Comparison of methods for assessing thyroid function in nonthyroidal illness

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

Melmed, S.; Geola, F.L.; Reed, A.W.

1982-02-01

Various tests of thyroid function were studied in sick patients with nonthyroidal illness (NTI) in order to determine the utility of each test for differentiating these patients from a group with hypothyroidism. We evaluated each test in 22 healthy volunteers who served as controls, 20 patients with hypothyroidism, 14 patients admitted to medical intensive care unit whose serum T/sub 4/ was less than 5 ..mu..g/dl, 13 patients with chronic liver disease, 32 patients on chronic hemodialysis for renal failure, 13 ambulatory oncology patients receiving chemotherapy 16 pregnant women, 7 women on estrogens, and 20 hyperthyroid patients. On all samples, wemore » measured serum T/sub 4/, the free T/sub 4/ index by several methods, free T/sub 4/ by equilibrium dialysis, free T/sub 4/ calculated from thyronine-binding globulin (TBG) RIA, free T/sub 4/ by three commercial kits (Gammacoat, Immophase, and Liquisol), T/sub 3/, rT/sub 3/, and TSH (by 3 different RIA). Although all of the methods used for measuring free T/sub 4/ (including free T/sub 4/ index, free T/sub 4/ by dialysis, free T/sub 4/ assessed by TBG, and free T/sub 4/ assessed by the 3 commercial kits) were excellent for the diagnosis of hypothyroidism, hyperthyroidism, and euthyroidism in the presence of high TBG, none of these methods showed that free T/sub 4/ was consistently normal in patients with NTI; with each method, a number of NTI patients had subnormal values. In the NTI groups, free T/sub 4/ measured by dialysis and the free T/sub 4/ index generally correlated significantly with the commercial free T/sub 4/ methods. Serum rT/sub 3/ was elevated or normal in NTI patients and low in hypothyroid subjects. Serum TSH provided the most reliable differentiation between patients with primary hypothyroidism and those with NTI and low serum T/sub 4/ levels.« less

A prospective, randomised, clinical study to compare the use of McGrath(®), Truview(®) and Macintosh laryngoscopes for endotracheal intubation by novice and experienced Anaesthesiologists.

PubMed

Bakshi, Sumitra G; Vanjari, Vinayak S; Divatia, Jigeeshu V

2015-07-01

Video laryngoscopy has been recommended as an alternative during difficult conventional direct laryngoscopy using the Macintosh blade (MAC). However, successful visualisation of the larynx and tracheal intubation using some of the indirect laryngoscopes or video laryngoscopes (VL) requires hand-eye coordination. We conducted this study to determine whether non-channel VLs are easy to use for novices and whether there is any association between expertise with MAC and ease of tracheal intubation with VLs. Anaesthesiologists participating in the study were divided into three groups: Group novice to intubation (NTI), Group novice to videoscope (NVL)- experienced with MAC, novice to VLs and Group expert (EXP) experienced in all. Group NTI, NVL received prior mannequin training. VLs- Truview(®) and McGrath series 5 (MGR) were compared with MAC. One hundred and twenty six adult patients with normal airway were randomised to both, the intubating anaesthesiologist and laryngoscope. The time taken to intubate (TTI) and participants' rating of the ease of use was recorded on a scale of 1-10 (10-most difficult). In Group NTI, there was no difference in mean TTI with the three scopes (P = 0.938). In Group NVL, TTI was longer with the VLs than MAC (P < 0.001). In Group EXP, TTI with VL took 20 s more (P < 0.001). There was significant difference in participants' rating of ease of use of laryngoscope in Group NVL (P = 0.001) but not in the NTI (P = 0.205), EXP (P = 0.529) groups. A high failure was seen with MGR in Group NTI and NVL. In Group NTI, TTI and the ease of use were similar for all scopes. Expertise with standard direct laryngoscopy does not translate to expertise with VLs. Separate training and experience with VLs is required.

A prospective, randomised, clinical study to compare the use of McGrath®, Truview® and Macintosh laryngoscopes for endotracheal intubation by novice and experienced Anaesthesiologists

PubMed Central

Bakshi, Sumitra G; Vanjari, Vinayak S; Divatia, Jigeeshu V

2015-01-01

Background and Aims: Video laryngoscopy has been recommended as an alternative during difficult conventional direct laryngoscopy using the Macintosh blade (MAC). However, successful visualisation of the larynx and tracheal intubation using some of the indirect laryngoscopes or video laryngoscopes (VL) requires hand-eye coordination. We conducted this study to determine whether non-channel VLs are easy to use for novices and whether there is any association between expertise with MAC and ease of tracheal intubation with VLs. Methods: Anaesthesiologists participating in the study were divided into three groups: Group novice to intubation (NTI), Group novice to videoscope (NVL)- experienced with MAC, novice to VLs and Group expert (EXP) experienced in all. Group NTI, NVL received prior mannequin training. VLs- Truview® and McGrath series 5 (MGR) were compared with MAC. One hundred and twenty six adult patients with normal airway were randomised to both, the intubating anaesthesiologist and laryngoscope. The time taken to intubate (TTI) and participants’ rating of the ease of use was recorded on a scale of 1–10 (10-most difficult). Results: In Group NTI, there was no difference in mean TTI with the three scopes (P = 0.938). In Group NVL, TTI was longer with the VLs than MAC (P < 0.001). In Group EXP, TTI with VL took 20 s more (P < 0.001). There was significant difference in participants’ rating of ease of use of laryngoscope in Group NVL (P = 0.001) but not in the NTI (P = 0.205), EXP (P = 0.529) groups. A high failure was seen with MGR in Group NTI and NVL. Conclusion: In Group NTI, TTI and the ease of use were similar for all scopes. Expertise with standard direct laryngoscopy does not translate to expertise with VLs. Separate training and experience with VLs is required. PMID:26257415

Reflections of a ZERO TO THREE National Training Institute Neophyte

ERIC Educational Resources Information Center

Simpson, Tanika

2013-01-01

In this article Tanika Simpson reflects on her experience at the 2012 three-day ZERO TO THREE National Training Institute (NTI) held in Los Angeles, California. The week began with a two-day pre-NTI retreat convening a national league of state Infant Mental Health Associations that are intensely committed to the work of implementing Michigan's…

Founder of systems chemistry and foundational theoretical biologist: Tibor Gánti (1933-2009).

PubMed

Szathmáry, Eörs

2015-09-21

With his chemoton theory theoretical biologist and chemical engineer Tibor Gánti was one of the most outstanding intellects behind systems chemistry and the at the foundations of theoretical biology. A brief review of his oeuvre is presented. This essay introduces a special issue dedicated to his memory. Copyright © 2015. Published by Elsevier Ltd.

The Costs and Benefits of Substance Abuse Treatment: Findings from the National Treatment Improvement Evaluation Study (NTIES).

ERIC Educational Resources Information Center

Koenig, Lane; Denmead, Gabrielle; Nguyen, Robert; Harrison, Margaret; Harwood, Henrick

This study seeks to quantify the costs and benefits of alcohol and drug abuse treatment and the resulting economic benefits to society. Using data from the National Treatment Improvement Evaluation Study (NTIES), and client questionnaires, estimates were made of the average costs per client in terms of crime-related costs, health care costs, and…

Alterations of Mental Status and Thyroid Hormones after Thermal Injury

DTIC Science & Technology

1985-01-01

steroid, dopamine, or iodine treatment . At to weeks before death, this association N~ing~ndependent ofeach sa pling, the level of obtundation (LO...was deter ined on treatment with drugs dcting on mental s as or thyroi func- a 6-point scale from normal to deep coma. Whereas initially low tion. (J...other types of nonthyroidal illnes,. of wounds were performed when indicated. Treatment did not (NTI) (4, 5). Previous studies of a variety of NTI

Neural breathing patterns in preterm newborns supported with non-invasive neurally adjusted ventilatory assist.

PubMed

García-Muñoz Rodrigo, Fermín; Urquía Martí, Lourdes; Galán Henríquez, Gloria; Rivero Rodríguez, Sonia; Hernández Gómez, Alberto

2018-06-18

To characterize the neural breathing pattern in preterm infants supported with non-invasive neurally adjusted ventilatory assist (NIV-NAVA). Single-center prospective observational study. The electrical activity of the diaphragm (EAdi) was periodically recorded in 30-second series with the Edi catheter and the Servo-n software (Maquet, Solna, Sweden) in preterm infants supported with NIV-NAVA. The EAdi Peak , EAdi Min , EAdi Tonic , EAdi Phasic , neural inspiratory, and expiratory times (nTi and nTe) and the neural respiratory rate (nRR) were calculated. EAdi curves were generated by Excel for visual examination and classified according to the predominant pattern. 291 observations were analyzed in 19 patients with a mean GA of 27.3 weeks (range 24-36 weeks), birth weight 1028 g (510-2945 g), and a median (IQR) postnatal age of 18 days (4-27 days). The distribution of respiratory patterns was phasic without tonic activity 61.9%, phasic with basal tonic activity 18.6, tonic burst 3.8%, central apnea 7.9%, and mixed pattern 7.9%. In addition, 12% of the records showed apneas of >10 seconds, and 50.2% one or more "sighs", defined as breaths with an EAdi Peak and/or nTi greater than twice the average EAdi Peak and/or nTi of the recording. Neural times were measurable in 252 observations. The nTi was, median (IQR): 279 ms (253-285 ms), the nTe 764 ms (642-925 ms), and the nRR 63 bpm (51-70), with a great intra and inter-subjects variability. The neural breathing patterns in preterm infants supported with NIV-NAVA are quite variable and are characterized by the presence of significant tonic activity. Central apneas and sighs are common in this group of patients. The nTi seems to be shorter than the mechanical Ti commonly used in assisted ventilation.

Preparation and characterization of a novel highly hydrophilic and antifouling polysulfone/nanoporous TiO2 nanocomposite membrane.

PubMed

Bidsorkhi, H Cheraghi; Riazi, H; Emadzadeh, D; Ghanbari, M; Matsuura, T; Lau, W J; Ismail, A F

2016-10-14

In this research, novel ultrafiltration nanocomposite membranes were prepared by incorporating self-synthesized nanoporous titanium dioxide (NTiO2) nanoparticles into polysulfone. The surface of the nanoparticle was treated with a silane-based modifier to improve its distribution in the host polymer. Atomic-force microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller, transmission electron microscopy, energy-dispersive x-ray spectroscopy, porosity and contact angle tests were conducted to characterize the properties of the particles as well as the fabricated nanocomposite membranes. The effects of the nanoparticle incorporation were evaluated by conducting ultrafiltration experiments. It was reported that the membrane pure water flux was increased with increasing NTiO2 loading owing to the high porosity of the nanoparticles embedded and/or formation of enlarged pores upon addition of them. The antifouling capacity of the membranes was also tested by ultrafiltration of bovine serum albumin fouling solution. It was found that both water flux and antifouling capacity tended to reach desired level if the NTiO2 added was at optimized loading.

Large-scale molecular dynamics simulations of TiN/TiN(001) epitaxial film growth

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

Edström, Daniel, E-mail: daned@ifm.liu.se; Sangiovanni, Davide G.; Hultman, Lars

2016-07-15

Large-scale classical molecular dynamics simulations of epitaxial TiN/TiN(001) thin film growth at 1200 K are carried out using incident flux ratios N/Ti = 1, 2, and 4. The films are analyzed as a function of composition, island size distribution, island edge orientation, and vacancy formation. Results show that N/Ti = 1 films are globally understoichiometric with dispersed Ti-rich surface regions which serve as traps to nucleate 111-oriented islands, leading to local epitaxial breakdown. Films grown with N/Ti = 2 are approximately stoichiometric and the growth mode is closer to layer-by-layer, while N/Ti = 4 films are stoichiometric with N-rich surfaces. As N/Ti is increased from 1 to 4, islandmore » edges are increasingly polar, i.e., 110-oriented, and N-terminated to accommodate the excess N flux, some of which is lost by reflection of incident N atoms. N vacancies are produced in the surface layer during film deposition with N/Ti = 1 due to the formation and subsequent desorption of N{sub 2} molecules composed of a N adatom and a N surface atom, as well as itinerant Ti adatoms pulling up N surface atoms. The N vacancy concentration is significantly reduced as N/Ti is increased to 2; with N/Ti = 4, Ti vacancies dominate. Overall, our results show that an insufficient N/Ti ratio leads to surface roughening via nucleation of small dispersed 111 islands, whereas high N/Ti ratios result in surface roughening due to more rapid upper-layer nucleation and mound formation. The growth mode of N/Ti = 2 films, which have smoother surfaces, is closer to layer-by-layer.« less

Tungsten Bronze Barium Neodymium Titanate (Ba(6-3n)Nd(8+2n)Ti(18)O(54)): An Intrinsic Nanostructured Material and Its Defect Distribution.

PubMed

Azough, Feridoon; Cernik, Robert Joseph; Schaffer, Bernhard; Kepaptsoglou, Demie; Ramasse, Quentin Mathieu; Bigatti, Marco; Ali, Amir; MacLaren, Ian; Barthel, Juri; Molinari, Marco; Baran, Jakub Dominik; Parker, Stephen Charles; Freer, Robert

2016-04-04

We investigated the structure of the tungsten bronze barium neodymium titanates Ba(6-3n)Nd(8+2n)Ti(18)O(54), which are exploited as microwave dielectric ceramics. They form a complex nanostructure, which resembles a nanofilm with stacking layers of ∼12 Å thickness. The synthesized samples of Ba(6-3n)Nd(8+2n)Ti(18)O(54) (n = 0, 0.3, 0.4, 0.5) are characterized by pentagonal and tetragonal columns, where the A cations are distributed in three symmetrically inequivalent sites. Synchrotron X-ray diffraction and electron energy loss spectroscopy allowed for quantitative analysis of the site occupancy, which determines the defect distribution. This is corroborated by density functional theory calculations. Pentagonal columns are dominated by Ba, and tetragonal columns are dominated by Nd, although specific Nd sites exhibit significant concentrations of Ba. The data indicated significant elongation of the Ba columns in the pentagonal positions and of the Nd columns in tetragonal positions involving a zigzag arrangement of atoms along the b lattice direction. We found that the preferred Ba substitution occurs at Nd[3]/[4] followed by Nd[2] and Nd[1]/[5] sites, which is significantly different to that proposed in earlier studies. Our results on the Ba(6-3n)Nd(8+2n)Ti(18)O(54) "perovskite" superstructure and its defect distribution are particularly valuable in those applications where the optimization of material properties of oxides is imperative; these include not only microwave ceramics but also thermoelectric materials, where the nanostructure and the distribution of the dopants will reduce the thermal conductivity.

Functional Analysis of Plant Promoter rpL34 Using the GUS Marker Gene in New Tr,tnsgene Expression Vector pZD428

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

Mauzey-Amato, Jacqueline M.; Dai, Ziyu

2000-11-01

Optimization of the transgene expression system is one of the critical steps for the high level production of heterologous proteins in plants, where the promoter is a key component regulating transgene expression. In this study, the activity of the rpL34 promoter was analyzed in transgenic tobacco (Nicotiana tabacum) NTI calli. A DNA fragment containing the rpL34 promoter and the reporter gene B-D-glucuronidase (GUS) were cloned into binary vector pZD427 to generate the transgene expression vector pZD428. The insertion was verified by enzyme restriction digestion and agarose gel electrophoresis analyses. The DNA fragment containing the rpL34 promoter and GUS reporter genemore » was then integrated into the tobacco genomes via Agrobacterium funiefaciens-mediated NT suspension cell transformation. The transformed CaNi were induced on Murashige and Skoog (MS) plates containing proper amounts of 2,4-D, cefotoxime, and kanamycin. Two hundred and sixty transformed calli were harvested for GUS activity and protein concentration measurements. GUS activity analyses revealed the specific activity up to 278,358 units per milligram total soluble protein. The GUS activity under the control of the rpL34 promoter is much higher than that under the control of the cauliflower mosaic virus 35S promoter, a commonly used promoter in plant biology. These results suggest that the rpL34 promoter is one of the most active promoters that can be used for heterologous protein production in calli and suspension cells.« less

A meta-analysis of prehospital airway control techniques part I: orotracheal and nasotracheal intubation success rates.

PubMed

Hubble, Michael W; Brown, Lawrence; Wilfong, Denise A; Hertelendy, Attila; Benner, Randall W; Richards, Michael E

2010-01-01

Airway management is a key component of prehospital care for seriously ill and injured patients. Although endotracheal intubation has been a commonly performed prehospital procedure for nearly three decades, the safety and efficacy profile of prehospital intubation has been challenged in the last decade. Reported intubation success rates vary widely, and established benchmarks are lacking. We sought to determine pooled estimates for oral endotracheal intubation (OETI) and nasotracheal intubation (NTI) placement success rates through a meta-analysis of the literature. We performed a systematic literature search for all English-language articles reporting placement success rates for prehospital intubation. Studies of field procedures performed by prehospital personnel from any nation were included. All titles were reviewed independently by two authors using prespecified inclusion criteria. Pooled estimates of success rates for each airway technique, including drug-facilitated intubation (DFI) and rapid-sequence intubation (RSI), were calculated using a random-effects model. Historical trends were evaluated using meta-regression. Of 2,005 identified titles reviewed, 117 studies addressed OETI and 23 addressed NTI, encompassing a total of 57,132 prehospital patients. There was substantial interrater reliability in the review process (kappa = 0.81). The pooled estimates (and 95% confidence intervals [CIs]) for intervention success for nonphysician clinicians were as follows: overall non-RSI/non-DFI OETI success rate: 86.3% (82.6%-89.4%); OETI for non-cardiac arrest patients: 69.8% (50.9%-83.8%); DFI 86.8% (80.2%-91.4%); and RSI 96.7% (94.7%-98.0%). For pediatric patients, the paramedic OETI success rate was 83.2% (55.2%-95.2%). The overall NTI success rate for nonphysician clinicians was 75.9% (65.9%-83.7%). The historical trend of OETI reflects a 0.49% decline in success rates per year. We provide pooled estimates of placement success rates for prehospital airway interventions. For some patient and clinician characteristics, OETI has relatively low success rates. For nonarrest patients, DFI and RSI appear to increase success rates. Across all clinicians, NTI has a low rate of success, raising questions about the safety and efficacy of this procedure.

Habituation and desensitization as methods for reducing fearful behavior in singly housed rhesus macaques.

PubMed

Clay, Andrea W; Bloomsmith, Mollie A; Marr, M Jackson; Maple, Terry L

2009-01-01

Operant conditioning using positive reinforcement techniques has been used extensively in the management of nonhuman primates in both zoological and laboratory settings. This research project was intended to test the usefulness of counter-conditioning techniques in reducing the fear-responses of singly housed male rhesus macaques living in the laboratory environment. A total of 18 male rhesus macaques (Macaca mulatta) were selected for this project and randomly assigned to one of three groups: a desensitization training group, a husbandry training group, or a control group. Behavioral data were collected before and after a 6 weeks training and/or habituation period during which the first two groups received a total of 125 min of positive reinforcement training (and also were assumed to undergo habituation to the environment) and the control group experienced only simple habituation to the environment. Based on a Wilcoxon Matched-Pairs Sign Test, we found that a significant proportion of animals exposed to desensitization training showed a reduction in the rate at which they engaged in cringing toward humans (exact significance=0.016, one-tailed, N-ties=6), cringing in general (exact significance=0.016, one-tailed, N-ties=6), and in stress-related behaviors (exact significance=0.016, one-tailed, N-ties=6). This was not the case for animals exposed to basic husbandry training or animals in the control group. A significant proportion of desensitization-exposed animals also showed a reduction in the duration of time spent cringing toward humans (exact significance=0.016, one-tailed, N-ties=6), but not in cringing behaviors in general or in stress-related behaviors. There were not a significant proportion of animals in either the husbandry training group or the control group that showed a decrease in duration of these behaviors. Results of this study could enhance both laboratory animal welfare and laboratory animal research, and could be a first step in developing techniques for reducing fearful behavior in rhesus monkeys in the laboratory environment. (c) 2008 Wiley-Liss, Inc.

The National Trauma Institute: Lessons learned in the funding and conduct of 16 trauma research studies.

PubMed

Price, Michelle A; Beilman, Gregory J; Fabian, Timothy C; Hoyt, David B; Jurkovich, Gregory J; Knudson, M Margaret; MacKenzie, Ellen J; Marshall, Vivienne S; Overton, Kimberly E; Peitzman, Andrew B; Phillips, Monica J; Pruitt, Basil A; Smith, Sharon L; Stewart, Ronald M; Jenkins, Donald H

2016-09-01

To increase trauma-related research and elevate trauma on the national research agenda, the National Trauma Institute (NTI) issued calls for proposals, selected funding recipients, and coordinated 16 federally funded (Department of Defense) trauma research awards over a 4-year period. We sought to collect and describe the lessons learned from this activity to inform future researchers of barriers and facilitators. Fifteen principal investigators participated in semistructured interviews focused on study management issues such as securing institutional approvals, screening and enrollment, multisite trials management, project funding, staffing, and institutional support. NTI Science Committee meeting minutes and study management data were included in the analysis. Simple descriptive statistics were generated and textual data were analyzed for common themes. Principal investigators reported challenges in obtaining institutional approvals, delays in study initiation, screening and enrollment, multisite management, and study funding. Most were able to successfully resolve challenges and have been productive in terms of scholarly publications, securing additional research funding, and training future trauma investigators. Lessons learned in the conduct of the first two funding rounds managed by NTI are instructive in four key areas: regulatory processes, multisite coordination, adequate funding, and the importance of an established research infrastructure to ensure study success. Recommendations for addressing institution-related and investigator-related challenges are discussed along with ongoing advocacy efforts to secure sustained federal funding of a national trauma research program commensurate with the burden of injury.

Proposal for mars express: detailed dds-test in the "inca city" and "csontváry" areas

NASA Astrophysics Data System (ADS)

Horvath, A.; Manrubia, S. C.; Ganti, T.; Berczi, S.; Gesztesi, A.; Fernandez-Remolar, D.; Prieto Ballesteros, O.; Szathmary, E.

2003-04-01

Analyis of Mars Global Surveyor MOC images taken in Martian winter and spring has revealed a peculiar spotting phenomenon on the dark dunes in the polar region of Mars [1]. These spots are named Dark Dune Spots (DDSs) and various hypotheses have been put forward for their origin and formation process, which fall into two main groups: geophysical and biological [2, 3, 4, 5 and 6]. Because the high-resolution images by MGS-MOC have shown well-developed and recurrent DDSs on some dark dune fields since the Southern winter of 1999 [5, 6 and 7], we have selected two areas of them. They are many dozen kilometers in size in the Southern polar region. Namely: the "Inca City" area (λ=295.3^oE, ϕ=81.5^oS) and the Northern part of Pityusa Patera (λ=37^oE, ϕ=66^oS), which we call "Csontváry" area. These two areas could be excellent test areas for Mars Express in order to reveal the mechanism of the formation, development and annual recurrence of the DDSs. For this we propose, that different instruments (HRSC, spectrometers, etc.) of the orbiter of the ESA Mars Express Mission should produce high-resolution images and spectral measurements of the frosted surface of the dark dunes of the "Inca City" and the Pityusa Patera from the second half of the Southern winter till the end of spring, with weekly regularity, because this may be sufficient to choose between the abiogenic and the biogenic origin of DDSs. Referenes [1] Malin, M. C. and Edgett, K. S.: 2000, Frosting and defrosting of Martian polar dunes, LPS XXXI, #1056, Houston-CD. [2] Horváth, A., Gánti, T., Gesztesi, A., Bérczi, Sz., Szathmáry, E., 2001, Probable evidences of recent biological activity on Mars: appearance and growing of dark dune spots in the south polar region. LPS XXXII, # 1543, Houston-CD. [3] Malin, M. C. and Edgett, K. S.: 2001, The Mars Global Surveyor Mars Orbiter Camera: Interplanetary Cruise through Primary Mission. J. Geophys. Res. 106 E10, p. 23,429-23,570. [4] Gánti, T., Horváth, A., Gesztesi, A., Bérczi, Sz., Szathmáry E.: 2002, Defrosting and Melting, not Defrosting Alone, Lunar Planetary Science XXXIII, #1221, Houston-CD. [5] Horváth, A., Bérczi, Sz., Gánti, T., Gesztesi, A., Szathmáry E.: 2002, The “Inca City” Region of Mars: Test field for Dark Dune Spots Origin, LPS XXXIII, #1109, Houston-CD. [6] Gánti, T., Horváth, A., Gesztesi, A., Bérczi, Sz., Szathmáry, E., 2003, Dark dune spots: possible biomarkers on Mars? OLEB in print. [7] Horváth, A., Gánti, T., Bérczi, Sz., Gesztesi, A., Szathmáry, E., 2003, Morphological analysis of annual recurrence of dark dune spots on Southern Polar Region, LPS XXXIV.

The World Health Organization and public health research and practice in tuberculosis in India.

PubMed

Banerji, Debabar

2012-01-01

Two major research studies carried out in India fundamentally affected tuberculosis treatment practices worldwide. One study demonstrated that home treatment of the disease is as efficacious as sanatorium treatment. The other showed that BCG vaccination is of little protective value from a public health viewpoint. India had brought together an interdisciplinary team at the National Tuberculosis Institute (NTI) with a mandate to formulate a nationally applicable, socially acceptable, and epidemiologically sound National Tuberculosis Programme (NTP). Work at the NTI laid the foundation for developing an operational research approach to dealing with tuberculosis as a public health problem. The starting point for this was not operational research as enunciated by experts in this field; rather, the NTI achieved operational research by starting from the people. This approach was enthusiastically welcomed by the World Health Organization's Expert Committee on Tuberculosis of 1964. The NTP was designed to "sink or sail with the general health services of the country." The program was dealt a major blow when, starting in 1967, a virtual hysteria was worked up to mobilize most of the health services for imposing birth control on the people. Another blow to the general health services occurred when the WHO joined the rich countries in instituting a number of vertical programs called "Global Initiatives". An ill-conceived, ill-designed, and ill-managed Global Programme for Tuberculosis was one outcome. The WHO has shown rank public health incompetence in taking a very casual approach to operational research and has been downright quixotic in its thinking on controlling tuberculosis worldwide.

General, kappa, delta and mu opioid receptor antagonists mediate feeding elicited by the GABA-B agonist baclofen in the ventral tegmental area and nucleus accumbens shell in rats: reciprocal and regional interactions.

PubMed

Miner, Patricia; Shimonova, Lyudmila; Khaimov, Arthur; Borukhova, Yaffa; Ilyayeva, Ester; Ranaldi, Robert; Bodnar, Richard J

2012-03-14

Food intake is significantly increased following administration of agonists of GABA and opioid receptors into the nucleus accumbens shell (NACs) and ventral tegmental area (VTA). GABA-A or GABA-B receptor antagonist pretreatment within the VTA or NACs differentially affects mu-opioid agonist-induced feeding elicited from the same site. Correspondingly, general or selective opioid receptor antagonist pretreatment within the VTA or NACs differentially affects GABA agonist-induced feeding elicited from the same site. Regional interactions have been evaluated in feeding studies by administering antagonists in one site prior to agonist administration in a second site. Thus, opioid antagonist-opioid agonist and GABA antagonist-GABA agonist feeding interactions have been identified between the VTA and NACs. However, pretreatment with GABA-A or GABA-B receptor antagonists in the VTA failed to affect mu opioid agonist-induced feeding elicited from the NACs, and correspondingly, these antagonists administered in the NACs failed to affect mu opioid-induced feeding elicited from the VTA. To evaluate whether regional and reciprocal VTA and NACs feeding interactions occur for opioid receptor modulation of GABA agonist-mediated feeding, the present study examined whether feeding elicited by the GABA-B agonist, baclofen microinjected into the NACs was dose-dependently blocked by pretreatment with general (naltrexone: NTX), mu (beta-funaltrexamine: BFNA), kappa (nor-binaltorphamine: NBNI) or delta (naltrindole: NTI) opioid antagonists in the VTA, and correspondingly, whether VTA baclofen-induced feeding was dose-dependently blocked by NACs pretreatment with NTX, BFNA, NBNI or NTI in rats. Bilateral pairs of cannulae aimed at the VTA and NACs were stereotaxically implanted in rats, and their food intakes were assessed following vehicle and baclofen (200 ng) in each site. Baclofen produced similar magnitudes of increased food intake following VTA and NACs treatment. Baclofen administration in the VTA or NACs was also preceded by administration of NTX (0.1, 1, 5 μg, 0.5 h), BFNA (0.4, 4 μg, 24 h), NBNI (0.6, 6 μg, 0.5 h) or NTI (0.4, 4 μg, 0.5 h) into the other site with intake measured 1, 2 and 4 h after agonist treatment. VTA NTX significantly reduced NACs baclofen-induced feeding. Correspondingly, NACs NTX significantly reduced VTA baclofen-induced feeding, indicating a robust and bidirectional general opioid and GABA-B receptor feeding interaction. Whereas the high, but not low VTA BFNA dose reduced NACs baclofen-induced feeding, NACs BFNA failed to affect VTA baclofen-induced feeding, indicating a unidirectional mu opioid and GABA-B receptor feeding interaction. Whereas VTA NBNI at both doses reduced NACs baclofen-induced feeding, the high, but not low NACs NBNI dose significantly reduced VTA baclofen-induced feeding, indicating a bidirectional kappa opioid and GABA-B receptor feeding interaction. Whereas VTA NTI only transiently reduced NACs baclofen-induced feeding, NACs NTI failed to affect VTA baclofen-induced feeding, indicating a weak unidirectional delta opioid and GABA-B receptor interaction. Whereas administration of NTX or BFNA into the NACs or VTA marginally reduced spontaneous food intake, NBNI or NTI into the same sites failed to alter food intake alone. Therefore, the present study suggests that GABA employs a distributed brain network in mediating its ingestive effects that is dependent upon intact opioid receptor signaling with kappa opioid receptors more involved than mu and delta opioid receptors underlying these regional effects. An alternative hypothesis to be considered is that these effects could be the sum of two independent drug effects (opioid antagonists decreasing and baclofen increasing food intake). Copyright © 2012 Elsevier B.V. All rights reserved.

76 FR 72750 - Meeting Notice-Federal Interagency Committee on Emergency Medical Services

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

... DEPARTMENT OF TRANSPORTATION National Highway Traffic Safety Administration [NHTSA Docket No...: National Highway Traffic Safety Administration (NHTSA), DOT. ACTION: Meeting notice. SUMMARY: NHTSA... Emergency Medical Services, National Highway Traffic Safety Administration, 1200 New Jersey Avenue SE., NTI...

75 FR 42643 - National Tunnel Inspection Standards

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-22

... inspectors; inspection frequencies; and a National Tunnel Inventory (NTI). DATES: Comments must be received... elements and specify an appropriate inspection frequency. Additionally, the DOT Inspector General (IG), in... with respect to how frequently tunnels are inspected. The frequency of tunnel inspections varies from...

78 FR 47488 - Reports, Forms, and Record Keeping Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-05

... DEPARTMENT OF TRANSPORTATION National Highway Traffic Safety Administration [U.S. DOT Docket No. NHTSA-2013-0085] Reports, Forms, and Record Keeping Requirements AGENCY: National Highway Traffic Safety... Safety Research (NTI-131), National Highway Traffic Safety Administration, 1200 New Jersey Avenue SE...

Surface roughness of zirconia for full-contour crowns after clinically simulated grinding and polishing.

PubMed

Hmaidouch, Rim; Müller, Wolf-Dieter; Lauer, Hans-Christoph; Weigl, Paul

2014-12-01

The aim of this study was to evaluate the effect of controlled intraoral grinding and polishing on the roughness of full-contour zirconia compared to classical veneered zirconia. Thirty bar-shaped zirconia specimens were fabricated and divided into two groups (n=15). Fifteen specimens (group 1) were glazed and 15 specimens (group 2) were veneered with feldspathic ceramic and then glazed. Prior to grinding, maximum roughness depth (Rmax) values were measured using a profilometer, 5 times per specimen. Simulated clinical grinding and polishing were performed on the specimens under water coolant for 15 s and 2 N pressure. For grinding, NTI diamonds burs with grain sizes of 20 µm, 10 µm, and 7.5 µm were used sequentially. The ground surfaces were polished using NTI kits with coarse, medium and fine polishers. After each step, Rmax values were determined. Differences between groups were examined using one-way analysis of variance (ANOVA). The roughness of group 1 was significantly lower than that of group 2. The roughness increased significantly after coarse grinding in both groups. The results after glazing were similar to those obtained after fine grinding for non-veneered zirconia. However, fine-ground veneered zirconia had significantly higher roughness than venerred, glazed zirconia. No significant difference was found between fine-polished and glazed zirconia, but after the fine polishing of veneered zirconia, the roughness was significantly higher than after glazing. It can be concluded that for full-contour zirconia, fewer defects and lower roughness values resulted after grinding and polishing compared to veneered zirconia. After polishing zirconia, lower roughness values were achieved compared to glazing; more interesting was that the grinding of glazed zirconia using the NTI three-step system could deliver smooth surfaces comparable to untreated glazed zirconia surfaces.

Surface roughness of zirconia for full-contour crowns after clinically simulated grinding and polishing

PubMed Central

Hmaidouch, Rim; Müller, Wolf-Dieter; Lauer, Hans-Christoph; Weigl, Paul

2014-01-01

The aim of this study was to evaluate the effect of controlled intraoral grinding and polishing on the roughness of full-contour zirconia compared to classical veneered zirconia. Thirty bar-shaped zirconia specimens were fabricated and divided into two groups (n=15). Fifteen specimens (group 1) were glazed and 15 specimens (group 2) were veneered with feldspathic ceramic and then glazed. Prior to grinding, maximum roughness depth (Rmax) values were measured using a profilometer, 5 times per specimen. Simulated clinical grinding and polishing were performed on the specimens under water coolant for 15 s and 2 N pressure. For grinding, NTI diamonds burs with grain sizes of 20 µm, 10 µm, and 7.5 µm were used sequentially. The ground surfaces were polished using NTI kits with coarse, medium and fine polishers. After each step, Rmax values were determined. Differences between groups were examined using one-way analysis of variance (ANOVA). The roughness of group 1 was significantly lower than that of group 2. The roughness increased significantly after coarse grinding in both groups. The results after glazing were similar to those obtained after fine grinding for non-veneered zirconia. However, fine-ground veneered zirconia had significantly higher roughness than venerred, glazed zirconia. No significant difference was found between fine-polished and glazed zirconia, but after the fine polishing of veneered zirconia, the roughness was significantly higher than after glazing. It can be concluded that for full-contour zirconia, fewer defects and lower roughness values resulted after grinding and polishing compared to veneered zirconia. After polishing zirconia, lower roughness values were achieved compared to glazing; more interesting was that the grinding of glazed zirconia using the NTI three-step system could deliver smooth surfaces comparable to untreated glazed zirconia surfaces. PMID:25059249

Supermodes in Coupled Multi-Core Waveguide Structures

DTIC Science & Technology

2016-04-01

and therefore can be treated as linear polarization (LP) modes. In essence, the LP modes are scalar approximations of the vector mode fields and contain...field, including the discovery of optical discrete solitons , Bragg and vector solitons in fibers, nonlinear surface waves, and the discovery of self...increased for an isolated core, it can guide high-order modes. For optical fibers with low re- fractive index contrast, the vector modes are weakly guided

Comparison of astigmatic correction after femtosecond lenticule extraction and wavefront-guided LASIK for myopic astigmatism.

PubMed

Ali, Mohamed A; Kobashi, Hidenaga; Kamiya, Kazutaka; Igarashi, Akihito; Miyake, Toshiyuki; Elewa, Mohamed Ehab M; Komatsu, Mari; Shimizu, Kimiya

2014-12-01

To compare postoperative astigmatic correction between femtosecond lenticule extraction (FLEx) and wavefront-guided LASIK in eyes with myopic astigmatism. Fifty-eight eyes of 41 patients undergoing FLEx and 49 eyes of 29 patients undergoing wavefront-guided LASIK to correct myopic astigmatism were examined. Visual acuity, cylindrical refraction, predictability of the astigmatic correction, and astigmatic vector components were compared between groups 6 months after surgery. There was no statistically significant difference in manifest cylindrical refraction (P = .08) or percentage of eyes within ± 0.50 diopter (D) of its refraction (P = .11) between the surgical procedures. The index of success in FLEx was statistically significantly better than that of wavefront-guided LASIK (P = .02), although there was no significant difference between the groups in other indices (eg, surgically induced astigmatism, target-induced astigmatism, astigmatic correction index, angle of error, difference vector, and flattening index). Subgroup analysis showed that FLEx had a better index of success (P = .02) and difference vector (P = .04) than wavefront-guided LASIK in the low cylinder subgroup; the angle of error in FLEx was significantly smaller than that of wavefront-guided LASIK in the moderate cylinder subgroup (P = .03). Both FLEx and wavefront-guided LASIK worked well for the correction of myopic astigmatism by the 6-month follow-up visit. Although FLEx had a better index of success than wavefront-guided LASIK when using vector analysis, it appears equivalent to wavefront-guided LASIK in terms of visual acuity and the correction of astigmatism. Copyright 2014, SLACK Incorporated.

Report: EPA’s Method for Calculating Air Toxics Emissions for Reporting Results Needs Improvement

EPA Pesticide Factsheets

Report #2004-P-00012, March 31, 2004. Although the methods by which air toxics emissions are estimated have improved substantially, unvalidated assumptions and other limitations underlying the NTI continue to impact its use as a GPRA performance measure.

78 FR 23824 - Reports, Forms, and Record Keeping Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-22

..., Contracting Officer's Technical Representative, Office of Behavioral Safety Research (NTI-132), National... descriptive solicitation. The drivers will be asked a series of seven questions to determine eligibility to... on the Nation's highways. As part of this statutory mandate, NHTSA is authorized to conduct research...

75 FR 32838 - Reports, Forms, and Recordkeeping Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-09

... Eichelberger, Ph.D., Office of Behavioral Safety Research (NTI-132), 1200 New Jersey Avenue, SE., Washington... Administration (NHTSA) proposes to collect observational data on correct and incorrect use of child restraint... FMVSS 225, Child Restraint Anchorage Systems), in order to provide another, easier method of attaching a...

78 FR 68902 - Reports, Forms, and Recordkeeping Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

... Research (NTI-132), National Highway Traffic Safety Administration, 1200 New Jersey Avenue SE., W46-472... on the Nation's highways. As part of this statutory mandate, NHTSA is authorized to conduct research... research indicates that gains in physical fitness improve a number of functional abilities important for...

78 FR 34152 - Reports, Forms, and Record Keeping Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... Research (NTI- 131), National Highway Traffic Safety Administration, 1200 New Jersey Avenue SE., W46-499... comment on the following proposed collection of information: Motor Vehicle Occupant Safety Survey (MVOSS... Collection of Information--NHTSA proposes to conduct the Motor Vehicle Occupant Safety Survey (MVOSS) among a...

Treatment Components and Their Relationships with Drug and Alcohol Abstinence.

ERIC Educational Resources Information Center

Orwin, Rob; Ellis, Bruce

This study evaluates the effect of treatment components through a secondary analysis of data from the National Treatment Improvement Evaluation Study (NTIES). The study examines the relationship between treatment components, client-level factors, and treatment outcomes, and how these relationships vary by treatment modality. It seeks to understand…

The National Treatment Improvement Evaluation Study: Retention Analysis.

ERIC Educational Resources Information Center

Orwin, Rob; Williams, Valerie

This study focuses on programmatic factors that predict retention for individuals in drug and alcohol treatment programs through secondary analysis of data from the National Treatment Improvement Evaluation Study (NTIES). It addresses the relationships between completion rates, lengths of stay, and treatment modality. It examines the effect of…

U.S. EPA, Pesticide Product Label, , 07/13/1983

EPA Pesticide Factsheets

2011-04-21

... 1'1;. '. , Net \\ ight __ _ MIT ICI f!?G'~n~le-;':r~fo~?n~/~on~~~~a~e~le ·ELq\\VJ~~r t~ ttl{' F!·,~pr:tl In~f'('tj("idE'. Il'tmgicidi. i~.'l H(~!t'nti('id(· Act ...

Notetaking Skills Instruction for Development of Middle School Students' Notetaking Performance

ERIC Educational Resources Information Center

Ilter, Ilhan

2017-01-01

The objective of this study was to investigate the effects of explicit instruction in notetaking skills on the notetaking performance of seventh-grade students at different reading ability levels. The students in the notetaking instruction condition (NTI) received classroom-based notetaking skills instruction (approximately 40 minutes) every week…

A Tale of Three Teachers

ERIC Educational Resources Information Center

Prater, Marcella G.; Backes, Charles; McElvey, Randy

2005-01-01

In order to attract trade and industrial teachers and to help them perform successfully in the classroom, states across the nation must make teaching an attractive choice for skilled professionals and offer them adequate and accessible training in order to smooth the transition from industry to education. The New Teacher Institute (NTI) is a…

PGA/MOEAD: a preference-guided evolutionary algorithm for multi-objective decision-making problems with interval-valued fuzzy preferences

NASA Astrophysics Data System (ADS)

Luo, Bin; Lin, Lin; Zhong, ShiSheng

2018-02-01

In this research, we propose a preference-guided optimisation algorithm for multi-criteria decision-making (MCDM) problems with interval-valued fuzzy preferences. The interval-valued fuzzy preferences are decomposed into a series of precise and evenly distributed preference-vectors (reference directions) regarding the objectives to be optimised on the basis of uniform design strategy firstly. Then the preference information is further incorporated into the preference-vectors based on the boundary intersection approach, meanwhile, the MCDM problem with interval-valued fuzzy preferences is reformulated into a series of single-objective optimisation sub-problems (each sub-problem corresponds to a decomposed preference-vector). Finally, a preference-guided optimisation algorithm based on MOEA/D (multi-objective evolutionary algorithm based on decomposition) is proposed to solve the sub-problems in a single run. The proposed algorithm incorporates the preference-vectors within the optimisation process for guiding the search procedure towards a more promising subset of the efficient solutions matching the interval-valued fuzzy preferences. In particular, lots of test instances and an engineering application are employed to validate the performance of the proposed algorithm, and the results demonstrate the effectiveness and feasibility of the algorithm.

The Military Family: A Selected Bibliography. Revision

DTIC Science & Technology

1990-11-01

Commercial (717) 245-3660. "A healthy family environment is a force multiplier." - General John A. Wickham, Jr. NTiS C’. - Statement "A" per telecon...11. Kreyche, Gerald F. "Day Care: The New Surrogacy ." USA TODAY, Vol. 118, September 1989, pp. 91-93. Landrum, Cecile S. "The Changing Military

78 FR 23825 - Information Collection Activities: Submission for the Office of Management and Budget (OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-22

... survey is designed to obtain that information. NHTSA proposes to collect information from all known... at the National Highway Traffic Safety Administration, Office of Behavioral Safety Research (NTI-131...: OMB Control Number: 2127-New. Title: Survey of DWI Courts. Form No.: NHTSA Form 1175. Type of Review...

Prediction task guided representation learning of medical codes in EHR.

PubMed

Cui, Liwen; Xie, Xiaolei; Shen, Zuojun

2018-06-18

There have been rapidly growing applications using machine learning models for predictive analytics in Electronic Health Records (EHR) to improve the quality of hospital services and the efficiency of healthcare resource utilization. A fundamental and crucial step in developing such models is to convert medical codes in EHR to feature vectors. These medical codes are used to represent diagnoses or procedures. Their vector representations have a tremendous impact on the performance of machine learning models. Recently, some researchers have utilized representation learning methods from Natural Language Processing (NLP) to learn vector representations of medical codes. However, most previous approaches are unsupervised, i.e. the generation of medical code vectors is independent from prediction tasks. Thus, the obtained feature vectors may be inappropriate for a specific prediction task. Moreover, unsupervised methods often require a lot of samples to obtain reliable results, but most practical problems have very limited patient samples. In this paper, we develop a new method called Prediction Task Guided Health Record Aggregation (PTGHRA), which aggregates health records guided by prediction tasks, to construct training corpus for various representation learning models. Compared with unsupervised approaches, representation learning models integrated with PTGHRA yield a significant improvement in predictive capability of generated medical code vectors, especially for limited training samples. Copyright © 2018. Published by Elsevier Inc.

Web Support for Weight-Loss Interventions: PREDIRCAM2 Clinical Trial Baseline Characteristics and Preliminary Results.

PubMed

Alcántara-Aragón, Valeria; Rodrigo-Cano, Susana; Lupianez-Barbero, Ascension; Martinez, María José; Martinez, Carmen; Tapia, José; Iniesta, José Manuel; Tenes, Susana; Urgell, Eulalia; Navarro, Gemma; Hernando, M Elena; Merino-Torres, Juan Francisco; de Leiva, Alberto; Gonzalez, Cintia

2018-05-01

An ongoing clinical trial is testing the efficacy of web telematic support in a structured program for obesity treatment and diabetes prevention. Participants were recruited from two tertiary-care hospitals and randomized to receive either a telematic intervention (TI) supported by PREDIRCAM2 web platform or a non-telematic intervention (NTI). All receive 1-year follow-up. Both interventions consist of tailored dietary and exercise prescriptions, based on a Mediterranean dietary pattern and general WHO exercise recommendations for adults. At 6 months, both groups have received 7 contacts, 3 exclusively telematic for the TI group. This is a preliminary result intention-to-treat analysis. One hundred eighty-three participants were recruited, with a mean body mass index of 34.75 ± 2.75 kg/m 2 . General dropout rate at 6 months was 26.8%. Weight changes were statistically significant at months 3 and 6 compared to baseline, -2.915 ± 0.24 kg, -3.29 ± 0.36 kg, respectively (P < 0.001), but not statistically significant between the 3- and 6-month time points -0.37 ± 0.21 kg (P = 0.24). Mean group differences showed that the TI group lost 1.61 ± 1.88 kg more than the NTI group (P = 0.39). Waist, waist/hip ratio, resting heart rate, blood pressure, HbA1c, and low-density lipoprotein cholesterol also showed statistically significant changes at 6 months, with no significant differences between groups. Weight loss in the TI group shows similar results as the usual care NTI group for weight loss and control of obesity comorbidities. At completion of the clinical trial, these results will be reevaluated to assess the potential role of web support in weight-loss maintenance and its cost-effectiveness.

Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

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

Yim, Jackie; Suttie, Clare; Bromley, Regina

We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with themore » 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.« less

Comparison of Moderate- to High-Astigmatism Corrections Using WaveFront-Guided Laser In Situ Keratomileusis and Small-Incision Lenticule Extraction.

PubMed

Zhang, Jiamei; Wang, Yan; Chen, Xiaoqin

2016-04-01

To evaluate and compare refractive outcomes of moderate- and high-astigmatism correction after wavefront-guided laser in situ keratomileusis (LASIK) and small-incision lenticule extraction (SMILE). This comparative study enrolled a total of 64 eyes that had undergone SMILE (42 eyes) and wavefront-guided LASIK (22 eyes). Preoperative cylindrical diopters were ≤-2.25 D in moderate- and >-2.25 D in high-astigmatism subgroups. The refractive results were analyzed based on the Alpins vector method that included target-induced astigmatism, surgically induced astigmatism, difference vector, correction index, index of success, magnitude of error, angle of error, and flattening index. All subjects completed the 3-month follow-up. No significant differences were found in the target-induced astigmatism, surgically induced astigmatism, and difference vector between SMILE and wavefront-guided LASIK. However, the average angle of error value was -1.00 ± 3.16 after wavefront-guided LASIK and 1.22 ± 3.85 after SMILE with statistical significance (P < 0.05). The absolute angle of error value was statistically correlated with difference vector and index of success after both procedures. In the moderate-astigmatism group, correction index was 1.04 ± 0.15 after wavefront-guided LASIK and 0.88 ± 0.15 after SMILE (P < 0.05). However, in the high-astigmatism group, correction index was 0.87 ± 0.13 after wavefront-guided LASIK and 0.88 ± 0.12 after SMILE (P = 0.889). Both procedures showed preferable outcomes in the correction of moderate and high astigmatism. However, high astigmatism was undercorrected after both procedures. Axial error of astigmatic correction may be one of the potential factors for the undercorrection.

Characterization of the first complete genome sequence of an Impatiens necrotic spot orthotospovirus isolate from the United States and worldwide phylogenetic analyses of INSV isolates.

PubMed

Zhao, Kaixi; Margaria, Paolo; Rosa, Cristina

2018-05-10

Impatiens necrotic spot orthotospovirus (INSV) can impact economically important ornamental plants and vegetables worldwide. Characterization studies on INSV are limited. For most INSV isolates, there are no complete genome sequences available. This lack of genomic information has a negative impact on the understanding of the INSV genetic diversity and evolution. Here we report the first complete nucleotide sequence of a US INSV isolate. INSV-UP01 was isolated from an impatiens in Pennsylvania, US. RT-PCR was used to clone its full-length genome and Vector NTI to assemble overlapping sequences. Phylogenetic trees were constructed by using MEGA7 software to show the phylogenetic relationships with other available INSV sequences worldwide. This US isolate has genome and biological features classical of INSV species and clusters in the Western Hemisphere clade, but its origin appears to be recent. Furthermore, INSV-UP01 might have been involved in a recombination event with an Italian isolate belonging to the Asian clade. Our analyses support that INSV isolates infect a broad plant-host range they group by geographic origin and not by host, and are subjected to frequent recombination events. These results justify the need to generate and analyze complete genome sequences of orthotospoviruses in general and INSV in particular.

Sensitivity of S-Cat to Sleep Deprivation

DTIC Science & Technology

2006-01-01

DIRECTORATE BIOSCIENCES AND PROTECTION DVSION BIOBEHAVIORAL PERFORMANCE BRANCH 2485 GILLINGHAM DRIVE BROOKS CITY-BASE TX 78235 Approved for public...7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT Embry-Riddle Arrorautical CHII Systemns, Inc. NTI, Inc. Lyndon B...non-invasive means to objectively evaluate the cognitive ability of astronauts to perform ruission critical tasks, particularly during extended

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

9 CFR 381.76 - Post-mortem inspection, when required; extent; traditional, Streamlined Inspection System (SIS...

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Post-mortem inspection, when required... INSPECTION REGULATIONS Post Mortem Inspection; Disposition of Carcasses and Parts § 381.76 Post-mortem...) Inspection System and the New Turkey Inspection (NTI) System; rate of inspection. (a) A post-mortem...

Protracted Low-Dose Ionizing Radiation Effects upon Primate Performance

DTIC Science & Technology

1977-12-01

61 G. Dosimetry ................................ ............. 74 NTiS Whife Sectle ) U A N O U C E D JUSTIFICATION...AECL facility. Standard dosimetry techniques were utilized during radiation expo- sur.. In addition, extensive preexposure calibration was conducted...During each of the epochs, the five basic variables were deter- mined. These calculations were accomplished on an analog computer, Electronics Associates

Automatic/Control Processing Concepts and Their Implications for the Training of Skills.

DTIC Science & Technology

1982-04-01

driving a car are examples of automatic processes. Controll p s is comparatively slow, serial, limited by short-term memory, and requires subject effort...development has convinced us that moivation a oftn more Jmportn nti mAn =other iJli velLJoa jjthpgy gI. njj Lautomatic U_2,LLjjk. Motivation Is much more

Electromagnetic Pulse/Transient Threat Testing of Protection Devices for Amateur/Military Affiliate Radio System Equipment. Volume 2

DTIC Science & Technology

1985-10-31

4-45 4-1 SPC =. NTiC)NS I SPIKEGUARD SUPPRESSORS NANOSECOND TRANSIENT PROTECTION MODELS AVAILABLE FOR ,u * COAXIAL LINES...molded epoxy casc 4-40 General1- ~ *Sewiconductor4*industries,, Inc. Squats D oE.!v! MAXIMUM RATINGS DESCRIPTION coNro CASE 19 * Steady State POWr I

Teachers' Factors as Determinants of the Professional Competence of the Nigeria Certificate in Education Teachers

ERIC Educational Resources Information Center

Adetayo, Janet Oyebola

2016-01-01

The National Teachers' Institute (NTI) has been involved in training teachers for the Nigeria Certificate in Education (NCE) for over three decades through Distance Learning Programme. The quality of these teachers has been queried particularly when compared with those who run full-time NCE Programme. This study, therefore, determined the…

Teachers' Factors as Determinants of the Professional Competence of the Nigeria Certificate in Education (NCE) Teachers

ERIC Educational Resources Information Center

Adetayo, Janet Oyebola

2016-01-01

The National Teachers' Institute (NTI) has been involved in training teachers for the Nigeria Certificate in Education (NCE) for over three decades through Distance Learning Programme. The quality of these teachers has been queried particularly when compared with those who run full-time NCE Programme. This study, therefore, determined the…

Full-field drift Hamiltonian particle orbits in 3D geometry

NASA Astrophysics Data System (ADS)

Cooper, W. A.; Graves, J. P.; Brunner, S.; Isaev, M. Yu

2011-02-01

A Hamiltonian/Lagrangian theory to describe guiding centre orbit drift motion which is canonical in the Boozer coordinate frame has been extended to include full electromagnetic perturbed fields in anisotropic pressure 3D equilibria with nested magnetic flux surfaces. A redefinition of the guiding centre velocity to eliminate the motion due to finite equilibrium radial magnetic fields and the choice of a gauge condition that sets the radial component of the electromagnetic vector potential to zero are invoked to guarantee that the Boozer angular coordinates retain the canonical structure. The canonical momenta are identified and the guiding centre particle radial drift motion and parallel gyroradius evolution are derived. The particle coordinate position is linearly modified by wave-particle interactions. All the nonlinear wave-wave interactions appear explicitly only in the evolution of the parallel gyroradius. The radial variation of the electrostatic potential is related to the binormal component of the displacement vector for MHD-type perturbations. The electromagnetic vector potential projections can then be determined from the electrostatic potential and the radial component of the MHD displacement vector.

Visualization of the energy flow for guided forward and backward waves in and around a fluid-loaded elastic cylindrical shell via the Poynting vector field

NASA Astrophysics Data System (ADS)

Dean, Cleon E.; Braselton, James P.

2004-05-01

Color-coded and vector-arrow grid representations of the Poynting vector field are used to show the energy flow in and around a fluid-loaded elastic cylindrical shell for both forward- and backward-propagating waves. The present work uses a method adapted from a simpler technique due to Kaduchak and Marston [G. Kaduchak and P. L. Marston, ``Traveling-wave decomposition of surface displacements associated with scattering by a cylindrical shell: Numerical evaluation displaying guided forward and backward wave properties,'' J. Acoust. Soc. Am. 98, 3501-3507 (1995)] to isolate unidirectional energy flows.

A National Coordinating Center for Trauma Research

DTIC Science & Technology

2016-10-01

of ketamine during the first three days following injury has a sustained effect on reducing the incidence or severity of Post -Traumatic Stress... design , medical modeling, physical modeling, engineering and system integration. Progress Reported: The subcontract was fully executed on 05...were posted on the NTI website (www.nationaltraumainstitute.org). The goal is to comprehensively disseminate published works to the wider trauma

Concomitant Alterations of Desmosomes, Adhesiveness, and Diffusion through Gap Junction Channels in a Rat Ovarian Transformation Model System

DTIC Science & Technology

1993-01-01

while using a sterile glass slide, held parallel to the monolayer, as a MATERIALS AND METHODS straight edge. Cultures were photographed using phase...contrastmicrosoyo tonoa~r movng ofi I spheria mi rocr rie bed ntI h CEILL CELIL CONTACT AND DIFFU SION 23 and cytokeratin 8 antibodies (refer to Figs. 4a

Nuclear Parity with China?

DTIC Science & Technology

2012-01-01

reviewers, and others who read the paper and offered constructive suggestions, including Victor Utgoff, Heather Williams , and Jessica Knight of IDA...Energy Agency (IAEA) assumptions about the amount of fissile material needed to make a first- generation weapon. 6 Nuclear Threat Initiative (NTI...administration, recorded in the 2001 NPR, and was championed by the Republican presidential nominee, John McCain, in the 2008 presidential election . 15

Prospective and Retrospective Studies of Substance Abuse Treatment Outcomes: Methods and Results of Four Large-Scale Follow-Up Studies.

ERIC Educational Resources Information Center

Gerstein, Dean R.; Johnson, Robert A.

This report compares the research methods, provider and patient characteristics, and outcome results from four large-scale followup studies of drug treatment during the 1990s: (1) the California Drug and Alcohol Treatment Assessment (CALDATA); (2) Services Research Outcomes Study (SROS); (3) National Treatment Improvement Evaluation Study (NTIES);…

Involvement of the kappa-opioid receptor in the anxiogenic-like effect of CP 55,940 in male rats.

PubMed

Marín, S; Marco, E; Biscaia, M; Fernández, B; Rubio, M; Guaza, C; Schmidhammer, H; Viveros, M P

2003-02-01

We have studied the possible interaction between three selective opioid-receptor antagonists, nor-binaltorphimine (NB: kappa) (5 mg/kg), cyprodime (CY: mu) (10 mg/kg) and naltrindole (NTI: delta) (1 mg/kg), and the cannabinoid receptor agonist CP 55,940, in the modulation of anxiety (plus-maze) and adrenocortical activity (serum corticosterone levels by radioimmunoassay) in male rats. The holeboard was used to evaluate motor activity and directed exploration. CP 55,940 (75 microg/kg, but not 10 microg/kg) induced an anxiogenic-like effect, which was antagonised by NB. The other effects of CP 55,940 (75 microg/kg), a decreased holeboard activity and stimulation of adrenocortical activity, were not antagonised by any of the three opioid receptor antagonists. CY and NTI, when administered alone, induced marked reductions in motor activity, anxiogenic-like effects and stimulation of adrenocortical activity. The selective kappa-opioid receptor antagonist NB, on its own, did not modify the level of anxiety but stimulated adrenocortical activity. We provide the first pharmacological evidence about the involvement of the kappa-opioid receptor in the anxiogenic-like effect of CP 55,940.

Synthesis and evaluation of novel opioid ligands with a C-homomorphinan skeleton.

PubMed

Ishikawa, Kyoko; Mochizuki, Yusuke; Hirayama, Shigeto; Nemoto, Toru; Nagai, Kenichiro; Itoh, Kennosuke; Fujii, Hideaki

2016-05-15

As the reports about C-homomorphinans with the seven-membered C-ring are much fewer than those of morphinan derivatives with a six-membered C-ring, we attempted to synthesize C-homomorphinan derivatives and to evaluate their opioid activities. C-Homomorphinan 5 showed sufficient binding affinities to the opioid receptors. C-Homomorphinan derivatives possessing the δ address moiety such as indole (NTI-type), quinoline, or benzylidene (BNTX-type) functionalities showed the strongest binding affinities for the δ receptor among the three types of opioid receptors, which indicated that the C-homomorphinan skeleton sufficiently functions as a message-part in the ligand. Although NTI-type compound 8 and quinoline compound 9 with C-homomorphinan scaffold exhibited lower affinities and selectivities for the δ receptor than the corresponding morphinan derivatives did, both the binding affinity and selectivity for the δ receptor of BNTX-type compound 12 with a seven-membered C-ring were improved compared with the corresponding compounds with a six-membered C-ring including BNTX itself. BNTX-Type compound 12 was the most selective δ receptor antagonist among the tested compounds. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dengue and Chikungunya Vector Control Pocket Guide

USDA-ARS?s Scientific Manuscript database

This technical guide consolidates information and procedures for surveillance and control of mosquitoes that transmit dengue and chikungunya viruses. The guide focuses on mosquitoes that transmit dengue but also makes reference to chikungunya and yellow fever because the pathogens that cause these ...

Cell-Penetrating Peptide-Mediated Delivery of Cas9 Protein and Guide RNA for Genome Editing.

PubMed

Suresh, Bharathi; Ramakrishna, Suresh; Kim, Hyongbum

2017-01-01

The clustered, regularly interspaced, short palindromic repeat (CRISPR)-associated (Cas) system represents an efficient tool for genome editing. It consists of two components: the Cas9 protein and a guide RNA. To date, delivery of these two components has been achieved using either plasmid or viral vectors or direct delivery of protein and RNA. Plasmid- and virus-free direct delivery of Cas9 protein and guide RNA has several advantages over the conventional plasmid-mediated approach. Direct delivery results in shorter exposure time at the cellular level, which in turn leads to lower toxicity and fewer off-target mutations with reduced host immune responses, whereas plasmid- or viral vector-mediated delivery can result in uncontrolled integration of the vector sequence into the host genome and unwanted immune responses. Cell-penetrating peptide (CPP), a peptide that has an intrinsic ability to translocate across cell membranes, has been adopted as a means of achieving efficient Cas9 protein and guide RNA delivery. We developed a method for treating human cell lines with CPP-conjugated recombinant Cas9 protein and CPP-complexed guide RNAs that leads to endogenous gene disruption. Here we describe a protocol for preparing an efficient CPP-conjugated recombinant Cas9 protein and CPP-complexed guide RNAs, as well as treatment methods to achieve safe genome editing in human cell lines.

Magnetically enhanced adeno-associated viral vector delivery for human neural stem cell infection.

PubMed

Kim, Eunmi; Oh, Ji-Seon; Ahn, Ik-Sung; Park, Kook In; Jang, Jae-Hyung

2011-11-01

Gene therapy technology is a powerful tool to elucidate the molecular cues that precisely regulate stem cell fates, but developing safe vehicles or mechanisms that are capable of delivering genes to stem cells with high efficiency remains a challenge. In this study, we developed a magnetically guided adeno-associated virus (AAV) delivery system for gene delivery to human neural stem cells (hNSCs). Magnetically guided AAV delivery resulted in rapid accumulation of vectors on target cells followed by forced penetration of the vectors across the plasma membrane, ultimately leading to fast and efficient cellular transduction. To combine AAV vectors with the magnetically guided delivery, AAV was genetically modified to display hexa-histidine (6xHis) on the physically exposed loop of the AAV2 capsid (6xHis AAV), which interacted with nickel ions chelated on NTA-biotin conjugated to streptavidin-coated superparamagnetic iron oxide nanoparticles (NiStNPs). NiStNP-mediated 6xHis AAV delivery under magnetic fields led to significantly enhanced cellular transduction in a non-permissive cell type (i.e., hNSCs). In addition, this delivery method reduced the viral exposure times required to induce a high level of transduction by as much as to 2-10 min of hNSC infection, thus demonstrating the great potential of magnetically guided AAV delivery for numerous gene therapy and stem cell applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

Structural damage detection using deep learning of ultrasonic guided waves

NASA Astrophysics Data System (ADS)

Melville, Joseph; Alguri, K. Supreet; Deemer, Chris; Harley, Joel B.

2018-04-01

Structural health monitoring using ultrasonic guided waves relies on accurate interpretation of guided wave propagation to distinguish damage state indicators. However, traditional physics based models do not provide an accurate representation, and classic data driven techniques, such as a support vector machine, are too simplistic to capture the complex nature of ultrasonic guide waves. To address this challenge, this paper uses a deep learning interpretation of ultrasonic guided waves to achieve fast, accurate, and automated structural damaged detection. To achieve this, full wavefield scans of thin metal plates are used, half from the undamaged state and half from the damaged state. This data is used to train our deep network to predict the damage state of a plate with 99.98% accuracy given signals from just 10 spatial locations on the plate, as compared to that of a support vector machine (SVM), which achieved a 62% accuracy.

Using Simultaneous Prompting to Teach Restaurant Words and Classifications as Non-Target Information to Secondary Students with Moderate to Severe Disabilities

ERIC Educational Resources Information Center

Smith, Bethany R.; Schuster, John W.; Collins, Belva; Kleinert, Harold

2011-01-01

This paper reviews selected literature pertaining to simultaneous prompting and the acquisition of non-target information for individuals with moderate to severe disabilities. The purpose of this review was to discuss the definition of non-target information (NTI) and the various places it can be embedded within an instructional trial. The…

Macromolecular Calculations for the XTAL-System of Crystallographic Programs

DTIC Science & Technology

1989-06-01

INSTRUMENT DE NTiFiCAT C 1.1BE R ORG!A%,ZAT:ON1 (if applicable) Office of Naval Research ONR N00014-88-K-0323 8c A:):)R -S ( Citr . Sta te, and ZIP Code) 10...of prio, difference, and updated maps, in addition to the usual BDF handling, is simple but a fruitful source of confusion. For the usual iterative

Guided Radiation Beams in Free Electron Lasers.

DTIC Science & Technology

1988-05-19

the electron beam in an FEL that the radiation beam will remain guided. 0 20 II. Refractive Index Associated with FELs In our model, the vector ...eIAw/ymOc(exp(ikwz) + c.c.) ex/2 , is the wiggle velocity, y is the Lorentz factor, Aw is the vector potential amplitude of the planar wiggler...Balboa Avenue Palo Alto, CA 94303 San Diego, CA 92123 38 Dr. S. Krinsky Nat. Synchrotron Light Source Dr. Michael Lavan Brookhaven National Laboratory U.S

Automation of the guiding center expansion

NASA Astrophysics Data System (ADS)

Burby, J. W.; Squire, J.; Qin, H.

2013-07-01

We report on the use of the recently developed Mathematica package VEST (Vector Einstein Summation Tools) to automatically derive the guiding center transformation. Our Mathematica code employs a recursive procedure to derive the transformation order-by-order. This procedure has several novel features. (1) It is designed to allow the user to easily explore the guiding center transformation's numerous non-unique forms or representations. (2) The procedure proceeds entirely in cartesian position and velocity coordinates, thereby producing manifestly gyrogauge invariant results; the commonly used perpendicular unit vector fields e1,e2 are never even introduced. (3) It is easy to apply in the derivation of higher-order contributions to the guiding center transformation without fear of human error. Our code therefore stands as a useful tool for exploring subtle issues related to the physics of toroidal momentum conservation in tokamaks.

Automation of The Guiding Center Expansion

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

J. W. Burby, J. Squire and H. Qin

2013-03-19

We report on the use of the recently-developed Mathematica package VEST (Vector Einstein Summation Tools) to automatically derive the guiding center transformation. Our Mathematica code employs a recursive procedure to derive the transformation order-by-order. This procedure has several novel features. (1) It is designed to allow the user to easily explore the guiding center transformation's numerous nonunique forms or representations. (2) The procedure proceeds entirely in cartesian position and velocity coordinates, thereby producing manifestly gyrogauge invariant results; the commonly-used perpendicular unit vector fields e1, e2 are never even introduced. (3) It is easy to apply in the derivation of higher-ordermore » contributions to the guiding center transformation without fear of human error. Our code therefore stands as a useful tool for exploring subtle issues related to the physics of toroidal momentum conservation in tokamaks« less

Nuclear routing networks span between nuclear pore complexes and genomic DNA to guide nucleoplasmic trafficking of biomolecules

PubMed Central

Malecki, Marek; Malecki, Bianca

2012-01-01

In health and disease, biomolecules, which are involved in gene expression, recombination, or reprogramming have to traffic through the nucleoplasm, between nuclear pore complexes (NPCs) and genomic DNA (gDNA). This trafficking is guided by the recently revealed nuclear routing networks (NRNs). In this study, we aimed to investigate, if the NRNs have established associations with the genomic DNA in situ and if the NRNs have capabilities to bind the DNA de novo. Moreover, we aimed to study further, if nucleoplasmic trafficking of the histones, rRNA, and transgenes’ vectors, between the NPCs and gDNA, is guided by the NRNs. We used Xenopus laevis oocytes as the model system. We engineered the transgenes’ DNA vectors equipped with the SV40 LTA nuclear localization signals (NLS) and/or HIV Rev nuclear export signals (NES). We purified histones, 5S rRNA, and gDNA. We rendered all these molecules superparamagnetic and fluorescent for detection with nuclear magnetic resonance (NMR), total reflection x-ray fluorescence (TXRF), energy dispersive x-ray spectroscopy (EDXS), and electron energy loss spectroscopy (EELS). The NRNs span between the NPCs and genomic DNA. They form firm bonds with the gDNA in situ. After complete digestion of the nucleic acids with the RNases and DNases, the newly added DNA - modified with the dNTP analogs, bonds firmly to the NRNs. Moreover, the NRNs guide the trafficking of the DNA transgenes’ vectors - modified with the SV40 LTA NLS, following their import into the nuclei through the NPCs. The pathway is identical to that of histones. The NRNs also guide the trafficking of the DNA transgenes’ vectors, modified with the HIV Rev NES, to the NPCs, followed by their export out of the nuclei. Ribosomal RNAs follow the same pathway. To summarize, the NRNs are the structures connecting the NPCs and the gDNA. They guide the trafficking of the biomolecules between the NPCs and the gDNA. PMID:23275893

Clinically Employed Opioid Analgesics Produce Antinociception via μ-δ Opioid Receptor Heteromers in Rhesus Monkeys

PubMed Central

2012-01-01

Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans. PMID:23019498

Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

PubMed

Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

2012-09-19

Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

Automation of the guiding center expansion

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

Burby, J. W.; Squire, J.; Qin, H.

2013-07-15

We report on the use of the recently developed Mathematica package VEST (Vector Einstein Summation Tools) to automatically derive the guiding center transformation. Our Mathematica code employs a recursive procedure to derive the transformation order-by-order. This procedure has several novel features. (1) It is designed to allow the user to easily explore the guiding center transformation's numerous non-unique forms or representations. (2) The procedure proceeds entirely in cartesian position and velocity coordinates, thereby producing manifestly gyrogauge invariant results; the commonly used perpendicular unit vector fields e{sub 1},e{sub 2} are never even introduced. (3) It is easy to apply in themore » derivation of higher-order contributions to the guiding center transformation without fear of human error. Our code therefore stands as a useful tool for exploring subtle issues related to the physics of toroidal momentum conservation in tokamaks.« less

A novel double fine guide sensor design on space telescope

NASA Astrophysics Data System (ADS)

Zhang, Xu-xu; Yin, Da-yi

2018-02-01

To get high precision attitude for space telescope, a double marginal FOV (field of view) FGS (Fine Guide Sensor) is proposed. It is composed of two large area APS CMOS sensors and both share the same lens in main light of sight. More star vectors can be get by two FGS and be used for high precision attitude determination. To improve star identification speed, the vector cross product in inter-star angles for small marginal FOV different from traditional way is elaborated and parallel processing method is applied to pyramid algorithm. The star vectors from two sensors are then used to attitude fusion with traditional QUEST algorithm. The simulation results show that the system can get high accuracy three axis attitudes and the scheme is feasibility.

Reverse chemical ecology approach for the identification of a mosquito oviposition attractant

USDA-ARS?s Scientific Manuscript database

Pheromones and other semiochemicals play a crucial role in today’s integrated pest and vector management strategies for controlling populations of insects causing loses to agriculture and vectoring diseases to humans. These semiochemicals are typically discovered by bioassay-guided approaches. Here,...

Hypermetabolic Low Triiodothyronine Syndrome of Burn Injury

DTIC Science & Technology

1982-12-01

from the ones entered) which significantly (p for TSH. Pooled hypothyroid, normal. and hyperthyroid < 0.05) reduced the residual variance of the...34 ...that found in other forms of NTI." These results are . " .compatible with failure of brain centers controlling the thyroid axis2’ or with direct...Wilkinson AW, Cuth- tients with other nonthyroidal illnesses develop a hyper- bertson D (Eds). Chicago, Year Book Medical Publishers. Inc., metabolic low T

Dark-bright soliton pairs in nonlocal nonlinear media.

PubMed

Lin, Yuan Yao; Lee, Ray-Kuang

2007-07-09

We study the formation of dark-bright vector soliton pairs in nonlocal Kerr-type nonlinear medium. We show, by analytical analysis and direct numerical calculation, that in addition to stabilize of vector soliton pairs nonlocal nonlinearity also helps to reduce the threshold power for forming a guided bright soliton. With help of the nonlocality, it is expected that the observation of dark-bright vector soliton pairs in experiments becomes more workable.

Insecticide Resistance Management

DTIC Science & Technology

2013-01-01

been a side effect of insect vector control programs since 1914, and insect disease vectors in over 45 countries are resistant to at least one...the CDC and WHO bioassays can be performed on various insects , the remainder of the guide will focus specifically on how to detect resistance in...mosquito vector populations. For a description of how to develop a bioassay for resistance testing in other groups of insects , refer to the following

AAV viral vector delivery to the brain by shape-conforming MR-guided infusions.

PubMed

Bankiewicz, Krystof S; Sudhakar, Vivek; Samaranch, Lluis; San Sebastian, Waldy; Bringas, John; Forsayeth, John

2016-10-28

Gene transfer technology offers great promise as a potential therapeutic approach to the brain but has to be viewed as a very complex technology. Success of ongoing clinical gene therapy trials depends on many factors such as selection of the correct genetic and anatomical target in the brain. In addition, selection of the viral vector capable of transfer of therapeutic gene into target cells, along with long-term expression that avoids immunotoxicity has to be established. As with any drug development strategy, delivery of gene therapy has to be consistent and predictable in each study subject. Failed drug and vector delivery will lead to failed clinical trials. In this article, we describe our experience with AAV viral vector delivery system, that allows us to optimize and monitor in real time viral vector administration into affected regions of the brain. In addition to discussing MRI-guided technology for administration of AAV vectors we have developed and now employ in current clinical trials, we also describe ways in which infusion cannula design and stereotactic trajectory may be used to maximize the anatomical coverage by using fluid backflow. This innovative approach enables more precise coverage by fitting the shape of the infusion to the shape of the anatomical target. Copyright © 2016 Elsevier B.V. All rights reserved.

A Neurocomputational Model of Goal-Directed Navigation in Insect-Inspired Artificial Agents

PubMed Central

Goldschmidt, Dennis; Manoonpong, Poramate; Dasgupta, Sakyasingha

2017-01-01

Despite their small size, insect brains are able to produce robust and efficient navigation in complex environments. Specifically in social insects, such as ants and bees, these navigational capabilities are guided by orientation directing vectors generated by a process called path integration. During this process, they integrate compass and odometric cues to estimate their current location as a vector, called the home vector for guiding them back home on a straight path. They further acquire and retrieve path integration-based vector memories globally to the nest or based on visual landmarks. Although existing computational models reproduced similar behaviors, a neurocomputational model of vector navigation including the acquisition of vector representations has not been described before. Here we present a model of neural mechanisms in a modular closed-loop control—enabling vector navigation in artificial agents. The model consists of a path integration mechanism, reward-modulated global learning, random search, and action selection. The path integration mechanism integrates compass and odometric cues to compute a vectorial representation of the agent's current location as neural activity patterns in circular arrays. A reward-modulated learning rule enables the acquisition of vector memories by associating the local food reward with the path integration state. A motor output is computed based on the combination of vector memories and random exploration. In simulation, we show that the neural mechanisms enable robust homing and localization, even in the presence of external sensory noise. The proposed learning rules lead to goal-directed navigation and route formation performed under realistic conditions. Consequently, we provide a novel approach for vector learning and navigation in a simulated, situated agent linking behavioral observations to their possible underlying neural substrates. PMID:28446872

A Neurocomputational Model of Goal-Directed Navigation in Insect-Inspired Artificial Agents.

PubMed

Goldschmidt, Dennis; Manoonpong, Poramate; Dasgupta, Sakyasingha

2017-01-01

Despite their small size, insect brains are able to produce robust and efficient navigation in complex environments. Specifically in social insects, such as ants and bees, these navigational capabilities are guided by orientation directing vectors generated by a process called path integration. During this process, they integrate compass and odometric cues to estimate their current location as a vector, called the home vector for guiding them back home on a straight path. They further acquire and retrieve path integration-based vector memories globally to the nest or based on visual landmarks. Although existing computational models reproduced similar behaviors, a neurocomputational model of vector navigation including the acquisition of vector representations has not been described before. Here we present a model of neural mechanisms in a modular closed-loop control-enabling vector navigation in artificial agents. The model consists of a path integration mechanism, reward-modulated global learning, random search, and action selection. The path integration mechanism integrates compass and odometric cues to compute a vectorial representation of the agent's current location as neural activity patterns in circular arrays. A reward-modulated learning rule enables the acquisition of vector memories by associating the local food reward with the path integration state. A motor output is computed based on the combination of vector memories and random exploration. In simulation, we show that the neural mechanisms enable robust homing and localization, even in the presence of external sensory noise. The proposed learning rules lead to goal-directed navigation and route formation performed under realistic conditions. Consequently, we provide a novel approach for vector learning and navigation in a simulated, situated agent linking behavioral observations to their possible underlying neural substrates.

United States Air Force Guide to Operational Surveillance of Medically Important Vectors and Pests Operational Entomology

DTIC Science & Technology

2006-08-15

Programs Section 3. Sampling Equipment Sampling Equipment Solid-State Army Miniature (SSAM) trap ABC style trap Encephalitis Vector Survey Trap CDC...Baseline Survey - these are conducted to determine the types of vectors and pests occurring in the area of operations, their respective breeding sites...or source habitat, and seasonal activity patterns. Operational Survey - data collected in an operational survey are used specifically to aid pest

Targeted genome editing in a quail cell line using a customized CRISPR/Cas9 system.

PubMed

Ahn, Jinsoo; Lee, Joonbum; Park, Ju Yeon; Oh, Keon Bong; Hwang, Seongsoo; Lee, Chang-Won; Lee, Kichoon

2017-05-01

Soon after RNA-guided Cas9 (CRISPR-associated protein 9) endonuclease opened a new era of targeted genome editing, the CRISPR/Cas9 platform began to be extensively used to modify genes in various types of cells and organisms. However, successful CRISPR/Cas9-mediated insertion/deletion (indel) mutation remains to be demonstrated in avian cell lines. The objective of this study was to design a poultry-specific CRISPR/Cas9 system to efficiently introduce targeted deletion mutation in chromosomes of the quail muscle clone 7 (QM7) cell line using a customized quail CRISPR vector. In this study, two avian-specific promoters, quail 7SK (q7SK) promoter and CBh promoter, the hybrid form of cytomegalovirus and chicken β-actin promoters, were cloned into a CRISPR vector for the expression of guide RNA and Cas9 protein, respectively. Then, guide RNA, which was designed to target 20-base pair (bp) nucleotides in the quail melanophilin (MLPH) locus, was ligated to the modified CRISPR vector and transfected to QM7 cells. Our results showed multiple indel mutations in the quail MLPH locus in nearly half of the alleles being tested, suggesting the high efficiency of the system for targeted gene modification. The new CRISPR vector developed from this study has the potential application to generate knockout avian cell lines and knockout poultry. © 2016 Poultry Science Association Inc.

Spin wave filtering and guiding in Permalloy/iron nanowires

NASA Astrophysics Data System (ADS)

Silvani, R.; Kostylev, M.; Adeyeye, A. O.; Gubbiotti, G.

2018-03-01

We have investigated the spin wave filtering and guiding properties of periodic array of single (Permalloy and Fe) and bi-layer (Py/Fe) nanowires (NWs) by means of Brillouin light scattering measurements and micromagnetic simulations. For all the nanowire arrays, the thickness of the layers is 10 nm while all NWs have the same width of 340 nm and edge-to-edge separation of 100 nm. Spin wave dispersion has been measured in the Damon-Eshbach configuration for wave vector either parallel or perpendicular to the nanowire length. This study reveals the filtering property of the spin waves when the wave vector is perpendicular to the NW length, with frequency ranges where the spin wave propagation is permitted separated by frequency band gaps, and the guiding property of NW when the wave vector is oriented parallel to the NW, with spin wave modes propagating in parallel channels in the central and edge regions of the NW. The measured dispersions were well reproduced by micromagnetic simulations, which also deliver the spatial profiles for the modes at zero wave vector. To reproduce the dispersion of the modes localized close to the NW edges, uniaxial anisotropy has been introduced. In the case of Permalloy/iron NWs, the obtained results have been compared with those for a 20 nm thick effective NW having average magnetic properties of the two materials.

HAL/S programmer's guide. [space shuttle flight software language

NASA Technical Reports Server (NTRS)

Newbold, P. M.; Hotz, R. L.

1974-01-01

HAL/S is a programming language developed to satisfy the flight software requirements for the space shuttle program. The user's guide explains pertinent language operating procedures and described the various HAL/S facilities for manipulating integer, scalar, vector, and matrix data types.

The Role of recA Protein in the Multiplicity Reactivation Pathway of Phage T4.

DTIC Science & Technology

1983-01-01

shown below: HARRIS BERNSTEIN DATE Professor of Medical Molecular Microbiology i To Jane and Brian they make it all worthwhile Aeoession For NTiSi...Department of Molecular and Medical Microbiology , University of Arizona College of Medicine, Tucson, Arizona, 85724. Media The following growth media...M. and Prescott , C. (1983) Inducable expression of a gene specific to the recF pathway for recombination in Escherichia coli K12. Mol Gen Genet 190

Size 12 Leather Personnel Carriers: Tactical Mobility and the Light Infantry,

DTIC Science & Technology

1990-12-15

PERFORMING ORGANIZATION NAME(S) AND AGORESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER A~nti fT2L- SLJV Vo 9. SPONSORING/ MONITORING AGENCY NAME(S) AND... perform terrain analysis in light of their units’ mission and evaluate the terrain’s potential for cover and concealment, its impact on their own and...modern mounted infantryman would require three functions in one, "stalker, athelete , and marksman", reflected long term training and professionalism

A review of the vector management methods to prevent and control outbreaks of West Nile virus infection and the challenge for Europe

PubMed Central

2014-01-01

West Nile virus infection is a growing concern in Europe. Vector management is often the primary option to prevent and control outbreaks of the disease. Its implementation is, however, complex and needs to be supported by integrated multidisciplinary surveillance systems and to be organized within the framework of predefined response plans. The impact of the vector control measures depends on multiple factors and the identification of the best combination of vector control methods is therefore not always straightforward. Therefore, this contribution aims at critically reviewing the existing vector control methods to prevent and control outbreaks of West Nile virus infection and to present the challenges for Europe. Most West Nile virus vector control experiences have been recently developed in the US, where ecological conditions are different from the EU and vector control is organized under a different regulatory frame. The extrapolation of information produced in North America to Europe might be limited because of the seemingly different epidemiology in the European region. Therefore, there is an urgent need to analyse the European experiences of the prevention and control of outbreaks of West Nile virus infection and to perform robust cost-benefit analysis that can guide the implementation of the appropriate control measures. Furthermore, to be effective, vector control programs require a strong organisational backbone relying on a previously defined plan, skilled technicians and operators, appropriate equipment, and sufficient financial resources. A decision making guide scheme is proposed which may assist in the process of implementation of vector control measures tailored on specific areas and considering the available information and possible scenarios. PMID:25015004

Dengue and Chikungunya Vector Control Pocket Guide

DTIC Science & Technology

2012-01-27

Aedes aegypti readily bites people indoors and will rest on wall surfaces after taking a...countries are areas where dengue risk is well known. Aedes aegypti , Ae. albopictus and Ae. polynesiensis are three mosquito species that are...vectors of dengue. Aedes aegypti accounts for >95% of all cases worldwide. During deployments, all three species must be

The influence of learning on host plant preference in a significant phytopathogen vector, Diaphorina citri

USDA-ARS?s Scientific Manuscript database

Although specialist herbivorous insects are guided by innate responses to host plant cues, host plant preference may be influenced by experience and is not dictated by instinct alone. The effect of learning on host plant preference was examined in the Asian citrus psyllid, Diaphorina citri, vector ...

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

PubMed

Schwartz, Matthew L; Jorgensen, Erik M

2016-04-01

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

Terror and Reprisal - An Ethical Perspective.

DTIC Science & Technology

1985-03-19

partial fulfillment of the requirements for LL.5 the degree of Master of Arts in Philosophy . LA.C-31 I .o.. r.’ 17-m SECURITY CLASSIFICATION OF THIS...Chapel Hill in partial fulfillment of the requirements for the degree of Master of Arts in Philosophy . i9. KEY WORDS (Continue on reverse aide if...for the degree of Master of Arts in the Department of Philosophy . Chapel Hill 1985 Aoceessio For NTI: & DTTC ’P [l r j-’ :t- ./’ 1 . :Iid/3r - -1 ILIi

The Development of Enhanced Heat Transfer Condenser Tubing

DTIC Science & Technology

1973-07-01

side coeffic ient. The profiled tube condensing coefficient h’ is derived by analogy with the Nusselt ( 8 ) equation for the average condensing ... condensing coefficient value s = 0.925 was derived by Nusselt for laminar flow cnditions. It is well known that under turbulent film flow with waves...DTICSEL ECTE SEPA 0O1981ŕ jjH E DEVELOPME NTI OF ENHANCED HEAT TRANSFER CONDENSER TUBING! I H .EWSON T. D. AODGSON ! 0L L U I-.L V.i 1-- Chemical

Nonlinear Ocean Waves

DTIC Science & Technology

1993-01-12

work is the fact that the equation due to Kadomtsev & Petviashvili (1970), ax(atU + UaxU + a, 3 U) + ay2 U = 0, (KP) describes approximately the...B.B. Kadomtsev & V.1 Petviashvili , Soy. Phys. Doklady, 15, pp. 539- 541, 1970 NTI QRIA@lo310 For, STis GRAU ], DTIC TAB 0 jJUSo catzio DiSt AV ...numerical discretizations of the nonlinear Schr6dinger equation , i atV + axEV + 21VI2V = 0, (NLS) with periodic boundary conditions. This equation is a well

Weather Extremes Around the World

DTIC Science & Technology

1974-04-01

the lowest temperature has been recorded at Ust’Shchiigor in the Soviet Union at about 55°N, 50°E.4S This station, located near the Siberian border... Siberian taiga (northern coniferous forest). It is an area of extreme eontinentality, lying near the eastern end of the world’s largest landmass and...HO hours per year Mouse I’ciik Lighthouse, Mistake Island. Maine l"\\ig is a cloud al the surface of Ihe earth, eonsislinj» of a nti’ltilude of

The BESCT Lung Cancer Program (Biology, Education, Screening, Chemoprevention, and Treatment)

DTIC Science & Technology

2005-03-01

So 0 lDF Ep < a 185Total Nti of No, of NoWo 5t 1I 282 ir 47:419%) IN " 81 t~rlr’ 3 r 35 47 74 7 Fwrs 12 5 0 12 130 24 24 1 23 60 6238 S 1A 83 S.II...drugs. (NSAIDs)? In vitro versus in vivo results and the relevance for the prevention and treatment of cancer. Biochemn Pharmacol 2002; 63:343- 347 , 21

Binding Assays for the Quantitative Detection of P. brevis Polyether Neurotoxins in Biological Samples and Antibodies as Therapeutic Aids for Polyether Marine Intoxication

DTIC Science & Technology

1987-12-01

editions are obsolete. -I Block 19 continued structure. Preliminary experiments involving conversion of the radio- immunoassay to a urease enzyme linked...the radioimmunoassay to a urease I enzyme linked form have been successful. DTIC GTAB Di tributioul AV~i~b~±~YCoded Avsi abi11i ntY___ tat Special...necessary prior to thin- layer chromatography. A preparative thin- layer chromatography step using silica gel plates (1000 u thickness) utilizes acetone

KSOS Secure Unix Verification Plan (Kernelized Secure Operating System).

DTIC Science & Technology

1980-12-01

shall be handled as proprietary information untii 5 Apri 1978. After that time, the Government m-. distribute the document as it sees fit. UNIX and PWB...Accession For P-’(’ T.’i3 :- NTI G.;:’... &I : " \\ " Y: Codes mdlc/or 71!O lii WDL-TR7809 KSOS VERIFICATION PLAN SECTION I INTRODUCTION "’The purpose...funding, additional tools may be available by the time they are needed for FSOS verification. We intend to use the best available technology in

The War in the North Sea. Volume I. From the Beginning of the War to the First of September, 1914. Part 2. Chapters 5,6; Appendices 14-21; Charts 18-35

DTIC Science & Technology

1937-01-01

firrt British Fleet in the North Sea. Indirect preliminary preparations for war by Great Britain since 1904. Operation studies in case Great Britain...34 , , • f>ri*i5h and German Gunfire. . ßnti’sh Gunfire; JQRTH SEA Vot. I / CHART E3. ’ i \\ tj’SO C Of Qrg<n«»^^. Noetic «! M’ilcs LEGETHD

Interim Terrain Data (ITD) and Vector Product Interim Terrain Data (VITD) user's guide

DOT National Transportation Integrated Search

1996-09-01

This guide is intended to be a convenient reference for users of these types of terrain analysis data. ITD is a digitized version of the standard 1:50,000-scale tactical terrain analysis data base (TTADB) product produced by the Defense Mapping Agenc...

Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking (ICArUS): Phase 1 Test and Evaluation Development Guide

DTIC Science & Technology

2014-11-01

Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking (ICArUS): Phase 1 Test and Evaluation Development Guide Craig...Self-initiated sensemaking ........................................................................................... 19 Feature Vector Format: Tasks...The Integrated Cognitive-neuroscience Architectures for Understanding Sensemaking (ICArUS) Program aimed to build computational cognitive

Topography-Guided Transepithelial Surface Ablation in the Treatment of Moderate to High Astigmatism.

PubMed

Chen, Xiangjun; Stojanovic, Aleksandar; Simonsen, David; Wang, Xiaorui; Liu, Yanhua; Utheim, Tor Paaske

2016-06-01

To analyze the outcomes of treatment of astigmatism of 2.00 diopters (D) or greater with topography-guided transepithelial surface ablation. Retrospective analysis of a series of 206 eyes divided into two groups: myopic astigmatism (153 eyes) and mixed astigmatism (53 eyes). All cases were treated with topography-guided transepithelial surface ablation. Efficacy, safety, and predictability were evaluated, and vector analysis of cylindrical correction was performed. The median preoperative spherical equivalent was -2.63 and -0.63 D for the myopic and mixed astigmatism groups, respectively, with median cylinder of -2.50 D. Postoperative uncorrected distance visual acuity was 20/20 or better in 92% and 83% of eyes in the myopic and mixed astigmatism groups, respectively; the corresponding efficacy indices were 1.00 and 0.96 and residual astigmatism of 0.50 D or less was present in 82.4% and 56.7% of eyes in the myopic and mixed astigmatism groups, respectively. The arithmetic mean magnitude of the difference vector was 0.38 (myopic) and 0.65 (mixed) D. Difference vector magnitude was positively correlated with the magnitude of target induced astigmatism in both groups. The geometric mean coefficient of adjustment index was 1.04 and 1.19, representing undercorrection of 4% and 19% in the myopic and mixed astigmatism groups, respectively. Topography-guided transepithelial ablation is a safe, effective, and predictable treatment for moderate to high astigmatism. [J Refract Surg. 2016;32(6):418-425.]. Copyright 2016, SLACK Incorporated.

Design of single-polarization wavelength splitter based on photonic crystal fiber.

PubMed

Zhang, Shanshan; Zhang, Weigang; Geng, Pengcheng; Li, Xiaolan; Ruan, Juan

2011-12-20

A new single-polarization wavelength splitter based on the photonic crystal fiber (PCF) has been proposed. The full-vector finite-element method (FEM) is applied to analyze the single-polarization single-mode guiding properties. Splitting of two different wavelengths is realized by adjusting the structural parameters. The semi-vector three-dimensional beam propagation method is employed to confirm the wavelength splitting characteristics of the PCF. Numerical simulations show that the wavelengths of 1.3 μm and 1.55 μm are split for a fiber length of 10.7 mm with single-polarization guiding in each core. The crosstalk between the two cores is low over appreciable optical bandwidths.

Guiding automated left ventricular chamber segmentation in cardiac imaging using the concept of conserved myocardial volume.

PubMed

Garson, Christopher D; Li, Bing; Acton, Scott T; Hossack, John A

2008-06-01

The active surface technique using gradient vector flow allows semi-automated segmentation of ventricular borders. The accuracy of the algorithm depends on the optimal selection of several key parameters. We investigated the use of conservation of myocardial volume for quantitative assessment of each of these parameters using synthetic and in vivo data. We predicted that for a given set of model parameters, strong conservation of volume would correlate with accurate segmentation. The metric was most useful when applied to the gradient vector field weighting and temporal step-size parameters, but less effective in guiding an optimal choice of the active surface tension and rigidity parameters.

Equivalence and interchangeability of narrow therapeutic index drugs in organ transplantation

PubMed Central

Johnston, Atholl

2013-01-01

The calcineurin inhibitors (CNIs), ciclosporin and tacrolimus, are the mainstay of immunosuppression in solid organ transplantation. Generic formulations of these drugs are now available. With increasing pressure on healthcare budgets and the consequent need to match health expectations to available resources, substitution with a generic product appears an attractive option to reduce costs. Approval of generic products differs from innovator drugs, and narrow therapeutic index drugs (NTIs; including CNIs) bring their own particular considerations. With NTIs, small variations in drug exposure could result in reduced immunosuppression or drug toxicity with potentially adverse effects on patient outcomes. NTIs are subject to stricter regulatory approval versus many other generic drugs. However, different generic formulations may still not necessarily be therapeutically equivalent in individuals, raising the possibility of significant differences in exposure between products. Although regional recommendations vary, many guidelines emphasise the need for NTI drug substitution to be initiated by the transplant physician, thus ensuring careful therapeutic monitoring and reduced negative patient impact. The need for therapeutic monitoring during generic substitution has important implications for the overall costs of generic treatment as these costs have to be factored in to the potential savings made from using generic formulations. The reduced acquisition costs of generic products may not necessarily translate into lower overall healthcare costs. This article examines the issue of equivalence and interchangeability of NTI drugs used in organ transplantation, the implications of the approval process for generic drugs on treatment efficacy and safety, and the effective management of substitutions between products. PMID:24089632

The Plasmodium bottleneck: malaria parasite losses in the mosquito vector

PubMed Central

Smith, Ryan C; Vega-Rodríguez, Joel; Jacobs-Lorena, Marcelo

2014-01-01

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission. PMID:25185005

A Deterministic Model to Quantify Risk and Guide Mitigation Strategies to Reduce Bluetongue Virus Transmission in California Dairy Cattle

PubMed Central

Mayo, Christie; Shelley, Courtney; MacLachlan, N. James; Gardner, Ian; Hartley, David; Barker, Christopher

2016-01-01

The global distribution of bluetongue virus (BTV) has been changing recently, perhaps as a result of climate change. To evaluate the risk of BTV infection and transmission in a BTV-endemic region of California, sentinel dairy cows were evaluated for BTV infection, and populations of Culicoides vectors were collected at different sites using carbon dioxide. A deterministic model was developed to quantify risk and guide future mitigation strategies to reduce BTV infection in California dairy cattle. The greatest risk of BTV transmission was predicted within the warm Central Valley of California that contains the highest density of dairy cattle in the United States. Temperature and parameters associated with Culicoides vectors (transmission probabilities, carrying capacity, and survivorship) had the greatest effect on BTV’s basic reproduction number, R0. Based on these analyses, optimal control strategies for reducing BTV infection risk in dairy cattle will be highly reliant upon early efforts to reduce vector abundance during the months prior to peak transmission. PMID:27812161

Automatic Vehicle Scheduling (AVS) Programmer’s Instruction Manual for the Burroughs B3500 Computers.

DTIC Science & Technology

1981-02-01

N E. Of CAPA:;hINTRK) INCAP AV; TNJ73 170 GO t) 3000 A V.; T NI 1 7 3100 NT=I A V’ NI 17 SUBROUTINE AVSlN 74./74 OPTzg ROUND-*/ YRACE FTN N.lj# 4bD ...bSTOP FRR 6 tD ERR 7 SUFRUUTIKE LNCF(ICEVI ENflF 2 INiTLt.Ei% DATL.02.IPARK.REGPI53l.EPAL1501 ENDF 3 ,RLAL ISHFT ENnF 1 ALPHA INAIIEI5C ).0§IG(501

Cultural Resources Sample Survey of the Bayou Cocodrie and Tributaries Project, St. Landry, Evangeline and Avoyelles Parishes, Louisiana.

DTIC Science & Technology

1987-02-06

noweinv m idensitir 6F block ntiAbe) - This report presents the results of a probabilistic survey T of five per cent f -the wooded areas within the...bottle necks, and one piece of slag . The lack of structural remains, such as bricks or nails, 105 THIS PAGE BLANK 106 0 loom IWO I > - MIRE SITE .q...melted 1 Slag 1 Total 26 146 CHAPTER VII A COMPARISON OF SITE DISTRIBUTIONS IN THE PROJECT AREA Using the data gathered during this survey, comparisons

Lanchester-Type Models of Warfare. Volume I

DTIC Science & Technology

1980-10-01

1 / - -I SLEVEL 0 LANCHESTER-TYPE MODELS OF WARFARE VOLUME I$ by James G. Taylor Professor of Operations Research Naval Postgraduate School Monterey...California a DTIC¢-• 1 tELECTED S• OCT 28 1980 • D bFiFTr--••5i•:hii:rfl 8 00 O 20 01 9 Approved for public 8e0 -.;209-’ )Distribution Unlimited KL...34’:•-~ l,,, I " .. .. .. . . .. ... , . . , • •_. . .• .: _ - •’ .. - ..A ] . ......LJ- srcr.’NTY CL ASS 1CATl.,N OF’ TNH 4 a. , 1 A t HI At) IN .TWV

Environmental Impact Analysis Process. Draft Environmental Assessment. SAC Low-Altitude Flight Operations at the Airburst Range, Colorado

DTIC Science & Technology

1990-01-01

Aircraft Descriptions Appendix D- Practice Munitions Appendix E : B-52/BDU-48 Drop Activities Appendix F: Definition of Noise Impacts Appendix G: Contact...in southcentral Colorado. 1.1 PURPOSE AN’) NEED 1.1.1 Low-Level Training Low-altitude flight operations a.- e essential to the Air Forec for a...strategic and tactical bombing, and strategic/t’. "cal air!*-".. Aircre,-, 91 (ct y is e nti" if the Air Force is to perform its assigned mission

Naval Aviation IMA Repair Capability: A Readiness to Resources Approach.

DTIC Science & Technology

1983-12-01

systems commands and offices. 3, .-. e , No. cFE 0000 CP15PATL OR BMS REouWE gKIATRE_ woms CENTIP KEOscu. coNTiO.mI AMoCES COPYw co 5( US &Lp6J4 PE PM3K...U December 1983 " Thesis Advisor: A. W. McMasters Approved for public release; distribution unlimited. 4𔃺 8 4 04 25 069 -* ,** *- a’’ e ...29 2. Maintenance/Supply InterrelationshiDs ------ 32 E . MAINTENANCE DATA SYSTEM ------------------------- 33 IV. PLANNING "I" LEVEL

Calibration and Initialization of the NPS Modified Infrared Search and Target Designation (IRSTD) System.

DTIC Science & Technology

1987-12-01

level of performance comparable to the original ADM configuration. ’p, OTIC CPY Acesion For NTiS CRA&I UTNY’ TAB [ arinc ,:,cced 0 C yfi.’ hb .vC.Je i...levels below standard. This modified system was found to be operating at a level of performance comparable to the original ADM configuration. 4’ TABLE OF...requirements for systems that function under conditions of emissions control (EMCON). The AN/SAR-8, currently in the Engineering Development Phase , is an

Process for obtaining multiple sheet resistances for thin film hybrid microcircuit resistors

DOEpatents

Norwood, David P.

1989-01-01

A standard thin film circuit containing Ta.sub.2 N (100 ohms/square) resirs is fabricated by depositing on a dielectric substrate successive layers of Ta.sub.2 N, Ti and Pd, with a gold layer to provide conductors. The addition of a few simple photoprocessing steps to the standeard TFN manufacturing process enables the formation of Ta.sub.2 N+Ti (10 ohms/square) and Ta.sub.2 N+Ti+Pd (1 ohm/square) resistors in the same otherwise standard thin film circuit structure.

Specular Scattering of Acoustic Waves from a Rough Surface in the Fraunhofer and Fresnel Approximations

DTIC Science & Technology

1969-01-01

ted in Fi g 4v er •it the te nt ti t ~ ~ ~ ~ ~ ~ ~ ~ o teslt obrnd y(ulnad ay he (1962) , who scatee Eou4d siWnal .4 frtn th surfac of the oea TheirW...and11 NT YPy’hik, Thbiz-_ :17 Nti-rlý Sr t z ciPout, AfzaimiQ PreNis !w Trýc, ( Wun . F.. P., "Antp1 4tudA ncA Phstocd Fluictuft-d.0on of at 3%Iund WfAve

Specific Absorption Rate in a Sitting Rhesus Model at 225, 1290, and 5950 MHz for E, H, and K Polarizations.

DTIC Science & Technology

1984-04-23

Olsen SI• 23 April-198A ! Lf), i’-iApproved for public release; distribution unli~mited. S •~~i 4 0 9 .- 020 . Approved for public release... Houk , MC, USN Chief Scientific Advisor Commanding Officer 23 April 1984 NAVAL, AEROSPACE MEDICAL RESEARCH LABORATORY ,NVAL AIR STATION PENSACOLA, FLORIDA...Distrl ,oit i nti/ Avaiiab! itv Codes Avaw I !/or ii L- - - • - -•. . .. . T . . . . .. . . . v ’ - • q T ’ : • : ,-t INTRODUCTION Radio

The Generalization of Visuomotor Learning to Untrained Movements and Movement Sequences Based on Movement Vector and Goal Location Remapping

PubMed Central

Wu, Howard G.

2013-01-01

The planning of goal-directed movements is highly adaptable; however, the basic mechanisms underlying this adaptability are not well understood. Even the features of movement that drive adaptation are hotly debated, with some studies suggesting remapping of goal locations and others suggesting remapping of the movement vectors leading to goal locations. However, several previous motor learning studies and the multiplicity of the neural coding underlying visually guided reaching movements stand in contrast to this either/or debate on the modes of motor planning and adaptation. Here we hypothesize that, during visuomotor learning, the target location and movement vector of trained movements are separately remapped, and we propose a novel computational model for how motor plans based on these remappings are combined during the control of visually guided reaching in humans. To test this hypothesis, we designed a set of experimental manipulations that effectively dissociated the effects of remapping goal location and movement vector by examining the transfer of visuomotor adaptation to untrained movements and movement sequences throughout the workspace. The results reveal that (1) motor adaptation differentially remaps goal locations and movement vectors, and (2) separate motor plans based on these features are effectively averaged during motor execution. We then show that, without any free parameters, the computational model we developed for combining movement-vector-based and goal-location-based planning predicts nearly 90% of the variance in novel movement sequences, even when multiple attributes are simultaneously adapted, demonstrating for the first time the ability to predict how motor adaptation affects movement sequence planning. PMID:23804099

Interaction of Flavivirus with their mosquito vectors and their impact on the human health in the Americas.

PubMed

Valderrama, Anayansi; Díaz, Yamilka; López-Vergès, Sandra

2017-10-28

Some of the major arboviruses with public health importance, such as dengue, yellow fever, Zika and West Nile virus are mosquito-borne or mosquito-transmitted Flavivirus. Their principal vectors are from the family Culicidae, Aedes aegypti and Aedes albopictus being responsible of the urban cycles of dengue, Zika and yellow fever virus. These vectors are highly competent for transmission of many arboviruses. The genetic variability of the vectors, the environment and the viral diversity modulate the vector competence, in this context, it is important to determine which vector species is responsible of an outbreak in areas where many vectors coexist. As some vectors can transmit several flaviviruses and some flaviviruses can be transmitted by different species of vectors, through this review we expose importance of yellow fever, dengue and Zika virus in the world and the Americas, as well as the updated knowledge about these flaviviruses in their interaction with their mosquito vectors, guiding us on what is probably the beginning of a new stage in which the simultaneity of outbreaks will occur more frequently. Copyright © 2017 Elsevier Inc. All rights reserved.

VEST: Abstract Vector Calculus Simplification in Mathematica

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

J. Squire, J. Burby and H. Qin

2013-03-12

We present a new package, VEST (Vector Einstein Summation Tools), that performs abstract vector calculus computations in Mathematica. Through the use of index notation, VEST is able to reduce scalar and vector expressions of a very general type using a systematic canonicalization procedure. In addition, utilizing properties of the Levi-Civita symbol, the program can derive types of multi-term vector identities that are not recognized by canonicalization, subsequently applying these to simplify large expressions. In a companion paper [1], we employ VEST in the automation of the calculation of Lagrangians for the single particle guiding center system in plasma physics, amore » computation which illustrates its ability to handle very large expressions. VEST has been designed to be simple and intuitive to use, both for basic checking of work and more involved computations. __________________________________________________« less

VEST: Abstract vector calculus simplification in Mathematica

NASA Astrophysics Data System (ADS)

Squire, J.; Burby, J.; Qin, H.

2014-01-01

We present a new package, VEST (Vector Einstein Summation Tools), that performs abstract vector calculus computations in Mathematica. Through the use of index notation, VEST is able to reduce three-dimensional scalar and vector expressions of a very general type to a well defined standard form. In addition, utilizing properties of the Levi-Civita symbol, the program can derive types of multi-term vector identities that are not recognized by reduction, subsequently applying these to simplify large expressions. In a companion paper Burby et al. (2013) [12], we employ VEST in the automation of the calculation of high-order Lagrangians for the single particle guiding center system in plasma physics, a computation which illustrates its ability to handle very large expressions. VEST has been designed to be simple and intuitive to use, both for basic checking of work and more involved computations.

Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors

PubMed Central

Chorny, Michael; Fishbein, Ilia; Tengood, Jillian E.; Adamo, Richard F.; Alferiev, Ivan S.; Levy, Robert J.

2013-01-01

Gene therapeutic strategies have shown promise in treating vascular disease. However, their translation into clinical use requires pharmaceutical carriers enabling effective, site-specific delivery as well as providing sustained transgene expression in blood vessels. While replication-deficient adenovirus (Ad) offers several important advantages as a vector for vascular gene therapy, its clinical applicability is limited by rapid inactivation, suboptimal transduction efficiency in vascular cells, and serious systemic adverse effects. We hypothesized that novel zinc oleate-based magnetic nanoparticles (MNPs) loaded with Ad would enable effective arterial cell transduction by shifting vector processing to an alternative pathway, protect Ad from inactivation by neutralizing factors, and allow site-specific gene transfer to arteries treated with stent angioplasty using a 2-source magnetic guidance strategy. Ad-loaded MNPs effectively transduced cultured endothelial and smooth muscle cells under magnetic conditions compared to controls and retained capacity for gene transfer after exposure to neutralizing antibodies and lithium iodide, a lytic agent causing disruption of free Ad. Localized arterial gene expression significantly stronger than in control animal groups was demonstrated after magnetically guided MNP delivery in a rat stenting model 2 and 9 d post-treatment, confirming feasibility of using Ad-loaded MNPs to achieve site-specific transduction in stented blood vessels. In conclusion, Ad-loaded MNPs formed by controlled precipitation of zinc oleate represent a novel delivery system, well-suited for efficient, magnetically targeted vascular gene transfer.—Chorny, M., Fishbein, I., Tengood, J. E., Adamo, R. F., Alferiev, I. S., Levy, R. J. Site-specific gene delivery to stented arteries using magnetically guided zinc oleate-based nanoparticles loaded with adenoviral vectors. PMID:23407712

Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys.

PubMed

Fleuriet, Jérome; Walton, Mark M G; Ono, Seiji; Mustari, Michael J

2016-06-01

Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract.

Densities of Active species in N2/H2 RF and HF afterglows: application to surface nitriding of TiO2 nanocrystals

NASA Astrophysics Data System (ADS)

Ricard, André; Sarrette, Jean-Philippe; Wang, Yunfei; Kim, Yu-Kwon

2017-10-01

N2/0-5% H2 flowing afterglows from Radio Frequency (RF) and High Frequency (HF) sources have been analyzed by optical emission spectroscopy. In similar conditions (pressure 5-6 Torr, flow rate 0.5 slm and power 100 W), it is found in pure N2 a nearly constant N-atom density from the pink to the late afterglow, which is higher in HF than in RF: (1-2) and 0.4 × 1015 cm-3, respectively. With a N2/2% H2 gas mixture, the early afterglows is changed to a late afterglow with about the same N-atom density for both RF and HF cases: (8-9) × 1014 cm-3. Anatase TiO2 nanocrystals and Atomic Layer Deposition-grown films were exposed to the RF afterglows at room temperature. XPS analysis of the samples has shown that the highest N/Ti ratio of 0.24 can be achieved with the pure N2 late afterglow. In the HF pure N2 late afterglow, however, the N/Ti coverage was limited to 0.04 in spite of higher N-atom density. Such differences in the N content between the two RF and HF cases are attributed to the presence of a high O-atom impurity of 2 × 1013 cm-3 in HF as compared to that (8 × 1011 cm-3) in RF. Contribution to the topical issue "Plasma Sources and Plasma Processes (PSPP)", edited by Luis Lemos Alves, Thierry Belmonte and Tiberiu Minea

User's guide to PANCOR: A panel method program for interference assessment in slotted-wall wind tunnels

NASA Technical Reports Server (NTRS)

Kemp, William B., Jr.

1990-01-01

Guidelines are presented for use of the computer program PANCOR to assess the interference due to tunnel walls and model support in a slotted wind tunnel test section at subsonic speeds. Input data requirements are described in detail and program output and general program usage are described. The program is written for effective automatic vectorization on a CDC CYBER 200 class vector processing system.

Computational Study of Fluidic Thrust Vectoring using Separation Control in a Nozzle

NASA Technical Reports Server (NTRS)

Deere, Karen; Berrier, Bobby L.; Flamm, Jeffrey D.; Johnson, Stuart K.

2003-01-01

A computational investigation of a two- dimensional nozzle was completed to assess the use of fluidic injection to manipulate flow separation and cause thrust vectoring of the primary jet thrust. The nozzle was designed with a recessed cavity to enhance the throat shifting method of fluidic thrust vectoring. The structured-grid, computational fluid dynamics code PAB3D was used to guide the design and analyze over 60 configurations. Nozzle design variables included cavity convergence angle, cavity length, fluidic injection angle, upstream minimum height, aft deck angle, and aft deck shape. All simulations were computed with a static freestream Mach number of 0.05. a nozzle pressure ratio of 3.858, and a fluidic injection flow rate equal to 6 percent of the primary flow rate. Results indicate that the recessed cavity enhances the throat shifting method of fluidic thrust vectoring and allows for greater thrust-vector angles without compromising thrust efficiency.

Improving Vector Evaluated Particle Swarm Optimisation by Incorporating Nondominated Solutions

PubMed Central

Lim, Kian Sheng; Ibrahim, Zuwairie; Buyamin, Salinda; Ahmad, Anita; Naim, Faradila; Ghazali, Kamarul Hawari; Mokhtar, Norrima

2013-01-01

The Vector Evaluated Particle Swarm Optimisation algorithm is widely used to solve multiobjective optimisation problems. This algorithm optimises one objective using a swarm of particles where their movements are guided by the best solution found by another swarm. However, the best solution of a swarm is only updated when a newly generated solution has better fitness than the best solution at the objective function optimised by that swarm, yielding poor solutions for the multiobjective optimisation problems. Thus, an improved Vector Evaluated Particle Swarm Optimisation algorithm is introduced by incorporating the nondominated solutions as the guidance for a swarm rather than using the best solution from another swarm. In this paper, the performance of improved Vector Evaluated Particle Swarm Optimisation algorithm is investigated using performance measures such as the number of nondominated solutions found, the generational distance, the spread, and the hypervolume. The results suggest that the improved Vector Evaluated Particle Swarm Optimisation algorithm has impressive performance compared with the conventional Vector Evaluated Particle Swarm Optimisation algorithm. PMID:23737718

Improving Vector Evaluated Particle Swarm Optimisation by incorporating nondominated solutions.

PubMed

Lim, Kian Sheng; Ibrahim, Zuwairie; Buyamin, Salinda; Ahmad, Anita; Naim, Faradila; Ghazali, Kamarul Hawari; Mokhtar, Norrima

2013-01-01

The Vector Evaluated Particle Swarm Optimisation algorithm is widely used to solve multiobjective optimisation problems. This algorithm optimises one objective using a swarm of particles where their movements are guided by the best solution found by another swarm. However, the best solution of a swarm is only updated when a newly generated solution has better fitness than the best solution at the objective function optimised by that swarm, yielding poor solutions for the multiobjective optimisation problems. Thus, an improved Vector Evaluated Particle Swarm Optimisation algorithm is introduced by incorporating the nondominated solutions as the guidance for a swarm rather than using the best solution from another swarm. In this paper, the performance of improved Vector Evaluated Particle Swarm Optimisation algorithm is investigated using performance measures such as the number of nondominated solutions found, the generational distance, the spread, and the hypervolume. The results suggest that the improved Vector Evaluated Particle Swarm Optimisation algorithm has impressive performance compared with the conventional Vector Evaluated Particle Swarm Optimisation algorithm.

Unique Safety Issues Associated with Virus Vectored Vaccines: Potential for and Theoretical Consequences of Recombination with Wild Type Virus Strains

PubMed Central

Condit, Richard C.; Williamson, Anna-Lise; Sheets, Rebecca; Seligman, Stephen J.; Monath, Thomas P.; Excler, Jean-Louis; Gurwith, Marc; Bok, Karin; Robertson, James S.; Kim, Denny; Hendry, Michael; Singh, Vidisha; Mac, Lisa M.; Chen, Robert T.

2016-01-01

In 2003 and 2013, the World Health Organization convened informal consultations on characterization and quality aspects of vaccines based on live virus vectors. In the resulting reports, one of several issues raised for future study was the potential for recombination of virus-vectored vaccines with wild type pathogenic virus strains. This paper presents an assessment of this issue formulated by the Brighton Collaboration. To provide an appropriate context for understanding the potential for recombination of virus-vectored vaccines, we review briefly the current status of virus vectored vaccines, mechanisms of recombination between viruses, experience with recombination involving live attenuated vaccines in the field, and concerns raised previously in the literature regarding recombination of virus-vectored vaccines with wild type virus strains. We then present a discussion of the major variables that could influence recombination between a virus-vectored vaccine and circulating wild type virus and the consequences of such recombination, including intrinsic recombination properties of the parent virus used as a vector; sequence relatedness of vector and wild virus; virus host range, pathogenesis and transmission; replication competency of vector in target host; mechanism of vector attenuation; additional factors potentially affecting virulence; and circulation of multiple recombinant vectors in the same target population. Finally, we present some guiding principles for vector design and testing intended to anticipate and mitigate the potential for and consequences of recombination of virus-vectored vaccines with wild type pathogenic virus strains. PMID:27346303

Vector vortex beam generation with dolphin-shaped cell meta-surface.

PubMed

Yang, Zhuo; Kuang, Deng-Feng; Cheng, Fang

2017-09-18

We present a dolphin-shaped cell meta-surface, which is a combination of dolphin-shaped metallic cells and dielectric substrate, for vector vortex beam generation with the illumination of linearly polarized light. Surface plasmon polaritons are excited at the boundary of the metallic cells, then guided by the metallic structures, and finally squeezed to the tips to form highly localized strong electromagnetic fields, which generate the intensity of vector vortex beams at z component. Synchronously, the abrupt phase change produced by the meta-surface is utilized to explain the vortex phase generated by elements. The new kind of structure can be utilized for communication, bioscience, and materiality.

Army Air Forces Statistical Digest, World War II

DTIC Science & Technology

1945-12-01

1,626 2,491 2,033 453 750 60- - - - - - 3 16 24 35 35 56 102 67- - - - - - 3 16 24 35 35 56 99 47- - - - - - - - - - - - 3 2018 128 1,020 594 14 4 16...YAnti- I Enem ,y Anti- I~h Ene~ Anti- Enem ;yAnti-Month Total Air- Air- ig:=s Total Air- Air- er Total Air- Air- other Total Air- Air- other Cl𔄂tt !Cl...AIRPLANE AND BY CAUSE OF LOSS: JUN 1942 TO AUG 1945 EneII;y I~nti- Enem ;rAnti_, ! 1Enem;r Anti- Enem ;rAnti- Total Air- !Air- eaOtherTotal Air- Air

Real-time solar magnetograph operation system software design and user's guide

NASA Technical Reports Server (NTRS)

Wang, C.

1984-01-01

The Real Time Solar Magnetograph (RTSM) Operation system software design on PDP11/23+ is presented along with the User's Guide. The RTSM operation software is for real time instrumentation control, data collection and data management. The data is used for vector analysis, plotting or graphics display. The processed data is then easily compared with solar data from other sources, such as the Solar Maximum Mission (SMM).

User's guide for vectorized code EQUIL for calculating equilibrium chemistry on Control Data STAR-100 computer

NASA Technical Reports Server (NTRS)

Kumar, A.; Graves, R. A., Jr.; Weilmuenster, K. J.

1980-01-01

A vectorized code, EQUIL, was developed for calculating the equilibrium chemistry of a reacting gas mixture on the Control Data STAR-100 computer. The code provides species mole fractions, mass fractions, and thermodynamic and transport properties of the mixture for given temperature, pressure, and elemental mass fractions. The code is set up for the electrons H, He, C, O, N system of elements. In all, 24 chemical species are included.

Precision targeting in guided munition using IR sensor and MmW radar

NASA Astrophysics Data System (ADS)

Sreeja, S.; Hablani, H. B.; Arya, H.

2015-10-01

Conventional munitions are not guided with sensors and therefore miss the target, particularly if the target is mobile. The miss distance of these munitions can be decreased by incorporating sensors to detect the target and guide the munition during flight. This paper is concerned with a Precision Guided Munition(PGM) equipped with an infrared sensor and a millimeter wave radar [IR and MmW, for short]. Three-dimensional flight of the munition and its pitch and yaw motion models are developed and simulated. The forward and lateral motion of a target tank on the ground is modeled as two independent second-order Gauss-Markov process. To estimate the target location on the ground and the line-of-sight rate to intercept it an Extended Kalman Filter is composed whose state vector consists of cascaded state vectors of missile dynamics and target dynamics. The line-of-sight angle measurement from the infrared seeker is by centroiding the target image in 40 Hz. The centroid estimation of the images in the focal plane is at a frequency of 10 Hz. Every 10 Hz, centroids of four consecutive images are averaged, yielding a time-averaged centroid, implying some measurement delay. The miss distance achieved by including by image processing delays is 1:45m.

Precision targeting in guided munition using infrared sensor and millimeter wave radar

NASA Astrophysics Data System (ADS)

Sulochana, Sreeja; Hablani, Hari B.; Arya, Hemendra

2016-07-01

Conventional munitions are not guided with sensors and therefore miss the target, particularly if the target is mobile. The miss distance of these munitions can be decreased by incorporating sensors to detect the target and guide the munition during flight. This paper is concerned with a precision guided munition equipped with an infrared (IR) sensor and a millimeter wave radar (MmW). Three-dimensional flight of the munition and its pitch and yaw motion models are developed and simulated. The forward and lateral motion of a target tank on the ground is modeled as two independent second-order Gauss-Markov processes. To estimate the target location on the ground and the line-of-sight (LOS) rate to intercept it, an extended Kalman filter is composed whose state vector consists of cascaded state vectors of missile dynamics and target dynamics. The LOS angle measurement from the IR seeker is by centroiding the target image in 40 Hz. The centroid estimation of the images in the focal plane is at a frequency of 10 Hz. Every 10 Hz, centroids of four consecutive images are averaged, yielding a time-averaged centroid, implying some measurement delay. The miss distance achieved by including image processing delays is 1.45 m.

Electrical Microstimulation of the Superior Colliculus in Strabismic Monkeys

PubMed Central

Fleuriet, Jérome; Walton, Mark M. G.; Ono, Seiji; Mustari, Michael J.

2016-01-01

Purpose Visually guided saccades are disconjugate in human and nonhuman strabismic primates. The superior colliculus (SC) is a region of the brain topographically organized in visual and motor maps where the saccade goal is spatially coded. The present study was designed to investigate if a site of stimulation on the topographic motor map was evoking similar or different saccade vectors for each eye. Methods We used microelectrical stimulation (MS) of the SC in two strabismic (one esotrope and one exotrope) and two control macaques under binocular and monocular viewing conditions. We compared the saccade amplitudes and directions for each SC site and each condition independently of the fixating eye and then between each fixating eye. A comparison with disconjugacies of visually guided saccades was also performed. Results We observed different saccade vectors for the two eyes in strabismic monkeys, but conjugate saccades in normal monkeys. Evoked saccade vectors for the left eye when that eye was fixating the target were different from those of the right eye when it was fixating. The disconjugacies evoked by the MS were not identical but similar to those observed for visually guided saccades especially for the dominant eye. Conclusions Our results suggest that, in strabismus, the saccade generator does not interpret activation of a single location of the SC as the same desired displacement for each eye. This finding is important for advancing understanding of the development of neural circuits in strabismus. French Abstract PMID:27309621

Plant DNA barcodes and assessment of phylogenetic community structure of a tropical mixed dipterocarp forest in Brunei Darussalam (Borneo)

PubMed Central

Abu Salim, Kamariah; Chase, Mark W.; Dexter, Kyle G.; Pennington, R. Toby; Tan, Sylvester; Kaye, Maria Ellen; Samuel, Rosabelle

2017-01-01

DNA barcoding is a fast and reliable tool to assess and monitor biodiversity and, via community phylogenetics, to investigate ecological and evolutionary processes that may be responsible for the community structure of forests. In this study, DNA barcodes for the two widely used plastid coding regions rbcL and matK are used to contribute to identification of morphologically undetermined individuals, as well as to investigate phylogenetic structure of tree communities in 70 subplots (10 × 10m) of a 25-ha forest-dynamics plot in Brunei (Borneo, Southeast Asia). The combined matrix (rbcL + matK) comprised 555 haplotypes (from ≥154 genera, 68 families and 25 orders sensu APG, Angiosperm Phylogeny Group, 2016), making a substantial contribution to tree barcode sequences from Southeast Asia. Barcode sequences were used to reconstruct phylogenetic relationships using maximum likelihood, both with and without constraining the topology of taxonomic orders to match that proposed by the Angiosperm Phylogeny Group. A third phylogenetic tree was reconstructed using the program Phylomatic to investigate the influence of phylogenetic resolution on results. Detection of non-random patterns of community assembly was determined by net relatedness index (NRI) and nearest taxon index (NTI). In most cases, community assembly was either random or phylogenetically clustered, which likely indicates the importance to community structure of habitat filtering based on phylogenetically correlated traits in determining community structure. Different phylogenetic trees gave similar overall results, but the Phylomatic tree produced greater variation across plots for NRI and NTI values, presumably due to noise introduced by using an unresolved phylogenetic tree. Our results suggest that using a DNA barcode tree has benefits over the traditionally used Phylomatic approach by increasing precision and accuracy and allowing the incorporation of taxonomically unidentified individuals into analyses. PMID:29049301

Analysis of Composition and Structure of Coastal to Mesopelagic Bacterioplankton Communities in the Northern Gulf of Mexico

PubMed Central

King, Gary M.; Smith, Conor B.; Tolar, Bradley; Hollibaugh, James T.

2013-01-01

16S rRNA gene amplicons were pyrosequenced to assess bacterioplankton community composition, diversity, and phylogenetic community structure for 17 stations in the northern Gulf of Mexico (nGoM) sampled in March 2010. Statistical analyses showed that samples from depths ≤100 m differed distinctly from deeper samples. SAR 11 α-Proteobacteria and Bacteroidetes dominated communities at depths ≤100 m, which were characterized by high α-Proteobacteria/γ-Proteobacteria ratios (α/γ > 1.7). Thaumarchaeota, Firmicutes, and δ-Proteobacteria were relatively abundant in deeper waters, and α/γ ratios were low (<1). Canonical correlation analysis indicated that δ- and γ-Proteobacteria, Thaumarchaeota, and Firmicutes correlated positively with depth; α-Proteobacteria and Bacteroidetes correlated positively with temperature and dissolved oxygen; Actinobacteria, β-Proteobacteria, and Verrucomicrobia correlated positively with a measure of suspended particles. Diversity indices did not vary with depth or other factors, which indicated that richness and evenness elements of bacterioplankton communities might develop independently of nGoM physical-chemical variables. Phylogenetic community structure as measured by the net relatedness (NRI) and nearest taxon (NTI) indices also did not vary with depth. NRI values indicated that most of the communities were comprised of OTUs more distantly related to each other in whole community comparisons than expected by chance. NTI values derived from phylogenetic distances of the closest neighbor for each OTU in a given community indicated that OTUs tended to occur in clusters to a greater extent than expected by chance. This indicates that “habitat filtering” might play an important role in nGoM bacterioplankton species assembly, and that such filtering occurs throughout the water column. PMID:23346078

Automotive applications of superconductors

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

Ginsberg, M.

1987-01-01

These proceedings compile papers on supercomputers in the automobile industry. Titles include: An automotive engineer's guide to the effective use of scalar, vector, and parallel computers; fluid mechanics, finite elements, and supercomputers; and Automotive crashworthiness performance on a supercomputer.

Evaluation of Commercial and Field-Expedient Baited Traps for House Flies, Musca domestica L. (Diptera: Muscidae)

DTIC Science & Technology

2009-01-09

Vector Ecology 34 (1): 99-103. 2009. Keyword Index : House fly, Musca domestica, trapping. INTRODUCTION Traps have been a mainstay of house fly (Musca...attract synanthropic flies. Proc. Pap. 46th Ann. Conf. Calif. Mosq. Vector Contr. Assoc. pp. 70-73. Pickens, L. G. and R. W. Miller. 1987. Techniques...1139: 279- 284. SAS Institute. 1992. SAS users guide: statistics. SAS Institute, Cary, NC. Warner, W. B. 1991. Attractant composition for synanthropic

Walking Drosophila align with the e-vector of linearly polarized light through directed modulation of angular acceleration

PubMed Central

Velez, Mariel M.; Wernet, Mathias F.; Clark, Damon A.

2014-01-01

Understanding the mechanisms that link sensory stimuli to animal behavior is a central challenge in neuroscience. The quantitative description of behavioral responses to defined stimuli has led to a rich understanding of different behavioral strategies in many species. One important navigational cue perceived by many vertebrates and insects is the e-vector orientation of linearly polarized light. Drosophila manifests an innate orientation response to this cue (‘polarotaxis’), aligning its body axis with the e-vector field. We have established a population-based behavioral paradigm for the genetic dissection of neural circuits guiding polarotaxis to both celestial as well as reflected polarized stimuli. However, the behavioral mechanisms by which flies align with a linearly polarized stimulus remain unknown. Here, we present a detailed quantitative description of Drosophila polarotaxis, systematically measuring behavioral parameters that are modulated by the stimulus. We show that angular acceleration is modulated during alignment, and this single parameter may be sufficient for alignment. Furthermore, using monocular deprivation, we show that each eye is necessary for modulating turns in the ipsilateral direction. This analysis lays the foundation for understanding how neural circuits guide these important visual behaviors. PMID:24810784

MRI Guided Brain Stimulation without the Use of a Neuronavigation System

PubMed Central

Vaghefi, Ehsan; Byblow, Winston D.; Stinear, Cathy M.; Thompson, Benjamin

2015-01-01

A key issue in the field of noninvasive brain stimulation (NIBS) is the accurate localization of scalp positions that correspond to targeted cortical areas. The current gold standard is to combine structural and functional brain imaging with a commercially available “neuronavigation” system. However, neuronavigation systems are not commonplace outside of specialized research environments. Here we describe a technique that allows for the use of participant-specific functional and structural MRI data to guide NIBS without a neuronavigation system. Surface mesh representations of the head were generated using Brain Voyager and vectors linking key anatomical landmarks were drawn on the mesh. Our technique was then used to calculate the precise distances on the scalp corresponding to these vectors. These calculations were verified using actual measurements of the head and the technique was used to identify a scalp position corresponding to a brain area localized using functional MRI. PMID:26413537

Magnetofection™ of NMDA Receptor Subunits GluN1 and GluN2A Expression Vectors in Non-Neuronal Host Cells.

PubMed

Bruneau, Nadine; Szepetowski, Pierre

2017-01-01

The functional study of reconstituted NMDA receptors (NMDARs) in host cells requires that the corresponding vectors for the expression of the NMDAR subunits are co-transfected with high efficiency. Magnetofection™ is a technology used to deliver nucleic acids to cells. It is driven and site-specifically guided by the attractive forces of magnetic fields acting on magnetic nanoparticles that are associated with nucleic acid vectors. In magnetofection™, cationic lipids form self-assembled complexes with the nucleic acid vectors of interest. Those complexes are then associated with magnetic nanoparticles that are concentrated at the surface of cultured cells by applying a permanent magnetic field. Magnetofection™ is a simple method to transfect cultured cells with high transfection rates. Satisfactory expression levels are obtained with very low amounts of nucleic acid vector. Moreover, incubation time with host cells is less than 1 h, as compared with the several hours needed with standard transfection assays.

Energy-exchange collisions of dark-bright-bright vector solitons.

PubMed

Radhakrishnan, R; Manikandan, N; Aravinthan, K

2015-12-01

We find a dark component guiding the practically interesting bright-bright vector one-soliton to two different parametric domains giving rise to different physical situations by constructing a more general form of three-component dark-bright-bright mixed vector one-soliton solution of the generalized Manakov model with nine free real parameters. Moreover our main investigation of the collision dynamics of such mixed vector solitons by constructing the multisoliton solution of the generalized Manakov model with the help of Hirota technique reveals that the dark-bright-bright vector two-soliton supports energy-exchange collision dynamics. In particular the dark component preserves its initial form and the energy-exchange collision property of the bright-bright vector two-soliton solution of the Manakov model during collision. In addition the interactions between bound state dark-bright-bright vector solitons reveal oscillations in their amplitudes. A similar kind of breathing effect was also experimentally observed in the Bose-Einstein condensates. Some possible ways are theoretically suggested not only to control this breathing effect but also to manage the beating, bouncing, jumping, and attraction effects in the collision dynamics of dark-bright-bright vector solitons. The role of multiple free parameters in our solution is examined to define polarization vector, envelope speed, envelope width, envelope amplitude, grayness, and complex modulation of our solution. It is interesting to note that the polarization vector of our mixed vector one-soliton evolves in sphere or hyperboloid depending upon the initial parametric choices.

Interpreting linear support vector machine models with heat map molecule coloring

PubMed Central

2011-01-01

Background Model-based virtual screening plays an important role in the early drug discovery stage. The outcomes of high-throughput screenings are a valuable source for machine learning algorithms to infer such models. Besides a strong performance, the interpretability of a machine learning model is a desired property to guide the optimization of a compound in later drug discovery stages. Linear support vector machines showed to have a convincing performance on large-scale data sets. The goal of this study is to present a heat map molecule coloring technique to interpret linear support vector machine models. Based on the weights of a linear model, the visualization approach colors each atom and bond of a compound according to its importance for activity. Results We evaluated our approach on a toxicity data set, a chromosome aberration data set, and the maximum unbiased validation data sets. The experiments show that our method sensibly visualizes structure-property and structure-activity relationships of a linear support vector machine model. The coloring of ligands in the binding pocket of several crystal structures of a maximum unbiased validation data set target indicates that our approach assists to determine the correct ligand orientation in the binding pocket. Additionally, the heat map coloring enables the identification of substructures important for the binding of an inhibitor. Conclusions In combination with heat map coloring, linear support vector machine models can help to guide the modification of a compound in later stages of drug discovery. Particularly substructures identified as important by our method might be a starting point for optimization of a lead compound. The heat map coloring should be considered as complementary to structure based modeling approaches. As such, it helps to get a better understanding of the binding mode of an inhibitor. PMID:21439031

Vector species richness increases haemorrhagic disease prevalence through functional diversity modulating the duration of seasonal transmission.

PubMed

Park, Andrew W; Cleveland, Christopher A; Dallas, Tad A; Corn, Joseph L

2016-06-01

Although many parasites are transmitted between hosts by a suite of arthropod vectors, the impact of vector biodiversity on parasite transmission is poorly understood. Positive relationships between host infection prevalence and vector species richness (SR) may operate through multiple mechanisms, including (i) increased vector abundance, (ii) a sampling effect in which species of high vectorial capacity are more likely to occur in species-rich communities, and (iii) functional diversity whereby communities comprised species with distinct phenologies may extend the duration of seasonal transmission. Teasing such mechanisms apart is impeded by a lack of appropriate data, yet could highlight a neglected role for functional diversity in parasite transmission. We used statistical modelling of extensive host, vector and microparasite data to test the hypothesis that functional diversity leading to longer seasonal transmission explained variable levels of disease in a wildlife population. We additionally developed a simple transmission model to guide our expectation of how an increased transmission season translates to infection prevalence. Our study demonstrates that vector SR is associated with increased levels of disease reporting, but not via increases in vector abundance or via a sampling effect. Rather, the relationship operates by extending the length of seasonal transmission, in line with theoretical predictions.

Defect pair formation in fluorine and nitrogen codoped TiO2

NASA Astrophysics Data System (ADS)

Kordatos, A.; Kelaidis, N.; Chroneos, A.

2018-04-01

Titanium oxide is extensively investigated because of its high chemical stability and its photocatalytic properties; nevertheless, the large band gap limits its activity to a small portion of the solar spectrum. Nitrogen and fluorine codoping is an efficient defect engineering strategy to increase the photocatalytic activity of titanium oxide. In the present study, we apply density functional theory to investigate the interaction of nitrogen with fluorine and the formation of defect pairs. We show that in fluorine and nitrogen codoped titanium oxide, the FiNi, FONi, and FiNTi defects can form. Their impact on the electronic structure of titanium oxide is discussed.

Processing-in-Memory Technology for Knowledge Discovery Algorithms

DTIC Science & Technology

2006-07-01

e MP EG 2-d ist1 EP IC -u nq ua nti ze GS M- Ca lcu lat ion Sp ee du p ov er b as el in e MIT-SLP SLP SLPCF SLPCF+SLL 15 8 our infrastructure...to non-threat groups as well. Figure 15: Summary of ARDA/Eagle Data Sets. D at as et #o f N od es (P eo pl e ) #o f L in ks A vg . F an ou t Ph...on e C al ls Te le co ns Te le co n R es po nd en ts A vg . T el ec on Pa rt

Obstacle-avoiding navigation system

DOEpatents

Borenstein, Johann; Koren, Yoram; Levine, Simon P.

1991-01-01

A system for guiding an autonomous or semi-autonomous vehicle through a field of operation having obstacles thereon to be avoided employs a memory for containing data which defines an array of grid cells which correspond to respective subfields in the field of operation of the vehicle. Each grid cell in the memory contains a value which is indicative of the likelihood, or probability, that an obstacle is present in the respectively associated subfield. The values in the grid cells are incremented individually in response to each scan of the subfields, and precomputation and use of a look-up table avoids complex trigonometric functions. A further array of grid cells is fixed with respect to the vehicle form a conceptual active window which overlies the incremented grid cells. Thus, when the cells in the active window overly grid cell having values which are indicative of the presence of obstacles, the value therein is used as a multiplier of the precomputed vectorial values. The resulting plurality of vectorial values are summed vectorially in one embodiment of the invention to produce a virtual composite repulsive vector which is then summed vectorially with a target-directed vector for producing a resultant vector for guiding the vehicle. In an alternative embodiment, a plurality of vectors surrounding the vehicle are computed, each having a value corresponding to obstacle density. In such an embodiment, target location information is used to select between alternative directions of travel having low associated obstacle densities.

User's Guide for Monthly Vector Wind Profile Model

NASA Technical Reports Server (NTRS)

Adelfang, S. I.

1999-01-01

The background, theoretical concepts, and methodology for construction of vector wind profiles based on a statistical model are presented. The derived monthly vector wind profiles are to be applied by the launch vehicle design community for establishing realistic estimates of critical vehicle design parameter dispersions related to wind profile dispersions. During initial studies a number of months are used to establish the model profiles that produce the largest monthly dispersions of ascent vehicle aerodynamic load indicators. The largest monthly dispersions for wind, which occur during the winter high-wind months, are used for establishing the design reference dispersions for the aerodynamic load indicators. This document includes a description of the computational process for the vector wind model including specification of input data, parameter settings, and output data formats. Sample output data listings are provided to aid the user in the verification of test output.

Rule-Based Design of Plant Expression Vectors Using GenoCAD.

PubMed

Coll, Anna; Wilson, Mandy L; Gruden, Kristina; Peccoud, Jean

2015-01-01

Plant synthetic biology requires software tools to assist on the design of complex multi-genic expression plasmids. Here a vector design strategy to express genes in plants is formalized and implemented as a grammar in GenoCAD, a Computer-Aided Design software for synthetic biology. It includes a library of plant biological parts organized in structural categories and a set of rules describing how to assemble these parts into large constructs. Rules developed here are organized and divided into three main subsections according to the aim of the final construct: protein localization studies, promoter analysis and protein-protein interaction experiments. The GenoCAD plant grammar guides the user through the design while allowing users to customize vectors according to their needs. Therefore the plant grammar implemented in GenoCAD will help plant biologists take advantage of methods from synthetic biology to design expression vectors supporting their research projects.

Wide-angle full-vector beam propagation method based on an alternating direction implicit preconditioner

NASA Astrophysics Data System (ADS)

Chui, Siu Lit; Lu, Ya Yan

2004-03-01

Wide-angle full-vector beam propagation methods (BPMs) for three-dimensional wave-guiding structures can be derived on the basis of rational approximants of a square root operator or its exponential (i.e., the one-way propagator). While the less accurate BPM based on the slowly varying envelope approximation can be efficiently solved by the alternating direction implicit (ADI) method, the wide-angle variants involve linear systems that are more difficult to handle. We present an efficient solver for these linear systems that is based on a Krylov subspace method with an ADI preconditioner. The resulting wide-angle full-vector BPM is used to simulate the propagation of wave fields in a Y branch and a taper.

Wide-angle full-vector beam propagation method based on an alternating direction implicit preconditioner.

PubMed

Chui, Siu Lit; Lu, Ya Yan

2004-03-01

Wide-angle full-vector beam propagation methods (BPMs) for three-dimensional wave-guiding structures can be derived on the basis of rational approximants of a square root operator or its exponential (i.e., the one-way propagator). While the less accurate BPM based on the slowly varying envelope approximation can be efficiently solved by the alternating direction implicit (ADI) method, the wide-angle variants involve linear systems that are more difficult to handle. We present an efficient solver for these linear systems that is based on a Krylov subspace method with an ADI preconditioner. The resulting wide-angle full-vector BPM is used to simulate the propagation of wave fields in a Y branch and a taper.

Ultrafast Optics: Vector Cavity Fiber Lasers - Physics and Technology

DTIC Science & Technology

2016-06-14

with a quasi- vector cavity both numerically and experimentally. It is expected that through the study a deep and comprehensive understanding on the...799-801, Jun. 1997. 31. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like pulse in a gain-guided soliton fiber laser," Opt...solitons in a ring fiber laser," Optics Communications 281 (22), 5614 (2008). 110. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like

Ultrafast Optics: Vector Cavity Laser - Physics and Technology

DTIC Science & Technology

2016-06-14

with a quasi- vector cavity both numerically and experimentally. It is expected that through the study a deep and comprehensive understanding on the...799-801, Jun. 1997. 31. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like pulse in a gain-guided soliton fiber laser," Opt...solitons in a ring fiber laser," Optics Communications 281 (22), 5614 (2008). 110. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like

Ultrafast Optics - Vector Cavity Lasers: Physics and Technology

DTIC Science & Technology

2016-06-14

with a quasi- vector cavity both numerically and experimentally. It is expected that through the study a deep and comprehensive understanding on the...799-801, Jun. 1997. 31. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like pulse in a gain-guided soliton fiber laser," Opt...solitons in a ring fiber laser," Optics Communications 281 (22), 5614 (2008). 110. L. M. Zhao, D. Y. Tang, J. Wu, X. Q. Fu, and S. C. Wen , "Noise-like

Monte Carlo simulation of a dynamical fermion problem: The light q sup 2 q sup 2 system

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

Grondin, G.

1991-01-01

We present results from a Guided Random Walk Monte Carlo simulation of the light q{sup 2}{bar q}{sup 2} system in a Coulomb-plus-linear quark potential model using an Intel iPSC/860 hypercube. A solvable model problem is first considered, after which we study the full q{sup 2}{bar q}{sup 2} system in (J,I) = (2,2) and (2,0) sectors. We find evidence for no bound states below the vector-vector threshold in these systems. 17 refs., 6 figs.

Computational Study of an Axisymmetric Dual Throat Fluidic Thrust Vectoring Nozzle for a Supersonic Aircraft Application

NASA Technical Reports Server (NTRS)

Deere, Karen A.; Flamm, Jeffrey D.; Berrier, Bobby L.; Johnson, Stuart K.

2007-01-01

A computational investigation of an axisymmetric Dual Throat Nozzle concept has been conducted. This fluidic thrust-vectoring nozzle was designed with a recessed cavity to enhance the throat shifting technique for improved thrust vectoring. The structured-grid, unsteady Reynolds- Averaged Navier-Stokes flow solver PAB3D was used to guide the nozzle design and analyze performance. Nozzle design variables included extent of circumferential injection, cavity divergence angle, cavity length, and cavity convergence angle. Internal nozzle performance (wind-off conditions) and thrust vector angles were computed for several configurations over a range of nozzle pressure ratios from 1.89 to 10, with the fluidic injection flow rate equal to zero and up to 4 percent of the primary flow rate. The effect of a variable expansion ratio on nozzle performance over a range of freestream Mach numbers up to 2 was investigated. Results indicated that a 60 circumferential injection was a good compromise between large thrust vector angles and efficient internal nozzle performance. A cavity divergence angle greater than 10 was detrimental to thrust vector angle. Shortening the cavity length improved internal nozzle performance with a small penalty to thrust vector angle. Contrary to expectations, a variable expansion ratio did not improve thrust efficiency at the flight conditions investigated.

Intracellular trafficking of hybrid gene delivery vectors.

PubMed

Keswani, Rahul K; Lazebnik, Mihael; Pack, Daniel W

2015-06-10

Viral and non-viral gene delivery vectors are in development for human gene therapy, but both exhibit disadvantages such as inadequate efficiency, lack of cell-specific targeting or safety concerns. We have recently reported the design of hybrid delivery vectors combining retrovirus-like particles with synthetic polymers or lipids that are efficient, provide sustained gene expression and are more stable compared to native retroviruses. To guide further development of this promising class of gene delivery vectors, we have investigated their mechanisms of intracellular trafficking. Moloney murine leukemia virus-like particles (M-VLPs) were complexed with chitosan (Chi) or liposomes (Lip) comprising DOTAP, DOPE and cholesterol to form the hybrid vectors (Chi/M-VLPs and Lip/M-VLPs, respectively). Transfection efficiency and cellular internalization of the vectors were quantified in the presence of a panel of inhibitors of various endocytic pathways. Intracellular transport and trafficking kinetics of the hybrid vectors were dependent on the synthetic component and used a combination of clathrin- and caveolar-dependent endocytosis and macropinocytosis. Chi/M-VLPs were slower to transfect compared to Lip/M-VLPs due to the delayed detachment of the synthetic component. The synthetic component of hybrid gene delivery vectors plays a significant role in their cellular interactions and processing and is a key parameter for the design of more efficient gene delivery vehicles. Copyright © 2015 Elsevier B.V. All rights reserved.

Magnetic nanoparticles for efficient cell transduction with Semliki Forest virus.

PubMed

Kurena, Baiba; Vežāne, Aleksandra; Skrastiņa, Dace; Trofimova, Olga; Zajakina, Anna

2017-07-01

Semliki Forest virus (SFV) is a potential cancer gene therapy vector capable of providing high and transient expression of heterologous proteins in mammalian cells. However, SFV has shown suboptimal transduction levels in several cancer cell types as well as wide biodistribution of SFV has been observed after in vivo applications. Magnetic nanoparticles (MNPs) have been shown to increase cell transduction with several viral vectors in vitro under an external magnetic field and enhance magnetically guided viral vector delivery. Here, we examined a panel of MNPs for enhanced cancer cell transduction with SFV vector. Magneto-transduction using positively charged MNPs increased Semliki Forest virus transduction in TS/A mouse mammary carcinoma cells in vitro in the presence of fetal bovine serum. Positively charged MNPs efficiently captured SFV particles independently of capturing medium, and MNPs-SFV complexes were successfully separated from suspension by magnetic precipitation. These results reveal the potential application of MNPs for enhanced gene delivery by SFV vector as well as proposes magnetic precipitation for efficient concentration of SFV particles from different media. Copyright © 2017 Elsevier B.V. All rights reserved.

Zoonotic aspects of vector-borne infections.

PubMed

Failloux, A-B; Moutailler, S

2015-04-01

Vector-borne diseases are principally zoonotic diseases transmitted to humans by animals. Pathogens such as bacteria, parasites and viruses are primarily maintained within an enzootic cycle between populations of non-human primates or other mammals and largely non-anthropophilic vectors. This 'wild' cycle sometimes spills over in the form of occasional infections of humans and domestic animals. Lifestyle changes, incursions by humans into natural habitats and changes in agropastoral practices create opportunities that make the borders between wildlife and humans more permeable. Some vector-borne diseases have dispensed with the need for amplification in wild or domestic animals and they can now be directly transmitted to humans. This applies to some viruses (dengue and chikungunya) that have caused major epidemics. Bacteria of the genus Bartonella have reduced their transmission cycle to the minimum, with humans acting as reservoir, amplifier and disseminator. The design of control strategies for vector-borne diseases should be guided by research into emergence mechanisms in order to understand how a wild cycle can produce a pathogen that goes on to cause devastating urban epidemics.

Accurate shade image matching by using a smartphone camera.

PubMed

Tam, Weng-Kong; Lee, Hsi-Jian

2017-04-01

Dental shade matching by using digital images may be feasible when suitable color features are properly manipulated. Separating the color features into feature spaces facilitates favorable matching. We propose using support vector machines (SVM), which are outstanding classifiers, in shade classification. A total of 1300 shade tab images were captured using a smartphone camera with auto-mode settings and no flash. The images were shot at angled distances of 14-20cm from a shade guide at a clinic equipped with light tubes that produced a 4000K color temperature. The Group 1 samples comprised 1040 tab images, for which the shade guide was randomly positioned in the clinic, and the Group 2 samples comprised 260 tab images, for which the shade guide had a fixed position in the clinic. Rectangular content was cropped manually on each shade tab image and further divided into 10×2 blocks. The color features extracted from the blocks were described using a feature vector. The feature vectors in each group underwent SVM training and classification by using the "leave-one-out" strategy. The top one and three accuracies of Group 1 were 0.86 and 0.98, respectively, and those of Group 2 were 0.97 and 1.00, respectively. This study provides a feasible technique for dental shade classification that uses the camera of a mobile device. The findings reveal that the proposed SVM classification might outperform the shade-matching results of previous studies that have performed similarity measurements of ΔE levels or used an S, a*, b* feature set. Copyright © 2016 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

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 are then attracted to and internalized into the intended target cells via the expressed cognate strongly binding extra-cellular receptor, causing escalation of gene transfer into these cells and increasing the copy number of the therapeutic gene expression modules. Such self-focusing swarms of gene vectors can be either homogeneous, with 'scout' and 'therapeutic' members of the swarm being structurally identical, or, alternatively, heterogeneous (split), with 'scout' and 'therapeutic' members of the swarm being structurally specialized. It is hoped that the proposed self-focusing cell-targeted gene vector swarms with receptor-mediated intra-swarm signalling could be particularly effective in 'top-up' gene delivery scenarios, achieving high-level and sustained expression of therapeutic transgenes that are prone to shut-down through degradation and silencing. Crucially, in contrast to low-precision 'general location' vector guidance by diffusible chemo-attractants, ear-marking non-diffusible receptors can provide high-accuracy targeting of therapeutic vector particles to the specific cell, which has undergone a 'successful cell-specific hit' by a 'scout' vector particle. Opportunities for cell targeting could be expanded, since in the proposed model of self-focusing it could be possible to probe a broad selection of intra-cellular determinants of cell-specificity and not just to rely exclusively on extra-cellular markers of cell-specificity. By employing such self-focusing gene vectors for the improvement of cell-targeted delivery of therapeutic genes, e.g., in cancer therapy or gene addition therapy of recessive genetic diseases, it could be possible to broaden a leeway for the reduction of the vector load and, consequently, to minimize undesired vector cytotoxicity, immune reactions, and the risk of inadvertent genetic modification of germline cells in genetic treatment in vivo. Copyright © 2014 Elsevier B.V. All rights reserved.

[Mechanism of protective effects of tumor necrosis factor receptor associated protein 1 on hypoxic cardiomyocytes of rats].

PubMed

Xiang, F; Zhang, D X; Ma, S Y; Huang, Y S

2016-12-20

Objective: To investigate the mechanism of protective effects of tumor necrosis factor receptor associated protein 1 (TRAP1) on hypoxic cardiomyocytes of rats. Methods: Primary cultured cardiomyocytes were obtained from neonatal Sprague-Dawley rats (aged 1 to 3 days) and then used in the following experiments. (1) Cells were divided into group TRAP1 and control group according to the random number table (the same grouping method below), and then the total protein of cells was extracted. Total protein of cells in group TRAP1 was added with mouse anti-rat TRAP1 monoclonal antibody, while that in control group was added with the same type of IgG from mouse. Co-immunoprecipitation and protein mass spectrography analysis were used to determine the possible proteins interacted with TRAP1. (2) Cells were divided into normoxia blank control group (NBC), normoxia+ TRAP1 interference control group (NTIC), normoxia+ TRAP1 interference group (NTI), normoxia+ TRAP1 over-expression control group (NTOC), and normoxia+ TRAP1 over-expression group (NTO), with 1 well in each group. Cells in group NBC were routinely cultured, while cells in the latter four groups were respectively added with TRAP1 RNA interference empty virus vector, TRAP1 RNA interference adenovirus vector, TRAP1 over-expression empty virus vector, and TRAP1 over-expression adenovirus vector. Another batch of cells were divided into group NBC, hypoxic blank control group (HBC), hypoxic+ TRAP1 interference control group (HTIC), hypoxic+ TRAP1 interference group (HTI), hypoxic+ TRAP1 over-expression control group (HTOC), and hypoxic+ TRAP1 over-expression group (HTO), with 1 well in each group. Cells in hypoxic groups were under hypoxic condition for 6 hours after being treated as those in the corresponding normoxia groups, respectively. The mRNA expression of cytochrome c oxidase subunit Ⅱ (COXⅡ) of cells in each group was detected by real time fluorescent quantitive reverse transcription polymerase chain reaction. Experiments were repeated for three times. (3) Cells were divided into group NBC, group HBC, group HTOC, group HTO, hypoxic+ TRAP1 over-expression+ COXⅡinterference control group (HTOCIC), and hypoxic+ TRAP1 over-expression+ COXⅡinterference group (HTOCI), with 3 wells in each group. Cells in the previous 4 groups were treated as those in experiment (2). Cells in group HTOCIC and HTOCI were respectively transfected with COXⅡ RNA interference empty virus vector and COXⅡ RNA interference adenovirus vector, and then both added with TRAP1 over-expression adenovirus vector. The proliferation activity of cells was determined by cell counting kit 8 and microplate reader, and the ratio of death cells was measured by propidium lodide and Hoechst 33342 staining. Another batch of cells were divided into group NBC, group HBC, group HTIC, group HTI, hypoxic+ TRAP1 interference+ COXⅡover-expression control group (HTICOC), and hypoxic+ TRAP1 interference+ COXⅡ over-expression group (HTICO), with 3 wells in each group. Cells in the previous 4 groups were treated as those in experiment (2). Cells in group HTICOC and HTICO were both transfected with TRAP1 RNA interference adenovirus vector, and then respectively added with COXⅡ over-expression empty virus vector and COXⅡ over-expression adenovirus vector. The proliferation activity of cells and the ratio of death cells were detected as before. Experiments were repeated for three times. Data were processed with one-way analysis of variance and LSD test. Results: (1) The expression of TRAP1 was found in cells of group TRAP1, while that was not found in cells of control group. The possible proteins interacted with TRAP1 were keratin, COXⅡ, and an unknown protein with predicted molecular weight 13×10 3 . (2) Compared with that in group NBC, the mRNA expression of COXⅡof cells had no significant change in group NTIC and group NTOC (with P values above 0.05), but significantly decreased in group NTI ( P <0.01), and significantly increased in group NTO ( P <0.01). Compared with that in group NBC, the mRNA expression of COXⅡof cells in group HBC was significantly decreased ( P <0.01). Compared with that in group HBC, the mRNA expression of COXⅡof cells had no significant change in group HTIC and group HTOC (with P values above 0.05), but significantly decreased in group HTI ( P <0.01), and significantly increased in group HTO ( P <0.01). (3) The proliferation activity of cells in group NBC, group HBC, group HTOC, group HTO, group HTOCIC, and group HTOCI was respectively 0.498±0.022, 0.303±0.018, 0.313±0.032, 0.456±0.031, 0.448±0.034, and 0.335±0.026, and the ratios of death cells in above groups were respectively (4.7±1.5)%, (24.7±3.1)%, (26.0±2.7)%, (13.3±2.5)%, (12.7±2.1)%, and (21.0±1.7)%. Compared with those in group NBC, the proliferation activity of cells in HBC was decreased, while the ratio of death cells was increased (with P values below 0.01). Compared with those in group HBC, the proliferation activity of cells and the ratio of death cells in group HTOC had no significant change (with P values above 0.05), while the proliferation activity of cells was increased and the ratio of death cells was decreased in group HTO (with P values below 0.01). Compared with those in group HTO, the proliferation activity of cells and the ratio of death cells in group HTOCIC had no significant change (with P values above 0.05), while the proliferation activity of cells was decreased and the ratio of death cells was increased in group HTOCI (with P values below 0.01). (4) The proliferation activity of cells in group NBC, group HBC, group HTIC, group HTI, group HTICOC, and group HTICO was respectively 0.444±0.025, 0.275±0.016, 0.283±0.021, 0.150±0.009, 0.135±0.011, and 0.237±0.017, and the ratios of death cells in above groups were respectively (3.7±0.6)%, (21.0±2.7)%, (20.3±3.1)%, (31.7±2.5)%, (33.3±3.2)%, and (19.3±1.5)%. Compared with those in group HBC, the proliferation activity of cells and the ratio of death cells in group HTIC had no significant change (with P values above 0.05). Compared with those in group HBC and group HTIC, the proliferation activity of cells was decreased and the ratio of death cells was significantly increased in group HTI (with P values below 0.01). Compared with those in group HTI, the proliferation activity of cells and the ratio of death cells in group HTICOC had no significant change (with P values above 0.05), while the proliferation activity of cells was increased and the ratio of death cells was significantly decreased in group HTICO (with P values below 0.01). Conclusions: TRAP1 can up-regulate the expression of COXⅡ mRNA, and COXⅡ is one of the downstream effector molecules that TRAP1 mediates its protective effects on hypoxic cardiomyocytes.

State-vector formalism and the Legendre polynomial solution for modelling guided waves in anisotropic plates

NASA Astrophysics Data System (ADS)

Zheng, Mingfang; He, Cunfu; Lu, Yan; Wu, Bin

2018-01-01

We presented a numerical method to solve phase dispersion curve in general anisotropic plates. This approach involves an exact solution to the problem in the form of the Legendre polynomial of multiple integrals, which we substituted into the state-vector formalism. In order to improve the efficiency of the proposed method, we made a special effort to demonstrate the analytical methodology. Furthermore, we analyzed the algebraic symmetries of the matrices in the state-vector formalism for anisotropic plates. The basic feature of the proposed method was the expansion of field quantities by Legendre polynomials. The Legendre polynomial method avoid to solve the transcendental dispersion equation, which can only be solved numerically. This state-vector formalism combined with Legendre polynomial expansion distinguished the adjacent dispersion mode clearly, even when the modes were very close. We then illustrated the theoretical solutions of the dispersion curves by this method for isotropic and anisotropic plates. Finally, we compared the proposed method with the global matrix method (GMM), which shows excellent agreement.

Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy

PubMed Central

Bengtsson, Niclas E.; Hall, John K.; Odom, Guy L.; Phelps, Michael P.; Andrus, Colin R.; Hawkins, R. David; Hauschka, Stephen D.; Chamberlain, Joel R.; Chamberlain, Jeffrey S.

2017-01-01

Gene replacement therapies utilizing adeno-associated viral (AAV) vectors hold great promise for treating Duchenne muscular dystrophy (DMD). A related approach uses AAV vectors to edit specific regions of the DMD gene using CRISPR/Cas9. Here we develop multiple approaches for editing the mutation in dystrophic mdx4cv mice using single and dual AAV vector delivery of a muscle-specific Cas9 cassette together with single-guide RNA cassettes and, in one approach, a dystrophin homology region to fully correct the mutation. Muscle-restricted Cas9 expression enables direct editing of the mutation, multi-exon deletion or complete gene correction via homologous recombination in myogenic cells. Treated muscles express dystrophin in up to 70% of the myogenic area and increased force generation following intramuscular delivery. Furthermore, systemic administration of the vectors results in widespread expression of dystrophin in both skeletal and cardiac muscles. Our results demonstrate that AAV-mediated muscle-specific gene editing has significant potential for therapy of neuromuscular disorders. PMID:28195574

Generating an Open Reading Frame (ORF) Entry Clone and Destination Clone.

PubMed

Reece-Hoyes, John S; Walhout, Albertha J M

2018-01-02

This protocol describes using the Gateway recombinatorial cloning system to create an Entry clone carrying an open reading frame (ORF) and then to transfer the ORF into a Destination vector. In this example, BP recombination is used to clone an ORF from a cDNA source into the Donor vector pDONR 221. The ORF from the resulting Entry clone is then transferred into the Destination vector pDEST-15; the product (the Destination clone) will express the ORF as an amino-terminal GST-fusion. The technique can be used as a guide for cloning any other DNA fragment of interest-a promoter sequence or 3' untranslated region (UTR), for example-with substitutions of different genetic material such as genomic DNA, att sites, and vectors as required. The series of constructions and transformations requires 9-15 d, not including time that may be required for sequence confirmation, if desired/necessary. © 2018 Cold Spring Harbor Laboratory Press.

Considerations for the use of human participants in vector biology research: a tool for investigators and regulators.

PubMed

Achee, Nicole L; Youngblood, Laura; Bangs, Michael J; Lavery, James V; James, Stephanie

2015-02-01

A thorough search of the existing literature has revealed that there are currently no published recommendations or guidelines for the interpretation of US regulations on the use of human participants in vector biology research (VBR). An informal survey of vector biologists has indicated that issues related to human participation in vector research have been largely debated by academic, national, and local Institutional Review Boards (IRBs) in the countries where the research is being conducted, and that interpretations and subsequent requirements made by these IRBs have varied widely. This document is intended to provide investigators and corresponding scientific and ethical review committee members an introduction to VBR methods involving human participation and the legal and ethical framework in which such studies are conducted with a focus on US Federal Regulations. It is also intended to provide a common perspective for guiding researchers, IRB members, and other interested parties (i.e., public health officials conducting routine entomological surveillance) in the interpretation of human subjects regulations pertaining to VBR.

A Guided Tour of Mathematical Methods

NASA Astrophysics Data System (ADS)

Snieder, Roel

2009-04-01

1. Introduction; 2. Dimensional analysis; 3. Power series; 4. Spherical and cylindrical co-ordinates; 5. The gradient; 6. The divergence of a vector field; 7. The curl of a vector field; 8. The theorem of Gauss; 9. The theorem of Stokes; 10. The Laplacian; 11. Conservation laws; 12. Scale analysis; 13. Linear algebra; 14. The Dirac delta function; 15. Fourier analysis; 16. Analytic functions; 17. Complex integration; 18. Green's functions: principles; 19. Green's functions: examples; 20. Normal modes; 21. Potential theory; 22. Cartesian tensors; 23. Perturbation theory; 24. Asymptotic evaluation of integrals; 25. Variational calculus; 26. Epilogue, on power and knowledge; References.

Configurations of a two-tiered amplified gene expression system in adenoviral vectors designed to improve the specificity of in vivo prostate cancer imaging

PubMed Central

Sato, M; Figueiredo, ML; Burton, JB; Johnson, M; Chen, M; Powell, R; Gambhir, SS; Carey, M; Wu, L

2009-01-01

Effective treatment for recurrent, disseminated prostate cancer is notably limited. We have developed adenoviral vectors with a prostate-specific two-step transcriptional amplification (TSTA) system that would express therapeutic genes at a robust level to target metastatic disease. The TSTA system employs the prostate-specific antigen (PSA) promoter/enhancer to drive a potent synthetic activator, which in turn activates the expression of the therapeutic gene. In this study, we explored different configurations of this bipartite system and discovered that physical separation of the two TSTA components into E1 and E3 regions of adenovirus was able to enhance androgen regulation and cell-discriminatory expression. The TSTA vectors that express imaging reporter genes were assessed by noninvasive imaging technologies in animal models. The improved selectivity of the E1E3 configured vector was reflected in silenced ectopic expression in the lung. Significantly, the enhanced specificity of the E1E3 vector enabled the detection of lung metastasis of prostate cancer. An E1E3 TSTA vector that expresses the herpes simplex virus thymidine kinase gene can effectively direct positron emission tomography (PET) imaging of the tumor. The prostate-targeted gene delivery vectors with robust and cell-specific expression capability will advance the development of safe and effective imaging guided therapy for recurrent metastatic stages of prostate cancer. PMID:18305574

Modeling Malaria Vector Distribution under Climate Change Scenarios in Kenya

NASA Astrophysics Data System (ADS)

Ngaina, J. N.

2017-12-01

Projecting the distribution of malaria vectors under climate change is essential for planning integrated vector control strategies for sustaining elimination and preventing reintroduction of malaria. However, in Kenya, little knowledge exists on the possible effects of climate change on malaria vectors. Here we assess the potential impact of future climate change on locally dominant Anopheles vectors including Anopheles gambiae, Anopheles arabiensis, Anopheles merus, Anopheles funestus, Anopheles pharoensis and Anopheles nili. Environmental data (Climate, Land cover and elevation) and primary empirical geo-located species-presence data were identified. The principle of maximum entropy (Maxent) was used to model the species' potential distribution area under paleoclimate, current and future climates. The Maxent model was highly accurate with a statistically significant AUC value. Simulation-based estimates suggest that the environmentally suitable area (ESA) for Anopheles gambiae, An. arabiensis, An. funestus and An. pharoensis would increase under all two scenarios for mid-century (2016-2045), but decrease for end century (2071-2100). An increase in ESA of An. Funestus was estimated under medium stabilizing (RCP4.5) and very heavy (RCP8.5) emission scenarios for mid-century. Our findings can be applied in various ways such as the identification of additional localities where Anopheles malaria vectors may already exist, but has not yet been detected and the recognition of localities where it is likely to spread to. Moreover, it will help guide future sampling location decisions, help with the planning of vector control suites nationally and encourage broader research inquiry into vector species niche modeling

Analysis of Genetic Algorithm for Rule-Set Production (GARP) modeling approach for predicting distributions of fleas implicated as vectors of plague, Yersinia pestis, in California.

PubMed

Adjemian, Jennifer C Z; Girvetz, Evan H; Beckett, Laurel; Foley, Janet E

2006-01-01

More than 20 species of fleas in California are implicated as potential vectors of Yersinia pestis. Extremely limited spatial data exist for plague vectors-a key component to understanding where the greatest risks for human, domestic animal, and wildlife health exist. This study increases the spatial data available for 13 potential plague vectors by using the ecological niche modeling system Genetic Algorithm for Rule-Set Production (GARP) to predict their respective distributions. Because the available sample sizes in our data set varied greatly from one species to another, we also performed an analysis of the robustness of GARP by using the data available for flea Oropsylla montana (Baker) to quantify the effects that sample size and the chosen explanatory variables have on the final species distribution map. GARP effectively modeled the distributions of 13 vector species. Furthermore, our analyses show that all of these modeled ranges are robust, with a sample size of six fleas or greater not significantly impacting the percentage of the in-state area where the flea was predicted to be found, or the testing accuracy of the model. The results of this study will help guide the sampling efforts of future studies focusing on plague vectors.

Generic Drugs - Decreasing Costs and Room for Increased Number of Kidney Transplantations.

PubMed

Spasovski, Goce

2015-01-01

Kidney transplantation is the best treatment option in comparison to dialysis, although patients are obliged to receive life-long medical treatment with immunosuppressive drugs (ISDs) for prevention of the graft rejection. Such immunosuppressive treatment may be costly and associated with multiple adverse effects. Since costs are viewed as one of the major constraints for the increasing number of transplantation, the use of generic ISDs may decrease the overall cost of transplantation and raise the possibility for its further development. An ideal ISD should have the security margin between toxic and therapeutic dose, and prevent development of acute or chronic rejection of the transplanted kidney. This is particularly important for drugs with a "narrow therapeutical index" (NTI), where small differences in dose or concentration lead to dose and concentration-dependent, serious therapeutic failures and/or adverse drug reactions. The NTI generic drug is approved if within 90%-112% of the area under the curve of the original product the pharmacokinetics fulfills the strict criteria of pharmaceutical equivalence and bioequivalence. Every generic has to be proven to be bioequivalent to the innovator product, and not to other generic products because of the possible generic "drift". Thus, the generic ISDs may be economically attractive, but theoretically, they may pose a risk to transplant patients. Such risks may be reduced if a long-term clinical studies showing cost-effectiveness of generic ISDs in de novo and prevalent transplant patients for every new generic ISD are performed. In conclusion, the increased number of solid organ transplantation goes in line with the increased health care expenditure for ISDs. The generic immunosuppressants could be a possible solution if safely substituted for innovator products or other generic drug of choice. The substantial cost reduction needs to be redirected into organ donation initiatives so that more patients can benefit from the further increase in transplantation.

Targeted gene knock-in by homology-directed genome editing using Cas9 ribonucleoprotein and AAV donor delivery.

PubMed

Gaj, Thomas; Staahl, Brett T; Rodrigues, Gonçalo M C; Limsirichai, Prajit; Ekman, Freja K; Doudna, Jennifer A; Schaffer, David V

2017-06-20

Realizing the full potential of genome editing requires the development of efficient and broadly applicable methods for delivering programmable nucleases and donor templates for homology-directed repair (HDR). The RNA-guided Cas9 endonuclease can be introduced into cells as a purified protein in complex with a single guide RNA (sgRNA). Such ribonucleoproteins (RNPs) can facilitate the high-fidelity introduction of single-base substitutions via HDR following co-delivery with a single-stranded DNA oligonucleotide. However, combining RNPs with transgene-containing donor templates for targeted gene addition has proven challenging, which in turn has limited the capabilities of the RNP-mediated genome editing toolbox. Here, we demonstrate that combining RNP delivery with naturally recombinogenic adeno-associated virus (AAV) donor vectors enables site-specific gene insertion by homology-directed genome editing. Compared to conventional plasmid-based expression vectors and donor templates, we show that combining RNP and AAV donor delivery increases the efficiency of gene addition by up to 12-fold, enabling the creation of lineage reporters that can be used to track the conversion of striatal neurons from human fibroblasts in real time. These results thus illustrate the potential for unifying nuclease protein delivery with AAV donor vectors for homology-directed genome editing. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Virally delivered Channelrhodopsin-2 Safely and Effectively Restores Visual Function in Multiple Mouse Models of Blindness

PubMed Central

Doroudchi, M Mehdi; Greenberg, Kenneth P; Liu, Jianwen; Silka, Kimberly A; Boyden, Edward S; Lockridge, Jennifer A; Arman, A Cyrus; Janani, Ramesh; Boye, Shannon E; Boye, Sanford L; Gordon, Gabriel M; Matteo, Benjamin C; Sampath, Alapakkam P; Hauswirth, William W; Horsager, Alan

2011-01-01

Previous work established retinal expression of channelrhodopsin-2 (ChR2), an algal cation channel gated by light, restored physiological and behavioral visual responses in otherwise blind rd1 mice. However, a viable ChR2-based human therapy must meet several key criteria: (i) ChR2 expression must be targeted, robust, and long-term, (ii) ChR2 must provide long-term and continuous therapeutic efficacy, and (iii) both viral vector delivery and ChR2 expression must be safe. Here, we demonstrate the development of a clinically relevant therapy for late stage retinal degeneration using ChR2. We achieved specific and stable expression of ChR2 in ON bipolar cells using a recombinant adeno-associated viral vector (rAAV) packaged in a tyrosine-mutated capsid. Targeted expression led to ChR2-driven electrophysiological ON responses in postsynaptic retinal ganglion cells and significant improvement in visually guided behavior for multiple models of blindness up to 10 months postinjection. Light levels to elicit visually guided behavioral responses were within the physiological range of cone photoreceptors. Finally, chronic ChR2 expression was nontoxic, with transgene biodistribution limited to the eye. No measurable immune or inflammatory response was observed following intraocular vector administration. Together, these data indicate that virally delivered ChR2 can provide a viable and efficacious clinical therapy for photoreceptor disease-related blindness. PMID:21505421

Cylindrical Vector Beams for Rapid Polarization-Dependent Measurements in Atomic Systems

DTIC Science & Technology

2011-12-05

www.opticsinfobase.org/abstract.cfm?URI=oe-18-24-25035. 16. S. Tripathi and K. C. Toussaint, Jr., “Rapid Mueller matrix polarimetry based on parallelized...optical trapping [11], atom guiding [12], laser machining [13], charged particle acceleration [14,15], and polarimetry [16]. Yet despite numerous

The maxillary palp of aedes aegypti, a model of multisensory integration

USDA-ARS?s Scientific Manuscript database

Female yellow-fever mosquitoes, Aedes aegypti, are obligate blood-feeders and vectors of the pathogens that cause dengue fever, yellow fever and Chikungunya. This feeding behavior concludes a series of multisensory events guiding the mosquito to its host from a distance. The antennae and maxillary...

A hitchhiker's guide to the Maritimes: anthropogenic transport facilitates long-distance dispersal of an invasive marine crab to Newfoundland

EPA Science Inventory

We analyzed mitochondrial and microsatellite genetic data from European and Northwest Atlantic populations sampled during 1999-2002 to determine probable source locations and vectors for the Placentia Bay introduction discovered in 2007. We also analyzed Placentia Bay demographi...

Mapping of courses on vector biology and vector-borne diseases systems: time for a worldwide effort.

PubMed

Casas, Jérôme; Lazzari, Claudio; Insausti, Teresita; Launois, Pascal; Fouque, Florence

2016-11-01

Major emergency efforts are being mounted for each vector-borne disease epidemiological crisis anew, while knowledge about the biology of arthropods vectors is dwindling slowly but continuously, as is the number of field entomologists. The discrepancy between the rates of production of knowledge and its use and need for solving crises is widening, in particular due to the highly differing time spans of the two concurrent processes. A worldwide web based search using multiple key words and search engines of onsite and online courses in English, Spanish, Portuguese, French, Italian and German concerned with the biology of vectors identified over 140 courses. They are geographically and thematically scattered, the vast majority of them are on-site, with very few courses using the latest massive open online course (MOOC) powerfulness. Over two third of them is given in English and Western Africa is particularity poorly represented. The taxonomic groups covered are highly unbalanced towards mosquitoes. A worldwide unique portal to guide students of all grades and levels of expertise, in particular those in remote locations, is badly needed. This is the objective a new activity supported by the Special Programme for Research and Training in Tropical Diseases (TDR).

Reanalyzing the "far medial" (transcondylar-transtubercular) approach based on three anatomical vectors: the ventral posterolateral corridor.

PubMed

Chakravarthi, Srikant; Monroy-Sosa, Alejandro; Gonen, Lior; Fukui, Melanie; Rovin, Richard; Kojis, Nathaniel; Lindsay, Mark; Khalili, Sammy; Celix, Juanita; Corsten, Martin; Kassam, Amin B

2018-06-01

Endoscopic endonasal access to the jugular foramen and occipital condyle - the transcondylar-transtubercular approach - is anatomically complex and requires detailed knowledge of the relative position of critical neurovascular structures, in order to avoid inadvertent injury and resultant complications. However, access to this region can be confusing as the orientation and relationships of osseous, vascular, and neural structures are very much different from traditional dorsal approaches. This review aims at providing an organizational construct for a more understandable framework in accessing the transcondylar-transtubercular window. The region can be conceptualized using a three-vector coordinate system: vector 1 represents a dorsal or ventral corridor, vector 2 represents the outer and inner circumferential anatomical limits; in an "onion-skin" fashion, key osseous, vascular, and neural landmarks are organized based on a 360-degree skull base model, and vector 3 represents the final core or target of the surgical corridor. The creation of an organized "global-positioning system" may better guide the surgeon in accessing the far-medial transcondylar-transtubercular region, and related pathologies, and help understand the surgical limits to the occipital condyle and jugular foramen - the ventral posterolateral corridor - via the endoscopic endonasal approach.

Mapping of courses on vector biology and vector-borne diseases systems: time for a worldwide effort

PubMed Central

Casas, Jérôme; Lazzari, Claudio; Insausti, Teresita; Launois, Pascal; Fouque, Florence

2016-01-01

Major emergency efforts are being mounted for each vector-borne disease epidemiological crisis anew, while knowledge about the biology of arthropods vectors is dwindling slowly but continuously, as is the number of field entomologists. The discrepancy between the rates of production of knowledge and its use and need for solving crises is widening, in particular due to the highly differing time spans of the two concurrent processes. A worldwide web based search using multiple key words and search engines of onsite and online courses in English, Spanish, Portuguese, French, Italian and German concerned with the biology of vectors identified over 140 courses. They are geographically and thematically scattered, the vast majority of them are on-site, with very few courses using the latest massive open online course (MOOC) powerfulness. Over two third of them is given in English and Western Africa is particularity poorly represented. The taxonomic groups covered are highly unbalanced towards mosquitoes. A worldwide unique portal to guide students of all grades and levels of expertise, in particular those in remote locations, is badly needed. This is the objective a new activity supported by the Special Programme for Research and Training in Tropical Diseases (TDR). PMID:27759770

Air Force Human Resources Laboratory Annual Report - Fiscal Year 1979.

DTIC Science & Technology

1980-09-01

Nut ’ilt’. I itg l I ntI it I v aten voi b% ch p l t. he r stit, bo’vijt rli i’lei . tt oill’tt i u atas : l t iittil ti hual for )it If ffri~i% an( v...and logistivs factors in weapon system design and dv. ch ,lnent studies (Dol) Iirectives 5000.1 and Benefits: The models of Maintenance Resources 5(1o.2...miii or s.kills. Ili o.i~vced a ie’’’. inis’’tine as thlt first gricizp of tit-e F-l0 %veajiiiil -Stlemi. training skills 1-i h r ch lo ’oclq . hIsr the

Optimization of Performance of Arc Welding Using Fluxes in Welded Ship Structures from HY-100 and HY-130 KPSI.

DTIC Science & Technology

1981-09-01

production and formulation for several decades. NMgO + NCaO + NMnO + NFeO + NAI 20 3Basicity = NSiO 2 + NTi0 2 + NZr0 2 + NA1 203 This differs from the widely...20 3 100 (CaO-SiO, )(40) slag CaO/SiO 2 0.15 none 2600 NCaO /NSiO2 0.17 8% FeSi 1900 16% FeSi 1700 32% FeSi 1400 52 I Table 8 (continued). Islag Ca0...SiO~e .79 none 1200 NCaO /NSiOz .84 2% FeSi 1000 4% FeSi 900 16% FeSi 500 32% FeSi 500 Mechanical Property Tests Mechanical property weldments were

A Guided Tour of Mathematical Methods for the Physical Sciences

NASA Astrophysics Data System (ADS)

Snieder, Roel; van Wijk, Kasper

2015-05-01

1. Introduction; 2. Dimensional analysis; 3. Power series; 4. Spherical and cylindrical coordinates; 5. Gradient; 6. Divergence of a vector field; 7. Curl of a vector field; 8. Theorem of Gauss; 9. Theorem of Stokes; 10. The Laplacian; 11. Scale analysis; 12. Linear algebra; 13. Dirac delta function; 14. Fourier analysis; 15. Analytic functions; 16. Complex integration; 17. Green's functions: principles; 18. Green's functions: examples; 19. Normal modes; 20. Potential-field theory; 21. Probability and statistics; 22. Inverse problems; 23. Perturbation theory; 24. Asymptotic evaluation of integrals; 25. Conservation laws; 26. Cartesian tensors; 27. Variational calculus; 28. Epilogue on power and knowledge.

Diversity of breeding habitats of anophelines (Diptera: Culicidae) in Ramgarh district, Jharkhand, India.

PubMed

Pandey, Siddharth; Das, M K; Dhiman, Ramesh C

2016-01-01

The Ramgarh district of Jharkhand state, India is highly malarious owing to abundance of different malaria vector species, namely Anopheles culicifacies, An. fluviatilis and An. annularis. In spite of high prevalence of malaria vectors in Ramgarh, their larval ecology and climatic conditions affecting malaria dynamics have never been studied. Therefore, the objective of this study was to identify the diversity of potential breeding habitats and breeding preferences of anopheline vectors in the Ramgarh district. Anopheles immature collection was carried out at potential aquatic habitats in Ramgarh and Gola sites using the standard dipper on fortnightly basis from August 2012 to July 2013. The immatures were reared till adult emergence and further identified using standard keys. Temperature of outdoor and water bodies was recorded through temperature data loggers, and rainfall through standard rain gauges installed at each site. A total of 6495 immature specimens representing 17 Anopheles species including three malaria vectors, viz. An. culicifacies, An. fluviatilis and An. annularis were collected from 11 types of breeding habitats. The highly preferred breeding habitats of vector anophelines were river bed pools, rivulets, wells, ponds, river margins, ditches and irrigation channels. Larval abundance of vector species showed site-specific variation with temperature and rainfall patterns throughout the year. The Shannon-Weiner diversity index ranged from 0.19 to 1.94 at Ramgarh site and 0.16 to 1.76 at Gola site. The study revealed that malaria vector species have been adapted to breed in a wide range of water bodies. The regular monitoring of such specific vector breeding sites under changing ecological and environmental conditions will be useful in guiding larval control operations selectively for effective vector/ malaria control.

Impact damage imaging in a curved composite panel with wavenumber index via Riesz transform

NASA Astrophysics Data System (ADS)

Chang, Huan-Yu; Yuan, Fuh-Gwo

2018-03-01

The barely visible impact damages reduce the strength of composite structures significantly; however, they are difficult to be detected during regular visual inspection. A guided wave based damage imaging condition method is developed and applied on a curved composite panel, which is a part of an aileron from a retired Boeing C-17 Globemaster III. Ultrasonic guided waves are excited by a piezoelectric transducer (PZT) and then captured by a laser Doppler vibrometer (LDV). The wavefield images are constructed by measuring the out-of-plane velocity point by point within interrogation region, and the anomalies at the damage area can be observed with naked eye. The discontinuities of material properties leads to the change of wavenumber while the wave propagating through the damaged area. These differences in wavenumber can be observed by deriving instantaneous wave vector via Riesz transform (RT), and then be shown and highlighted with the proposed imaging condition named wavenumber index (WI). RT can be introduced as a two-dimensional (2-D) generalization of Hilbert transform (HT) to derive instantaneous phases, amplitudes, orientations of a guided-wave field. WI employs the instantaneous wave vector and weighted instantaneous wave energy computed from the instantaneous amplitudes, yielding high sensitivity and sharp damage image with computational efficiency. The BVID of the composite structure becomes therefore "visible" with the developed technique.

Safety and tolerability of MRI-guided infusion of AAV2-hAADC into the mid-brain of nonhuman primate

PubMed Central

Sebastian, Waldy San; Kells, Adrian P; Bringas, John; Samaranch, Lluis; Hadaczek, Piotr; Ciesielska, Agnieszka; Macayan, Michael J; Pivirotto, Phillip J; Forsayeth, John; Osborne, Sheryl; Wright, J Fraser; Green, Foad; Heller, Gregory; Bankiewicz, Krystof S

2014-01-01

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, autosomal-recessive neurological disorder caused by mutations in the DDC gene that leads to an inability to synthesize catecholamines and serotonin. As a result, patients suffer compromised development, particularly in motor function. A recent gene replacement clinical trial explored putaminal delivery of recombinant adeno-associated virus serotype 2 vector encoding human AADC (AAV2-hAADC) in AADC-deficient children. Unfortunately, patients presented only modest amelioration of motor symptoms, which authors acknowledged could be due to insufficient transduction of putamen. We hypothesize that, with the development of a highly accurate MRI-guided cannula placement technology, a more effective approach might be to target the affected mid-brain neurons directly. Transduction of AADC-deficient dopaminergic neurons in the substantia nigra and ventral tegmental area with locally infused AAV2-hAADC would be expected to lead to restoration of normal dopamine levels in affected children. The objective of this study was to assess the long-term safety and tolerability of bilateral AAV2-hAADC MRI-guided pressurized infusion into the mid-brain of nonhuman primates. Animals received either vehicle, low or high AAV2-hAADC vector dose and were euthanized 1, 3, or 9 months after surgery. Our data indicate that effective mid-brain transduction was achieved without untoward effects. PMID:25541617

Justice foundations for the Comprehensive Law Movement.

PubMed

Dewhurst, Dale

2010-01-01

Authors examining the developing dispute resolution alternatives to the adversarial system have identified nine converging "vectors" or alternatives in what has been termed the Comprehensive Law Movement. These authors have sought to understand how the developing vectors can remain separate and vibrant movements while sharing common ground. Some analyze these developments as being within law and legal practice, others see them as alternative approaches to law, and still others take a combined approach. It will be impossible to understand how these vectors have meaningful differences from law and legal practice if the search is limited to looking within law and legal practice. It will be impossible to understand how these vectors have meaningful commonalities with law and legal practice if the search is limited to looking external to law and legal practice. Instead of comparing the vectors with the adversarial system, higher order criteria are required. What is needed is a comprehensive and internally consistent super-system of norms; one that can be used to evaluate the adversarial system and the evolving vectors on an equal footing. An Aristotelian natural law virtue theory of justice can: (a) provide a functional guiding definition of justice; (b) serve as a comprehensive and internally consistent super-system of norms; and (c) provide the theoretical and evaluative foundation required to clarify the relationships among the adversarial system and the developing vectors. Finally, it will become clear why the Comprehensive Law Movement might be more appropriately conceptualized as the Comprehensive Justice Movement. Copyright © 2010 Elsevier Ltd. All rights reserved.

Transcriptomics-guided development of RNA interference strategies to manage whiteflies: a globally distributed vector of crop viruses

USDA-ARS?s Scientific Manuscript database

Over 300 viruses are transmitted by the whitefly, Bemisia tabaci, with 90% of them belonging to the genus, Begomovirus. Begomoviruses are exclusively transmitted by whiteflies to a range of agriculture crops, resulting in billions of dollars lost annually, while jeopardizing food security worldwide....

Gravity related features of plant growth behavior studied with rotating machines

NASA Technical Reports Server (NTRS)

Brown, A. H.

1996-01-01

Research in plant physiology consists mostly of studies on plant growth because almost everything a plant does is done by growing. Most aspects of plant growth are strongly influenced by the earth's gravity vector. Research on those phenomena address scientific questions specifically about how plants use gravity to guide their growth processes.

Environmental and social-demographic predictors of the southern house mosquito Culex quinquefasciatus in New Orleans, Louisiana

USDA-ARS?s Scientific Manuscript database

Flooding events have become common throughout the world yet our understanding of how these events affect the spatial and temporal distribution of disease vectors such as mosquitoes is limited. This knowledge can guide development of effective and timely strategies for mitigating mosquito-borne disea...

Investigation of Performance Improvements Including Application of Inlet Guide Vanes to a Cross-flow Fan

DTIC Science & Technology

2009-09-01

25 Figure 17. IGV Cut Out from Fluid Domain...Figure 22. Installed IGVS as Viewed from the CFF Inlet.................................................30 Figure 23. Schematic of Turbine Test Rig (TTR...44 Figure 28. Close In View of Velocity Vector Plot Near IGVS for 6IGV Model..............45 Figure 29

Industrial Prep, Volume Four, Junior Year--Contents: Mathematics and Guidance.

ERIC Educational Resources Information Center

Hackensack Public Schools, NJ.

As part of a 3-year comprehensive interdisciplinary program in industrial preparation for vocational students, this 11th Grade teaching guide consists of units on technical mathematics and guidance. Designed as supportive material for related physics and English curriculums, the first four sections of Volume 4 on algebra, vectors, simple machines,…

Experimental Characterization of Guided Waves by Their Surface Displacement Vector Field

NASA Astrophysics Data System (ADS)

Barth, M.; Köhler, B.; Schubert, L.

2009-03-01

The development new nondestructive evaluation (NDE) and structural health monitoring (SHM) methods utilizing guided elastic waves needs a good understanding of wave propagation properties and the interaction of the waves with structures and defects. If the geometrical and stiffness properties of the components are well known, these effects can be studied very efficiently by numerical modeling. But very often there is a lack of precise knowledge of all necessary elastic properties; accurate and non-disturbing measurements are without alternative in these cases. The mapping of wave fields can be done by scanning laser vibrometers as demonstrated in a number of cases. Originally, a laser vibrometer provides only information from one displacement component. To get all three displacement components, the simultaneous measurement with three vibrometers is offered commercially. This is a very expensive approach. The paper describes a method which uses only one vibrometer sequentially for getting all three vector components. It allows determining additional parameters for characterizing wave modes as e.g. the ellipticity. The capability of this approach is demonstrated for the characterization of Lamb waves.

ML 3.1 developer's guide.

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

Sala, Marzio; Hu, Jonathan Joseph; Tuminaro, Raymond Stephen

2004-05-01

ML development was started in 1997 by Ray Tuminaro and Charles Tong. Currently, there are several full- and part-time developers. The kernel of ML is written in ANSI C, and there is a rich C++ interface for Trilinos users and developers. ML can be customized to run geometric and algebraic multigrid; it can solve a scalar or a vector equation (with constant number of equations per grid node), and it can solve a form of Maxwell's equations. For a general introduction to ML and its applications, we refer to the Users Guide [SHT04], and to the ML web site, http://software.sandia.gov/ml.

Vector radiative transfer code SORD: Performance analysis and quick start guide

NASA Astrophysics Data System (ADS)

Korkin, Sergey; Lyapustin, Alexei; Sinyuk, Alexander; Holben, Brent; Kokhanovsky, Alexander

2017-10-01

We present a new open source polarized radiative transfer code SORD written in Fortran 90/95. SORD numerically simulates propagation of monochromatic solar radiation in a plane-parallel atmosphere over a reflecting surface using the method of successive orders of scattering (hence the name). Thermal emission is ignored. We did not improve the method in any way, but report the accuracy and runtime in 52 benchmark scenarios. This paper also serves as a quick start user's guide for the code available from ftp://maiac.gsfc.nasa.gov/pub/skorkin, from the JQSRT website, or from the corresponding (first) author.

User's guide for NASCRIN: A vectorized code for calculating two-dimensional supersonic internal flow fields

NASA Technical Reports Server (NTRS)

Kumar, A.

1984-01-01

A computer program NASCRIN has been developed for analyzing two-dimensional flow fields in high-speed inlets. It solves the two-dimensional Euler or Navier-Stokes equations in conservation form by an explicit, two-step finite-difference method. An explicit-implicit method can also be used at the user's discretion for viscous flow calculations. For turbulent flow, an algebraic, two-layer eddy-viscosity model is used. The code is operational on the CDC CYBER 203 computer system and is highly vectorized to take full advantage of the vector-processing capability of the system. It is highly user oriented and is structured in such a way that for most supersonic flow problems, the user has to make only a few changes. Although the code is primarily written for supersonic internal flow, it can be used with suitable changes in the boundary conditions for a variety of other problems.

B-physics anomalies: a guide to combined explanations

NASA Astrophysics Data System (ADS)

Buttazzo, Dario; Greljo, Admir; Isidori, Gino; Marzocca, David

2017-11-01

Motivated by additional experimental hints of Lepton Flavour Universality violation in B decays, both in charged- and in neutral-current processes, we analyse the ingredients necessary to provide a combined description of these phenomena. By means of an Effective Field Theory (EFT) approach, based on the hypothesis of New Physics coupled predominantly to the third generation of left-handed quarks and leptons, we show how this is possible. We demonstrate, in particular, how to solve the problems posed by electroweak precision tests and direct searches with a rather natural choice of model parameters, within the context of a U(2) q ×U(2)ℓ flavour symmetry. We further exemplify the general EFT findings by means of simplified models with explicit mediators in the TeV range: coloured scalar or vector leptoquarks and colour-less vectors. Among these, the case of an SU(2) L -singlet vector leptoquark emerges as a particularly simple and successful framework.

PubMed

Gómez, Luis Alberto; Montoya, Gladis; Rivera, Hernán Mauricio; Hernández, Juan Carlos

2017-04-01

Introducción. El virus del Zika (ZIKV) es un flavivirus con envoltura, transmitido a los seres humanos principalmente por el vector Aedes aegypti. La infección por ZIKV se ha asociado con un gran neurotropismo y con efectos neuropáticos, como el síndrome de Guillain-Barré en el adulto y la microcefalia fetal y posnatal, así como con un síndrome de infección congénita similar al producido por el virus de la rubéola (RV).Objetivo. Comparar las estructuras moleculares de la proteína de envoltura E del virus del Zika (E-ZIKV) y de la E1 del virus de la rubéola (E1-RV), y plantear posibles implicaciones en el neurotropismo y en las alteraciones del sistema nervioso asociadas con el ZIKV.Materiales y métodos. La secuencia de aminoácidos de la proteína E-ZIKV (PDB: 5iZ7) se alineó con la de la glucopreteína E1 del virus de la rubéola (PDB: 4ADG). Los elementos de la estructura secundaria se determinaron usando los programas Vector NTI Advance®, DSSP y POSA, así como herramientas de gestión de datos (AlignX®). Uno de los criterios principales de comparación y alineación fue la asignación de residuos estructuralmente equivalentes, con más de 70 % de identidad.Resultados. La organización estructural de la proteína E-ZIKV (PDB: 5iZ7) fue similar a la de E1-RV (PDB: 4ADG) (70 a 80 % de identidad), y se observó una correspondencia con la estructura definida para las glucoproteínas de fusión de membrana de clase II de los virus con envoltura. E-ZIKV y E1-RV exhibieron elementos estructurales de fusión muy conservados en la región distal del dominio II, asociados con la unión a los receptores celulares de entrada del virus de la rubéola (glucoproteína de mielina del oligodendrocito, Myelin Oligodendrocyte Glycoprotein, MOG), y con los receptores celulares Axl del ZIKV y de otros flavivirus.Conclusión. La comparación de las proteínas E-ZIKV y E1-RV es un paso necesario hacia la definición de otros factores moleculares determinantes del neurotropismo y la patogenia del ZIKV, el cual puede contribuir a generar estrategias de diagnóstico, prevención y tratamiento de las complicaciones neurológicas inducidas por el ZIKV.

A Computational Study of a New Dual Throat Fluidic Thrust Vectoring Nozzle Concept

NASA Technical Reports Server (NTRS)

Deere, Karen A.; Berrier, Bobby L.; Flamm, Jeffrey D.; Johnson, Stuart K.

2005-01-01

A computational investigation of a two-dimensional nozzle was completed to assess the use of fluidic injection to manipulate flow separation and cause thrust vectoring of the primary jet thrust. The nozzle was designed with a recessed cavity to enhance the throat shifting method of fluidic thrust vectoring. Several design cycles with the structured-grid, computational fluid dynamics code PAB3D and with experiments in the NASA Langley Research Center Jet Exit Test Facility have been completed to guide the nozzle design and analyze performance. This paper presents computational results on potential design improvements for best experimental configuration tested to date. Nozzle design variables included cavity divergence angle, cavity convergence angle and upstream throat height. Pulsed fluidic injection was also investigated for its ability to decrease mass flow requirements. Internal nozzle performance (wind-off conditions) and thrust vector angles were computed for several configurations over a range of nozzle pressure ratios from 2 to 7, with the fluidic injection flow rate equal to 3 percent of the primary flow rate. Computational results indicate that increasing cavity divergence angle beyond 10 is detrimental to thrust vectoring efficiency, while increasing cavity convergence angle from 20 to 30 improves thrust vectoring efficiency at nozzle pressure ratios greater than 2, albeit at the expense of discharge coefficient. Pulsed injection was no more efficient than steady injection for the Dual Throat Nozzle concept.

Considerations for the Use of Human Participants in Vector Biology Research: A Tool for Investigators and Regulators

PubMed Central

Youngblood, Laura; Bangs, Michael J.; Lavery, James V.; James, Stephanie

2015-01-01

Abstract A thorough search of the existing literature has revealed that there are currently no published recommendations or guidelines for the interpretation of US regulations on the use of human participants in vector biology research (VBR). An informal survey of vector biologists has indicated that issues related to human participation in vector research have been largely debated by academic, national, and local Institutional Review Boards (IRBs) in the countries where the research is being conducted, and that interpretations and subsequent requirements made by these IRBs have varied widely. This document is intended to provide investigators and corresponding scientific and ethical review committee members an introduction to VBR methods involving human participation and the legal and ethical framework in which such studies are conducted with a focus on US Federal Regulations. It is also intended to provide a common perspective for guiding researchers, IRB members, and other interested parties (i.e., public health officials conducting routine entomological surveillance) in the interpretation of human subjects regulations pertaining to VBR. PMID:25700039

Formation mechanism of guided resonances and bound states in the continuum in photonic crystal slabs

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

Gao, Xingwei; Hsu, Chia Wei; Zhen, Bo

2016-08-25

We develop a formalism, based on the mode expansion method, to describe the guided resonances and bound states in the continuum (BICs) in photonic crystal slabs with one-dimensional periodicity. This approach provides analytic insights to the formation mechanisms of these states: the guided resonances arise from the transverse Fabry–Pérot condition, and the divergence of the resonance lifetimes at the BICs is explained by a destructive interference of radiation from different propagating components inside the slab. As a result, we show BICs at the center and on the edge of the Brillouin zone protected by symmetry, BICs at generic wave vectorsmore » not protected by symmetry, and the annihilation of BICs at low-symmetry wave vectors.« less

Iron oxide nanoparticles for magnetically-guided and magnetically-responsive drug delivery.

PubMed

Estelrich, Joan; Escribano, Elvira; Queralt, Josep; Busquets, Maria Antònia

2015-04-10

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.

Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery

PubMed Central

Estelrich, Joan; Escribano, Elvira; Queralt, Josep; Busquets, Maria Antònia

2015-01-01

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release. PMID:25867479

CCR5 Gene Disruption via Lentiviral Vectors Expressing Cas9 and Single Guided RNA Renders Cells Resistant to HIV-1 Infection

PubMed Central

Liu, Jingjing; Zhang, Di; Kimata, Jason T.; Zhou, Paul

2014-01-01

CCR5, a coreceptor for HIV-1 entry, is a major target for drug and genetic intervention against HIV-1. Genetic intervention strategies have knocked down CCR5 expression levels by shRNA or disrupted the CCR5 gene using zinc finger nucleases (ZFN) or Transcription activator-like effector nuclease (TALEN). In the present study, we silenced CCR5 via CRISPR associated protein 9 (Cas9) and single guided RNAs (sgRNAs). We constructed lentiviral vectors expressing Cas9 and CCR5 sgRNAs. We show that a single round transduction of lentiviral vectors expressing Cas9 and CCR5 sgRNAs into HIV-1 susceptible human CD4+ cells yields high frequencies of CCR5 gene disruption. CCR5 gene-disrupted cells are not only resistant to R5-tropic HIV-1, including transmitted/founder (T/F) HIV-1 isolates, but also have selective advantage over CCR5 gene-undisrupted cells during R5-tropic HIV-1 infection. Importantly, using T7 endonuclease I assay we did not detect genome mutations at potential off-target sites that are highly homologous to these CCR5 sgRNAs in stably transduced cells even at 84 days post transduction. Thus we conclude that silencing of CCR5 via Cas9 and CCR5-specific sgRNAs could be a viable alternative strategy for engineering resistance against HIV-1. PMID:25541967

Normal mode-guided transition pathway generation in proteins

PubMed Central

Lee, Byung Ho; Seo, Sangjae; Kim, Min Hyeok; Kim, Youngjin; Jo, Soojin; Choi, Moon-ki; Lee, Hoomin; Choi, Jae Boong

2017-01-01

The biological function of proteins is closely related to its structural motion. For instance, structurally misfolded proteins do not function properly. Although we are able to experimentally obtain structural information on proteins, it is still challenging to capture their dynamics, such as transition processes. Therefore, we need a simulation method to predict the transition pathways of a protein in order to understand and study large functional deformations. Here, we present a new simulation method called normal mode-guided elastic network interpolation (NGENI) that performs normal modes analysis iteratively to predict transition pathways of proteins. To be more specific, NGENI obtains displacement vectors that determine intermediate structures by interpolating the distance between two end-point conformations, similar to a morphing method called elastic network interpolation. However, the displacement vector is regarded as a linear combination of the normal mode vectors of each intermediate structure, in order to enhance the physical sense of the proposed pathways. As a result, we can generate more reasonable transition pathways geometrically and thermodynamically. By using not only all normal modes, but also in part using only the lowest normal modes, NGENI can still generate reasonable pathways for large deformations in proteins. This study shows that global protein transitions are dominated by collective motion, which means that a few lowest normal modes play an important role in this process. NGENI has considerable merit in terms of computational cost because it is possible to generate transition pathways by partial degrees of freedom, while conventional methods are not capable of this. PMID:29020017

Clinical Outcomes of SMILE With a Triple Centration Technique and Corneal Wavefront-Guided Transepithelial PRK in High Astigmatism.

PubMed

Jun, Ikhyun; Kang, David Sung Yong; Reinstein, Dan Z; Arba-Mosquera, Samuel; Archer, Timothy J; Seo, Kyoung Yul; Kim, Tae-Im

2018-03-01

To comparatively investigate the clinical outcomes, vector parameters, and corneal aberrations of small incision lenticule extraction (SMILE) with a triple centration technique and corneal wavefront-guided transepithelial photorefractive keratectomy (PRK) for the correction of high astigmatism. This retrospective, comparative case series study included 89 eyes (89 patients) that received treatment for myopia with high astigmatism (≥ 2.50 diopters) using SMILE with a triple centration technique (SMILE group; 45 eyes) and corneal wavefront-guided transepithelial PRK (transepithelial PRK group; 44 eyes). Visual acuity measurement, manifest refraction, slit-lamp examination, autokeratometry, corneal topography, and evaluation of corneal wavefront aberration were performed preoperatively and at 1, 3, and 6 months after surgery. The safety, efficacy, vector parameters, and corneal aberrations at 6 months after surgery were compared between the two groups. At 6 months after surgery, the transepithelial PRK and SMILE groups exhibited comparable mean uncorrected distance visual acuities (-0.06 ± 0.07 and -0.05 ± 0.07 logMAR, respectively), safety, efficacy, and predictability of refractive and visual outcomes. There was a slight but statistically significant difference in the correction index between the transepithelial PRK and SMILE groups (0.96 ± 0.11 and 0.91 ± 0.10, respectively). Whereas the transepithelial PRK group exhibited increased corneal spherical aberration and significantly reduced corneal coma and trefoil, no changes in aberrometric values were noted in the SMILE group. Both SMILE with a triple centration technique and corneal wavefront-guided transepithelial PRK are effective and provide predictable outcomes for the correction of high myopic astigmatism, although slight undercorrection was observed in the SMILE group. The triple centration technique was helpful in astigmatism correction by SMILE. [J Refract Surg. 2018;34(3):156-163.]. Copyright 2018, SLACK Incorporated.

Gyro-gauge-independent formulation of the guiding-center reduction to arbitrary order in the Larmor radius

NASA Astrophysics Data System (ADS)

de Guillebon, L.; Vittot, M.

2013-10-01

Guiding-center reduction is studied using gyro-gauge-independent coordinates. The Lagrangian 1-form of charged particle dynamics is Lie transformed without introducing a gyro-gauge, but using directly the unit vector of the component of the velocity perpendicular to the magnetic field as the coordinate corresponding to Larmor gyration. The reduction is shown to provide a maximal reduction for the Lagrangian and to work for all orders in the Larmor radius, following exactly the same procedure as when working with the standard gauge-dependent coordinate. The gauge-dependence is removed from the coordinate system by using a constrained variable for the gyro-angle. The closed 1-form dθ is replaced by a more general non-closed 1-form, which is equal to dθ in the gauge-dependent case. The gauge vector is replaced by a more general connection in the definition of the gradient, which behaves as a covariant derivative, in perfect agreement with the circle-bundle picture. This explains some results of previous works, whose gauge-independent expressions did not correspond to gauge fixing but did indeed correspond to connection fixing. In addition, some general results are obtained for the guiding-center reduction. The expansion is polynomial in the cotangent of the pitch-angle as an effect of the structure of the Lagrangian, preserved by Lie derivatives. The induction for the reduction is shown to rely on the inversion of a matrix, which is the same for all orders higher than three. It is inverted and explicit induction relations are obtained to go to an arbitrary order in the perturbation expansion. The Hamiltonian and symplectic representations of the guiding-center reduction are recovered, but conditions for the symplectic representation at each order are emphasized.

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies.

PubMed

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A

2017-08-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy.

Modeling of Mean-VaR portfolio optimization by risk tolerance when the utility function is quadratic

NASA Astrophysics Data System (ADS)

Sukono, Sidi, Pramono; Bon, Abdul Talib bin; Supian, Sudradjat

2017-03-01

The problems of investing in financial assets are to choose a combination of weighting a portfolio can be maximized return expectations and minimizing the risk. This paper discusses the modeling of Mean-VaR portfolio optimization by risk tolerance, when square-shaped utility functions. It is assumed that the asset return has a certain distribution, and the risk of the portfolio is measured using the Value-at-Risk (VaR). So, the process of optimization of the portfolio is done based on the model of Mean-VaR portfolio optimization model for the Mean-VaR done using matrix algebra approach, and the Lagrange multiplier method, as well as Khun-Tucker. The results of the modeling portfolio optimization is in the form of a weighting vector equations depends on the vector mean return vector assets, identities, and matrix covariance between return of assets, as well as a factor in risk tolerance. As an illustration of numeric, analyzed five shares traded on the stock market in Indonesia. Based on analysis of five stocks return data gained the vector of weight composition and graphics of efficient surface of portfolio. Vector composition weighting weights and efficient surface charts can be used as a guide for investors in decisions to invest.

A Guide to Approaching Regulatory Considerations for Lentiviral-Mediated Gene Therapies

PubMed Central

White, Michael; Whittaker, Roger; Gándara, Carolina; Stoll, Elizabeth A.

2017-01-01

Lentiviral vectors are increasingly the gene transfer tool of choice for gene or cell therapies, with multiple clinical investigations showing promise for this viral vector in terms of both safety and efficacy. The third-generation vector system is well characterized, effectively delivers genetic material and maintains long-term stable expression in target cells, delivers larger amounts of genetic material than other methods, is nonpathogenic, and does not cause an inflammatory response in the recipient. This report aims to help academic scientists and regulatory managers negotiate the governance framework to achieve successful translation of a lentiviral vector-based gene therapy. The focus is on European regulations and how they are administered in the United Kingdom, although many of the principles will be similar for other regions, including the United States. The report justifies the rationale for using third-generation lentiviral vectors to achieve gene delivery for in vivo and ex vivo applications; briefly summarizes the extant regulatory guidance for gene therapies, categorized as advanced therapeutic medicinal products (ATMPs); provides guidance on specific regulatory issues regarding gene therapies; presents an overview of the key stakeholders to be approached when pursuing clinical trials authorization for an ATMP; and includes a brief catalogue of the documentation required to submit an application for regulatory approval of a new gene therapy. PMID:28817344

Insights in luteovirid structural biology guided by chemical cross-linking and high resolution mass spectrometry

USDA-ARS?s Scientific Manuscript database

Interactions among plant pathogenic viruses in the family /react-text Luteoviridae react-text: 233 and their plant hosts and insect vectors are governed by the topology of the viral capsid, which is the sole vehicle for long distance movement of the viral genome. Previous application of a mass spect...

Toward Automating Web Protocol Configuration for a Programmable Logic Controller Emulator

DTIC Science & Technology

2014-06-19

Security Risks for Industrial Control Systems ,” VDE 2004 Congress, Berlin, Germany, October 2004, pp. 1-7. [Cis12] Cisco, NetFlow Configuration Guide...Date 29 May 2014 Date AFIT-ENG-T-14-J-4 Abstract Industrial Control Systems (ICS) remain vulnerable through attack vectors that exist within programmable...5 2.2 Industrial Control Systems

Study on the precision of the guide control system of independent wheel

NASA Astrophysics Data System (ADS)

ji, Y.; Ren, L.; Li, R.; Sun, W.

2016-09-01

The torque ripple of permanent magnet synchronous motor vector with active control is studied in this paper. The ripple appears because of the impact of position detection and current detection, the error generated in inverter and the influence of motor ontology (magnetic chain harmonic and the cogging effect and so on). Then, the simulation dynamic model of bogie with permanent magnet synchronous motor vector control system is established with MATLAB/Simulink. The stability of bogie with steering control is studied. The relationship between the error of the motor and the precision of the control system is studied. The result shows that the existing motor does not meet the requirements of the control system.

Improving Vector Evaluated Particle Swarm Optimisation Using Multiple Nondominated Leaders

PubMed Central

Lim, Kian Sheng; Buyamin, Salinda; Ahmad, Anita; Shapiai, Mohd Ibrahim; Naim, Faradila; Mubin, Marizan; Kim, Dong Hwa

2014-01-01

The vector evaluated particle swarm optimisation (VEPSO) algorithm was previously improved by incorporating nondominated solutions for solving multiobjective optimisation problems. However, the obtained solutions did not converge close to the Pareto front and also did not distribute evenly over the Pareto front. Therefore, in this study, the concept of multiple nondominated leaders is incorporated to further improve the VEPSO algorithm. Hence, multiple nondominated solutions that are best at a respective objective function are used to guide particles in finding optimal solutions. The improved VEPSO is measured by the number of nondominated solutions found, generational distance, spread, and hypervolume. The results from the conducted experiments show that the proposed VEPSO significantly improved the existing VEPSO algorithms. PMID:24883386

The inference of vector magnetic fields from polarization measurements with limited spectral resolution

NASA Technical Reports Server (NTRS)

Lites, B. W.; Skumanich, A.

1985-01-01

A method is presented for recovery of the vector magnetic field and thermodynamic parameters from polarization measurement of photospheric line profiles measured with filtergraphs. The method includes magneto-optic effects and may be utilized on data sampled at arbitrary wavelengths within the line profile. The accuracy of this method is explored through inversion of synthetic Stokes profiles subjected to varying levels of random noise, instrumental wave-length resolution, and line profile sampling. The level of error introduced by the systematic effect of profile sampling over a finite fraction of the 5 minute oscillation cycle is also investigated. The results presented here are intended to guide instrumental design and observational procedure.

Amplitude and dynamics of polarization-plane signaling in the central complex of the locust brain

PubMed Central

Bockhorst, Tobias

2015-01-01

The polarization pattern of skylight provides a compass cue that various insect species use for allocentric orientation. In the desert locust, Schistocerca gregaria, a network of neurons tuned to the electric field vector (E-vector) angle of polarized light is present in the central complex of the brain. Preferred E-vector angles vary along slices of neuropils in a compasslike fashion (polarotopy). We studied how the activity in this polarotopic population is modulated in ways suited to control compass-guided locomotion. To this end, we analyzed tuning profiles using measures of correlation between spike rate and E-vector angle and, furthermore, tested for adaptation to stationary angles. The results suggest that the polarotopy is stabilized by antagonistic integration across neurons with opponent tuning. Downstream to the input stage of the network, responses to stationary E-vector angles adapted quickly, which may correlate with a tendency to steer a steady course previously observed in tethered flying locusts. By contrast, rotating E-vectors corresponding to changes in heading direction under a natural sky elicited nonadapting responses. However, response amplitudes were particularly variable at the output stage, covarying with the level of ongoing activity. Moreover, the responses to rotating E-vector angles depended on the direction of rotation in an anticipatory manner. Our observations support a view of the central complex as a substrate of higher-stage processing that could assign contextual meaning to sensory input for motor control in goal-driven behaviors. Parallels to higher-stage processing of sensory information in vertebrates are discussed. PMID:25609107

China and the United States in the Indian Ocean: An Emerging Strategic Triangle

DTIC Science & Technology

2008-01-01

eration,” Nuclear Threat Initiative, July 2005, www.nti.org/e_research/e3_67a.html. 30. 章明 [Zhang Ming], “马六甲困局与中国海军 的 战 略抉择” [The Malacca Dilemma...in India Which Cherishes the Dream of Becoming a Major Country,” Ta Kung Pao, 4 June 2001. 32. 谢值军 [Xie Zhijun], “21世纪亚洲海洋: 群雄 争 霸 中国怎么办?” [Asian Seas...Xiaolin and Qu Yutao], “从近海到远洋延伸—印度海军 战 略的演进” [From Offshore Defense to Open Ocean Extension—The Evolution of Indian Naval Strategy], 学习时报 [Study Times

modlAMP: Python for antimicrobial peptides.

PubMed

Müller, Alex T; Gabernet, Gisela; Hiss, Jan A; Schneider, Gisbert

2017-09-01

We have implemented the lecular esign aboratory's nti icrobial eptides package ( ), a Python-based software package for the design, classification and visual representation of peptide data. modlAMP offers functions for molecular descriptor calculation and the retrieval of amino acid sequences from public or local sequence databases, and provides instant access to precompiled datasets for machine learning. The package also contains methods for the analysis and representation of circular dichroism spectra. The modlAMP Python package is available under the BSD license from URL http://doi.org/10.5905/ethz-1007-72 or via pip from the Python Package Index (PyPI). gisbert.schneider@pharma.ethz.ch. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Assessment of the pharmacodynamics of intranasal, intravenous and oral scopolamine

NASA Technical Reports Server (NTRS)

Tietze, Karen J.

1990-01-01

Space motion sickness is an important issue in the space medical sciences program. One of the objectives of the ongoing clinical experimental protocol Pharmacokinetics of Intranasal Scopolamine in Normal Subjects is to evaluate the pharmacodynamics of scopolamine using salivary flow rate and pH profiles and cognitive performance tests as pharmacodynamic parameters. Normal volunteers collected saliva and performed the NTI Multiresource Performance Battery tests at designed time intervals to establish control saliva flow rates, salivary pH profiles, and the characteristics of the learning curve for the performance program under normal conditions. In the clinical part of the study, saliva samples and performance test scores are collected from healthy nonsmoking subjects after receiving a single 0.4 mg dose of either intranasal, intravenous, or oral scopolamine.

CTC Sentinel. Volume 3, Issue 1, January 2010. The Facade of Allegiance: Bin Ladin’s Dubious Pledge to Mullah Omar

DTIC Science & Technology

2010-01-01

Academy, the Department of the Army, or any other agency of the U.s. Government. C o M B A T I n G T E R R o R I s M C E n T E R A T W E s T...p o I n T o B j E C T I V E . R E L E V A n T . R I G o R o U s CTC SeNTiNeL Usama bin Ladin explains why he declared jihad against the United...Taliban professed today by al- Qa`ida and its Pakistan-based allies— including the Haqqani network and Tehrik- i -Taliban Pakistan (TTP)—is more a

Fiber-guided modes conversion using superposed helical gratings

NASA Astrophysics Data System (ADS)

Ma, Yancheng; Fang, Liang; Wu, Guoan

2017-03-01

Optical fibers can support various modal forms, including vector modes, linear polarization (LP) modes, and orbital angular momentum (OAM) modes, etc. The modal correlation among these modes is investigated via Jones matrix, associated with polarization and helical phase corresponding to spin angular momentum (SAM) and OAM of light, respectively. We can generate different modal forms by adopting superposed helical gratings (SHGs) with opposite helix orientations. Detailed analysis and discussion on mode conversion is given as for mode coupling in optical fibers with both low and high contrast index, respectively. Our study may deepen the understanding for various fiber-guided modes and mode conversion among them via fiber gratings.

Inhibition of HIV-1 gene expression by retroviral vector-mediated small-guide RNAs that direct specific RNA cleavage by tRNase ZL

PubMed Central

Habu, Yuichiro; Miyano-Kurosaki, Naoko; Kitano, Michiko; Endo, Yumihiko; Yukita, Masakazu; Ohira, Shigeru; Takaku, Hiroaki; Nashimoto, Masayuki; Takaku, Hiroshi

2005-01-01

The tRNA 3′-processing endoribonuclease (tRNase Z or 3′ tRNase; EC 3.1.26.11) is an essential enzyme that removes the 3′ trailer from pre-tRNA. The long form (tRNase ZL) can cleave a target RNA in vitro at the site directed by an appropriate small-guide RNA (sgRNA). Here, we investigated whether this sgRNA/tRNase ZL strategy could be applied to gene therapy for AIDS. We tested the ability of four sgRNA-expression plasmids to inhibit HIV-1 gene expression in COS cells, using a transient-expression assay. The three sgRNAs guide inhibition of HIV-1 gene expression in cultured COS cells. Analysis of the HIV-1 mRNA levels suggested that sgRNA directed the tRNase ZL to mediate the degradation of target RNA. The observation that sgRNA was localized primarily in nuclei suggests that tRNase ZL cleaves the HIV-1 mRNA when complexed with sgRNA in this location. We also examined the ability of two retroviral vectors expressing sgRNA to suppress HIV-1 expression in HIV-1-infected Jurkat T cells. sgRNA-SL4 suppressed HIV-1 expression almost completely in infected cells for up to 18 days. These results suggest that the sgRNA/tRNase ZL approach is effective in downregulating HIV-1 gene expression. PMID:15647506

Construction of CRISPR Libraries for Functional Screening.

PubMed

Carstens, Carsten P; Felts, Katherine A; Johns, Sarah E

2018-01-01

Identification of gene function has been aided by the ability to generate targeted gene knockouts or transcriptional repression using the CRISPR/CAS9 system. Using pooled libraries of guide RNA expression vectors that direct CAS9 to a specific genomic site allows identification of genes that are either enriched or depleted in response to a selection scheme, thus linking the affected gene to the chosen phenotype. The quality of the data generated by the screening is dependent on the quality of the guide RNA delivery library with regards to error rates and especially evenness of distribution of the guides. Here, we describe a method for constructing complex plasmid libraries based on pooled designed oligomers with high representation and tight distributions. The procedure allows construction of plasmid libraries of >60,000 members with a 95th/5th percentile ratio of less than 3.5.

Strengthening tactical planning and operational frameworks for vector control: the roadmap for malaria elimination in Namibia.

PubMed

Chanda, Emmanuel; Ameneshewa, Birkinesh; Angula, Hans A; Iitula, Iitula; Uusiku, Pentrina; Trune, Desta; Islam, Quazi M; Govere, John M

2015-08-05

Namibia has made tremendous gains in malaria control and the epidemiological trend of the disease has changed significantly over the past years. In 2010, the country reoriented from the objective of reducing disease morbidity and mortality to the goal of achieving malaria elimination by 2020. This manuscript outlines the processes undertaken in strengthening tactical planning and operational frameworks for vector control to facilitate expeditious malaria elimination in Namibia. The information sources for this study included all available data and accessible archived documentary records on malaria vector control in Namibia. A methodical assessment of published and unpublished documents was conducted via a literature search of online electronic databases, Google Scholar, PubMed and WHO, using a combination of search terms. To attain the goal of elimination in Namibia, systems are being strengthened to identify and clear all infections, and significantly reduce human-mosquito contact. Particularly, consolidating vector control for reducing transmission at the identified malaria foci will be critical for accelerated malaria elimination. Thus, guarding against potential challenges and the need for evidence-based and sustainable vector control instigated the strengthening of strategic frameworks by: adopting the integrated vector management (IVM) strategy; initiating implementation of the global plan for insecticide resistance management (GPIRM); intensifying malaria vector surveillance; improving data collection and reporting systems on DDT; updating the indoor residual spraying (IRS) data collection and reporting tool; and, improving geographical reconnaissance using geographical information system-based satellite imagery. Universal coverage with IRS and long-lasting insecticidal nets, supplemented by larval source management in the context of IVM and guided by vector surveillance coupled with rational operationalization of the GPIRM, will enable expeditious attainment of elimination in Namibia. However, national capacity to plan, implement, monitor and evaluate interventions will require adequate and sustained support for technical, physical infrastructure, and human and financial resources for entomology and vector control operations.

Heading-vector navigation based on head-direction cells and path integration.

PubMed

Kubie, John L; Fenton, André A

2009-05-01

Insect navigation is guided by heading vectors that are computed by path integration. Mammalian navigation models, on the other hand, are typically based on map-like place representations provided by hippocampal place cells. Such models compute optimal routes as a continuous series of locations that connect the current location to a goal. We propose a "heading-vector" model in which head-direction cells or their derivatives serve both as key elements in constructing the optimal route and as the straight-line guidance during route execution. The model is based on a memory structure termed the "shortcut matrix," which is constructed during the initial exploration of an environment when a set of shortcut vectors between sequential pairs of visited waypoint locations is stored. A mechanism is proposed for calculating and storing these vectors that relies on a hypothesized cell type termed an "accumulating head-direction cell." Following exploration, shortcut vectors connecting all pairs of waypoint locations are computed by vector arithmetic and stored in the shortcut matrix. On re-entry, when local view or place representations query the shortcut matrix with a current waypoint and goal, a shortcut trajectory is retrieved. Since the trajectory direction is in head-direction compass coordinates, navigation is accomplished by tracking the firing of head-direction cells that are tuned to the heading angle. Section 1 of the manuscript describes the properties of accumulating head-direction cells. It then shows how accumulating head-direction cells can store local vectors and perform vector arithmetic to perform path-integration-based homing. Section 2 describes the construction and use of the shortcut matrix for computing direct paths between any pair of locations that have been registered in the shortcut matrix. In the discussion, we analyze the advantages of heading-based navigation over map-based navigation. Finally, we survey behavioral evidence that nonhippocampal, heading-based navigation is used in small mammals and humans. Copyright 2008 Wiley-Liss, Inc.

MRI-Guided Delivery of Viral Vectors.

PubMed

Salegio, Ernesto A; Bringas, John; Bankiewicz, Krystof S

2016-01-01

Gene therapy has emerged as a potential avenue of treatment for many neurological disorders. Technological advances in imaging techniques allow for the monitoring of real-time infusions into the brain of rodents, nonhuman primates, and humans. Here, we discuss the use of magnetic resonance imaging (MRI) as a tool in the delivery of adeno-associated viral (AAV) particles into brain of nonhuman primates.

Experimental Study of an Axisymmetric Dual Throat Fluidic Thrust Vectoring Nozzle for Supersonic Aircraft Application

NASA Technical Reports Server (NTRS)

Flamm, Jeffrey D.; Deere, Karen A.; Mason, Mary L.; Berrier, Bobby L.; Johnson, Stuart K.

2007-01-01

An axisymmetric version of the Dual Throat Nozzle concept with a variable expansion ratio has been studied to determine the impacts on thrust vectoring and nozzle performance. The nozzle design, applicable to a supersonic aircraft, was guided using the unsteady Reynolds-averaged Navier-Stokes computational fluid dynamics code, PAB3D. The axisymmetric Dual Throat Nozzle concept was tested statically in the Jet Exit Test Facility at the NASA Langley Research Center. The nozzle geometric design variables included circumferential span of injection, cavity length, cavity convergence angle, and nozzle expansion ratio for conditions corresponding to take-off and landing, mid climb and cruise. Internal nozzle performance and thrust vectoring performance was determined for nozzle pressure ratios up to 10 with secondary injection rates up to 10 percent of the primary flow rate. The 60 degree span of injection generally performed better than the 90 degree span of injection using an equivalent injection area and number of holes, in agreement with computational results. For injection rates less than 7 percent, thrust vector angle for the 60 degree span of injection was 1.5 to 2 degrees higher than the 90 degree span of injection. Decreasing cavity length improved thrust ratio and discharge coefficient, but decreased thrust vector angle and thrust vectoring efficiency. Increasing cavity convergence angle from 20 to 30 degrees increased thrust vector angle by 1 degree over the range of injection rates tested, but adversely affected system thrust ratio and discharge coefficient. The dual throat nozzle concept generated the best thrust vectoring performance with an expansion ratio of 1.0 (a cavity in between two equal minimum areas). The variable expansion ratio geometry did not provide the expected improvements in discharge coefficient and system thrust ratio throughout the flight envelope of typical a supersonic aircraft. At mid-climb and cruise conditions, the variable geometry design compromised thrust vector angle achieved, but some thrust vector control would be available, potentially for aircraft trim. The fixed area, expansion ratio of 1.0, Dual Throat Nozzle provided the best overall compromise for thrust vectoring and nozzle internal performance over the range of NPR tested compared to the variable geometry Dual Throat Nozzle.

O Electromagnetic Power Waves and Power Density Components.

NASA Astrophysics Data System (ADS)

Petzold, Donald Wayne

1980-12-01

On January 10, 1884 Lord Rayleigh presented a paper entitled "On the Transfer of Energy in the Electromagnetic Field" to the Royal Society of London. This paper had been authored by the late Fellow of Trinity College, Cambridge, Professor J. H. Poynting and in it he claimed that there was a general law for the transfer of electromagnetic energy. He argued that associated with each point in space is a quantity, that has since been called the Poynting vector, that is a measure of the rate of energy flow per unit area. His analysis was concerned with the integration of this power density vector at all points over an enclosing surface of a specific volume. The interpretation of this Poynting vector as a true measure of the local power density was viewed with great skepticism unless the vector was integrated over a closed surface, as the development of the concept required. However, within the last decade or so Shadowitz indicates that a number of prominent authors have argued that the criticism of the interpretation of Poynting's vector as a local power density vector is unjustified. The present paper is not concerned with these arguments but instead is concerned with a decomposition of Poynting's power density vector into two and only two components: one vector which has the same direction as Poynting's vector and which is called the forward power density vector, and another vector, directed opposite to the Poynting vector and called the reverse power density vector. These new local forward and reverse power density vectors will be shown to be dependent upon forward and reverse power wave vectors and these vectors in turn will be related to newly defined forward and reverse components of the electric and magnetic fields. The sum of these forward and reverse power density vectors, which is simply the original Poynting vector, is associated with the total electromagnetic energy traveling past the local point. Another vector which is the difference between the forward and reverse power density vectors and which will be shown to be associated with the total electric and magnetic field energy densities existing at a local point will also be introduced. These local forward and reverse power density vectors may be integrated over a surface to determine the forward and reverse powers and from these results problems related to maximum power transfer or efficiency of electromagnetic energy transmission in space may be studied in a manner similar to that presently being done with transmission lines, wave guides, and more recently with two port multiport lumped parameter systems. These new forward and reverse power density vectors at a point in space are analogous to the forward and revoltages or currents and power waves as used with the transmission line, waveguide, or port. These power wave vectors in space are a generalization of the power waves as developed by Penfield, Youla, and Kurokawa and used with the scattering parameters associated with transmission lines, waveguides and ports.

Potential Distribution of Chagas Disease Vectors (Hemiptera, Reduviidae, Triatominae) in Colombia, Based on Ecological Niche Modeling

PubMed Central

Suárez-Escudero, Laura C.; González-Caro, Sebastián

2016-01-01

Ecological niche modeling of Triatominae bugs allow us to establish the local risk of transmission of the parasite Trypanosoma cruzi, which causes Chagas disease. This information could help to guide health authority recommendations on infection monitoring, prevention, and control. In this study, we estimated the geographic distribution of triatomine species in Colombia and identified the relationship between landscape structure and climatic factors influencing their occurrence. A total of 2451 records of 4 triatomine species (Panstrongylus geniculatus, Rhodnius pallescens, R. prolixus, and Triatoma maculata) were analyzed. The variables that provided more information to explain the ecologic niche of these vectors were related to precipitation, altitude, and temperature. We found that the species with the broadest potential geographic distribution were P. geniculatus, R. pallescens, and R. prolixus. In general, the models predicted the highest occurrence probability of these vectors in the eastern slope of the Eastern Cordillera, the southern region of the Magdalena valley, and the Sierra Nevada of Santa Marta. PMID:28115946

The Gene Therapy Resource Program: A Decade of Dedication to Translational Research by the National Heart, Lung, and Blood Institute.

PubMed

Flotte, Terence R; Daniels, Eric; Benson, Janet; Bevett-Rose, Jeneé M; Cornetta, Kenneth; Diggins, Margaret; Johnston, Julie; Sepelak, Susan; van der Loo, Johannes C M; Wilson, James M; McDonald, Cheryl L

2017-12-01

Over a 10-year period, the Gene Therapy Resource Program (GTRP) of the National Heart Lung and Blood Institute has provided a set of core services to investigators to facilitate the clinical translation of gene therapy. These services have included a preclinical (research-grade) vector production core; current Good Manufacturing Practice clinical-grade vector cores for recombinant adeno-associated virus and lentivirus vectors; a pharmacology and toxicology core; and a coordinating center to manage program logistics and to provide regulatory and financial support to early-phase clinical trials. In addition, the GTRP has utilized a Steering Committee and a Scientific Review Board to guide overall progress and effectiveness and to evaluate individual proposals. These resources have been deployed to assist 82 investigators with 172 approved service proposals. These efforts have assisted in clinical trial implementation across a wide range of genetic, cardiac, pulmonary, and blood diseases. Program outcomes and potential future directions of the program are discussed.

All-in-One CRISPR-Cas9/FokI-dCas9 Vector-Mediated Multiplex Genome Engineering in Cultured Cells.

PubMed

Sakuma, Tetsushi; Sakamoto, Takuya; Yamamoto, Takashi

2017-01-01

CRISPR-Cas9 enables highly convenient multiplex genome engineering in cultured cells, because it utilizes generic Cas9 nuclease and an easily customizable single-guide RNA (sgRNA) for site-specific DNA double-strand break induction. We previously established a multiplex CRISPR-Cas9 assembly system for constructing an all-in-one vector simultaneously expressing multiple sgRNAs and Cas9 nuclease or other Cas9 variants including FokI-dCas9, which supersedes the wild-type Cas9 with regard to high specificity. In this chapter, we describe a streamlined protocol to design and construct multiplex CRISPR-Cas9 or FokI-dCas9 vectors, to introduce them into cultured cells by lipofection or electroporation, to enrich the genomically edited cells with a transient puromycin selection, to validate the mutation efficiency by Surveyor nuclease assay, and to perform off-target analyses. We show that our protocol enables highly efficient multiplex genome engineering even in hard-to-transfect HepG2 cells.

Potential Distribution of Chagas Disease Vectors (Hemiptera, Reduviidae, Triatominae) in Colombia, Based on Ecological Niche Modeling.

PubMed

Parra-Henao, Gabriel; Suárez-Escudero, Laura C; González-Caro, Sebastián

2016-01-01

Ecological niche modeling of Triatominae bugs allow us to establish the local risk of transmission of the parasite Trypanosoma cruzi, which causes Chagas disease. This information could help to guide health authority recommendations on infection monitoring, prevention, and control. In this study, we estimated the geographic distribution of triatomine species in Colombia and identified the relationship between landscape structure and climatic factors influencing their occurrence. A total of 2451 records of 4 triatomine species ( Panstrongylus geniculatus , Rhodnius pallescens , R. prolixus , and Triatoma maculata ) were analyzed. The variables that provided more information to explain the ecologic niche of these vectors were related to precipitation, altitude, and temperature. We found that the species with the broadest potential geographic distribution were P. geniculatus , R. pallescens , and R. prolixus . In general, the models predicted the highest occurrence probability of these vectors in the eastern slope of the Eastern Cordillera, the southern region of the Magdalena valley, and the Sierra Nevada of Santa Marta.

Sparse Solutions for Single Class SVMs: A Bi-Criterion Approach

NASA Technical Reports Server (NTRS)

Das, Santanu; Oza, Nikunj C.

2011-01-01

In this paper we propose an innovative learning algorithm - a variation of One-class nu Support Vector Machines (SVMs) learning algorithm to produce sparser solutions with much reduced computational complexities. The proposed technique returns an approximate solution, nearly as good as the solution set obtained by the classical approach, by minimizing the original risk function along with a regularization term. We introduce a bi-criterion optimization that helps guide the search towards the optimal set in much reduced time. The outcome of the proposed learning technique was compared with the benchmark one-class Support Vector machines algorithm which more often leads to solutions with redundant support vectors. Through out the analysis, the problem size for both optimization routines was kept consistent. We have tested the proposed algorithm on a variety of data sources under different conditions to demonstrate the effectiveness. In all cases the proposed algorithm closely preserves the accuracy of standard one-class nu SVMs while reducing both training time and test time by several factors.

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination

PubMed Central

Brady, Oliver J.; Godfray, H. Charles J.; Tatem, Andrew J.; Gething, Peter W.; Cohen, Justin M.; McKenzie, F. Ellis; Perkins, T. Alex; Reiner, Robert C.; Tusting, Lucy S.; Sinka, Marianne E.; Moyes, Catherine L.; Eckhoff, Philip A.; Scott, Thomas W.; Lindsay, Steven W.; Hay, Simon I.; Smith, David L.

2016-01-01

Background Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. Methods and Results Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. Conclusions Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions. PMID:26822603

Milestone Completion Report WBS 1.3.5.05 ECP/VTK-m FY17Q3 [MS-17/02] Faceted Surface Normals STDA05-3.

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

Moreland, Kenneth D.

2017-07-01

The FY17Q3 milestone of the ECP/VTK-m project includes the completion of a VTK-m filter that computes normal vectors for surfaces. Normal vectors are those that point perpendicular to the surface and are an important direction when rendering the surface. The implementation includes the parallel algorithm itself, a filter module to simplify integrating it into other software, and documentation in the VTK-m Users’ Guide. With the completion of this milestone, we are able to necessary information to rendering systems to provide appropriate shading of surfaces. This milestone also feeds into subsequent milestones that progressively improve the approximation of surface direction.

Coupled-mode theory and Fano resonances in guided-mode resonant gratings: the conical diffraction mounting.

PubMed

Bykov, Dmitry A; Doskolovich, Leonid L; Soifer, Victor A

2017-01-23

We study resonances of guided-mode resonant gratings in conical mounting. By developing 2D time-dependent coupled-mode theory we obtain simple approximations of the transmission and reflection coefficients. Being functions of the incident light's frequency and in-plane wave vector components, the obtained approximations can be considered as multi-variable generalizations of the Fano line shape. We show that the approximations are in good agreement with the rigorously calculated transmission and reflection spectra. We use the developed theory to investigate angular tolerances of the considered structures and to obtain mode excitation conditions. In particular, we obtain the cross-polarization mode excitation conditions in the case of conical mounting.

Selenium recovery from kiln powder of cement manufacturing by chemical leaching and bioreduction.

PubMed

Soda, S; Hasegawa, A; Kuroda, M; Hanada, A; Yamashita, M; Ike, M

2015-01-01

A novel process by using chemical leaching followed by bacterial reductive precipitation was proposed for selenium recovery from kiln powder as a byproduct of cement manufacturing. The kiln powder at a slurry concentration of 10 w/v% with 0.25 M Na2CO3 at 28°C produced wastewater containing about 30 mg-Se/L selenium. The wastewater was diluted four-fold and adjusted to pH 8.0 as preconditioning for bioreduction. A bacterial strain Pseudomonas stutzeri NT-I, capable of reducing selenate and selenite into insoluble elemental selenium, could recover about 90% selenium from the preconditioned wastewater containing selenium of 5 mg-Se/L when supplemented with lactate or glycerol. The selenium concentrations in the treated wastewater were low around the regulated effluent concentration of 0.1 mg-Se/L in Japan.

Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain

PubMed Central

Murlidharan, Giridhar; Crowther, Andrew; Reardon, Rebecca A.; Song, Juan

2016-01-01

Adeno-associated viruses (AAV) are currently being evaluated in clinical trials for gene therapy of CNS disorders. However, host factors that influence the spread, clearance, and transduction efficiency of AAV vectors in the brain are not well understood. Recent studies have demonstrated that fluid flow mediated by aquaporin-4 (AQP4) channels located on astroglial end feet is essential for exchange of solutes between interstitial and cerebrospinal fluid. This phenomenon, which is essential for interstitial clearance of solutes from the CNS, has been termed glial-associated lymphatic transport or glymphatic transport. In the current study, we demonstrate that glymphatic transport profoundly affects various aspects of AAV gene transfer in the CNS. Altered localization of AQP4 in aged mouse brains correlated with significantly increased retention of AAV vectors in the parenchyma and reduced systemic leakage following ventricular administration. We observed a similar increase in AAV retention and transgene expression upon i.c.v. administration in AQP4–/– mice. Consistent with this observation, fluorophore-labeled AAV vectors showed markedly reduced flux from the ventricles of AQP4–/– mice compared with WT mice. These results were further corroborated by reduced AAV clearance from the AQP4-null brain, as demonstrated by reduced transgene expression and vector genome accumulation in systemic organs. We postulate that deregulation of glymphatic transport in aged and diseased brains could markedly affect the parenchymal spread, clearance, and gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the kinetics of CSF flux in prospective gene therapy patients might inform variable treatment outcomes and guide future clinical trial design. PMID:27699236

User's guide to STIPPAN: A panel method program for slotted tunnel interference prediction

NASA Technical Reports Server (NTRS)

Kemp, W. B., Jr.

1985-01-01

Guidelines are presented for use of the computer program STIPPAN to simulate the subsonic flow in a slotted wind tunnel test section with a known model disturbance. Input data requirements are defined in detail and other aspects of the program usage are discussed in more general terms. The program is written for use in a CDC CYBER 200 class vector processing system.

Study Guide for a Beginning Course in Ground-Water Hydrology: Part 1 -- Course Participants

DTIC Science & Technology

1990-01-01

and Lonnquist, 1971 , fig. 7.) . . . . . . . . . . . . . . . . . . . . . . 99 Vector areas associated with branches in a square-mesh finite...water reservoir. (From Bennett and Giusti, 1971 .). 112 Location and general geographic features of Long Island, New York. (From Franke and...Techniques of Water- Resources Investigations of the U.S. Geological Survey, Book 2, Chapter Fl, 97 p. Stallman, R. W., 1971 , Aquifer-test design

Simplified CRISPR tools for efficient genome editing and streamlined protocols for their delivery into mammalian cells and mouse zygotes.

PubMed

Jacobi, Ashley M; Rettig, Garrett R; Turk, Rolf; Collingwood, Michael A; Zeiner, Sarah A; Quadros, Rolen M; Harms, Donald W; Bonthuis, Paul J; Gregg, Christopher; Ohtsuka, Masato; Gurumurthy, Channabasavaiah B; Behlke, Mark A

2017-05-15

Genome editing using the CRISPR/Cas9 system requires the presence of guide RNAs bound to the Cas9 endonuclease as a ribonucleoprotein (RNP) complex in cells, which cleaves the host cell genome at sites specified by the guide RNAs. New genetic material may be introduced during repair of the double-stranded break via homology dependent repair (HDR) if suitable DNA templates are delivered with the CRISPR components. Early methods used plasmid or viral vectors to make these components in the host cell, however newer approaches using recombinant Cas9 protein with synthetic guide RNAs introduced directly as an RNP complex into cells shows faster onset of action with fewer off-target effects. This approach also enables use of chemically modified synthetic guide RNAs that have improved nuclease stability and reduces the risk of triggering an innate immune response in the host cell. This article provides detailed methods for genome editing using the RNP approach with synthetic guide RNAs using lipofection or electroporation in mammalian cells or using microinjection in murine zygotes, with or without addition of a single-stranded HDR template DNA. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Directional nonlinear guided wave mixing: Case study of counter-propagating shear horizontal waves

NASA Astrophysics Data System (ADS)

Hasanian, Mostafa; Lissenden, Cliff J.

2018-04-01

While much nonlinear ultrasonics research has been conducted on higher harmonic generation, wave mixing provides the potential for sensitive measurements of incipient damage unencumbered by instrumentation nonlinearity. Studies of nonlinear ultrasonic wave mixing, both collinear and noncollinear, for bulk waves have shown the robust capability of wave mixing for early damage detection. One merit of bulk wave mixing lies in their non-dispersive nature, but guided waves enable inspection of otherwise inaccessible material and a variety of mixing options. Co-directional guided wave mixing was studied previously, but arbitrary direction guided wave mixing has not been addressed until recently. Wave vector analysis is applied to study variable mixing angles to find wave mode triplets (two primary waves and a secondary wave) resulting in the phase matching condition. As a case study, counter-propagating Shear Horizontal (SH) guided wave mixing is analyzed. SH wave interactions generate a secondary Lamb wave mode that is readily receivable. Reception of the secondary Lamb wave mode is compared for an angle beam transducer, an air coupled transducer, and a laser Doppler vibrometer (LDV). Results from the angle beam and air coupled transducers are quite consistent, while the LDV measurement is plagued by variability issues.

A Biomechanical Modeling Guided CBCT Estimation Technique

PubMed Central

Zhang, You; Tehrani, Joubin Nasehi; Wang, Jing

2017-01-01

Two-dimensional-to-three-dimensional (2D-3D) deformation has emerged as a new technique to estimate cone-beam computed tomography (CBCT) images. The technique is based on deforming a prior high-quality 3D CT/CBCT image to form a new CBCT image, guided by limited-view 2D projections. The accuracy of this intensity-based technique, however, is often limited in low-contrast image regions with subtle intensity differences. The solved deformation vector fields (DVFs) can also be biomechanically unrealistic. To address these problems, we have developed a biomechanical modeling guided CBCT estimation technique (Bio-CBCT-est) by combining 2D-3D deformation with finite element analysis (FEA)-based biomechanical modeling of anatomical structures. Specifically, Bio-CBCT-est first extracts the 2D-3D deformation-generated displacement vectors at the high-contrast anatomical structure boundaries. The extracted surface deformation fields are subsequently used as the boundary conditions to drive structure-based FEA to correct and fine-tune the overall deformation fields, especially those at low-contrast regions within the structure. The resulting FEA-corrected deformation fields are then fed back into 2D-3D deformation to form an iterative loop, combining the benefits of intensity-based deformation and biomechanical modeling for CBCT estimation. Using eleven lung cancer patient cases, the accuracy of the Bio-CBCT-est technique has been compared to that of the 2D-3D deformation technique and the traditional CBCT reconstruction techniques. The accuracy was evaluated in the image domain, and also in the DVF domain through clinician-tracked lung landmarks. PMID:27831866

Stem cells’ guided gene therapy of cancer: New frontier in personalized and targeted therapy

PubMed Central

Mavroudi, Maria; Zarogoulidis, Paul; Porpodis, Konstantinos; Kioumis, Ioannis; Lampaki, Sofia; Yarmus, Lonny; Malecki, Raf; Zarogoulidis, Konstantinos; Malecki, Marek

2014-01-01

Introduction Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The statistics speak for themselves with the grim reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem cells’ guided gene therapy. Review of therapeutic strategies in preclinical and clinical trials Stem cells have the unique potential for self renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells only. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for therapeutic use of stem cells is their cancerous transformation. Therefore, we discuss various strategies to safeguard stem cell guided gene therapy against iatrogenic cancerogenesis. Perspectives Defining cancer biomarkers to facilitate early diagnosis, elucidating cancer genomics and proteomics with modern tools of next generation sequencing, and analyzing patients’ gene expression profiles provide essential data to elucidate molecular dynamics of cancer and to consider them for crafting pharmacogenomics-based personalized therapies. Streamlining of these data into genetic engineering of stem cells facilitates their use as the vectors delivering therapeutic genes into specific cancer cells. In this realm, stem cells guided gene therapy becomes a promising new frontier in personalized and targeted therapy of cancer. PMID:24860662

Databases post-processing in Tensoral

NASA Technical Reports Server (NTRS)

Dresselhaus, Eliot

1994-01-01

The Center for Turbulent Research (CTR) post-processing effort aims to make turbulence simulations and data more readily and usefully available to the research and industrial communities. The Tensoral language, introduced in this document and currently existing in prototype form, is the foundation of this effort. Tensoral provides a convenient and powerful protocol to connect users who wish to analyze fluids databases with the authors who generate them. In this document we introduce Tensoral and its prototype implementation in the form of a user's guide. This guide focuses on use of Tensoral for post-processing turbulence databases. The corresponding document - the Tensoral 'author's guide' - which focuses on how authors can make databases available to users via the Tensoral system - is currently unwritten. Section 1 of this user's guide defines Tensoral's basic notions: we explain the class of problems at hand and how Tensoral abstracts them. Section 2 defines Tensoral syntax for mathematical expressions. Section 3 shows how these expressions make up Tensoral statements. Section 4 shows how Tensoral statements and expressions are embedded into other computer languages (such as C or Vectoral) to make Tensoral programs. We conclude with a complete example program.

A Vector with a Single Promoter for In Vitro Transcription and Mammalian Cell Expression of CRISPR gRNAs.

PubMed

Romanienko, Peter J; Giacalone, Joseph; Ingenito, Joanne; Wang, Yijie; Isaka, Mayumi; Johnson, Thomas; You, Yun; Mark, Willie H

2016-01-01

The genomes of more than 50 organisms have now been manipulated due to rapid advancement of gene editing technology. One way to perform gene editing in the mouse using the CRISPR/CAS system, guide RNA (gRNA) and CAS9 mRNA transcribed in vitro are microinjected into fertilized eggs that are then allowed to develop to term. As a rule, gRNAs are tested first in tissue culture cells and the one with the highest locus-specific cleavage activity is chosen for microinjection. For cell transfections, gRNAs are typically expressed using the human U6 promoter (hU6). However, gRNAs for microinjection into zygotes are obtained by in vitro transcription from a T7 bacteriophage promoter in a separate plasmid vector. Here, we describe the design and construction of a combined U6T7 hybrid promoter from which the same gRNA sequence can be expressed. An expression vector containing such a hybrid promoter can now be used to generate gRNA for testing in mammalian cells as well as for microinjection purposes. The gRNAs expressed and transcribed from this vector are found to be functional in cells as well as in mice.

Triatomine Infestation in Guatemala: Spatial Assessment after Two Rounds of Vector Control

PubMed Central

Manne, Jennifer; Nakagawa, Jun; Yamagata, Yoichi; Goehler, Alexander; Brownstein, John S.; Castro, Marcia C.

2012-01-01

In 2000, the Guatemalan Ministry of Health initiated a Chagas disease program to control Rhodnius prolixus and Triatoma dimidiata by periodic house spraying with pyrethroid insecticides to characterize infestation patterns and analyze the contribution of programmatic practices to these patterns. Spatial infestation patterns at three time points were identified using the Getis-Ord Gi*(d) test. Logistic regression was used to assess predictors of reinfestation after pyrethroid insecticide administration. Spatial analysis showed high and low clusters of infestation at three time points. After two rounds of spray, 178 communities persistently fell in high infestation clusters. A time lapse between rounds of vector control greater than 6 months was associated with 1.54 (95% confidence interval = 1.07–2.23) times increased odds of reinfestation after first spray, whereas a time lapse of greater than 1 year was associated with 2.66 (95% confidence interval = 1.85–3.83) times increased odds of reinfestation after first spray compared with localities where the time lapse was less than 180 days. The time lapse between rounds of vector control should remain under 1 year. Spatial analysis can guide targeted vector control efforts by enabling tracking of reinfestation hotspots and improved targeting of resources. PMID:22403315

Consolidating tactical planning and implementation frameworks for integrated vector management in Uganda.

PubMed

Okia, Michael; Okui, Peter; Lugemwa, Myers; Govere, John M; Katamba, Vincent; Rwakimari, John B; Mpeka, Betty; Chanda, Emmanuel

2016-04-14

Integrated vector management (IVM) is the recommended approach for controlling some vector-borne diseases (VBD). In the face of current challenges to disease vector control, IVM is vital to achieve national targets set for VBD control. Though global efforts, especially for combating malaria, now focus on elimination and eradication, IVM remains useful for Uganda which is principally still in the control phase of the malaria continuum. This paper outlines the processes undertaken to consolidate tactical planning and implementation frameworks for IVM in Uganda. The Uganda National Malaria Control Programme with its efforts to implement an IVM approach to vector control was the 'case' for this study. Integrated management of malaria vectors in Uganda remained an underdeveloped component of malaria control policy. In 2012, knowledge and perceptions of malaria vector control policy and IVM were assessed, and recommendations for a specific IVM policy were made. In 2014, a thorough vector control needs assessment (VCNA) was conducted according to WHO recommendations. The findings of the VCNA informed the development of the national IVM strategic guidelines. Information sources for this study included all available data and accessible archived documentary records on VBD control in Uganda. The literature was reviewed and adapted to the local context and translated into the consolidated tactical framework. WHO recommends implementation of IVM as the main strategy to vector control and has encouraged member states to adopt the approach. However, many VBD-endemic countries lack IVM policy frameworks to guide implementation of the approach. In Uganda most VBD coexists and could be managed more effectively if done in tandem. In order to successfully control malaria and other VBD and move towards their elimination, the country needs to scale up proven and effective vector control interventions and also learn from the experience of other countries. The IVM strategy is important in consolidating inter-sectoral collaboration and coordination and providing the tactical direction for effective deployment of vector control interventions along the five key elements of the approach and to align them with contemporary epidemiology of VBD in the country. Uganda has successfully established an evidence-based IVM approach and consolidated strategic planning and operational frameworks for VBD control. However, operating implementation arrangements as outlined in the national strategic guidelines for IVM and managing insecticide resistance, as well as improving vector surveillance, are imperative. In addition, strengthened information, education and communication/behaviour change and communication, collaboration and coordination will be crucial in scaling up and using vector control interventions.

MicroRNA-Regulated Non-Viral Vectors with Improved Tumor Specificity in an Orthotopic Rat Model of Hepatocellular Carcinoma

PubMed Central

Ronald, John A.; Katzenberg, Regina; Nielsen, Carsten H.; Jae, Hwan Jun; Hofmann, Lawrence V.; Gambhir, Sanjiv S.

2013-01-01

In hepatocellular carcinoma, tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs are powerful negative regulators of gene expression and many are down-regulated in human HCC. We identified seven miRNAs that are also down-regulated in tumors in a rat hepatoma model (p<0.05) and attempted to improve tumor specificity by constructing a panel of luciferase-expressing vectors containing binding sites for these microRNAs. Attenuation of luciferase expression by the corresponding microRNAs was confirmed across various cell lines and in mouse liver. We then tested our vectors in tumor-bearing rats and identified two microRNAs, miR-26a and miR-122, that significantly decreased expression in liver compared to control vector (6.40% and 0.26%, respectively; p<0.05). In tumor, miR-122 had a non-significant trend towards decreased (~50%) expression , while miR-26 had no significant effect on tumor expression. To our knowledge this is the first work using differentially expressed microRNAs to de-target transgene expression in an orthotopic hepatoma model and identification of miR-26a in addition to miR-122 for de-targeting liver. Considering the heterogeneity of microRNA expression in human HCC, this information will be important in guiding development of more personalized vectors for the treatment of this devastating disease. PMID:23719066

Vectorial capacity and vector control: reconsidering sensitivity to parameters for malaria elimination.

PubMed

Brady, Oliver J; Godfray, H Charles J; Tatem, Andrew J; Gething, Peter W; Cohen, Justin M; McKenzie, F Ellis; Perkins, T Alex; Reiner, Robert C; Tusting, Lucy S; Sinka, Marianne E; Moyes, Catherine L; Eckhoff, Philip A; Scott, Thomas W; Lindsay, Steven W; Hay, Simon I; Smith, David L

2016-02-01

Major gains have been made in reducing malaria transmission in many parts of the world, principally by scaling-up coverage with long-lasting insecticidal nets and indoor residual spraying. Historically, choice of vector control intervention has been largely guided by a parameter sensitivity analysis of George Macdonald's theory of vectorial capacity that suggested prioritizing methods that kill adult mosquitoes. While this advice has been highly successful for transmission suppression, there is a need to revisit these arguments as policymakers in certain areas consider which combinations of interventions are required to eliminate malaria. Using analytical solutions to updated equations for vectorial capacity we build on previous work to show that, while adult killing methods can be highly effective under many circumstances, other vector control methods are frequently required to fill effective coverage gaps. These can arise due to pre-existing or developing mosquito physiological and behavioral refractoriness but also due to additive changes in the relative importance of different vector species for transmission. Furthermore, the optimal combination of interventions will depend on the operational constraints and costs associated with reaching high coverage levels with each intervention. Reaching specific policy goals, such as elimination, in defined contexts requires increasingly non-generic advice from modelling. Our results emphasize the importance of measuring baseline epidemiology, intervention coverage, vector ecology and program operational constraints in predicting expected outcomes with different combinations of interventions. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

Dengue and Chikungunya Vector Control Pocket Guide

DTIC Science & Technology

2014-05-01

mosquito eggs, larvae, or pupae. Examples of such items are tarps, discarded bottles, flower pot saucers, and rain gauges. In areas where there...coconut husks, (4) tires, (5) barrels, (6) water storage tanks, (7) bromeliads and axils of banana trees, (8) obstructed roof gutters, (9) plant pot...regularly Store under roof Fill with sand Throw Away/ Recycle Buckets X X X Flower Pot Saucers X X Roof Gutters X Discarded

Study Modules for Calculus-Based General Physics. [Includes Modules 3-5: Planar Motion; Newton's Laws; and Vector Multiplication].

ERIC Educational Resources Information Center

Fuller, Robert G., Ed.; And Others

This is part of a series of 42 Calculus Based Physics (CBP) modules totaling about 1,000 pages. The modules include study guides, practice tests, and mastery tests for a full-year individualized course in calculus-based physics based on the Personalized System of Instruction (PSI). The units are not intended to be used without outside materials;…

Image quality guided approach for adaptive modelling of biometric intra-class variations

NASA Astrophysics Data System (ADS)

Abboud, Ali J.; Jassim, Sabah A.

2010-04-01

The high intra-class variability of acquired biometric data can be attributed to several factors such as quality of acquisition sensor (e.g. thermal), environmental (e.g. lighting), behavioural (e.g. change face pose). Such large fuzziness of biometric data can cause a big difference between an acquired and stored biometric data that will eventually lead to reduced performance. Many systems store multiple templates in order to account for such variations in the biometric data during enrolment stage. The number and typicality of these templates are the most important factors that affect system performance than other factors. In this paper, a novel offline approach is proposed for systematic modelling of intra-class variability and typicality in biometric data by regularly selecting new templates from a set of available biometric images. Our proposed technique is a two stage algorithm whereby in the first stage image samples are clustered in terms of their image quality profile vectors, rather than their biometric feature vectors, and in the second stage a per cluster template is selected from a small number of samples in each clusters to create an ultimate template sets. These experiments have been conducted on five face image databases and their results will demonstrate the effectiveness of proposed quality guided approach.

Multiplex CRISPR/Cas9-based genome engineering from a single lentiviral vector

PubMed Central

Kabadi, Ami M.; Ousterout, David G.; Hilton, Isaac B.; Gersbach, Charles A.

2014-01-01

Engineered DNA-binding proteins that manipulate the human genome and transcriptome have enabled rapid advances in biomedical research. In particular, the RNA-guided CRISPR/Cas9 system has recently been engineered to create site-specific double-strand breaks for genome editing or to direct targeted transcriptional regulation. A unique capability of the CRISPR/Cas9 system is multiplex genome engineering by delivering a single Cas9 enzyme and two or more single guide RNAs (sgRNAs) targeted to distinct genomic sites. This approach can be used to simultaneously create multiple DNA breaks or to target multiple transcriptional activators to a single promoter for synergistic enhancement of gene induction. To address the need for uniform and sustained delivery of multiplex CRISPR/Cas9-based genome engineering tools, we developed a single lentiviral system to express a Cas9 variant, a reporter gene and up to four sgRNAs from independent RNA polymerase III promoters that are incorporated into the vector by a convenient Golden Gate cloning method. Each sgRNA is efficiently expressed and can mediate multiplex gene editing and sustained transcriptional activation in immortalized and primary human cells. This delivery system will be significant to enabling the potential of CRISPR/Cas9-based multiplex genome engineering in diverse cell types. PMID:25122746

Targeting vector construction through recombineering.

PubMed

Malureanu, Liviu A

2011-01-01

Gene targeting in mouse embryonic stem cells is an essential, yet still very expensive and highly time-consuming, tool and method to study gene function at the organismal level or to create mouse models of human diseases. Conventional cloning-based methods have been largely used for generating targeting vectors, but are hampered by a number of limiting factors, including the variety and location of restriction enzymes in the gene locus of interest, the specific PCR amplification of repetitive DNA sequences, and cloning of large DNA fragments. Recombineering is a technique that exploits the highly efficient homologous recombination function encoded by λ phage in Escherichia coli. Bacteriophage-based recombination can recombine homologous sequences as short as 30-50 bases, allowing manipulations such as insertion, deletion, or mutation of virtually any genomic region. The large availability of mouse genomic bacterial artificial chromosome (BAC) libraries covering most of the genome facilitates the retrieval of genomic DNA sequences from the bacterial chromosomes through recombineering. This chapter describes a successfully applied protocol and aims to be a detailed guide through the steps of generation of targeting vectors through recombineering.

Comparison of Aedes aegypti (Diptera: Culicidae) resting behavior on two fabric types under consideration for insecticide treatment in a push-pull strategy.

PubMed

Tainchum, Krajana; Polsomboon, Suppaluck; Grieco, John P; Suwonkerd, Wannapa; Prabaripai, Atchariya; Sungvornyothin, Sungsit; Chareonviriyaphap, Theeraphap; Achee, Nicole L

2013-01-01

Aedes aegypti (L.), the primary vector of dengue and dengue hemorrhagic fever, breeds and rests predominately inside human dwellings. With no current vaccine available, vector control remains the mainstay for dengue management and novel approaches continue to be needed to reduce virus transmission. This requires a full understanding of Ae. aegypti ecology to design effective strategies. One novel approach is the use of contact irritants at target resting sites inside homes to make the surface unacceptable and cause vectors to escape before biting. The objective of the current study was to observe indoor resting behavior patterns of female Ae. aegypti within experimental huts in response to two fabrics under consideration for insecticide treatment: cotton and polyester. Results indicate that fabric type, coverage ratio of dark to light fabric and placement configuration (vertical vs. horizontal) all influenced the resting pattern of mosquito cohorts. Findings from this study will guide evaluations of a push-pull strategy designed to exploit contact irritant behaviors and drive Ae. aegypti out of homes prefeeding.

On the Improvement of Convergence Performance for Integrated Design of Wind Turbine Blade Using a Vector Dominating Multi-objective Evolution Algorithm

NASA Astrophysics Data System (ADS)

Wang, L.; Wang, T. G.; Wu, J. H.; Cheng, G. P.

2016-09-01

A novel multi-objective optimization algorithm incorporating evolution strategies and vector mechanisms, referred as VD-MOEA, is proposed and applied in aerodynamic- structural integrated design of wind turbine blade. In the algorithm, a set of uniformly distributed vectors is constructed to guide population in moving forward to the Pareto front rapidly and maintain population diversity with high efficiency. For example, two- and three- objective designs of 1.5MW wind turbine blade are subsequently carried out for the optimization objectives of maximum annual energy production, minimum blade mass, and minimum extreme root thrust. The results show that the Pareto optimal solutions can be obtained in one single simulation run and uniformly distributed in the objective space, maximally maintaining the population diversity. In comparison to conventional evolution algorithms, VD-MOEA displays dramatic improvement of algorithm performance in both convergence and diversity preservation for handling complex problems of multi-variables, multi-objectives and multi-constraints. This provides a reliable high-performance optimization approach for the aerodynamic-structural integrated design of wind turbine blade.

Studies of machinable ceramics for dental applications. 1. Color analysis.

PubMed

Taira, M; Wakasa, K; Yamaki, M; Tanaka, N; Shintani, H

1989-12-01

Machinable ceramics that can be cut and even lathed have recently been developed in industry. As a first step in evaluating the feasibility of such ceramics in dentistry, eight machinable ceramics were examined for color using the Vita shade guide and a chroma-meter reflectance instrument. We discovered that the studied machinable ceramics varied significantly from the Vita shade guide by the color difference vector, delta E. These machinable ceramics appeared very white and strongly opaque due to their high brightness (L*) values. For intra-oral applications, we expect that L* values of machinable ceramics will be reduced by modification of their microstructures, including their matrix and dispersed phases, while their excellent machinability due to the cleavage of dispersed crystals should be retained.

Small But Increasingly Mighty: Latest Advances in AAV Vector Research, Design, and Evolution.

PubMed

Grimm, Dirk; Büning, Hildegard

2017-11-01

Recombinant gene delivery vectors derived from naturally occurring or genetically engineered adeno-associated viruses (AAV) have taken center stage in human gene therapy, fueled by rapidly accumulating and highly encouraging clinical data. Nonetheless, it has also become evident that the current generation of AAV vectors will require improvements in transduction potency, antibody evasion, and cell specificity in order to realize their full potential and to widen applicability in larger patient cohorts. Fortunately, in the recent past, the field has seen a flurry of exciting new developments that enhance our understanding of AAV vector biology, including virus-host interactions, and/or that expand our arsenal of technologies for AAV capsid design and evolution. This review highlights a collection of latest advances in these areas, which, in the authors' opinion, hold particular promise to propel the AAV vector field forward in the near future, especially when applied in combination. These include fundamental novel insights into the AAV life cycle, from an unexpected role of autophagy and interactions with other viruses to the (re-)discovery of a universal AAV receptor and the function of AAV-AAP for capsid assembly. Concurrently, recent successes in the rational design of next-generation synthetic AAV capsids are pointed out, exemplified by the structure-guided derivation of AAV mutants displaying robust in vivo immune evasion. Finally, a variety of new and innovative strategies for high-throughput generation and screening of AAV capsid libraries are briefly reviewed, including Cre recombinase-based selection, ancestral AAV capsid reconstruction, and DNA barcoding of AAV genomes. All of these examples showcase the present momentum in the AAV field and, together with work by many other academic or industrial entities, raise substantial optimism that the remaining hurdles for human gene therapy with AAV vectors will (soon) be overcome.

Research on gesture recognition of augmented reality maintenance guiding system based on improved SVM

NASA Astrophysics Data System (ADS)

Zhao, Shouwei; Zhang, Yong; Zhou, Bin; Ma, Dongxi

2014-09-01

Interaction is one of the key techniques of augmented reality (AR) maintenance guiding system. Because of the complexity of the maintenance guiding system's image background and the high dimensionality of gesture characteristics, the whole process of gesture recognition can be divided into three stages which are gesture segmentation, gesture characteristic feature modeling and trick recognition. In segmentation stage, for solving the misrecognition of skin-like region, a segmentation algorithm combing background mode and skin color to preclude some skin-like regions is adopted. In gesture characteristic feature modeling of image attributes stage, plenty of characteristic features are analyzed and acquired, such as structure characteristics, Hu invariant moments features and Fourier descriptor. In trick recognition stage, a classifier based on Support Vector Machine (SVM) is introduced into the augmented reality maintenance guiding process. SVM is a novel learning method based on statistical learning theory, processing academic foundation and excellent learning ability, having a lot of issues in machine learning area and special advantages in dealing with small samples, non-linear pattern recognition at high dimension. The gesture recognition of augmented reality maintenance guiding system is realized by SVM after the granulation of all the characteristic features. The experimental results of the simulation of number gesture recognition and its application in augmented reality maintenance guiding system show that the real-time performance and robustness of gesture recognition of AR maintenance guiding system can be greatly enhanced by improved SVM.

Canine serum thyroglobulin autoantibodies in health, hypothyroidism and non-thyroidal illness.

PubMed

Dixon, R M; Mooney, C T

1999-06-01

Thyroglobulin autoantibody (TGAA) was measured in serum from dogs with hypothyroidism (n = 42), non-thyroidal illness (NTI) (n = 77) and clinically healthy dogs (n = 70) using a commercially available enzyme immunoassay kit. Precision studies were consistent with good intra-assay and inter-assay repeatability. TGAA positive results occurred in 15 of the 42 (36 per cent) hypothyroid and four healthy dogs of the remaining 147 animals resulting in a lower incidence of false positive results than obtained with previous TGAA assays. The presence of TGAA was not influenced by age, sex, neutering or pedigree status. Of the four apparently healthy TGAA -positive dogs, two had additional clinicopathological evidence of hypothyroidism. TGAA was positive in 43 per cent of hypothyroid dogs with unexpectedly normal serum c TSH concentrations and was particularly useful in the classification of these cases. Copyright 1999 W.B. Saunders Company Ltd.

Environmental sampling and analysis in support of NTI-3

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

McGuire, R.R.; Harrar, J.E.; Haas, J.S.

1991-04-06

The third National Trail Inspection took place at the Monsanto Chemical Plant in Luling, Louisiana. In order to test the effectiveness of environmental sampling (soil, water and air) in determining the nature of the chemical process in a given production plant and to examine the distance from a process building that samples can effectively be taken, we needed to select some materials that constituted components of process streams. Three materials were selected: 1. isopropyl amine for air monitoring, 2. 4-nitrophenol, one of the precursors in the acetaminophen process, and 3. an intermediate in the production of glyphosate for ROUNDUP thatmore » is known simply as glyphosate intermediated. LLNL did not participate in the air sampling nor the analysis for isopropyl amine. This paper discussed the steps in this experiment including sample collection, sample workshop, sample analysis the results and discussion and the conclusion. 3 figs., 6 tabs.« less

Second order harmonic guided wave mutual interactions in plate: Vector analysis, numerical simulation, and experimental results

NASA Astrophysics Data System (ADS)

Hasanian, Mostafa; Lissenden, Cliff J.

2017-08-01

The extraordinary sensitivity of nonlinear ultrasonic waves to the early stages of material degradation makes them excellent candidates for nondestructive material characterization. However, distinguishing weak material nonlinearity from instrumentation nonlinearity remains problematic for second harmonic generation approaches. A solution to this problem is to mix waves having different frequencies and to let their mutual interaction generate sum and difference harmonics at frequencies far from those of the instrumentation. Mixing of bulk waves and surface waves has been researched for some time, but mixing of guided waves has not yet been investigated in depth. A unique aspect of guided waves is their dispersive nature, which means we need to assure that a wave can propagate at the sum or difference frequency. A wave vector analysis is conducted that enables selection of primary waves traveling in any direction that generate phase matched secondary waves. We have tabulated many sets of primary waves and phase matched sum and difference harmonics. An example wave mode triplet of two counter-propagating collinear shear horizontal waves that interact to generate a symmetric Lamb wave at the sum frequency is simulated using finite element analysis and then laboratory experiments are conducted. The finite element simulation eliminates issues associated with instrumentation nonlinearities and signal-to-noise ratio. A straightforward subtraction method is used in the experiments to identify the material nonlinearity induced mutual interaction and show that the generated Lamb wave propagates on its own and is large enough to measure. Since the Lamb wave has different polarity than the shear horizontal waves the material nonlinearity is clearly identifiable. Thus, the mutual interactions of shear horizontal waves in plates could enable volumetric characterization of material in remote regions from transducers mounted on just one side of the plate.

The AAV-mediated and RNA-guided CRISPR/Cas9 system for gene therapy of DMD and BMD.

PubMed

Wang, Jing-Zhang; Wu, Peng; Shi, Zhi-Min; Xu, Yan-Li; Liu, Zhi-Jun

2017-08-01

Mutations in the dystrophin gene (Dmd) result in Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), which afflict many newborn boys. In 2016, Brain and Development published several interesting articles on DMD treatment with antisense oligonucleotide, kinase inhibitor, and prednisolone. Even more strikingly, three articles in the issue 6271 of Science in 2016 provide new insights into gene therapy of DMD and BMD via the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9). In brief, adeno-associated virus (AAV) vectors transport guided RNAs (gRNAs) and Cas9 into mdx mouse model, gRNAs recognize the mutated Dmd exon 23 (having a stop codon), and Cas9 cut the mutated exon 23 off the Dmd gene. These manipulations restored expression of truncated but partially functional dystrophin, improved skeletal and cardiac muscle function, and increased survival of mdx mice significantly. This review concisely summarized the related advancements and discussed their primary implications in the future gene therapy of DMD, including AAV-vector selection, gRNA designing, Cas9 optimization, dystrophin-restoration efficiency, administration routes, and systemic and long-term therapeutic efficacy. Future orientations, including off-target effects, safety concerns, immune responses, precision medicine, and Dmd-editing in the brain (potentially blocked by the blood-brain barrier) were also elucidated briefly. Collectively, the AAV-mediated and RNA-guided CRISPR/Cas9 system has major superiorities compared with traditional gene therapy, and might contribute to the treatment of DMD and BMD substantially in the near future. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Technology platforms: opportunities and development perspectives

NASA Astrophysics Data System (ADS)

Belyakov, G. P.; Avramchikova, N. T.; Belyakova, G. Y.; Chuvashova, M. N.

2016-11-01

The term “technology platform” is used to define thematic scopes in terms of which technological priorities are formed concerning state, business, science and education cooperation that are aimed to solve the problem of state technological independence. The authors have examined the implementation of this tool so that to concentrate essential resources in priority-driven vectors of science and technological advancement of a guiding cluster of innovative technologies in the field of space applications.

Study Modules for Calculus-Based General Physics. [Includes Modules 1 and 2: Dimensions and Vector Addition; Rectilinear Motion; plus a Trigonometry and Calculus Review].

ERIC Educational Resources Information Center

Fuller, Robert G., Ed.; And Others

This is part of a series of 42 Calculus Based Physics (CBP) modules totaling about 1,000 pages. The modules include study guides, practice tests, and mastery tests for a full-year individualized course in calculus-based physics based on the Personalized System of Instruction (PSI). The units are not intended to be used without outside materials;…

High Efficiency CRISPR/Cas9-mediated Gene Editing in Primary Human T-cells Using Mutant Adenoviral E4orf6/E1b55k "Helper" Proteins.

PubMed

Gwiazda, Kamila S; Grier, Alexandra E; Sahni, Jaya; Burleigh, Stephen M; Martin, Unja; Yang, Julia G; Popp, Nicholas A; Krutein, Michelle C; Khan, Iram F; Jacoby, Kyle; Jensen, Michael C; Rawlings, David J; Scharenberg, Andrew M

2016-09-29

Many future therapeutic applications of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 and related RNA-guided nucleases are likely to require their use to promote gene targeting, thus necessitating development of methods that provide for delivery of three components-Cas9, guide RNAs and recombination templates-to primary cells rendered proficient for homology-directed repair. Here, we demonstrate an electroporation/transduction codelivery method that utilizes mRNA to express both Cas9 and mutant adenoviral E4orf6 and E1b55k helper proteins in association with adeno-associated virus (AAV) vectors expressing guide RNAs and recombination templates. By transiently enhancing target cell permissiveness to AAV transduction and gene editing efficiency, this novel approach promotes efficient gene disruption and/or gene targeting at multiple loci in primary human T-cells, illustrating its broad potential for application in translational gene editing.

Genome-scale CRISPR-Cas9 Knockout and Transcriptional Activation Screening

PubMed Central

Joung, Julia; Konermann, Silvana; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Platt, Randall J.; Brigham, Mark D.; Sanjana, Neville E.; Zhang, Feng

2017-01-01

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified from the screen, we further describe strategies for confirming the screening phenotype as well as genetic perturbation through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9–15 weeks followed by 4–5 weeks of validation. PMID:28333914

Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening.

PubMed

Joung, Julia; Konermann, Silvana; Gootenberg, Jonathan S; Abudayyeh, Omar O; Platt, Randall J; Brigham, Mark D; Sanjana, Neville E; Zhang, Feng

2017-04-01

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified by the screen, we further describe strategies for confirming the screening phenotype, as well as genetic perturbation, through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9-15 weeks, followed by 4-5 weeks of validation.

Mission Accomplished? We Need a Guide to the 'Post Release' World of Wolbachia for Aedes-borne Disease Control.

PubMed

Ritchie, Scott A; van den Hurk, Andrew F; Smout, Michael J; Staunton, Kyran M; Hoffmann, Ary A

2018-03-01

Historically, sustained control of Aedes aegypti, the vector of dengue, chikungunya, yellow fever, and Zika viruses, has been largely ineffective. Subsequently, two novel 'rear and release' control strategies utilizing mosquitoes infected with Wolbachia are currently being developed and deployed widely. In the incompatible insect technique, male Aedes mosquitoes, infected with Wolbachia, suppress populations through unproductive mating. In the transinfection strategy, both male and female Wolbachia-infected Ae. aegypti mosquitoes rapidly infect the wild population with Wolbachia, blocking virus transmission. It is critical to monitor the long-term stability of Wolbachia in host populations, and also the ability of this bacterium to continually inhibit virus transmission. Ongoing release and monitoring programs must be future-proofed should political support weaken when these vectors are successfully controlled. Copyright © 2017 Elsevier Ltd. All rights reserved.

GenoCAD Plant Grammar to Design Plant Expression Vectors for Promoter Analysis.

PubMed

Coll, Anna; Wilson, Mandy L; Gruden, Kristina; Peccoud, Jean

2016-01-01

With the rapid advances in prediction tools for discovery of new promoters and their cis-elements, there is a need to improve plant expression methodologies in order to facilitate a high-throughput functional validation of these promoters in planta. The promoter-reporter analysis is an indispensible approach for characterization of plant promoters. It requires the design of complex plant expression vectors, which can be challenging. Here, we describe the use of a plant grammar implemented in GenoCAD that will allow the users to quickly design constructs for promoter analysis experiments but also for other in planta functional studies. The GenoCAD plant grammar includes a library of plant biological parts organized in structural categories to facilitate their use and management and a set of rules that guides the process of assembling these biological parts into large constructs.

Optimizing fusion PIC code performance at scale on Cori Phase 2

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

Koskela, T. S.; Deslippe, J.

In this paper we present the results of optimizing the performance of the gyrokinetic full-f fusion PIC code XGC1 on the Cori Phase Two Knights Landing system. The code has undergone substantial development to enable the use of vector instructions in its most expensive kernels within the NERSC Exascale Science Applications Program. We study the single-node performance of the code on an absolute scale using the roofline methodology to guide optimization efforts. We have obtained 2x speedups in single node performance due to enabling vectorization and performing memory layout optimizations. On multiple nodes, the code is shown to scale wellmore » up to 4000 nodes, near half the size of the machine. We discuss some communication bottlenecks that were identified and resolved during the work.« less

The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction.

PubMed

Tsafa, Effrosyni; Al-Bahrani, Mariam; Bentayebi, Kaoutar; Przystal, Justyna; Suwan, Keittisak; Hajitou, Amin

2016-08-09

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP.

A Field Trial of Alternative Targeted Screening Strategies for Chagas Disease in Arequipa, Peru

PubMed Central

Hunter, Gabrielle C.; Borrini-Mayorí, Katty; Ancca Juárez, Jenny; Castillo Neyra, Ricardo; Verastegui, Manuela R.; Malaga Chavez, Fernando S.; Cornejo del Carpio, Juan Geny; Córdova Benzaquen, Eleazar; Náquira, César; Gilman, Robert H.; Bern, Caryn; Levy, Michael Z.

2012-01-01

Background Chagas disease is endemic in the rural areas of southern Peru and a growing urban problem in the regional capital of Arequipa, population ∼860,000. It is unclear how to implement cost-effective screening programs across a large urban and periurban environment. Methods We compared four alternative screening strategies in 18 periurban communities, testing individuals in houses with 1) infected vectors; 2) high vector densities; 3) low vector densities; and 4) no vectors. Vector data were obtained from routine Ministry of Health insecticide application campaigns. We performed ring case detection (radius of 15 m) around seropositive individuals, and collected data on costs of implementation for each strategy. Results Infection was detected in 21 of 923 (2.28%) participants. Cases had lived more time on average in rural places than non-cases (7.20 years versus 3.31 years, respectively). Significant risk factors on univariate logistic regression for infection were age (OR 1.02; p = 0.041), time lived in a rural location (OR 1.04; p = 0.022), and time lived in an infested area (OR 1.04; p = 0.008). No multivariate model with these variables fit the data better than a simple model including only the time lived in an area with triatomine bugs. There was no significant difference in prevalence across the screening strategies; however a self-assessment of disease risk may have biased participation, inflating prevalence among residents of houses where no infestation was detected. Testing houses with infected-vectors was least expensive. Ring case detection yielded four secondary cases in only one community, possibly due to vector-borne transmission in this community, apparently absent in the others. Conclusions Targeted screening for urban Chagas disease is promising in areas with ongoing vector-borne transmission; however, these pockets of epidemic transmission remain difficult to detect a priori. The flexibility to adapt to the epidemiology that emerges during screening is key to an efficient case detection intervention. In heterogeneous urban environments, self-assessments of risk and simple residence history questionnaires may be useful to identify those at highest risk for Chagas disease to guide diagnostic efforts. PMID:22253939

A field trial of alternative targeted screening strategies for Chagas disease in Arequipa, Peru.

PubMed

Hunter, Gabrielle C; Borrini-Mayorí, Katty; Ancca Juárez, Jenny; Castillo Neyra, Ricardo; Verastegui, Manuela R; Malaga Chavez, Fernando S; Cornejo del Carpio, Juan Geny; Córdova Benzaquen, Eleazar; Náquira, César; Gilman, Robert H; Bern, Caryn; Levy, Michael Z

2012-01-01

Chagas disease is endemic in the rural areas of southern Peru and a growing urban problem in the regional capital of Arequipa, population ∼860,000. It is unclear how to implement cost-effective screening programs across a large urban and periurban environment. We compared four alternative screening strategies in 18 periurban communities, testing individuals in houses with 1) infected vectors; 2) high vector densities; 3) low vector densities; and 4) no vectors. Vector data were obtained from routine Ministry of Health insecticide application campaigns. We performed ring case detection (radius of 15 m) around seropositive individuals, and collected data on costs of implementation for each strategy. Infection was detected in 21 of 923 (2.28%) participants. Cases had lived more time on average in rural places than non-cases (7.20 years versus 3.31 years, respectively). Significant risk factors on univariate logistic regression for infection were age (OR 1.02; p = 0.041), time lived in a rural location (OR 1.04; p = 0.022), and time lived in an infested area (OR 1.04; p = 0.008). No multivariate model with these variables fit the data better than a simple model including only the time lived in an area with triatomine bugs. There was no significant difference in prevalence across the screening strategies; however a self-assessment of disease risk may have biased participation, inflating prevalence among residents of houses where no infestation was detected. Testing houses with infected-vectors was least expensive. Ring case detection yielded four secondary cases in only one community, possibly due to vector-borne transmission in this community, apparently absent in the others. Targeted screening for urban Chagas disease is promising in areas with ongoing vector-borne transmission; however, these pockets of epidemic transmission remain difficult to detect a priori. The flexibility to adapt to the epidemiology that emerges during screening is key to an efficient case detection intervention. In heterogeneous urban environments, self-assessments of risk and simple residence history questionnaires may be useful to identify those at highest risk for Chagas disease to guide diagnostic efforts.

CRISPR/Cas9-Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development.

PubMed

Okoli, Arinze; Okeke, Malachy I; Tryland, Morten; Moens, Ugo

2018-01-22

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of Vaccinia virus paves the way for its application in editing other vaccine/vector-relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors, including sub-optimal immunogenicity; transgene and genome instability; reversion of attenuation; potential of spread of transgenes to wildtype strains and close contacts, which are important biosafety and risk assessment considerations. In this article, we review the published literature on the application of CRISPR/Cas9 in virus genome editing and discuss the potentials of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also discuss the application of CRISPR/Cas9 in combating viruses of clinical relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome them.

Reviewing molecular adaptations of Lyme borreliosis spirochetes in the context of reproductive fitness in natural transmission cycles.

PubMed

Tsao, Jean I

2009-01-01

Lyme borreliosis (LB) is caused by a group of pathogenic spirochetes - most often Borrelia burgdorferi, B. afzelii, and B. garinii - that are vectored by hard ticks in the Ixodes ricinus-persulcatus complex, which feed on a variety of mammals, birds, and lizards. Although LB is one of the best-studied vector-borne zoonoses, the annual incidence in North America and Europe leads other vector-borne diseases and continues to increase. What factors make the LB system so successful, and how can researchers hope to reduce disease risk - either through vaccinating humans or reducing the risk of contacting infected ticks in nature? Discoveries of molecular interactions involved in the transmission of LB spirochetes have accelerated recently, revealing complex interactions among the spirochete-tick-vertebrate triad. These interactions involve multiple, and often redundant, pathways that reflect the evolution of general and specific mechanisms by which the spirochetes survive and reproduce. Previous reviews have focused on the molecular interactions or population biology of the system. Here molecular interactions among the LB spirochete, its vector, and vertebrate hosts are reviewed in the context of natural maintenance cycles, which represent the ecological and evolutionary contexts that shape these interactions. This holistic system approach may help researchers develop additional testable hypotheses about transmission processes, interpret laboratory results, and guide development of future LB control measures and management.

Optical coherence tomography guided microinjections in live mouse embryos: high-resolution targeted manipulation for mouse embryonic research.

PubMed

Syed, Saba H; Coughlin, Andrew J; Garcia, Monica D; Wang, Shang; West, Jennifer L; Larin, Kirill V; Larina, Irina V

2015-05-01

The ability to conduct highly localized delivery of contrast agents, viral vectors, therapeutic or pharmacological agents, and signaling molecules or dyes to live mammalian embryos is greatly desired to enable a variety of studies in the field of developmental biology, such as investigating the molecular regulation of cardiovascular morphogenesis. To meet such a demand, we introduce, for the first time, the concept of employing optical coherence tomography (OCT)-guide microinjections in live mouse embryos, which provides precisely targeted manipulation with spatial resolution at the micrometer scale. The feasibility demonstration is performed with experimental studies on cultured live mouse embryos at E8.5 and E9.5. Additionally, we investigate the OCT-guided microinjection of gold–silica nanoshells to the yolk sac vasculature of live cultured mouse embryos at the stage when the heart just starts to beat, as a potential approach for dynamic assessment of cardiovascular form and function before the onset of blood cell circulation. Also, the capability of OCT to quantitatively monitor and measure injection volume is presented. Our results indicate that OCT-guided microinjection could be a useful tool for mouse embryonic research.

Optical coherence tomography guided microinjections in live mouse embryos: high-resolution targeted manipulation for mouse embryonic research

PubMed Central

Syed, Saba H.; Coughlin, Andrew J.; Garcia, Monica D.; Wang, Shang; West, Jennifer L.; Larin, Kirill V.; Larina, Irina V.

2015-01-01

Abstract. The ability to conduct highly localized delivery of contrast agents, viral vectors, therapeutic or pharmacological agents, and signaling molecules or dyes to live mammalian embryos is greatly desired to enable a variety of studies in the field of developmental biology, such as investigating the molecular regulation of cardiovascular morphogenesis. To meet such a demand, we introduce, for the first time, the concept of employing optical coherence tomography (OCT)-guide microinjections in live mouse embryos, which provides precisely targeted manipulation with spatial resolution at the micrometer scale. The feasibility demonstration is performed with experimental studies on cultured live mouse embryos at E8.5 and E9.5. Additionally, we investigate the OCT-guided microinjection of gold–silica nanoshells to the yolk sac vasculature of live cultured mouse embryos at the stage when the heart just starts to beat, as a potential approach for dynamic assessment of cardiovascular form and function before the onset of blood cell circulation. Also, the capability of OCT to quantitatively monitor and measure injection volume is presented. Our results indicate that OCT-guided microinjection could be a useful tool for mouse embryonic research. PMID:25581495

Nature, Mind, and Medicine: A Model for Mind-Body Healing.

PubMed

Kaufman, Jason A

2018-04-27

The human mind-body possesses a remarkable innate ability to heal. Grounded in the evolutionarily conserved systems of the brain and body, nature appears to function as the fundamental source of wellness along the two vectors of attention and relaxation. Yet, our species is moving away from nature at a time when humanity is just beginning to rediscover its benefits. Exposure to natural environments may provide a "window" of healing that can be extended through a continuum of intervention through the use of guided meditation and ultimately hypnotic suggestion. The result may be an improved ability to promote greater executive functioning and more robust immune regulation. The time has come for a more holistic medicine guided by the hand of nature. Copyright © 2018 Elsevier Inc. All rights reserved.

The Causal Mediation Formula - A Guide to the Assessment of Pathways and Mechanisms

DTIC Science & Technology

2011-10-01

for estimating CDE(z) in observational studies (in the presence of unobserved confounders) can be derived using do- calculus (Pearl, 2009, pp. 85–88...2011; Albert and Nelson , 2011). 7In the presence of measured and unmeasured confounders, the general conditions under which NDE is estimable from...achieve this independence (see footnote 7), that Z may represent a vector of variables, and that integrals should replace summations when dealing with

Patient-specific targeting guides compared with traditional instrumentation for glenoid component placement in shoulder arthroplasty: a multi-surgeon study in 70 arthritic cadaver specimens.

PubMed

Throckmorton, Thomas W; Gulotta, Lawrence V; Bonnarens, Frank O; Wright, Stephen A; Hartzell, Jeffrey L; Rozzi, William B; Hurst, Jason M; Frostick, Simon P; Sperling, John W

2015-06-01

The purpose of this study was to compare the accuracy of patient-specific guides for total shoulder arthroplasty (TSA) with traditional instrumentation in arthritic cadaver shoulders. We hypothesized that the patient-specific guides would place components more accurately than standard instrumentation. Seventy cadaver shoulders with radiographically confirmed arthritis were randomized in equal groups to 5 surgeons of varying experience levels who were not involved in development of the patient-specific guidance system. Specimens were then randomized to patient-specific guides based off of computed tomography scanning, standard instrumentation, and anatomic TSA or reverse TSA. Variances in version or inclination of more than 10° and more than 4 mm in starting point were considered indications of significant component malposition. TSA glenoid components placed with patient-specific guides averaged 5° of deviation from the intended position in version and 3° in inclination; those with standard instrumentation averaged 8° of deviation in version and 7° in inclination. These differences were significant for version (P = .04) and inclination (P = .01). Multivariate analysis of variance to compare the overall accuracy for the entire cohort (TSA and reverse TSA) revealed patient-specific guides to be significantly more accurate (P = .01) for the combined vectors of version and inclination. Patient-specific guides also had fewer instances of significant component malposition than standard instrumentation did. Patient-specific targeting guides were more accurate than traditional instrumentation and had fewer instances of component malposition for glenoid component placement in this multi-surgeon cadaver study of arthritic shoulders. Long-term clinical studies are needed to determine if these improvements produce improved functional outcomes. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Treatment of Parkinson's disease in rats by Nrf2 transfection using MRI-guided focused ultrasound delivery of nanomicrobubbles

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

Long, Ling; Cai, Xiaodong; Guo, Ruomi

Parkinson's disease (PD) is a very common neurological disorder. However, effective therapy is lacking. Although the blood-brain-barrier (BBB) protects the brain, it prevents the delivery of about 90% of drugs and nucleotides into the brain, thereby hindering the development of gene therapy for PD. Magnetic resonance imaging (MRI)-guided focused ultrasound delivery of microbubbles enhances the delivery of gene therapy vectors across the BBB and improves transfection efficiency. In the present study, we delivered nuclear factor E2-related factor 2 (Nrf2, NFE2L2) contained in nanomicrobubbles into the substantia nigra of PD rats by MRI-guided focused ultrasound, and we examined the effect ofmore » Nrf2 over-expression in this animal model of PD. The rat model of PD was established by injecting 6-OHDA in the right substantia nigra stereotactically. Plasmids (pDC315 or pDC315/Nrf2) were loaded onto nanomicrobubbles, and then injected through the tail vein with the assistance of MRI-guided focused ultrasound. MRI-guided focused ultrasound delivery of nanomicrobubbles increased gene transfection efficiency. Furthermore, Nrf2 gene transfection reduced reactive oxygen species levels, thereby protecting neurons in the target region. - Highlights: • MRI-guided focused ultrasound enhances gene transfection into the brain of rats. • Increased Nrf2 expression protects neurons in the rat model of PD. • Nrf2 protects neurons in PD by inhibiting ROS production.« less

Control-group feature normalization for multivariate pattern analysis of structural MRI data using the support vector machine.

PubMed

Linn, Kristin A; Gaonkar, Bilwaj; Satterthwaite, Theodore D; Doshi, Jimit; Davatzikos, Christos; Shinohara, Russell T

2016-05-15

Normalization of feature vector values is a common practice in machine learning. Generally, each feature value is standardized to the unit hypercube or by normalizing to zero mean and unit variance. Classification decisions based on support vector machines (SVMs) or by other methods are sensitive to the specific normalization used on the features. In the context of multivariate pattern analysis using neuroimaging data, standardization effectively up- and down-weights features based on their individual variability. Since the standard approach uses the entire data set to guide the normalization, it utilizes the total variability of these features. This total variation is inevitably dependent on the amount of marginal separation between groups. Thus, such a normalization may attenuate the separability of the data in high dimensional space. In this work we propose an alternate approach that uses an estimate of the control-group standard deviation to normalize features before training. We study our proposed approach in the context of group classification using structural MRI data. We show that control-based normalization leads to better reproducibility of estimated multivariate disease patterns and improves the classifier performance in many cases. Copyright © 2016 Elsevier Inc. All rights reserved.

Precision of computer-assisted core decompression drilling of the knee.

PubMed

Beckmann, J; Goetz, J; Bäthis, H; Kalteis, T; Grifka, J; Perlick, L

2006-06-01

Core decompression by exact drilling into the ischemic areas is the treatment of choice in early stages of osteonecrosis of the femoral condyle. Computer-aided surgery might enhance the precision of the drilling and lower the radiation exposure time of both staff and patients. The aim of this study was to evaluate the precision of the fluoroscopically based VectorVision-navigation system in an in vitro model. Thirty sawbones were prepared with a defect filled up with a radiopaque gypsum sphere mimicking the osteonecrosis. 20 sawbones were drilled by guidance of an intraoperative navigation system VectorVision (BrainLAB, Munich, Germany). Ten sawbones were drilled by fluoroscopic control only. A statistically significant difference with a mean distance of 0.58 mm in the navigated group and 0.98 mm in the control group regarding the distance to the desired mid-point of the lesion could be stated. Significant difference was further found in the number of drilling corrections as well as radiation time needed. The fluoroscopic-based VectorVision-navigation system shows a high feasibility and precision of computer-guided drilling with simultaneously reduction of radiation time and therefore could be integrated into clinical routine.

Taiwan's Travel and Border Health Measures in Response to Zika.

PubMed

Ho, Li-Li; Tsai, Yu-Hui; Lee, Wang-Ping; Liao, Szu-Tsai; Wu, Li-Gin; Wu, Yi-Chun

Zika virus has recently emerged as a worldwide public health concern. Travel and border health measures stand as one of the main strategies and frontline defenses in responding to international epidemics. As of October 31, 2016, Taiwan has reported 13 imported cases, 5 of which were detected through routine entry screening and active monitoring at international airports. This article shares Taiwan's disease surveillance activities at designated points of entry and travel and border health measures in response to Zika. The Taiwan government collaborates with its tourism industry to disseminate information about precautionary measures and encourages tour guides to report suspected individuals or events to activate early response measures. Taiwan also engages in vector control activities at points of entry, including targeting aircraft from countries where vector-borne diseases are endemic, implementing mosquito sweep measures, and collecting vector surveillance data. In future emerging and reemerging disease events, entry surveillance at designated points of entry may enable early detection of diseases of international origin and more rapid activation of public health preparedness activities and international collaboration. Taiwan will continue to maximize border and travel health measures in compliance with IHR (2005) requirements, which rely on continued risk assessment, practical implementation activities, and engagement with all stakeholders.

Design and efficacy of an Ecohealth competency-based course on the prevention and control of vector diseases in Latin America.

PubMed

Magaña-Valladares, Laura; Rodríguez, Mario Henry; Betanzos-Reyes, Ángel Francisco; Riojas-Rodríguez, Horacio; Quezada-Jiménez, María Laura; Suárez-Conejero, Juana Elvira; Lamadrid-Figueroa, Héctor

2018-01-01

To design and analyze the efficacy of an Ecohealth competency-based course on the prevention and control of vector-borne-diseases for specific stakeholders. Multiple stakeholders and sectors of the region were consulted to identify Ecohealth group-specific competencies using an adjusted analysis matrix. Eight courses based on the competencies were implemented to train EA tutors. The effectiveness of the course was evaluated through the use of paired- t-tests by intervention group. Strategic, tactical, academia and community stakeholder groups and their competencies were identified. An overall gain of 43 percentage points (p<0.001) was observed in terms of competencies score in trained tutors, which further trained 1 033 people. The identification of the stakeholders and their competencies proved to be useful to guide training courses to significantly improve the initial competencies and create a critical mass to further advance the EA in the region.

Lipid nanoparticle vectorization of indocyanine green improves fluorescence imaging for tumor diagnosis and lymph node resection.

PubMed

Navarro, Fabrice P; Berger, Michel; Guillermet, Stéphanie; Josserand, Véronique; Guyon, Laurent; Neumann, Emmanuelle; Vinet, Françoise; Texier, Isabelle

2012-10-01

Fluorescence imaging is opening a new era in image-guided surgery and other medical applications. The only FDA approved contrast agent in the near infrared is IndoCyanine Green (ICG), which despites its low toxicity, displays poor chemical and optical properties for long-term and sensitive imaging applications in human. Lipid nanoparticles are investigated for improving ICG optical properties and in vivo fluorescence imaging sensitivity. 30 nm diameter lipid nanoparticles (LNP) are loaded with ICG. Their characterization and use for tumor and lymph node imaging are described. Nano-formulation benefits dye optical properties (6 times improved brightness) and chemical stability (>6 months at 4 degrees C in aqueous buffer). More importantly, LNP vectorization allows never reported sensitive and prolonged (>1 day) labeling of tumors and lymph nodes. Composed of human-use approved ingredients, this novel ICG nanometric formulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.

TALEN- and CRISPR/Cas9-Mediated Gene Editing in Human Pluripotent Stem Cells Using Lipid-Based Transfection.

PubMed

Hendriks, William T; Jiang, Xin; Daheron, Laurence; Cowan, Chad A

2015-08-03

Using custom-engineered nuclease-mediated genome editing, such as Transcription Activator-Like Effector Nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) RNA-guided Cas9 nucleases, human pluripotent stem cell (hPSC) lines with knockout or mutant alleles can be generated and differentiated into various cell types. This strategy of genome engineering in hPSCs will prove invaluable for studying human biology and disease. Here, we provide a detailed protocol for design and construction of TALEN and CRISPR vectors, testing of their nuclease activity, and delivery of TALEN or CRISPR vectors into hPSCs. In addition, we describe the use of single-stranded oligodeoxynucleotides (ssODNs) to introduce or repair point mutations. Next, we describe the identification of edited hPSC clones without antibiotic selection, including their clonal selection, genotyping, and expansion for downstream applications. Copyright © 2015 John Wiley & Sons, Inc.

Top partner-resonance interplay in a composite Higgs framework

NASA Astrophysics Data System (ADS)

Yepes, Juan; Zerwekh, Alfonso

2018-04-01

Guided us by the scenario of weak scale naturalness and the possible existence of exotic resonances, we have explored in a SO(5) Composite Higgs setup the interplay among three matter sectors: elementary, top partners and vector resonances. We parametrize it through explicit interactions of spin-1 SO(4)-resonances, coupled to the SO(5)-invariant fermionic currents and tensors presented in this work. Such invariants are built upon the Standard Model fermion sector as well as top partners sourced by the unbroken SO(4). The mass scales entailed by the top partner and vector resonance sectors will control the low energy effects emerging from our interplaying model. Its phenomenological impact and parameter spaces have been considered via flavor-dijet processes and electric dipole moments bounds. Finally, the strength of the Nambu-Goldstone symmetry breaking and the extra couplings implied by the top partner mass scales are measured in accordance with expected estimations.

Effective 2D-3D medical image registration using Support Vector Machine.

PubMed

Qi, Wenyuan; Gu, Lixu; Zhao, Qiang

2008-01-01

Registration of pre-operative 3D volume dataset and intra-operative 2D images gradually becomes an important technique to assist radiologists in diagnosing complicated diseases easily and quickly. In this paper, we proposed a novel 2D/3D registration framework based on Support Vector Machine (SVM) to compensate the disadvantages of generating large number of DRR images in the stage of intra-operation. Estimated similarity metric distribution could be built up from the relationship between parameters of transform and prior sparse target metric values by means of SVR method. Based on which, global optimal parameters of transform are finally searched out by an optimizer in order to guide 3D volume dataset to match intra-operative 2D image. Experiments reveal that our proposed registration method improved performance compared to conventional registration method and also provided a precise registration result efficiently.

Tensoral for post-processing users and simulation authors

NASA Technical Reports Server (NTRS)

Dresselhaus, Eliot

1993-01-01

The CTR post-processing effort aims to make turbulence simulations and data more readily and usefully available to the research and industrial communities. The Tensoral language, which provides the foundation for this effort, is introduced here in the form of a user's guide. The Tensoral user's guide is presented in two main sections. Section one acts as a general introduction and guides database users who wish to post-process simulation databases. Section two gives a brief description of how database authors and other advanced users can make simulation codes and/or the databases they generate available to the user community via Tensoral database back ends. The two-part structure of this document conforms to the two-level design structure of the Tensoral language. Tensoral has been designed to be a general computer language for performing tensor calculus and statistics on numerical data. Tensoral's generality allows it to be used for stand-alone native coding of high-level post-processing tasks (as described in section one of this guide). At the same time, Tensoral's specialization to a minute task (namely, to numerical tensor calculus and statistics) allows it to be easily embedded into applications written partly in Tensoral and partly in other computer languages (here, C and Vectoral). Embedded Tensoral, aimed at advanced users for more general coding (e.g. of efficient simulations, for interfacing with pre-existing software, for visualization, etc.), is described in section two of this guide.

The natural dietary genistein boosts bacteriophage-mediated cancer cell killing by improving phage-targeted tumor cell transduction

PubMed Central

Tsafa, Effrosyni; Al-Bahrani, Mariam; Bentayebi, Kaoutar; Przystal, Justyna; Suwan, Keittisak; Hajitou, Amin

2016-01-01

Gene therapy has long been regarded as a promising treatment for cancer. However, cancer gene therapy is still facing the challenge of targeting gene delivery vectors specifically to tumors when administered via clinically acceptable non-invasive systemic routes (i.e. intravenous). The bacteria virus, bacteriophage (phage), represents a new generation of promising vectors in systemic gene delivery since their targeting can be achieved through phage capsid display ligands, which enable them to home to specific tumor receptors without the need to ablate any native eukaryotic tropism. We have previously reported a tumor specific bacteriophage vector named adeno-associated virus/phage, or AAVP, in which gene expression is under a recombinant human rAAV2 virus genome targeted to tumors via a ligand-directed phage capsid. However, cancer gene therapy with this tumor-targeted vector achieved variable outcomes ranging from tumor regression to no effect in both experimental and natural preclinical models. Herein, we hypothesized that combining the natural dietary genistein, with proven anticancer activity, would improve bacteriophage anticancer safe therapy. We show that combination treatment with genistein and AAVP increased targeted cancer cell killing by AAVP carrying the gene for Herpes simplex virus thymidine kinase (HSVtk) in 2D tissue cultures and 3D tumor spheroids. We found this increased tumor cell killing was associated with enhanced AAVP-mediated gene expression. Next, we established that genistein protects AAVP against proteasome degradation and enhances vector genome accumulation in the nucleus. Combination of genistein and phage-guided virotherapy is a safe and promising strategy that should be considered in anticancer therapy with AAVP. PMID:27437775

Bioinspired Star-Shaped Poly(l-lysine) Polypeptides: Efficient Polymeric Nanocarriers for the Delivery of DNA to Mesenchymal Stem Cells.

PubMed

Walsh, David P; Murphy, Robert D; Panarella, Angela; Raftery, Rosanne M; Cavanagh, Brenton; Simpson, Jeremy C; O'Brien, Fergal J; Heise, Andreas; Cryan, Sally-Ann

2018-05-07

The field of tissue engineering is increasingly recognizing that gene therapy can be employed for modulating in vivo cellular response thereby guiding tissue regeneration. However, the field lacks a versatile and biocompatible gene delivery platform capable of efficiently delivering transgenes to mesenchymal stem cells (MSCs), a cell type often refractory to transfection. Herein, we describe the extensive and systematic exploration of three architectural variations of star-shaped poly(l-lysine) polypeptide (star-PLL) with varying number and length of poly(l-lysine) arms as potential nonviral gene delivery vectors for MSCs. We demonstrate that star-PLL vectors are capable of self-assembling with pDNA to form stable, cationic nanomedicines. Utilizing high content screening, live cell imaging, and mechanistic uptake studies we confirm the intracellular delivery of pDNA by star-PLLs to MSCs is a rapid process, which likely proceeds via a clathrin-independent mechanism. We identify a star-PLL composition with 64 poly(l-lysine) arms and five l-lysine subunits per arm as a particularly efficient vector that is capable of delivering both reporter genes and the therapeutic transgenes bone morphogenetic protein-2 and vascular endothelial growth factor to MSCs. This composition facilitated a 1000-fold increase in transgene expression in MSCs compared to its linear analogue, linear poly(l-lysine). Furthermore, it demonstrated comparable transgene expression to the widely used vector polyethylenimine using a lower pDNA dose with significantly less cytotoxicity. Overall, this study illustrates the ability of the star-PLL vectors to facilitate efficient, nontoxic nucleic acid delivery to MSCs thereby functioning as an innovative nanomedicine platform for tissue engineering applications.

Addressing vulnerability, building resilience: community-based adaptation to vector-borne diseases in the context of global change.

PubMed

Bardosh, Kevin Louis; Ryan, Sadie J; Ebi, Kris; Welburn, Susan; Singer, Burton

2017-12-11

The threat of a rapidly changing planet - of coupled social, environmental and climatic change - pose new conceptual and practical challenges in responding to vector-borne diseases. These include non-linear and uncertain spatial-temporal change dynamics associated with climate, animals, land, water, food, settlement, conflict, ecology and human socio-cultural, economic and political-institutional systems. To date, research efforts have been dominated by disease modeling, which has provided limited practical advice to policymakers and practitioners in developing policies and programmes on the ground. In this paper, we provide an alternative biosocial perspective grounded in social science insights, drawing upon concepts of vulnerability, resilience, participation and community-based adaptation. Our analysis was informed by a realist review (provided in the Additional file 2) focused on seven major climate-sensitive vector-borne diseases: malaria, schistosomiasis, dengue, leishmaniasis, sleeping sickness, chagas disease, and rift valley fever. Here, we situate our analysis of existing community-based interventions within the context of global change processes and the wider social science literature. We identify and discuss best practices and conceptual principles that should guide future community-based efforts to mitigate human vulnerability to vector-borne diseases. We argue that more focused attention and investments are needed in meaningful public participation, appropriate technologies, the strengthening of health systems, sustainable development, wider institutional changes and attention to the social determinants of health, including the drivers of co-infection. In order to respond effectively to uncertain future scenarios for vector-borne disease in a changing world, more attention needs to be given to building resilient and equitable systems in the present.

Decade-Long Safety and Function of Retroviral-Modified Chimeric Antigen Receptor T-cells

PubMed Central

Scholler, John; Brady, Troy L.; Binder-Scholl, Gwendolyn; Hwang, Wei-Ting; Plesa, Gabriela; Hege, Kristen M.; Vogel, Ashley N.; Kalos, Michael; Riley, James L.; Deeks, Steven G.; Mitsuyasu, Ronald T.; Bernstein, Wendy B.; Aronson, Naomi E.; Levine, Bruce L.; Bushman, Frederic D.; June, Carl H.

2015-01-01

The success of adoptive T cell gene transfer for treatment of cancer and HIV is predicated on generating a response that is both durable and safe. Here we report long term results from three clinical trials to evaluate gammaretroviral vector engineered T-cells for HIV. The vector encoded a chimeric antigen receptor (CAR) comprised of CD4 linked to the CD3-ζ signaling chain (CD4ζ). CAR T-cells were detected in 98% of samples tested for at least 11 years post-infusion at frequencies that exceed average T cell levels after most vaccine approaches. The CD4ζ transgene retained expression and function. There was no evidence of vector-induced immortalization of cells as integration site distributions showed no evidence of persistent clonal expansion or enrichment for integration sites near genes implicated in growth control or transformation. The CD4ζ T cells have stable levels of engraftment, with decay half-lives that exceed 16 years, in marked contrast to previous trials testing engineered T cells. These findings indicate that host immunosuppression prior to T cell transfer is not required in order to achieve long term persistence of gene-modified T cells. Further, our results emphasize the safety of T cells modified by retroviral gene transfer in clinical application, as measured in >500 patient years of follow up. Thus, previous safety issues with integrating viral vectors are hematopoietic stem cell or transgene intrinsic, and not a general feature of retroviral vectors. Engineered T cells are a promising form of synthetic biology for long term delivery of protein based therapeutics. These results provide a framework to guide the therapy of a wide spectrum of human diseases. PMID:22553251

Quantitative evaluation of first, second, and third generation hairpin systems reveals the limit of mammalian vector-based RNAi

PubMed Central

Watanabe, Colin; Cuellar, Trinna L.; Haley, Benjamin

2016-01-01

ABSTRACT Incorporating miRNA-like features into vector-based hairpin scaffolds has been shown to augment small RNA processing and RNAi efficiency. Therefore, defining an optimal, native hairpin context may obviate a need for hairpin-specific targeting design schemes, which confound the movement of functional siRNAs into shRNA/artificial miRNA backbones, or large-scale screens to identify efficacious sequences. Thus, we used quantitative cell-based assays to compare separate third generation artificial miRNA systems, miR-E (based on miR-30a) and miR-3G (based on miR-16-2 and first described in this study) to widely-adopted, first and second generation formats in both Pol-II and Pol-III expression vector contexts. Despite their unique structures and strandedness, and in contrast to first and second-generation RNAi triggers, the third generation formats operated with remarkable similarity to one another, and strong silencing was observed with a significant fraction of the evaluated target sequences within either promoter context. By pairing an established siRNA design algorithm with the third generation vectors we could readily identify targeting sequences that matched or exceeded the potency of those discovered through large-scale sensor-based assays. We find that third generation hairpin systems enable the maximal level of siRNA function, likely through enhanced processing and accumulation of precisely-defined guide RNAs. Therefore, we predict future gains in RNAi potency will come from improved hairpin expression and identification of optimal siRNA-intrinsic silencing properties rather than further modification of these scaffolds. Consequently, third generation systems should be the primary format for vector-based RNAi studies; miR-3G is advantageous due to its small expression cassette and simplified, cost-efficient cloning scheme. PMID:26786363

Potential for Mosquitoes (Diptera: Culicidae) From Florida to Transmit Rift Valley Fever Virus

DTIC Science & Technology

2013-09-01

Guide for the Care and Use of Laboratory Animals, NationalResearchCouncil, 2011. Theuse of any speciÞcproduct does not constitute endorsement of that...from North America are competent vectors and might be involved in the natural transmission cycle so that the appropriate control measures can be used if...collected in sufÞ- cient numbers for evaluation (Table 1). Viruses and Virus Assay.We used the ZH501 strain of RVFV, isolated in 1977 from the blood of a 10

SU-E-J-45: The Correlation Between CBCT Flat Panel Misalignment and 3D Image Guidance Accuracy

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

Kenton, O; Valdes, G; Yin, L

Purpose To simulate the impact of CBCT flat panel misalignment on the image quality, the calculated correction vectors in 3D image guided proton therapy and to determine if these calibration errors can be caught in our QA process. Methods The X-ray source and detector geometrical calibration (flexmap) file of the CBCT system in the AdaPTinsight software (IBA proton therapy) was edited to induce known changes in the rotational and translational calibrations of the imaging panel. Translations of up to ±10 mm in the x, y and z directions (see supplemental) and rotational errors of up to ±3° were induced. Themore » calibration files were then used to reconstruct the CBCT image of a pancreatic patient and CatPhan phantom. Correction vectors were calculated for the patient using the software’s auto match system and compared to baseline values. The CatPhan CBCT images were used for quantitative evaluation of image quality for each type of induced error. Results Translations of 1 to 3 mm in the x and y calibration resulted in corresponding correction vector errors of equal magnitude. Similar 10mm shifts were seen in the y-direction; however, in the x-direction, the image quality was too degraded for a match. These translational errors can be identified through differences in isocenter from orthogonal kV images taken during routine QA. Errors in the z-direction had no effect on the correction vector and image quality.Rotations of the imaging panel calibration resulted in corresponding correction vector rotations of the patient images. These rotations also resulted in degraded image quality which can be identified through quantitative image quality metrics. Conclusion Misalignment of CBCT geometry can lead to incorrect translational and rotational patient correction vectors. These errors can be identified through QA of the imaging isocenter as compared to orthogonal images combined with monitoring of CBCT image quality.« less

CRISPR/Cas9 mediates efficient conditional mutagenesis in Drosophila.

PubMed

Xue, Zhaoyu; Wu, Menghua; Wen, Kejia; Ren, Menda; Long, Li; Zhang, Xuedi; Gao, Guanjun

2014-09-05

Existing transgenic RNA interference (RNAi) methods greatly facilitate functional genome studies via controlled silencing of targeted mRNA in Drosophila. Although the RNAi approach is extremely powerful, concerns still linger about its low efficiency. Here, we developed a CRISPR/Cas9-mediated conditional mutagenesis system by combining tissue-specific expression of Cas9 driven by the Gal4/upstream activating site system with various ubiquitously expressed guide RNA transgenes to effectively inactivate gene expression in a temporally and spatially controlled manner. Furthermore, by including multiple guide RNAs in a transgenic vector to target a single gene, we achieved a high degree of gene mutagenesis in specific tissues. The CRISPR/Cas9-mediated conditional mutagenesis system provides a simple and effective tool for gene function analysis, and complements the existing RNAi approach. Copyright © 2014 Xue et al.

Climate Influence on Emerging Risk Areas for Rift Valley Fever Epidemics in Tanzania.

PubMed

Mweya, Clement N; Mboera, Leonard E G; Kimera, Sharadhuli I

2017-07-01

Rift Valley Fever (RVF) is a climate-related arboviral infection of animals and humans. Climate is thought to represent a threat toward emerging risk areas for RVF epidemics globally. The objective of this study was to evaluate influence of climate on distribution of suitable breeding habitats for Culex pipiens complex, potential mosquito vector responsible for transmission and distribution of disease epidemics risk areas in Tanzania. We used ecological niche models to estimate potential distribution of disease risk areas based on vectors and disease co-occurrence data approach. Climatic variables for the current and future scenarios were used as model inputs. Changes in mosquito vectors' habitat suitability in relation to disease risk areas were estimated. We used partial receiver operating characteristic and the area under the curves approach to evaluate model predictive performance and significance. Habitat suitability for Cx. pipiens complex indicated broad-scale potential for change and shift in the distribution of the vectors and disease for both 2020 and 2050 climatic scenarios. Risk areas indicated more intensification in the areas surrounding Lake Victoria and northeastern part of the country through 2050 climate scenario. Models show higher probability of emerging risk areas spreading toward the western parts of Tanzania from northeastern areas and decrease in the southern part of the country. Results presented here identified sites for consideration to guide surveillance and control interventions to reduce risk of RVF disease epidemics in Tanzania. A collaborative approach is recommended to develop and adapt climate-related disease control and prevention strategies.

CRISPR/Cas9—Advancing Orthopoxvirus Genome Editing for Vaccine and Vector Development

PubMed Central

Okoli, Arinze; Okeke, Malachy I.; Tryland, Morten; Moens, Ugo

2018-01-01

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated protein 9 (Cas9) technology is revolutionizing genome editing approaches. Its high efficiency, specificity, versatility, flexibility, simplicity and low cost have made the CRISPR/Cas9 system preferable to other guided site-specific nuclease-based systems such as TALENs (Transcription Activator-like Effector Nucleases) and ZFNs (Zinc Finger Nucleases) in genome editing of viruses. CRISPR/Cas9 is presently being applied in constructing viral mutants, preventing virus infections, eradicating proviral DNA, and inhibiting viral replication in infected cells. The successful adaptation of CRISPR/Cas9 to editing the genome of Vaccinia virus paves the way for its application in editing other vaccine/vector-relevant orthopoxvirus (OPXV) strains. Thus, CRISPR/Cas9 can be used to resolve some of the major hindrances to the development of OPXV-based recombinant vaccines and vectors, including sub-optimal immunogenicity; transgene and genome instability; reversion of attenuation; potential of spread of transgenes to wildtype strains and close contacts, which are important biosafety and risk assessment considerations. In this article, we review the published literature on the application of CRISPR/Cas9 in virus genome editing and discuss the potentials of CRISPR/Cas9 in advancing OPXV-based recombinant vaccines and vectors. We also discuss the application of CRISPR/Cas9 in combating viruses of clinical relevance, the limitations of CRISPR/Cas9 and the current strategies to overcome them. PMID:29361752

Associated patterns of insecticide resistance in field populations of malaria vectors across Africa.

PubMed

Hancock, Penelope A; Wiebe, Antoinette; Gleave, Katherine A; Bhatt, Samir; Cameron, Ewan; Trett, Anna; Weetman, David; Smith, David L; Hemingway, Janet; Coleman, Michael; Gething, Peter W; Moyes, Catherine L

2018-06-05

The development of insecticide resistance in African malaria vectors threatens the continued efficacy of important vector control methods that rely on a limited set of insecticides. To understand the operational significance of resistance we require quantitative information about levels of resistance in field populations to the suite of vector control insecticides. Estimation of resistance is complicated by the sparsity of observations in field populations, variation in resistance over time and space at local and regional scales, and cross-resistance between different insecticide types. Using observations of the prevalence of resistance in mosquito species from the Anopheles gambiae complex sampled from 1,183 locations throughout Africa, we applied Bayesian geostatistical models to quantify patterns of covariation in resistance phenotypes across different insecticides. For resistance to the three pyrethroids tested, deltamethrin, permethrin, and λ-cyhalothrin, we found consistent forms of covariation across sub-Saharan Africa and covariation between resistance to these pyrethroids and resistance to DDT. We found no evidence of resistance interactions between carbamate and organophosphate insecticides or between these insecticides and those from other classes. For pyrethroids and DDT we found significant associations between predicted mean resistance and the observed frequency of kdr mutations in the Vgsc gene in field mosquito samples, with DDT showing the strongest association. These results improve our capacity to understand and predict resistance patterns throughout Africa and can guide the development of monitoring strategies. Copyright © 2018 the Author(s). Published by PNAS.

Lack of Trypanosoma cruzi Infection in Urban Roof Rats (Rattus rattus) at a Texas Facility Housing Naturally Infected Nonhuman Primates

PubMed Central

Hodo, Carolyn L; Bertolini, Nicole R; Bernal, John C; VandeBerg, John L; Hamer, Sarah A

2017-01-01

The protozoan parasite Trypanosoma cruzi causes Chagas disease, uses kissing bugs as a vector, and is maintained in nature by a variety of wildlife reservoirs. Many natural cases of Chagas disease have been reported in NHP at facilities across the southern United States, where infected vectors and wildlife occur. Infection of NHP with T. cruzi can diminish their value as research models and lead to health problems and death. Identifying the modes of transmission and role of wildlife reservoirs in these facilities is therefore critical to guide interventions to reduce transmission. Here we investigated the role of roof rats (Rattus rattus), the most abundant nuisance species at a primate facility in San Antonio, in the maintenance and transmission of T. cruzi. The hearts and blood from the carcasses of the 145 rats collected underwent 2 independent PCR assays for detection of T. cruzi and other trypanosomes. The 145 hearts and 61 blood samples were all negative for T. cruzi. This population sample of 145 subjects would allow the detection of disease prevalence of 0.020 with a confidence level of 95%. The limited active vector surveillance efforts by our team combined with passive surveillance by facility personnel yielded no kissing bugs during the study period. Our results suggest that roof rats are unlikely to be important local reservoirs of T. cruzi at this facility. Further investigation of transmission dynamics across multiple years and more comprehensive vector surveillance is warranted. PMID:28905716

Lack of Trypanosoma cruzi Infection in Urban Roof Rats (Rattus rattus) at a Texas Facility Housing Naturally Infected Nonhuman Primates.

PubMed

Hodo, Carolyn L; Bertolini, Nicole R; Bernal, John C; VandeBerg, John L; Hamer, Sarah A

2017-01-01

The protozoan parasite Trypanosoma cruzi causes Chagas disease, uses kissing bugs as a vector, and is maintained in nature by a variety of wildlife reservoirs. Many natural cases of Chagas disease have been reported in NHP at facilities across the southern United States, where infected vectors and wildlife occur. Infection of NHP with T. cruzi can diminish their value as research models and lead to health problems and death. Identifying the modes of transmission and role of wildlife reservoirs in these facilities is therefore critical to guide interventions to reduce transmission. Here we investigated the role of roof rats (Rattus rattus), the most abundant nuisance species at a primate facility in San Antonio, in the maintenance and transmission of T. cruzi. The hearts and blood from the carcasses of the 145 rats collected underwent 2 independent PCR assays for detection of T. cruzi and other trypanosomes. The 145 hearts and 61 blood samples were all negative for T. cruzi. This population sample of 145 subjects would allow the detection of disease prevalence of 0.020 with a confidence level of 95%. The limited active vector surveillance efforts by our team combined with passive surveillance by facility personnel yielded no kissing bugs during the study period. Our results suggest that roof rats are unlikely to be important local reservoirs of T. cruzi at this facility. Further investigation of transmission dynamics across multiple years and more comprehensive vector surveillance is warranted.

Fuzzy inference enhanced information recovery from digital PIV using cross-correlation combined with particle tracking

NASA Technical Reports Server (NTRS)

Wernet, Mark P.

1995-01-01

Particle Image Velocimetry provides a means of measuring the instantaneous 2-component velocity field across a planar region of a seeded flowfield. In this work only two camera, single exposure images are considered where both cameras have the same view of the illumination plane. Two competing techniques which yield unambiguous velocity vector direction information have been widely used for reducing the single exposure, multiple image data: cross-correlation and particle tracking. Correlation techniques yield averaged velocity estimates over subregions of the flow, whereas particle tracking techniques give individual particle velocity estimates. The correlation technique requires identification of the correlation peak on the correlation plane corresponding to the average displacement of particles across the subregion. Noise on the images and particle dropout contribute to spurious peaks on the correlation plane, leading to misidentification of the true correlation peak. The subsequent velocity vector maps contain spurious vectors where the displacement peaks have been improperly identified. Typically these spurious vectors are replaced by a weighted average of the neighboring vectors, thereby decreasing the independence of the measurements. In this work fuzzy logic techniques are used to determine the true correlation displacement peak even when it is not the maximum peak on the correlation plane, hence maximizing the information recovery from the correlation operation, maintaining the number of independent measurements and minimizing the number of spurious velocity vectors. Correlation peaks are correctly identified in both high and low seed density cases. The correlation velocity vector map can then be used as a guide for the particle tracking operation. Again fuzzy logic techniques are used, this time to identify the correct particle image pairings between exposures to determine particle displacements, and thus velocity. The advantage of this technique is the improved spatial resolution which is available from the particle tracking operation. Particle tracking alone may not be possible in the high seed density images typically required for achieving good results from the correlation technique. This two staged approach offers a velocimetric technique capable of measuring particle velocities with high spatial resolution over a broad range of seeding densities.

Microsimulation Modeling for Health Decision Sciences Using R: A Tutorial.

PubMed

Krijkamp, Eline M; Alarid-Escudero, Fernando; Enns, Eva A; Jalal, Hawre J; Hunink, M G Myriam; Pechlivanoglou, Petros

2018-04-01

Microsimulation models are becoming increasingly common in the field of decision modeling for health. Because microsimulation models are computationally more demanding than traditional Markov cohort models, the use of computer programming languages in their development has become more common. R is a programming language that has gained recognition within the field of decision modeling. It has the capacity to perform microsimulation models more efficiently than software commonly used for decision modeling, incorporate statistical analyses within decision models, and produce more transparent models and reproducible results. However, no clear guidance for the implementation of microsimulation models in R exists. In this tutorial, we provide a step-by-step guide to build microsimulation models in R and illustrate the use of this guide on a simple, but transferable, hypothetical decision problem. We guide the reader through the necessary steps and provide generic R code that is flexible and can be adapted for other models. We also show how this code can be extended to address more complex model structures and provide an efficient microsimulation approach that relies on vectorization solutions.

Methods for multiple-telescope beam imaging and guiding in the near-infrared

NASA Astrophysics Data System (ADS)

Anugu, N.; Amorim, A.; Gordo, P.; Eisenhauer, F.; Pfuhl, O.; Haug, M.; Wieprecht, E.; Wiezorrek, E.; Lima, J.; Perrin, G.; Brandner, W.; Straubmeier, C.; Le Bouquin, J.-B.; Garcia, P. J. V.

2018-05-01

Atmospheric turbulence and precise measurement of the astrometric baseline vector between any two telescopes are two major challenges in implementing phase-referenced interferometric astrometry and imaging. They limit the performance of a fibre-fed interferometer by degrading the instrument sensitivity and the precision of astrometric measurements and by introducing image reconstruction errors due to inaccurate phases. A multiple-beam acquisition and guiding camera was built to meet these challenges for a recently commissioned four-beam combiner instrument, GRAVITY, at the European Southern Observatory Very Large Telescope Interferometer. For each telescope beam, it measures (a) field tip-tilts by imaging stars in the sky, (b) telescope pupil shifts by imaging pupil reference laser beacons installed on each telescope using a 2 × 2 lenslet and (c) higher-order aberrations using a 9 × 9 Shack-Hartmann. The telescope pupils are imaged to provide visual monitoring while observing. These measurements enable active field and pupil guiding by actuating a train of tip-tilt mirrors placed in the pupil and field planes, respectively. The Shack-Hartmann measured quasi-static aberrations are used to focus the auxiliary telescopes and allow the possibility of correcting the non-common path errors between the adaptive optics systems of the unit telescopes and GRAVITY. The guiding stabilizes the light injection into single-mode fibres, increasing sensitivity and reducing the astrometric and image reconstruction errors. The beam guiding enables us to achieve an astrometric error of less than 50 μas. Here, we report on the data reduction methods and laboratory tests of the multiple-beam acquisition and guiding camera and its performance on-sky.

Magnetic guide-wire navigation in pulmonary and systemic arterial catheterization: initial experience in pigs.

PubMed

Grosse-Wortmann, Lars; Grabitz, Ralf; Seghaye, Marie-Christine

2007-04-01

Cardiovascular catheterization can be challenging whenever a stenosis or an abnormal vascular course interferes with probing the target vessel. This study addresses the feasibility of navigating a guide wire with a magnetic tip by an external magnetic field through pulmonary and systemic arteries in an experimental porcine model. We investigated six piglets using magnetic guide-wire navigation. Two pulmonary arteriograms were taken from different angles in order to reconstruct the three-dimensional vessel anatomy. A computer interface then calculated three-dimensional coordinates for the vessel in space. Using these coordinates, two external magnets were positioned to create magnetic vectors along the expected vessel course. Magnetically enabled guide wires were then navigated into the vessels using the magnetic field to orient the guide-wire tips. Aortic and renal branches were addressed in a similar fashion. Difficulty in reaching the target vessel was reflected by the number of attempts that were necessary. After 10 failed attempts, the maneuver was recorded to have failed. Thirty-five of 37 (94.6%) arteries with branches at acute angles were reached successfully using magnetic navigation. In two pigs, the left upper lobe artery could not be probed. Peripheral arteries of small diameter were easier to reach than large central arteries, requiring less attempts. Magnetic guide-wire navigation is feasible in the arteries of the lungs, the head and neck, and the kidneys. It is particularly useful in entering small arterial branches at acute angles and may facilitate interventional therapy in a variety of vascular diseases in children and adults.

Preparation of Titanium nitride nanomaterials for electrode and application in energy storage

NASA Astrophysics Data System (ADS)

Tang, Shun; Cheng, Qi; Zhao, Jinxing; Liang, Jiyuan; Liu, Chang; Lan, Qian; Cao, Yuan-Cheng; Liu, Jiyan

The Titanium nitride was made by the carbamide and titanic chloride precursors. XRD results indicate that the precursor ratio N:Ti 3:1 leads to higher crystallinity. SEM and EDX demonstrated that Ti and N elements were distributed uniformly with the ratio of 1:1. The TiN used as the electrode material for supercapacitor was also studied. The specific capacities were changed from 407 F.g-1 to 385 F.g-1, 364 F.g-1 and 312 F.g-1, when the current densities were changed from 1 A.g-1 to 2 A.g-1, 5 A.g-1 and 10 A.g-1, respectively. Chronopotentiometry tests showed high coulombic efficiency. Cycling performance of the TiN electrode was evaluated by CV at a scanning rate of 50 mV.s-1 for 20,000 cycles and there was about 9.8% loss. These results indicate that TiN is a promising electrode material for the supercapacitors.

What Shapes the Phylogenetic Structure of Anuran Communities in a Seasonal Environment? The Influence of Determinism at Regional Scale to Stochasticity or Antagonistic Forces at Local Scale

PubMed Central

Ferreira, Vanda Lúcia; Strüssmann, Christine; Tomas, Walfrido Moraes

2015-01-01

Ecological communities are structured by both deterministic and stochastic processes. We investigated phylogenetic patterns at regional and local scales to understand the influences of seasonal processes in shaping the structure of anuran communities in the southern Pantanal wetland, Brazil. We assessed the phylogenetic structure at different scales, using the Net Relatedness Index (NRI), the Nearest Taxon Index (NTI), and phylobetadiversity indexes, as well as a permutation test, to evaluate the effect of seasonality. The anuran community was represented by a non-random set of species with a high degree of phylogenetic relatedness at the regional scale. However, at the local scale the phylogenetic structure of the community was weakly related with the seasonality of the system, indicating that oriented stochastic processes (e.g. colonization, extinction and ecological drift) and/or antagonist forces drive the structure of such communities in the southern Pantanal. PMID:26102202

What Shapes the Phylogenetic Structure of Anuran Communities in a Seasonal Environment? The Influence of Determinism at Regional Scale to Stochasticity or Antagonistic Forces at Local Scale.

PubMed

Martins, Clarissa de Araújo; Roque, Fabio de Oliveira; Santos, Bráulio A; Ferreira, Vanda Lúcia; Strüssmann, Christine; Tomas, Walfrido Moraes

2015-01-01

Ecological communities are structured by both deterministic and stochastic processes. We investigated phylogenetic patterns at regional and local scales to understand the influences of seasonal processes in shaping the structure of anuran communities in the southern Pantanal wetland, Brazil. We assessed the phylogenetic structure at different scales, using the Net Relatedness Index (NRI), the Nearest Taxon Index (NTI), and phylobetadiversity indexes, as well as a permutation test, to evaluate the effect of seasonality. The anuran community was represented by a non-random set of species with a high degree of phylogenetic relatedness at the regional scale. However, at the local scale the phylogenetic structure of the community was weakly related with the seasonality of the system, indicating that oriented stochastic processes (e.g. colonization, extinction and ecological drift) and/or antagonist forces drive the structure of such communities in the southern Pantanal.

Inhibition of CRISPR/Cas9-Mediated Genome Engineering by a Type I Interferon-Induced Reduction in Guide RNA Expression.

PubMed

Machitani, Mitsuhiro; Sakurai, Fuminori; Wakabayashi, Keisaku; Nakatani, Kosuke; Takayama, Kazuo; Tachibana, Masashi; Mizuguchi, Hiroyuki

2017-01-01

Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated genome engineering technology is a powerful tool for generation of cells and animals with engineered mutations in their genomes. In order to introduce the CRISPR/Cas9 system into target cells, nonviral and viral vectors are often used; however, such vectors trigger innate immune responses associated with production of type I interferons (IFNs). We have recently demonstrated that type I IFNs inhibit short-hairpin RNA-mediated gene silencing, which led us to hypothesize that type I IFNs may also inhibit CRISPR/Cas9-mediated genome mutagenesis. Here we investigated this hypothesis. A single-strand annealing assay using a reporter plasmid demonstrated that CRISPR/Cas9-mediated cleavage efficiencies of the target double-stranded DNA were significantly reduced by IFNα. A mismatch recognition nuclease-dependent genotyping assay also demonstrated that IFNα reduced insertion or deletion (indel) mutation levels by approximately half. Treatment with IFNα did not alter Cas9 protein expression levels, whereas the copy numbers of guide RNA (gRNA) were significantly reduced by IFNα stimulation. These results indicate that type I IFNs significantly reduce gRNA expression levels following introduction of the CRISPR/Cas9 system in the cells, leading to a reduction in the efficiencies of CRISPR/Cas9-mediated genome mutagenesis. Our findings provide important clues for the achievement of efficient genome engineering using the CRISPR/Cas9 system.

Comparison of five-axis milling and rapid prototyping for implant surgical templates.

PubMed

Park, Ji-Man; Yi, Tae-Kyoung; Koak, Jai-Young; Kim, Seong-Kyoon; Park, Eun-Jin; Heo, Seong-Joo

2014-01-01

This study aims to compare and evaluate the accuracy of surgical templates fabricated using coordinate synchronization processing with five-axis milling and design-related processing with rapid prototyping (RP). Master phantoms with 10 embedded gutta-percha cylinders hidden under artificial gingiva were fabricated and imaged using cone beam computed tomography. Vectors of the hidden cylinders were extracted and transferred to those of the planned implants through reverse engineering using virtual planning software. An RP-produced template was fabricated by stereolithography in photopolymer at the RP center according to planned data. Metal sleeves were bonded after holes were bored (group RP). For the milled template, milling coordinates were synchronized using the conversion process for the coordinate synchronization platform located on the model's bottom. Metal bushings were set on holes milled on the five-axis milling machine, on which the model was fixed through the coordinate synchronization plate, and the framework was constructed on the model using orthodontic resin (group CS). A computed tomography image was taken with templates firmly fixed on models using anchor pins (RP) or anchor screws (CS). The accuracy was analyzed via reverse engineering. Differences between the two groups were compared by repeated measures two-factor analysis. From the reverse-engineered image of the template on the experimental model, RP-produced templates showed significantly larger deviations than did milled surgical guides. Maximum deviations of the group RP were 1.58 mm (horizontal), 1.68 mm (vertical), and 8.51 degrees (angular); those of the group CS were 0.68 mm (horizontal), 0.41 mm (vertical), and 3.23 degrees (angular). A comparison of milling and RP template production methods showed that a vector-milled surgical guide had significantly smaller deviations than did an RP-produced template. The accuracy of computer-guided milled surgical templates was within the safety margin of previous studies.

Broad-host-range vector system for synthetic biology and biotechnology in cyanobacteria

PubMed Central

Taton, Arnaud; Unglaub, Federico; Wright, Nicole E.; Zeng, Wei Yue; Paz-Yepes, Javier; Brahamsha, Bianca; Palenik, Brian; Peterson, Todd C.; Haerizadeh, Farzad; Golden, Susan S.; Golden, James W.

2014-01-01

Inspired by the developments of synthetic biology and the need for improved genetic tools to exploit cyanobacteria for the production of renewable bioproducts, we developed a versatile platform for the construction of broad-host-range vector systems. This platform includes the following features: (i) an efficient assembly strategy in which modules released from 3 to 4 donor plasmids or produced by polymerase chain reaction are assembled by isothermal assembly guided by short GC-rich overlap sequences. (ii) A growing library of molecular devices categorized in three major groups: (a) replication and chromosomal integration; (b) antibiotic resistance; (c) functional modules. These modules can be assembled in different combinations to construct a variety of autonomously replicating plasmids and suicide plasmids for gene knockout and knockin. (iii) A web service, the CYANO-VECTOR assembly portal, which was built to organize the various modules, facilitate the in silico construction of plasmids, and encourage the use of this system. This work also resulted in the construction of an improved broad-host-range replicon derived from RSF1010, which replicates in several phylogenetically distinct strains including a new experimental model strain Synechocystis sp. WHSyn, and the characterization of nine antibiotic cassettes, four reporter genes, four promoters, and a ribozyme-based insulator in several diverse cyanobacterial strains. PMID:25074377

Environmental and social-demographic predictors of the southern house mosquito Culex quinquefasciatus in New Orleans, Louisiana.

PubMed

Moise, Imelda K; Riegel, Claudia; Muturi, Ephantus J

2018-04-17

Understanding the major predictors of disease vectors such as mosquitoes can guide the development of effective and timely strategies for mitigating vector-borne disease outbreaks. This study examined the influence of selected environmental, weather and sociodemographic factors on the spatial and temporal distribution of the southern house mosquito Culex quinquefasciatus Say in New Orleans, Louisiana, USA. Adult mosquitoes were collected over a 4-year period (2006, 2008, 2009 and 2010) using CDC gravid traps. Socio-demographic predictors were obtained from the United States Census Bureau, 2005-2009 American Community Survey and the City of New Orleans Department of Code Enforcement. Linear mixed effects models and ERDAS image processing software were used for statistical analysis and image processing. Only two of the 22 predictors examined were significant predictors of Cx. quinquefasciatus abundance. Mean temperature during the week of mosquito collection was positively associated with Cx. quinquefasciatus abundance while developed high intensity areas were negatively associated with Cx. quinquefasciatus abundance. The findings of this study illustrate the power and utility of integrating biophysical and sociodemographic data using GIS analysis to identify the biophysical and sociodemographic processes that increase the risk of vector mosquito abundance. This knowledge can inform development of accurate predictive models that ensure timely implementation of mosquito control interventions.

Theories of Matter, Space and Time; Classical theories

NASA Astrophysics Data System (ADS)

Evans, N.; King, S. F.

2017-12-01

This book and its sequel ('Theories of Matter Space and Time: Quantum Theories') are taken from third and fourth year undergraduate Physics courses at Southampton University, UK. The aim of both books is to move beyond the initial courses in classical mechanics, special relativity, electromagnetism, and quantum theory to more sophisticated views of these subjects and their interdependence. The goal is to guide undergraduates through some of the trickier areas of theoretical physics with concise analysis while revealing the key elegance of each subject. The first chapter introduces the key areas of the principle of least action, an alternative treatment of Newtownian dynamics, that provides new understanding of conservation laws. In particular, it shows how the formalism evolved from Fermat's principle of least time in optics. The second introduces special relativity leading quickly to the need and form of four-vectors. It develops four-vectors for all kinematic variables and generalize Newton's second law to the relativistic environment; then returns to the principle of least action for a free relativistic particle. The third chapter presents a review of the integral and differential forms of Maxwell's equations before massaging them to four-vector form so that the Lorentz boost properties of electric and magnetic fields are transparent. Again, it then returns to the action principle to formulate minimal substitution for an electrically charged particle.

Taiwan's Travel and Border Health Measures in Response to Zika

PubMed Central

Ho, Li-Li; Tsai, Yu-Hui; Lee, Wang-Ping; Liao, Szu-Tsai; Wu, Li-Gin

2017-01-01

Zika virus has recently emerged as a worldwide public health concern. Travel and border health measures stand as one of the main strategies and frontline defenses in responding to international epidemics. As of October 31, 2016, Taiwan has reported 13 imported cases, 5 of which were detected through routine entry screening and active monitoring at international airports. This article shares Taiwan's disease surveillance activities at designated points of entry and travel and border health measures in response to Zika. The Taiwan government collaborates with its tourism industry to disseminate information about precautionary measures and encourages tour guides to report suspected individuals or events to activate early response measures. Taiwan also engages in vector control activities at points of entry, including targeting aircraft from countries where vector-borne diseases are endemic, implementing mosquito sweep measures, and collecting vector surveillance data. In future emerging and reemerging disease events, entry surveillance at designated points of entry may enable early detection of diseases of international origin and more rapid activation of public health preparedness activities and international collaboration. Taiwan will continue to maximize border and travel health measures in compliance with IHR (2005) requirements, which rely on continued risk assessment, practical implementation activities, and engagement with all stakeholders. PMID:28418744

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

Kurt Derr; Milos Manic

Location Based Services (LBS), context aware applications, and people and object tracking depend on the ability to locate mobile devices, also known as localization, in the wireless landscape. Localization enables a diverse set of applications that include, but are not limited to, vehicle guidance in an industrial environment, security monitoring, self-guided tours, personalized communications services, resource tracking, mobile commerce services, guiding emergency workers during fire emergencies, habitat monitoring, environmental surveillance, and receiving alerts. This paper presents a new neural network approach (LENSR) based on a competitive topological Counter Propagation Network (CPN) with k-nearest neighborhood vector mapping, for indoor location estimationmore » based on received signal strength. The advantage of this approach is both speed and accuracy. The tested accuracy of the algorithm was 90.6% within 1 meter and 96.4% within 1.5 meters. Several approaches for location estimation using WLAN technology were reviewed for comparison of results.« less

Intelligent vision guide for automatic ventilation grommet insertion into the tympanic membrane.

PubMed

Gao, Wenchao; Tan, Kok Kiong; Liang, Wenyu; Gan, Chee Wee; Lim, Hsueh Yee

2016-03-01

Otitis media with effusion is a worldwide ear disease. The current treatment is to surgically insert a ventilation grommet into the tympanic membrane. A robotic device allowing automatic grommet insertion has been designed in a previous study; however, the part of the membrane where the malleus bone is attached to the inner surface is to be avoided during the insertion process. This paper proposes a synergy of optical flow technique and a gradient vector flow active contours algorithm to achieve an online tracking of the malleus under endoscopic vision, to guide the working channel to move efficiently during the surgery. The proposed method shows a more stable and accurate tracking performance than the current tracking methods in preclinical tests. With satisfactory tracking results, vision guidance of a suitable insertion spot can be provided to the device to perform the surgery in an automatic way. Copyright © 2015 John Wiley & Sons, Ltd.

Kinetic and microstructural study of titanium nitride deposited by laser chemical vapor deposition

NASA Astrophysics Data System (ADS)

Egland, Keith Maynard

Titanium nitride (TiN) films were deposited onto Ti-6Al-4V substrates by laser chemical vapor deposition using a cw COsb2 laser and TiClsb4,\\ Nsb2, and Hsb2 reactant gases. In-situ laser induced fluorescence (LIF) and multi-wavelength pyrometry determined relative titanium gas phase atomic number density and deposition temperature, respectively. Deposited films were yellow to gold in color. Transmission electron microscopy on one sample revealed a face-centered cubic structure with a lattice parameter (0.4237 nm) expected for TiN. Auger electron spectroscopy found substoichiometric compositions with a N/Ti ratio between 0.7 and 0.9. Variables decreasing grain size (lower temperature, higher TiClsb4 input) decreased the N/Ti ratio. Higher Nsb2 input increased stoichiometry, while larger Hsb2 input decreased stoichiometry. The deposit substoichiometry is believed to be caused by diffusion of nitrogen through TiN grain boundaries to the titanium alloy substrate. The morphology starts as a dense polycrystalline structure evolving into a columnar structure having facets or nodules at the surface with crystallite sizes ranging from 10-1000 nm. TiClsb4 input had a inverse correlation with crystallite size, while Nsb2:Hsb2 ratio had minimal effect; the crystallite size (G) varied exponentially with temperature (T) for a given irradiation time, i.e., G = C exp (-28000/T), with constant C reflecting substrate roughness and gas composition. Microhardness tests revealed substrate contributions; nevertheless, films appeared to have a minimum hardness of 2000 Hsbv. The deposition apparent activation energy was calculated as 122 ± 9 kJ/mole using growth rates measured by film height and 117 ± 23 kJ/mole using growth rates measured by LIF signals. This puts the process in the surface kinetic growth regime over the temperature range 1370-1610 K. Above Nsb2 and Hsb2 levels of 1.25% and below TiClsb4 input of 4.5%, the growth rate has a half-order dependence on nitrogen and a linear dependence on hydrogen and is approximated by$r = {{kPsb{TiClsb4}Psb{Hsb2}Psbsp{Nsb2}{1/2}exp≤ft({{-}Esb{a}/ {RT}right)}/{1 + Psb{Ar}}}}.Since nitrogen positively affects growth rate (when added to a TiClsb4+Hsb2 mixture), stepwise reduction of TiClsb4 to Ti by hydrogen does not occur. NHsb{x} complexes are clearly involved in the growth mechanism; a likely combination of rate determining steps is the formation of NH and the initial reduction of TiClsb4$ by hydrogen.

Use of the flight simulator in the design of a STOL research aircraft.

NASA Technical Reports Server (NTRS)

Spitzer, R. E.; Rumsey, P. C.; Quigley, H. C.

1972-01-01

Piloted simulator tests on the NASA-Ames Flight Simulator for Advanced Aircraft motion base played a major role in guiding the design of the Modified C-8A 'Buffalo' augmentor wing jet flap STOL research airplane. Design results are presented for the flight control systems, lateral-directional SAS, hydraulic systems, and engine and thrust vector controls. Emphasis is given to lateral control characteristics on STOL landing approach, engine-out control and recovery techniques in the powered-lift regime, and operational flight procedures which affected airplane design.

A User’s Guide to the SEVP (Stabilized Error Vector Propagation) Solver: An Efficient Direct Solver for Elliptic Partial Differential Equations

DTIC Science & Technology

1989-04-13

19 5.3 The Solution, BSM2 , BSM3 . ...................................... 21 6. Description of test example...are modified for the boundary conditions. The sections on the preprocessor subroutine BSM1 and the solution subroutines BSM2 , BSM3 may be skipped by...interior row j = N-1 to the solution error C5 on the second row j = IE(2) of the last block, so that P3 = C5 R31 (5.18) 20 5.3 The Solution. BSM2

University Physics, Study Guide, Revised Edition

NASA Astrophysics Data System (ADS)

Benson, Harris

1996-01-01

Partial table of contents: Vectors. One-Dimensional Kinematics. Particle Dynamics II. Work and Energy. Linear Momentum. Systems of Particles. Angular Momentum and Statics. Gravitation. Solids and Fluids. Oscillations. Mechanical Waves. Sound. First Law of Thermodynamics. Kinetic Theory. Entropy and the Second Law of Thermodynamics. Electrostatics. The Electric Field. Gauss's Law. Electric Potential. Current and Resistance. The Magnetic Field. Sources of the Magnetic Field. Electromagnetic Induction. Light: Reflection and Refraction. Lenses and Optical Instruments. Wave Optics I. Special Relativity. Early Quantum Theory. Nuclear Physics. Appendices. Answers to Odd-Numbered Exercises and Problems. Index.

Aedes aegypti (L.) in Latin American and Caribbean region: With growing evidence for vector adaptation to climate change?

PubMed

Chadee, Dave D; Martinez, Raymond

2016-04-01

Within Latin America and the Caribbean region the impact of climate change has been associated with the effects of rainfall and temperature on seasonal outbreaks of dengue but few studies have been conducted on the impacts of climate on the behaviour and ecology of Aedes aegypti mosquitoes.This study was conducted to examine the adaptive behaviours currently being employed by A. aegypti mosquitoes exposed to the force of climate change in LAC countries. The literature on the association between climate and dengue incidence is small and sometimes speculative. Few laboratory and field studies have identified research gaps. Laboratory and field experiments were designed and conducted to better understand the container preferences, climate-associated-adaptive behaviour, ecology and the effects of different temperatures and light regimens on the life history of A. aegypti mosquitoes. A. aegypti adaptive behaviours and changes in container preferences demonstrate how complex dengue transmission dynamics is, in different ecosystems. The use of underground drains and septic tanks represents a major behaviour change identified and compounds an already difficult task to control A. aegypti populations. A business as usual approach will exacerbate the problem and lead to more frequent outbreaks of dengue and chikungunya in LAC countries unless both area-wide and targeted vector control approaches are adopted. The current evidence and the results from proposed transdisciplinary research on dengue within different ecosystems will help guide the development of new vector control strategies and foster a better understanding of climate change impacts on vector-borne disease transmission. Copyright © 2016 Elsevier B.V. All rights reserved.

Condition Assessment of Foundation Piles and Utility Poles Based on Guided Wave Propagation Using a Network of Tactile Transducers and Support Vector Machines

PubMed Central

Yu, Yang; Niederleithinger, Ernst; Li, Jianchun; Wiggenhauser, Herbert

2017-01-01

This paper presents a novel non-destructive testing and health monitoring system using a network of tactile transducers and accelerometers for the condition assessment and damage classification of foundation piles and utility poles. While in traditional pile integrity testing an impact hammer with broadband frequency excitation is typically used, the proposed testing system utilizes an innovative excitation system based on a network of tactile transducers to induce controlled narrow-band frequency stress waves. Thereby, the simultaneous excitation of multiple stress wave types and modes is avoided (or at least reduced), and targeted wave forms can be generated. The new testing system enables the testing and monitoring of foundation piles and utility poles where the top is inaccessible, making the new testing system suitable, for example, for the condition assessment of pile structures with obstructed heads and of poles with live wires. For system validation, the new system was experimentally tested on nine timber and concrete poles that were inflicted with several types of damage. The tactile transducers were excited with continuous sine wave signals of 1 kHz frequency. Support vector machines were employed together with advanced signal processing algorithms to distinguish recorded stress wave signals from pole structures with different types of damage. The results show that using fast Fourier transform signals, combined with principal component analysis as the input feature vector for support vector machine (SVM) classifiers with different kernel functions, can achieve damage classification with accuracies of 92.5% ± 7.5%. PMID:29258274

Performance of a novel micro force vector sensor and outlook into its biomedical applications

NASA Astrophysics Data System (ADS)

Meiss, Thorsten; Rossner, Tim; Minamisava Faria, Carlos; Völlmeke, Stefan; Opitz, Thomas; Werthschützky, Roland

2011-05-01

For the HapCath system, which provides haptic feedback of the forces acting on a guide wire's tip during vascular catheterization, very small piezoresistive force sensors of 200•200•640μm3 have been developed. This paper focuses on the characterization of the measurement performance and on possible new applications. Besides the determination of the dynamic measurement performance, special focus is put onto the results of the 3- component force vector calibration. This article addresses special advantageous characteristics of the sensor, but also the limits of applicability will be addressed. As for the special characteristics of the sensor, the second part of the article demonstrates new applications which can be opened up with the novel force sensor, like automatic navigation of medical or biological instruments without impacting surrounding tissue, surface roughness evaluation in biomedical systems, needle insertion with tactile or higher level feedback, or even building tactile hairs for artificial organisms.

Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

PubMed

Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

2014-05-01

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

Hamiltonian and Thermodynamic Modeling of Quantum Turbulence

NASA Astrophysics Data System (ADS)

Grmela, Miroslav

2010-10-01

The state variables in the novel model introduced in this paper are the fields playing this role in the classical Landau-Tisza model and additional fields of mass, entropy (or temperature), superfluid velocity, and gradient of the superfluid velocity, all depending on the position vector and another tree dimensional vector labeling the scale, describing the small-scale structure developed in 4He superfluid experiencing turbulent motion. The fluxes of mass, momentum, energy, and entropy in the position space as well as the fluxes of energy and entropy in scales, appear in the time evolution equations as explicit functions of the state variables and of their conjugates. The fundamental thermodynamic relation relating the fields to their conjugates is left in this paper undetermined. The GENERIC structure of the equations serves two purposes: (i) it guarantees that solutions to the governing equations, independently of the choice of the fundamental thermodynamic relation, agree with the observed compatibility with thermodynamics, and (ii) it is used as a guide in the construction of the novel model.

Polarized Kink Waves in Magnetic Elements: Evidence for Chromospheric Helical Waves

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

Stangalini, M.; Giannattasio, F.; Erdélyi, R.

In recent years, new high spatial resolution observations of the Sun's atmosphere have revealed the presence of a plethora of small-scale magnetic elements down to the resolution limit of the current cohort of solar telescopes (∼100–120 km on the solar photosphere). These small magnetic field concentrations, due to the granular buffeting, can support and guide several magnetohydrodynamic wave modes that would eventually contribute to the energy budget of the upper layers of the atmosphere. In this work, exploiting the high spatial and temporal resolution chromospheric data acquired with the Swedish 1 m Solar Telescope, and applying the empirical mode decompositionmore » technique to the tracking of the solar magnetic features, we analyze the perturbations of the horizontal velocity vector of a set of chromospheric magnetic elements. We find observational evidence that suggests a phase relation between the two components of the velocity vector itself, resulting in its helical motion.« less

Chico High School Students' Astrometric Observations of the Visual Double Star STF 1657

NASA Astrophysics Data System (ADS)

Ahiligwo, Jonelle; Bergamini, Clara; Berglund, Kallan; Bhardwaj, Mohit; Chelson, Spud; Costa, Amanda; Epis, Ashley; Grant, Azure; Osteen, Courtney; Reiner, Skyla; Rose, Adam; Schmidt, Emily; Sears, Forest; Sullivan-Hames, Maddie; Johnson, Jolyon

2012-01-01

In the spring of 2011, Chico Senior High School students participated in an astronomy seminar at the Gateway Science Museum, University of California, Chico. The observers used a Celestron NexStar 6 SE telescope and a Celestron MicroGuide eyepiece to determine the separation and position angle of the visual double star STF 1657. Observations were made in approximately one hour on the evening of May 1, 2011. The observers determined that the separation of STF 1657 was 22.1" and the position angle was 273.4&°. Seminar members then used the spectral type, parallax, and proper motion vectors of the two stars to determine if they are a line-of-sight optical pair or physically bound by gravity. Due to large errors in the parallax and the proper motion vector for the secondary star, the results were inconclusive. Through this experience, the students learned the skills needed to observe, analyze, and report on double stars.

Investigation of the Wave Propagation of Vector Modes of Light in a Spherically Symmetric Refractive Index Profile

NASA Astrophysics Data System (ADS)

Pozderac, Preston; Leary, Cody

We investigated the solutions to the Helmholtz equation in the case of a spherically symmetric refractive index using three different methods. The first method involves solving the Helmholtz equation for a step index profile and applying further constraints contained in Maxwell's equations. Utilizing these equations, we can simultaneously solve for the electric and magnetic fields as well as the allowed energies of photons propagating in this system. The second method applies a perturbative correction to these energies, which surfaces when deriving a Helmholtz type equation in a medium with an inhomogeneous refractive index. Applying first order perturbation theory, we examine how the correction term affects the energy of the photon. In the third method, we investigate the effects of the above perturbation upon solutions to the scalar Helmholtz equation, which are separable with respect to its polarization and spatial degrees of freedom. This work provides insights into the vector field structure of a photon guided by a glass microsphere.

Evaluation and rational design of guide RNAs for efficient CRISPR/Cas9-mediated mutagenesis in Ciona

PubMed Central

Gandhi, Shashank; Haeussler, Maximilian; Razy-Krajka, Florian; Christiaen, Lionel; Stolfi, Alberto

2017-01-01

The CRISPR/Cas9 system has emerged as an important tool for various genome engineering applications. A current obstacle to high throughput applications of CRISPR/Cas9 is the imprecise prediction of highly active single guide RNAs (sgRNAs). We previously implemented the CRISPR/Cas9 system to induce tissue-specific mutations in the tunicate Ciona. In the present study, we designed and tested 83 single guide RNA (sgRNA) vectors targeting 23 genes expressed in the cardiopharyngeal progenitors and surrounding tissues of Ciona embryo. Using high-throughput sequencing of mutagenized alleles, we identified guide sequences that correlate with sgRNA mutagenesis activity and used this information for the rational design of all possible sgRNAs targeting the Ciona transcriptome. We also describe a one-step cloning-free protocol for the assembly of sgRNA expression cassettes. These cassettes can be directly electroporated as unpurified PCR products into Ciona embryos for sgRNA expression in vivo, resulting in high frequency of CRISPR/Cas9-mediated mutagenesis in somatic cells of electroporated embryos. We found a strong correlation between the frequency of an Ebf loss-of-function phenotype and the mutagenesis efficacies of individual Ebf-targeting sgRNAs tested using this method. We anticipate that our approach can be scaled up to systematically design and deliver highly efficient sgRNAs for the tissue-specific investigation of gene functions in Ciona. PMID:28341547

Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

PubMed Central

Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines. PMID:25446819

Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

PubMed

Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of information. The Brighton Collaboration V3SWG template may also be useful as a guide to the evaluation of other recombinant viral vector vaccines. Copyright © 2014. Published by Elsevier Ltd.

Rapid construction of insulated genetic circuits via synthetic sequence-guided isothermal assembly

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

Torella, JP; Boehm, CR; Lienert, F

2013-12-28

In vitro recombination methods have enabled one-step construction of large DNA sequences from multiple parts. Although synthetic biological circuits can in principle be assembled in the same fashion, they typically contain repeated sequence elements such as standard promoters and terminators that interfere with homologous recombination. Here we use a computational approach to design synthetic, biologically inactive unique nucleotide sequences (UNSes) that facilitate accurate ordered assembly. Importantly, our designed UNSes make it possible to assemble parts with repeated terminator and insulator sequences, and thereby create insulated functional genetic circuits in bacteria and mammalian cells. Using UNS-guided assembly to construct repeating promoter-gene-terminatormore » parts, we systematically varied gene expression to optimize production of a deoxychromoviridans biosynthetic pathway in Escherichia coli. We then used this system to construct complex eukaryotic AND-logic gates for genomic integration into embryonic stem cells. Construction was performed by using a standardized series of UNS-bearing BioBrick-compatible vectors, which enable modular assembly and facilitate reuse of individual parts. UNS-guided isothermal assembly is broadly applicable to the construction and optimization of genetic circuits and particularly those requiring tight insulation, such as complex biosynthetic pathways, sensors, counters and logic gates.« less

Computational and experimental analysis of TMS-induced electric field vectors critical to neuronal activation

NASA Astrophysics Data System (ADS)

Krieg, Todd D.; Salinas, Felipe S.; Narayana, Shalini; Fox, Peter T.; Mogul, David J.

2015-08-01

Objective. Transcranial magnetic stimulation (TMS) represents a powerful technique to noninvasively modulate cortical neurophysiology in the brain. However, the relationship between the magnetic fields created by TMS coils and neuronal activation in the cortex is still not well-understood, making predictable cortical activation by TMS difficult to achieve. Our goal in this study was to investigate the relationship between induced electric fields and cortical activation measured by blood flow response. Particularly, we sought to discover the E-field characteristics that lead to cortical activation. Approach. Subject-specific finite element models (FEMs) of the head and brain were constructed for each of six subjects using magnetic resonance image scans. Positron emission tomography (PET) measured each subject’s cortical response to image-guided robotically-positioned TMS to the primary motor cortex. FEM models that employed the given coil position, orientation, and stimulus intensity in experimental applications of TMS were used to calculate the electric field (E-field) vectors within a region of interest for each subject. TMS-induced E-fields were analyzed to better understand what vector components led to regional cerebral blood flow (CBF) responses recorded by PET. Main results. This study found that decomposing the E-field into orthogonal vector components based on the cortical surface geometry (and hence, cortical neuron directions) led to significant differences between the regions of cortex that were active and nonactive. Specifically, active regions had significantly higher E-field components in the normal inward direction (i.e., parallel to pyramidal neurons in the dendrite-to-axon orientation) and in the tangential direction (i.e., parallel to interneurons) at high gradient. In contrast, nonactive regions had higher E-field vectors in the outward normal direction suggesting inhibitory responses. Significance. These results provide critical new understanding of the factors by which TMS induces cortical activation necessary for predictive and repeatable use of this noninvasive stimulation modality.

Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy.

PubMed

Tirados, Inaki; Esterhuizen, Johan; Kovacic, Vanja; Mangwiro, T N Clement; Vale, Glyn A; Hastings, Ian; Solano, Philippe; Lehane, Michael J; Torr, Steve J

2015-01-01

Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised.

Long-Term Effect of Gene Therapy on Leber’s Congenital Amaurosis

PubMed Central

Bainbridge, J.W.B.; Mehat, M.S.; Sundaram, V.; Robbie, S.J.; Barker, S.E.; Ripamonti, C.; Georgiadis, A.; Mowat, F.M.; Beattie, S.G.; Gardner, P.J.; Feathers, K.L.; Luong, V.A.; Yzer, S.; Balaggan, K.; Viswanathan, A.; de Ravel, T.J.L.; Casteels, I.; Holder, G.E.; Tyler, N.; Fitzke, F.W.; Weleber, R.G.; Nardini, M.; Moore, A.T.; Thompson, D.A.; Petersen-Jones, S.M.; Michaelides, M.; van den Born, L.I.; Stockman, A.; Smith, A.J.; Rubin, G.; Ali, R.R.

2015-01-01

BACKGROUND Mutations in RPE65 cause Leber’s congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. METHODS We performed a phase 1–2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. RESULTS Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. CONCLUSIONS Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.) PMID:25938638

Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy

PubMed Central

Kovacic, Vanja; Mangwiro, T. N. Clement; Vale, Glyn A.; Hastings, Ian; Solano, Philippe; Lehane, Michael J.; Torr, Steve J.

2015-01-01

Background Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. Methods and Findings The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. Interpretation The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised. PMID:26267814

Criteria for the prioritization of public health interventions for climate-sensitive vector-borne diseases in Quebec.

PubMed

Hongoh, Valerie; Gosselin, Pierre; Michel, Pascal; Ravel, André; Waaub, Jean-Philippe; Campagna, Céline; Samoura, Karim

2017-01-01

Prioritizing resources for optimal responses to an ever growing list of existing and emerging infectious diseases represents an important challenge to public health. In the context of climate change, there is increasing anticipated variability in the occurrence of infectious diseases, notably climate-sensitive vector-borne diseases. An essential step in prioritizing efforts is to identify what considerations and concerns to take into account to guide decisions and thus set disease priorities. This study was designed to perform a comprehensive review of criteria for vector-borne disease prioritization, assess their applicability in a context of climate change with a diverse cross-section of stakeholders in order to produce a baseline list of considerations to use in this decision-making context. Differences in stakeholder choices were examined with regards to prioritization of these criteria for research, surveillance and disease prevention and control objectives. A preliminary list of criteria was identified following a review of the literature. Discussions with stakeholders were held to consolidate and validate this list of criteria and examine their effects on disease prioritization. After this validation phase, a total of 21 criteria were retained. A pilot vector-borne disease prioritization exercise was conducted using PROMETHEE to examine the effects of the retained criteria on prioritization in different intervention domains. Overall, concerns expressed by stakeholders for prioritization were well aligned with categories of criteria identified in previous prioritization studies. Weighting by category was consistent between stakeholders overall, though some significant differences were found between public health and non-public health stakeholders. From this exercise, a general model for climate-sensitive vector-borne disease prioritization has been developed that can be used as a starting point for further public health prioritization exercises relating to research, surveillance, and prevention and control interventions in a context of climate change. Multi-stakeholder engagement in prioritization can help broaden the range of criteria taken into account, offer opportunities for early identification of potential challenges and may facilitate acceptability of any resulting decisions.

A data-driven approach of load monitoring on laminated composite plates using support vector machine

NASA Astrophysics Data System (ADS)

Gwon, Y. S.; Fekrmandi, H.

2018-03-01

In this study, the surface response to excitation method (SuRE) is investigated using a data-driven method for load monitoring on a laminated composite plate structure. The SuRE method is an emerging approach in ultrasonic wavebased structural health monitoring (SHM) field. In this method, a range of high-frequency, surface-guided waves are excited on the structure using piezoceramic elements. The waves propagate on the structure and interact with internal or surface damages. Initially, a baseline data of the intact structure is created by measuring the frequency transfer function between the excitation and sensing point. The integrity of structure is evaluated by monitoring changes in the frequency spectrums. The SuRE method has effectively been used for a variety of SHM applications including the detection of loose bolts, delamination in composite structures, internal corrosion in pipelines, and load and impact monitoring. Data obtained using the SuRE method was used for identifying the location of the applied load on a laminated composite plate using Support Vector Machine (SVM). A set of two piezoelectric elements were attached on the surface of the plate. A sweep excitation (150-250 kHz) generated surface-guided waves, and the transmitted waves were monitored at the sensory positions. The reference data set was measured simultaneously from the sensors. The plate was subjected to static loads while health monitoring data was being captured using the SuRE method. The confusion matrix indicated that the model classified correctly with up to 99.8% accuracy.

Accuracy of a cone beam computed tomography-guided surgical stent for orthodontic mini-implant placement.

PubMed

Yu, Jae-Jung; Kim, Gyu-Tae; Choi, Yong-Suk; Hwang, Eui-Hwan; Paek, Janghyun; Kim, Seong-Hun; Huang, John C

2012-03-01

To validate the accuracy of a cone-beam computed tomography (CBCT)-guided surgical stent for orthodontic mini-implant (OMI) placement by quantitatively evaluating the difference between CBCT-prescribed and actual position of mini-implants in preoperative and postoperative CBCT images. A surgical stent was fabricated using Teflon-Perfluoroalkoxy, which has appropriate biological x-ray attenuation properties. Polyvinylsiloxane impression material was used to secure the custom-made surgical stent onto swine mandibles. CBCT scanning was done with the stent in place to virtually plan mini-implants using a three-dimensional (3D) software program. An appropriate insertion point was determined using 3D reconstruction data, and the vertical and horizontal angulations were determined using four prescribed angles. A custom-designed surveyor was used to drill a guide hole within the surgical stent as prescribed on the CBCT images for insertion of 32 OMIs. The mandibles with a surgical stent in place were rescanned with CBCT to measure the deviations between the virtual planning data and surgical results. The difference between the prescribed and actual vertical angle was 1.01 ± 7.25, and the horizontal difference was 1.16 ± 6.08. The correlation coefficient confirms that there was no intrarater variability in either the horizontal (R  =  .97) or vertical (R  =  .74) vectors. The surgical stent in this study guides mini-implants to the prescribed position as planned in CBCT. Since the statistical difference was not significant, the surgical stent can be considered to be an accurate guide tool for mini-implant placement in clinical use.

Aztec user`s guide. Version 1

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

Hutchinson, S.A.; Shadid, J.N.; Tuminaro, R.S.

1995-10-01

Aztec is an iterative library that greatly simplifies the parallelization process when solving the linear systems of equations Ax = b where A is a user supplied n x n sparse matrix, b is a user supplied vector of length n and x is a vector of length n to be computed. Aztec is intended as a software tool for users who want to avoid cumbersome parallel programming details but who have large sparse linear systems which require an efficiently utilized parallel processing system. A collection of data transformation tools are provided that allow for easy creation of distributed sparsemore » unstructured matrices for parallel solution. Once the distributed matrix is created, computation can be performed on any of the parallel machines running Aztec: nCUBE 2, IBM SP2 and Intel Paragon, MPI platforms as well as standard serial and vector platforms. Aztec includes a number of Krylov iterative methods such as conjugate gradient (CG), generalized minimum residual (GMRES) and stabilized biconjugate gradient (BICGSTAB) to solve systems of equations. These Krylov methods are used in conjunction with various preconditioners such as polynomial or domain decomposition methods using LU or incomplete LU factorizations within subdomains. Although the matrix A can be general, the package has been designed for matrices arising from the approximation of partial differential equations (PDEs). In particular, the Aztec package is oriented toward systems arising from PDE applications.« less

User's guide to Model Viewer, a program for three-dimensional visualization of ground-water model results

USGS Publications Warehouse

Hsieh, Paul A.; Winston, Richard B.

2002-01-01

Model Viewer is a computer program that displays the results of three-dimensional groundwater models. Scalar data (such as hydraulic head or solute concentration) may be displayed as a solid or a set of isosurfaces, using a red-to-blue color spectrum to represent a range of scalar values. Vector data (such as velocity or specific discharge) are represented by lines oriented to the vector direction and scaled to the vector magnitude. Model Viewer can also display pathlines, cells or nodes that represent model features such as streams and wells, and auxiliary graphic objects such as grid lines and coordinate axes. Users may crop the model grid in different orientations to examine the interior structure of the data. For transient simulations, Model Viewer can animate the time evolution of the simulated quantities. The current version (1.0) of Model Viewer runs on Microsoft Windows 95, 98, NT and 2000 operating systems, and supports the following models: MODFLOW-2000, MODFLOW-2000 with the Ground-Water Transport Process, MODFLOW-96, MOC3D (Version 3.5), MODPATH, MT3DMS, and SUTRA (Version 2D3D.1). Model Viewer is designed to directly read input and output files from these models, thus minimizing the need for additional postprocessing. This report provides an overview of Model Viewer. Complete instructions on how to use the software are provided in the on-line help pages.

A Protocol for Multiple Gene Knockout in Mouse Small Intestinal Organoids Using a CRISPR-concatemer.

PubMed

Merenda, Alessandra; Andersson-Rolf, Amanda; Mustata, Roxana C; Li, Taibo; Kim, Hyunki; Koo, Bon-Kyoung

2017-07-12

CRISPR/Cas9 technology has greatly improved the feasibility and speed of loss-of-function studies that are essential in understanding gene function. In higher eukaryotes, paralogous genes can mask a potential phenotype by compensating the loss of a gene, thus limiting the information that can be obtained from genetic studies relying on single gene knockouts. We have developed a novel, rapid cloning method for guide RNA (gRNA) concatemers in order to create multi-gene knockouts following a single round of transfection in mouse small intestinal organoids. Our strategy allows for the concatemerization of up to four individual gRNAs into a single vector by performing a single Golden Gate shuffling reaction with annealed gRNA oligos and a pre-designed retroviral vector. This allows either the simultaneous knockout of up to four different genes, or increased knockout efficiency following the targeting of one gene by multiple gRNAs. In this protocol, we show in detail how to efficiently clone multiple gRNAs into the retroviral CRISPR-concatemer vector and how to achieve highly efficient electroporation in intestinal organoids. As an example, we show that simultaneous knockout of two pairs of genes encoding negative regulators of the Wnt signaling pathway (Axin1/2 and Rnf43/Znrf3) renders intestinal organoids resistant to the withdrawal of key growth factors.

Robust RNAi enhancement via human Argonaute-2 overexpression from plasmids, viral vectors and cell lines

PubMed Central

Börner, Kathleen; Niopek, Dominik; Cotugno, Gabriella; Kaldenbach, Michaela; Pankert, Teresa; Willemsen, Joschka; Zhang, Xian; Schürmann, Nina; Mockenhaupt, Stefan; Serva, Andrius; Hiet, Marie-Sophie; Wiedtke, Ellen; Castoldi, Mirco; Starkuviene, Vytaute; Erfle, Holger; Gilbert, Daniel F.; Bartenschlager, Ralf; Boutros, Michael; Binder, Marco; Streetz, Konrad; Kräusslich, Hans-Georg; Grimm, Dirk

2013-01-01

As the only mammalian Argonaute protein capable of directly cleaving mRNAs in a small RNA-guided manner, Argonaute-2 (Ago2) is a keyplayer in RNA interference (RNAi) silencing via small interfering (si) or short hairpin (sh) RNAs. It is also a rate-limiting factor whose saturation by si/shRNAs limits RNAi efficiency and causes numerous adverse side effects. Here, we report a set of versatile tools and widely applicable strategies for transient or stable Ago2 co-expression, which overcome these concerns. Specifically, we engineered plasmids and viral vectors to co-encode a codon-optimized human Ago2 cDNA along with custom shRNAs. Furthermore, we stably integrated this Ago2 cDNA into a panel of standard human cell lines via plasmid transfection or lentiviral transduction. Using various endo- or exogenous targets, we demonstrate the potential of all three strategies to boost mRNA silencing efficiencies in cell culture by up to 10-fold, and to facilitate combinatorial knockdowns. Importantly, these robust improvements were reflected by augmented RNAi phenotypes and accompanied by reduced off-targeting effects. We moreover show that Ago2/shRNA-co-encoding vectors can enhance and prolong transgene silencing in livers of adult mice, while concurrently alleviating hepatotoxicity. Our customizable reagents and avenues should broadly improve future in vitro and in vivo RNAi experiments in mammalian systems. PMID:24049077

Radio-guided sentinel lymph node identification by lymphoscintigraphy fused with an anatomical vector profile: clinical applications.

PubMed

Niccoli Asabella, A; Antonica, F; Renna, M A; Rubini, D; Notaristefano, A; Nicoletti, A; Rubini, G

2013-12-01

To develop a method to fuse lymphoscintigraphic images with an adaptable anatomical vector profile and to evaluate its role in the clinical practice. We used Adobe Illustrator CS6 to create different vector profiles, we fused those profiles, using Adobe Photoshop CS6, with lymphoscintigraphic images of the patient. We processed 197 lymphoscintigraphies performed in patients with cutaneous melanomas, breast cancer or delayed lymph drainage. Our models can be adapted to every patient attitude or position and contain different levels of anatomical details ranging from external body profiles to the internal anatomical structures like bones, muscles, vessels, and lymph nodes. If needed, more new anatomical details can be added and embedded in the profile without redrawing them, saving a lot of time. Details can also be easily hidden, allowing the physician to view only relevant information and structures. Fusion times are about 85 s. The diagnostic confidence of the observers increased significantly. The validation process showed a slight shift (mean 4.9 mm). We have created a new, practical, inexpensive digital technique based on commercial software for fusing lymphoscintigraphic images with built-in anatomical reference profiles. It is easily reproducible and does not alter the original scintigraphic image. Our method allows a more meaningful interpretation of lymphoscintigraphies, an easier recognition of the anatomical site and better lymph node dissection planning.

Lessons from HIV-1 vaccine efficacy trials.

PubMed

Excler, Jean-Louis; Michael, Nelson L

2016-11-01

Only four HIV-1 vaccine concepts have been tested in six efficacy trials with no product licensed to date. Several scientific and programmatic lessons can be learned from these studies generating new hypotheses and guiding future steps. RV144 [ALVAC-HIV (canarypox vector) and AIDSVAX B/E (bivalent gp120 HIV-1 subtype B and CRF01_AE)] remains the only efficacy trial that demonstrated a modest vaccine efficacy, which led to the identification of immune correlates of risk. Progress on subtype-specific, ALVAC (canarypox vector) and gp120 vaccine prime-boost approaches has been slow, but we are finally close to the launch of an efficacy study in Africa in 2016. The quest of a globally effective HIV-1 vaccine has led to the development of new approaches. Efficacy studies of combinations of Adenovirus type 26 (Ad26)/Modified Vaccinia Ankara (MVA)/gp140 vaccines with mosaic designs will enter efficacy studies mid-2017 and cytomegalovirus (CMV)-vectored vaccines begin Phase I studies at the same time. Future HIV-1 vaccine efficacy trials face practical challenges as effective nonvaccine prevention programs are projected to decrease HIV-1 incidence. An HIV-1 vaccine is urgently needed. Increased industry involvement, mobilization of resources, expansion of a robust pipeline of new concepts, and robust preclinical challenge studies will be essential to accelerate efficacy testing of next generation HIV-1 vaccine candidates.

Effect of Survivin gene therapy via lentivirus vector on the course of intervertebral disc degeneration in an in vivo rabbit model.

PubMed

Yue, Bin; Lin, Yazhou; Ma, Xuexiao; Zhang, Guoqing; Chen, Bohua

2016-11-01

The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography‑guided puncture was performed at the L3‑L4 and L4‑L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration.

Creating an arsenal of Adeno-associated virus (AAV) gene delivery stealth vehicles.

PubMed

Smith, J Kennon; Agbandje-McKenna, Mavis

2018-05-01

The Adeno-associated virus (AAV) gene delivery system is ushering in a new and exciting era in the United States; following the first approved gene therapy (Glybera) in Europe, the FDA has approved a second therapy, Luxturna [1]. However, challenges to this system remain. In viral gene therapy, the surface of the capsid is an important determinant of tissue tropism, impacts gene transfer efficiency, and is targeted by the human immune system. Preexisting immunity is a significant challenge to this approach, and the ability to visualize areas of antibody binding ("footprints") can inform efforts to improve the efficacy of viral vectors. Atomic resolution, smaller proteins, and asymmetric structures are the goals to attain in cryo-electron microscopy and image reconstruction (cryo-EM) as of late. The versatility of the technique and the ability to vitrify a wide range of heterogeneous molecules in solution allow structural biologists to characterize a variety of protein-DNA and protein-protein interactions at lower resolution. Cryo-EM has served as an important means to study key surface areas of the AAV gene delivery vehicle-specifically, those involved with binding neutralizing antibodies (NAbs) [2-4]. This method offers a unique opportunity for visualizing antibody binding "hotspots" on the surface of these and other viral vectors. When combined with mutagenesis, one can eliminate these hotspots to create viral vectors with the ability to avoid preexisting host immune recognition during gene delivery and genetic defect correction in disease treatment. Here, we discuss the use of structure-guided site-directed mutagenesis and directed evolution to create "stealth" AAV vectors with modified surface amino acid sequences that allow NAb avoidance while maintaining natural capsid functions or gaining desired novel tropisms.

Establishment of a reliable dual-vector system for the phage display of antibody fragments.

PubMed

Joo, Hyun-yoo; Hur, Byung-ung; Lee, Kyung-woo; Song, Suk-yoon; Cha, Sang-hoon

2008-04-20

To resolve some of the technical limitations in a phage-displayed Fab library, we have designed two dual-vector systems, DVS-I and DVS-II, composed of a set of replicon-compatible plasmid (pLA-1 or pLT-2) for producing soluble L chain fragments and phagemid (pHf1g3T-1 or pHf1g3A-2) for expressing Fd (V(H)+C(H1))-DeltapIII fusion molecules as well as a genotype-phenotype linkage. Compared to the DVS-I (pLA-1 and pHf1g3T-1), the DVS-II (pLT-2 and pHf1g3A-2) showed stable transformation efficiency regardless of the order of the vectors introduced into the host cells. In addition, expression of soluble Fab molecules with antigen-binding reactivity, recombinant phage titer and display level of functional Fab-DeltapIII on the phage progenies of the DVS-II were comparable with a conventional phage display system using a single phagemid vector. More importantly, the phage displaying target-specific Fab-DeltapIII molecules was successfully enriched by panning, which allows isolation of the pHf1g3A-2 phagemid encoding antigen-specific Fd molecules. We believe that the DVS-II may provide a valuable tool in the construction of a combinatorial phage-displayed Fab library with large diversity. Furthermore, it can be readily applied to isolation of desired antibody clones if L chain promiscuity of antibodies in determining antigen-binding specificity is considered, or in guided-selection or chain shuffling of mAbs of non-human origin.

Creating an arsenal of Adeno-associated virus (AAV) gene delivery stealth vehicles

PubMed Central

Agbandje-McKenna, Mavis

2018-01-01

The Adeno-associated virus (AAV) gene delivery system is ushering in a new and exciting era in the United States; following the first approved gene therapy (Glybera) in Europe, the FDA has approved a second therapy, Luxturna [1]. However, challenges to this system remain. In viral gene therapy, the surface of the capsid is an important determinant of tissue tropism, impacts gene transfer efficiency, and is targeted by the human immune system. Preexisting immunity is a significant challenge to this approach, and the ability to visualize areas of antibody binding (“footprints”) can inform efforts to improve the efficacy of viral vectors. Atomic resolution, smaller proteins, and asymmetric structures are the goals to attain in cryo-electron microscopy and image reconstruction (cryo-EM) as of late. The versatility of the technique and the ability to vitrify a wide range of heterogeneous molecules in solution allow structural biologists to characterize a variety of protein–DNA and protein–protein interactions at lower resolution. Cryo-EM has served as an important means to study key surface areas of the AAV gene delivery vehicle—specifically, those involved with binding neutralizing antibodies (NAbs) [2–4]. This method offers a unique opportunity for visualizing antibody binding “hotspots” on the surface of these and other viral vectors. When combined with mutagenesis, one can eliminate these hotspots to create viral vectors with the ability to avoid preexisting host immune recognition during gene delivery and genetic defect correction in disease treatment. Here, we discuss the use of structure-guided site-directed mutagenesis and directed evolution to create “stealth” AAV vectors with modified surface amino acid sequences that allow NAb avoidance while maintaining natural capsid functions or gaining desired novel tropisms. PMID:29723270

Gene Editing Vectors for Studying Nicotinic Acetylcholine Receptors in Cholinergic Transmission.

PubMed

Peng, Can; Yan, Yijin; Kim, Veronica J; Engle, Staci E; Berry, Jennifer N; McIntosh, J Michael; Neve, Rachael L; Drenan, Ryan M

2018-05-19

Nicotinic acetylcholine receptors (nAChRs), prototype members of the cys-loop ligand gated ion channel family, are key mediators of cholinergic transmission in the central nervous system. Despite their importance, technical gaps exist in our ability to dissect the function of individual subunits in the brain. To overcome these barriers, we designed CRISPR/Cas9 small guide RNA sequences (sgRNAs) for production of loss-of-function alleles in mouse nAChR genes. These sgRNAs were validated in vitro via deep sequencing. We subsequently targeted candidate nAChR genes in vivo by creating herpes simplex virus (HSV) vectors delivering sgRNAs and Cas9 expression to mouse brain. Production of loss-of-function insertions or deletions (indels) by these "all-in-one" HSV vectors was confirmed using brain slice patch clamp electrophysiology coupled with pharmacological analysis. Next, we developed a scheme for cell type-specific gene editing in mouse brain. Knockin mice expressing Cas9 in a Cre-dependent manner were validated using viral microinjections and genetic crosses to common Cre-driver mouse lines. We subsequently confirmed functional Cas9 activity by targeting the ubiquitous neuronal protein, NeuN, using adeno associated virus (AAV) delivery of sgRNAs. Finally, the mouse β2 nAChR gene was successfully targeted in dopamine transporter (DAT) positive neurons via CRISPR/Cas9. The sgRNA sequences and viral vectors, including our scheme for Cre-dependent gene editing, should be generally useful to the scientific research community. These tools could lead to new discoveries related to the function of nAChRs in neurotransmission and behavioral processes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Two Different Template Replicators Coexisting in the Same Protocell: Stochastic Simulation of an Extended Chemoton Model

PubMed Central

Zachar, István; Fedor, Anna; Szathmáry, Eörs

2011-01-01

The simulation of complex biochemical systems, consisting of intertwined subsystems, is a challenging task in computational biology. The complex biochemical organization of the cell is effectively modeled by the minimal cell model called chemoton, proposed by Gánti. Since the chemoton is a system consisting of a large but fixed number of interacting molecular species, it can effectively be implemented in a process algebra-based language such as the BlenX programming language. The stochastic model behaves comparably to previous continuous deterministic models of the chemoton. Additionally to the well-known chemoton, we also implemented an extended version with two competing template cycles. The new insight from our study is that the coupling of reactions in the chemoton ensures that these templates coexist providing an alternative solution to Eigen's paradox. Our technical innovation involves the introduction of a two-state switch to control cell growth and division, thus providing an example for hybrid methods in BlenX. Further developments to the BlenX language are suggested in the Appendix. PMID:21818258

Two different template replicators coexisting in the same protocell: stochastic simulation of an extended chemoton model.

PubMed

Zachar, István; Fedor, Anna; Szathmáry, Eörs

2011-01-01

The simulation of complex biochemical systems, consisting of intertwined subsystems, is a challenging task in computational biology. The complex biochemical organization of the cell is effectively modeled by the minimal cell model called chemoton, proposed by Gánti. Since the chemoton is a system consisting of a large but fixed number of interacting molecular species, it can effectively be implemented in a process algebra-based language such as the BlenX programming language. The stochastic model behaves comparably to previous continuous deterministic models of the chemoton. Additionally to the well-known chemoton, we also implemented an extended version with two competing template cycles. The new insight from our study is that the coupling of reactions in the chemoton ensures that these templates coexist providing an alternative solution to Eigen's paradox. Our technical innovation involves the introduction of a two-state switch to control cell growth and division, thus providing an example for hybrid methods in BlenX. Further developments to the BlenX language are suggested in the Appendix.

Design, Fabrication, and Testing of a TiN Ti TiN Trilayer KID Array for 3mm CMB Observations

NASA Technical Reports Server (NTRS)

Lowitz, A. E.; Brown, A. D.; Mikula, V.; Stevenson, T. R.; Timbie, P. T.; Wollack, E. J.

2016-01-01

Kinetic inductance detectors (KIDs) are a promising technology for astronomical observations over a wide range of wavelengths in the mm and sub-mm regime. Simple fabrication, in as little as one lithographic layer, and passive frequency-domain multiplexing, with readout of up to 1000 pixels on a single line with a single cold amplifier, make KIDs an attractive solution for high-pixel-count detector arrays. We are developing an array that optimizes KIDs for optical frequencies near 100GHz to expand their usefulness in mm-wave applications, with a particular focus on CMBB-mode measurement efforts in association with the QUBIC telescope. We have designed, fabricated, and tested a 20-pixel prototype array using a simple quasi lumped microstrip design and pulsed DC reactive magnetron-sputtered TiNTiTiN trilayer resonators, optimized for detecting 100GHz (3mm) signals. Here we present a discussion of design considerations for the array, as well as preliminary detector characterization measurements and results from a study of TiN trilayer properties.

Gender Disparities in Utilization and Outcome of Comprehensive Substance Abuse Treatment Among Racial/Ethnic Groups

PubMed Central

Guerrero, Erick G.; Marsh, Jeanne C.; Cao, Dingcai; Shin, Hee-Choon; Andrews, Christina

2014-01-01

This study examined gender differences within Black, Latino, and White subgroups in the utilization of comprehensive services and their relation to posttreatment substance use. Survey data were collected during the National Treatment Improvement Evaluation Study (NTIES), a prospective, longitudinal, multisite study of substance abuse treatment programs and their clients in the United States. The analytic sample consisted of 1,812 Blacks (734 women and 1,078 men), 486 Latinos (147 women and 339 men), and 844 Whites (147 women and 339 men) from 59 service delivery organizations. Results related to service utilization indicated that compared to men, women in all racial and ethnic groups needed and received more services targeted to their needs and reported more positive relations with service providers. Gender was a significant moderator of the relationship between service receipt and treatment outcomes for all racial and ethnic groups, but especially for the Latino subsample. Findings point to the need to consider race-specific gender differences in the development of culturally competent, comprehensive substance abuse treatment. PMID:24560127

Adeno-Associated Viral Vector (Serotype 2)-Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial.

PubMed

Rafii, Michael S; Tuszynski, Mark H; Thomas, Ronald G; Barba, David; Brewer, James B; Rissman, Robert A; Siffert, Joao; Aisen, Paul S

2018-03-26

Nerve growth factor (NGF) is an endogenous neurotrophic factor that prevents the death and augments the functional state of cholinergic neurons of the basal forebrain, a cell population that undergoes extensive degeneration in Alzheimer disease (AD). To determine whether stereotactically guided intracerebral injections of adeno-associated viral vector (serotype 2)-nerve growth factor (AAV2-NGF) are well tolerated and exhibit preliminary evidence of impact on cognitive decline in mild to moderate AD-associated dementia. In a multicenter phase 2 trial, 49 participants with mild to moderate AD were randomly assigned in a 1:1 ratio to receive stereotactically guided intracerebral injections of AAV2-NGF or sham surgery. Participants were enrolled between November 2009 and December 2012. Analyses began in February 2015. The study was conducted at 10 US academic medical centers. Eligibility required a diagnosis of mild to moderate dementia due to AD and individuals aged 55 to 80 years. A total of 39 participants did not pass screening; the most common reason was Mini-Mental State Examination scores below cutoff. Analyses were intention-to-treat. Stereotactically guided intracerebral injections of AAV2-NGF into the nucleus basalis of Meynert of each hemisphere or sham surgery. Change from baseline on the Alzheimer Disease Assessment Scale-cognitive subscale at month 24. Among 49 participants, 21 (43%) were women, 42 (86%) self-identified as white, and the mean (SD) age was 68 (6.4) years. AAV2-NGF was safe and well-tolerated through 24 months. No significant difference was noted between the treatment group and placebo on the primary outcome measure, the Alzheimer Disease Assessment Scale-cognitive subscale (mean [SD] score, 14.52 [4.66] vs 9.11 [4.65], P = .17). This multicenter randomized clinical trial demonstrated the feasibility of sham-surgery-controlled stereotactic gene delivery studies in patients with AD. AAV2-NGF delivery was well-tolerated but did not affect clinical outcomes or selected AD biomarkers. Pathological confirmation of accurate gene targeting is needed. clinicaltrials.gov Identifier NCT00876863.

Orbitofrontal Cortex Signals Expected Outcomes with Predictive Codes When Stable Contingencies Promote the Integration of Reward History

PubMed Central

Shapiro, Matthew L.

2017-01-01

Memory can inform goal-directed behavior by linking current opportunities to past outcomes. The orbitofrontal cortex (OFC) may guide value-based responses by integrating the history of stimulus–reward associations into expected outcomes, representations of predicted hedonic value and quality. Alternatively, the OFC may rapidly compute flexible “online” reward predictions by associating stimuli with the latest outcome. OFC neurons develop predictive codes when rats learn to associate arbitrary stimuli with outcomes, but the extent to which predictive coding depends on most recent events and the integrated history of rewards is unclear. To investigate how reward history modulates OFC activity, we recorded OFC ensembles as rats performed spatial discriminations that differed only in the number of rewarded trials between goal reversals. The firing rate of single OFC neurons distinguished identical behaviors guided by different goals. When >20 rewarded trials separated goal switches, OFC ensembles developed stable and anticorrelated population vectors that predicted overall choice accuracy and the goal selected in single trials. When <10 rewarded trials separated goal switches, OFC population vectors decorrelated rapidly after each switch, but did not develop anticorrelated firing patterns or predict choice accuracy. The results show that, whereas OFC signals respond rapidly to contingency changes, they predict choices only when reward history is relatively stable, suggesting that consecutive rewarded episodes are needed for OFC computations that integrate reward history into expected outcomes. SIGNIFICANCE STATEMENT Adapting to changing contingencies and making decisions engages the orbitofrontal cortex (OFC). Previous work shows that OFC function can either improve or impair learning depending on reward stability, suggesting that OFC guides behavior optimally when contingencies apply consistently. The mechanisms that link reward history to OFC computations remain obscure. Here, we examined OFC unit activity as rodents performed tasks controlled by contingencies that varied reward history. When contingencies were stable, OFC neurons signaled past, present, and pending events; when contingencies were unstable, past and present coding persisted, but predictive coding diminished. The results suggest that OFC mechanisms require stable contingencies across consecutive episodes to integrate reward history, represent predicted outcomes, and inform goal-directed choices. PMID:28115481

A manual for microcomputer image analysis

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

Rich, P.M.; Ranken, D.M.; George, J.S.

1989-12-01

This manual is intended to serve three basic purposes: as a primer in microcomputer image analysis theory and techniques, as a guide to the use of IMAGE{copyright}, a public domain microcomputer program for image analysis, and as a stimulus to encourage programmers to develop microcomputer software suited for scientific use. Topics discussed include the principals of image processing and analysis, use of standard video for input and display, spatial measurement techniques, and the future of microcomputer image analysis. A complete reference guide that lists the commands for IMAGE is provided. IMAGE includes capabilities for digitization, input and output of images,more » hardware display lookup table control, editing, edge detection, histogram calculation, measurement along lines and curves, measurement of areas, examination of intensity values, output of analytical results, conversion between raster and vector formats, and region movement and rescaling. The control structure of IMAGE emphasizes efficiency, precision of measurement, and scientific utility. 18 refs., 18 figs., 2 tabs.« less

Gap maps and intrinsic diffraction losses in one-dimensional photonic crystal slabs.

PubMed

Gerace, Dario; Andreani, Lucio Claudio

2004-05-01

A theoretical study of photonic bands for one-dimensional (1D) lattices embedded in planar waveguides with strong refractive index contrast is presented. The approach relies on expanding the electromagnetic field on the basis of guided modes of an effective waveguide, and on treating the coupling to radiative modes by perturbation theory. Photonic mode dispersion, gap maps, and intrinsic diffraction losses of quasi guided modes are calculated for the case of self-standing membranes as well as for silicon-on-insulator structures. Photonic band gaps in a waveguide are found to depend strongly on the core thickness and on polarization, so that the gaps for transverse electric and transverse magnetic modes most often do not overlap. Radiative losses of quasiguided modes above the light line depend in a nontrivial way on structure parameters, mode index, and wave vector. The results of this study may be useful for the design of integrated 1D photonic structures with low radiative losses.

Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library.

PubMed

Koike-Yusa, Hiroko; Li, Yilong; Tan, E-Pien; Velasco-Herrera, Martin Del Castillo; Yusa, Kosuke

2014-03-01

Identification of genes influencing a phenotype of interest is frequently achieved through genetic screening by RNA interference (RNAi) or knockouts. However, RNAi may only achieve partial depletion of gene activity, and knockout-based screens are difficult in diploid mammalian cells. Here we took advantage of the efficiency and high throughput of genome editing based on type II, clustered, regularly interspaced, short palindromic repeats (CRISPR)-CRISPR-associated (Cas) systems to introduce genome-wide targeted mutations in mouse embryonic stem cells (ESCs). We designed 87,897 guide RNAs (gRNAs) targeting 19,150 mouse protein-coding genes and used a lentiviral vector to express these gRNAs in ESCs that constitutively express Cas9. Screening the resulting ESC mutant libraries for resistance to either Clostridium septicum alpha-toxin or 6-thioguanine identified 27 known and 4 previously unknown genes implicated in these phenotypes. Our results demonstrate the potential for efficient loss-of-function screening using the CRISPR-Cas9 system.

Characteristics of solid-core square-lattice microstructured optical fibers using an analytical field model

NASA Astrophysics Data System (ADS)

Sharma, Dinesh Kumar; Sharma, Anurag; Tripathi, Saurabh Mani

2017-11-01

The excellent propagation properties of square-lattice microstructured optical fibers (MOFs) have been widely recognized. We generalized our recently developed analytical field model (Sharma and Sharma, 2016), for index-guiding MOFs with square-lattice of circular air-holes in the photonic crystal cladding. Using the field model, we have studied the propagation properties of the fundamental mode of index-guiding square-lattice MOFs with different hole-to-hole spacing and the air-hole diameter. Results for the modal effective index, near and the far-field patterns and the group-velocity dispersion have been included. The evolution of the mode shape has been investigated in transition from the near to the far-field domain. We have also studied the splice losses between two identical square-lattice MOFs and also between an MOF and a traditional step-index single-mode fiber. Comparisons with available numerical simulation results, e.g., those based on the full-vector finite element method have also been included.

Evaluation and rational design of guide RNAs for efficient CRISPR/Cas9-mediated mutagenesis in Ciona.

PubMed

Gandhi, Shashank; Haeussler, Maximilian; Razy-Krajka, Florian; Christiaen, Lionel; Stolfi, Alberto

2017-05-01

The CRISPR/Cas9 system has emerged as an important tool for various genome engineering applications. A current obstacle to high throughput applications of CRISPR/Cas9 is the imprecise prediction of highly active single guide RNAs (sgRNAs). We previously implemented the CRISPR/Cas9 system to induce tissue-specific mutations in the tunicate Ciona. In the present study, we designed and tested 83 single guide RNA (sgRNA) vectors targeting 23 genes expressed in the cardiopharyngeal progenitors and surrounding tissues of Ciona embryo. Using high-throughput sequencing of mutagenized alleles, we identified guide sequences that correlate with sgRNA mutagenesis activity and used this information for the rational design of all possible sgRNAs targeting the Ciona transcriptome. We also describe a one-step cloning-free protocol for the assembly of sgRNA expression cassettes. These cassettes can be directly electroporated as unpurified PCR products into Ciona embryos for sgRNA expression in vivo, resulting in high frequency of CRISPR/Cas9-mediated mutagenesis in somatic cells of electroporated embryos. We found a strong correlation between the frequency of an Ebf loss-of-function phenotype and the mutagenesis efficacies of individual Ebf-targeting sgRNAs tested using this method. We anticipate that our approach can be scaled up to systematically design and deliver highly efficient sgRNAs for the tissue-specific investigation of gene functions in Ciona. Copyright © 2017 Elsevier Inc. All rights reserved.

Postnatal Cardiac Gene Editing Using CRISPR/Cas9 With AAV9-Mediated Delivery of Short Guide RNAs Results in Mosaic Gene Disruption.

PubMed

Johansen, Anne Katrine; Molenaar, Bas; Versteeg, Danielle; Leitoguinho, Ana Rita; Demkes, Charlotte; Spanjaard, Bastiaan; de Ruiter, Hesther; Akbari Moqadam, Farhad; Kooijman, Lieneke; Zentilin, Lorena; Giacca, Mauro; van Rooij, Eva

2017-10-27

CRISPR/Cas9 (clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9)-based DNA editing has rapidly evolved as an attractive tool to modify the genome. Although CRISPR/Cas9 has been extensively used to manipulate the germline in zygotes, its application in postnatal gene editing remains incompletely characterized. To evaluate the feasibility of CRISPR/Cas9-based cardiac genome editing in vivo in postnatal mice. We generated cardiomyocyte-specific Cas9 mice and demonstrated that Cas9 expression does not affect cardiac function or gene expression. As a proof-of-concept, we delivered short guide RNAs targeting 3 genes critical for cardiac physiology, Myh6 , Sav1 , and Tbx20 , using a cardiotropic adeno-associated viral vector 9. Despite a similar degree of DNA disruption and subsequent mRNA downregulation, only disruption of Myh6 was sufficient to induce a cardiac phenotype, irrespective of short guide RNA exposure or the level of Cas9 expression. DNA sequencing analysis revealed target-dependent mutations that were highly reproducible across mice resulting in differential rates of in- and out-of-frame mutations. Finally, we applied a dual short guide RNA approach to effectively delete an important coding region of Sav1 , which increased the editing efficiency. Our results indicate that the effect of postnatal CRISPR/Cas9-based cardiac gene editing using adeno-associated virus serotype 9 to deliver a single short guide RNA is target dependent. We demonstrate a mosaic pattern of gene disruption, which hinders the application of the technology to study gene function. Further studies are required to expand the versatility of CRISPR/Cas9 as a robust tool to study novel cardiac gene functions in vivo. © 2017 American Heart Association, Inc.

Particle tracking velocimetry using echocardiographic data resolves flow in the left ventricle

NASA Astrophysics Data System (ADS)

Sampath, Kaushik; Abd, Thura T.; George, Richard T.; Katz, Joseph

2015-11-01

Two dimensional contrast echocardiography was performed on patients with a history of left ventricular (LV) thrombus. The 636 x 434 pixels electrocardiograms were recorded using a GE Vivid 9E system with (M5S-D and 4V-D) probes in a 2-D mode at a magnification of 0.3 mm/pix. The concentration of 2-4.5 micron seed bubbles was adjusted to obtain individually discernable traces, and a data acquisition rate of 60-90 fps kept the inter-frame displacements suitable for matching traces, and calculating vectors, but yet low enough to allow a scanning depth and width of upto 13 cm and 60 degrees respectively. Particle tracking velocimetry (PTV) guided by initial particle image velocimetry (PIV) was used to obtain the velocity distributions inside the LV with vector spacing of 3-5 mm. The data quality was greatly enhanced by implementing an iterative particle specific enhancement and tracking algorithm. Data covering 20 heart beats facilitated phase averaging. The results elucidated blood flow in the intra-ventricular septal region, lateral wall region, the apex of the LV and the mitral valve region.

Data layer integration for the national map of the united states

USGS Publications Warehouse

Usery, E.L.; Finn, M.P.; Starbuck, M.

2009-01-01

The integration of geographic data layers in multiple raster and vector formats, from many different organizations and at a variety of resolutions and scales, is a significant problem for The National Map of the United States being developed by the U.S. Geological Survey. Our research has examined data integration from a layer-based approach for five of The National Map data layers: digital orthoimages, elevation, land cover, hydrography, and transportation. An empirical approach has included visual assessment by a set of respondents with statistical analysis to establish the meaning of various types of integration. A separate theoretical approach with established hypotheses tested against actual data sets has resulted in an automated procedure for integration of specific layers and is being tested. The empirical analysis has established resolution bounds on meanings of integration with raster datasets and distance bounds for vector data. The theoretical approach has used a combination of theories on cartographic transformation and generalization, such as T??pfer's radical law, and additional research concerning optimum viewing scales for digital images to establish a set of guiding principles for integrating data of different resolutions.

Interactive computer modeling of combustion chemistry and coalescence-dispersion modeling of turbulent combustion

NASA Technical Reports Server (NTRS)

Pratt, D. T.

1984-01-01

An interactive computer code for simulation of a high-intensity turbulent combustor as a single point inhomogeneous stirred reactor was developed from an existing batch processing computer code CDPSR. The interactive CDPSR code was used as a guide for interpretation and direction of DOE-sponsored companion experiments utilizing Xenon tracer with optical laser diagnostic techniques to experimentally determine the appropriate mixing frequency, and for validation of CDPSR as a mixing-chemistry model for a laboratory jet-stirred reactor. The coalescence-dispersion model for finite rate mixing was incorporated into an existing interactive code AVCO-MARK I, to enable simulation of a combustor as a modular array of stirred flow and plug flow elements, each having a prescribed finite mixing frequency, or axial distribution of mixing frequency, as appropriate. Further increase the speed and reliability of the batch kinetics integrator code CREKID was increased by rewriting in vectorized form for execution on a vector or parallel processor, and by incorporating numerical techniques which enhance execution speed by permitting specification of a very low accuracy tolerance.

Biochemometrics for Natural Products Research: Comparison of Data Analysis Approaches and Application to Identification of Bioactive Compounds.

PubMed

Kellogg, Joshua J; Todd, Daniel A; Egan, Joseph M; Raja, Huzefa A; Oberlies, Nicholas H; Kvalheim, Olav M; Cech, Nadja B

2016-02-26

A central challenge of natural products research is assigning bioactive compounds from complex mixtures. The gold standard approach to address this challenge, bioassay-guided fractionation, is often biased toward abundant, rather than bioactive, mixture components. This study evaluated the combination of bioassay-guided fractionation with untargeted metabolite profiling to improve active component identification early in the fractionation process. Key to this methodology was statistical modeling of the integrated biological and chemical data sets (biochemometric analysis). Three data analysis approaches for biochemometric analysis were compared, namely, partial least-squares loading vectors, S-plots, and the selectivity ratio. Extracts from the endophytic fungi Alternaria sp. and Pyrenochaeta sp. with antimicrobial activity against Staphylococcus aureus served as test cases. Biochemometric analysis incorporating the selectivity ratio performed best in identifying bioactive ions from these extracts early in the fractionation process, yielding altersetin (3, MIC 0.23 μg/mL) and macrosphelide A (4, MIC 75 μg/mL) as antibacterial constituents from Alternaria sp. and Pyrenochaeta sp., respectively. This study demonstrates the potential of biochemometrics coupled with bioassay-guided fractionation to identify bioactive mixture components. A benefit of this approach is the ability to integrate multiple stages of fractionation and bioassay data into a single analysis.

Ensembles of novelty detection classifiers for structural health monitoring using guided waves

NASA Astrophysics Data System (ADS)

Dib, Gerges; Karpenko, Oleksii; Koricho, Ermias; Khomenko, Anton; Haq, Mahmoodul; Udpa, Lalita

2018-01-01

Guided wave structural health monitoring uses sparse sensor networks embedded in sophisticated structures for defect detection and characterization. The biggest challenge of those sensor networks is developing robust techniques for reliable damage detection under changing environmental and operating conditions (EOC). To address this challenge, we develop a novelty classifier for damage detection based on one class support vector machines. We identify appropriate features for damage detection and introduce a feature aggregation method which quadratically increases the number of available training observations. We adopt a two-level voting scheme by using an ensemble of classifiers and predictions. Each classifier is trained on a different segment of the guided wave signal, and each classifier makes an ensemble of predictions based on a single observation. Using this approach, the classifier can be trained using a small number of baseline signals. We study the performance using Monte-Carlo simulations of an analytical model and data from impact damage experiments on a glass fiber composite plate. We also demonstrate the classifier performance using two types of baseline signals: fixed and rolling baseline training set. The former requires prior knowledge of baseline signals from all EOC, while the latter does not and leverages the fact that EOC vary slowly over time and can be modeled as a Gaussian process.

Using machine learning algorithms to guide rehabilitation planning for home care clients.

PubMed

Zhu, Mu; Zhang, Zhanyang; Hirdes, John P; Stolee, Paul

2007-12-20

Targeting older clients for rehabilitation is a clinical challenge and a research priority. We investigate the potential of machine learning algorithms - Support Vector Machine (SVM) and K-Nearest Neighbors (KNN) - to guide rehabilitation planning for home care clients. This study is a secondary analysis of data on 24,724 longer-term clients from eight home care programs in Ontario. Data were collected with the RAI-HC assessment system, in which the Activities of Daily Living Clinical Assessment Protocol (ADLCAP) is used to identify clients with rehabilitation potential. For study purposes, a client is defined as having rehabilitation potential if there was: i) improvement in ADL functioning, or ii) discharge home. SVM and KNN results are compared with those obtained using the ADLCAP. For comparison, the machine learning algorithms use the same functional and health status indicators as the ADLCAP. The KNN and SVM algorithms achieved similar substantially improved performance over the ADLCAP, although false positive and false negative rates were still fairly high (FP > .18, FN > .34 versus FP > .29, FN. > .58 for ADLCAP). Results are used to suggest potential revisions to the ADLCAP. Machine learning algorithms achieved superior predictions than the current protocol. Machine learning results are less readily interpretable, but can also be used to guide development of improved clinical protocols.

Comparative analysis of the efficacy of astigmatic correction after wavefront-guided and wavefront-optimized LASIK in low and moderate myopic eyes

PubMed Central

Khalifa, Mounir A.; Alsahn, Mahmoud F.; Shaheen, Mohamed Shafik; Pinero, David P.

2017-01-01

AIM To evaluate and compare the efficacy of the astigmatic correction achieved with laser in situ keratomileusis (LASIK) in eyes with myopic astigmatism using wavefront-guided (WFG) and wavefront-optimized (WFO) ablation profiles. METHODS Prospective study included 221 eyes undergoing LASIK: 99 and 122 eyes with low and moderate myopic astigmatism (low and moderate myopia groups). Two subgroups were differentiated in each group according to the ablation profile: WFG subgroup, 109 eyes (45/64, low/moderate myopia groups) treated using the Advanced CustomVue platform (Abbott Medical Optics Inc.), and WFO subgroup, 112 eyes (54/58, low/moderate myopia groups) treated using the EX-500 platform (Alcon). Clinical outcomes were evaluated during a 6-month follow-up, including a vector analysis of astigmatic changes. RESULTS Significantly better postoperative uncorrected visual acuity and efficacy index was found in the WFG subgroups of each group (P≤0.041). Postoperative spherical equivalent and cylinder were significantly higher in WFO subgroups (P≤0.003). In moderate myopia group, a higher percentage of eyes with a postoperative cylinder ≤0.25 D was found in the WFG subgroup (90.6% vs 65.5%, P=0.002). In low and moderate myopia groups, the difference vector was significantly higher in the WFO subgroup compared to WFG (P<0.001). In moderate myopia group, the magnitude (P=0.008) and angle of error (P<0.001) were also significantly higher in the WFO subgroup. Significantly less induction of high order aberrations were found with WFG treatments in both low and moderate myopia groups (P≤0.006). CONCLUSION A more efficacious correction of myopic astigmatism providing a better visual outcome is achieved with WFG LASIK compared to WFO LASIK. PMID:28251090

Hybrid simulations of radial transport driven by the Rayleigh-Taylor instability

NASA Astrophysics Data System (ADS)

Delamere, P. A.; Stauffer, B. H.; Ma, X.

2017-12-01

Plasma transport in the rapidly rotating giant magnetospheres is thought to involve a centrifugally-driven flux tube interchange instability, similar to the Rayleigh-Taylor (RT) instability. In three dimensions, the convective flow patterns associated with the RT instability can produce strong guide field reconnection, allowing plasma mass to move radially outward while conserving magnetic flux (Ma et al., 2016). We present a set of hybrid (kinetic ion / fluid electron) plasma simulations of the RT instability using high plasma beta conditions appropriate for Jupiter's inner and middle magnetosphere. A density gradient, combined with a centrifugal force, provide appropriate RT onset conditions. Pressure balance is achieved by initializing two ion populations: one with fixed temperature, but varying density, and the other with fixed density, but a temperature gradient that offsets the density gradient from the first population and the centrifugal force (effective gravity). We first analyze two-dimensional results for the plane perpendicular to the magnetic field by comparing growth rates as a function of wave vector following Huba et al. (1998). Prescribed perpendicular wave modes are seeded with an initial velocity perturbation. We then extend the model to three dimensions, introducing a stabilizing parallel wave vector. Boundary conditions in the parallel direction prohibit motion of the magnetic field line footprints to model the eigenmodes of the magnetodisc's resonant cavity. We again compare growth rates based on perpendicular wave number, but also on the parallel extent of the resonant cavity, which fixes the size of the largest parallel wavelength. Finally, we search for evidence of strong guide field magnetic reconnection within the domain by identifying areas with large parallel electric fields or changes in magnetic field topology.

AAV-CRISPR/Cas9-Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro.

PubMed

Wu, Wenyi; Duan, Yajian; Ma, Gaoen; Zhou, Guohong; Park-Windhol, Cindy; D'Amore, Patricia A; Lei, Hetian

2017-12-01

Pathologic angiogenesis is a component of many diseases, including neovascular age-related macular degeneration, proliferation diabetic retinopathy, as well as tumor growth and metastasis. The purpose of this project was to examine whether the system of adeno-associated viral (AAV)-mediated CRISPR (clustered regularly interspaced short palindromic repeats)-associated endonuclease (Cas)9 can be used to deplete expression of VEGF receptor 2 (VEGFR2) in human vascular endothelial cells in vitro and thus suppress its downstream signaling events. The dual AAV system of CRISPR/Cas9 from Streptococcus pyogenes (AAV-SpGuide and -SpCas9) was adapted to edit genomic VEGFR2 in primary human retinal microvascular endothelial cells (HRECs). In this system, the endothelial-specific promoter for intercellular adhesion molecule 2 (ICAM2) was cloned into the dual AAV vectors of SpGuide and SpCas9 for driving expression of green fluorescence protein (GFP) and SpCas9, respectively. These two AAV vectors were applied to production of recombinant AAV serotype 5 (rAAV5), which were used to infect HRECs for depletion of VEGFR2. Protein expression was determined by Western blot; and cell proliferation, migration, as well as tube formation were examined. AAV5 effectively infected vascular endothelial cells (ECs) and retinal pigment epithelial (RPE) cells; the ICAM2 promoter drove expression of GFP and SpCas9 in HRECs, but not in RPE cells. The results showed that the rAAV5-CRISPR/Cas9 depleted VEGFR2 by 80% and completely blocked VEGF-induced activation of Akt, and proliferation, migration as well as tube formation of HRECs. AAV-CRISRP/Cas9-mediated depletion of VEGFR2 is a potential therapeutic strategy for pathologic angiogenesis.

Computer-assisted surgery of the paranasal sinuses: technical and clinical experience with 368 patients, using the Vector Vision Compact system.

PubMed

Stelter, K; Andratschke, M; Leunig, A; Hagedorn, H

2006-12-01

This paper presents our experience with a navigation system for functional endoscopic sinus surgery. In this study, we took particular note of the surgical indications and risks and the measurement precision and preparation time required, and we present one brief case report as an example. Between 2000 and 2004, we performed functional endoscopic sinus surgery on 368 patients at the Ludwig Maximilians University, Munich, Germany. We used the Vector Vision Compact system (BrainLAB) with laser registration. The indications for surgery ranged from severe nasal polyps and chronic sinusitis to malignant tumours of the paranasal sinuses and skull base. The time needed for data preparation was less than five minutes. The time required for preparation and patient registration depended on the method used and the experience of the user. In the later cases, it took 11 minutes on average, using Z-Touch registration. The clinical plausibility test produced an average deviation of 1.3 mm. The complications of system use comprised one intra-operative re-registration (18 per cent) and one complete failure (5 per cent). Despite the assistance of an accurate working computer, the anterior ethmoidal artery was incised in one case. However, in all 368 cases, we experienced no cerebrospinal fluid leaks, optic nerve lesions, retrobulbar haematomas or intracerebral bleeding. There were no deaths. From our experience with computer-guided surgical procedures, we conclude that computer-guided navigational systems are so accurate that the risk of misleading the surgeon is minimal. In the future, their use in certain specialized procedures will be not only sensible but mandatory. We recommend their use not only in difficult surgical situations but also in routine procedures and for surgical training.

Climate change effects on Chikungunya transmission in Europe: geospatial analysis of vector's climatic suitability and virus' temperature requirements.

PubMed

Fischer, Dominik; Thomas, Stephanie M; Suk, Jonathan E; Sudre, Bertrand; Hess, Andrea; Tjaden, Nils B; Beierkuhnlein, Carl; Semenza, Jan C

2013-11-12

Chikungunya was, from the European perspective, considered to be a travel-related tropical mosquito-borne disease prior to the first European outbreak in Northern Italy in 2007. This was followed by cases of autochthonous transmission reported in South-eastern France in 2010. Both events occurred after the introduction, establishment and expansion of the Chikungunya-competent and highly invasive disease vector Aedes albopictus (Asian tiger mosquito) in Europe. In order to assess whether these outbreaks are indicative of the beginning of a trend or one-off events, there is a need to further examine the factors driving the potential transmission of Chikungunya in Europe. The climatic suitability, both now and in the future, is an essential starting point for such an analysis. The climatic suitability for Chikungunya outbreaks was determined by using bioclimatic factors that influence, both vector and, pathogen. Climatic suitability for the European distribution of the vector Aedes albopictus was based upon previous correlative environmental niche models. Climatic risk classes were derived by combining climatic suitability for the vector with known temperature requirements for pathogen transmission, obtained from outbreak regions. In addition, the longest potential intra-annual season for Chikungunya transmission was estimated for regions with expected vector occurrences.In order to analyse spatio-temporal trends for risk exposure and season of transmission in Europe, climate change impacts are projected for three time-frames (2011-2040, 2041-2070 and 2071-2100) and two climate scenarios (A1B and B1) from the Intergovernmental Panel on Climate Change (IPCC). These climatic projections are based on regional climate model COSMO-CLM, which builds on the global model ECHAM5. European areas with current and future climatic suitability of Chikungunya transmission are identified. An increase in risk is projected for Western Europe (e.g. France and Benelux-States) in the first half of the 21st century and from mid-century onwards for central parts of Europe (e.g. Germany). Interestingly, the southernmost parts of Europe do not generally provide suitable conditions in these projections. Nevertheless, many Mediterranean regions will persist to be climatically suitable for transmission. Overall, the highest risk of transmission by the end of the 21st century was projected for France, Northern Italy and the Pannonian Basin (East-Central Europe). This general tendency is depicted in both, the A1B and B1 climate change scenarios. In order to guide preparedness for further outbreaks, it is crucial to anticipate risk as to identify areas where specific public health measures, such as surveillance and vector control, can be implemented. However, public health practitioners need to be aware that climate is only one factor driving the transmission of vector-borne disease.

Real-time MRI-guided hyperthermia treatment using a fast adaptive algorithm

NASA Astrophysics Data System (ADS)

Stakhursky, Vadim L.; Arabe, Omar; Cheng, Kung-Shan; MacFall, James; Maccarini, Paolo; Craciunescu, Oana; Dewhirst, Mark; Stauffer, Paul; Das, Shiva K.

2009-04-01

Magnetic resonance (MR) imaging is promising for monitoring and guiding hyperthermia treatments. The goal of this work is to investigate the stability of an algorithm for online MR thermal image guided steering and focusing of heat into the target volume. The control platform comprised a four-antenna mini-annular phased array (MAPA) applicator operating at 140 MHz (used for extremity sarcoma heating) and a GE Signa Excite 1.5 T MR system, both of which were driven by a control workstation. MR proton resonance frequency shift images acquired during heating were used to iteratively update a model of the heated object, starting with an initial finite element computed model estimate. At each iterative step, the current model was used to compute a focusing vector, which was then used to drive the next iteration, until convergence. Perturbation of the driving vector was used to prevent the process from stalling away from the desired focus. Experimental validation of the performance of the automatic treatment platform was conducted with two cylindrical phantom studies, one homogeneous and one muscle equivalent with tumor tissue (conductivity 50% higher) inserted, with initial focal spots being intentionally rotated 90° and 50° away from the desired focus, mimicking initial setup errors in applicator rotation. The integrated MR-HT treatment platform steered the focus of heating into the desired target volume in two quite different phantom tissue loads which model expected patient treatment configurations. For the homogeneous phantom test where the target was intentionally offset by 90° rotation of the applicator, convergence to the proper phase focus in the target occurred after 16 iterations of the algorithm. For the more realistic test with a muscle equivalent phantom with tumor inserted with 50° applicator displacement, only two iterations were necessary to steer the focus into the tumor target. Convergence improved the heating efficacy (the ratio of integral temperature in the tumor to integral temperature in normal tissue) by up to six-fold, compared to the first iteration. The integrated MR-HT treatment algorithm successfully steered the focus of heating into the desired target volume for both the simple homogeneous and the more challenging muscle equivalent phantom with tumor insert models of human extremity sarcomas after 16 and 2 iterations, correspondingly. The adaptive method for MR thermal image guided focal steering shows promise when tested in phantom experiments on a four-antenna phased array applicator.

Seasonal Variation in Biting Rates of Simulium damnosum sensu lato, Vector of Onchocerca volvulus, in Two Sudanese Foci

PubMed Central

Zarroug, Isam M. A.; Hashim, Kamal; Elaagip, Arwa H.; Samy, Abdallah M.; Frah, Ehab A.; ElMubarak, Wigdan A.; Mohamed, Hanan A.; Deran, Tong Chor M.; Aziz, Nabil; Higazi, Tarig B.

2016-01-01

Background The abundance of onchocerciasis vectors affects the epidemiology of disease in Sudan, therefore, studies of vector dynamics are crucial for onchocerciasis control/elimination programs. This study aims to compare the relative abundance, monthly biting-rates (MBR) and hourly-based distribution of onchocerciasis vectors in Abu-Hamed and Galabat foci. These seasonally-based factors can be used to structure vector control efforts to reduce fly-biting rates as a component of onchocerciasis elimination programs. Methods A cross-sectional study was conducted in four endemic villages in Abu-Hamed and Galabat foci during two non-consecutive years (2007–2008 and 2009–2010). Both adults and aquatic stages of the potential onchocerciasis vector Simulium damnosum sensu lato were collected following standard procedures during wet and dry seasons. Adult flies were collected using human landing capture for 5 days/month. The data was recorded on handheld data collection sheets to calculate the relative abundance, MBR, and hourly-based distribution associated with climatic factors. The data analysis was carried out using ANOVA and Spearman rank correlation tests. Results Data on vector surveillance revealed higher relative abundance of S. damnosum s.l. in Abu- Hamed (39,934 flies) than Galabat (8,202 flies). In Abu-Hamed, vector populations increased in January-April then declined in June-July until they disappeared in August-October. Highest black fly density and MBR were found in March 2007 (N = 9,444, MBR = 58,552.8 bites/person/month), and March 2010 (N = 2,603, MBR = 16,138.6 bites/person/month) while none of flies were collected in August-October (MBR = 0 bites/person/month). In Galabat, vectors increased in September-December, then decreased in February-June. The highest vector density and MBR were recorded in September 2007 (N = 1,138, MBR = 6,828 bites/person/month) and September 2010 (N = 1,163, MBR = 6,978 bites/person/month), whereas, none appeared in collection from April to June. There was a significant difference in mean monthly density of S. damnosum s.l. across the two foci in 2007–2008 (df = 3, F = 3.91, P = 0.011). Minimum temperature showed significant correlation with adult flies counts in four areas sampled; the adult counts were increased in Nady village (rs = 0.799) and were decreased in Kalasecal (rs = - 0.676), Gumaiza (rs = - 0.585), and Hilat Khateir (rs = - 0.496). Maximum temperature showed positive correlation with black fly counts only in Galabat focus. Precipitation was significantly correlated with adult flies counts in Nady village, Abu-Hamed, but no significance was found in the rest of the sampled villages in both foci. Hourly-based distribution of black flies showed a unimodal pattern in Abu-Hamed with one peak (10:00–18:00), while a bimodal pattern with two peaks (07:00–10:00) and (14:00–18:00) was exhibited in Galabat. Conclusion Transmission of onchocerciasis in both foci showed marked differences in seasonality, which may be attributed to ecology, microclimate and proximity of breeding sites to collection sites. The seasonal shifts between the two foci might be related to variations in climate zones. This information on black fly vector seasonality, ecology, distribution and biting activity has obvious implications in monitoring transmission levels to guide the national and regional onchocerciasis elimination programs in Sudan. PMID:26943668

Multispectral Image Road Extraction Based Upon Automated Map Conflation

NASA Astrophysics Data System (ADS)

Chen, Bin

Road network extraction from remotely sensed imagery enables many important and diverse applications such as vehicle tracking, drone navigation, and intelligent transportation studies. There are, however, a number of challenges to road detection from an image. Road pavement material, width, direction, and topology vary across a scene. Complete or partial occlusions caused by nearby buildings, trees, and the shadows cast by them, make maintaining road connectivity difficult. The problems posed by occlusions are exacerbated with the increasing use of oblique imagery from aerial and satellite platforms. Further, common objects such as rooftops and parking lots are made of materials similar or identical to road pavements. This problem of common materials is a classic case of a single land cover material existing for different land use scenarios. This work addresses these problems in road extraction from geo-referenced imagery by leveraging the OpenStreetMap digital road map to guide image-based road extraction. The crowd-sourced cartography has the advantages of worldwide coverage that is constantly updated. The derived road vectors follow only roads and so can serve to guide image-based road extraction with minimal confusion from occlusions and changes in road material. On the other hand, the vector road map has no information on road widths and misalignments between the vector map and the geo-referenced image are small but nonsystematic. Properly correcting misalignment between two geospatial datasets, also known as map conflation, is an essential step. A generic framework requiring minimal human intervention is described for multispectral image road extraction and automatic road map conflation. The approach relies on the road feature generation of a binary mask and a corresponding curvilinear image. A method for generating the binary road mask from the image by applying a spectral measure is presented. The spectral measure, called anisotropy-tunable distance (ATD), differs from conventional measures and is created to account for both changes of spectral direction and spectral magnitude in a unified fashion. The ATD measure is particularly suitable for differentiating urban targets such as roads and building rooftops. The curvilinear image provides estimates of the width and orientation of potential road segments. Road vectors derived from OpenStreetMap are then conflated to image road features by applying junction matching and intermediate point matching, followed by refinement with mean-shift clustering and morphological processing to produce a road mask with piecewise width estimates. The proposed approach is tested on a set of challenging, large, and diverse image data sets and the performance accuracy is assessed. The method is effective for road detection and width estimation of roads, even in challenging scenarios when extensive occlusion occurs.

Cost of dengue outbreaks: literature review and country case studies

PubMed Central

2013-01-01

Background Dengue disease surveillance and vector surveillance are presumed to detect dengue outbreaks at an early stage and to save – through early response activities – resources, and reduce the social and economic impact of outbreaks on individuals, health systems and economies. The aim of this study is to unveil evidence on the cost of dengue outbreaks. Methods Economic evidence on dengue outbreaks was gathered by conducting a literature review and collecting information on the costs of recent dengue outbreaks in 4 countries: Peru, Dominican Republic, Vietnam, and Indonesia. The literature review distinguished between costs of dengue illness including cost of dengue outbreaks, cost of interventions and cost-effectiveness of interventions. Results Seventeen publications on cost of dengue showed a large range of costs from 0.2 Million US$ in Venezuela to 135.2 Million US$ in Brazil. However, these figures were not standardized to make them comparable. Furthermore, dengue outbreak costs are calculated differently across the publications, and cost of dengue illness is used interchangeably with cost of dengue outbreaks. Only one paper from Australia analysed the resources saved through active dengue surveillance. Costs of vector control interventions have been reported in 4 studies, indicating that the costs of such interventions are lower than those of actual outbreaks. Nine papers focussed on the cost-effectiveness of dengue vaccines or dengue vector control; they do not provide any direct information on cost of dengue outbreaks, but their modelling methodologies could guide future research on cost-effectiveness of national surveillance systems. The country case studies – conducted in very different geographic and health system settings - unveiled rough estimates for 2011 outbreak costs of: 12 million US$ in Vietnam, 6.75 million US$ in Indonesia, 4.5 million US$ in Peru and 2.8 million US$ in Dominican Republic (all in 2012 US$). The proportions of the different cost components (vector control; surveillance; information, education and communication; direct medical and indirect costs), as percentage of total costs, differed across the respective countries. Resources used for dengue disease control and treatment were country specific. Conclusions The evidence so far collected further confirms the methodological challenges in this field: 1) to define technically dengue outbreaks (what do we measure?) and 2) to measure accurately the costs in prospective field studies (how do we measure?). Currently, consensus on the technical definition of an outbreak is sought through the International Research Consortium on Dengue Risk Assessment, Management and Surveillance (IDAMS). Best practice guidelines should be further developed, also to improve the quality and comparability of cost study findings. Modelling the costs of dengue outbreaks and validating these models through field studies should guide further research. PMID:24195519

Cost of dengue outbreaks: literature review and country case studies.

PubMed

Stahl, Hans-Christian; Butenschoen, Vicki Marie; Tran, Hien Tinh; Gozzer, Ernesto; Skewes, Ronald; Mahendradhata, Yodi; Runge-Ranzinger, Silvia; Kroeger, Axel; Farlow, Andrew

2013-11-06

Dengue disease surveillance and vector surveillance are presumed to detect dengue outbreaks at an early stage and to save--through early response activities--resources, and reduce the social and economic impact of outbreaks on individuals, health systems and economies. The aim of this study is to unveil evidence on the cost of dengue outbreaks. Economic evidence on dengue outbreaks was gathered by conducting a literature review and collecting information on the costs of recent dengue outbreaks in 4 countries: Peru, Dominican Republic, Vietnam, and Indonesia. The literature review distinguished between costs of dengue illness including cost of dengue outbreaks, cost of interventions and cost-effectiveness of interventions. Seventeen publications on cost of dengue showed a large range of costs from 0.2 Million US$ in Venezuela to 135.2 Million US$ in Brazil. However, these figures were not standardized to make them comparable. Furthermore, dengue outbreak costs are calculated differently across the publications, and cost of dengue illness is used interchangeably with cost of dengue outbreaks. Only one paper from Australia analysed the resources saved through active dengue surveillance. Costs of vector control interventions have been reported in 4 studies, indicating that the costs of such interventions are lower than those of actual outbreaks. Nine papers focussed on the cost-effectiveness of dengue vaccines or dengue vector control; they do not provide any direct information on cost of dengue outbreaks, but their modelling methodologies could guide future research on cost-effectiveness of national surveillance systems.The country case studies--conducted in very different geographic and health system settings - unveiled rough estimates for 2011 outbreak costs of: 12 million US$ in Vietnam, 6.75 million US$ in Indonesia, 4.5 million US$ in Peru and 2.8 million US$ in Dominican Republic (all in 2012 US$). The proportions of the different cost components (vector control; surveillance; information, education and communication; direct medical and indirect costs), as percentage of total costs, differed across the respective countries. Resources used for dengue disease control and treatment were country specific. The evidence so far collected further confirms the methodological challenges in this field: 1) to define technically dengue outbreaks (what do we measure?) and 2) to measure accurately the costs in prospective field studies (how do we measure?). Currently, consensus on the technical definition of an outbreak is sought through the International Research Consortium on Dengue Risk Assessment, Management and Surveillance (IDAMS). Best practice guidelines should be further developed, also to improve the quality and comparability of cost study findings. Modelling the costs of dengue outbreaks and validating these models through field studies should guide further research.

A Multipurpose Toolkit to Enable Advanced Genome Engineering in Plants[OPEN

PubMed Central

Gil-Humanes, Javier; Čegan, Radim; Kono, Thomas J.Y.; Konečná, Eva; Belanto, Joseph J.; Starker, Colby G.

2017-01-01

We report a comprehensive toolkit that enables targeted, specific modification of monocot and dicot genomes using a variety of genome engineering approaches. Our reagents, based on transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, are systematized for fast, modular cloning and accommodate diverse regulatory sequences to drive reagent expression. Vectors are optimized to create either single or multiple gene knockouts and large chromosomal deletions. Moreover, integration of geminivirus-based vectors enables precise gene editing through homologous recombination. Regulation of transcription is also possible. A Web-based tool streamlines vector selection and construction. One advantage of our platform is the use of the Csy-type (CRISPR system yersinia) ribonuclease 4 (Csy4) and tRNA processing enzymes to simultaneously express multiple guide RNAs (gRNAs). For example, we demonstrate targeted deletions in up to six genes by expressing 12 gRNAs from a single transcript. Csy4 and tRNA expression systems are almost twice as effective in inducing mutations as gRNAs expressed from individual RNA polymerase III promoters. Mutagenesis can be further enhanced 2.5-fold by incorporating the Trex2 exonuclease. Finally, we demonstrate that Cas9 nickases induce gene targeting at frequencies comparable to native Cas9 when they are delivered on geminivirus replicons. The reagents have been successfully validated in tomato (Solanum lycopersicum), tobacco (Nicotiana tabacum), Medicago truncatula, wheat (Triticum aestivum), and barley (Hordeum vulgare). PMID:28522548

A multi-purpose toolkit to enable advanced genome engineering in plants

DOE PAGES

Cermak, Tomas; Curtin, Shaun J.; Gil-Humanes, Javier; ...

2017-05-18

Here, we report a comprehensive toolkit that enables targeted, specific modification of monocot and dicot genomes using a variety of genome engineering approaches. Our reagents, based on Transcription Activator-Like Effector Nucleases TALENs and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system, are systematized for fast, modular cloning and accommodate diverse regulatory sequences to drive reagent expression. Vectors are optimized to create either single or multiple gene knockouts and large chromosomal deletions. Moreover, integration of geminivirus-based vectors enables precise gene editing through homologous recombination. Regulation of transcription is also possible. A web-based tool streamlines vector selection and construction. One advantagemore » of our platform is the use of the Csy-type (CRISPR system yersinia) ribonuclease 4 Csy4 and tRNA processing enzymes to simultaneously express multiple guide RNAs (gRNAs). For example, we demonstrate targeted deletions in up to six genes by expressing twelve gRNAs from a single transcript. Csy4 and tRNA expression systems are almost twice as effective in inducing mutations as gRNAs expressed from individual RNA polymerase III promoters. Mutagenesis can be further enhanced 2.5-fold by incorporating the Trex2 exonuclease. Finally, we demonstrate that Cas9 nickases induce gene targeting at frequencies comparable to native Cas9 when they are delivered on geminivirus replicons. The reagents have been successfully validated in tomato (Solanum lycopersicum), tobacco (Nicotiana tabacum), Medicago truncatula, wheat (Triticum aestivum), and barley (Hordeum vulgare).« less

A multi-purpose toolkit to enable advanced genome engineering in plants

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

Cermak, Tomas; Curtin, Shaun J.; Gil-Humanes, Javier

Here, we report a comprehensive toolkit that enables targeted, specific modification of monocot and dicot genomes using a variety of genome engineering approaches. Our reagents, based on Transcription Activator-Like Effector Nucleases TALENs and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 system, are systematized for fast, modular cloning and accommodate diverse regulatory sequences to drive reagent expression. Vectors are optimized to create either single or multiple gene knockouts and large chromosomal deletions. Moreover, integration of geminivirus-based vectors enables precise gene editing through homologous recombination. Regulation of transcription is also possible. A web-based tool streamlines vector selection and construction. One advantagemore » of our platform is the use of the Csy-type (CRISPR system yersinia) ribonuclease 4 Csy4 and tRNA processing enzymes to simultaneously express multiple guide RNAs (gRNAs). For example, we demonstrate targeted deletions in up to six genes by expressing twelve gRNAs from a single transcript. Csy4 and tRNA expression systems are almost twice as effective in inducing mutations as gRNAs expressed from individual RNA polymerase III promoters. Mutagenesis can be further enhanced 2.5-fold by incorporating the Trex2 exonuclease. Finally, we demonstrate that Cas9 nickases induce gene targeting at frequencies comparable to native Cas9 when they are delivered on geminivirus replicons. The reagents have been successfully validated in tomato (Solanum lycopersicum), tobacco (Nicotiana tabacum), Medicago truncatula, wheat (Triticum aestivum), and barley (Hordeum vulgare).« less

Spatial Distribution of Phlebotomine Sand Fly Species (Diptera: Psychodidae) in Qom Province, Central Iran.

PubMed

Saghafipour, Abedin; Vatandoost, Hassan; Zahraei-Ramazani, Ali Reza; Yaghoobi-Ershadi, Mohammad Reza; Rassi, Yavar; Shirzadi, Mohammad Reza; Akhavan, Amir Ahmad

2017-01-01

Zoonotic cutaneous leishmaniasis (ZCL) is transmitted to humans by phlebotomine sand fly bites. ZCL is a major health problem in Iran, where basic knowledge gaps about sand fly species diversity persist in some ZCL-endemic areas. This paper describes the richness and spatial distribution of sand fly species, collected with sticky traps, in Qom province, a ZCL-endemic area in central Iran, where sand fly fauna has been poorly studied. Collected species were mapped on urban and rural digital maps based on a scale of 1/50,000. All analyses were undertaken with rural- and urban-level precision, i.e., rural and urban levels were our basic units of analysis. After identifying the sand flies, high-risk foci were determined. For spatial analysis of vector species population, the entomological sampling sites were geo-referenced using GPS. Arc GIS 9.3 software was used to determine the foci with leishmaniasis vector species. Following the analyses, two genera (Phlebotomus and Sergentomyia) and 14 species were identified. Based on the mapping and sand fly dispersion analysis, the rural districts were categorized into three groups-infection reported, without infection, and no report. Based on Geographical Information System analyses, Kahak and Markazi districts were identified as high-risk foci with leishmaniasis vector species. These findings can act as a help guide to direct active control measures to the identified high-risk foci and, eventually, lead to reduction in incidence of the disease. © Crown copyright 2016.

pKAMA-ITACHI Vectors for Highly Efficient CRISPR/Cas9-Mediated Gene Knockout in Arabidopsis thaliana

PubMed Central

2017-01-01

The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) system is widely used as a tool for genome engineering in various organisms. A complex consisting of Cas9 and single guide RNA (sgRNA) induces a DNA double-strand break in a sequence-specific manner, resulting in knockout. Some binary vectors for CRISPR/Cas9 in plants have been reported, but there is a problem with low efficiency. Here, we present a newly developed, highly efficient CRISPR/Cas9 vector for Arabidopsis thaliana, pKAMA-ITACHI Red (pKIR), harboring the RIBOSOMAL PROTEIN S5 A (RPS5A) promoter to drive Cas9. The RPS5A promoter maintains high constitutive expression at all developmental stages starting from the egg cell and including meristematic cells. Even in the T1 generation, pKIR induced null phenotypes in some genes: PHYTOENE DESATURASE 3 (PDS3), AGAMOUS (AG) and DUO POLLEN 1 (DUO1). Mutations induced by pKIR were carried in the germ cell line of the T1 generation. Surprisingly, in some lines, 100% of the T2 plants had the adh1 (ALCOHOL DEHYDROGENASE 1) null phenotype, indicating that pKIR strongly induced heritable mutations. Cas9-free T2 mutant plants were obtained by removing T2 seeds expressing a fluorescent marker in pKIR. Our results suggest that the pKIR system is a powerful molecular tool for genome engineering in Arabidopsis. PMID:27856772

Inhibition of hepatitis B virus replication via HBV DNA cleavage by Cas9 from Staphylococcus aureus.

PubMed

Liu, Yu; Zhao, Miaoxian; Gong, Mingxing; Xu, Ying; Xie, Cantao; Deng, Haohui; Li, Xueying; Wu, Hongkai; Wang, Zhanhui

2018-04-01

Chronic hepatitis B virus (HBV) infection is difficult to cure due to the presence of covalently closed circular DNA (cccDNA). Accumulating evidence indicates that the CRISPR/Cas9 system effectively disrupts HBV genome, including cccDNA, in vitro and in vivo. However, efficient delivery of CRISPR/Cas9 system to the liver or hepatocytes using an adeno-associated virus (AAV) vector remains challenging due to the large size of Cas9 from Streptococcus pyogenes (Sp). The recently identified Cas9 protein from Staphylococcus aureus (Sa) is smaller than SpCas9 and thus is able to be packaged into the AAV vector. To examine the efficacy of SaCas9 system on HBV genome destruction, we designed 5 guide RNAs (gRNAs) that targeted different HBV genotypes, 3 of which were shown to be effective. The SaCas9 system significantly reduced HBV antigen expression, as well as pgRNA and cccDNA levels, in Huh7, HepG2.2.15 and HepAD38 cells. The dual expression of gRNAs/SaCas9 in these cell lines resulted in more efficient HBV genome cleavage. In the mouse model, hydrodynamic injection of gRNA/SaCas9 plasmids resulted in significantly lower levels of HBV protein expression. We also delivered the SaCas9 system into mice with persistent HBV replication using an AAV vector. Both the AAV vector and the mRNA of Cas9 could be detected in the C3H mouse liver cells. Decreased hepatitis B surface antigen (HBsAg), HBV DNA and pgRNA levels were observed when a higher titer of AAV was injected, although this decrease was not significantly different from the control. In summary, the SaCas9 system accurately and efficiently targeted the HBV genome and inhibited HBV replication both in vitro and in vivo. The system was delivered by an AAV vector and maybe used as a novel therapeutic strategy against chronic HBV infection. Copyright © 2018 Elsevier B.V. All rights reserved.

Modulation of extracellular matrix in cancer is associated with enhanced tumor cell targeting by bacteriophage vectors.

PubMed

Yata, Teerapong; Lee, Eugene L Q; Suwan, Keittisak; Syed, Nelofer; Asavarut, Paladd; Hajitou, Amin

2015-06-03

Gene therapy has been an attractive paradigm for cancer treatment. However, cancer gene therapy has been challenged by the inherent limitation of vectors that are able to deliver therapeutic genes to tumors specifically and efficiently following systemic administration. Bacteriophage (phage) are viruses that have shown promise for targeted systemic gene delivery. Yet, they are considered poor vectors for gene transfer. Recently, we generated a tumor-targeted phage named adeno-associated virus/phage (AAVP), which is a filamentous phage particle whose genome contains the adeno-associated virus genome. Its effectiveness in delivering therapeutic genes to tumors specifically both in vitro and in vivo has been shown in numerous studies. Despite being a clinically useful vector, a multitude of barriers impede gene transduction to tumor cells. We hypothesized that one such factor is the tumor extracellular matrix (ECM). We used a number of tumor cell lines from different species and histological types in 2D monolayers or 3D multicellular tumor spheroid (MCTS) models. To assess whether the ECM is a barrier to tumor cell targeting by AAVP, we depleted the ECM using collagenase, hyaluronidase, or combination of both. We employed multiple techniques to investigate and quantify the effect of ECM depletion on ECM composition (including collagen type I, hyaluronic acid, fibronectin and laminin), and how AAVP adsorption, internalisation, gene expression and therapeutic efficacy are subsequently affected. Data were analyzed using a student's t test when comparing two groups or one-way ANOVA and post hoc Tukey tests when using more than two groups. We demonstrate that collagenase and hyaluronidase-mediated degradation of tumor ECM affects the composition of collagen, hyaluronic acid and fibronectin. Consequently, AAVP diffusion, internalisation, gene expression and tumor cell killing were enhanced after enzymatic treatment. Our data suggest that enhancement of gene transfer by the AAVP is solely attributed to ECM depletion. We provide substantial evidence that ECM modulation is relevant in clinically applicable settings by using 3D MCTS, which simulates in vivo environments more accurately. Our findings suggest that ECM depletion is an effective strategy to enhance the efficiency of viral vector-guided gene therapy.

Criteria for the prioritization of public health interventions for climate-sensitive vector-borne diseases in Quebec

PubMed Central

Gosselin, Pierre; Michel, Pascal; Ravel, André; Waaub, Jean-Philippe; Campagna, Céline; Samoura, Karim

2017-01-01

Prioritizing resources for optimal responses to an ever growing list of existing and emerging infectious diseases represents an important challenge to public health. In the context of climate change, there is increasing anticipated variability in the occurrence of infectious diseases, notably climate-sensitive vector-borne diseases. An essential step in prioritizing efforts is to identify what considerations and concerns to take into account to guide decisions and thus set disease priorities. This study was designed to perform a comprehensive review of criteria for vector-borne disease prioritization, assess their applicability in a context of climate change with a diverse cross-section of stakeholders in order to produce a baseline list of considerations to use in this decision-making context. Differences in stakeholder choices were examined with regards to prioritization of these criteria for research, surveillance and disease prevention and control objectives. A preliminary list of criteria was identified following a review of the literature. Discussions with stakeholders were held to consolidate and validate this list of criteria and examine their effects on disease prioritization. After this validation phase, a total of 21 criteria were retained. A pilot vector-borne disease prioritization exercise was conducted using PROMETHEE to examine the effects of the retained criteria on prioritization in different intervention domains. Overall, concerns expressed by stakeholders for prioritization were well aligned with categories of criteria identified in previous prioritization studies. Weighting by category was consistent between stakeholders overall, though some significant differences were found between public health and non-public health stakeholders. From this exercise, a general model for climate-sensitive vector-borne disease prioritization has been developed that can be used as a starting point for further public health prioritization exercises relating to research, surveillance, and prevention and control interventions in a context of climate change. Multi-stakeholder engagement in prioritization can help broaden the range of criteria taken into account, offer opportunities for early identification of potential challenges and may facilitate acceptability of any resulting decisions. PMID:29281726

Active control of lateral leakage in thin-ridge SOI waveguide structures

NASA Astrophysics Data System (ADS)

Dalvand, Naser; Nguyen, Thach G.; Tummidi, Ravi S.; Koch, Thomas L.; Mitchell, Arnan

2011-12-01

We report on the design and simulation of a novel Silicon-On-Insulator waveguide structures which when excited with TM guided light, emit TE polarized radiation with controlled radiation characteristics[1]. The structures utilize parallel leaky waveguides of specific separations. The structures are simulated using a full-vector mode-matching approach which allows visualisation of the evolution of the propagating and radiating fields over the length of the waveguide structure. It is shown that radiation can be resonantly enhanced or suppressed in different directions depending on the choice of the phase of the excitation of the waveguide components. Steps toward practical demonstration are identified.

Phi-s correlation and dynamic time warping - Two methods for tracking ice floes in SAR images

NASA Technical Reports Server (NTRS)

Mcconnell, Ross; Kober, Wolfgang; Kwok, Ronald; Curlander, John C.; Pang, Shirley S.

1991-01-01

The authors present two algorithms for performing shape matching on ice floe boundaries in SAR (synthetic aperture radar) images. These algorithms quickly produce a set of ice motion and rotation vectors that can be used to guide a pixel value correlator. The algorithms match a shape descriptor known as the Phi-s curve. The first algorithm uses normalized correlation to match the Phi-s curves, while the second uses dynamic programming to compute an elastic match that better accommodates ice floe deformation. Some empirical data on the performance of the algorithms on Seasat SAR images are presented.

Well-posed two-temperature constitutive equations for stable dense fluid shock waves using molecular dynamics and generalizations of Navier-Stokes-Fourier continuum mechanics.

PubMed

Hoover, Wm G; Hoover, Carol G

2010-04-01

Guided by molecular dynamics simulations, we generalize the Navier-Stokes-Fourier constitutive equations and the continuum motion equations to include both transverse and longitudinal temperatures. To do so we partition the contributions of the heat transfer, the work done, and the heat flux vector between the longitudinal and transverse temperatures. With shockwave boundary conditions time-dependent solutions of these equations converge to give stationary shockwave profiles. The profiles include anisotropic temperature and can be fitted to molecular dynamics results, demonstrating the utility and simplicity of a two-temperature description of far-from-equilibrium states.

Development of a kernel function for clinical data.

PubMed

Daemen, Anneleen; De Moor, Bart

2009-01-01

For most diseases and examinations, clinical data such as age, gender and medical history guides clinical management, despite the rise of high-throughput technologies. To fully exploit such clinical information, appropriate modeling of relevant parameters is required. As the widely used linear kernel function has several disadvantages when applied to clinical data, we propose a new kernel function specifically developed for this data. This "clinical kernel function" more accurately represents similarities between patients. Evidently, three data sets were studied and significantly better performances were obtained with a Least Squares Support Vector Machine when based on the clinical kernel function compared to the linear kernel function.

Waves in a plane graphene - dielectric waveguide structure

NASA Astrophysics Data System (ADS)

Evseev, Dmitry A.; Eliseeva, Svetlana V.; Sementsov, Dmitry I.

2017-10-01

The features of the guided TE modes propagation have been investigated on the basis of computer simulations in a planar structure consisting of a set of alternating layers of dielectric and graphene. Within the framework of the effective medium approximation, the dispersion relations have been received for symmetric and antisymmetric waveguide modes, determined by the frequency range of their existence. The wave field distribution by structure, frequency dependences of the constants of propagation and transverse components of the wave vectors, as well as group and phase velocities of waveguide modes have been obtained, the effect of the graphene part in a structure on the waveguide mode behavior has been shown.

Evaluation of the setup margins for cone beam computed tomography–guided cranial radiosurgery: A phantom study

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

Calvo Ortega, Juan Francisco, E-mail: jfcdrr@yahoo.es; Wunderink, Wouter; Delgado, David

The aim of this study is to evaluate the setup margins from the clinical target volume (CTV) to planning target volume (PTV) for cranial stereotactic radiosurgery (SRS) treatments guided by cone beam computed tomography (CBCT). We designed an end-to-end (E2E) test using a skull phantom with an embedded 6mm tungsten ball (target). A noncoplanar plan was computed (E2E plan) to irradiate the target. The CBCT-guided positioning of the skull phantom on the linac was performed. Megavoltage portal images were acquired after 15 independent deliveries of the E2E plan. The displacement 2-dimensional (2D) vector between the centers of the square fieldmore » and the ball target on each portal image was used to quantify the isocenter accuracy. Geometrical margins on each patient's direction (left-right or LR, anterior-posterior or AP, superior-inferior or SI) were calculated. Dosimetric validation of the margins was performed in 5 real SRS cases: 3-dimesional (3D) isocenter deviations were mimicked, and changes in CTV dose coverage and organs-at-risk (OARs) dosage were analyzed. The CTV-PTV margins of 1.1 mm in LR direction, and 0.7 mm in AP and SI directions were derived from the E2E tests. The dosimetric analysis revealed that a 1-mm uniform margin was sufficient to ensure the CTV dose coverage, without compromising the OAR dose tolerances. The effect of isocenter uncertainty has been estimated to be 1 mm in our CBCT-guided SRS approach.« less

Effect of Iris registration on visual outcome in wavefront-guided LASEK for myopic astigmatism.

PubMed

Lee, Jong Joo; Kim, Mee Kum; Wee, Won Ryang

2018-04-01

This study aimed to investigate the effect of iris registration (IR) on visual outcomes in wavefront-guided LASEK for myopic astigmatism. The retrospective chart review was performed for wavefront-guided LASEK using VISX Star S4 in patients with myopic astigmatism (cylinder ≥ 1.00 diopter[D]). Eyes were divided into IR group (LASEK with IR at the time of surgery) and Non-IR group (LASEK without IR system + failed-IR engagement during LASEK). Visual acuity (VA), astigmatism, higher-order aberration (HOA), and contrast sensitivity were assessed preoperatively and 3 months postoperatively. The IR and Non-IR groups were subcategorized depending on the spherical equivalent (lower myopia ≤-5.00 D vs. higher myopia >-5.00 D) for the comparison of HOA changes. Postoperative uncorrected VAs showed no differences between IR (n = 30) and Non-IR (n = 46). In astigmatic vector analyses, no differences were noted in the mean magnitude of error and the mean angle of error between two groups. There were no differences in postoperative total HOA, spherical aberration (SA), coma, and trefoil between the groups, either. The total HOA and SA increased in both groups, while coma increased only in Non-IR. In higher myopia, ΔRMS of coma was smaller in IR. Preoperative and postoperative total HOA were linearly correlated in Non-IR, but not for IR. Contrast sensitivity of 12 cycles per degree improved in both groups. IR had similar outcomes to conventional trackers in wavefront-guided LASEK, with less tendency of inducing coma, especially in higher myopia.

Ecotope-Based Entomological Surveillance and Molecular Xenomonitoring of Multidrug Resistant Malaria Parasites in Anopheles Vectors

PubMed Central

2014-01-01

The emergence and spread of multidrug resistant (MDR) malaria caused by Plasmodium falciparum or Plasmodium vivax have become increasingly important in the Greater Mekong Subregion (GMS). MDR malaria is the heritable and hypermutable property of human malarial parasite populations that can decrease in vitro and in vivo susceptibility to proven antimalarial drugs as they exhibit dose-dependent drug resistance and delayed parasite clearance time in treated patients. MDR malaria risk situations reflect consequences of the national policy and strategy as this influences the ongoing national-level or subnational-level implementation of malaria control strategies in endemic GMS countries. Based on our experience along with current literature review, the design of ecotope-based entomological surveillance (EES) and molecular xenomonitoring of MDR falciparum and vivax malaria parasites in Anopheles vectors is proposed to monitor infection pockets in transmission control areas of forest and forest fringe-related malaria, so as to bridge malaria landscape ecology (ecotope and ecotone) and epidemiology. Malaria ecotope and ecotone are confined to a malaria transmission area geographically associated with the infestation of Anopheles vectors and particular environments to which human activities are related. This enables the EES to encompass mosquito collection and identification, salivary gland DNA extraction, Plasmodium- and species-specific identification, molecular marker-based PCR detection methods for putative drug resistance genes, and data management. The EES establishes strong evidence of Anopheles vectors carrying MDR P. vivax in infection pockets epidemiologically linked with other data obtained during which a course of follow-up treatment of the notified P. vivax patients receiving the first-line treatment was conducted. For regional and global perspectives, the EES would augment the epidemiological surveillance and monitoring of MDR falciparum and vivax malaria parasites in hotspots or suspected areas established in most endemic GMS countries implementing the National Malaria Control Programs, in addition to what is guided by the World Health Organization. PMID:25349605

EMIRA: Ecologic Malaria Reduction for Africa--innovative tools for integrated malaria control.

PubMed

Dambach, Peter; Traoré, Issouf; Becker, Norbert; Kaiser, Achim; Sié, Ali; Sauerborn, Rainer

2014-01-01

Malaria control is based on early treatment of cases and on vector control. The current measures for malaria vector control in Africa are mainly based on long-lasting insecticide treated nets (LLINs) and to a much smaller extent on indoor residual spraying (IRS). A third pillar in the fight against the malaria vector, larval source management (LSM), has virtually not been used in Africa since the ban of DDT in the 1960s. Within the light of recent WHO recommendations for Bacillus thuringiensis israelensis (Bti) use against malaria and other vector species, larval source management could see a revival in the upcoming years. In this project we analyze the ecologic and health impacts as well as the cost effectiveness of larval source management under different larviciding scenarios in a health district in Burkina Faso. The project is designed as prospective intervention study with duration of three years (2013-2015). Its spatial scale includes three arms of interventions and control, comprising a total of 127 villages and the district capital Nouna in the extended HDSS (Health Demographic Surveillance System) of the Kossi province. Baseline data on mosquito abundance, parasitemia in U5 children, and malaria related morbidity and mortality are gathered over the project duration. Besides the outcome on ecologic and health parameters, the economic costs are seized and valued against the achieved health benefits. Risk map based, guided larvicide application might be a possibility to further decrease economic cost of LSM and facilitate its faster incorporation to integrated malaria control programs. Given the limited resources in many malaria endemic countries, it is of utmost importance to relate the costs of novel strategies for malaria prevention to their effect on the burden of the disease. Occurring costs and the impact on the health situation will be made comparable to other, existing intervention strategies, allowing stakeholders and policymakers decision making.

Effects of camera location on the reconstruction of 3D flare trajectory with two cameras

NASA Astrophysics Data System (ADS)

Özsaraç, Seçkin; Yeşilkaya, Muhammed

2015-05-01

Flares are used as valuable electronic warfare assets for the battle against infrared guided missiles. The trajectory of the flare is one of the most important factors that determine the effectiveness of the counter measure. Reconstruction of the three dimensional (3D) position of a point, which is seen by multiple cameras, is a common problem. Camera placement, camera calibration, corresponding pixel determination in between the images of different cameras and also the triangulation algorithm affect the performance of 3D position estimation. In this paper, we specifically investigate the effects of camera placement on the flare trajectory estimation performance by simulations. Firstly, 3D trajectory of a flare and also the aircraft, which dispenses the flare, are generated with simple motion models. Then, we place two virtual ideal pinhole camera models on different locations. Assuming the cameras are tracking the aircraft perfectly, the view vectors of the cameras are computed. Afterwards, using the view vector of each camera and also the 3D position of the flare, image plane coordinates of the flare on both cameras are computed using the field of view (FOV) values. To increase the fidelity of the simulation, we have used two sources of error. One is used to model the uncertainties in the determination of the camera view vectors, i.e. the orientations of the cameras are measured noisy. Second noise source is used to model the imperfections of the corresponding pixel determination of the flare in between the two cameras. Finally, 3D position of the flare is estimated using the corresponding pixel indices, view vector and also the FOV of the cameras by triangulation. All the processes mentioned so far are repeated for different relative camera placements so that the optimum estimation error performance is found for the given aircraft and are trajectories.

Ensembles of novelty detection classifiers for structural health monitoring using guided waves

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

Dib, Gerges; Karpenko, Oleksii; Koricho, Ermias

Guided wave structural health monitoring uses sparse sensor networks embedded in sophisticated structures for defect detection and characterization. The biggest challenge of those sensor networks is developing robust techniques for reliable damage detection under changing environmental and operating conditions. To address this challenge, we develop a novelty classifier for damage detection based on one class support vector machines. We identify appropriate features for damage detection and introduce a feature aggregation method which quadratically increases the number of available training observations.We adopt a two-level voting scheme by using an ensemble of classifiers and predictions. Each classifier is trained on a differentmore » segment of the guided wave signal, and each classifier makes an ensemble of predictions based on a single observation. Using this approach, the classifier can be trained using a small number of baseline signals. We study the performance using monte-carlo simulations of an analytical model and data from impact damage experiments on a glass fiber composite plate.We also demonstrate the classifier performance using two types of baseline signals: fixed and rolling baseline training set. The former requires prior knowledge of baseline signals from all environmental and operating conditions, while the latter does not and leverages the fact that environmental and operating conditions vary slowly over time and can be modeled as a Gaussian process.« less

A practical guide to big data research in psychology.

PubMed

Chen, Eric Evan; Wojcik, Sean P

2016-12-01

The massive volume of data that now covers a wide variety of human behaviors offers researchers in psychology an unprecedented opportunity to conduct innovative theory- and data-driven field research. This article is a practical guide to conducting big data research, covering data management, acquisition, processing, and analytics (including key supervised and unsupervised learning data mining methods). It is accompanied by walkthrough tutorials on data acquisition, text analysis with latent Dirichlet allocation topic modeling, and classification with support vector machines. Big data practitioners in academia, industry, and the community have built a comprehensive base of tools and knowledge that makes big data research accessible to researchers in a broad range of fields. However, big data research does require knowledge of software programming and a different analytical mindset. For those willing to acquire the requisite skills, innovative analyses of unexpected or previously untapped data sources can offer fresh ways to develop, test, and extend theories. When conducted with care and respect, big data research can become an essential complement to traditional research. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Interplay between topological phase and self-acceleration in a vortex symmetric Airy beam.

PubMed

Fang, Zhao-Xiang; Chen, Yue; Ren, Yu-Xuan; Gong, Lei; Lu, Rong-De; Zhang, An-Qi; Zhao, Hong-Ze; Wang, Pei

2018-03-19

Photons in an optical vortex usually carry orbital angular momentum, which boosts the application of the micro-rotation of absorbing particles and quantum information encoding. Such photons propagate along a straight line in free space or follow a curved trace once guided by an optical fiber. Teleportation of an optical vortex using a beam with non-diffraction and self-healing is quite challenging. We demonstrate the manipulation of the propagation trace of an optical vortex with a symmetric Airy beam (SAB) and found that the SAB experiences self-rotation with the implementation of a topological phase structure of coaxial vortex. Slight misalignment of the vortex and the SAB enables the guiding of the vortex into one of the self-accelerating channels. Multiple off-axis vortices embedded in SAB are also demonstrated to follow the trajectory of the major lobe for the SAB beam. The Poynting vector for the beams proves the direction of the energy flow corresponding to the intensity distribution. Hence, we anticipate that the proposed vortex symmetric Airy beam (VSAB) will provide new possibilities for optical manipulation and optical communication.

Robot Acquisition of Active Maps Through Teleoperation and Vector Space Analysis

NASA Technical Reports Server (NTRS)

Peters, Richard Alan, II

2003-01-01

The work performed under this contract was in the area of intelligent robotics. The problem being studied was the acquisition of intelligent behaviors by a robot. The method was to acquire action maps that describe tasks as sequences of reflexive behaviors. Action maps (a.k.a. topological maps) are graphs whose nodes represent sensorimotor states and whose edges represent the motor actions that cause the robot to proceed from one state to the next. The maps were acquired by the robot after being teleoperated or otherwise guided by a person through a task several times. During a guided task, the robot records all its sensorimotor signals. The signals from several task trials are partitioned into episodes of static behavior. The corresponding episodes from each trial are averaged to produce a task description as a sequence of characteristic episodes. The sensorimotor states that indicate episode boundaries become the nodes, and the static behaviors, the edges. It was demonstrated that if compound maps are constructed from a set of tasks then the robot can perform new tasks in which it was never explicitly trained.

High-efficiency targeted editing of large viral genomes by RNA-guided nucleases.

PubMed

Bi, Yanwei; Sun, Le; Gao, Dandan; Ding, Chen; Li, Zhihua; Li, Yadong; Cun, Wei; Li, Qihan

2014-05-01

A facile and efficient method for the precise editing of large viral genomes is required for the selection of attenuated vaccine strains and the construction of gene therapy vectors. The type II prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)) RNA-guided nuclease system can be introduced into host cells during viral replication. The CRISPR-Cas9 system robustly stimulates targeted double-stranded breaks in the genomes of DNA viruses, where the non-homologous end joining (NHEJ) and homology-directed repair (HDR) pathways can be exploited to introduce site-specific indels or insert heterologous genes with high frequency. Furthermore, CRISPR-Cas9 can specifically inhibit the replication of the original virus, thereby significantly increasing the abundance of the recombinant virus among progeny virus. As a result, purified recombinant virus can be obtained with only a single round of selection. In this study, we used recombinant adenovirus and type I herpes simplex virus as examples to demonstrate that the CRISPR-Cas9 system is a valuable tool for editing the genomes of large DNA viruses.

High-Efficiency Targeted Editing of Large Viral Genomes by RNA-Guided Nucleases

PubMed Central

Gao, Dandan; Ding, Chen; Li, Zhihua; Li, Yadong; Cun, Wei; Li, Qihan

2014-01-01

A facile and efficient method for the precise editing of large viral genomes is required for the selection of attenuated vaccine strains and the construction of gene therapy vectors. The type II prokaryotic CRISPR-Cas (clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas)) RNA-guided nuclease system can be introduced into host cells during viral replication. The CRISPR-Cas9 system robustly stimulates targeted double-stranded breaks in the genomes of DNA viruses, where the non-homologous end joining (NHEJ) and homology-directed repair (HDR) pathways can be exploited to introduce site-specific indels or insert heterologous genes with high frequency. Furthermore, CRISPR-Cas9 can specifically inhibit the replication of the original virus, thereby significantly increasing the abundance of the recombinant virus among progeny virus. As a result, purified recombinant virus can be obtained with only a single round of selection. In this study, we used recombinant adenovirus and type I herpes simplex virus as examples to demonstrate that the CRISPR-Cas9 system is a valuable tool for editing the genomes of large DNA viruses. PMID:24788700

Generating a stationary infinite range tractor force via a multimode optical fibre

NASA Astrophysics Data System (ADS)

Ebongue, C. A.; Holzmann, D.; Ostermann, S.; Ritsch, H.

2017-06-01

Optical fibres confine and guide light almost unattenuated and thus convey light forces to polarizable nano-particles over very long distances. Radiation pressure forces arise from scattering of guided photons into free space while gradient forces are based on coherent scattering between different fibre modes or propagation directions. Interestingly, even scattering between co-propagating modes induces longitudinal forces as the transverse confinement of the light modes creates mode dependent longitudinal wave-vectors and photon momenta. We generalize a proven scattering matrix based approach to calculate single as well as inter-particle forces to include several forward and backward propagating modes. We show that an injection of the higher order mode only in a two mode fibre will induce a stationary tractor force against the injection direction, when the mode coupling to the lower order mode dominates against backscattering and free space losses. Generically this arises for non-absorbing particles at the centre of a waveguide. The model also gives improved predictions for inter-particle forces in evanescent nanofibre fields as experimentally observed recently. Surprisingly strong tractor forces can also act on whole optically bound arrays.

Fuzzy Logic Particle Tracking

NASA Technical Reports Server (NTRS)

2005-01-01

A new all-electronic Particle Image Velocimetry technique that can efficiently map high speed gas flows has been developed in-house at the NASA Lewis Research Center. Particle Image Velocimetry is an optical technique for measuring the instantaneous two component velocity field across a planar region of a seeded flow field. A pulsed laser light sheet is used to illuminate the seed particles entrained in the flow field at two instances in time. One or more charged coupled device (CCD) cameras can be used to record the instantaneous positions of particles. Using the time between light sheet pulses and determining either the individual particle displacements or the average displacement of particles over a small subregion of the recorded image enables the calculation of the fluid velocity. Fuzzy logic minimizes the required operator intervention in identifying particles and computing velocity. Using two cameras that have the same view of the illumination plane yields two single exposure image frames. Two competing techniques that yield unambiguous velocity vector direction information have been widely used for reducing the single-exposure, multiple image frame data: (1) cross-correlation and (2) particle tracking. Correlation techniques yield averaged velocity estimates over subregions of the flow, whereas particle tracking techniques give individual particle velocity estimates. For the correlation technique, the correlation peak corresponding to the average displacement of particles across the subregion must be identified. Noise on the images and particle dropout result in misidentification of the true correlation peak. The subsequent velocity vector maps contain spurious vectors where the displacement peaks have been improperly identified. Typically these spurious vectors are replaced by a weighted average of the neighboring vectors, thereby decreasing the independence of the measurements. In this work, fuzzy logic techniques are used to determine the true correlation displacement peak even when it is not the maximum peak, hence maximizing the information recovery from the correlation operation, maintaining the number of independent measurements, and minimizing the number of spurious velocity vectors. Correlation peaks are correctly identified in both high and low seed density cases. The correlation velocity vector map can then be used as a guide for the particle-tracking operation. Again fuzzy logic techniques are used, this time to identify the correct particle image pairings between exposures to determine particle displacements, and thus the velocity. Combining these two techniques makes use of the higher spatial resolution available from the particle tracking. Particle tracking alone may not be possible in the high seed density images typically required for achieving good results from the correlation technique. This two-staged velocimetric technique can measure particle velocities with high spatial resolution over a broad range of seeding densities.

Delta Opioid Receptor (DOR) Ligands and Pharmacology: Development of Indolo- and Quinolinomorphinan Derivatives Based on the Message-Address Concept.

PubMed

Saitoh, Akiyoshi; Nagase, Hiroshi

2016-10-28

The pharmacology of the delta opioid receptor (DOR) has lagged, mainly due to the lack of an agonist with high potency and selectivity in vivo. The DOR is now receiving increasing attention, and there has been progress in the synthesis of better novel ligands. The discovery of a selective receptor DOR antagonist, naltrindole (NTI), stimulated the design and synthesis of (±)TAN-67, which was designed based on the message-address concept and the accessory site theory. Intensive studies using (±)TAN-67 determined the DOR-mediated various pharmacological effects, such as antinociceptive effects for painful diabetic neuropathy and cardiovascular protective effects. We improved the agonist activity of TAN-67 to afford SN-28, which was modified to KNT-127, a novel compound that improved the blood-brain barrier permeability. In addition, KNT-127 showed higher selectivity for the DOR and had potent agonist activity following systemic administration. Interestingly, KNT-127 produced no convulsive effects, unlike prototype DOR agonists. The KNT-127 type derivatives with a quinolinomorphinan structure are expected to be promising candidates for the development of therapeutic DOR agonists.

Automated astatination of biomolecules – a stepping stone towards multicenter clinical trials

PubMed Central

Aneheim, Emma; Albertsson, Per; Bäck, Tom; Jensen, Holger; Palm, Stig; Lindegren, Sture

2015-01-01

To facilitate multicentre clinical studies on targeted alpha therapy, it is necessary to develop an automated, on-site procedure for conjugating rare, short-lived, alpha-emitting radionuclides to biomolecules. Astatine-211 is one of the few alpha-emitting nuclides with appropriate chemical and physical properties for use in targeted therapies for cancer. Due to the very short range of the emitted α-particles, this therapy is particularly suited to treating occult, disseminated cancers. Astatine is not intrinsically tumour-specific; therefore, it requires an appropriate tumour-specific targeting vector, which can guide the radiation to the cancer cells. Consequently, an appropriate method is required for coupling the nuclide to the vector. To increase the availability of astatine-211 radiopharmaceuticals for targeted alpha therapy, their production should be automated. Here, we present a method that combines dry distillation of astatine-211 and a synthesis module for producing radiopharmaceuticals into a process platform. This platform will standardize production of astatinated radiopharmaceuticals, and hence, it will facilitate large clinical studies focused on this promising, but chemically challenging, alpha-emitting radionuclide. In this work, we describe the process platform, and we demonstrate the production of both astaine-211, for preclinical use, and astatine-211 labelled antibodies. PMID:26169786

Molecular and Functional Characterization of Odorant-Binding Protein Genes in an Invasive Vector Mosquito, Aedes albopictus

PubMed Central

Deng, Yuhua; Yan, Hui; Gu, Jinbao; Xu, Jiabao; Wu, Kun; Tu, Zhijian; James, Anthony A.; Chen, Xiaoguang

2013-01-01

Aedes albopictus is a major vector of dengue and Chikungunya viruses. Olfaction plays a vital role in guiding mosquito behaviors and contributes to their ability to transmit pathogens. Odorant-binding proteins (OBPs) are abundant in insect olfactory tissues and involved in the first step of odorant reception. While comprehensive descriptions are available of OBPs from Aedes aegypti, Culex quinquefasciatus and Anopheles gambiae, only a few genes from Ae. albopictus have been reported. In this study, twenty-one putative AalbOBP genes were cloned using their homologues in Ae. aegypti to query an Ae. albopictus partial genome sequence. Two antenna-specific OBPs, AalbOBP37 and AalbOBP39, display a remarkable similarity in their overall folding and binding pockets, according to molecular modeling. Binding affinity assays indicated that AalbOBP37 and AalbOBP39 had overlapping ligand affinities and are affected in different pH condition. Electroantennagrams (EAG) and behavioral tests show that these two genes were involved in olfactory reception. An improved understanding of the Ae. albopictus OBPs is expected to contribute to the development of more efficient and environmentally-friendly mosquito control strategies. PMID:23935894

Engineered Viruses as Genome Editing Devices.

PubMed

Chen, Xiaoyu; Gonçalves, Manuel A F V

2016-03-01

Genome editing based on sequence-specific designer nucleases, also known as programmable nucleases, seeks to modify in a targeted and precise manner the genetic information content of living cells. Delivering into cells designer nucleases alone or together with donor DNA templates, which serve as surrogate homologous recombination (HR) substrates, can result in gene knockouts or gene knock-ins, respectively. As engineered replication-defective viruses, viral vectors are having an increasingly important role as delivery vehicles for donor DNA templates and designer nucleases, namely, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated Cas9 (CRISPR-Cas9) nucleases, also known as RNA-guided nucleases (RGNs). We review this dual role played by engineered viral particles on genome editing while focusing on their main scaffolds, consisting of lentiviruses, adeno-associated viruses, and adenoviruses. In addition, the coverage of the growing body of research on the repurposing of viral vectors as delivery systems for genome editing tools is complemented with information regarding their main characteristics, pros, and cons. Finally, this information is framed by a concise description of the chief principles, tools, and applications of the genome editing field as a whole.

DyNAVacS: an integrative tool for optimized DNA vaccine design.

PubMed

Harish, Nagarajan; Gupta, Rekha; Agarwal, Parul; Scaria, Vinod; Pillai, Beena

2006-07-01

DNA vaccines have slowly emerged as keystones in preventive immunology due to their versatility in inducing both cell-mediated as well as humoral immune responses. The design of an efficient DNA vaccine, involves choice of a suitable expression vector, ensuring optimal expression by codon optimization, engineering CpG motifs for enhancing immune responses and providing additional sequence signals for efficient translation. DyNAVacS is a web-based tool created for rapid and easy design of DNA vaccines. It follows a step-wise design flow, which guides the user through the various sequential steps in the design of the vaccine. Further, it allows restriction enzyme mapping, design of primers spanning user specified sequences and provides information regarding the vectors currently used for generation of DNA vaccines. The web version uses Apache HTTP server. The interface was written in HTML and utilizes the Common Gateway Interface scripts written in PERL for functionality. DyNAVacS is an integrated tool consisting of user-friendly programs, which require minimal information from the user. The software is available free of cost, as a web based application at URL: http://miracle.igib.res.in/dynavac/.

Engineered Viruses as Genome Editing Devices

PubMed Central

Chen, Xiaoyu; Gonçalves, Manuel A F V

2016-01-01

Genome editing based on sequence-specific designer nucleases, also known as programmable nucleases, seeks to modify in a targeted and precise manner the genetic information content of living cells. Delivering into cells designer nucleases alone or together with donor DNA templates, which serve as surrogate homologous recombination (HR) substrates, can result in gene knockouts or gene knock-ins, respectively. As engineered replication-defective viruses, viral vectors are having an increasingly important role as delivery vehicles for donor DNA templates and designer nucleases, namely, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated Cas9 (CRISPR−Cas9) nucleases, also known as RNA-guided nucleases (RGNs). We review this dual role played by engineered viral particles on genome editing while focusing on their main scaffolds, consisting of lentiviruses, adeno-associated viruses, and adenoviruses. In addition, the coverage of the growing body of research on the repurposing of viral vectors as delivery systems for genome editing tools is complemented with information regarding their main characteristics, pros, and cons. Finally, this information is framed by a concise description of the chief principles, tools, and applications of the genome editing field as a whole. PMID:26336974

Automatic respiration tracking for radiotherapy using optical 3D camera

NASA Astrophysics Data System (ADS)

Li, Tuotuo; Geng, Jason; Li, Shidong

2013-03-01

Rapid optical three-dimensional (O3D) imaging systems provide accurate digitized 3D surface data in real-time, with no patient contact nor radiation. The accurate 3D surface images offer crucial information in image-guided radiation therapy (IGRT) treatments for accurate patient repositioning and respiration management. However, applications of O3D imaging techniques to image-guided radiotherapy have been clinically challenged by body deformation, pathological and anatomical variations among individual patients, extremely high dimensionality of the 3D surface data, and irregular respiration motion. In existing clinical radiation therapy (RT) procedures target displacements are caused by (1) inter-fractional anatomy changes due to weight, swell, food/water intake; (2) intra-fractional variations from anatomy changes within any treatment session due to voluntary/involuntary physiologic processes (e.g. respiration, muscle relaxation); (3) patient setup misalignment in daily reposition due to user errors; and (4) changes of marker or positioning device, etc. Presently, viable solution is lacking for in-vivo tracking of target motion and anatomy changes during the beam-on time without exposing patient with additional ionized radiation or high magnet field. Current O3D-guided radiotherapy systems relay on selected points or areas in the 3D surface to track surface motion. The configuration of the marks or areas may change with time that makes it inconsistent in quantifying and interpreting the respiration patterns. To meet the challenge of performing real-time respiration tracking using O3D imaging technology in IGRT, we propose a new approach to automatic respiration motion analysis based on linear dimensionality reduction technique based on PCA (principle component analysis). Optical 3D image sequence is decomposed with principle component analysis into a limited number of independent (orthogonal) motion patterns (a low dimension eigen-space span by eigen-vectors). New images can be accurately represented as weighted summation of those eigen-vectors, which can be easily discriminated with a trained classifier. We developed algorithms, software and integrated with an O3D imaging system to perform the respiration tracking automatically. The resulting respiration tracking system requires no human intervene during it tracking operation. Experimental results show that our approach to respiration tracking is more accurate and robust than the methods using manual selected markers, even in the presence of incomplete imaging data.

Inhibition of HBV replication in vivo using helper-dependent adenovirus vectors to deliver antiviral RNA interference expression cassettes.

PubMed

Crowther, Carol; Mowa, Mohube B; Ely, Abdullah; Arbuthnot, Patrick B

2014-01-01

HBV is hyperendemic to southern Africa and parts of Asia, but licensed antivirals have little effect on limiting life-threatening complications of the infection. Although RNA interference (RNAi)-based gene silencing has shown therapeutic potential, difficulties with delivery of anti-HBV RNAi effectors remain an obstacle to their clinical use. To address concerns about the transient nature of transgene expression and toxicity resulting from immunostimulation by recombinant adenovirus vectors (Ads), utility of RNAi-activating anti-HBV helper-dependent (HD) Ads were assessed in this study. Following intravenous administration of 5×10(9) unmodified or pegylated HD Ad infectious particles to HBV transgenic mice, HBV viral loads and serum HBV surface antigen levels were monitored for 12 weeks. Immunostimulation of HD Ads was assessed by measuring inflammatory cytokines, hepatic function and immune response to the co-delivered LacZ reporter gene. Unmodified and pegylated HD Ads transduced 80-90% of hepatocytes and expressed short hairpin RNAs (shRNAs) were processed to generate intended HBV-targeting guides. Markers of HBV replication were decreased by approximately 95% and silencing was sustained for 8 weeks. Unmodified HD Ads induced release of proinflammatory cytokines and there was evidence of an adaptive immune response to β-galactosidase. However the HD Ad-induced innate immune response was minimal in preparations that were enriched with infectious particles. HD Ads have potential utility for delivery of therapeutic HBV-silencing sequences and alterations of these vectors to attenuate their immune responses may further improve their efficacy.

pKAMA-ITACHI Vectors for Highly Efficient CRISPR/Cas9-Mediated Gene Knockout in Arabidopsis thaliana.

PubMed

Tsutsui, Hiroki; Higashiyama, Tetsuya

2017-01-01

The CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated 9) system is widely used as a tool for genome engineering in various organisms. A complex consisting of Cas9 and single guide RNA (sgRNA) induces a DNA double-strand break in a sequence-specific manner, resulting in knockout. Some binary vectors for CRISPR/Cas9 in plants have been reported, but there is a problem with low efficiency. Here, we present a newly developed, highly efficient CRISPR/Cas9 vector for Arabidopsis thaliana, pKAMA-ITACHI Red (pKIR), harboring the RIBOSOMAL PROTEIN S5 A (RPS5A) promoter to drive Cas9. The RPS5A promoter maintains high constitutive expression at all developmental stages starting from the egg cell and including meristematic cells. Even in the T1 generation, pKIR induced null phenotypes in some genes: PHYTOENE DESATURASE 3 (PDS3), AGAMOUS (AG) and DUO POLLEN 1 (DUO1). Mutations induced by pKIR were carried in the germ cell line of the T1 generation. Surprisingly, in some lines, 100% of the T2 plants had the adh1 (ALCOHOL DEHYDROGENASE 1) null phenotype, indicating that pKIR strongly induced heritable mutations. Cas9-free T2 mutant plants were obtained by removing T2 seeds expressing a fluorescent marker in pKIR. Our results suggest that the pKIR system is a powerful molecular tool for genome engineering in Arabidopsis. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists.

The Development of a Viral Mediated CRISPR/Cas9 System with Doxycycline Dependent gRNA Expression for Inducible In vitro and In vivo Genome Editing

PubMed Central

de Solis, Christopher A.; Ho, Anthony; Holehonnur, Roopashri; Ploski, Jonathan E.

2016-01-01

The RNA-guided Cas9 nuclease, from the type II prokaryotic Clustered Regularly Interspersed Short Palindromic Repeats (CRISPR) adaptive immune system, has been adapted and utilized by scientists to edit the genomes of eukaryotic cells. Here, we report the development of a viral mediated CRISPR/Cas9 system that can be rendered inducible utilizing doxycycline (Dox) and can be delivered to cells in vitro and in vivo utilizing adeno-associated virus (AAV). Specifically, we developed an inducible gRNA (gRNAi) AAV vector that is designed to express the gRNA from a H1/TO promoter. This AAV vector is also designed to express the Tet repressor (TetR) to regulate the expression of the gRNAi in a Dox dependent manner. We show that H1/TO promoters of varying length and a U6/TO promoter can edit DNA with similar efficiency in vitro, in a Dox dependent manner. We also demonstrate that our inducible gRNAi vector can be used to edit the genomes of neurons in vivo within the mouse brain in a Dox dependent manner. Genome editing can be induced in vivo with this system by supplying animals Dox containing food for as little as 1 day. This system might be cross compatible with many existing S. pyogenes Cas9 systems (i.e., Cas9 mouse, CRISPRi, etc.), and therefore it likely can be used to render these systems inducible as well. PMID:27587996

Age-related pathology after adenoviral overexpression of the leucine-rich repeat kinase 2 in the mouse striatum.

PubMed

Kritzinger, Astrid; Ferger, Boris; Gillardon, Frank; Stierstorfer, Birgit; Birk, Gerald; Kochanek, Stefan; Ciossek, Thomas

2018-06-01

Mutations in leucine-rich repeat kinase 2 (LRRK2) age-dependently cause Parkinson's disease and are associated with several inflammatory diseases. So far, the potential role of LRRK2 expression in glial cells as mediators of neuroinflammation and the influence of aging have not been investigated in viral vector-based LRRK2 animal models. In this study, we compared the effect of striatal injection of high-capacity adenoviral vectors expressing either a kinase-overactive LRRK2 with the familial G2019S mutation or a kinase-inactive LRRK2 variant in young and old C57BL/6J mice. The intrinsic adenovirus tropism guided preferentially glial transduction, and the vector design led to stable expression for at least 6 months. In histopathological analysis, young mice expressing either LRRK2 variant presented with transient vacuolization of striatal white fiber tracts accompanied by accumulation of microglial cells and astrogliosis, but inflammation resolved without permanent damage. Old mice had a stronger and prolonged inflammatory reaction and experienced permanent damage in form of partial neuron loss after 3 months exclusively in case of LRRK2_G2019S expression. The autophagic receptor p62 accumulated in cells with high levels of either LRRK2 variant, even more so in old mice. We conclude that the aging mouse brain is more susceptible to LRRK2-associated pathology, and in this model, glial LRRK2 expression significantly contributed to neuroinflammation, ultimately causing neurodegeneration. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Inhibition of histone deacetylation and DNA methylation improves gene expression mediated by the adeno-associated virus/phage in cancer cells.

PubMed

Kia, Azadeh; Yata, Teerapong; Hajji, Nabil; Hajitou, Amin

2013-10-22

Bacteriophage (phage), viruses that infect bacteria only, have become promising vectors for targeted systemic delivery of genes to cancer, although, with poor efficiency. We previously designed an improved phage vector by incorporating cis genetic elements of adeno-associated virus (AAV). This novel AAV/phage hybrid (AAVP) specifically targeted systemic delivery of therapeutic genes into tumors. To advance the AAVP vector, we recently introduced the stress-inducible Grp78 tumor specific promoter and found that this dual tumor-targeted AAVP provides persistent gene expression, over time, in cancer cells compared to silenced gene expression from the CMV promoter in the parental AAVP. Herein, we investigated the effect of histone deacetylation and DNA methylation on AAVP-mediated gene expression in cancer cells and explored the effect of cell confluence state on AAVP gene expression efficacy. Using a combination of AAVP expressing the GFP reporter gene, flow cytometry, inhibitors of histone deacetylation, and DNA methylation, we have demonstrated that histone deacetylation and DNA methylation are associated with silencing of gene expression from the CMV promoter in the parental AAVP. Importantly, inhibitors of histone deacetylases boost gene expression in cancer cells from the Grp78 promoter in the dual tumor-targeted AAVP. However, cell confluence had no effect on AAVP-guided gene expression. Our findings prove that combination of histone deacetylase inhibitor drugs with the Grp78 promoter is an effective approach to improve AAVP-mediated gene expression in cancer cells and should be considered for AAVP-based clinical cancer gene therapy.

Bayesian analogy with relational transformations.

PubMed

Lu, Hongjing; Chen, Dawn; Holyoak, Keith J

2012-07-01

How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. Copyright 2012 APA, all rights reserved.

Limited variance control in statistical low thrust guidance analysis. [stochastic algorithm for SEP comet Encke flyby mission

NASA Technical Reports Server (NTRS)

Jacobson, R. A.

1975-01-01

Difficulties arise in guiding a solar electric propulsion spacecraft due to nongravitational accelerations caused by random fluctuations in the magnitude and direction of the thrust vector. These difficulties may be handled by using a low thrust guidance law based on the linear-quadratic-Gaussian problem of stochastic control theory with a minimum terminal miss performance criterion. Explicit constraints are imposed on the variances of the control parameters, and an algorithm based on the Hilbert space extension of a parameter optimization method is presented for calculation of gains in the guidance law. The terminal navigation of a 1980 flyby mission to the comet Encke is used as an example.

Surge Flow in a Centrifugal Compressor Measured by Digital Particle Image Velocimetry

NASA Technical Reports Server (NTRS)

Wernet, Mark P.

2000-01-01

A planar optical velocity measurement technique known as Particle Image Velocimetry (PIV) is being used to study transient events in compressors. In PIV, a pulsed laser light sheet is used to record the positions of particles entrained in a fluid at two instances in time across a planar region of the flow. Determining the recorded particle displacement between exposures yields an instantaneous velocity vector map across the illuminated plane. Detailed flow mappings obtained using PIV in high-speed rotating turbomachinery components are used to improve the accuracy of computational fluid dynamics (CFD) simulations, which in turn, are used to guide advances in state-of-the-art aircraft engine hardware designs.

Ultrasound-guided microinjection into the mouse forebrain in utero at E9.5.

PubMed

Pierfelice, Tarran J; Gaiano, Nicholas

2010-11-13

In utero survival surgery in mice permits the molecular manipulation of gene expression during development. However, because the uterine wall is opaque during early embryogenesis, the ability to target specific parts of the embryo for microinjection is greatly limited. Fortunately, high-frequency ultrasound imaging permits the generation of images that can be used in real time to guide a microinjection needle into the embryonic region of interest. Here we describe the use of such imaging to guide the injection of retroviral vectors into the ventricular system of the mouse forebrain at embryonic day (E) 9.5. This method uses a laparotomy to permit access to the uterine horns, and a specially designed plate that permits host embryos to be bathed in saline while they are imaged and injected. Successful surgeries often result in most or all of the injected embryos surviving to any subsequent time point of interest (embryonically or postnatally). The principles described here can be used with slight modifications to perform injections into the amnionic fluid of E8.5 embryos (thereby permitting infection along the anterior posterior extent of the neural tube, which has not yet closed), or into the ventricular system of the brain at E10.5/11.5. Furthermore, at mid-neurogenic ages (~E13.5), ultrasound imaging can be used direct injection into specific brain regions for viral infection or cell transplantation. The use of ultrasound imaging to guide in utero injections in mice is a very powerful technique that permits the molecular and cellular manipulation of mouse embryos in ways that would otherwise be exceptionally difficult if not impossible.

Spatial and temporal distribution of house infestation by Triatoma infestans in the Toro Toro municipality, Potosi, Bolivia.

PubMed

Espinoza Echeverria, Jorge; Rodriguez, Antonio Nogales; Cortez, Mirko Rojas; Diotaiuti, Liléia Gonçalves; Gorla, David E

2017-02-02

Triatoma infestans is the main vector of Trypanosoma cruzi in Bolivia. The species is present both in domestic and peridomestic structures of rural areas, and in wild ecotopes of the Andean valleys and the Great Chaco. The identification of areas persistently showing low and high house infestation by the vector is important for the management of vector control programs. This study aimed at analyzing the temporal and spatial distribution of house infestation by T. infestans in the Toro Toro municipality (Potosi, Bolivia) between 2009 and 2014, and its association with environmental variables. House infestation and T. infestans density were calculated from entomological surveys of houses in the study area, using a fixed-time effort sampling technique. The spatial heterogeneity of house infestation was evaluated using the SatScan statistic. Association between house infestation with Bioclim variables (Worldclim database) and altitude was analyzed using a generalized linear model (GLM) with a logit link. Model selection was based on the Akaike information criteria after eliminating collinearity between variables using the variable inflation factor. The final model was used to create a probability map of house infestation for the Toro Toro municipality. A total of 73 communities and 16,489 house evaluation events were analyzed. Presence of T. infestans was recorded on 480 house evaluation events, giving an overall annual infestation of 2.9% during the studied period (range 1.5-5.4% in 2009 and 2012). Vector density remained at about 1.25 insects/ house. Infestation was highly aggregated in five clusters, including 11 communities. Relative risk of infestation within these clusters was 1.7-3.9 times the value for the regional average. Four environmental variables were identified as good descriptors of house infestation, explaining 57% of house infestation variability. The model allowed the estimation of a house infestation surface for the Toro Toro municipality. This study shows that residual and persistent populations of T. infestans maintain low house infestation, representing a potential risk for the transmission of T. cruzi in these communities, and it is possible to stratify house infestation using EV, and produce a risk map to guide the activities of vector control interventions in the municipality of Toro Toro (Potosi, Bolivia).

Vector-borne disease surveillance in livestock populations: A critical review of literature recommendations and implemented surveillance (BTV-8) in five European countries.

PubMed

Dórea, Fernanda C; Elbers, Armin R W; Hendrikx, Pascal; Enoe, Claes; Kirkeby, Carsten; Hoinville, Linda; Lindberg, Ann

2016-03-01

Preparedness against vector-borne threats depends on the existence of a long-term, sustainable surveillance of vector-borne disease and their relevant vectors. This work reviewed the availability of such surveillance systems in five European countries (Denmark, France, The Netherlands, Sweden and United Kingdom, part of the CoVetLab network). A qualitative assessment was then performed focusing on surveillance directed particularly to BTV-8. Information regarding surveillance activities were reviewed for the years 2008 and 2012. The results were then complemented with a critical scoping review of the literature aimed at identifying disease surveillance strategies and methods that are currently suggested as best suited to target vector-borne diseases in order to guide future development of surveillance in the countries in question. Passive surveillance was found to be efficient for early detection of diseases during the early phase of introduction into a free country. However, its value diminished once the disease has been established in a territory. Detection of emerging diseases was found to be very context and area specific, and thus active surveillance designs need to take the available epidemiological, ecological and entomological information into account. This was demonstrated by the effectiveness of the bulk milk surveillance in detecting the first case in Sweden, highlighting the need for output based standards to allow the most effective, context dependent, surveillance strategies to be used. Preparedness was of fundamental importance in determining the timeliness of detection and control in each country and that this in turn was heavily influenced by knowledge of emerging diseases in neighboring countries. Therefore it is crucial to share information on outbreaks between researchers and decision-makers and across borders continuously in order to react timely in case of an outbreak. Furthermore, timely reaction to an outbreak was heavily influenced by availability of control measures (vaccines), which is also strengthened if knowledge is shared quickly between countries. The assessment of the bluetongue surveillance in the affected countries showed that the degree of voluntary engagement varied, and that it is important to engage the public by general awareness and dissemination of results. The degree of engagement will also aid in establishing a passive surveillance system. Copyright © 2016 Elsevier B.V. All rights reserved.

Impacts of the creation, expansion and management of English wetlands on mosquito presence and abundance - developing strategies for future disease mitigation.

PubMed

Medlock, Jolyon M; Vaux, Alexander G C

2015-03-03

The incidence of mosquito-borne diseases is increasing in Europe, partly due to the incursion of a number of invasive species known to be vectors of dengue and chikungunya viruses, but also due to the involvement of native species in the transmission of West Nile virus and malaria. For some of these pathogens, there is a risk of the re-emergence of vector-borne diseases that were once widespread in Europe, but declined partly due to large-scale land-drainage projects. Some mosquito species exploit container habitats as breeding sites in urban areas; an adaptation to human-made micro-habitats resulting from increased urbanisation. However, many species thrive in natural wetland ecosystems. Owing to the impacts of climate change there is an urgent need for environmental adaptation, such as the creation of new wetlands to mitigate coastal and inland flooding. In some cases, these initiatives can be coupled with environmental change strategies to protect a range of endangered flora and fauna species by enhancing and extending wetland landscapes, which may by driven by European legislation, particularly in urban areas. This paper reviews field studies conducted in England to assess the impact of newly created wetlands on mosquito colonisation in a) coastal, b) urban and c) arable reversion habitats. It also considers the impact of wetland management on mosquito populations and explores the implications of various water and vegetation management options on the range of British mosquito species. Understanding the impact of wetland creation and management strategies on mosquito prevalence and the potential risk of increasing the levels of nuisance or disease vector species will be crucial in informing health and well-being risk assessments, guiding targeted control, and anticipating the social effects of extreme weather and climate change. Although new wetlands will certainly extend aquatic habitats for mosquitoes, not all species will become a major nuisance or a vector concern as a result. Understanding how the design and management of wetlands might exacerbate mosquito densities is crucial if we are to manage nuisance mosquitoes and control vector species in the event of a disease outbreak. This entomological evidence-base will ensure that control strategies achieve optimal efficacy at minimal cost.

National Positioning, Navigation, and Timing Architecture Study

NASA Astrophysics Data System (ADS)

van Dyke, K.; Vicario, J.; Hothem, L.

2007-12-01

The purpose of the National Positioning, Navigation and Timing (PNT) Architecture effort is to help guide future PNT system-of-systems investment and implementation decisions. The Assistant Secretary of Defense for Networks and Information Integration and the Under Secretary of Transportation for Policy sponsored a National PNT Architecture study to provide more effective and efficient PNT capabilities focused on the 2025 timeframe and an evolutionary path for government provided systems and services. U.S. Space-Based PNT Policy states that the U.S. must continue to improve and maintain GPS, augmentations to GPS, and back-up capabilities to meet growing national, homeland, and economic security needs. PNT touches almost every aspect of people´s lives today. PNT is essential for Defense and Civilian applications ranging from the Department of Defense´s Joint network centric and precision operations to the transportation and telecommunications sectors, improving efficiency, increasing safety, and being more productive. Absence of an approved PNT architecture results in uncoordinated research efforts, lack of clear developmental paths, potentially wasteful procurements and inefficient deployment of PNT resources. The national PNT architecture effort evaluated alternative future mixes of global (space and non space-based) and regional PNT solutions, PNT augmentations, and autonomous PNT capabilities to address priorities identified in the DoD PNT Joint Capabilities Document (JCD) and civil equivalents. The path to achieving the Should-Be architecture is described by the National PNT Architecture's Guiding Principles, representing an overarching Vision of the US' role in PNT, an architectural Strategy to fulfill that Vision, and four Vectors which support the Strategy. The National PNT Architecture effort has developed nineteen recommendations. Five foundational recommendations are tied directly to the Strategy while the remaining fourteen individually support one of the Vectors, as will be described in this presentation. The results of this effort will support future decisions of bodies such as the DoD PNT and Civil Pos/Nav Executive Committees, as well as the National Space-Based PNT Executive Committee (EXCOM).

A Pretargeted Approach for the Multimodal PET/NIRF Imaging of Colorectal Cancer.

PubMed

Adumeau, Pierre; Carnazza, Kathryn E; Brand, Christian; Carlin, Sean D; Reiner, Thomas; Agnew, Brian J; Lewis, Jason S; Zeglis, Brian M

2016-01-01

The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89 Zr poses two important clinical complications: high radiation doses to the patient and the need for significant lag time between imaging and surgery. In vivo pretargeting strategies that decouple the targeting vector from the radioactivity at the time of injection have the potential to circumvent these issues by facilitating the use of positron-emitting radioisotopes with far shorter half-lives. Here, we report the synthesis, characterization, and in vivo validation of a pretargeted strategy for the multimodal PET and NIRF imaging of colorectal carcinoma. This approach is based on the rapid and bioorthogonal ligation between a trans -cyclooctene- and fluorophore-bearing immunoconjugate of the huA33 antibody (huA33-Dye800-TCO) and a 64 Cu-labeled tetrazine radioligand ( 64 Cu-Tz-SarAr). In vivo imaging experiments in mice bearing A33 antigen-expressing SW1222 colorectal cancer xenografts clearly demonstrate that this approach enables the non-invasive visualization of tumors and the image-guided resection of malignant tissue, all at only a fraction of the radiation dose created by a directly labeled radioimmunoconjugate. Additional in vivo experiments in peritoneal and patient-derived xenograft models of colorectal carcinoma reinforce the efficacy of this methodology and underscore its potential as an innovative and useful clinical tool.

Antiosteoporotic compounds from seeds of Cuscuta chinensis.

PubMed

Yang, Lijuan; Chen, Qianfeng; Wang, Fei; Zhang, Guolin

2011-05-17

The seeds of Cuscuta chinensis (Tu-Si-Zi, TSZ) have long been used for the treatment of osteoporosis in China and some Asian countries. The compounds in TSZ responsible for the antiosteoporotic activity are still poorly understood. The present study was designed to investigate the osteogenic compounds in TSZ, and to evaluate their antiosteoporotic effects in osteoblastic cells. Osteoblast-like UMR-106 cells were used for bioactivity-guided isolation of the active compounds. The activity of alkaline phosphatase (ALP) in UMR-106 cells was measured by p-nitrophenyl sodium phosphate assay. The proliferation of UMR-106 cells was assayed by Alamar-Blue method. Estrogenic activity of the extracts and isolated compounds was evaluated by activation of estrogen response element (ERE) luciferase reporter expression in HeLa cells co-transfected with human estrogen receptor subtypes (ERα or ERβ) expression vectors and 5×ERE luciferase reporter plasmid. Antiestrogenic activity of the extracts and isolated compounds were evaluated by activation of activator protein-1 (AP-1) luciferase reporter expression in HeLa cells co-transfected with human estrogen receptor subtypes (ERα or ERβ) expression vectors and 6×AP-1 luciferase reporter plasmid. ALP-guided fractionation led to the isolation of five known flavonoids, quercetin, kaempferol, isorhamnetin, hyperoside and astragalin from the crude ethanolic extract of TSZ. Further study showed that kaempferol and hyperoside significantly increased the ALP activity in UMR-106 cells. Astragalin promoted the proliferation of UMR-106 cells whereas other compounds had no such effect. The isolated compounds showed estrogenic activity but quercetin, kaempferol and isorhamnetin showed more potent ERβ agonist activity. However, compared with their ER agonist activity, only quercetin and kaempferol showed potent ER antagonist activity by activating ERα/β-mediated AP-1 reporter expression. Our findings validated the clinical use of TSZ in the treatment of osteoporosis, and demonstrated that kaempferol and hyperoside are the active compounds in TSZ for the osteogenic effect. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Safeguarding Stem Cell-Based Regenerative Therapy against Iatrogenic Cancerogenesis: Transgenic Expression of DNASE1, DNASE1L3, DNASE2, DFFB Controlled By POLA1 Promoter in Proliferating and Directed Differentiation Resisting Human Autologous Pluripotent Induced Stem Cells Leads to their Death

PubMed Central

Malecki, Marek; LaVanne, Christine; Alhambra, Dominique; Dodivenaka, Chaitanya; Nagel, Sarah; Malecki, Raf

2014-01-01

Introduction The worst possible complication of using stem cells for regenerative therapy is iatrogenic cancerogenesis. The ultimate goal of our work is to develop a self-triggering feedback mechanism aimed at causing death of all stem cells, which resist directed differentiation, keep proliferating, and can grow into tumors. Specific aim The specific aim was threefold: (1) to genetically engineer the DNA constructs for the human, recombinant DNASE1, DNASE1L3, DNASE2, DFFB controlled by POLA promoter; (2) to bioengineer anti-SSEA-4 antibody guided vectors delivering transgenes to human undifferentiated and proliferating pluripotent stem cells; (3) to cause death of proliferating and directed differentiation resisting stem cells by transgenic expression of the human recombinant the DNases (hrDNases). Methods The DNA constructs for the human, recombinant DNASE1, DNASE1L3, DNASE2, DFFB controlled by POLA promoter were genetically engineered. The vectors targeting specifically SSEA-4 expressing stem cells were bioengineered. The healthy volunteers’ bone marrow mononuclear cells (BMMCs) were induced into human, autologous, pluripotent stem cells with non-integrating plasmids. Directed differentiation of the induced stem cells into endothelial cells was accomplished with EGF and BMP. The anti-SSEA 4 antibodies’ guided DNA vectors delivered the transgenes for the human recombinant DNases’ into proliferating stem cells. Results Differentiation of the pluripotent induced stem cells into the endothelial cells was verified by highlighting formation of tight and adherens junctions through transgenic expression of recombinant fluorescent fusion proteins: VE cadherin, claudin, zona occludens 1, and catenin. Proliferation of the stem cells was determined through highlighting transgenic expression of recombinant fluorescent proteins controlled by POLA promoter, while also reporting expression of the transgenes for the hrDNases. Expression of the transgenes for the DNases resulted in complete collapse of the chromatin architecture and degradation of the proliferating cells’ genomic DNA. The proliferating stem cells, but not the differentiating ones, were effectively induced to die. Conclusion Herein, we describe attaining the proof-of-concept for the strategy, whereby transgenic expression of the genetically engineered human recombinant DNases in proliferating and directed differentiation resisting stem cells leads to their death. This novel strategy reduces the risk of iatrogenic neoplasms in stem cell therapy. PMID:25045589

Effective learning strategies for real-time image-guided adaptive control of multiple-source hyperthermia applicators.

PubMed

Cheng, Kung-Shan; Dewhirst, Mark W; Stauffer, Paul R; Das, Shiva

2010-03-01

This paper investigates overall theoretical requirements for reducing the times required for the iterative learning of a real-time image-guided adaptive control routine for multiple-source heat applicators, as used in hyperthermia and thermal ablative therapy for cancer. Methods for partial reconstruction of the physical system with and without model reduction to find solutions within a clinically practical timeframe were analyzed. A mathematical analysis based on the Fredholm alternative theorem (FAT) was used to compactly analyze the existence and uniqueness of the optimal heating vector under two fundamental situations: (1) noiseless partial reconstruction and (2) noisy partial reconstruction. These results were coupled with a method for further acceleration of the solution using virtual source (VS) model reduction. The matrix approximation theorem (MAT) was used to choose the optimal vectors spanning the reduced-order subspace to reduce the time for system reconstruction and to determine the associated approximation error. Numerical simulations of the adaptive control of hyperthermia using VS were also performed to test the predictions derived from the theoretical analysis. A thigh sarcoma patient model surrounded by a ten-antenna phased-array applicator was retained for this purpose. The impacts of the convective cooling from blood flow and the presence of sudden increase of perfusion in muscle and tumor were also simulated. By FAT, partial system reconstruction directly conducted in the full space of the physical variables such as phases and magnitudes of the heat sources cannot guarantee reconstructing the optimal system to determine the global optimal setting of the heat sources. A remedy for this limitation is to conduct the partial reconstruction within a reduced-order subspace spanned by the first few maximum eigenvectors of the true system matrix. By MAT, this VS subspace is the optimal one when the goal is to maximize the average tumor temperature. When more than 6 sources present, the steps required for a nonlinear learning scheme is theoretically fewer than that of a linear one, however, finite number of iterative corrections is necessary for a single learning step of a nonlinear algorithm. Thus, the actual computational workload for a nonlinear algorithm is not necessarily less than that required by a linear algorithm. Based on the analysis presented herein, obtaining a unique global optimal heating vector for a multiple-source applicator within the constraints of real-time clinical hyperthermia treatments and thermal ablative therapies appears attainable using partial reconstruction with minimum norm least-squares method with supplemental equations. One way to supplement equations is the inclusion of a method of model reduction.

Clinical experience with image-guided radiotherapy in an accelerated partial breast intensity-modulated radiotherapy protocol.

PubMed

Leonard, Charles E; Tallhamer, Michael; Johnson, Tim; Hunter, Kari; Howell, Kathryn; Kercher, Jane; Widener, Jodi; Kaske, Terese; Paul, Devchand; Sedlacek, Scot; Carter, Dennis L

2010-02-01

To explore the feasibility of fiducial markers for the use of image-guided radiotherapy (IGRT) in an accelerated partial breast intensity modulated radiotherapy protocol. Nineteen patients consented to an institutional review board approved protocol of accelerated partial breast intensity-modulated radiotherapy with fiducial marker placement and treatment with IGRT. Patients (1 patient with bilateral breast cancer; 20 total breasts) underwent ultrasound guided implantation of three 1.2- x 3-mm gold markers placed around the surgical cavity. For each patient, table shifts (inferior/superior, right/left lateral, and anterior/posterior) and minimum, maximum, mean error with standard deviation were recorded for each of the 10 BID treatments. The dose contribution of daily orthogonal films was also examined. All IGRT patients underwent successful marker placement. In all, 200 IGRT treatment sessions were performed. The average vector displacement was 4 mm (range, 2-7 mm). The average superior/inferior shift was 2 mm (range, 0-5 mm), the average lateral shift was 2 mm (range, 1-4 mm), and the average anterior/posterior shift was 3 mm (range, 1 5 mm). This study shows that the use of IGRT can be successfully used in an accelerated partial breast intensity-modulated radiotherapy protocol. The authors believe that this technique has increased daily treatment accuracy and permitted reduction in the margin added to the clinical target volume to form the planning target volume. Copyright 2010 Elsevier Inc. All rights reserved.

Using latent semantic analysis and the predication algorithm to improve extraction of meanings from a diagnostic corpus.

PubMed

Jorge-Botana, Guillermo; Olmos, Ricardo; León, José Antonio

2009-11-01

There is currently a widespread interest in indexing and extracting taxonomic information from large text collections. An example is the automatic categorization of informally written medical or psychological diagnoses, followed by the extraction of epidemiological information or even terms and structures needed to formulate guiding questions as an heuristic tool for helping doctors. Vector space models have been successfully used to this end (Lee, Cimino, Zhu, Sable, Shanker, Ely & Yu, 2006; Pakhomov, Buntrock & Chute, 2006). In this study we use a computational model known as Latent Semantic Analysis (LSA) on a diagnostic corpus with the aim of retrieving definitions (in the form of lists of semantic neighbors) of common structures it contains (e.g. "storm phobia", "dog phobia") or less common structures that might be formed by logical combinations of categories and diagnostic symptoms (e.g. "gun personality" or "germ personality"). In the quest to bring definitions into line with the meaning of structures and make them in some way representative, various problems commonly arise while recovering content using vector space models. We propose some approaches which bypass these problems, such as Kintsch's (2001) predication algorithm and some corrections to the way lists of neighbors are obtained, which have already been tested on semantic spaces in a non-specific domain (Jorge-Botana, León, Olmos & Hassan-Montero, under review). The results support the idea that the predication algorithm may also be useful for extracting more precise meanings of certain structures from scientific corpora, and that the introduction of some corrections based on vector length may increases its efficiency on non-representative terms.

Dynamical generation of a repulsive vector contribution to the quark pressure

NASA Astrophysics Data System (ADS)

Restrepo, Tulio E.; Macias, Juan Camilo; Pinto, Marcus Benghi; Ferrari, Gabriel N.

2015-03-01

Lattice QCD results for the coefficient c2 appearing in the Taylor expansion of the pressure show that this quantity increases with the temperature towards the Stefan-Boltzmann limit. On the other hand, model approximations predict that when a vector repulsion, parametrized by GV, is present this coefficient reaches a maximum just after Tc and then deviates from the lattice predictions. Recently, this discrepancy has been used as a guide to constrain the (presently unknown) value of GV within the framework of effective models at large Nc (LN). In the present investigation we show that, due to finite Nc effects, c2 may also develop a maximum even when GV=0 since a vector repulsive term can be dynamically generated by exchange-type radiative corrections. Here we apply the optimized perturbation theory (OPT) method to the two-flavor Polyakov-Nambu-Jona-Lasinio model (at GV=0 ) and compare the results with those furnished by lattice simulations and by the LN approximation at GV=0 and also at GV≠0 . The OPT numerical results for c2 are impressively accurate for T ≲1.2 Tc but, as expected, they predict that this quantity develops a maximum at high T . After identifying the mathematical origin of this extremum we argue that such a discrepant behavior may naturally arise within this type of effective quark theories (at GV=0 ) whenever the first 1 /Nc corrections are taken into account. We then interpret this hypothesis as an indication that beyond the large-Nc limit the correct high-temperature (perturbative) behavior of c2 will be faithfully described by effective models only if they also mimic the asymptotic freedom phenomenon.

On Docking, Scoring and Assessing Protein-DNA Complexes in a Rigid-Body Framework

PubMed Central

Parisien, Marc; Freed, Karl F.; Sosnick, Tobin R.

2012-01-01

We consider the identification of interacting protein-nucleic acid partners using the rigid body docking method FTdock, which is systematic and exhaustive in the exploration of docking conformations. The accuracy of rigid body docking methods is tested using known protein-DNA complexes for which the docked and undocked structures are both available. Additional tests with large decoy sets probe the efficacy of two published statistically derived scoring functions that contain a huge number of parameters. In contrast, we demonstrate that state-of-the-art machine learning techniques can enormously reduce the number of parameters required, thereby identifying the relevant docking features using a miniscule fraction of the number of parameters in the prior works. The present machine learning study considers a 300 dimensional vector (dependent on only 15 parameters), termed the Chemical Context Profile (CCP), where each dimension reflects a specific type of protein amino acid-nucleic acid base interaction. The CCP is designed to capture the chemical complementarities of the interface and is well suited for machine learning techniques. Our objective function is the Chemical Context Discrepancy (CCD), which is defined as the angle between the native system's CCP vector and the decoy's vector and which serves as a substitute for the more commonly used root mean squared deviation (RMSD). We demonstrate that the CCP provides a useful scoring function when certain dimensions are properly weighted. Finally, we explore how the amino acids on a protein's surface can help guide DNA binding, first through long-range interactions, followed by direct contacts, according to specific preferences for either the major or minor grooves of the DNA. PMID:22393431

[Navigated drilling for femoral head necrosis. Experimental and clinical results].

PubMed

Beckmann, J; Tingart, M; Perlick, L; Lüring, C; Grifka, J; Anders, S

2007-05-01

In the early stages of osteonecrosis of the femoral head, core decompression by exact drilling into the ischemic areas can reduce pain and achieve reperfusion. Using computer aided surgery, the precision of the drilling can be improved while simultaneously lowering radiation exposure time for both staff and patients. We describe the experimental and clinical results of drilling under the guidance of the fluoroscopically-based VectorVision navigation system (BrainLAB, Munich, Germany). A total of 70 sawbones were prepared mimicking an osteonecrosis of the femoral head. In two experimental models, bone only and obesity, as well as in a clinical setting involving ten patients with osteonecrosis of the femoral head, the precision and the duration of radiation exposure were compared between the VectorVision system and conventional drilling. No target was missed. For both models, there was a statistically significant difference in terms of the precision, the number of drilling corrections as well as the radiation exposure time. The average distance to the desired midpoint of the lesion of both models was 0.48 mm for navigated drilling and 1.06 mm for conventional drilling, the average drilling corrections were 0.175 and 2.1, and the radiation exposure time less than 1 s and 3.6 s, respectively. In the clinical setting, the reduction of radiation exposure (below 1 s for navigation compared to 56 s for the conventional technique) as well as of drilling corrections (0.2 compared to 3.4) was also significant. Computer guided drilling using the fluoroscopically based VectorVision navigation system shows a clearly improved precision with a enormous simultaneous reduction in radiation exposure. It is therefore recommended for clinical routine.

Precision of computer-assisted core decompression drilling of the femoral head.

PubMed

Beckmann, J; Goetz, J; Baethis, H; Kalteis, T; Grifka, J; Perlick, L

2006-08-01

Osteonecrosis of the femoral head is a local destructive disease with progression into devastating stages. Left untreated it mostly leads to severe secondary osteoarthrosis and early endoprosthetic joint replacement. Core decompression by exact drilling into the ischemic areas can be performed in early stages according to Ficat or ARCO. Computer-aided surgery might enhance the precision of the drilling and lower the radiation exposure time of both staff and patients. The aim of this study was to evaluate the precision of the fluoroscopically based VectorVision navigation system in an in vitro model. Thirty sawbones were prepared with a defect filled up with a radiopaque gypsum sphere mimicking the osteonecrosis. Twenty sawbones were drilled by guidance of an intraoperative navigation system VectorVision (BrainLAB, Munich, Germany) and 10 sawbones by fluoroscopic control only. No gypsum sphere was missed. There was a statistically significant difference regarding the three-dimensional deviation (Euclidian norm) as well as maximum deviation in x-, y- or z-direction (maximum norm) to the desired mid-point of the lesion, with a mean of 0.51 and 0.4 mm in the navigated group and 1.1 and 0.88 mm in the control group, respectively. Furthermore, significant difference was found in the number of drilling corrections as well as the radiation time needed: no second drilling or correction of drilling direction was necessary in the navigated group compared to 1.4 in the control group. The radiation time needed was less than 1 s compared to 3.1 s, respectively. The fluoroscopy-based VectorVision navigation system shows a high feasibility of computer-guided drilling with a clear reduction of radiation exposure time and can therefore be integrated into clinical routine. The additional time needed is acceptable regarding the simultaneous reduction of radiation time.

Establishment of expanded and streamlined pipeline of PITCh knock-in – a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO

PubMed Central

Nakamae, Kazuki; Nishimura, Yuki; Takenaga, Mitsumasa; Sakamoto, Naoaki; Ide, Hiroshi; Sakuma, Tetsushi; Yamamoto, Takashi

2017-01-01

ABSTRACT The emerging genome editing technology has enabled the creation of gene knock-in cells easily, efficiently, and rapidly, which has dramatically accelerated research in the field of mammalian functional genomics, including in humans. We recently developed a microhomology-mediated end-joining-based gene knock-in method, termed the PITCh system, and presented various examples of its application. Since the PITCh system only requires very short microhomologies (up to 40 bp) and single-guide RNA target sites on the donor vector, the targeting construct can be rapidly prepared compared with the conventional targeting vector for homologous recombination-based knock-in. Here, we established a streamlined pipeline to design and perform PITCh knock-in to further expand the availability of this method by creating web-based design software, PITCh designer (http://www.mls.sci.hiroshima-u.ac.jp/smg/PITChdesigner/index.html), as well as presenting an experimental example of versatile gene cassette knock-in. PITCh designer can automatically design not only the appropriate microhomologies but also the primers to construct locus-specific donor vectors for PITCh knock-in. By using our newly established pipeline, a reporter cell line for monitoring endogenous gene expression, and transgenesis (TG) or knock-in/knockout (KIKO) cell line can be produced systematically. Using these new variations of PITCh, an exogenous promoter-driven gene cassette expressing fluorescent protein gene and drug resistance gene can be integrated into a safe harbor or a specific gene locus to create transgenic reporter cells (PITCh-TG) or knockout cells with reporter knock-in (PITCh-KIKO), respectively. PMID:28453368

Establishment of expanded and streamlined pipeline of PITCh knock-in - a web-based design tool for MMEJ-mediated gene knock-in, PITCh designer, and the variations of PITCh, PITCh-TG and PITCh-KIKO.

PubMed

Nakamae, Kazuki; Nishimura, Yuki; Takenaga, Mitsumasa; Nakade, Shota; Sakamoto, Naoaki; Ide, Hiroshi; Sakuma, Tetsushi; Yamamoto, Takashi

2017-05-04

The emerging genome editing technology has enabled the creation of gene knock-in cells easily, efficiently, and rapidly, which has dramatically accelerated research in the field of mammalian functional genomics, including in humans. We recently developed a microhomology-mediated end-joining-based gene knock-in method, termed the PITCh system, and presented various examples of its application. Since the PITCh system only requires very short microhomologies (up to 40 bp) and single-guide RNA target sites on the donor vector, the targeting construct can be rapidly prepared compared with the conventional targeting vector for homologous recombination-based knock-in. Here, we established a streamlined pipeline to design and perform PITCh knock-in to further expand the availability of this method by creating web-based design software, PITCh designer ( http://www.mls.sci.hiroshima-u.ac.jp/smg/PITChdesigner/index.html ), as well as presenting an experimental example of versatile gene cassette knock-in. PITCh designer can automatically design not only the appropriate microhomologies but also the primers to construct locus-specific donor vectors for PITCh knock-in. By using our newly established pipeline, a reporter cell line for monitoring endogenous gene expression, and transgenesis (TG) or knock-in/knockout (KIKO) cell line can be produced systematically. Using these new variations of PITCh, an exogenous promoter-driven gene cassette expressing fluorescent protein gene and drug resistance gene can be integrated into a safe harbor or a specific gene locus to create transgenic reporter cells (PITCh-TG) or knockout cells with reporter knock-in (PITCh-KIKO), respectively.

Consciousness of Unification: The Mind-Matter Phallacy Bites the Dust

NASA Astrophysics Data System (ADS)

Beichler, James E.

A complete theoretical model of how consciousness arises in neural nets can be developed based on a mixed quantum/classical basis. Both mind and consciousness are multi-leveled scalar and vector electromagnetic complexity patterns, respectively, which emerge within all living organisms through the process of evolution. Like life, the mind and consciousness patterns extend throughout living organisms (bodies), but the neural nets and higher level groupings that distinguish higher levels of consciousness only exist in the brain so mind and consciousness have been traditionally associated with the brain alone. A close study of neurons and neural nets in the brain shows that the microtubules within axons are classical bio-magnetic inductors that emit and absorb electromagnetic pulses from each other. These pulses establish interference patterns that influence the quantized vector potential patterns of interstitial water molecules within the neurons as well as create the coherence within neurons and neural nets that scientists normally associate with more complex memories, thought processes and streams of thought. Memory storage and recall are guided by the microtubules and the actual memory patterns are stored as magnetic vector potential complexity patterns in the points of space at the quantum level occupied by the water molecules. This model also accounts for the plasticity of the brain and implies that mind and consciousness, like life itself, are the result of evolutionary processes. However, consciousness can evolve independent of an organism's birth genetics once it has evolved by normal bottom-up genetic processes and thus force a new type of top-down evolution on living organisms and species as a whole that can be explained by expanding the laws of thermodynamics to include orderly systems.

Tsetse Fly (G.f. fuscipes) Distribution in the Lake Victoria Basin of Uganda

PubMed Central

Albert, Mugenyi; Wardrop, Nicola A; Atkinson, Peter M; Torr, Steve J; Welburn, Susan C

2015-01-01

Tsetse flies transmit trypanosomes, the causative agent of human and animal African trypanosomiasis. The tsetse vector is extensively distributed across sub-Saharan Africa. Trypanosomiasis maintenance is determined by the interrelationship of three elements: vertebrate host, parasite and the vector responsible for transmission. Mapping the distribution and abundance of tsetse flies assists in predicting trypanosomiasis distributions and developing rational strategies for disease and vector control. Given scarce resources to carry out regular full scale field tsetse surveys to up-date existing tsetse maps, there is a need to devise inexpensive means for regularly obtaining dependable area-wide tsetse data to guide control activities. In this study we used spatial epidemiological modelling techniques (logistic regression) involving 5000 field-based tsetse-data (G. f. fuscipes) points over an area of 40,000 km2, with satellite-derived environmental surrogates composed of precipitation, temperature, land cover, normalised difference vegetation index (NDVI) and elevation at the sub-national level. We used these extensive tsetse data to analyse the relationships between presence of tsetse (G. f. fuscipes) and environmental variables. The strength of the results was enhanced through the application of a spatial autologistic regression model (SARM). Using the SARM we showed that the probability of tsetse presence increased with proportion of forest cover and riverine vegetation. The key outputs are a predictive tsetse distribution map for the Lake Victoria basin of Uganda and an improved understanding of the association between tsetse presence and environmental variables. The predicted spatial distribution of tsetse in the Lake Victoria basin of Uganda will provide significant new information to assist with the spatial targeting of tsetse and trypanosomiasis control. PMID:25875201

Ecology, biology and distribution of spotted-fever tick vectors in Brazil.

PubMed

Szabó, Matias P J; Pinter, Adriano; Labruna, Marcelo B

2013-01-01

Spotted-fever-caused Rickettsia rickettsii infection is in Brazil the major tick-borne zoonotic disease. Recently, a second and milder human rickettsiosis caused by an agent genetically related to R. parkeri was discovered in the country (Atlantic rainforest strain). Both diseases clearly have an ecological background linked to a few tick species and their environment. Capybaras (Hydrochoerus hydrochaeris) and Amblyomma cajennense ticks in urban and rural areas close to water sources are the main and long-known epidemiological feature behind R. rickettsii-caused spotted-fever. Unfortunately, this ecological background seems to be increasing in the country and disease spreading may be foreseen. Metropolitan area of São Paulo, the most populous of the country, is embedded in Atlantic rainforest that harbors another important R. rickettsii vector, the tick Amblyomma aureolatum. Thus, at the city-forest interface, dogs carry infected ticks to human dwellings and human infection occurs. A role for R. rickettsii vectoring to humans of a third tick species, Rhipicephalus sanguineus in Brazil, has not been proven; however, there is circumstantial evidence for that. A R. parkeri-like strain was found in A. ovale ticks from Atlantic rainforest and was shown to be responsible for a milder febrile human disease. Rickettsia-infected A. ovale ticks are known to be spread over large areas along the Atlantic coast of the country, and diagnosis of human infection is increasing with awareness and proper diagnostic tools. In this review, ecological features of the tick species mentioned, and that are important for Rickettsia transmission to humans, are updated and discussed. Specific knowledge gaps in the epidemiology of such diseases are highlighted to guide forthcoming research.

Ecology, biology and distribution of spotted-fever tick vectors in Brazil

PubMed Central

Szabó, Matias P. J.; Pinter, Adriano; Labruna, Marcelo B.

2013-01-01

Spotted-fever-caused Rickettsia rickettsii infection is in Brazil the major tick-borne zoonotic disease. Recently, a second and milder human rickettsiosis caused by an agent genetically related to R. parkeri was discovered in the country (Atlantic rainforest strain). Both diseases clearly have an ecological background linked to a few tick species and their environment. Capybaras (Hydrochoerus hydrochaeris) and Amblyomma cajennense ticks in urban and rural areas close to water sources are the main and long-known epidemiological feature behind R. rickettsii-caused spotted-fever. Unfortunately, this ecological background seems to be increasing in the country and disease spreading may be foreseen. Metropolitan area of São Paulo, the most populous of the country, is embedded in Atlantic rainforest that harbors another important R. rickettsii vector, the tick Amblyomma aureolatum. Thus, at the city–forest interface, dogs carry infected ticks to human dwellings and human infection occurs. A role for R. rickettsii vectoring to humans of a third tick species, Rhipicephalus sanguineus in Brazil, has not been proven; however, there is circumstantial evidence for that. A R. parkeri-like strain was found in A. ovale ticks from Atlantic rainforest and was shown to be responsible for a milder febrile human disease. Rickettsia-infected A. ovale ticks are known to be spread over large areas along the Atlantic coast of the country, and diagnosis of human infection is increasing with awareness and proper diagnostic tools. In this review, ecological features of the tick species mentioned, and that are important for Rickettsia transmission to humans, are updated and discussed. Specific knowledge gaps in the epidemiology of such diseases are highlighted to guide forthcoming research. PMID:23875178

Acquisition and expression of memories of distance and direction in navigating wood ants.

PubMed

Fernandes, A Sofia D; Philippides, Andrew; Collett, Tom S; Niven, Jeremy E

2015-11-01

Wood ants, like other central place foragers, rely on route memories to guide them to and from a reliable food source. They use visual memories of the surrounding scene and probably compass information to control their direction. Do they also remember the length of their route and do they link memories of direction and distance? To answer these questions, we trained wood ant (Formica rufa) foragers in a channel to perform either a single short foraging route or two foraging routes in opposite directions. By shifting the starting position of the route within the channel, but keeping the direction and distance fixed, we tried to ensure that the ants would rely upon vector memories rather than visual memories to decide when to stop. The homeward memories that the ants formed were revealed by placing fed or unfed ants directly into a channel and assessing the direction and distance that they walked without prior performance of the food-ward leg of the journey. This procedure prevented the distance and direction walked being affected by a home vector derived from path integration. Ants that were unfed walked in the feeder direction. Fed ants walked in the opposite direction for a distance related to the separation between start and feeder. Vector memories of a return route can thus be primed by the ants' feeding state and expressed even when the ants have not performed the food-ward route. Tests on ants that have acquired two routes indicate that memories of the direction and distance of the return routes are linked, suggesting that they may be encoded by a common neural population within the ant brain. © 2015. Published by The Company of Biologists Ltd.

Coinfection by the tick-borne pathogens Babesia microti and Borrelia burgdorferi: ecological, epidemiological and clinical consequences

PubMed Central

Diuk-Wasser, Maria A.; Vannier, Edouard

2015-01-01

Ixodes ticks maintain a large and diverse array of human pathogens in the enzootic cycle, including Borrelia burgdorferi and Babesia microti. Despite the poor ecological fitness of B. microti, babesiosis has recently emerged in areas endemic for Lyme disease. Studies in ticks, reservoir hosts and humans indicate that coinfection with B. burgdorferi and B. microti is common, promotes transmission and emergence of B. microti in the enzootic cycle, and causes greater disease severity and duration in humans. These integrative studies may serve as a paradigm for the study of other vector-borne coinfections. Identifying ecological drivers of pathogen emergence and host factors that fuel disease severity will help guide the design of effective curative and prevention strategies. PMID:26613664

Rotation Flaps-Principles and Locations.

PubMed

LoPiccolo, Matteo C

2015-10-01

The rotation flap is a classic method of tissue rearrangement. It is a simple yet effective tool for recruiting tissue from areas of laxity and redirecting vectors of tension to reconstruct wounds not amenable to primary closure. This article presents the basic design principles and specific applications of the rotation flap in dermatologic surgery. A Medline search of articles describing rotation flaps published prior to April 1, 2015 was performed, and several prominent texts in dermatologic surgery were reviewed. Information gathered from the above sources is combined with the clinical experience of the author and editors to present surgeons with a guide for planning and executing various rotation flaps. Mastering the technique of the rotation flap will allow a surgeon to repair a wide variety of cutaneous defects.

Efficient computation of photonic crystal waveguide modes with dispersive material.

PubMed

Schmidt, Kersten; Kappeler, Roman

2010-03-29

The optimization of PhC waveguides is a key issue for successfully designing PhC devices. Since this design task is computationally expensive, efficient methods are demanded. The available codes for computing photonic bands are also applied to PhC waveguides. They are reliable but not very efficient, which is even more pronounced for dispersive material. We present a method based on higher order finite elements with curved cells, which allows to solve for the band structure taking directly into account the dispersiveness of the materials. This is accomplished by reformulating the wave equations as a linear eigenproblem in the complex wave-vectors k. For this method, we demonstrate the high efficiency for the computation of guided PhC waveguide modes by a convergence analysis.

Highly birefringent large negative dispersion-flattened photonic crystal fibre for broadband residual dispersion compensation

NASA Astrophysics Data System (ADS)

Faisal, Mohammad; Bala, Animesh; Roy Chowdhury, Kanan; Mia, Md. Borhan

2018-07-01

A triangular lattice photonic crystal fibre is presented in this paper for residual dispersion compensation. The fibre exhibits a flattened negative dispersion of -992.01 ± 6.93 ps/(nm-km) over S+C+L wavelength bands and -995.83 ± 0.42 ps/(nm-km) over C-band. The birefringence is about 4.4 × 10-2 at the excitation wavelength of 1550 nm which is also very high. Full vector finite element method (FEM) with a perfectly matched absorbing layer (PML) boundary condition is applied to numerically investigate the guiding properties of this PCF. The fibre operates at fundamental mode only. All these properties endorse this fibre as a suitable candidate for compensating residual dispersion and polarization maintaining applications.

On three-dimensional misorientation spaces.

PubMed

Krakow, Robert; Bennett, Robbie J; Johnstone, Duncan N; Vukmanovic, Zoja; Solano-Alvarez, Wilberth; Lainé, Steven J; Einsle, Joshua F; Midgley, Paul A; Rae, Catherine M F; Hielscher, Ralf

2017-10-01

Determining the local orientation of crystals in engineering and geological materials has become routine with the advent of modern crystallographic mapping techniques. These techniques enable many thousands of orientation measurements to be made, directing attention towards how such orientation data are best studied. Here, we provide a guide to the visualization of misorientation data in three-dimensional vector spaces, reduced by crystal symmetry, to reveal crystallographic orientation relationships. Domains for all point group symmetries are presented and an analysis methodology is developed and applied to identify crystallographic relationships, indicated by clusters in the misorientation space, in examples from materials science and geology. This analysis aids the determination of active deformation mechanisms and evaluation of cluster centres and spread enables more accurate description of transformation processes supporting arguments regarding provenance.

Core data elements tracking elder sexual abuse.

PubMed

Hanrahan, Nancy P; Burgess, Ann W; Gerolamo, Angela M

2005-05-01

Sexual abuse in the older adult population is an understudied vector of violent crimes with significant physical and psychological consequences for victims and families. Research requires a theoretical framework that delineates core elements using a standardized instrument. To develop a conceptual framework and identify core data elements specific to the older adult population, clinical, administrative, and criminal experts were consulted using a nominal group method to revise an existing sexual assault instrument. The revised instrument could be used to establish a national database of elder sexual abuse. The database could become a standard reference to guide the detection, assessment, and prosecution of elder sexual abuse crimes as well as build a base from which policy makers could plan and evaluate interventions that targeted risk factors.

Illuminating the gateway of gene silencing: perspective of RNA interference technology in clinical therapeutics.

PubMed

Sindhu, Annu; Arora, Pooja; Chaudhury, Ashok

2012-07-01

A novel laboratory revolution for disease therapy, the RNA interference (RNAi) technology, has adopted a new era of molecular research as the next generation "Gene-targeted prophylaxis." In this review, we have focused on the chief technological challenges associated with the efforts to develop RNAi-based therapeutics that may guide the biomedical researchers. Many non-curable maladies, like neurodegenerative diseases and cancers have effectively been cured using this technology. Rapid advances are still in progress for the development of RNAi-based technologies that will be having a major impact on medical research. We have highlighted the recent discoveries associated with the phenomenon of RNAi, expression of silencing molecules in mammals along with the vector systems used for disease therapeutics.

On three-dimensional misorientation spaces

NASA Astrophysics Data System (ADS)

Krakow, Robert; Bennett, Robbie J.; Johnstone, Duncan N.; Vukmanovic, Zoja; Solano-Alvarez, Wilberth; Lainé, Steven J.; Einsle, Joshua F.; Midgley, Paul A.; Rae, Catherine M. F.; Hielscher, Ralf

2017-10-01

Determining the local orientation of crystals in engineering and geological materials has become routine with the advent of modern crystallographic mapping techniques. These techniques enable many thousands of orientation measurements to be made, directing attention towards how such orientation data are best studied. Here, we provide a guide to the visualization of misorientation data in three-dimensional vector spaces, reduced by crystal symmetry, to reveal crystallographic orientation relationships. Domains for all point group symmetries are presented and an analysis methodology is developed and applied to identify crystallographic relationships, indicated by clusters in the misorientation space, in examples from materials science and geology. This analysis aids the determination of active deformation mechanisms and evaluation of cluster centres and spread enables more accurate description of transformation processes supporting arguments regarding provenance.

Informational ergonomics and design: signage design for Monte Sião Camp.

PubMed

Marques, Luiz Guilherme Oliveira; Cardoso, Vânia Maria Batalha

2012-01-01

This paper refers to the development of a signage system, driven by the vector of Signage Design and Informational Ergonomics associated with Regulatory Standards. The methodology of the Ergonomic Intervention of Moraes and Mont'Alvão (2003), in its early stages, and the Method of the Signage Pyramid of Calori (2007) were used to develop the research, data collection and analysis and to guide the design by a signaling system. The system contemplated by this job is called Mount Zion, a site of 19 hectares, which has signs of disturbance. As a result, we obtained a signaling system, with graphic features that refer to formal-site, capable of meeting the needs of orientation and displacement inherent to the site.

ac-driven vortices and the Hall effect in a superconductor with a tilted washboard pinning potential

NASA Astrophysics Data System (ADS)

Shklovskij, Valerij A.; Dobrovolskiy, Oleksandr V.

2008-09-01

The Langevin equation for a two-dimensional (2D) nonlinear guided vortex motion in a tilted cosine pinning potential in the presence of an ac is exactly solved in terms of a matrix continued fraction at arbitrary value of the Hall effect. The influence of an ac of arbitrary amplitude and frequency on the dc and ac magnetoresistivity tensors is analyzed. The ac density and frequency dependence of the overall shape and the number and position of the Shapiro steps on the anisotropic current-voltage characteristics are considered. The influence of a subcritical or overcritical dc on the time-dependent stationary ac longitudinal and transverse resistive vortex responses (on the frequency of an ac drive Ω ) in terms of the nonlinear impedance tensor Ẑ and the nonlinear ac response at Ω harmonics are studied. Analytical formulas for 2D temperature-dependent linear impedance tensor ẐL in the presence of a dc which depend on the angle α between the current-density vector and the guiding direction of the washboard planar pinning potential are derived and analyzed. Influence of α anisotropy and the Hall effect on the nonlinear power absorption by vortices is discussed.

Geologic Carbon Sequestration Leakage Detection: A Physics-Guided Machine Learning Approach

NASA Astrophysics Data System (ADS)

Lin, Y.; Harp, D. R.; Chen, B.; Pawar, R.

2017-12-01

One of the risks of large-scale geologic carbon sequestration is the potential migration of fluids out of the storage formations. Accurate and fast detection of this fluids migration is not only important but also challenging, due to the large subsurface uncertainty and complex governing physics. Traditional leakage detection and monitoring techniques rely on geophysical observations including pressure. However, the resulting accuracy of these methods is limited because of indirect information they provide requiring expert interpretation, therefore yielding in-accurate estimates of leakage rates and locations. In this work, we develop a novel machine-learning technique based on support vector regression to effectively and efficiently predict the leakage locations and leakage rates based on limited number of pressure observations. Compared to the conventional data-driven approaches, which can be usually seem as a "black box" procedure, we develop a physics-guided machine learning method to incorporate the governing physics into the learning procedure. To validate the performance of our proposed leakage detection method, we employ our method to both 2D and 3D synthetic subsurface models. Our novel CO2 leakage detection method has shown high detection accuracy in the example problems.

Thirty Meter Telescope narrow-field infrared adaptive optics system real-time controller prototyping results

NASA Astrophysics Data System (ADS)

Smith, Malcolm; Kerley, Dan; Chapin, Edward L.; Dunn, Jennifer; Herriot, Glen; Véran, Jean-Pierre; Boyer, Corinne; Ellerbroek, Brent; Gilles, Luc; Wang, Lianqi

2016-07-01

Prototyping and benchmarking was performed for the Real-Time Controller (RTC) of the Narrow Field InfraRed Adaptive Optics System (NFIRAOS). To perform wavefront correction, NFIRAOS utilizes two deformable mirrors (DM) and one tip/tilt stage (TTS). The RTC receives wavefront information from six Laser Guide Star (LGS) Shack- Hartmann WaveFront Sensors (WFS), one high-order Natural Guide Star Pyramid WaveFront Sensor (PWFS) and multiple low-order instrument detectors. The RTC uses this information to determine the commands to send to the wavefront correctors. NFIRAOS is the first light AO system for the Thirty Meter Telescope (TMT). The prototyping was performed using dual-socket high performance Linux servers with the real-time (PREEMPT_RT) patch and demonstrated the viability of a commercial off-the-shelf (COTS) hardware approach to large scale AO reconstruction. In particular, a large custom matrix vector multiplication (MVM) was benchmarked which met the required latency requirements. In addition all major inter-machine communication was verified to be adequate using 10Gb and 40Gb Ethernet. The results of this prototyping has enabled a CPU-based NFIRAOS RTC design to proceed with confidence and that COTS hardware can be used to meet the demanding performance requirements.

Laser guide star wavefront sensing for ground-layer adaptive optics on extremely large telescopes.

PubMed

Clare, Richard M; Le Louarn, Miska; Béchet, Clementine

2011-02-01

We propose ground-layer adaptive optics (GLAO) to improve the seeing on the 42 m European Extremely Large Telescope. Shack-Hartmann wavefront sensors (WFSs) with laser guide stars (LGSs) will experience significant spot elongation due to off-axis observation. This spot elongation influences the design of the laser launch location, laser power, WFS detector, and centroiding algorithm for LGS GLAO on an extremely large telescope. We show, using end-to-end numerical simulations, that with a noise-weighted matrix-vector-multiply reconstructor, the performance in terms of 50% ensquared energy (EE) of the side and central launch of the lasers is equivalent, the matched filter and weighted center of gravity centroiding algorithms are the most promising, and approximately 10×10 undersampled pixels are optimal. Significant improvement in the 50% EE can be observed with a few tens of photons/subaperture/frame, and no significant gain is seen by adding more than 200 photons/subaperture/frame. The LGS GLAO is not particularly sensitive to the sodium profile present in the mesosphere nor to a short-timescale (less than 100 s) evolution of the sodium profile. The performance of LGS GLAO is, however, sensitive to the atmospheric turbulence profile.

A novel Zeonex based oligoporous-core photonic crystal fiber for polarization preserving terahertz applications

NASA Astrophysics Data System (ADS)

Islam, Md. Saiful; Sultana, Jakeya; Dinovitser, Alex; Ng, Brian W.-H.; Abbott, Derek

2018-04-01

A novel waveguide consisting of oligo-porous core photonic crystal fiber (PCF) with a kagome lattice cladding has been designed for highly birefringent and near zero dispersion flattened applications of terahertz waves. The wave guiding properties of the designed PCF including birefringence, dispersion, effective material loss (EML), core power fraction, confinement loss, and modal effective area are investigated using a full vector Finite Element Method (FEM) with Perfectly Matched Layer (PML) absorbing boundary condition. Simulation results demonstrate that an ultra-high birefringence of 0.079, low EML of 0.05 cm-1, higher core power fraction of 44% and negligible confinement loss of 7 . 24 × 10-7 cm-1 can be achieved at 1 THz. Furthermore, for the y-polarization mode a near zero flattened dispersion of 0 . 49 ± 0 . 05 ps/THz/cm is achieved within a broad frequency range of 0.8-1.7 THz. The fabrication of the proposed fiber is feasible using the existing fabrication technology. Due to favorable wave-guiding properties, the proposed fiber has potential for terahertz imaging, sensing and polarization maintaining applications in the terahertz frequency range.

Guiding and amplification properties of rod-type photonic crystal fibers with sectioned core doping

NASA Astrophysics Data System (ADS)

Selleri, S.; Poli, F.; Passaro, D.; Cucinotta, A.; Lægsgaard, J.; Broeng, J.

2009-05-01

Rod-type photonic crystal fibers are large mode area double-cladding fibers with an outer diameter of few millimeters which can provide important advantages for high-power lasers and amplifiers. Numerical studies have recently demonstrated the guidance of higher-order modes in these fibers, which can worsen the output beam quality of lasers and amplifiers. In the present analysis a sectioned core doping has been proposed for Ybdoped rod-type photonic crystal fibers, with the aim to improve the higher-order mode suppression. A full-vector modal solver based on the finite element method has been applied to properly design the low refractive index ring in the fiber core, which can provide an increase of the differential overlap between the fundamental and the higher-order mode. Then, the gain competition among the guided modes along the Yb-doped rod-type fibers has been investigated with a spatial and spectral amplifier model. Simulation results have shown the effectiveness of the sectioned core doping in worsening the higher-order mode overlap on the doped area, thus providing an effective single-mode behavior of the Yb-doped rod-type photonic crystal fibers.

Structure-guided evolution of antigenically distinct adeno-associated virus variants for immune evasion.

PubMed

Tse, Longping Victor; Klinc, Kelli A; Madigan, Victoria J; Castellanos Rivera, Ruth M; Wells, Lindsey F; Havlik, L Patrick; Smith, J Kennon; Agbandje-McKenna, Mavis; Asokan, Aravind

2017-06-13

Preexisting neutralizing antibodies (NAbs) against adeno-associated viruses (AAVs) pose a major, unresolved challenge that restricts patient enrollment in gene therapy clinical trials using recombinant AAV vectors. Structural studies suggest that despite a high degree of sequence variability, antibody recognition sites or antigenic hotspots on AAVs and other related parvoviruses might be evolutionarily conserved. To test this hypothesis, we developed a structure-guided evolution approach that does not require selective pressure exerted by NAbs. This strategy yielded highly divergent antigenic footprints that do not exist in natural AAV isolates. Specifically, synthetic variants obtained by evolving murine antigenic epitopes on an AAV serotype 1 capsid template can evade NAbs without compromising titer, transduction efficiency, or tissue tropism. One lead AAV variant generated by combining multiple evolved antigenic sites effectively evades polyclonal anti-AAV1 neutralizing sera from immunized mice and rhesus macaques. Furthermore, this variant displays robust immune evasion in nonhuman primate and human serum samples at dilution factors as high as 1:5, currently mandated by several clinical trials. Our results provide evidence that antibody recognition of AAV capsids is conserved across species. This approach can be applied to any AAV strain to evade NAbs in prospective patients for human gene therapy.

Interactive orbital proximity operations planning system instruction and training guide

NASA Technical Reports Server (NTRS)

Grunwald, Arthur J.; Ellis, Stephen R.

1994-01-01

This guide instructs users in the operation of a Proximity Operations Planning System. This system uses an interactive graphical method for planning fuel-efficient rendezvous trajectories in the multi-spacecraft environment of the space station and allows the operator to compose a multi-burn transfer trajectory between orbit initial chaser and target trajectories. The available task time (window) of the mission is predetermined and the maneuver is subject to various operational constraints, such as departure, arrival, spatial, plume impingement, and en route passage constraints. The maneuvers are described in terms of the relative motion experienced in a space station centered coordinate system. Both in-orbital plane as well as out-of-orbital plane maneuvering is considered. A number of visual optimization aids are used for assisting the operator in reaching fuel-efficient solutions. These optimization aids are based on the Primer Vector theory. The visual feedback of trajectory shapes, operational constraints, and optimization functions, provided by user-transparent and continuously active background computations, allows the operator to make fast, iterative design changes that rapidly converge to fuel-efficient solutions. The planning tool is an example of operator-assisted optimization of nonlinear cost functions.

A CRISPR-Cas9 sex-ratio distortion system for genetic control

PubMed Central

Galizi, Roberto; Hammond, Andrew; Kyrou, Kyros; Taxiarchi, Chrysanthi; Bernardini, Federica; O’Loughlin, Samantha M.; Papathanos, Philippos-Aris; Nolan, Tony; Windbichler, Nikolai; Crisanti, Andrea

2016-01-01

Genetic control aims to reduce the ability of insect pest populations to cause harm via the release of modified insects. One strategy is to bias the reproductive sex ratio towards males so that a population decreases in size or is eliminated altogether due to a lack of females. We have shown previously that sex ratio distortion can be generated synthetically in the main human malaria vector Anopheles gambiae, by selectively destroying the X-chromosome during spermatogenesis, through the activity of a naturally-occurring endonuclease that targets a repetitive rDNA sequence highly-conserved in a wide range of organisms. Here we describe a CRISPR-Cas9 sex distortion system that targets ribosomal sequences restricted to the member species of the Anopheles gambiae complex. Expression of Cas9 during spermatogenesis resulted in RNA-guided shredding of the X-chromosome during male meiosis and produced extreme male bias among progeny in the absence of any significant reduction in fertility. The flexibility of CRISPR-Cas9 combined with the availability of genomic data for a range of insects renders this strategy broadly applicable for the species-specific control of any pest or vector species with an XY sex-determination system by targeting sequences exclusive to the female sex chromosome. PMID:27484623

ML 3.0 smoothed aggregation user's guide.

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

Sala, Marzio; Hu, Jonathan Joseph; Tuminaro, Raymond Stephen

2004-05-01

ML is a multigrid preconditioning package intended to solve linear systems of equations Az = b where A is a user supplied n x n sparse matrix, b is a user supplied vector of length n and x is a vector of length n to be computed. ML should be used on large sparse linear systems arising from partial differential equation (PDE) discretizations. While technically any linear system can be considered, ML should be used on linear systems that correspond to things that work well with multigrid methods (e.g. elliptic PDEs). ML can be used as a stand-alone package ormore » to generate preconditioners for a traditional iterative solver package (e.g. Krylov methods). We have supplied support for working with the AZTEC 2.1 and AZTECOO iterative package [15]. However, other solvers can be used by supplying a few functions. This document describes one specific algebraic multigrid approach: smoothed aggregation. This approach is used within several specialized multigrid methods: one for the eddy current formulation for Maxwell's equations, and a multilevel and domain decomposition method for symmetric and non-symmetric systems of equations (like elliptic equations, or compressible and incompressible fluid dynamics problems). Other methods exist within ML but are not described in this document. Examples are given illustrating the problem definition and exercising multigrid options.« less

ML 3.1 smoothed aggregation user's guide.

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

Sala, Marzio; Hu, Jonathan Joseph; Tuminaro, Raymond Stephen

2004-10-01

ML is a multigrid preconditioning package intended to solve linear systems of equations Ax = b where A is a user supplied n x n sparse matrix, b is a user supplied vector of length n and x is a vector of length n to be computed. ML should be used on large sparse linear systems arising from partial differential equation (PDE) discretizations. While technically any linear system can be considered, ML should be used on linear systems that correspond to things that work well with multigrid methods (e.g. elliptic PDEs). ML can be used as a stand-alone package ormore » to generate preconditioners for a traditional iterative solver package (e.g. Krylov methods). We have supplied support for working with the Aztec 2.1 and AztecOO iterative package [16]. However, other solvers can be used by supplying a few functions. This document describes one specific algebraic multigrid approach: smoothed aggregation. This approach is used within several specialized multigrid methods: one for the eddy current formulation for Maxwell's equations, and a multilevel and domain decomposition method for symmetric and nonsymmetric systems of equations (like elliptic equations, or compressible and incompressible fluid dynamics problems). Other methods exist within ML but are not described in this document. Examples are given illustrating the problem definition and exercising multigrid options.« less

Autonomous dynamic obstacle avoidance for bacteria-powered microrobots (BPMs) with modified vector field histogram

PubMed Central

Kim, Hoyeon; Cheang, U. Kei

2017-01-01

In order to broaden the use of microrobots in practical fields, autonomous control algorithms such as obstacle avoidance must be further developed. However, most previous studies of microrobots used manual motion control to navigate past tight spaces and obstacles while very few studies demonstrated the use of autonomous motion. In this paper, we demonstrated a dynamic obstacle avoidance algorithm for bacteria-powered microrobots (BPMs) using electric field in fluidic environments. A BPM consists of an artificial body, which is made of SU-8, and a high dense layer of harnessed bacteria. BPMs can be controlled using externally applied electric fields due to the electrokinetic property of bacteria. For developing dynamic obstacle avoidance for BPMs, a kinematic model of BPMs was utilized to prevent collision and a finite element model was used to characteristic the deformation of an electric field near the obstacle walls. In order to avoid fast moving obstacles, we modified our previously static obstacle avoidance approach using a modified vector field histogram (VFH) method. To validate the advanced algorithm in experiments, magnetically controlled moving obstacles were used to intercept the BPMs as the BPMs move from the initial position to final position. The algorithm was able to successfully guide the BPMs to reach their respective goal positions while avoiding the dynamic obstacles. PMID:29020016

Evaluation of a peridomestic mosquito trap for integration into an Aedes aegypti (Diptera: Culicidae) push-pull control strategy.

PubMed

Salazar, Ferdinand V; Achee, Nicole L; Grieco, John P; Prabaripai, Atchariya; Eisen, Lars; Shah, Pankhil; Chareonviriyaphap, Theeraphap

2012-06-01

We determined the feasibility of using the BG-Sentinel™ mosquito trap (BGS) as the pull component in a push-pull strategy to reduce indoor biting by Aedes aegypti. This included evaluating varying numbers of traps (1-4) and mosquito release numbers (10, 25, 50, 100, 150, 200, and 250) on recapture rates under screen house conditions. Based on these variations in trap and mosquito numbers, release intervals were rotated through a completely randomized design with environmental factors (temperature, relative humidity, and light intensity) and monitored throughout each experiment. Data from four sampling time points (05:30, 09:30, 13:30, and 17:30) indicate a recapture range among treatments of 66-98%. Furthermore, 2-3 traps were as effective in recapturing mosquitoes as 4 traps for all mosquito release numbers. Time trends indicate Day 1 (the day the mosquitoes were released) as the "impact period" for recapture with peak numbers of marked mosquitoes collected at 09:30 or 4 h post-release. Information from this study will be used to guide the configuration of the BGS trap component of a push-pull vector control strategy currently in the proof-of-concept stage of development in Thailand and Peru. © 2012 The Society for Vector Ecology.

Genome profiling of sterol synthesis shows convergent evolution in parasites and guides chemotherapeutic attack.

PubMed

Fügi, Matthias A; Gunasekera, Kapila; Ochsenreiter, Torsten; Guan, Xueli; Wenk, Markus R; Mäser, Pascal

2014-05-01

Sterols are an essential class of lipids in eukaryotes, where they serve as structural components of membranes and play important roles as signaling molecules. Sterols are also of high pharmacological significance: cholesterol-lowering drugs are blockbusters in human health, and inhibitors of ergosterol biosynthesis are widely used as antifungals. Inhibitors of ergosterol synthesis are also being developed for Chagas's disease, caused by Trypanosoma cruzi. Here we develop an in silico pipeline to globally evaluate sterol metabolism and perform comparative genomics. We generate a library of hidden Markov model-based profiles for 42 sterol biosynthetic enzymes, which allows expressing the genomic makeup of a given species as a numerical vector. Hierarchical clustering of these vectors functionally groups eukaryote proteomes and reveals convergent evolution, in particular metabolic reduction in obligate endoparasites. We experimentally explore sterol metabolism by testing a set of sterol biosynthesis inhibitors against trypanosomatids, Plasmodium falciparum, Giardia, and mammalian cells, and by quantifying the expression levels of sterol biosynthetic genes during the different life stages of T. cruzi and Trypanosoma brucei. The phenotypic data correlate with genomic makeup for simvastatin, which showed activity against trypanosomatids. Other findings, such as the activity of terbinafine against Giardia, are not in agreement with the genotypic profile.

An age-structured model to evaluate the potential of novel malaria-control interventions: a case study of fungal biopesticide sprays

PubMed Central

Hancock, P.A; Thomas, M.B; Godfray, H.C.J

2008-01-01

It has recently been proposed that mosquito vectors of human diseases, particularly malaria, may be controlled by spraying with fungal biopesticides that increase the rate of adult mortality. Though fungal pathogens do not cause instantaneous mortality, they can kill mosquitoes before they are old enough to transmit disease. A model is developed (i) to explore the potential for fungal entomopathogens to reduce significantly infectious mosquito populations, (ii) to assess the relative value of the many different fungal strains that might be used, and (iii) to help guide the tactical design of vector-control programmes. The model follows the dynamics of different classes of adult mosquitoes with the risk of mortality due to the fungus being assumed to be a function of time since infection (modelled using the Weibull distribution). It is shown that substantial reductions in mosquito numbers are feasible for realistic assumptions about mosquito, fungus and malaria biology and moderate to low daily fungal infection probability. The choice of optimal fungal strain and spraying regime is shown to depend on local mosquito and malaria biology. Fungal pathogens may also influence the ability of mosquitoes to transmit malaria and such effects are shown to further reduce vectorial capacity. PMID:18765347

[Establishment of policy indicators of adaptation to the impact of climate change on the transmission of schistosomiasis and malaria in China].

PubMed

Qian, Ying-Jun; Li, Shi-Zhu; Xu, Jun-Fang; Zhang, Li; Fu, Qing; Zhou, Xiao-Nong

2013-12-01

To set up a framework of indicators for schistosomiasis and malaria to guide the formulation and evaluation of vector-borne disease control policies focusing on adaptation to the negative impact of climate change. A 2-level indicator framework was set up on the basis of literature review, and Delphi method was applied to a total of 22 and 19 experts working on schistosomiasis and malaria, respectively. The result was analyzed to calculate the weight of various indicators. A total of 41 questionnaires was delivered, and 38 with valid response (92.7%). The system included 4 indicators at first level, i.e. surveillance, scientific research, disease control and intervention, and adaptation capacity building, with 25 indicators for schistosomiasis and 21 for malaria at the second level. Among indicators at the first level, disease surveillance ranked first with a weight of 0.32. Among the indicators at the second level, vector monitoring scored the highest in terms of both schistosomiasis and malaria. The indicators set up by Delphi method are practical,universal and effective ones using in the field, which is also useful to technically support the establishment of adaptation to climate change in the field of public health.

High Performance Distributed Computing in a Supercomputer Environment: Computational Services and Applications Issues

NASA Technical Reports Server (NTRS)

Kramer, Williams T. C.; Simon, Horst D.

1994-01-01

This tutorial proposes to be a practical guide for the uninitiated to the main topics and themes of high-performance computing (HPC), with particular emphasis to distributed computing. The intent is first to provide some guidance and directions in the rapidly increasing field of scientific computing using both massively parallel and traditional supercomputers. Because of their considerable potential computational power, loosely or tightly coupled clusters of workstations are increasingly considered as a third alternative to both the more conventional supercomputers based on a small number of powerful vector processors, as well as high massively parallel processors. Even though many research issues concerning the effective use of workstation clusters and their integration into a large scale production facility are still unresolved, such clusters are already used for production computing. In this tutorial we will utilize the unique experience made at the NAS facility at NASA Ames Research Center. Over the last five years at NAS massively parallel supercomputers such as the Connection Machines CM-2 and CM-5 from Thinking Machines Corporation and the iPSC/860 (Touchstone Gamma Machine) and Paragon Machines from Intel were used in a production supercomputer center alongside with traditional vector supercomputers such as the Cray Y-MP and C90.

Measurement Scale of the SOLIS Vector Spectromagnetograph

NASA Technical Reports Server (NTRS)

Jones, Harrison P.; Harvey, John W.; Henney, Carl J.; Keller, Christoph U.; Malanushenko, Olena M.

2004-01-01

Longitudinal magnetograms obtained with thc SOLIS Vector Spectromagnetograph (VSM) during a cross-calibration period are compared with similar data from the NASA/NSO Spectromagnetograph (SPM) at the NSO/Kitt Peak Vacuum Telescope as well as with SOHO/MDI and GONG magnetogram. The VSM began observation at the University of Arizona agricultural test site and collaborative observations were obtained with both the VSM and SPM from 2003 Aug 05 through 2003 Sep 21 where the SPM was officially retired. The VSM replaces the SPM and continues the 3O-year NSO/Kitt Peak synoptic magnetogram record. Magnetograms are compared by equating histograms and, for selected examples, by pixel-by-pixel comparison of co-registered images. The VSM was not corrected for polarization crosstalk and was operated without hast guiding. Solar activity was at best moderate during this period. Over the range of observed fields, the VSM magnetograms show greatly improved sensitivity but are otherwise virtually identical with "raw" SPM magnetogram. GONG magnetograms are also closely comparable with the SPM while MDI flux values tend to be stronger by a factor of 1.2 - 1.4. Dependence of the results on seeing will be discussed. Partial funding for this work was provided through Solar and Heliospheric Research Supporting Research and Technology grants from NASA's Office of Space Sciences.

Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

PubMed

Bernal, Giovanna M; LaRiviere, Michael J; Mansour, Nassir; Pytel, Peter; Cahill, Kirk E; Voce, David J; Kang, Shijun; Spretz, Ruben; Welp, Ulrich; Noriega, Sandra E; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

2014-01-01

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma. GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles. © 2014.

Genome profiling of sterol synthesis shows convergent evolution in parasites and guides chemotherapeutic attack

PubMed Central

Fügi, Matthias A.; Gunasekera, Kapila; Ochsenreiter, Torsten; Guan, Xueli; Wenk, Markus R.; Mäser, Pascal

2014-01-01

Sterols are an essential class of lipids in eukaryotes, where they serve as structural components of membranes and play important roles as signaling molecules. Sterols are also of high pharmacological significance: cholesterol-lowering drugs are blockbusters in human health, and inhibitors of ergosterol biosynthesis are widely used as antifungals. Inhibitors of ergosterol synthesis are also being developed for Chagas’s disease, caused by Trypanosoma cruzi. Here we develop an in silico pipeline to globally evaluate sterol metabolism and perform comparative genomics. We generate a library of hidden Markov model-based profiles for 42 sterol biosynthetic enzymes, which allows expressing the genomic makeup of a given species as a numerical vector. Hierarchical clustering of these vectors functionally groups eukaryote proteomes and reveals convergent evolution, in particular metabolic reduction in obligate endoparasites. We experimentally explore sterol metabolism by testing a set of sterol biosynthesis inhibitors against trypanosomatids, Plasmodium falciparum, Giardia, and mammalian cells, and by quantifying the expression levels of sterol biosynthetic genes during the different life stages of T. cruzi and Trypanosoma brucei. The phenotypic data correlate with genomic makeup for simvastatin, which showed activity against trypanosomatids. Other findings, such as the activity of terbinafine against Giardia, are not in agreement with the genotypic profile. PMID:24627128

Molecular mechanisms of retroviral integration site selection

PubMed Central

Kvaratskhelia, Mamuka; Sharma, Amit; Larue, Ross C.; Serrao, Erik; Engelman, Alan

2014-01-01

Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic. PMID:25147212

Autonomous dynamic obstacle avoidance for bacteria-powered microrobots (BPMs) with modified vector field histogram.

PubMed

Kim, Hoyeon; Cheang, U Kei; Kim, Min Jun

2017-01-01

In order to broaden the use of microrobots in practical fields, autonomous control algorithms such as obstacle avoidance must be further developed. However, most previous studies of microrobots used manual motion control to navigate past tight spaces and obstacles while very few studies demonstrated the use of autonomous motion. In this paper, we demonstrated a dynamic obstacle avoidance algorithm for bacteria-powered microrobots (BPMs) using electric field in fluidic environments. A BPM consists of an artificial body, which is made of SU-8, and a high dense layer of harnessed bacteria. BPMs can be controlled using externally applied electric fields due to the electrokinetic property of bacteria. For developing dynamic obstacle avoidance for BPMs, a kinematic model of BPMs was utilized to prevent collision and a finite element model was used to characteristic the deformation of an electric field near the obstacle walls. In order to avoid fast moving obstacles, we modified our previously static obstacle avoidance approach using a modified vector field histogram (VFH) method. To validate the advanced algorithm in experiments, magnetically controlled moving obstacles were used to intercept the BPMs as the BPMs move from the initial position to final position. The algorithm was able to successfully guide the BPMs to reach their respective goal positions while avoiding the dynamic obstacles.

Modeling and Theory of RF Antenna Systems on Proto-MPEX

NASA Astrophysics Data System (ADS)

Piotrowicz, P. A.; Caneses, J. F.; Goulding, R. H.; Green, D.; Caughman, J. B. O.; Ruzic, D. N.; Proto-MPEX Team

2017-10-01

The RF wave coupling of the helicon and ICH antennas installed on the Prototype Material Plasma Exposure eXperiment (MPEX) has been explored theoretically and via a full wave model implemented in COMSOL Multiphysics. The high-density mode in Proto-MPEX has been shown to occur when exciting radial eigenmodes of the plasma column which coincides with entering a Trivelpiece Gould (TG) anti-resonant regime, therefore suppressing edge heating in favor of core power deposition. The fast wave launched by the helicon antenna has a large wavelength and travels at a steep group velocity angle with the background magnetic field; for this reason the fast wave launched by the helicon antenna efficiently couples power to the core plasma. However, the ICH heating scheme relies on a small wavelength slow wave to couple power to the core of the plasma column. Coupling slow wave power to the core of the plasma column is sensitive to the location of the Alfven resonance. The wave-vector and group velocity vector of the slow wave in this parameter regime undergoes a drastic change in behavior when approaching the Alfven resonance. Full wave simulation results and dispersion analysis will be presented with suggestions to guide experimental progress. This work was supported by the US. D.O.E. contract DE-AC05-00OR22725.

Prediction of human disease-associated phosphorylation sites with combined feature selection approach and support vector machine.

PubMed

Xu, Xiaoyi; Li, Ao; Wang, Minghui

2015-08-01

Phosphorylation is a crucial post-translational modification, which regulates almost all cellular processes in life. It has long been recognised that protein phosphorylation has close relationship with diseases, and therefore many researches are undertaken to predict phosphorylation sites for disease treatment and drug design. However, despite the success achieved by these approaches, no method focuses on disease-associated phosphorylation sites prediction. Herein, for the first time the authors propose a novel approach that is specially designed to identify associations between phosphorylation sites and human diseases. To take full advantage of local sequence information, a combined feature selection method-based support vector machine (CFS-SVM) that incorporates minimum-redundancy-maximum-relevance filtering process and forward feature selection process is developed. Performance evaluation shows that CFS-SVM is significantly better than the widely used classifiers including Bayesian decision theory, k nearest neighbour and random forest. With the extremely high specificity of 99%, CFS-SVM can still achieve a high sensitivity. Besides, tests on extra data confirm the effectiveness and general applicability of CFS-SVM approach on a variety of diseases. Finally, the analysis of selected features and corresponding kinases also help the understanding of the potential mechanism of disease-phosphorylation relationships and guide further experimental validations.

Multiple insecticide resistance mechanisms in Anopheles gambiae s.l. populations from Cameroon, Central Africa.

PubMed

Nwane, Philippe; Etang, Josiane; Chouaїbou, Mouhamadou; Toto, Jean Claude; Koffi, Alphonsine; Mimpfoundi, Rémy; Simard, Frédéric

2013-02-22

Increasing incidence of DDT and pyrethroid resistance in Anopheles mosquitoes is seen as a limiting factor for malaria vector control. The current study aimed at an in-depth characterization of An. gambiae s.l. resistance to insecticides in Cameroon, in order to guide malaria vector control interventions. Anopheles gambiae s.l. mosquitoes were collected as larvae and pupae from six localities spread throughout the four main biogeographical domains of Cameroon and reared to adults in insectaries. Standard WHO insecticide susceptibility tests were carried out with 4% DDT, 0.75% permethrin and 0.05% deltamethrin. Mortality rates and knockdown times (kdt50 and kdt95) were determined and the effect of pre-exposure to the synergists DEF, DEM and PBO was assessed. Tested mosquitoes were identified to species and molecular forms (M or S) using PCR-RFLP. The hot ligation method was used to depict kdr mutations and biochemical assays were conducted to assess detoxifying enzyme activities. The An. arabiensis population from Pitoa was fully susceptible to DDT and permethrin (mortality rates>98%) and showed reduced susceptibility to deltamethrin. Resistance to DDT was widespread in An. gambiae s.s. populations and heterogeneous levels of susceptibility to permethrin and deltamethrin were observed. In many cases, prior exposure to synergists partially restored insecticide knockdown effect and increased mortality rates, suggesting a role of detoxifying enzymes in increasing mosquito survival upon challenge by pyrethroids and, to a lower extent DDT. The distribution of kdr alleles suggested a major role of kdr-based resistance in the S form of An. gambiae. In biochemical tests, all but one mosquito population overexpressed P450 activity, whereas baseline GST activity was low and similar in all field mosquito populations and in the control. In Cameroon, multiple resistance mechanisms segregate in the S form of An. gambiae resulting in heterogeneous resistance profiles, whereas in the M form and An. arabiensis insecticide tolerance seems to be essentially mediated by enzyme-based detoxification. Synergists partially restored susceptibility to pyrethroid insecticides, and might help mitigate the impact of vector resistance in the field. However, additional vector control tools are needed to further impact on malaria transmission in such settings.