in Web of Science in the short-term period of the nearest three years. The priorities and reasonable goal-oriented efforts to meet the targets are proposed in the paper.

MR-guided adaptive focusing of ultrasound

PubMed Central

Larrat, Benoît; Pernot, Mathieu; Montaldo, Gabriel; Fink, Mathias; Tanter, Mickaël

2010-01-01

Adaptive focusing of ultrasonic waves under the guidance of a Magnetic Resonance (MR) system is demonstrated for medical applications. This technique is based on the maximization of the ultrasonic wave intensity at one targeted point in space. The wave intensity is indirectly estimated from the local tissue displacement induced at the chosen focus by the acoustic radiation force of ultrasonic beams. Coded ultrasonic waves are transmitted by an ultrasonic array and an MRI scanner is used to measure the resulting local displacements through a motion sensitive MR sequence. After the transmission of a set of spatially encoded ultrasonic waves, a non iterative inversion process is employed to accurately estimate the spatial-temporal aberration induced by the propagation medium and to maximize the acoustical intensity at the target. Both programmable and physical aberrating layers introducing strong distortions (up to 2π radians) were recovered within acceptable errors (<0.8 rad). This non invasive technique is shown to accurately correct phase aberrations in a phantom gel with negligible heat deposition and limited acquisition time. These refocusing performances demonstrate a major potential in the field of MR-Guided Ultrasound Therapy in particular for transcranial brain HIFU. PMID:20704061

The role of sleep in cognitive processing: focusing on memory consolidation.

PubMed

Chambers, Alexis M

2017-05-01

Research indicates that sleep promotes various cognitive functions, such as decision-making, language, categorization, and memory. Of these, most work has focused on the influence of sleep on memory, with ample work showing that sleep enhances memory consolidation, a process that stores new memories in the brain over time. Recent psychological and neurophysiological research has vastly increased understanding of this process. Such work not only suggests that consolidation relies on plasticity-related mechanisms that reactivate and stabilize memory representations, but also that this process may be experimentally manipulated by methods that target which memory traces are reactivated during sleep. Furthermore, aside from memory storage capabilities, memory consolidation also appears to reorganize and integrate memories with preexisting knowledge, which may facilitate the discovery of underlying rules and associations that benefit other cognitive functioning, including problem solving and creativity. WIREs Cogn Sci 2017, 8:e1433. doi: 10.1002/wcs.1433 For further resources related to this article, please visit the WIREs website. © 2017 Wiley Periodicals, Inc.

Using spatial uncertainty to manipulate the size of the attention focus.

PubMed

Huang, Dan; Xue, Linyan; Wang, Xin; Chen, Yao

2016-09-01

Preferentially processing behaviorally relevant information is vital for primate survival. In visuospatial attention studies, manipulating the spatial extent of attention focus is an important question. Although many studies have claimed to successfully adjust attention field size by either varying the uncertainty about the target location (spatial uncertainty) or adjusting the size of the cue orienting the attention focus, no systematic studies have assessed and compared the effectiveness of these methods. We used a multiple cue paradigm with 2.5° and 7.5° rings centered around a target position to measure the cue size effect, while the spatial uncertainty levels were manipulated by changing the number of cueing positions. We found that spatial uncertainty had a significant impact on reaction time during target detection, while the cue size effect was less robust. We also carefully varied the spatial scope of potential target locations within a small or large region and found that this amount of variation in spatial uncertainty can also significantly influence target detection speed. Our results indicate that adjusting spatial uncertainty is more effective than varying cue size when manipulating attention field size.

Transcranial MR-Guided Focused Ultrasound: A Review of the Technology and Neuro Applications

PubMed Central

Ghanouni, Pejman; Pauly, Kim Butts; Elias, W. Jeff; Henderson, Jaimie; Sheehan, Jason; Monteith, Stephen; Wintermark, Max

2015-01-01

MR guided focused ultrasound is a new, minimally invasive method of targeted tissue thermal ablation that may be of use to treat central neuropathic pain, essential tremor, Parkinson tremor, and brain tumors. The system has also been used to temporarily disrupt the blood-brain barrier to allow targeted drug delivery to brain tumors. This article reviews the physical principles of MR guided focused ultrasound and discusses current and potential applications of this exciting technology. PMID:26102394

Deorbit targeting

NASA Technical Reports Server (NTRS)

Tempelman, W. H.

1973-01-01

The navigation and control of the space shuttle during atmospheric entry are discussed. A functional flow diagram presenting the basic approach to the deorbit targeting problem is presented. The major inputs to be considered are: (1) vehicle state vector, (2) landing site location, (3) entry interface parameters, (4) earliest desired time of landing, and (5) maximum cross range. Mathematical models of the navigational procedures based on controlled thrust times are developed.

Target-Rich Environment

ERIC Educational Resources Information Center

Perna, Mark C.

2005-01-01

Target marketing is defining school enrollment goals and then developing a strategic plan to accomplish those goals through the use of specific communication vehicles and community focus. It is critical to reach the right audience, with the right message, at the right time, for the right cost. In this brief article, the author describes several…

FOREWORD: Focus on Advanced Ceramics Focus on Advanced Ceramics

NASA Astrophysics Data System (ADS)

Ohashi, Naoki

2011-06-01

Much research has been devoted recently to developing technologies for renewable energy and improving the efficiency of the processes and devices used in industry and everyday life. Efficient solutions have been found using novel materials such as platinum and palladium-based catalysts for car exhaust systems, samarium-cobalt and neodymium-iron-boron permanent magnets for electrical motors, and so on. However, their realization has resulted in an increasing demand for rare elements and in their deficit, the development of new materials based on more abundant elements and new functionalities of traditional materials. Moreover, increasing environmental and health concerns demand substitution of toxic or hazardous substances with nature-friendly alternatives. In this context, this focus issue on advanced ceramics aims to review current trends in ceramics science and technology. It is related to the International Conference on Science and Technology of Advanced Ceramics (STAC) held annually to discuss the emerging issues in the field of ceramics. An important direction of ceramic science is the collaboration between experimental and theoretical sciences. Recent developments in density functional theory and computer technology have enabled the prediction of physical and chemical properties of ceramics, thereby assisting the design of new materials. Therefore, this focus issue includes articles devoted to theory and advanced characterization techniques. As mentioned above, the potential shortage of rare elements is becoming critical to the industry and has resulted in a Japanese government initiative called the 'Ubiquitous Element Strategy'. This focus issue also includes articles related to this strategy and to the associated topics of energy conversion, such as phosphors for high-efficiency lighting and photocatalysts for solar-energy harvesting. We hope that this focus issue will provide a timely overview of current trends and problems in ceramics science and

The effectiveness of return-to-work interventions that incorporate work-focused problem-solving skills for workers with sickness absences related to mental disorders: a systematic literature review.

PubMed

Dewa, Carolyn S; Loong, Desmond; Bonato, Sarah; Joosen, Margot C W

2015-06-15

This paper reviews the current state of the published peer-reviewed literature related to return-to-work (RTW) interventions that incorporate work-related problem-solving skills for workers with sickness absences related to mental disorders. It addresses the question: What is the evidence for the effectiveness of these RTW interventions? Using a multiphase screening process, this systematic literature review was based on publically available peer-reviewed studies. Five electronic databases were searched: (1) Medline Current, (2) Medline In-process, (3) PsycINFO, (4) Econlit and (5) Web of Science. The focus was on RTW interventions for workers with medically certified sickness absences related to mental disorders. Workers with medically certified sickness absences related to mental disorders. RTW intervention included work-focused problem-solving skills. RTW rates and length of sickness absences. There were 4709 unique citations identified. Of these, eight articles representing a total of six studies were included in the review. In terms of bias avoidance, two of the six studies were rated as excellent, two as good and two as weak. Five studies were from the Netherlands; one was from Norway. There was variability among the studies with regard to RTW findings. Two of three studies reported significant differences in RTW rates between the intervention and control groups. One of six studies observed a significant difference in sickness absence duration between intervention and control groups. There is limited evidence that combinations of interventions that include work-related problem-solving skills are effective in RTW outcomes. The evidence could be strengthened if future studies included more detailed examinations of intervention adherence and changes in problem-solving skills. Future studies should also examine the long-term effects of problem-solving skills on sickness absence recurrence and work productivity. Published by the BMJ Publishing Group Limited. For

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.

Enhancing chemistry problem-solving achievement using problem categorization

NASA Astrophysics Data System (ADS)

Bunce, Diane M.; Gabel, Dorothy L.; Samuel, John V.

The enhancement of chemistry students' skill in problem solving through problem categorization is the focus of this study. Twenty-four students in a freshman chemistry course for health professionals are taught how to solve problems using the explicit method of problem solving (EMPS) (Bunce & Heikkinen, 1986). The EMPS is an organized approach to problem analysis which includes encoding the information given in a problem (Given, Asked For), relating this to what is already in long-term memory (Recall), and planning a solution (Overall Plan) before a mathematical solution is attempted. In addition to the EMPS training, treatment students receive three 40-minute sessions following achievement tests in which they are taught how to categorize problems. Control students use this time to review the EMPS solutions of test questions. Although problem categorization is involved in one section of the EMPS (Recall), treatment students who received specific training in problem categorization demonstrate significantly higher achievement on combination problems (those problems requiring the use of more than one chemical topic for their solution) at (p = 0.01) than their counterparts. Significantly higher achievement for treatment students is also measured on an unannounced test (p = 0.02). Analysis of interview transcripts of both treatment and control students illustrates a Rolodex approach to problem solving employed by all students in this study. The Rolodex approach involves organizing equations used to solve problems on mental index cards and flipping through them, matching units given when a new problem is to be solved. A second phenomenon observed during student interviews is the absence of a link in the conceptual understanding of the chemical concepts involved in a problem and the problem-solving skills employed to correctly solve problems. This study shows that explicit training in categorization skills and the EMPS can lead to higher achievement in complex problem

Three-dimensional spatiotemporal focusing of holographic patterns

PubMed Central

Hernandez, Oscar; Papagiakoumou, Eirini; Tanese, Dimitrii; Fidelin, Kevin; Wyart, Claire; Emiliani, Valentina

2016-01-01

Two-photon excitation with temporally focused pulses can be combined with phase-modulation approaches, such as computer-generated holography and generalized phase contrast, to efficiently distribute light into two-dimensional, axially confined, user-defined shapes. Adding lens-phase modulations to 2D-phase holograms enables remote axial pattern displacement as well as simultaneous pattern generation in multiple distinct planes. However, the axial confinement linearly degrades with lateral shape area in previous reports where axially shifted holographic shapes were not temporally focused. Here we report an optical system using two spatial light modulators to independently control transverse- and axial-target light distribution. This approach enables simultaneous axial translation of single or multiple spatiotemporally focused patterns across the sample volume while achieving the axial confinement of temporal focusing. We use the system's capability to photoconvert tens of Kaede-expressing neurons with single-cell resolution in live zebrafish larvae. PMID:27306044

Children's Exposure to Violence: The Underlying Effect of Posttraumatic Stress Symptoms on Behavior Problems.

PubMed

Yoon, Susan; Steigerwald, Stacey; Holmes, Megan R; Perzynski, Adam T

2016-02-01

In this study we investigated whether witnessing violence and violence victimization were associated with children's internalizing and externalizing behavior problems and examined the mediating role of posttraumatic stress (PTS) symptoms in these relationships. Secondary data analysis was conducted using 3 waves of data from the National Survey of Child and Adolescent Well-Being. Path analyses were conducted to test direct and indirect effects of violence exposure on behavior problems, using 2,064 children (ages 8-15 years) reported to Child Protective Services for maltreatment. Being a victim of violence in the home was directly associated with more internalizing (β = .06, p = .007) and externalizing behavior problems (β = .07, p = .002), whereas witnessing violence was not directly related to either internalizing (β = .04, p = .056) or externalizing behavior problems (β = .03, p = .130). PTS symptoms mediated the effects of witnessing violence and violence victimization on internalizing behavior problems (β = .02, p = .002). Our findings suggest that PTS symptoms may be a mechanism underlying the association between violence exposure and internalizing behavior problems (R(2) = .23), underscoring the potential importance of assessing PTS symptoms and providing targeted trauma-focused interventions for children exposed to violence at home. Copyright © 2016 International Society for Traumatic Stress Studies.

Mitochondrial Targets for Pharmacological Intervention in Human Disease

PubMed Central

2015-01-01

Over the past several years, mitochondrial dysfunction has been linked to an increasing number of human illnesses, making mitochondrial proteins (MPs) an ever more appealing target for therapeutic intervention. With 20% of the mitochondrial proteome (312 of an estimated 1500 MPs) having known interactions with small molecules, MPs appear to be highly targetable. Yet, despite these targeted proteins functioning in a range of biological processes (including induction of apoptosis, calcium homeostasis, and metabolism), very few of the compounds targeting MPs find clinical use. Recent work has greatly expanded the number of proteins known to localize to the mitochondria and has generated a considerable increase in MP 3D structures available in public databases, allowing experimental screening and in silico prediction of mitochondrial drug targets on an unprecedented scale. Here, we summarize the current literature on clinically active drugs that target MPs, with a focus on how existing drug targets are distributed across biochemical pathways and organelle substructures. Also, we examine current strategies for mitochondrial drug discovery, focusing on genetic, proteomic, and chemogenomic assays, and relevant model systems. As cell models and screening techniques improve, MPs appear poised to emerge as relevant targets for a wide range of complex human diseases, an eventuality that can be expedited through systematic analysis of MP function. PMID:25367773

Dynamics of laser-driven proton beam focusing and transport into solid density matter

NASA Astrophysics Data System (ADS)

Kim, J.; McGuffey, C.; Beg, F.; Wei, M.; Mariscal, D.; Chen, S.; Fuchs, J.

2016-10-01

Isochoric heating and local energy deposition capabilities make intense proton beams appealing for studying high energy density physics and the Fast Ignition of inertial confinement fusion. To study proton beam focusing that results in high beam density, experiments have been conducted using different target geometries irradiated by a kilojoule, 10 ps pulse of the OMEGA EP laser. The beam focus was measured by imaging beam-induced Cu K-alpha emission on a Cu foil that was positioned at a fixed distance. Compared to a free target, structured targets having shapes of wedge and cone show a brighter and narrower K-alpha radiation emission spot on a Cu foil indicating higher beam focusability. Experimentally observed images with proton radiography demonstrate the existence of transverse fields on the structures. Full-scale simulations including the contribution of a long pulse duration of the laser confirm that such fields can be caused by hot electrons moving through the structures. The simulated fields are strong enough to reflect the diverging main proton beam and pinch a transverse probe beam. Detailed simulation results including the beam focusing and transport of the focused intense proton beam in Cu foil will be presented. This work was supported by the National Laser User Facility Program through Award DE-NA0002034.

Understanding Individual Problem-Solving Style: A Key to Learning and Applying Creative Problem Solving

ERIC Educational Resources Information Center

Treffinger, Donald J.; Selby, Edwin C.; Isaksen, Scott G.

2008-01-01

More than five decades of research and development have focused on making the Creative Problem Solving process and tools accessible across a wide range of ages and contexts. Recent evidence indicates that when individuals, in both school and corporate settings, understand their own style of problem solving, they are able to learn and apply process…

Transcription Factors as Therapeutic Targets in Chronic Kidney Disease.

PubMed

Hishikawa, Akihito; Hayashi, Kaori; Itoh, Hiroshi

2018-05-09

The growing number of patients with chronic kidney disease (CKD) is recognized as an emerging problem worldwide. Recent studies have indicated that deregulation of transcription factors is associated with the onset or progression of kidney disease. Several clinical trials indicated that regression of CKD may be feasible via activation of the transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2), which suggests that transcription factors may be potential drug targets for CKD. Agents stabilizing hypoxia-inducible factor (HIF), which may be beneficial for renal anemia and renal protection, are also now under clinical trial. Recently, we have reported that the transcription factor Kruppel-like factor 4 (KLF4) regulates the glomerular podocyte epigenome, and that the antiproteinuric effect of the renin⁻angiotensin system blockade may be partially mediated by KLF4. KLF4 is one of the Yamanaka factors that induces iPS cells and is reported to be involved in epigenetic remodeling. In this article, we summarize the transcription factors associated with CKD and particularly focus on the possibility of transcription factors being novel drug targets for CKD through epigenetic modulation.

Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior.

PubMed

Burgess, Alison; Dubey, Sonam; Yeung, Sharon; Hough, Olivia; Eterman, Naomi; Aubert, Isabelle; Hynynen, Kullervo

2014-12-01

To validate whether repeated magnetic resonance (MR) imaging-guided focused ultrasound treatments targeted to the hippocampus, a brain structure relevant for Alzheimer disease ( AD Alzheimer disease ), could modulate pathologic abnormalities, plasticity, and behavior in a mouse model. All animal procedures were approved by the Animal Care Committee and are in accordance with the Canadian Council on Animal Care. Seven-month-old transgenic (TgCRND8) (Tg) mice and their nontransgenic (non-Tg) littermates were entered in the study. Mice were treated weekly with MR imaging-guided focused ultrasound in the bilateral hippocampus (1.68 MHz, 10-msec bursts, 1-Hz burst repetition frequency, 120-second total duration). After 1 month, spatial memory was tested in the Y maze with the novel arm prior to sacrifice and immunohistochemical analysis. The data were compared by using unpaired t tests and analysis of variance with Tukey post hoc analysis. Untreated Tg mice spent 61% less time than untreated non-Tg mice exploring the novel arm of the Y maze because of spatial memory impairments (P < .05). Following MR imaging-guided focused ultrasound, Tg mice spent 99% more time exploring the novel arm, performing as well as their non-Tg littermates. Changes in behavior were correlated with a reduction of the number and size of amyloid plaques in the MR imaging-guided focused ultrasound-treated animals (P < .01). Further, after MR imaging-guided focused ultrasound treatment, there was a 250% increase in the number of newborn neurons in the hippocampus (P < .01). The newborn neurons had longer dendrites and more arborization after MR imaging-guided focused ultrasound, as well (P < .01). Repeated MR imaging-guided focused ultrasound treatments led to spatial memory improvement in a Tg mouse model of AD Alzheimer disease . The behavior changes may be mediated by decreased amyloid pathologic abnormalities and increased neuronal plasticity. © RSNA, 2014.

Age differences in everyday problem-solving effectiveness: older adults select more effective strategies for interpersonal problems.

PubMed

Blanchard-Fields, Fredda; Mienaltowski, Andrew; Seay, Renee Baldi

2007-01-01

Using the Everyday Problem Solving Inventory of Cornelius and Caspi, we examined differences in problem-solving strategy endorsement and effectiveness in two domains of everyday functioning (instrumental or interpersonal, and a mixture of the two domains) and for four strategies (avoidance-denial, passive dependence, planful problem solving, and cognitive analysis). Consistent with past research, our research showed that older adults were more problem focused than young adults in their approach to solving instrumental problems, whereas older adults selected more avoidant-denial strategies than young adults when solving interpersonal problems. Overall, older adults were also more effective than young adults when solving everyday problems, in particular for interpersonal problems.

Teaching Thinking and Problem Solving.

ERIC Educational Resources Information Center

Bransford, John; And Others

1986-01-01

This article focuses on two approaches to teaching reasoning and problem solving. One emphasizes the role of domain-specific knowledge; the other emphasizes general strategic and metacognitive knowledge. Many instructional programs are based on the latter approach. The article concludes that these programs can be strengthened by focusing on domain…

Unification of automatic target tracking and automatic target recognition

NASA Astrophysics Data System (ADS)

Schachter, Bruce J.

2014-06-01

The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT∪ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

Teachers' ICT and Problem-Solving Skills: Competencies and Needs. Education Indicators in Focus. No. 40

ERIC Educational Resources Information Center

OECD Publishing, 2016

2016-01-01

The education sector performs well for information and communication technology (ICT) and problem-solving skills, although it still lags behind the professional, scientific and technical activities sector. Primary and secondary teachers have better ICT and problem-solving skills than the general population, and similar skills to other…

A focus group study of predictors of relapse in electronic gaming machine problem gambling, part 2: factors that 'pull' the gambler away from relapse.

PubMed

Oakes, J; Pols, R; Battersby, M; Lawn, S; Pulvirenti, M; Smith, D

2012-09-01

This study aimed to develop an empirically based description of relapse in Electronic Gaming Machine (EGM) problem gambling (PG) by describing the processes and factors that 'pull' the problem gambler away from relapse contrasted with the 'push' towards relapse. These conceptualisations describe two opposing, interacting emotional processes occurring within the problem gambler during any relapse episode. Each relapse episode comprises a complex set of psychological and social behaviours where many factors interact sequentially and simultaneously within the problem gambler to produce a series of mental and behaviour events that end (1) with relapse where 'push' overcomes 'pull' or (2) continued abstinence where 'pull' overcomes 'push'. Four focus groups comprising thirty participants who were EGM problem gamblers, gamblers' significant others, therapists and counsellors described their experiences and understanding of relapse. The groups were recorded, recordings were then transcribed and analysed using thematic textual analysis. It was established that vigilance, motivation to commit to change, positive social support, cognitive strategies such as remembering past gambling harms or distraction techniques to avoid thinking about gambling to enable gamblers to manage the urge to gamble and urge extinction were key factors that protected against relapse. Three complementary theories emerged from the analysis. Firstly, a process of reappraisal of personal gambling behaviour pulls the gambler away from relapse. This results in a commitment to change that develops over time and affects but is independent of each episode of relapse. Secondly, relapse may be halted by interacting factors that 'pull' the problem gambler away from the sequence of mental and behavioural events, which follow the triggering of the urge and cognitions to gamble. Thirdly, urge extinction and apparent 'cure' is possible for EGM gambling. This study provides a qualitative, empirical model for

Investigating Problem-Solving Perseverance Using Lesson Study

ERIC Educational Resources Information Center

Bieda, Kristen N.; Huhn, Craig

2017-01-01

Problem solving has long been a focus of research and curriculum reform (Kilpatrick 1985; Lester 1994; NCTM 1989, 2000; CCSSI 2010). The importance of problem solving is not new, but the Common Core introduced the idea of making sense of problems and persevering in solving them (CCSSI 2010, p. 6) as an aspect of problem solving. Perseverance is…

Living With Diabetes in Appalachia: A Focus Group Study.

PubMed

Carpenter, Roger; Smith, Mary Jane

This article presents an innovative holistic practice application based on evidence from a focus group study on managing diabetes. The purpose of this study addressed the research question: How do persons with type 2 diabetes describe ways of managing the challenge of living with diabetes? A second purpose was to link the findings on ways to manage diabetes to holistic nursing practice through story theory. Nine adults with type 2 diabetes living in rural West Virginia participated in 3 focus groups. Using content analysis, the study findings integrated themes with core qualities, and are as follows: living life as an evolving process is awakening to the present and doing it your way, being on guard is a vigilant ongoing responsibility, attending to bodily experience is awareness of body and facing life stress, and knowing the consequences is awareness of potential problems and taking charge. Merging the study findings with the concepts of story theory led to the development of an innovative practice application for managing diabetes. Managing diabetes in this practice application goes beyond problem-centeredness to a patient-centered approach, offering attention to individual preferences. Since managing diabetes is a major problem in Appalachia, there a need for innovative approaches. This study adds to the body of knowledge on how persons from Appalachia manage diabetes. In addition, it offers a story practice approach for managing diabetes-replacing a problem focus to a more holistic approach to practice leading to more meaningful and fulfilling outcomes.

Experimental detection and focusing in shallow water by decomposition of the time reversal operator.

PubMed

Prada, Claire; de Rosny, Julien; Clorennec, Dominique; Minonzio, Jean-Gabriel; Aubry, Alexandre; Fink, Mathias; Berniere, Lothar; Billand, Philippe; Hibral, Sidonie; Folegot, Thomas

2007-08-01

A rigid 24-element source-receiver array in the 10-15 kHz frequency band, connected to a programmable electronic system, was deployed in the Bay of Brest during spring 2005. In this 10- to 18-m-deep environment, backscattered data from submerged targets were recorded. Successful detection and focusing experiments in very shallow water using the decomposition of the time reversal operator (DORT method) are shown. The ability of the DORT method to separate the echo of a target from reverberation as well as the echo from two different targets at 250 m is shown. An example of active focusing within the waveguide using the first invariant of the time reversal operator is presented, showing the enhanced focusing capability. Furthermore, the localization of the scatterers in the water column is obtained using a range-dependent acoustic model.

High-intensity focused ultrasound: advances in technology and experimental trials support enhanced utility of focused ultrasound surgery in oncology

PubMed Central

Malietzis, G; Monzon, L; Hand, J; Wasan, H; Leen, E; Abel, M; Muhammad, A; Abel, P

2013-01-01

High-intensity focused ultrasound (HIFU) is a rapidly maturing technology with diverse clinical applications. In the field of oncology, the use of HIFU to non-invasively cause tissue necrosis in a defined target, a technique known as focused ultrasound surgery (FUS), has considerable potential for tumour ablation. In this article, we outline the development and underlying principles of HIFU, overview the limitations and commercially available equipment for FUS, then summarise some of the recent technological advances and experimental clinical trials that we predict will have a positive impact on extending the role of FUS in cancer therapy. PMID:23403455

Off-target model based OPC

NASA Astrophysics Data System (ADS)

Lu, Mark; Liang, Curtis; King, Dion; Melvin, Lawrence S., III

2005-11-01

Model-based Optical Proximity correction has become an indispensable tool for achieving wafer pattern to design fidelity at current manufacturing process nodes. Most model-based OPC is performed considering the nominal process condition, with limited consideration of through process manufacturing robustness. This study examines the use of off-target process models - models that represent non-nominal process states such as would occur with a dose or focus variation - to understands and manipulate the final pattern correction to a more process robust configuration. The study will first examine and validate the process of generating an off-target model, then examine the quality of the off-target model. Once the off-target model is proven, it will be used to demonstrate methods of generating process robust corrections. The concepts are demonstrated using a 0.13 μm logic gate process. Preliminary indications show success in both off-target model production and process robust corrections. With these off-target models as tools, mask production cycle times can be reduced.

Facility target insert shielding assessment

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

Mocko, Michal

2015-10-06

Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In themore » present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.« less

Focus information is used to interpret binocular images

PubMed Central

Hoffman, David M.; Banks, Martin S.

2011-01-01

Focus information—blur and accommodation—is highly correlated with depth in natural viewing. We examined the use of focus information in solving the binocular correspondence problem and in interpreting monocular occlusions. We presented transparent scenes consisting of two planes. Observers judged the slant of the farther plane, which was seen through the nearer plane. To do this, they had to solve the correspondence problem. In one condition, the two planes were presented with sharp rendering on one image plane, as is done in conventional stereo displays. In another condition, the planes were presented on two image planes at different focal distances, simulating focus information in natural viewing. Depth discrimination performance improved significantly when focus information was correct, which shows that the visual system utilizes the information contained in depth-of-field blur in solving binocular correspondence. In a second experiment, we presented images in which one eye could see texture behind an occluder that the other eye could not see. When the occluder's texture was sharp along with the occluded texture, binocular rivalry was prominent. When the occluded and occluding textures were presented with different blurs, rivalry was significantly reduced. This shows that blur aids the interpretation of scene layout near monocular occlusions. PMID:20616139

Particle Accelerator Focus Automation

NASA Astrophysics Data System (ADS)

Lopes, José; Rocha, Jorge; Redondo, Luís; Cruz, João

2017-08-01

The Laboratório de Aceleradores e Tecnologias de Radiação (LATR) at the Campus Tecnológico e Nuclear, of Instituto Superior Técnico (IST) has a horizontal electrostatic particle accelerator based on the Van de Graaff machine which is used for research in the area of material characterization. This machine produces alfa (He+) and proton (H+) beams of some μA currents up to 2 MeV/q energies. Beam focusing is obtained using a cylindrical lens of the Einzel type, assembled near the high voltage terminal. This paper describes the developed system that automatically focuses the ion beam, using a personal computer running the LabVIEW software, a multifunction input/output board and signal conditioning circuits. The focusing procedure consists of a scanning method to find the lens bias voltage which maximizes the beam current measured on a beam stopper target, which is used as feedback for the scanning cycle. This system, as part of a wider start up and shut down automation system built for this particle accelerator, brings great advantages to the operation of the accelerator by turning it faster and easier to operate, requiring less human presence, and adding the possibility of total remote control in safe conditions.

Multipass Target Search in Natural Environments

PubMed Central

Otte, Michael W.; Sofge, Donald; Gupta, Satyandra K.

2017-01-01

Consider a disaster scenario where search and rescue workers must search difficult to access buildings during an earthquake or flood. Often, finding survivors a few hours sooner results in a dramatic increase in saved lives, suggesting the use of drones for expedient rescue operations. Entropy can be used to quantify the generation and resolution of uncertainty. When searching for targets, maximizing mutual information of future sensor observations will minimize expected target location uncertainty by minimizing the entropy of the future estimate. Motion planning for multi-target autonomous search requires planning over an area with an imperfect sensor and may require multiple passes, which is hindered by the submodularity property of mutual information. Further, mission duration constraints must be handled accordingly, requiring consideration of the vehicle’s dynamics to generate feasible trajectories and must plan trajectories spanning the entire mission duration, something which most information gathering algorithms are incapable of doing. If unanticipated changes occur in an uncertain environment, new plans must be generated quickly. In addition, planning multipass trajectories requires evaluating path dependent rewards, requiring planning in the space of all previously selected actions, compounding the problem. We present an anytime algorithm for autonomous multipass target search in natural environments. The algorithm is capable of generating long duration dynamically feasible multipass coverage plans that maximize mutual information using a variety of techniques such as ϵ-admissible heuristics to speed up the search. To the authors’ knowledge this is the first attempt at efficiently solving multipass target search problems of such long duration. The proposed algorithm is based on best first branch and bound and is benchmarked against state of the art algorithms adapted to the problem in natural Simplex environments, gathering the most information in the

Targeted Therapies in NSCLC: Emerging oncogene targets following the success of EGFR

PubMed Central

Berge, Eamon M; Doebele, Robert C

2014-01-01

The diagnostic testing, treatment and prognosis of non-small cell lung cancer (NSCLC) has undergone a paradigm shift since the discovery of sensitizing mutations in the epidermal growth factor receptor (EGFR) gene in a subset of NSCLC patients. Several additional oncogenic mutations, including gene fusions and amplifications have since been discovered, with a number of drugs that target each specific oncogene. This review focuses on oncogenes in NSCLC other than EGFR and their companion ‘targeted therapies’. Particular emphasis is placed on the role of ALK, ROS1, RET, MET, BRAF, and HER2 in NSCLC. PMID:24565585

Multiple shell fusion targets

DOEpatents

Lindl, J.D.; Bangerter, R.O.

1975-10-31

Multiple shell fusion targets for use with electron beam and ion beam implosion systems are described. The multiple shell targets are of the low-power type and use a separate relatively low Z, low density ablator at large radius for the outer shell, which reduces the focusing and power requirements of the implosion system while maintaining reasonable aspect ratios. The targets use a high Z, high density pusher shell placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. For example, with ion beams as a power source, breakeven at 10-20 Terrawatts with 10 MeV alpha particles for imploding a multiple shell target can be accomplished.

Active Debris Removal of Multiple Priority Targets

NASA Astrophysics Data System (ADS)

Braun, Vitali; Flegel, Sven Kevin; Vörsmann, Peter; Wiedemann, Carsten; Gelhaus, Johannes; Moeckel, Marek; Kebschull, Christopher

2012-07-01

Today's space debris environment shows major concentrations of objects within distinct orbital regions for nearly all size regimes. The most critical region is found at orbital altitudes near 800 kilometers with high declinations. Within this region many satellites are operated in so called sun-synchronous orbits (SSO). Among those, there are Earth observation, communication and weather satellites. Due to the orbital geometry, head-on encounters with relative velocities of about 15 km/s are most probable and would thus result in highly energetic collisions, which are often referred to as catastrophic collisions, leading to the complete fragmentation of the participating objects. So called feedback collisions can then be triggered by the newly generated fragments, thus leading to a further population increase in the affected orbital region. This effect is known as the Kessler syndrome. Current studies show that catastrophic collisions are not a major problem today, but will become the main process for debris generation within the SSO region in the near future, even without any future launches. In order to avoid this effect, objects with a major impact on collisional cascading have to be actively removed from the critical region after their end of life. Not having the capability to perform an end-of-life maneuver in order to transfer to a graveyard orbit or to de-orbit, many satellites and rocket bodies would have to be de-orbited within a dedicated mission. In such a mission, a service satellite would perform a de-orbit maneuver, after having docked to a specific target. In this paper several systems, e.g. chemical and electrical engines are analysed with the main focus on removing multiple targets within one single mission. The service satellite has to undock from the previously de-orbited target in order to start the rendezvous and docking phase for a subsequent target. The targets are chosen from a previously defined priority list in order to enhance the mission

Ranking targets in structure-based virtual screening of three-dimensional protein libraries: methods and problems.

PubMed

Kellenberger, Esther; Foata, Nicolas; Rognan, Didier

2008-05-01

Structure-based virtual screening is a promising tool to identify putative targets for a specific ligand. Instead of docking multiple ligands into a single protein cavity, a single ligand is docked in a collection of binding sites. In inverse screening, hits are in fact targets which have been prioritized within the pool of best ranked proteins. The target rate depends on specificity and promiscuity in protein-ligand interactions and, to a considerable extent, on the effectiveness of the scoring function, which still is the Achilles' heel of molecular docking. In the present retrospective study, virtual screening of the sc-PDB target library by GOLD docking was carried out for four compounds (biotin, 4-hydroxy-tamoxifen, 6-hydroxy-1,6-dihydropurine ribonucleoside, and methotrexate) of known sc-PDB targets and, several ranking protocols based on GOLD fitness score and topological molecular interaction fingerprint (IFP) comparison were evaluated. For the four investigated ligands, the fusion of GOLD fitness and two IFP scores allowed the recovery of most targets, including the rare proteins which are not readily suitable for statistical analysis, while significantly filtering out most false positive entries. The current survey suggests that selecting a small number of targets (<20) for experimental evaluation is achievable with a pure structure-based approach.

Targeted therapy in esophageal cancer.

PubMed

Zhang, Lei; Ma, Jiaojiao; Han, Yu; Liu, Jinqiang; Zhou, Wei; Hong, Liu; Fan, Daiming

2016-01-01

An increasing number of patients are diagnosed with esophageal cancer at an advanced stages, and only a small group of them can benefit from the traditional chemotherapy and radiotherapy. So far, multiple monoclonal antibodies and tyrosine kinase inhibitors have been developed, alone or in combination with traditional therapy, to improve the prognosis of patients with advanced esophageal cancer. This review summarizes the recent advances of targeted therapies against EGFR, HER2, VEGFR and c-MET in esophageal cancer. More clinical trials should be performed to evaluate the efficacy and safety of various targeted therapy regimens. Future basic research should focus on investigating the molecular mechanisms of therapeutic targets in esophageal cancer.

Tour of a simple trigonometry problem

NASA Astrophysics Data System (ADS)

Poon, Kin-Keung

2012-06-01

This article focuses on a simple trigonometric problem that generates a strange phenomenon when different methods are applied to tackling it. A series of problem-solving activities are discussed, so that students can be alerted that the precision of diagrams is important when solving geometric problems. In addition, the problem-solving plan was implemented in a high school and the results indicated that students are relatively weak in problem-solving abilities but they understand and appreciate the thinking process in different stages and steps of the activities.

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.

A SYSTEMATIC REVIEW OF INTERVENTIONS TARGETING PATERNAL MENTAL HEALTH IN THE PERINATAL PERIOD.

PubMed

Rominov, Holly; Pilkington, Pamela D; Giallo, Rebecca; Whelan, Thomas A

2016-05-01

Interventions targeting parents' mental health in the perinatal period are critical due to potential consequences of perinatal mental illness for the parent, the infant, and their family. To date, most programs have targeted mothers. This systematic review explores the current status and evidence for intervention programs aiming to prevent or treat paternal mental illness in the perinatal period. Electronic databases were systematically searched to identify peer-reviewed studies that described an intervention targeting fathers' mental health in the perinatal period. Mental health outcomes included depression, anxiety, and stress as well as more general measures of psychological functioning. Eleven studies were identified. Three of five psychosocial interventions and three massage-technique interventions reported significant effects. None of the couple-based interventions reported significant effects. A number of methodological limitations were identified, including inadequate reporting of study designs, and issues with the timing of interventions. The variability in outcomes measures across the studies made it difficult to evaluate the overall effectiveness of the interventions. Father-focused interventions aimed at preventing perinatal mood problems will be improved if future studies utilize more rigorous research strategies. © 2016 Michigan Association for Infant Mental Health.

A semantic problem solving environment for integrative parasite research: identification of intervention targets for Trypanosoma cruzi.

PubMed

Parikh, Priti P; Minning, Todd A; Nguyen, Vinh; Lalithsena, Sarasi; Asiaee, Amir H; Sahoo, Satya S; Doshi, Prashant; Tarleton, Rick; Sheth, Amit P

2012-01-01

Research on the biology of parasites requires a sophisticated and integrated computational platform to query and analyze large volumes of data, representing both unpublished (internal) and public (external) data sources. Effective analysis of an integrated data resource using knowledge discovery tools would significantly aid biologists in conducting their research, for example, through identifying various intervention targets in parasites and in deciding the future direction of ongoing as well as planned projects. A key challenge in achieving this objective is the heterogeneity between the internal lab data, usually stored as flat files, Excel spreadsheets or custom-built databases, and the external databases. Reconciling the different forms of heterogeneity and effectively integrating data from disparate sources is a nontrivial task for biologists and requires a dedicated informatics infrastructure. Thus, we developed an integrated environment using Semantic Web technologies that may provide biologists the tools for managing and analyzing their data, without the need for acquiring in-depth computer science knowledge. We developed a semantic problem-solving environment (SPSE) that uses ontologies to integrate internal lab data with external resources in a Parasite Knowledge Base (PKB), which has the ability to query across these resources in a unified manner. The SPSE includes Web Ontology Language (OWL)-based ontologies, experimental data with its provenance information represented using the Resource Description Format (RDF), and a visual querying tool, Cuebee, that features integrated use of Web services. We demonstrate the use and benefit of SPSE using example queries for identifying gene knockout targets of Trypanosoma cruzi for vaccine development. Answers to these queries involve looking up multiple sources of data, linking them together and presenting the results. The SPSE facilitates parasitologists in leveraging the growing, but disparate, parasite data

Transcostal high-intensity-focused ultrasound: ex vivo adaptive focusing feasibility study

PubMed Central

Aubry, Jean-François; Pernot, Mathieu; Marquet, Fabrice; Tanter, Mickaël; Fink, Mathias

2008-01-01

Ex vivo experiments have been conducted through excised pork rib with bone, cartilage, muscle and skin. The aberrating effect of the ribcage has been experimentally evaluated. Adaptive ultrasonic focusing through ribs has been studied at low power. Without any correction, the pressure fields in the focal plane were both affected by inhomogeneous attenuation and phase distortion and three main effects were observed: a mean 2 mm shift of the main lobe, a mean 1.25 mm spreading of the half width of the main lobe and up to 20 dB increase of the secondary lobe level. Thanks to time reversal focusing, a 5-dB decrease in the secondary lobes was obtained and the ratio between the energy deposited at the target location and the total amount of energy emitted by the therapeutic array was 6 times higher than without correction. Time reversal minimizes the heating of the ribs by automatically sonicating between the ribs, as demonstrated by temperature measurements using thermocouples placed at different location on the ribcage. It is also discussed how this aberration correction process could be achieved non invasively for clinical application. PMID:18475006

Alcohol highway safety : problem update

DOT National Transportation Integrated Search

1998-04-01

Author's abstract: This document examines new literature and data on selected alcohol-crash targets or problems that have become available since the November 1989 State of Knowledge review. Specifically, this update addresses research since the 1989 ...

LEGO Robotics: An Authentic Problem Solving Tool?

ERIC Educational Resources Information Center

Castledine, Alanah-Rei; Chalmers, Chris

2011-01-01

With the current curriculum focus on correlating classroom problem solving lessons to real-world contexts, are LEGO robotics an effective problem solving tool? This present study was designed to investigate this question and to ascertain what problem solving strategies primary students engaged with when working with LEGO robotics and whether the…

Psychosocial interventions for disruptive behaviour problems in children in low- and middle-income countries: a systematic review and meta-analysis.

PubMed

Burkey, Matthew D; Hosein, Megan; Morton, Isabella; Purgato, Marianna; Adi, Ahmad; Kurzrok, Mark; Kohrt, Brandon A; Tol, Wietse A

2018-04-06

Most of the evidence for psychosocial interventions for disruptive behaviour problems comes from Western, high-income countries. The transferability of this evidence to culturally diverse, low-resource settings with few mental health specialists is unknown. We conducted a systematic review with random-effects meta-analysis of randomized controlled trials examining the effects of psychosocial interventions on reducing behaviour problems among children (under 18) living in low- and middle-income countries (LMIC). Twenty-six randomized controlled trials (representing 28 psychosocial interventions), evaluating 4,441 subjects, met selection criteria. Fifteen (54%) prevention interventions targeted general or at-risk populations, whereas 13 (46%) treatment interventions targeted children selected for elevated behaviour problems. Most interventions were delivered in group settings (96%) and half (50%) were administered by non-specialist providers. The overall effect (standardized mean difference, SMD) of prevention studies was -0.25 (95% confidence interval (CI): -0.41 to -0.09; I 2 : 78%) and of treatment studies was -0.56 (95% CI: -0.51 to -0.24; I 2 : 74%). Subgroup analyses demonstrated effectiveness for child-focused (SMD: -0.35; 95% CI: -0.57 to -0.14) and behavioural parenting interventions (SMD: -0.43; 95% CI: -0.66 to -0.20), and that interventions were effective across age ranges. Our meta-analysis supports the use of psychosocial interventions as a feasible and effective way to reduce disruptive behaviour problems among children in LMIC. Our study provides strong evidence for child-focused and behavioural parenting interventions, interventions across age ranges and interventions delivered in groups. Additional research is needed on training and supervision of non-specialists and on implementation of effective interventions in LMIC settings. © 2018 Association for Child and Adolescent Mental Health.

Curation of inhibitor-target data: process and impact on pathway analysis.

PubMed

Devidas, Sreenivas

2009-01-01

The past decade has seen a significant emergence in the availability and use of pathway analysis tools. The workflow that is supported by most of the pathway analysis tools is limited to either of the following: a. a network of genes based on the input data set, or b. the resultant network filtered down by a few criteria such as (but not limited to) i. disease association of the genes in the network; ii. targets known to be the target of one or more launched drugs; iii. targets known to be the target of one or more compounds in clinical trials; and iv. targets reasonably known to be potential candidate or clinical biomarkers. Almost all the tools in use today are biased towards the biological side and contain little, if any, information on the chemical inhibitors associated with the components of a given biological network. The limitation resides as follows: The fact that the number of inhibitors that have been published or patented is probably several fold (probably greater than 10-fold) more than the number of published protein-protein interactions. Curation of such data is both expensive and time consuming and could impact ROI significantly. The non-standardization associated with protein and gene names makes mapping reasonably non-straightforward. The number of patented and published inhibitors across target classes increases by over a million per year. Therefore, keeping the databases current becomes a monumental problem. Modifications required in the product architectures to accommodate chemistry-related content. GVK Bio has, over the past 7 years, curated the compound-target data that is necessary for the addition of such compound-centric workflows. This chapter focuses on identification, curation and utility of such data.

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

PubMed Central

Joshi, Bishnu P.; Wang, Thomas D.

2010-01-01

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. PMID:22180839

Sensor Compromise Detection in Multiple-Target Tracking Systems

PubMed Central

Doucette, Emily A.; Curtis, Jess W.

2018-01-01

Tracking multiple targets using a single estimator is a problem that is commonly approached within a trusted framework. There are many weaknesses that an adversary can exploit if it gains control over the sensors. Because the number of targets that the estimator has to track is not known with anticipation, an adversary could cause a loss of information or a degradation in the tracking precision. Other concerns include the introduction of false targets, which would result in a waste of computational and material resources, depending on the application. In this work, we study the problem of detecting compromised or faulty sensors in a multiple-target tracker, starting with the single-sensor case and then considering the multiple-sensor scenario. We propose an algorithm to detect a variety of attacks in the multiple-sensor case, via the application of finite set statistics (FISST), one-class classifiers and hypothesis testing using nonparametric techniques. PMID:29466314

Supervised target detection in hyperspectral images using one-class Fukunaga-Koontz Transform

NASA Astrophysics Data System (ADS)

Binol, Hamidullah; Bal, Abdullah

2016-05-01

A novel hyperspectral target detection technique based on Fukunaga-Koontz transform (FKT) is presented. FKT offers significant properties for feature selection and ordering. However, it can only be used to solve multi-pattern classification problems. Target detection may be considered as a two-class classification problem, i.e., target versus background clutter. Nevertheless, background clutter typically contains different types of materials. That's why; target detection techniques are different than classification methods by way of modeling clutter. To avoid the modeling of the background clutter, we have improved one-class FKT (OC-FKT) for target detection. The statistical properties of target training samples are used to define tunnel-like boundary of the target class. Non-target samples are then created synthetically as to be outside of the boundary. Thus, only limited target samples become adequate for training of FKT. The hyperspectral image experiments confirm that the proposed OC-FKT technique provides an effective means for target detection.

Focus group discussion in mathematical physics learning

NASA Astrophysics Data System (ADS)

Ellianawati; Rudiana, D.; Sabandar, J.; Subali, B.

2018-03-01

The Focus Group Discussion (FGD) activity in Mathematical Physics learning has helped students perform the stages of problem solving reflectively. The FGD implementation was conducted to explore the problems and find the right strategy to improve the students' ability to solve the problem accurately which is one of reflective thinking component that has been difficult to improve. The research method used is descriptive qualitative by using single subject response in Physics student. During the FGD process, one student was observed of her reflective thinking development in solving the physics problem. The strategy chosen in the discussion activity was the Cognitive Apprenticeship-Instruction (CA-I) syntax. Based on the results of this study, it is obtained the information that after going through a series of stages of discussion, the students' reflective thinking skills is increased significantly. The scaffolding stage in the CA-I model plays an important role in the process of solving physics problems accurately. Students are able to recognize and formulate problems by describing problem sketches, identifying the variables involved, applying mathematical equations that accord to physics concepts, executing accurately, and applying evaluation by explaining the solution to various contexts.

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.

A personalized and control systems engineering conceptual approach to target childhood anxiety in the contexts of cultural diversity.

PubMed

Pina, Armando A; Holly, Lindsay E; Zerr, Argero A; Rivera, Daniel E

2014-01-01

In the child and adolescent anxiety area, some progress has been made to develop evidence-based prevention protocols, but less is known about how to best target these problems in children and families of color. In general, data show differential program effects with some minority children benefiting significantly less. Our preliminary data, however, show promise and suggest cultural parameters to consider in the tailoring process beyond language and cultural symbols. It appears that a more focused approach to culture might help activate intervention components and its intended effects by focusing, for example, on the various facets of familismo when working with some Mexican parents. However, testing the effects and nuances of cultural adaption vis-à-vis a focused personalized approach is methodologically challenging. For this reason, we identify control systems engineering design methods and provide example scenarios relevant to our data and recent intervention work.

Backscattering of sound from targets in an Airy caustic formed by a curved reflecting surface

NASA Astrophysics Data System (ADS)

Dzikowicz, Benjamin Robert

The focusing of a caustic associated with the reflection of a locally curved sea floor or surface affects the scattering of sound by underwater targets. The most elementary caustic formed when sound reflects off a naturally curved surface is an Airy caustic. The case of a spherical target is examined here. With a point source acting also as a receiver, a point target lying in a shadow region returns only one echo directly from the target. When the target is on the Airy caustic, there are two echoes: one path is directly to the target and the other focuses off the curved surface. Echoes may be focused in both directions, the doubly focused case being the largest and the latest echo. With the target in the lit region, these different paths produce multiple echoes. For a finite sized sphere near an Airy caustic, all these echoes are manifest, but they occur at shifted target positions. Echoes of tone bursts reflecting only once overlap and interfere with each other, as do those reflecting twice. Catastrophe theory is used to analyze the echo amplitudes arising from these overlaps. The echo pressure for single reflections is shown to have a dependence on target position described by an Airy function for both a point and a finite target. With double focusing, this dependence is the square of an Airy function for a point target. With a finite sized target, (as in the experiment) this becomes a hyperbolic umbilic catastrophe integral with symmetric arguments. The arguments of each of these functions are derived from only the relative echo times of a transient pulse. Transient echo times are calculated using a numerical ray finding technique. Experiment confirms the predicted merging of transient echoes in the time domain, as well as the Airy and hyperbolic umbilic diffraction integral amplitudes for a tone burst. This method allows targets to be observed at greater distances in the presence of a focusing surface.

A survey of current operational problems

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

Prince, W.R.; Nielsen, E.K.; McNair, H.D.

1989-11-01

This paper is prepared for use in the Working Group on Current Operational Problems (COPS) forums with the goal of focusing attention of the industry on problems faced by those who are involved in actual power system operation. The results of a survey on operational problems are presented in this paper. Statistical information compiled for various categories of operational problems is given with some general observations about the results. A rough comparison is made from the results of this survey and the first COPS problem list of 1976.

What magnitude are observed non-target impacts from weed biocontrol?

USDA-ARS?s Scientific Manuscript database

A systematic review focused by plant on non-target impacts from agents deliberately introduced for the biological control of weeds found significant non-target impacts to be rare. The magnitude of direct impact of 43 biocontrol agents on 140 non-target plants was retrospectively categorized using a ...

Solution-Focused Counseling in Schools, Third Edition

ERIC Educational Resources Information Center

Murphy, John J.

2015-01-01

The third edition of this text covers the philosophical foundations and nuts and bolts of using solution focused counseling to help preschool-12 students resolve problems. Dr. Murphy's practical and respectful approach has been successfully applied throughout the world by school counselors, counselors in training, psychologists, social workers,…

Expected Trials under the Matching Rounds Problem

ERIC Educational Resources Information Center

Farmer, Jim

2014-01-01

This article reviews the famous "matching problem," with a particular focus on the expected number of objects that are correctly placed. The author discusses the following topics: three versions suitable for teaching the matching problem in the classroom; the solution to the matching problem; the use of the strong form of mathematical…

Community mobilization and the framing of alcohol-related problems.

PubMed

Herd, Denise

2010-03-01

The goal of this study was to describe how activists engaged in campaigns to change alcohol policies in inner city areas framed alcohol problems, and whether or not their frameworks reflected major models used in the field, such as the alcoholism as a disease model, an alcohol problems perspective, or a public health approach to alcohol problems. The findings showed that activists' models shared some aspects with dominant approaches which tend to focus on individuals and to a lesser extent on regulating alcohol marketing and sales. However, activists' models differed in significant ways by focusing on community level problems with alcohol; on problems with social norms regarding alcohol use; and on the relationship of alcohol use to illicit drugs.

A Mixed Integer Linear Programming Approach to Electrical Stimulation Optimization Problems.

PubMed

Abouelseoud, Gehan; Abouelseoud, Yasmine; Shoukry, Amin; Ismail, Nour; Mekky, Jaidaa

2018-02-01

Electrical stimulation optimization is a challenging problem. Even when a single region is targeted for excitation, the problem remains a constrained multi-objective optimization problem. The constrained nature of the problem results from safety concerns while its multi-objectives originate from the requirement that non-targeted regions should remain unaffected. In this paper, we propose a mixed integer linear programming formulation that can successfully address the challenges facing this problem. Moreover, the proposed framework can conclusively check the feasibility of the stimulation goals. This helps researchers to avoid wasting time trying to achieve goals that are impossible under a chosen stimulation setup. The superiority of the proposed framework over alternative methods is demonstrated through simulation examples.

Perceived organizational problems in health care: a pilot test of the structured problem and success inventory.

PubMed

Nyström, Monica E; Terris, Darcey D; Sparring, Vibeke; Tolf, Sara; Brown, Claire R

2012-01-01

Our objective was to test whether the Structured Problem and Success Inventory (SPI) instrument could capture mental representations of organizational and work-related problems as described by individuals working in health care organizations and to test whether these representations varied according to organizational position. A convenience sample (n = 56) of middle managers (n = 20), lower-level managers (n = 20), and staff (n = 16) from health care organizations in Stockholm (Sweden) attending organizational development courses during 2003-2004 was recruited. Participants used the SPI to describe the 3 most pressing organizational and work-related problems. Data were systematically reviewed to identify problem categories and themes. One hundred sixty-four problems were described, clustered into 13 problem categories. Generally, middle managers focused on organizational factors and managerial responsibilities, whereas lower-level managers and staff focused on operational issues and what others did or ought to do. Furthermore, we observed similarities and variation in perceptions and their association with respondents' position within an organization. Our results support the need for further evaluation of the SPI as a promising tool for health care organizations. Collecting structured inventories of organizational and work-related problems from multiple perspectives may assist in the development of shared understandings of organizational challenges and lead to more effective and efficient processes of solution planning and implementation.

The 3D elliptic restricted three-body problem: periodic orbits which bifurcate from limiting restricted problems. Complex instability

NASA Astrophysics Data System (ADS)

Ollé, Mercè; Pacha, Joan R.

1999-11-01

In the present work we use certain isolated symmetric periodic orbits found in some limiting Restricted Three-Body Problems to obtain, by numerical continuation, families of symmetric periodic orbits of the more general Spatial Elliptic Restricted Three Body Problem. In particular, the Planar Isosceles Restricted Three Body Problem, the Sitnikov Problem and the MacMillan problem are considered. A stability study for the periodic orbits of the families obtained - specially focused to detect transitions to complex instability - is also made.

Problem solving performance and learning strategies of undergraduate students who solved microbiology problems using IMMEX educational software

NASA Astrophysics Data System (ADS)

Ebomoyi, Josephine Itota

The objectives of this study were as follows: (1) Determine the relationship between learning strategies and performance in problem solving, (2) Explore the role of a student's declared major on performance in problem solving, (3) Understand the decision making process of high and low achievers during problem solving. Participants (N = 65) solved problems using the Interactive multimedia exercise (IMMEX) software. All participants not only solved "Microquest," which focuses on cellular processes and mode of action of antibiotics, but also "Creeping Crud," which focuses on the cause, origin and transmission of diseases. Participants also responded to the "Motivated Strategy Learning Questionnaire" (MSLQ). Hierarchical multiple regression was used for analysis with GPA (Gracie point average) as a control. There were 49 (78.6%) that successfully solved "Microquest" while 52 (82.5%) successfully solved "Creeping Crud". Metacognitive self regulation strategy was significantly (p < .10) related to ability to solve "Creeping Crud". Peer learning strategy showed a positive significant (p < .10) relationship with scores obtained from solving "Creeping Crud". Students' declared major made a significant (p < .05) difference on the ability to solve "Microquest". A subset (18) volunteered for a think aloud method to determine decision-making process. High achievers used fewer steps, and had more focused approach than low achievers. Common strategies and attributes included metacognitive skills, writing to keep track, using prior knowledge. Others included elements of frustration/confusion and self-esteem problems. The implications for educational and relevance to real life situations are discussed.

Enhanced methodology of focus control and monitoring on scanner tool

NASA Astrophysics Data System (ADS)

Chen, Yen-Jen; Kim, Young Ki; Hao, Xueli; Gomez, Juan-Manuel; Tian, Ye; Kamalizadeh, Ferhad; Hanson, Justin K.

2017-03-01

As the demand of the technology node shrinks from 14nm to 7nm, the reliability of tool monitoring techniques in advanced semiconductor fabs to achieve high yield and quality becomes more critical. Tool health monitoring methods involve periodic sampling of moderately processed test wafers to detect for particles, defects, and tool stability in order to ensure proper tool health. For lithography TWINSCAN scanner tools, the requirements for overlay stability and focus control are very strict. Current scanner tool health monitoring methods include running BaseLiner to ensure proper tool stability on a periodic basis. The focus measurement on YIELDSTAR by real-time or library-based reconstruction of critical dimensions (CD) and side wall angle (SWA) has been demonstrated as an accurate metrology input to the control loop. The high accuracy and repeatability of the YIELDSTAR focus measurement provides a common reference of scanner setup and user process. In order to further improve the metrology and matching performance, Diffraction Based Focus (DBF) metrology enabling accurate, fast, and non-destructive focus acquisition, has been successfully utilized for focus monitoring/control of TWINSCAN NXT immersion scanners. The optimal DBF target was determined to have minimized dose crosstalk, dynamic precision, set-get residual, and lens aberration sensitivity. By exploiting this new measurement target design, 80% improvement in tool-to-tool matching, >16% improvement in run-to-run mean focus stability, and >32% improvement in focus uniformity have been demonstrated compared to the previous BaseLiner methodology. Matching <2.4 nm across multiple NXT immersion scanners has been achieved with the new methodology of set baseline reference. This baseline technique, with either conventional BaseLiner low numerical aperture (NA=1.20) mode or advanced illumination high NA mode (NA=1.35), has also been evaluated to have consistent performance. This enhanced methodology of focus

LLNL Scientist is Passionate About Targets

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

Butlin, Becky

With a lifelong passion for problem-solving and a love of production, Becky Butlin has helped lead the National Ignition Facility Target Fabrication Team through obstacles and challenges for the past six years.

Revisiting the Velocity Selector Problem with VPython

ERIC Educational Resources Information Center

Milbourne, Jeff; Lim, Halson

2015-01-01

The velocity selector is a classic first-year physics problem that demonstrates the influence of perpendicular electric and magnetic fields on a charged particle. Traditionally textbooks introduce this problem in the context of balanced forces, often asking for field strengths that would allow a charged particle, with a specific target velocity,…

Support for the beam focusing hypothesis in the false killer whale.

PubMed

Kloepper, Laura N; Buck, John R; Smith, Adam B; Supin, Alexander Ya; Gaudette, Jason E; Nachtigall, Paul E

2015-08-01

The odontocete sound production system is complex and composed of tissues, air sacs and a fatty melon. Previous studies suggested that the emitted sonar beam might be actively focused, narrowing depending on target distance. In this study, we further tested this beam focusing hypothesis in a false killer whale. Using three linear arrays of hydrophones, we recorded the same emitted click at 2, 4 and 7 m distance and calculated the beamwidth, intensity, center frequency and bandwidth as recorded on each array at every distance. If the whale did not focus her beam, acoustics predicts the intensity would decay with range as a function of spherical spreading and the angular beamwidth would remain constant. On the contrary, our results show that as the distance from the whale to the array increases, the beamwidth is narrower and the received click intensity is higher than that predicted by a spherical spreading function. Each of these measurements is consistent with the animal focusing her beam on a target at a given range. These results support the hypothesis that the false killer whale is 'focusing' its sonar beam, producing a narrower and more intense signal than that predicted by spherical spreading. © 2015. Published by The Company of Biologists Ltd.

High efficiency focus neutron generator

NASA Astrophysics Data System (ADS)

Sadeghi, H.; Amrollahi, R.; Zare, M.; Fazelpour, S.

2017-12-01

In the present paper, the new idea to increase the neutron yield of plasma focus devices is investigated and the results are presented. Based on many studies, more than 90% of neutrons in plasma focus devices were produced by beam target interactions and only 10% of them were due to thermonuclear reactions. While propounding the new idea, the number of collisions between deuteron ions and deuterium gas atoms were increased remarkably well. The COMSOL Multiphysics 5.2 was used to study the given idea in the known 28 plasma focus devices. In this circumstance, the neutron yield of this system was also obtained and reported. Finally, it was found that in the ENEA device with 1 Hz working frequency, 1.1 × 109 and 1.1 × 1011 neutrons per second were produced by D-D and D-T reactions, respectively. In addition, in the NX2 device with 16 Hz working frequency, 1.34 × 1010 and 1.34 × 1012 neutrons per second were produced by D-D and D-T reactions, respectively. The results show that with regards to the sizes and energy of these devices, they can be used as the efficient neutron generators.

Self-assessing target with automatic feedback

DOEpatents

Larkin, Stephen W.; Kramer, Robert L.

2004-03-02

A self assessing target with four quadrants and a method of use thereof. Each quadrant containing possible causes for why shots are going into that particular quadrant rather than the center mass of the target. Each possible cause is followed by a solution intended to help the marksman correct the problem causing the marksman to shoot in that particular area. In addition, the self assessing target contains possible causes for general shooting errors and solutions to the causes of the general shooting error. The automatic feedback with instant suggestions and corrections enables the shooter to improve their marksmanship.

Child Abuse and Neglect: The Problem and Its Management. Volume 1: An Overview of the Problem.

ERIC Educational Resources Information Center

National Center on Child Abuse and Neglect (DHEW/OHD), Washington, DC.

This booklet, first of a three-volume series, presents an overview of the problems of child abuse and neglect. Discussions focus on child maltreatment from various perspectives, including characteristics of the parents and children, effects of abuse and neglect, a phychiatrist's view of the problem, and a discussion of state reporting laws. The…

Problems of Runaway Youth. Hearing before the Subcommittee on Juvenile Justice of the Committee on the Judiciary. United States Senate, Ninety-Seventh Congress, Second Session on Problems of and Services Provided for Runaway and Homeless Youth, Focusing on Support to State and Local Governments and Nonprofit Agencies for the Development of Community-Based Programs.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. Senate Committee on the Judiciary.