Influence of protoporphyrin IX loaded phloroglucinol succinic acid dendrimer in photodynamic therapy

NASA Astrophysics Data System (ADS)

Kumar, M. Suresh; Aruna, P.; Ganesan, S.

2018-03-01

One of the major problems reported clinically for photosensitizers (PS) in Photodynamic therapy (PDT) is, the cause of side-effects to normal tissue due to dark toxicity. The usefulness of photosensitizers can be made possible by reducing its dark toxicity nature. In such scenario, biocompatible carriers can be used as a drug delivery system to evade the problems that arises while using free (dark toxic) drugs. So in this study, we have developed a nano drug delivery system called Phloroglucinol Succinic acid (PGSA) dendrimer, entrapped a photosensitizer, protoporphyrin IX (PpIX) inside the system and investigated whether the photodynamic efficacy of the anionic surface charged dendrimer-PpIX nano formulation is enhanced than achieved by the free PpIX in HeLa cancer cell lines. Moreover, the Reactive oxygen species (ROS) production was monitored using 2‧,7‧-dichlorodihydrofluorescein diacetate (H2DCF-DA)- ROS Marker with phase contrast microscopy for the IC50 values of free and dendrimer-PpIX nano formulation. Similarly, the mode of cell death has been confirmed by cell cycle analysis for the same. For the in vitro PDT application, we have used a simple light source (Light Emitting Diode) with a power of 30-50 mW for 20 min irradiation. Hence, in this study we have taken steps to report this anionic drug delivery system is good to consider for the photodynamic therapy applications with the photosensitizer, PpIX which satisfied the prime requirement of PDT.

Expression Levels of ALA Dehydratase as a Marker of ALA-PDT Efficacy

NASA Astrophysics Data System (ADS)

Avital, Schauder; Tamar, Feuerstein; Zvi, Malik

2010-05-01

Accelerated synthesis of protoporphyrinIX (PpIX) following ALA pre-treatment followed by light irradiation is the principle of ALA-PDT. Several limiting enzymes were suggested to control PpIX accumulation and PDT efficacy, among them porphobilinogen deaminase (PBGD) and ferrochelatase. Here we reveal the centrality of ALA dehydratase (ALAD) activity in predicting ALA-PDT efficacy. Silencing of ALAD expression and activity was carried out in leukemic cells using shRNA plasmid transfection or Pb2+ intoxication. ALAD activity, porphyrin synthesis and mitochondrial activity were determined versus PDT efficacy. In K562 ALAD-silenced cells, ALAD activity and expression were reduced and as a result, PpIX synthesis was almost abolished. Following ALA treatment and irradiation, ALAD-silenced cells depicted normal mitochondrial activity, in contrast to control and non-silencing transfected cells where accumulated PpIX and irradiation caused ROS formation and mitochondrial damage. Morphological analysis by scanning electron microscopy (SEM) of ALA-PDT treated cells showed no morphological changes in ALAD-silenced cells, while controls exhibited cell deformations and lysis. Annexin V-FITC/PI staining as well as LDH-L leakage testing showed that membrane integrity was undamaged following ALA-PDT in ALAD silenced cells. Pb2+ treatment in MEL cells impaired ALAD activity and reduced PpIX synthesis but to a lesser extent. In conclusion, we show that a dramatic reduction in PpIX accumulation following down regulation of ALAD expression prevents an efficient PDT. Thus, ALAD has a major role in regulating PpIX synthesis and ALA-PDT therapeutic outcome. Monitoring ALAD expression or activity in various tumors may be useful as prognostic tool to predict PDT efficacy.

Experiences in Rural Mental Health. IX: Measuring and Monitoring Stress in Communities.

ERIC Educational Resources Information Center

Miller, Francis T.; And Others

Based on a North Carolina feasibility study (1967-73) which focused on development of a pattern for providing comprehensive mental health services to rural people, this guide deals with measuring and monitoring stress in the community. Emphasizing the "proactive" efforts developed in a stress model for Vance and Franklin counties, this…

ALA-PpIX variability quantitatively imaged in A431 epidermoid tumors using in vivo ultrasound fluorescence tomography and ex vivo assay

NASA Astrophysics Data System (ADS)

DSouza, Alisha V.; Flynn, Brendan P.; Gunn, Jason R.; Samkoe, Kimberley S.; Anand, Sanjay; Maytin, Edward V.; Hasan, Tayyaba; Pogue, Brian W.

2014-03-01

Treatment monitoring of Aminolevunilic-acid (ALA) - Photodynamic Therapy (PDT) of basal-cell carcinoma (BCC) calls for superficial and subsurface imaging techniques. While superficial imagers exist for this purpose, their ability to assess PpIX levels in thick lesions is poor; additionally few treatment centers have the capability to measure ALA-induced PpIX production. An area of active research is to improve treatments to deeper and nodular BCCs, because treatment is least effective in these. The goal of this work was to understand the logistics and technical capabilities to quantify PpIX at depths over 1mm, using a novel hybrid ultrasound-guided, fiber-based fluorescence molecular spectroscopictomography system. This system utilizes a 633nm excitation laser and detection using filtered spectrometers. Source and detection fibers are collinear so that their imaging plane matches that of ultrasound transducer. Validation with phantoms and tumor-simulating fluorescent inclusions in mice showed sensitivity to fluorophore concentrations as low as 0.025μg/ml at 4mm depth from surface, as presented in previous years. Image-guided quantification of ALA-induced PpIX production was completed in subcutaneous xenograft epidermoid cancer tumor model A431 in nude mice. A total of 32 animals were imaged in-vivo, using several time points, including pre-ALA, 4-hours post-ALA, and 24-hours post-ALA administration. On average, PpIX production in tumors increased by over 10-fold, 4-hours post-ALA. Statistical analysis of PpIX fluorescence showed significant difference among all groups; p<0.05. Results were validated by exvivo imaging of resected tumors. Details of imaging, analysis and results will be presented to illustrate variability and the potential for imaging these values at depth.

Comparison between two portable devices for widefield PpIX fluorescence during cervical intraepithelial neoplasia treatment

NASA Astrophysics Data System (ADS)

Carbinatto, Fernanda M.; Inada, Natalia Mayumi; Lombardi, Welington; Cossetin, Natália Fernandez; Varoto, Cinthia; Kurachi, Cristina; Bagnato, Vanderlei Salvador

2015-06-01

The use of portable electronic devices, in particular mobile phones such as smartphones is increasing not only for all known applications, but also for diagnosis of diseases and monitoring treatments like topical Photodynamic Therapy. The aim of the study is to evaluate the production of the photosensitizer Protoporphyrin IX (PpIX) after topical application of a cream containing methyl aminolevulinate (MAL) in the cervix with diagnosis of Cervical Intraepithelial Neoplasia (CIN) through the fluorescence images captured after one and three hours and compare the images using two devices (a Sony Xperia® mobile and an Apple Ipod®. Was observed an increasing fluorescence intensity of the cervix three hours after cream application, in both portable electronic devices. However, because was used a specific program for the treatment of images using the Ipod® device, these images presented better resolution than observed by the Sony cell phone without a specific program. One hour after cream application presented a more selective fluorescence than the group of three hours. In conclusion, the use of portable devices to obtain images of PpIX fluorescence shown to be an effective tool and is necessary the improvement of programs for achievement of better results.

A compact multi-channel fluorescence sensor with ambient light suppression

NASA Astrophysics Data System (ADS)

Egly, Dominik; Geörg, Daniel; Rädle, Matthias; Beuermann, Thomas

2012-03-01

A multi-channel fluorescence sensor has been developed for process monitoring and fluorescence diagnostics. It comprises a fiber-optic set-up with an immersion probe and an intensity-modulated high power ultraviolet light-emitting diode as a light source for fluorescence excitation. By applying an electronic lock-in procedure, fluorescence signals are selectively detectable at ambient light levels of 1000 000 times higher intensity. The sensor was designed to be compact, low cost and easily adaptable to a wide field of application. The set-up was used to simultaneously monitor three important metabolic fluorophores: NAD(P)H, flavins and porphyrins during the cultivation of a baker's yeast. Moreover, the accumulation and degradation kinetics of protoporphyrin IX induced by 5-aminolevulinic acid on the skin could be recorded by the sensor. The detection limit for protoporphyrin IX was determined to be 4 × 10-11 mol L-1. The linear signal amplification of the sensor and time courses of fluorescence signals monitored during yeast fermentations were validated using a commercial CCD spectrometer. The robust and flexible set-up of the fiber-optic measurement system promises easy implementation of this non-invasive analytical tool to fluorescence monitoring and diagnostics in R&D and production.

Effect of an oxygen pressure injection (OPI) device on the oxygen saturation of patients during dermatological methyl aminolevulinate photodynamic therapy.

PubMed

Blake, E; Allen, J; Thorn, C; Shore, A; Curnow, A

2013-05-01

Methyl aminolevulinate photodynamic therapy (MAL-PDT) (a topical treatment used for a number of precancerous skin conditions) utilizes the combined interaction of a photosensitizer (protoporphyrin IX (PpIX)), light of the appropriate wavelength, and molecular oxygen to produce singlet oxygen and other reactive oxygen species which induce cell death. During treatment, localized oxygen depletion occurs and is thought to contribute to decreased efficacy. The aim of this study was to investigate whether an oxygen pressure injection (OPI) device had an effect on localized oxygen saturation levels and/or PpIX fluorescence of skin lesions during MAL-PDT. This study employed an OPI device to apply oxygen under pressure to the skin lesions of patients undergoing standard MAL-PDT. Optical reflectance spectrometry and fluorescence imaging were used to noninvasively monitor the localized oxygen saturation and PpIX fluorescence of the treatment area, respectively. No significant changes in oxygen saturation were observed when these data were combined for the group with OPI and compared to the group that received standard MAL-PDT without OPI. Additionally, no significant difference in PpIX photobleaching or clinical outcome at 3 months between the groups of patients was observed, although the group that received standard MAL-PDT demonstrated a significant increase (p<0.05) in PpIX fluorescence initially and both groups produced a significant decrease (p<0.05) after light irradiation. In conclusion, with this sample size, this OPI device was not found to be an effective method with which to improve tissue oxygenation during MAL-PDT. Further investigation is therefore required to find a more effective method of MAL-PDT enhancement.

Enhancement of tumor responsiveness to aminolevulinate-photodynamic therapy (ALA-PDT) using differentiation-promoting agents in mouse models of skin carcinoma

NASA Astrophysics Data System (ADS)

Anand, Sanjay; Honari, Golara; Paliwal, Akshat; Hasan, Tayyaba; Maytin, Edward V.

2009-06-01

Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is an emerging treatment for cancers. ALA, given as a prodrug, selectively accumulates and is metabolized in cancer cells to form protoporphyrin IX (PpIX). Targeted local irradiation with light induces cell death. Since the efficacy of ALA-PDT for large or deep tumors is currently limited, we are developing a new approach that combines differentiation-inducing agents with ALA-PDT to improve the clinical response. Here, we tested this new combination paradigm in the following two models of skin carcinoma in mice: 1) tumors generated by topical application of chemical carcinogens (DMBA-TPA); 2) human SCC cells (A431) implanted subcutaneously. To achieve a differentiated state of the tumors, pretreatment with a low concentration of methotrexate (MTX) or Vitamin D (Vit D) was administered for 72 h prior to exposure to ALA. Confocal images of histological sections were captured and digitally analyzed to determine relative PpIX levels. PpIX in the tumors was also monitored by real-time in vivo fluorescence dosimetry. In both models, a significant increase in levels of PpIX was observed following pretreatment with MTX or Vit D, as compared to no-pretreatment controls. This enhancing effect was observed at very low, non-cytotoxic concentrations, and was highly specific to cancer cells as compared to normal cells. These results suggest that use of differentiating agents such as MTX or Vit D, as a short-term combination therapy given prior to ALA-PDT, can increase the production of PpIX photosensitizer and enhance the therapeutic response of skin cancers.

Recombinant to modified factor VIII and factor IX - chromogenic and one-stage assays issues.

PubMed

Kitchen, S; Kershaw, G; Tiefenbacher, S

2016-07-01

The recent development of modified recombinant factor VIII (FVIII) and factor IX (FIX) therapeutic products with extended half-lives will create challenges for the haemostasis laboratory in obtaining recovery estimates of these products in clinical samples using existing assays. The new long-acting therapeutic concentrates contain molecular modifications of Fc fusion, site-specific of polyethylene glycol or albumin fusion. The optimum methods for monitoring each new product will need to be assessed individually and laboratories should select an assay which gives similar results to the assay used to assign potency to the product in question. For some extended half-life FVIII and FIX products some one stage assays are entirely unsuitable for monitoring purposes. For most products and assay reagents studied so far, and reviewed in this manuscript, chromogenic FVIII or FIX assays can be safely used with conventional plasma standards. If one stage assays are used then they should be performed using carefully selected reagents/methods which have been shown to recover activity close to the labelled potency for the specific product being monitored. © 2016 John Wiley & Sons Ltd.

The indexed time table approach for planning and acting

NASA Technical Reports Server (NTRS)

Ghallab, Malik; Alaoui, Amine Mounir

1989-01-01

A representation is discussed of symbolic temporal relations, called IxTeT, that is both powerful enough at the reasoning level for tasks such as plan generation, refinement and modification, and efficient enough for dealing with real time constraints in action monitoring and reactive planning. Such representation for dealing with time is needed in a teleoperated space robot. After a brief survey of known approaches, the proposed representation shows its computational efficiency for managing a large data base of temporal relations. Reactive planning with IxTeT is described and exemplified through the problem of mission planning and modification for a simple surveying satellite.

33 CFR 104.210 - Company Security Officer (CSO).

Code of Federal Regulations, 2014 CFR

2014-07-01

... operational limitations; (vi) Methods of conducting audits, inspection and control and monitoring techniques... threats and patterns; (ix) Recognition and detection of dangerous substances and devices; (x) Recognition...) Techniques used to circumvent security measures; (xii) Methods of physical screening and non-intrusive...

33 CFR 104.210 - Company Security Officer (CSO).

Code of Federal Regulations, 2013 CFR

2013-07-01

... operational limitations; (vi) Methods of conducting audits, inspection and control and monitoring techniques... threats and patterns; (ix) Recognition and detection of dangerous substances and devices; (x) Recognition...) Techniques used to circumvent security measures; (xii) Methods of physical screening and non-intrusive...

33 CFR 104.210 - Company Security Officer (CSO).

Code of Federal Regulations, 2012 CFR

2012-07-01

... operational limitations; (vi) Methods of conducting audits, inspection and control and monitoring techniques... threats and patterns; (ix) Recognition and detection of dangerous substances and devices; (x) Recognition...) Techniques used to circumvent security measures; (xii) Methods of physical screening and non-intrusive...

Ares I-X Ground Diagnostic Prototype

NASA Technical Reports Server (NTRS)

Schwabacher, Mark; Martin, Rodney; Waterman, Robert; Oostdyk, Rebecca; Ossenfort, John; Matthews, Bryan

2010-01-01

Automating prelaunch diagnostics for launch vehicles offers three potential benefits. First, it potentially improves safety by detecting faults that might otherwise have been missed so that they can be corrected before launch. Second, it potentially reduces launch delays by more quickly diagnosing the cause of anomalies that occur during prelaunch processing. Reducing launch delays will be critical to the success of NASA's planned future missions that require in-orbit rendezvous. Third, it potentially reduces costs by reducing both launch delays and the number of people needed to monitor the prelaunch process. NASA is currently developing the Ares I launch vehicle to bring the Orion capsule and its crew of four astronauts to low-earth orbit on their way to the moon. Ares I-X will be the first unmanned test flight of Ares I. It is scheduled to launch on October 27, 2009. The Ares I-X Ground Diagnostic Prototype is a prototype ground diagnostic system that will provide anomaly detection, fault detection, fault isolation, and diagnostics for the Ares I-X first-stage thrust vector control (TVC) and for the associated ground hydraulics while it is in the Vehicle Assembly Building (VAB) at John F. Kennedy Space Center (KSC) and on the launch pad. It will serve as a prototype for a future operational ground diagnostic system for Ares I. The prototype combines three existing diagnostic tools. The first tool, TEAMS (Testability Engineering and Maintenance System), is a model-based tool that is commercially produced by Qualtech Systems, Inc. It uses a qualitative model of failure propagation to perform fault isolation and diagnostics. We adapted an existing TEAMS model of the TVC to use for diagnostics and developed a TEAMS model of the ground hydraulics. The second tool, Spacecraft Health Inference Engine (SHINE), is a rule-based expert system developed at the NASA Jet Propulsion Laboratory. We developed SHINE rules for fault detection and mode identification. The prototype uses the outputs of SHINE as inputs to TEAMS. The third tool, the Inductive Monitoring System (IMS), is an anomaly detection tool developed at NASA Ames Research Center and is currently used to monitor the International Space Station Control Moment Gyroscopes. IMS automatically "learns" a model of historical nominal data in the form of a set of clusters and signals an alarm when new data fails to match this model. IMS offers the potential to detect faults that have not been modeled. The three tools have been integrated and deployed to Hangar AE at KSC where they interface with live data from the Ares I-X vehicle and from the ground hydraulics. The outputs of the tools are displayed on a console in Hangar AE, one of the locations from which the Ares I-X launch will be monitored. The full paper will describe how the prototype performed before the launch. It will include an analysis of the prototype's accuracy, including false-positive rates, false-negative rates, and receiver operating characteristics (ROC) curves. It will also include a description of the prototype's computational requirements, including CPU usage, main memory usage, and disk usage. If the prototype detects any faults during the prelaunch period then the paper will include a description of those faults. Similarly, if the prototype has any false alarms then the paper will describe them and will attempt to explain their causes.

[GOAL-DIRECTED FLUID THERAPY IN SEVERE CONCOMITANT TRAUMA].

PubMed

Konkaev, A K; Gurbanova, E I; Mynbaeva, Z N

2015-01-01

We examined 78 patients with severe concomitant injury. Were evaluated the severity of the injury and indices of volumetric haemodynamic monitoring by PICCO. The retrospective comparison group consisted of 50 patients with severe concomitant injury who were treated in the ICU of Trauma Institution during 2009-2011. In patients with severe concomitant injury goal-directed fluid therapy based on PICCO monitoring parameters increasing the volume of infusion on the second and third post-traumatic days by 45% and 24%, respectively (< 0.05). Infusion-related pulmonary complications in the study group patients were not recorded Goal-directed fluid therapy was one of the factors that made it possible to reduce patient's mortality 2.1 times on conditions that severity of the injury and the initial state were similar. Colloid (6% HES 200/0.5) infusion was associated with increases in rate of transient azotemia.

Comparative kinetics of damage to the plasma and mitochondrial membranes by intra-cellularly synthesized and externally-provided photosensitizers using multi-color FACS.

PubMed

Haupt, Sara; Malik, Zvi; Ehrenberg, Benjamin

2014-01-01

Photodynamic therapy (PDT) of cancer involves inflicting lethal damage to the cells of malignant tumors, primarily by singlet oxygen that is generated following light-absorption in a photosensitizer molecule. Dysfunction of cells is manifested in many ways, including peroxidation of cellular components, membrane rupture, depolarization of electric potentials, termination of mitochondrial activity, onset of apoptosis and necrosis and eventually cell lysis. These events do not necessarily occur in linear fashion and different types of damage to cell components occur, most probably, in parallel. In this report we measured the relative rates of damage to two cellular membranes: the plasma membrane and the mitochondrial membrane. We employed photosensitizers of diverse hydrophobicities and used different incubation procedures, which lead to their different intra-cellular localizations. We monitored the damage that was inflicted on these membranes, by employing optical probes of membrane integrity, in a multi-color FACS experiment. The potentiometric indicator JC-1 monitored the electric cross-membrane potential of the mitochondria and the fluorometric indicator Draq7 monitored the rupture of the plasma membrane. We show that the electric depolarization of the mitochondrial membrane and the damage to the enveloping plasma membrane proceed with different kinetics that reflect the molecular character and intracellular location of the sensitizer: PpIX that is synthesized in the cells from ALA causes rapid mitochondrial damage and very slow damage to the plasma membrane, while externally added PpIX has an opposite effect. The hydrophilic sensitizer HypS4 can be taken up by the cells by different incubation conditions, and these affect its intracellular location, and as a consequence either the plasma membrane or the mitochondria is damaged first. A similar correlation was found for additional extracellularly-provided photosensitizers HP and PpIX.

Singlet oxygen feedback delayed fluorescence of protoporphyrin IX in organic solutions.

PubMed

Vinklárek, Ivo S; Scholz, Marek; Dědic, Roman; Hála, Jan

2017-04-12

Delayed fluorescence (DF) of protoporphyrin IX (PpIX) has been recently proposed as a tool for monitoring of mitochondrial oxygen tension in vivo as well as for observation of the effectiveness of photodynamic therapy (PDT) [E. G. Mik, Anesth. Analg., 2013, 117, 834-346; F. Piffaretti et al., J. Biomed. Opt., 2012, 17, 115007]. However, the efficiency of the mechanism of thermal activation (E-type DF), which was considered in the papers, is limited due to a large energy gap between the first excited singlet and the first triplet state of PpIX at room or body temperatures. Moreover, the energy gap is roughly equal to other porphyrinoid photosensitizers that generate DF mostly through the Singlet Oxygen Feedback-Induced mechanism (SOFDF) under certain conditions [M. Scholz and R. Dědic, Singlet Oxygen: Applications in Biosciences and Nanosciences, 2016, vol. 2, pp. 63-81]. The mechanisms of delayed fluorescence of PpIX dissolved either in dimethylformamide (DMF) or in the mixture of DMF with ethylene glycol (EG) were investigated at atmospheric partial pressure of oxygen by means of a simultaneous time-resolved detection of 1 O 2 phosphorescence and PpIX DF which makes a direct comparison of the kinetics and lifetimes of both the luminescence channels possible. Samples of PpIX (100 μM) exhibit concave DF kinetics, which is a typical footprint of the SOFDF mechanism. The dramatic decrease in the DF intensity after adding a selective 1 O 2 quencher sodium azide (NaN 3 , 10 mM) proves that >90% of DF is indeed generated through SOFDF. Moreover, the analysis of the DF kinetics in the presence of NaN 3 implies that the second significant mechanism of DF generation is the triplet-triplet annihilation (P-type DF). The bimolecular mechanism of DF was further confirmed by the decrease of the DF intensity in the more viscous mixture DMF/EG and by the increase of the ratio of DF to the prompt fluorescence (PF) intensity with the increasing excitation intensity. These results show the significant role of the SOFDF mechanism in the DF of PpIX at high concentrations and at atmospheric partial pressure of oxygen and should be considered when developing diagnostic tools for clinical applications.

42 CFR 493.15 - Laboratories performing waived tests.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Hemoglobin; (iv) Ketone; (v) Leukocytes; (vi) Nitrite; (vii) pH; (viii) Protein; (ix) Specific gravity; and... rate—non-automated; (6) Hemoglobin—copper sulfate—non-automated; (7) Blood glucose by glucose monitoring devices cleared by the FDA specifically for home use; (8) Spun microhematocrit; and (9) Hemoglobin...

42 CFR 493.15 - Laboratories performing waived tests.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Hemoglobin; (iv) Ketone; (v) Leukocytes; (vi) Nitrite; (vii) pH; (viii) Protein; (ix) Specific gravity; and... rate—non-automated; (6) Hemoglobin—copper sulfate—non-automated; (7) Blood glucose by glucose monitoring devices cleared by the FDA specifically for home use; (8) Spun microhematocrit; and (9) Hemoglobin...

ALA-mediated fluorescence-guided resection (FGR) and PDT of glioma

NASA Astrophysics Data System (ADS)

Johansson, Ann; Stepp, Herbert; Beck, Tobias; Beyer, Wolfgang; Pongratz, Thomas; Sroka, Ronald; Meinel, Thomas; Stummer, Walter; Kreth, Friedrich-Wilhelm; Tonn, Jörg-Christian; Baumgartner, Reinhold

2009-06-01

A summary of clinical trials employing photodynamic diagnosis (PDD) and photodynamic therapy (PDT) for the diagnosis and treatment of brain malignancies is presented. Intra-cavity PDT has been performed within the surgical cavity following FGR, employing oral administration of 5-aminolevulinic acid (5-ALA), either targeting fluorescing tissue regions that were not removed during FGR due to safety reasons (referred to as focal PDT, n=20) or illuminating the entire resection cavity (referred to as integral PDT, n=9). Both approaches proved technically feasible and safe. Spectroscopic measurements performed pre-, during and post-PDT revealed Protoporphyrin IX (PpIX)-photobleaching of more than 95% after the delivery of 200 J/cm2. This light dose did not induce any side effects. Furthermore, interstitial PDT (iPDT) has been employed within one feasibility trial (n=10) and one Phase I/II trial (n=15). Here, three to six cylindrical light diffusors (20-30 mm length, 200 mW/cm, 720 J/cm) were positioned within the target tissue under stereotactic guidance. Pre-treatment planning was performed with the intent to target the entire tumour volume with a sufficient light dose while also minimising the risk of any light-induced temperature increase. For the feasibility trial patients with small, recurrent gliomas were included, resulting in a median survival of 15 months as well as some unexpected longterm survivals (up to 5 years). The Phase I/II trial employed the same clinical procedures. Here, the 12-month survival was 35% and the median progression-free survival was 6 months. In summary, stereotactic iPDT in combination with treatment-planning could be shown to be a safe and feasible treatment modality. These trials are presently being extended to also include on-line monitoring of PpIX fluorescence and photobleaching kinetics. Preliminary data has revealed dramatically different PpIX levels and photobleaching kinetics. Such data could possibly be employed for realtime treatment monitoring and as an early prognostic marker for the PDT response.

Fluorescence spectroscopy in the visible range for the assessment of UVB radiation effects in hairless mice skin.

PubMed

de Paula Campos, Carolina; de Paula D'Almeida, Camila; Nogueira, Marcelo Saito; Moriyama, Lilian Tan; Pratavieira, Sebastião; Kurachi, Cristina

2017-12-01

Ultraviolet (UV) radiation may induce skin alterations as observed in photoaging. Some recognized modifications are epidermal hyperplasia, amorphous deposition of degraded elastic fibers and reduction in the number of collagen fibers. They alter the tissue biochemical properties that can be interrogated by steady state fluorescence spectroscopy (SSFS). In this study, we monitored the changes in endogenous fluorescence emission from hairless mice skin during a protocol of photoaging using UVB irradiation. To perform the fluorescence spectroscopy, it was used a violet laser (408nm) to induce the native fluorescence that is emitted in the visible range. Under 408nm excitation, the emission spectrum showed bands with peaks centered around 510, 633 and 668nm for irradiated and control groups. A relative increase of the fluorescence at 633nm emission on the flank was observed with time when compared to the ventral skin at the same animal and the non-irradiated control group. We correlated the emission at 633nm with protoporphyrin IX (PpIX), and our hypothesis is that the PpIX metabolism in the photoaged and aged skin are different. PpIX fluorescence intensity in the photoaged skin is higher and more heterogeneous than in the aged skin. Notwithstanding, more spectroscopic and biochemistry studies investigating the 510 and 633nm emission are needed to confirm this hypothesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and photochemical properties of a novel iron-sulfur-nitrosyl cluster derivatized with the pendant chromophore protoporphyrin IX.

PubMed

Conrado, Christa L; Wecksler, Stephen; Egler, Christian; Magde, Douglas; Ford, Peter C

2004-09-06

The novel Roussin red-salt ester (PPIX-RSE) with a pendant porphyrin chromophore was prepared and investigated as a precursor for the photochemical generation of nitric oxide. PPIX-RSE has the general formula Fe(2)(NO)(4)[(mu-S,mu-S')P] (where (S,S')P is the bis(2-thiolatoethyl) diester of protoporphyrin IX. The photoexcitation of PPIX-RSE with 436- or 546-nm light in an aerated chloroform solution led to the photodecomposition of the cluster with the respective quantum yields (5.2 +/- 0.7) x 10(-4) and (2.5 +/- 0.5 x 10(-4)) and the concomitant release of NO. PPIX-RSE is a significantly more effective NO generator at longer wavelength excitation than are other Fe(2)(mu-SR)(2)(NO)(4) esters for which R is a simple alkyl group such as CH(3)CH(2)- because of the much higher absorptivity of the pendant PPIX chromophore at these wavelengths and a modestly higher quantum yield. Fluorescence intensity and lifetime data indicate that the photoexcited porphyrin of PPIX-RSE is largely quenched by the energy transfer to the Fe(2)S(2)(NO)(4) cluster's core. However, a small fraction of this emission is not quenched, and it is proposed that PPIX-RSE may exist in solution as two conformers.

MEASUREMENT OF RURAL SULFUR DIOXIDE AND PARTICLE SULFATE: ANALYSIS OF CASTNET DATA, 1987 - 1996

EPA Science Inventory

The Clean Sir Status and Trends Network (CASTNet) was implemented by the U.S. Environmental Protection Agency (EPA) in 1991 in response to Title IX of the Clean Air Amendments of 1990, which mandated the deployment of a national ambient air monitoring network to track progress of...

23 CFR Appendix A to Subpart C of... - State Highway Agency Equal Employment Opportunity Programs

Code of Federal Regulations, 2011 CFR

2011-04-01

... results of its minority business enterprise efforts. IX. Liaison. Describe the liaison established by the... systems to monitor and measure progress regularly. If results are not satisfactory to meet goals... relation to the present and projected manpower needs of the agency and the employees' career goals. (4) The...

23 CFR Appendix A to Subpart C of... - State Highway Agency Equal Employment Opportunity Programs

Code of Federal Regulations, 2014 CFR

2014-04-01

... results of its minority business enterprise efforts. IX. Liaison. Describe the liaison established by the... systems to monitor and measure progress regularly. If results are not satisfactory to meet goals... relation to the present and projected manpower needs of the agency and the employees' career goals. (4) The...

23 CFR Appendix A to Subpart C of... - State Highway Agency Equal Employment Opportunity Programs

Code of Federal Regulations, 2012 CFR

2012-04-01

... results of its minority business enterprise efforts. IX. Liaison. Describe the liaison established by the... systems to monitor and measure progress regularly. If results are not satisfactory to meet goals... relation to the present and projected manpower needs of the agency and the employees' career goals. (4) The...

23 CFR Appendix A to Subpart C of... - State Highway Agency Equal Employment Opportunity Programs

Code of Federal Regulations, 2013 CFR

2013-04-01

... results of its minority business enterprise efforts. IX. Liaison. Describe the liaison established by the... systems to monitor and measure progress regularly. If results are not satisfactory to meet goals... relation to the present and projected manpower needs of the agency and the employees' career goals. (4) The...

23 CFR Appendix A to Subpart C of... - State Highway Agency Equal Employment Opportunity Programs

Code of Federal Regulations, 2010 CFR

2010-04-01

... results of its minority business enterprise efforts. IX. Liaison. Describe the liaison established by the... systems to monitor and measure progress regularly. If results are not satisfactory to meet goals... relation to the present and projected manpower needs of the agency and the employees' career goals. (4) The...

Qualification of a select one-stage activated partial thromboplastin time-based clotting assay and two chromogenic assays for the post-administration monitoring of nonacog beta pegol.

PubMed

Tiefenbacher, S; Bohra, R; Amiral, J; Bowyer, A; Kitchen, S; Lochu, A; Rosén, S; Ezban, M

2017-10-01

Essentials Nonacog beta pegol (N9-GP) is an extended half-life, recombinant human factor IX (FIX). One-stage clotting (OSC) and chromogenic FIX activity assays were assessed for N9-GP recovery. OSC STA ® -Cephascreen ® , ROX FIX and BIOPHEN FIX chromogenic assays were qualified for N9-GP. Other extended half-life factor products should be assessed in a similar way prior to approval. Background Nonacog beta pegol (N9-GP) is an extended half-life, glycoPEGylated recombinant human factor IX that is under development for the prophylaxis and treatment of bleeding episodes in hemophilia B patients. Considerable reagent-dependent variability has been observed when one-stage clotting assays are used to measure the recovery of recombinant FIX products, including N9-GP. Objective To qualify select one-stage clotting and chromogenic FIX activity assays for measuring N9-GP recovery. Methods The accuracy and precision of the one-stage clotting assay (with the STA-Cephascreen activated partial thromboplastin [APTT] reagent) and the ROX Factor IX and BIOPHEN Factor IX chromogenic assays for measuring N9-GP recovery were assessed in N9-GP-spiked hemophilia B plasma samples in a systematic manner at three independent sites, with manufacturer-recommended protocols and/or site-specific assay setups, including different instruments. Results For each of the three FIX activity assays qualified on five different reagent-instrument systems, acceptable intra-assay and interassay accuracy and precision, dilution integrity, reagent robustness and freeze-thaw and short-term sample stabilities were demonstrated. The STA-Cephascreen assay showed a limited reportable range at one of the three qualification sites, and the BIOPHEN Factor IX assay showed suspect low-end sensitivity at one of the three qualification sites. An individual laboratory would account for these limitations by adjusting the assay's reportable range; thus, these findings are not considered to impact the respective assay qualifications. Conclusion The one-stage clotting assay with the STA-Cephascreen APTT reagent, the ROX Factor IX chromogenic assay and the BIOPHEN Factor IX chromogenic assay are considered to be qualified for the measurement of N9-GP in 3.2% (0.109 m) citrated human plasma. © 2017 International Society on Thrombosis and Haemostasis.

5-Aminolevulinic Acid-Squalene Nanoassemblies for Tumor Photodetection and Therapy: In Vitro Studies

NASA Astrophysics Data System (ADS)

Babič, Andrej; Herceg, V.; Bastien, E.; Lassalle, H.-P.; Bezdetnaya, L.; Lange, Norbert

2018-01-01

Protoporphyrin IX (PpIX) as natural photosensitizer derived from administration of 5-aminolevulinic acid (5-ALA) has found clinical use for photodiagnosis and photodynamic therapy of several cancers. However, broader use of 5-ALA in oncology is hampered by its charge and polarity that result in its reduced capacity for passing biological barriers and reaching the tumor tissue. Advanced drug delivery platforms are needed to improve the biodistribution of 5-ALA. Here, we report a new approach for the delivery of 5-ALA. Squalenoylation strategy was used to covalently conjugate 5-ALA to squalene, a natural precursor of cholesterol. 5-ALA-SQ nanoassemblies were formed by self-assembly in water. The nanoassemblies were monodisperse with average size of 70 nm, polydispersity index of 0.12, and ζ-potential of + 36 mV. They showed good stability over several weeks. The drug loading of 5-ALA was very high at 26%. In human prostate cancer cells PC3 and human glioblastoma cells U87MG, PpIX production was monitored in vitro upon the incubation with nanoassemblies. They were more efficient in generating PpIX-induced fluorescence in cancer cells compared to 5-ALA-Hex at 1.0 to 3.3 mM at short and long incubation times. Compared to 5-ALA, they showed superior fluorescence performance at 4 h which was diminished at 24 h. 5-ALA-SQ presents a novel nano-delivery platform with great potential for the systemic administration of 5-ALA.

Improve efficacy of topical ALA-PDT by calcipotriol through up-regulation of coproporphyrinogen oxidase.

PubMed

Yang, Deng-Fu; Chen, Jia-Haur; Chiang, Chun-Pin; Huang, Zheng; Lee, Jeng-Woei; Liu, Chung-Ji; Chang, Junn-Liang; Hsu, Yih-Chih

2014-09-01

Topical 5-aminolevulinic acid-mediated photodynamic therapy (topical ALA-PDT) is effective for treating oral precancerous lesions. The aim of this in vivo and in vitro study was to examine whether the efficacy of topical ALA-PDT could be further improved by calcipotriol (CAL). Precancerous lesions in the buccal pouch of hamsters were induced by dimethylbenz(a)anthracene (DMBA). Lesions were treated with multiple topical ALA-PDT with or without CAL pretreatment. ALA-induced protoporphyrine IX (PpIX) was monitored by in situ fluorescence measurement. The effect of CAL on heme-related enzymes (CPOX, PPOX, and FECH) were examined in an in vitro model using human squamous cell carcinoma (SCC) cells (SCC4, SAS) using Western blots. Fluorescence spectroscopy revealed that PpIX reached its peak level in precancerous epithelial cells of buccal pouch at 2.5 or 3.5h without or with CAL pretreatment, respectively. Both treatment regimens showed similar response rates, but the complete response was achieved after 5 times of ALA-PDT and 3 times of CAL-ALA-PDT (p<0.001). Pretreatment of SCC cells with 10(-8) or 10(-7)M CAL could result in a significant cell death (p<0.05) and an elevation of CPOX protein level. Topical CAL can improve the efficacy of ALA-PDT in treating precancerous lesions, likely through the increase in CPOX level and in PpIX production. Copyright © 2014 Elsevier B.V. All rights reserved.

Laser-induced fluorescence diagnostics of basal cell carcinomas of the skin following topical ALA application

NASA Astrophysics Data System (ADS)

af Klinteberg, Claes; Nilsson, Annika M.; Wang-Nordman, Ingrid; Andersson-Engels, Stefan; Svanberg, Sune; Svanberg, Katarina

1996-12-01

Fourteen patients with superficial basal cell carcinomas (BCCs) and fifteen patients with nodular BCCs were investigated by means of laser-induced fluorescence (LIF) in connection with photodynamic therapy (PDT). Topical application of (delta) -amino levulinic acid (ALA) was performed six hours prior to the treatment session. Fluorescence spectra were recorded, using a point-monitoring system with an excitation wavelength of 405 nm. The measurements were performed in scans over the lesion and the surrounding normal skin before application of ALA, and immediately before and after the laser treatment. The selective uptake of the photosensitive resulted in a fluorescence intensity ratio of 2.4:1 for superficial BCCs and 2.5:1 for nodular BCCs. If the fluorescence intensity was divided by the autofluorescence, this resulted in a contrast enhancement of about a factor 6 for tumor tissue. In seven patients (five with nodular BCC and two with superficial BCC), additional fluorescence measurements were performed two and four hours following the ALA application, and two hours after the PDT procedure. Thus, the kinetics of the transformation of ALA to protoporphyrin IX (PpIX) could be followed, which indicated that the synthesis of PpIX was more rapid in the tumor than in the normal tissue. After four hours, the PpIX level inside the tumour was saturated, while there still was an accumulation in the surrounding skin. The highest contrast between tumor and normal skin was reached within two hours after the ALA application.

Response Surface Analysis of Stochastic Network Performance

DTIC Science & Technology

1988-12-01

Bl5/32768/, B16 /65536/,P/2147483647/ XHI-IX/B 16 XALO=(IX-XHI* Bl6 )*A LEFTLO=XALO/ Bl6 FHI=XHI*A+LEFTLO IC=FHI/B1 5 IX-(((XALO-LEFTLO* Bl6 )-P)4(FHI-K*Bl5...ELSE GO TO 50 END IF GO TO 50 100 END D-5 * RANDOM NUMBER GENERATOR FUNCTION RANDOM( IX) INTEGER AP, IX,B15, B16 ,XHI ,XALOI,LEFTLO,FHI ,K DATA A/16807... Bl6 )+K IF(IX.LT.O) IX=IX+P RANDOM-FLOAT( IX) *4.656612875E-1O RETURN END * NETWORK ENTRY and * PATHSET AND CUTSET GENERATION SUBROUTINE SUBROUTINE

Long-Term Safety and Efficacy of Factor IX Gene Therapy in Hemophilia B

PubMed Central

Nathwani, A.C.; Reiss, U.M.; Tuddenham, E.G.D.; Rosales, C.; Chowdary, P.; McIntosh, J.; Della Peruta, M.; Lheriteau, E.; Patel, N.; Raj, D.; Riddell, A.; Pie, J.; Rangarajan, S.; Bevan, D.; Recht, M.; Shen, Y.-M.; Halka, K.G.; Basner-Tschakarjan, E.; Mingozzi, F.; High, K.A.; Allay, J.; Kay, M.A.; Ng, C.Y.C.; Zhou, J.; Cancio, M.; Morton, C.L.; Gray, J.T.; Srivastava, D.; Nienhuis, A.W.; Davidoff, A.M.

2014-01-01

BACKGROUND In patients with severe hemophilia B, gene therapy that is mediated by a novel self-complementary adeno-associated virus serotype 8 (AAV8) vector has been shown to raise factor IX levels for periods of up to 16 months. We wanted to determine the durability of transgene expression, the vector dose–response relationship, and the level of persistent or late toxicity. METHODS We evaluated the stability of transgene expression and long-term safety in 10 patients with severe hemophilia B: 6 patients who had been enrolled in an initial phase 1 dose-escalation trial, with 2 patients each receiving a low, intermediate, or high dose, and 4 additional patients who received the high dose (2×1012 vector genomes per kilogram of body weight). The patients subsequently underwent extensive clinical and laboratory monitoring. RESULTS A single intravenous infusion of vector in all 10 patients with severe hemophilia B resulted in a dose-dependent increase in circulating factor IX to a level that was 1 to 6% of the normal value over a median period of 3.2 years, with observation ongoing. In the high-dose group, a consistent increase in the factor IX level to a mean (±SD) of 5.1±1.7% was observed in all 6 patients, which resulted in a reduction of more than 90% in both bleeding episodes and the use of prophylactic factor IX concentrate. A transient increase in the mean alanine aminotransferase level to 86 IU per liter (range, 36 to 202) occurred between week 7 and week 10 in 4 of the 6 patients in the high-dose group but resolved over a median of 5 days (range, 2 to 35) after prednisolone treatment. CONCLUSIONS In 10 patients with severe hemophilia B, the infusion of a single dose of AAV8 vector resulted in long-term therapeutic factor IX expression associated with clinical improvement. With a follow-up period of up to 3 years, no late toxic effects from the therapy were reported. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00979238.) PMID:25409372

Alloimmunization in Congenital Deficiencies of Platelet Surface Glycoproteins: Focus on Glanzmann's Thrombasthenia and Bernard-Soulier's Syndrome.

PubMed

Poon, Man-Chiu; d'Oiron, Roseline

2018-06-07

Glanzmann's thrombasthenia (GT) and Bernard-Soulier's syndrome (BSS) are well-understood congenital bleeding disorders, showing defect/deficiency of platelet glycoprotein (GP) IIb/IIIa (integrin αIIbβ3) and GPIb-IX-V complexes respectively, with relevant clinical, laboratory, biochemical, and genetic features. Following platelet transfusion, affected patients may develop antiplatelet antibodies (to human leukocyte antigen [HLA], and/or αIIbβ3 in GT or GPIb-IX in BSS), which may render future platelet transfusion ineffective. Anti-αIIbβ3 and anti-GPIb-IX may also cross the placenta during pregnancy to cause thrombocytopenia and bleeding in the fetus/neonate. This review will focus particularly on the better studied GT to illustrate the natural history and complications of platelet alloimmunization. BSS will be more briefly discussed. Platelet transfusion, if unavoidable, should be given judiciously with good indications. Patients following platelet transfusion, and women during and after pregnancy, should be monitored for the development of platelet antibodies. There is now a collection of data suggesting the safety and effectiveness of recombinant activated factor VII in the management of affected patients with platelet antibodies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

40 CFR Appendix Ix to Part 266 - Methods Manual for Compliance With the BIF Regulations

Code of Federal Regulations, 2010 CFR

2010-07-01

... Systems 2.1Performance Specifications for Continuous Emission Monitoring of Carbon Monoxide and Oxygen for... Methodology for Bevill Residue Determinations 8.0Procedures for Determining Default Values for Air Pollution Control System Removal Efficiencies 8.1APCS RE Default Values for Metals 8.2APCS RE Default Values for HC1...

40 CFR Appendix Ix to Part 266 - Methods Manual for Compliance With the BIF Regulations

Code of Federal Regulations, 2011 CFR

2011-07-01

... Systems 2.1Performance Specifications for Continuous Emission Monitoring of Carbon Monoxide and Oxygen for... Methodology for Bevill Residue Determinations 8.0Procedures for Determining Default Values for Air Pollution Control System Removal Efficiencies 8.1APCS RE Default Values for Metals 8.2APCS RE Default Values for HC1...

40 CFR 63.11585 - What are my notification, recordkeeping, and reporting requirements?

Code of Federal Regulations, 2010 CFR

2010-07-01

... of the bag leak detector, parameter monitor, or CPMS. (ix) If a CPMS is used, the date of the latest...) Records of all inspections as required by § 63.11584(b) and pressure measurement device checks (if... according to § 63.11583(f). (viii) Records of particulate control device manufacturing specifications and...

40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

Code of Federal Regulations, 2011 CFR

2011-07-01

... aldehyde 7421-93-4 1,2,4- Methenocyclopenta[cd] pentalene-5-carboxaldehyde, 2,2a,3,3,4,7...; Dichloromethane 75-09-2 Methane, dichloro- Methyl ethyl ketone; MEK; 78-93-3 2-Butanone Methyl iodide; Iodomethane...-Methyl-2-pentanone; Methyl isobutyl ketone 108-10-1 2-Pentanone, 4-methyl- Naphthalene 91-20-3...

40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

Code of Federal Regulations, 2012 CFR

2012-07-01

... aldehyde 7421-93-4 1,2,4- Methenocyclopenta[cd] pentalene-5-carboxaldehyde, 2,2a,3,3,4,7...; Dichloromethane 75-09-2 Methane, dichloro- Methyl ethyl ketone; MEK; 78-93-3 2-Butanone Methyl iodide; Iodomethane...-Methyl-2-pentanone; Methyl isobutyl ketone 108-10-1 2-Pentanone, 4-methyl- Naphthalene 91-20-3...

40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

Code of Federal Regulations, 2010 CFR

2010-07-01

... aldehyde 7421-93-4 1,2,4- Methenocyclopenta[cd] pentalene-5-carboxaldehyde, 2,2a,3,3,4,7...; Dichloromethane 75-09-2 Methane, dichloro- Methyl ethyl ketone; MEK; 78-93-3 2-Butanone Methyl iodide; Iodomethane...-Methyl-2-pentanone; Methyl isobutyl ketone 108-10-1 2-Pentanone, 4-methyl- Naphthalene 91-20-3...

40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

Code of Federal Regulations, 2014 CFR

2014-07-01

... aldehyde 7421-93-4 1,2,4- Methenocyclopenta[cd] pentalene-5-carboxaldehyde, 2,2a,3,3,4,7...; Dichloromethane 75-09-2 Methane, dichloro- Methyl ethyl ketone; MEK; 78-93-3 2-Butanone Methyl iodide; Iodomethane...-Methyl-2-pentanone; Methyl isobutyl ketone 108-10-1 2-Pentanone, 4-methyl- Naphthalene 91-20-3...

40 CFR Appendix Ix to Part 264 - Ground-Water Monitoring List

Code of Federal Regulations, 2013 CFR

2013-07-01

... aldehyde 7421-93-4 1,2,4- Methenocyclopenta[cd] pentalene-5-carboxaldehyde, 2,2a,3,3,4,7...; Dichloromethane 75-09-2 Methane, dichloro- Methyl ethyl ketone; MEK; 78-93-3 2-Butanone Methyl iodide; Iodomethane...-Methyl-2-pentanone; Methyl isobutyl ketone 108-10-1 2-Pentanone, 4-methyl- Naphthalene 91-20-3...

Cutaneous Respirometry as Novel Technique to Monitor Mitochondrial Function: A Feasibility Study in Healthy Volunteers

PubMed Central

Stolker, Robert Jan; Mik, Egbert

2016-01-01

Background The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) is proposed as a potential clinical non-invasive tool to monitor mitochondrial function. This technique has been evaluated in several animal studies. Mitochondrial respirometry allows measurement in vivo of mitochondrial oxygen tension (mitoPO2) and mitochondrial oxygen consumption (mitoVO2) in skin. This study describes the first use of a clinical prototype in skin of humans. Methods The clinical prototype was tested in 30 healthy volunteers. A self-adhesive patch containing 2 mg 5-aminolevulinic acid (ALA) was applied on the skin of the anterior chest wall (sternal) for induction of mitochondrial protoporphyrin IX and was protected from light for 5 h. MitoPO2 was measured by means of oxygen-dependent delayed fluorescence of protoporphyrin IX. MitoVO2 was determined by dynamic mitoPO2 measurements on the primed skin, while locally blocking oxygen supply by applying local pressure with the measurement probe. MitoPO2 was recorded before and during a 60-s period of compression of the microcirculation, at an interval of 1 Hz. Oxygen consumption (i.e. the local oxygen disappearance rate) was calculated from the decay of the mitoPO2 slope. Results Oxygen-dependent delayed fluorescence measurements were successfully performed in the skin of 27 volunteers. The average value (± SD) of mitoPO2 was 44 ± 17 mmHg and mean mitoVO2 values were 5.8 ± 2.3 and 6.1 ± 1.6 mmHg s-1 at a skin temperature of 34°C and 40°C, respectively. No major discomfort during measurement and no long-term dermatological abnormalities were reported in a survey performed 1 month after measurements. Conclusion These results show that the clinical prototype allows measurement of mitochondrial oxygenation and oxygen consumption in humans. The development of this clinically applicable device offers opportunities for further evaluation of the technique in humans and the start of first clinical studies. PMID:27455073

Effect of Photon Radiations in Semi-Rigid Artificial Tissue Sensitized by Protoporphyrin IX Encapsulated with Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Makhadmeh, Ghaseb N.; Aziz, Azlan Abdul; Razak, Khairunisak Abdul; Al-Akhras, M.-Ali H.

2018-02-01

This study involves the synthesis of Protoporphyrin IX (PpIX) encapsulated with Silica Nanoparticles (SiNPs) as an application for Photodynamic therapy. Semi-rigid artificial tissues with optical features similar to human tissue were used as sample materials to ascertain the efficacy of PpIX encapsulated with SiNPs. The disparity in optical characteristics (transmittance, reflectance, scattering, and absorption) of tissues treated with encapsulated PpIX and naked PpIX under light exposure (Intensity at 408 nm ~1.19 mW/cm2) was explored. The optimal exposure times required for naked PpIX and SiNPs encapsulated PpIX to engulf Red Blood Cells (RBCs) in the artificial tissue were subsequently measured. Comparative analysis showed that the encapsulated PpIX has a 91.5 % higher efficacy than naked PpIX. The results prove the applicability of PpIX encapsulated with SiNP on artificial tissue and possible use on human tissue.

Purification and characterization of an abnormal factor IX (Christmas factor) molecule. Factor IX Chapel Hill.

PubMed Central

Chung, K S; Madar, D A; Goldsmith, J C; Kingdon, H S; Roberts, H R

1978-01-01

Human Factor IX (Christmas factor) was isolated from the plasma of a patient with mild hemophilia B. The patient's plasma contained 5% Factor IX clotting activity but 100% Factor IX antigenic activity as determined by immunological assays, which included inhibitor neutralization and a radioimmunoassay for Factor IX. This abnormal Factor IX is called Factor IX Chapel Hill (Factor IXCH). Both normal Factor IX and Factor IXCH have tyrosine as the NH2-terminal amino acid. The two proteins have a similar molecular weight, a similar amino acid analysis, the same number of gamma-carboxyglutamic acid residues (10 gamma-carboxyglutamic acid residues), and a similar carbohydrate content. Both exist as a single-chain glycoprotein in plasma. The major difference between normal Factor IX and Factor IXCH is that the latter exhibits delayed activation to Factor IXa in the presence of Factor XIa and Ca2+. Thus, Factor IXCH differs from other previously described abnormal Factor IX molecules. Images PMID:711853

Genetics Home Reference: glycogen storage disease type IX

MedlinePlus

... Health Conditions Glycogen storage disease type IX Glycogen storage disease type IX Printable PDF Open All Close ... to view the expand/collapse boxes. Description Glycogen storage disease type IX (also known as GSD IX) ...

Encapsulation efficacy of natural and synthetic photosensitizers by silica nanoparticles for photodynamic applications.

PubMed

Makhadmeh, Ghaseb Naser; Abdul Aziz, Azlan; Abdul Razak, Khairunisak; Abu Noqta, Osama

2015-12-01

This study analysed the physical effects of Cichorium Pumilum (CP), as a natural photosensitizer (PS), and Protoporphyrin IX (PpIX), as a synthetic PS, encapsulated with silica nanoparticles (SiNPs) in photodynamic therapy. The optimum concentrations of CP and PpIX, needed to destroy Red Blood Cells (RBC), were determined and the efficacy of encapsulated CP and PpIX were compared with naked CP and PpIX was verified. The results confirmed the applicability of CP and PpIX encapsulated in SiNPs on RBCs, and established a relationship between the encapsulated CP and PpIX concentration and the time required to rupture 50% of the RBCs (t50). The CP and PpIX encapsulated in SiNPs exhibited higher efficacy compared with that of naked CP and PpIX, respectively, and CP had less efficacy compared with PpIX.

Single LED-based device to perform widefield fluorescence imaging and photodynamic therapy

NASA Astrophysics Data System (ADS)

Grecco, Clovis; Buzzá, Hilde H.; Stringasci, Mirian D.; Andrade, Cintia T.; Vollet-Filho, Jose D.; Pratavieira, Sebastião.; Zanchin, Anderson L.; Tuboy, Aparecida M.; Bagnato, Vanderlei S.

2015-06-01

Photodynamic therapy (PDT) is a treatment modality that can be indicated for several cancer types and pre-cancer lesions. One of the main applications of PDT is the treatment of superficial skin lesions such as basal cell carcinoma, Bowen's disease and actinic keratosis. Three elements are necessary in PDT, a photosensitizer (PS); light at specific wavelength to be absorbed by the PS, and molecular oxygen. A typical PS used for skin lesion is protoporphyrin IX (PpIX), which is an intrinsic PS; its production is stimulated by a pro-drug, such as 5-aminolevulinic acid (ALA). Before starting a treatment, it is very important to follow up the PpIX production (to ensure that enough PS was produced prior to a PDT application) and, during a PDT session, to monitor its photodegradation (as it is evidence of the photodynamic effect taking place). The aim of this paper is to present a unique device, LINCE (MMOptics - São Carlos, Brazil), that brings together two probes that can, respectively, allow for fluorescence imaging and work as a light source for PDT treatment. The fluorescence probe of the system is optically based on 400 nm LED (light emitting diodes) arrays that allow observing the fluorescence emission over 450 nm. The PDT illumination probe options are constituted of 630 nm LED arrays for small areas and, for large areas, of both 630 nm and 450 nm LED arrays. Joining both functions at the same device makes PDT treatment simpler, properly monitorable and, hence, more clinically feasible. LINCE has been used in almost 1000 PDT treatments of superficial skin lesions in Brazil, with 88.4% of clearance of superficial BCC.

Formation of Mg-Containing Chlorophyll Precursors from Protoporphyrin IX, δ-Aminolevulinic Acid, and Glutamate in Isolated, Photosynthetically Competent, Developing Chloroplasts 1

PubMed Central

Fufsler, Thomas P.; Castelfranco, Paul A.; Wong, Yum-Shing

1984-01-01

Intact developing chloroplasts isolated from greening cucumber (Cucumis sativus L. var Beit Alpha) cotyledons were found to contain all the enzymes necessary for the synthesis of chlorophyllide. Glutamate was converted to Mg-protoporphyrin IX (monomethyl ester) and protoclorophyllide. δ-Aminolevulinic acid and protoporphyrin IX were converted to Mg-protoporphyrin IX, Mg-protoporphyrin IX monomethyl ester, protochlorophyllide and chlorophyllide a. The conversion of δ-aminolevulinic acid or protoporphyrin IX to Mg-protoporphyrin IX (monomethyl ester) was inhibited by AMP and p-chloromercuribenzene sulfonate. Light stimulated the formation of Mg-protoporphyrin IX from all three substrates. In the case of δ-aminolevulinic acid and protoporphyrin IX, light could be replaced by exogenous ATP. In the case of glutamate, both ATP and reducing power were necessary to replace light. With all three substrates, glutamate, δ-aminolevulinic acid, and protoporphyrin IX, the stimulation of Mg-protoporphyrin IX accumulation in the light was abolished by DCMU, and this DCMU block was overcome by added ATP and reducing power. PMID:16663535

Carbonic Anhydrase IX Interacts with Bicarbonate Transporters in Lamellipodia and Increases Cell Migration via Its Catalytic Domain*

PubMed Central

Svastova, Eliska; Witarski, Wojciech; Csaderova, Lucia; Kosik, Ivan; Skvarkova, Lucia; Hulikova, Alzbeta; Zatovicova, Miriam; Barathova, Monika; Kopacek, Juraj; Pastorek, Jaromir; Pastorekova, Silvia

2012-01-01

Carbonic anhydrase IX (CA IX) is a hypoxia-induced cell surface enzyme expressed in solid tumors, and functionally involved in acidification of extracellular pH and destabilization of intercellular contacts. Since both extracellular acidosis and reduced cell adhesion facilitate invasion and metastasis, we investigated the role of CA IX in cell migration, which promotes the metastatic cascade. As demonstrated here, ectopically expressed CA IX increases scattering, wound healing and transwell migration of MDCK cells, while an inactive CA IX variant lacking the catalytic domain (ΔCA) fails to do so. Correspondingly, hypoxic HeLa cells exhibit diminished migration upon inactivation of the endogenous CA IX either by forced expression of the dominant-negative ΔCA variant or by treatment with CA inhibitor, implying that the catalytic activity is indispensable for the CA IX function. Interestingly, CA IX improves cell migration both in the absence and presence of hepatocyte growth factor (HGF), an established inducer of epithelial-mesenchymal transition. On the other hand, HGF up-regulates CA IX transcription and triggers CA IX protein accumulation at the leading edge of lamellipodia. In these membrane regions CA IX co-localizes with sodium bicarbonate co-transporter (NBCe1) and anion exchanger 2 (AE2) that are both components of the migration apparatus and form bicarbonate transport metabolon with CA IX. Moreover, CA IX physically interacts with AE2 and NBCe1 in situ, as shown here for the first time. Thus, our findings suggest that CA IX actively contributes to cell migration via its ability to facilitate ion transport and pH control at protruding fronts of moving cells. PMID:22170054

Comparison of the behavior of normal factor IX and the factor IX Bm variant Hilo in the prothrombin time test using tissue factors from bovine, human, and rabbit sources.

PubMed

Lefkowitz, J B; Monroe, D M; Kasper, C K; Roberts, H R

1993-07-01

A subset of hemophilia B patients have a prolonged bovine-brain prothrombin time. These CRM+ patients are classified as having hemophilia Bm. The prolongation of the prothrombin time has been reported only with bovine brain (referred to as ox brain in some literature) as the source of thromboplastin; prothrombin times determined with thromboplastin from rabbit brain or human brain are not reported to be prolonged. Factor IX from a hemophilia Bm patient (factor IX Hilo) was isolated. The activity of factor IX Hilo was compared to that of normal factor IX in prothrombin time assays when the thromboplastin source was of bovine, rabbit, or human origin. Factor IX, either normal or Hilo, prolonged a prothrombin time regardless of the tissue factor source. However, unless thromboplastin was from a bovine source, this prolongation required high concentrations of factor IX. Further, factor IX normal was as effective as factor IX Hilo in prolonging the prothrombin time when rabbit or human thromboplastin was used. With bovine thromboplastin, factor IX Hilo was significantly better than factor IX normal at prolonging the prothrombin time. The amount of prolongation was dependent on the amount of factor IX Hilo added. In addition, the prolongation was dependent on the concentration of factor X present in the sample. The prothrombin time changed as much as 20 seconds when the factor X concentration was varied from 50% to 150% to normal (fixed concentration of factor IX Hilo). These results demonstrate the difficulty of classifying the severity of a hemophilia Bm patient based on the bovine brain prothrombin time unless both the factor IX and factor X concentrations are known.

Defense and Development in Sub-Saharan Africa: Codebook.

DTIC Science & Technology

1988-03-01

countries by presenting the different data sources and explaining how they were compiled. The statistics in the 0 database cover 41 African countries for...February 1984, pp. 157-164 -vi Finally, in addition to the economic and military data , some statistics have been compiled that monitor social and...32 IX. SOCIAL/POLITICAL STATISTICS ....................................34 SOURCES AND NOTES ON COLLECTION OF DATA

δ-aminolevulinic acid–induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy

PubMed Central

Valdés, Pablo A.; Kim, Anthony; Brantsch, Marco; Niu, Carolyn; Moses, Ziev B.; Tosteson, Tor D.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

2011-01-01

Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of δ-aminolevulinic acid–induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR). Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (CPpIX) and Ki-67 immunohistochemistry to assess tissue proliferation. Samples displaying visible levels of fluorescence showed significantly higher levels of CPpIX and tissue proliferation. CPpIX was strongly correlated with histopathological score (nonparametric) and tissue proliferation (parametric), such that increasing levels of CPpIX were identified with regions of increasing malignancy. Furthermore, a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of CPpIX greater than 0.1 µg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery. PMID:21798847

Gadolinium and 5-Aminolevulinic Acid-induced Protoporphyrin IX Levels in Human Gliomas: An Ex Vivo Quantitative Study to Correlate Protoporphyrin IX Levels and Blood-Brain Barrier Breakdown

PubMed Central

Valdés, Pablo A.; Moses, Ziev B.; Kim, Anthony; Belden, Clifford J.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

2012-01-01

In recent years, 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence guidance has been used as a surgical adjunct to improve the extent of resection of gliomas. Exogenous administration of ALA prior to surgery leads to the accumulation of red fluorescent PpIX in tumor tissue that the surgeon can visualize and thereby discriminate between normal and tumor tissue. Selective accumulation of PpIX has been linked to numerous factors, of which blood-brain barrier (BBB) breakdown has been suggested to be a key factor. To test the hypothesis that PpIX concentration (CPpIX) positively correlates with gadolinium (Gd) concentrations (CGd), we performed ex vivo measurements of PpIX and of Gd using Inductively-Coupled Plasma Mass Spectrometry (ICP-MS) the latter as a quantitative biomarker of BBB breakdown; this was corroborated with immunohistochemistry of microvascular density in surgical biopsies of patients undergoing fluorescence guided surgery for glioma .We found positive correlations between CPpIX and CGd (r = 0.58, p < 0.0001), and between CPpIX and microvascular density (r = 0.55, p < 0.0001), suggesting a significant, yet limited association between BBB breakdown and ALA-induced PpIX fluorescence. To our knowledge, this is the first time that Gd measurements by ICP-MS have been used in human gliomas. PMID:22878664

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

Code of Federal Regulations, 2010 CFR

1998-10-01

... 45 Public Welfare 1 1998-10-01 1998-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ GENERAL ADMINISTRATION... FINANCIAL ASSISTANCE Procedures [Interim] Interim procedures. Pt. 86, Index Subject Index to Title IX...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

Code of Federal Regulations, 2010 CFR

1997-10-01

... 45 Public Welfare 1 1997-10-01 1997-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ GENERAL ADMINISTRATION... FINANCIAL ASSISTANCE Procedures [Interim] Interim procedures. Pt. 86, Index Subject Index to Title IX...

The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.

PubMed

Mahon, Brian P; Bhatt, Avni; Socorro, Lilien; Driscoll, Jenna M; Okoh, Cynthia; Lomelino, Carrie L; Mboge, Mam Y; Kurian, Justin J; Tu, Chingkuang; Agbandje-McKenna, Mavis; Frost, Susan C; McKenna, Robert

2016-08-23

Human carbonic anhydrase IX (hCA IX) expression in many cancers is associated with hypoxic tumors and poor patient outcome. Inhibitors of hCA IX have been used as anticancer agents with some entering Phase I clinical trials. hCA IX is transmembrane protein whose catalytic domain faces the extracellular tumor milieu, which is typically associated with an acidic microenvironment. Here, we show that the catalytic domain of hCA IX (hCA IX-c) exhibits the necessary biochemical and biophysical properties that allow for low pH stability and activity. Furthermore, the unfolding process of hCA IX-c appears to be reversible, and its catalytic efficiency is thought to be correlated directly with its stability between pH 3.0 and 8.0 but not above pH 8.0. To rationalize this, we determined the X-ray crystal structure of hCA IX-c to 1.6 Å resolution. Insights from this study suggest an understanding of hCA IX-c stability and activity in low-pH tumor microenvironments and may be applicable to determining pH-related effects on enzymes.

Ares I-X Ground Diagnostic Prototype

NASA Technical Reports Server (NTRS)

Schwabacher, Mark A.; Martin, Rodney Alexander; Waterman, Robert D.; Oostdyk, Rebecca Lynn; Ossenfort, John P.; Matthews, Bryan

2010-01-01

The automation of pre-launch diagnostics for launch vehicles offers three potential benefits: improving safety, reducing cost, and reducing launch delays. The Ares I-X Ground Diagnostic Prototype demonstrated anomaly detection, fault detection, fault isolation, and diagnostics for the Ares I-X first-stage Thrust Vector Control and for the associated ground hydraulics while the vehicle was in the Vehicle Assembly Building at Kennedy Space Center (KSC) and while it was on the launch pad. The prototype combines three existing tools. The first tool, TEAMS (Testability Engineering and Maintenance System), is a model-based tool from Qualtech Systems Inc. for fault isolation and diagnostics. The second tool, SHINE (Spacecraft Health Inference Engine), is a rule-based expert system that was developed at the NASA Jet Propulsion Laboratory. We developed SHINE rules for fault detection and mode identification, and used the outputs of SHINE as inputs to TEAMS. The third tool, IMS (Inductive Monitoring System), is an anomaly detection tool that was developed at NASA Ames Research Center. The three tools were integrated and deployed to KSC, where they were interfaced with live data. This paper describes how the prototype performed during the period of time before the launch, including accuracy and computer resource usage. The paper concludes with some of the lessons that we learned from the experience of developing and deploying the prototype.

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

Code of Federal Regulations, 2010 CFR

2000-10-01

... 45 Public Welfare 1 2000-10-01 2000-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ Public Welfare DEPARTMENT OF... procedures. Pt. 86, Index Subject Index to Title IX Preamble and Regulation \\1\\ 1 Preamble paragraph numbers...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2002-10-01

... 45 Public Welfare 1 2002-10-01 2002-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare GENERAL ADMINISTRATION... FINANCIAL ASSISTANCE Procedures [Interim] Interim procedures. Pt. 86, Index Subject Index to Title IX...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

Code of Federal Regulations, 2010 CFR

1999-10-01

... 45 Public Welfare 1 1999-10-01 1999-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ Public Welfare DEPARTMENT OF... procedures. Pt. 86, Index Subject Index to Title IX Preamble and Regulation \\1\\ 1 Preamble paragraph numbers...

ABCG2 transporter inhibitor restores the sensitivity of triple negative breast cancer cells to aminolevulinic acid-mediated photodynamic therapy.

PubMed

Palasuberniam, Pratheeba; Yang, Xue; Kraus, Daniel; Jones, Patrick; Myers, Kenneth A; Chen, Bin

2015-08-18

Photosensitizer protoporphyrin IX (PpIX) fluorescence, intracellular localization and cell response to photodynamic therapy (PDT) were analyzed in MCF10A normal breast epithelial cells and a panel of human breast cancer cells including estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) positive and triple negative breast cancer (TNBC) cells after treatment with PpIX precursor aminolevulinic acid (ALA). Although PpIX fluorescence was heterogeneous in different cells, TNBC cells showed significantly lower PpIX level than MCF10A and ER- or HER2-positive cells. PpIX fluorescence in TNBC cells also had much less mitochondrial localization than other cells. There was an inverse correlation between PpIX fluorescence and cell viability after PDT. Breast cancer cells with the highest PpIX fluorescence were the most sensitive to ALA-PDT and TNBC cells with the lowest PpIX level were resistant to PDT. Treatment of TNBC cells with ABCG2 transporter inhibitor Ko143 significantly increased ALA-PpIX fluorescence, enhanced PpIX mitochondrial accumulation and sensitized cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA-PDT in normal and ER- or HER2-positive cells. These results demonstrate that enhanced ABCG2 activity renders TNBC cell resistance to ALA-PDT and inhibiting ABCG2 transporter is a promising approach for targeting TNBC with ALA-based modality.

Comparative proteomic analysis of normal and collagen IX null mouse cartilage reveals altered extracellular matrix composition and novel components of the collagen IX interactome.

PubMed

Brachvogel, Bent; Zaucke, Frank; Dave, Keyur; Norris, Emma L; Stermann, Jacek; Dayakli, Münire; Koch, Manuel; Gorman, Jeffrey J; Bateman, John F; Wilson, Richard

2013-05-10

Collagen IX is an integral cartilage extracellular matrix component important in skeletal development and joint function. Proteomic analysis and validation studies revealed novel alterations in collagen IX null cartilage. Matrilin-4, collagen XII, thrombospondin-4, fibronectin, βig-h3, and epiphycan are components of the in vivo collagen IX interactome. We applied a proteomics approach to advance our understanding of collagen IX ablation in cartilage. The cartilage extracellular matrix is essential for endochondral bone development and joint function. In addition to the major aggrecan/collagen II framework, the interacting complex of collagen IX, matrilin-3, and cartilage oligomeric matrix protein (COMP) is essential for cartilage matrix stability, as mutations in Col9a1, Col9a2, Col9a3, Comp, and Matn3 genes cause multiple epiphyseal dysplasia, in which patients develop early onset osteoarthritis. In mice, collagen IX ablation results in severely disturbed growth plate organization, hypocellular regions, and abnormal chondrocyte shape. This abnormal differentiation is likely to involve altered cell-matrix interactions but the mechanism is not known. To investigate the molecular basis of the collagen IX null phenotype we analyzed global differences in protein abundance between wild-type and knock-out femoral head cartilage by capillary HPLC tandem mass spectrometry. We identified 297 proteins in 3-day cartilage and 397 proteins in 21-day cartilage. Components that were differentially abundant between wild-type and collagen IX-deficient cartilage included 15 extracellular matrix proteins. Collagen IX ablation was associated with dramatically reduced COMP and matrilin-3, consistent with known interactions. Matrilin-1, matrilin-4, epiphycan, and thrombospondin-4 levels were reduced in collagen IX null cartilage, providing the first in vivo evidence for these proteins belonging to the collagen IX interactome. Thrombospondin-4 expression was reduced at the mRNA level, whereas matrilin-4 was verified as a novel collagen IX-binding protein. Furthermore, changes in TGFβ-induced protein βig-h3 and fibronectin abundance were found in the collagen IX knock-out but not associated with COMP ablation, indicating specific involvement in the abnormal collagen IX null cartilage. In addition, the more widespread expression of collagen XII in the collagen IX-deficient cartilage suggests an attempted compensatory response to the absence of collagen IX. Our differential proteomic analysis of cartilage is a novel approach to identify candidate matrix protein interactions in vivo, underpinning further analysis of mutant cartilage lacking other matrix components or harboring disease-causing mutations.

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2011 CFR

2011-07-01

... 34 Education 1 2011-07-01 2011-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 1 2011-10-01 2011-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 1 2010-10-01 2010-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2010-07-01

... 34 Education 1 2010-07-01 2010-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2003-10-01

... 45 Public Welfare 1 2003-10-01 2003-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND.... Pt. 86, Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2009-07-01

... 34 Education 1 2009-07-01 2009-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

34 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2015-07-01

... 34 Education 1 2015-07-01 2015-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2003-07-01

... 34 Education 1 2003-07-01 2003-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

45 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2006-10-01

... 45 Public Welfare 1 2006-10-01 2006-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

34 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2016-07-01

... 34 Education 1 2016-07-01 2016-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2007-07-01

... 34 Education 1 2007-07-01 2007-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2004-07-01

... 34 Education 1 2004-07-01 2004-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

45 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2016-10-01

... 45 Public Welfare 1 2016-10-01 2016-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare Department of Health and... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2012-07-01

... 34 Education 1 2012-07-01 2012-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

45 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2017-10-01

... 45 Public Welfare 1 2017-10-01 2017-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare Department of Health and... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2008-07-01

... 34 Education 1 2008-07-01 2008-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2013-10-01

... 45 Public Welfare 1 2013-10-01 2013-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2009-10-01

... 45 Public Welfare 1 2009-10-01 2009-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2004-10-01

... 45 Public Welfare 1 2004-10-01 2004-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND.... Pt. 86, Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2014-10-01

... 45 Public Welfare 1 2014-10-01 2014-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare Department of Health and... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2012-10-01

... 45 Public Welfare 1 2012-10-01 2012-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2005-10-01

... 45 Public Welfare 1 2005-10-01 2005-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTH AND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2007-10-01

... 45 Public Welfare 1 2007-10-01 2007-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2006-07-01

... 34 Education 1 2006-07-01 2006-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2002-07-01

... 34 Education 1 2002-07-01 2002-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Regulations of the Offices of the Department...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2005-07-01

... 34 Education 1 2005-07-01 2005-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2001-10-01

... 45 Public Welfare 1 2001-10-01 2001-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND.... Pt. 86, Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2008-10-01

... 45 Public Welfare 1 2008-10-01 2008-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare DEPARTMENT OF HEALTHAND... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

34 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2013-07-01

... 34 Education 1 2013-07-01 2013-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

45 CFR Subject Index to Title Ix... - Subject Index to Title IX Preamble and Regulation \\1\\

Code of Federal Regulations, 2010 CFR

1996-10-01

... 45 Public Welfare 1 1996-10-01 1996-10-01 false Subject Index to Title IX Preamble and Regulation \\1\\ Index Subject Index to Title IX Preamble and Regulation \\1\\ NONDISCRIMINATION ON THE BASIS OF SEX... Procedures [Interim] Interim procedures. Pt. 86, Index Subject Index to Title IX Preamble and Regulation \\1...

45 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2015-10-01

... 45 Public Welfare 1 2015-10-01 2015-10-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Public Welfare Department of Health and... Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers are in brackets [ ]. A...

34 CFR Subject Index to Title IX... - Subject Index to Title IX Preamble and Regulation 1

Code of Federal Regulations, 2010 CFR

2017-07-01

... 34 Education 1 2017-07-01 2017-07-01 false Subject Index to Title IX Preamble and Regulation 1 Index Subject Index to Title IX Preamble and Regulation 1 Education Regulations of the Offices of the...] Procedures. Subject Index Subject Index to Title IX Preamble and Regulation 1 1 Preamble paragraph numbers...

Differentiation of plant age in grasses using remote sensing

NASA Astrophysics Data System (ADS)

Knox, Nichola M.; Skidmore, Andrew K.; van der Werff, Harald M. A.; Groen, Thomas A.; de Boer, Willem F.; Prins, Herbert H. T.; Kohi, Edward; Peel, Mike

2013-10-01

Phenological or plant age classification across a landscape allows for examination of micro-topographical effects on plant growth, improvement in the accuracy of species discrimination, and will improve our understanding of the spatial variation in plant growth. In this paper six vegetation indices used in phenological studies (including the newly proposed PhIX index) were analysed for their ability to statistically differentiate grasses of different ages in the sequence of their development. Spectra of grasses of different ages were collected from a greenhouse study. These were used to determine if NDVI, NDWI, CAI, EVI, EVI2 and the newly proposed PhIX index could sequentially discriminate grasses of different ages, and subsequently classify grasses into their respective age category. The PhIX index was defined as: (AVNIRn+log(ASWIR2n))/(AVNIRn-log(ASWIR2n)), where AVNIRn and ASWIR2n are the respective normalised areas under the continuum removed reflectance curve within the VNIR (500-800 nm) and SWIR2 (2000-2210 nm) regions. The PhIX index was found to produce the highest phenological classification accuracy (Overall Accuracy: 79%, and Kappa Accuracy: 75%) and similar to the NDVI, EVI and EVI2 indices it statistically sequentially separates out the developmental age classes. Discrimination between seedling and dormant age classes and the adult and flowering classes was problematic for most of the tested indices. Combining information from the visible near infrared (VNIR) and shortwave infrared region (SWIR) region into a single phenological index captures the phenological changes associated with plant pigments and the ligno-cellulose absorption feature, providing a robust method to discriminate the age classes of grasses. This work provides a valuable contribution into mapping spatial variation and monitoring plant growth across savanna and grassland ecosystems.

Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers.

PubMed

Yang, Deng-Fu; Lee, Jeng-Woei; Chen, Hsin-Ming; Hsu, Yih-Chih

2014-09-01

Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical ALA-PDT alone (topical ALA-PDT group, n = 10). The intracellular protoporphyrin IX (PpIX) level in another 12 precancerous lesions (n = 6 for either the topical MTX-ALA or topical ALA group) was monitored by fluorescence spectroscopy. The intracellular PpIX reached its peak level in precancerous lesions 6.5 hours and 2.5 hours after topical ALA application for the topical MTX-ALA group (5.63-fold higher in the lesion than in the normal mucosa) and topical ALA group (2.42-fold higher in the lesion than in the normal mucosa), respectively. The complete response rate of precancerous lesions was 80% for the topical MTX-ALA-PDT group and 70% for the topical ALA-PDT group. In addition, the topical MTX-ALA-PDT group required a significantly lower mean treatment number (2.1 ± 0.6) to achieve complete response than the topical ALA-PDT group (4.4 ± 1.3, p < 0.001)). Moreover, the topical MTX-ALA-PDT group had a lower recurrence rate (12.5%) than the topical ALA-PDT group (28.6%). We conclude that topical MTX-pretreatment can increase intracellular PpIX production in hamster buccal pouch precancerous lesions and significantly improves the outcomes of the precancerous lesions treated with topical ALA-PDT. Copyright © 2014. Published by Elsevier B.V.

Photodynamic therapy of acne vulgaris.

NASA Astrophysics Data System (ADS)

Ershova, Ekaterina Y.; Karimova, Lubov N.; Kharnas, Sergey S.; Kuzmin, Sergey G.; Loschenov, Victor B.

2003-06-01

Photodynamic therapy (PDT) with topical 5-aminolevulinic acid (ALA) was tested for the treatment of acne vulgaris. Patients with acne were treated with ALA plus red light. Ten percent water solution of ALA was applied with 1,5-2 h occlusion and then 18-45 J/cm2 630 nm light was given. Bacterial endogenous porphyrins fluorescence also was used for acne therapy. Treatment control and diagnostics was realized by fluorescence spectra and fluorescence image. Light sources and diagnostic systems were used: semiconductor laser (λ=630 nm, Pmax=1W), (LPhT-630-01-BIOSPEC); LED system for PDT and diagnostics with fluorescent imager (λ=635 nm, P=2W, p=50 mW/cm2), (UFPh-630-01-BIOSPEC); high sensitivity CCD video camera with narrow-band wavelength filter (central wavelength 630 nm); laser electronic spectrum analyzer for fluorescent diagnostics and photodynamic therapy monitoring (LESA-01-BIOSPEC). Protoporphyrin IX (PP IX) and endogenous porphyrins concentrations were measured by fluorescence at wavelength, correspondingly, 700 nm and 650 nm. It was shown that topical ALA is converted into PP IX in hair follicles, sebaceous glands and acne scars. The amount of resulting PP IX is sufficient for effective PDT. There was good clinical response and considerable clearance of acne lesion. ALA-PDT also had good cosmetic effect in treatment acne scars. PDT with ALA and red light assist in opening corked pores, destroying Propionibacterium acnes and decreasing sebum secretion. PDT treatment associated with several adverse effects: oedema and/or erytema for 3-5 days after PDT, epidermal exfoliation from 5th to 10th day and slight pigmentation during 1 month after PDT. ALA-PDT is effective for acne and can be used despite several side effects.

Correction for tissue optical properties enables quantitative skin fluorescence measurements using multi-diameter single fiber reflectance spectroscopy.

PubMed

Middelburg, T A; Hoy, C L; Neumann, H A M; Amelink, A; Robinson, D J

2015-07-01

Fluorescence measurements in the skin are very much affected by absorption and scattering but existing methods to correct for this are not applicable to superficial skin measurements. The first use of multiple-diameter single fiber reflectance (MDSFR) and single fiber fluorescence (SFF) spectroscopy in human skin was investigated. MDSFR spectroscopy allows a quantification of the full optical properties in superficial skin (μa, μs' and γ), which can next be used to retrieve the corrected - intrinsic - fluorescence of a fluorophore Qμa,x(f). Our goal was to investigate the importance of such correction for individual patients. We studied this in 22 patients undergoing photodynamic therapy (PDT) for actinic keratosis. The magnitude of correction of fluorescence was around 4 (for both autofluorescence and protoporphyrin IX). Moreover, it was variable between patients, but also within patients over the course of fractionated aminolevulinic acid PDT (range 2.7-7.5). Patients also varied in the amount of protoporphyrin IX synthesis, photobleaching percentages and resynthesis (>100× difference between the lowest and highest PpIX synthesis). The autofluorescence was lower in actinic keratosis than contralateral normal skin (0.0032 versus 0.0052; P<0.0005). Our results clearly demonstrate the importance of correcting the measured fluorescence for optical properties, because these vary considerably between individual patients and also during PDT. Protoporphyrin IX synthesis and photobleaching kinetics allow monitoring clinical PDT which facilitates individual-based PDT dosing and improvement of clinical treatment protocols. Furthermore, the skin autofluorescence can be relevant for diagnostic use in the skin, but it may also be interesting because of its association with several internal diseases. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

The effect of a nano-filled resin coating on the 3-year clinical performance of a conventional high-viscosity glass-ionomer cement.

PubMed

Diem, Vu Thi Kieu; Tyas, Martin J; Ngo, Hien C; Phuong, Lam Hoai; Khanh, Ngo Dong

2014-04-01

The main aim of the study was to compare the clinical performance of the conventional high-powder/liquid ratio glass-ionomer cement (GIC) Fuji IX GP Extra (F IX), Fuji IX GP Extra with a low-viscosity nano-filled resin coating, G-Coat Plus (F IX+GCP), and a resin composite, Solare (S), as a comparison material. Moderate-depth occlusal cavities in the first permanent molars of 91 11-12-year-old children (1-4 restorations per child) were restored with either F IX (87 restorations), F IX+GCP (84 restorations) or S (83 restorations). Direct clinical assessment, photographic assessment and assessment of stone casts of the restorations were carried out at 6 months, 1 year, 2 years and 3 years. The colour match with the tooth of the GIC restorations improved over the 3 years of the study. Marginal staining and marginal adaptation were minimal for all restorations; three restorations exhibited secondary caries at 3 years. From the assessment of the casts, at 2 years, there was significantly less wear of the F IX GP Extra+GCP restorations than the F IX GP Extra restorations (P < 0.005). At 3 years, approximately 37 % of F IX GP Extra restorations showed wear slightly more than the adjacent enamel, compared to 28 % of F IX GP Extra+GCP restorations and 21 % of Solare restorations. Although this was not statistically significant, there was a trend that GCP can protect F IX GP Extra against wear. Although both Fuji IX GP Extra and Fuji IX GP Extra with G-Coat Plus showed acceptable clinical performance in occlusal cavities in children, the application of G-Coat Plus gave some protection against wear. The application of G-Coat Plus to Fuji IX GP Extra glass-ionomer cement may be beneficial in reducing wear in occlusal cavities.

An update on anticancer drug development and delivery targeting carbonic anhydrase IX

PubMed Central

Parkkila, Seppo

2017-01-01

The expression of carbonic anhydrase (CA) IX is up-regulated in many types of solid tumors in humans under hypoxic and acidic microenvironment. Inhibition of CA IX enzymatic activity with selective inhibitors, antibodies or labeled probes has been shown to reverse the acidic environment of solid tumors and reduce the tumor growth establishing the significant role of CA IX in tumorigenesis. Thus, the development of potent antitumor drugs targeting CA IX with minimal toxic effects is important for the target-specific tumor therapy. Recently, several promising antitumor agents against CA IX have been developed to treat certain types of cancers in combination with radiation and chemotherapy. Here we review the inhibition of CA IX by small molecule compounds and monoclonal antibodies. The methods of enzymatic assays, biophysical methods, animal models including zebrafish and Xenopus oocytes, and techniques of diagnostic imaging to detect hypoxic tumors using CA IX-targeted conjugates are discussed with the aim to overview the recent progress related to novel therapeutic agents that target CA IX in hypoxic tumors. PMID:29181278

The Role of Title IX Coordinators on College and University Campuses

PubMed Central

Wiersma-Mosley, Jacquelyn D.; DiLoreto, James

2018-01-01

The purpose of this study was to better understand the role of Title IX coordinators and their policies across four-year universities and two-year community colleges in the United States (U.S.). There is little information regarding Title IX coordinators’ training, background, and policies on how they handle Title IX investigations regarding sexual violence. The data come from an online survey that included 692 Title IX coordinators across four-year (private and public) and two-year campuses and represented 42 different states in the US. The current study found that most Title IX coordinators were in part-time positions with less than three years of experience. Most of the coordinators and their investigators were trained in Title IX policies. Most coordinators provide Title IX training for their students and faculty, and most have completed a campus climate survey; however, 15% had not completed a survey. The findings suggest that the majority of campuses are continuing to increase their Title IX visibility; however, there are several recommendations for campuses to improve their policies. The current study was able to shed light on how Title IX coordinators do their jobs and the role they play in helping with the challenging issues surrounding sexual violence at institutions across the nation. PMID:29621177

A sucrose-binding site provides a lead towards an isoform-specific inhibitor of the cancer-associated enzyme carbonic anhydrase IX

DOE PAGES

Pinard, Melissa A.; Aggarwal, Mayank; Mahon, Brian P.; ...

2015-09-23

Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO 2to HCO 3 $-$, thereby playing a role in pH regulation. The majority of normal functioning cells exhibit low-level expression of CA IX. However, in cancer cells CA IX is upregulated as a consequence of a metabolic transition known as the Warburg effect. The upregulation of CA IX for cancer progression has drawn interest in it being a potential therapeutic target. CA IX is a transmembrane protein, and its purification, yield and crystallization have proven challenging to structure-basedmore » drug design, whereas the closely related cytosolic soluble isoform CA II can be expressed and crystallized with ease. Therefore, we have utilized structural alignments and site-directed mutagenesis to engineer a CA II that mimics the active site of CA IX. In this paper, the X-ray crystal structure of this CA IX mimic in complex with sucrose is presented and has been refined to a resolution of 1.5 Å, anR cryst of 18.0% and anR free of 21.2%. Finally, the binding of sucrose at the entrance to the active site of the CA IX mimic, and not CA II, in a non-inhibitory mechanism provides a novel carbohydrate moiety binding site that could be further exploited to design isoform-specific inhibitors of CA IX.« less

Reconsidering the Status of Title IX.

ERIC Educational Resources Information Center

Hammer, Ben

2003-01-01

Discusses the controversy over Title IX and women's participation in college athletics. Critics say the mandate shortchanges men's teams, while proponents say that women's sports programs remain underfunded in spite of Title IX. Describes some proposed modifications to Title IX and their potential effects. (SLD)

Scanning Fiber Endoscope Improves Detection of 5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence at the Boundary of Infiltrative Glioma.

PubMed

Belykh, Evgenii; Miller, Eric J; Hu, Danying; Martirosyan, Nikolay L; Woolf, Eric C; Scheck, Adrienne C; Byvaltsev, Vadim A; Nakaji, Peter; Nelson, Leonard Y; Seibel, Eric J; Preul, Mark C

2018-05-01

Fluorescence-guided surgery with protoporphyrin IX (PpIX) as a photodiagnostic marker is gaining acceptance for resection of malignant gliomas. Current wide-field imaging technologies do not have sufficient sensitivity to detect low PpIX concentrations. We evaluated a scanning fiber endoscope (SFE) for detection of PpIX fluorescence in gliomas and compared it to an operating microscope (OPMI) equipped with a fluorescence module and to a benchtop confocal laser scanning microscope (CLSM). 5-Aminolevulinic acid-induced PpIX fluorescence was assessed in GL261-Luc2 cells in vitro and in vivo after implantation in mouse brains, at an invading glioma growth stage, simulating residual tumor. Intraoperative fluorescence of high and low PpIX concentrations in normal brain and tumor regions with SFE, OPMI, CLSM, and histopathology were compared. SFE imaging of PpIX correlated to CLSM at the cellular level. PpIX accumulated in normal brain cells but significantly less than in glioma cells. SFE was more sensitive to accumulated PpIX in fluorescent brain areas than OPMI (P < 0.01) and dramatically increased imaging time (>6×) before tumor-to-background contrast was diminished because of photobleaching. SFE provides new endoscopic capabilities to view PpIX-fluorescing tumor regions at cellular resolution. SFE may allow accurate imaging of 5-aminolevulinic acid labeling of gliomas and other tumor types when current detection techniques have failed to provide reliable visualization. SFE was significantly more sensitive than OPMI to low PpIX concentrations, which is relevant to identifying the leading edge or metastasizing cells of malignant glioma or to treating low-grade gliomas. This new application has the potential to benefit surgical outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Syrian Refugees: Are They a Non Traditional Threat to Water Supplies in Lebanon and Jordan

DTIC Science & Technology

2016-09-01

THREAT TO WATER SUPPLIES IN LEBANON AND JORDAN? 5. FUNDING NUMBERS 6. AUTHOR(S) Stephen J. Klingseis 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS...ES) Naval Postgraduate School Monterey, CA 93943-5000 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING /MONITORING AGENCY NAME(S) AND...INTENTIONALLY LEFT BLANK ix LIST OF ACRONYMS AND ABBREVIATIONS MWI Ministry of Water and Irrigation NGO non-governmental organization OECD

In-vivo luminescence model for the study of tumor regression and regrowth following combination regimens with differentiation-promoting agents and photodynamic therapy

NASA Astrophysics Data System (ADS)

Rollakanti, K.; Anand, S.; Maytin, E. V.

2013-03-01

Photodynamic therapy with aminolevulinic acid can be modified by pretreatment regimens with drugs such as 5- Fluorouracil (5-FU) or Vitamin D (calcitriol) that enhance accumulation of protoporphyrin IX (PpIX) within tumor tissue which presumably will enhance the therapeutic response to light. However, histological approaches for monitoring therapeutic responses are poorly suited for studying long term survival because large numbers of mice need to be sacrificed. To address this limitation, a non-invasive model to monitor tumor regression and regrowth has been established. Breast cancer cells, stably transfected with firefly luciferase (MDA-Luc cell line), are implanted orthotopically in nude mice (0.25 - 1 x 106 cells/site), and monitored 0-60 min after s.c. injection of luciferin, with Xenogen in-vivo imaging system. Luminescence is detectable at day 1 post-implantation. Tumors are suitable for experimentation on day 6, when daily injections of pretreatment agents (5-FU, 300 mg/kg; calcitriol, 1 μg/kg) begin. On day 9, ALA (75 mg/kg i.p.) is given for 4 hr, followed by illumination (633 nm, 100 J/cm2). Tumor luminescence post- PDT is monitored daily and compared with caliper measurements. Pretreatments (5-FU, calcitriol) by themselves do not inhibit luciferase expression, and all tumors grow at a similar rate during the pretreatment period. Results from in vivo survival experiments can be correlated to survival responses of MDA-Luc cells grown in monolayer cultures +/- PDT and +/- pretreatments, and additional mechanistic information (e.g. Ki67 and E-cadherin expression) obtained. In summary, this noninvasive model will permit testing of the therapeutic survival advantages of various pretreatments during cPDT.

Comparative Proteomic Analysis of Normal and Collagen IX Null Mouse Cartilage Reveals Altered Extracellular Matrix Composition and Novel Components of the Collagen IX Interactome*

PubMed Central

Brachvogel, Bent; Zaucke, Frank; Dave, Keyur; Norris, Emma L.; Stermann, Jacek; Dayakli, Münire; Koch, Manuel; Gorman, Jeffrey J.; Bateman, John F.; Wilson, Richard

2013-01-01

The cartilage extracellular matrix is essential for endochondral bone development and joint function. In addition to the major aggrecan/collagen II framework, the interacting complex of collagen IX, matrilin-3, and cartilage oligomeric matrix protein (COMP) is essential for cartilage matrix stability, as mutations in Col9a1, Col9a2, Col9a3, Comp, and Matn3 genes cause multiple epiphyseal dysplasia, in which patients develop early onset osteoarthritis. In mice, collagen IX ablation results in severely disturbed growth plate organization, hypocellular regions, and abnormal chondrocyte shape. This abnormal differentiation is likely to involve altered cell-matrix interactions but the mechanism is not known. To investigate the molecular basis of the collagen IX null phenotype we analyzed global differences in protein abundance between wild-type and knock-out femoral head cartilage by capillary HPLC tandem mass spectrometry. We identified 297 proteins in 3-day cartilage and 397 proteins in 21-day cartilage. Components that were differentially abundant between wild-type and collagen IX-deficient cartilage included 15 extracellular matrix proteins. Collagen IX ablation was associated with dramatically reduced COMP and matrilin-3, consistent with known interactions. Matrilin-1, matrilin-4, epiphycan, and thrombospondin-4 levels were reduced in collagen IX null cartilage, providing the first in vivo evidence for these proteins belonging to the collagen IX interactome. Thrombospondin-4 expression was reduced at the mRNA level, whereas matrilin-4 was verified as a novel collagen IX-binding protein. Furthermore, changes in TGFβ-induced protein βig-h3 and fibronectin abundance were found in the collagen IX knock-out but not associated with COMP ablation, indicating specific involvement in the abnormal collagen IX null cartilage. In addition, the more widespread expression of collagen XII in the collagen IX-deficient cartilage suggests an attempted compensatory response to the absence of collagen IX. Our differential proteomic analysis of cartilage is a novel approach to identify candidate matrix protein interactions in vivo, underpinning further analysis of mutant cartilage lacking other matrix components or harboring disease-causing mutations. PMID:23530037

Evaluation of a Gadolinium-Based Nanoparticle (AGuIX) for Contrast-Enhanced MRI of the Liver in a Rat Model of Hepatic Colorectal Cancer Metastases at 9.4 Tesla.

PubMed

Fries, P; Morr, D; Müller, A; Lux, F; Tillement, O; Massmann, A; Seidel, R; Schäfer, T; Menger, M D; Schneider, G; Bücker, A

2015-12-01

The aim of this study was to compare a Gd-based nanoparticle (AGuIX) with a standard extracellular Gd-based contrast agent (Gd-DOTA) for MRI at 9.4 T in rats with hepatic colorectal cancer metastases. 12 rats with hepatic metastases were subjected to MRI using a 9.4 T animal scanner. T1w self-gated FLASH sequences (TR/TE = 45/2.5 ms, alpha = 45°, TA = 1: 23 min, FOV = 5.12 × 5.12 cm(2), matrix = 256 × 256) were acquired before and at 10 time points after contrast injection. Each animal received 0.1 mmol/kg BW Gd-DOTA i.v. 2 days later AGuIX was applied at 0.01 mmol/kg BW (representing equal Gd doses). The SNR of normal liver (SNRliver), hyper- and hypoenhancing parts of tumors (SNRtumor, hyperenh/SNRtumor, hypoenhanc), erector spinae muscle (SNRmuscle), CNR and lesion enhancement (LE) were calculated based on ROI measurements. Mean SNRliver (Gd-DOTA: 14.6 +/- 0.7; AGuIX: 28.2+/- 2.6, p < 0.001), SNRtumor, hyperenhanc (Gd-DOTA: 18.6 +/- 1.2; AGuIX: 29.6 +/- 2.8, p < 0.001), SNRtumor, hypoenhanc (Gd-DOTA: 12.0 +/- 0.7; AGuIX: 15.4 +/- 0.7, p < 0.001), SNRmuscle (Gd-DOTA: 12.3 +/- 0.3; AGuIX: 14.0 +/- 0.7, p < 0.001), mean CNR (Gd-DOTA: -2.5 +/- 0.2; AGuIX: -7.5 +/- 1.0, p < 0.001) and LE (Gd-DOTA: 3.8 +/- 0.7; AGuIX: 14.9 +/- 2.8, p = 0.001) were significantly higher using AGuIX. Regardless of the larger molecular size, AGuIX demonstrates an early peak enhancement followed by a continuous washout. AGuIX provides better enhancement at 9.4 T compared to Gd-DOTA for equal doses of applied Gd. This is based on the molecule structure and the subsequent increased interaction with protons leading to a higher relaxivity. AGuIX potentially ameliorates the conspicuity of focal liver lesions and may improve the sensitivity in diagnostic imaging of malignant hepatic tumors. AGuIX provides superior enhancement as compared to the extracellular compound Gd-DOTA at 9.4 T. AGuIX may improve the detection and diagnostic sensitivity of malignant focal liver lesions. The small size of AGuIX allows for fast renal clearance and prevents undesirable accumulation in the body. © Georg Thieme Verlag KG Stuttgart · New York.

DeltaPhage—a novel helper phage for high-valence pIX phagemid display

PubMed Central

Nilssen, Nicolay R.; Frigstad, Terje; Pollmann, Sylvie; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger; Løset, Geir Å.

2012-01-01

Phage display has been instrumental in discovery of novel binding peptides and folded domains for the past two decades. We recently reported a novel pIX phagemid display system that is characterized by a strong preference for phagemid packaging combined with low display levels, two key features that support highly efficient affinity selection. However, high diversity in selected repertoires are intimately coupled to high display levels during initial selection rounds. To incorporate this additional feature into the pIX display system, we have developed a novel helper phage termed DeltaPhage that allows for high-valence display on pIX. This was obtained by inserting two amber mutations close to the pIX start codon, but after the pVII translational stop, conditionally inactivating the helper phage encoded pIX. Until now, the general notion has been that display on pIX is dependent on wild-type complementation, making high-valence display unachievable. However, we found that DeltaPhage does facilitate high-valence pIX display when used with a non-suppressor host. Here, we report a side-by-side comparison with pIII display, and we find that this novel helper phage complements existing pIX phagemid display systems to allow both low and high-valence display, making pIX display a complete and efficient alternative to existing pIII phagemid display systems. PMID:22539265

DeltaPhage--a novel helper phage for high-valence pIX phagemid display.

PubMed

Nilssen, Nicolay R; Frigstad, Terje; Pollmann, Sylvie; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger; Løset, Geir Å

2012-09-01

Phage display has been instrumental in discovery of novel binding peptides and folded domains for the past two decades. We recently reported a novel pIX phagemid display system that is characterized by a strong preference for phagemid packaging combined with low display levels, two key features that support highly efficient affinity selection. However, high diversity in selected repertoires are intimately coupled to high display levels during initial selection rounds. To incorporate this additional feature into the pIX display system, we have developed a novel helper phage termed DeltaPhage that allows for high-valence display on pIX. This was obtained by inserting two amber mutations close to the pIX start codon, but after the pVII translational stop, conditionally inactivating the helper phage encoded pIX. Until now, the general notion has been that display on pIX is dependent on wild-type complementation, making high-valence display unachievable. However, we found that DeltaPhage does facilitate high-valence pIX display when used with a non-suppressor host. Here, we report a side-by-side comparison with pIII display, and we find that this novel helper phage complements existing pIX phagemid display systems to allow both low and high-valence display, making pIX display a complete and efficient alternative to existing pIII phagemid display systems.

Dexamethasone alone and in combination with desipramine, phenytoin, valproic acid or levetiracetam interferes with 5-ALA-mediated PpIX production and cellular retention in glioblastoma cells.

PubMed

Lawrence, Johnathan E; Steele, Christopher J; Rovin, Richard A; Belton, Robert J; Winn, Robert J

2016-03-01

Extent of resection of glioblastoma (GBM) correlates with overall survival. Fluorescence-guided resection (FGR) using 5-aminolevulinic acid (5-ALA) can improve the extent of resection. Unfortunately not all patients given 5-ALA accumulate sufficient quantities of protoporphyrin IX (PpIX) for successful FGR. In this study, we investigated the effects of dexamethasone, desipramine, phenytoin, valproic acid, and levetiracetam on the production and accumulation of PpIX in U87MG cells. All of these drugs, except levetiracetam, reduce the total amount of PpIX produced by GBM cells (p < 0.05). When dexamethasone is mixed with another drug (desipramine, phenytoin, valproic acid or levetiracetam) the amount of PpIX produced is further decreased (p < 0.01). However, when cells are analyzed for PpIX cellular retention, dexamethasone accumulated significantly more PpIX than the vehicle control (p < 0.05). Cellular retention of PpIX was not different from controls in cells treated with dexamethasone plus desipramine, valproic acid or levetiracetam, but was significantly less for dexamethasone plus phenytoin (p < 0.01). These data suggest that medications given before and during surgery may interfere with PpIX accumulation in malignant cells. At this time, levetiracetam appears to be the best medication in its class (anticonvulsants) for patients undergoing 5-ALA-mediated FGR.

Evaluation of PpIX formation in Cervical Intraepithelial Neoplasia I (CIN) using widefield fluorescence images

NASA Astrophysics Data System (ADS)

Carbinatto, Fernanda M.; Inada, Natalia M.; Fortunato, Thereza C.; Lombardi, Welington; da Silva, Eduardo V.; Vollet Filho, José D.; Kurachi, Cristina; Pratavieira, Sebastião.; Bagnato, Vanderlei S.

2016-03-01

Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.

Local anesthesia selection algorithm in patients with concomitant somatic diseases.

PubMed

Anisimova, E N; Sokhov, S T; Letunova, N Y; Orekhova, I V; Gromovik, M V; Erilin, E A; Ryazantsev, N A

2016-01-01

The paper presents basic principles of local anesthesia selection in patients with concomitant somatic diseases. These principles are history taking; analysis of drugs interaction with local anesthetic and sedation agents; determination of the functional status of the patient; patient anxiety correction; dental care with monitoring of hemodynamics parameters. It was found that adhering to this algorithm promotes prevention of urgent conditions in patients in outpatient dentistry.

6 CFR 17.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude... Federal law. (c) For purposes of these Title IX regulations, program or activity or program means: (1) All...

Implementing LPC (Linear Predictive Coding) Algorithms in the Study of Speech Processing.

DTIC Science & Technology

1983-12-01

DRAND(IX) DOUBLE PRECISION INTEGER IXAP.B15.B165XHI 5XALO.LEFTLO,FHIK DATA A/1&607D0/. B15/3276BD0/. Bl6 /65536D0/. P/2147483647D0/ XHI - IX/ B16 XHI...XHI -DMOD(XHI, IDO) XALO = (IX- XHI * B16 ) * A LEFTLO -XALO/1116 LEFTLO = LEFTLO - DMOD(LEFTLO. iDO)I FHI -XHI * A + LEFTLO K = FHI/B15 K = K - DMOD(K1...iDO) IX = (((XALO-LEFTL0*916)-P) +- (FHI-K*Bl5)* B16 )+K IF(IX.LT.O.DOe IX= X *FILENAME: GLOTI.FR DATE: 12: 2:83 TIME: 13:45:38 PAGE C C THIS SUBROUTINE

Protoporphyrin IX fluorescence for enhanced photodynamic diagnosis and photodynamic therapy in murine models of skin and breast cancer

NASA Astrophysics Data System (ADS)

Rollakanti, Kishore Reddy

Protoporphyrin IX (PpIX) is a photosensitizing agent derived from aminolevulinic acid. PpIX accumulates specifically within target cancer cells, where it fluoresces and produces cytotoxic reactive oxygen species. Our aims were to employ PpIX fluorescence to detect squamous cell carcinoma (SCC) of the skin (Photodynamic diagnosis, PDD), and to improve treatment efficacy (Photodynamic therapy, PDT) for basal cell carcinoma (BCC) and cutaneous breast cancer. Hyperspectral imaging and a spectrometer based dosimeter system were used to detect very early SCC in UVB-irradiated murine skin, using PpIX fluorescence. Regarding PDT, we showed that low non-toxic doses of vitamin D, given before ALA application, increase tumor specific PpIX accumulation and sensitize BCC and breast cancer cells to ALA-PDT. These optical imaging methods and the combination therapy regimen (vitamin D and ALA-PDT) are promising tools for effective management of skin and breast cancer.

Subsurface PpIX imaging in vivo with ultrasound-guided tomographic spectroscopy: reconstruction vs. born-normalized data

NASA Astrophysics Data System (ADS)

Flynn, Brendan P.; D'Souza, Alisha V.; Kanick, Stephen C.; Maytin, Edward; Hasan, Tayyaba; Pogue, Brian W.

2013-03-01

Aminolevulinic acid (ALA)-induced Protoporphyrin IX (PpIX)-based photodynamic therapy (PDT) is an effective treatment for skin cancers including basal cell carcinoma (BCC). Topically applied ALA promotes PpIX production preferentially in tumors, and many strategies have been developed to increase PpIX distribution and PDT treatment efficacy at depths > 1mm is not fully understood. While surface imaging techniques provide useful diagnosis, dosimetry, and efficacy information for superficial tumors, these methods cannot interrogate deeper tumors to provide in situ insight into spatial PpIX distributions. We have developed an ultrasound-guided, white-light-informed, tomographics spectroscopy system for the spatial measurement of subsurface PpIX. Detailed imaging system specifications, methodology, and optical-phantom-based characterization will be presented separately. Here we evaluate preliminary in vivo results using both full tomographic reconstruction and by plotting individual tomographic source-detector pair data against US images.

Political and Programmatic Impact of Affirmative Action Policy: The Case of Title IX.

ERIC Educational Resources Information Center

Bird, Patrick J.

Title IX legislation has had a widespread impact on institutions of higher education. Similar laws and regulations preceding Title IX include Executive Order 11246, the Comprehensive Health Manpower and Nurse Training Act, and the Equal Employment Opportunity Act. The pervasive influence of Title IX is indicated in its provisions concerning…

Title IX Resource Guide

ERIC Educational Resources Information Center

Office for Civil Rights, US Department of Education, 2015

2015-01-01

Title IX of the Education Amendments of 1972 (Title IX) prohibits discrimination based on sex in education programs and activities in federally funded schools at all levels. If any part of a school district or college receives any Federal funds for any purpose, all of the operations of the district or college are covered by Title IX. The essence…

Expression of cancer-related carbonic anhydrases IX and XII in normal skin and skin neoplasms.

PubMed

Syrjänen, Leo; Luukkaala, Tiina; Leppilampi, Mari; Kallioinen, Matti; Pastorekova, Silvia; Pastorek, Jaromir; Waheed, Abdul; Sly, William S; Parkkila, Seppo; Karttunen, Tuomo

2014-09-01

Purpose of the study was to evaluate the presence of hypoxia-inducible, tumour-associated carbonic anhydrases IX and XII in normal skin and a series of cutaneous tumours. Human tumour samples were taken during surgical operations performed on 245 patients and were immunohistochemically stained. A histological score value was calculated for statistical analyses which were performed using SPSS for Windows, versions 17.0 and 20.0. In normal skin, the highest expression of CA IX was detected in hair follicles, sebaceous glands, and basal parts of epidermis. CA XII was detected in all epithelial components of skin. Both CA IX and CA XII expression levels were significantly different in epidermal, appendigeal, and melanocytic tumour categories. Both CA IX and XII showed the most intense immunostaining in epidermal tumours, whereas virtually all melanocytic tumours were devoid of CA IX and XII immunostaining. In premalignant lesions, CA IX expression significantly increased when the tumours progressed to more severe dysplasia forms. Both CA IX and XII are highly expressed in different epithelial components of skin. They are also highly expressed in epidermal tumours, in which CA IX expression levels also correlate with the dysplasia grade. Interestingly, both isozymes are absent in melanocytic tumours. © 2014 APMIS. Published by John Wiley & Sons Ltd.

Comparative assessment of the environmental sustainability of existing and emerging perchlorate treatment technologies for drinking water.

PubMed

Choe, Jong Kwon; Mehnert, Michelle H; Guest, Jeremy S; Strathmann, Timothy J; Werth, Charles J

2013-05-07

Environmental impacts of conventional and emerging perchlorate drinking water treatment technologies were assessed using life cycle assessment (LCA). Comparison of two ion exchange (IX) technologies (i.e., nonselective IX with periodic regeneration using brines and perchlorate-selective IX without regeneration) at an existing plant shows that brine is the dominant contributor for nonselective IX, which shows higher impact than perchlorate-selective IX. Resource consumption during the operational phase comprises >80% of the total impacts. Having identified consumables as the driving force behind environmental impacts, the relative environmental sustainability of IX, biological treatment, and catalytic reduction technologies are compared more generally using consumable inputs. The analysis indicates that the environmental impacts of heterotrophic biological treatment are 2-5 times more sensitive to influent conditions (i.e., nitrate/oxygen concentration) and are 3-14 times higher compared to IX. However, autotrophic biological treatment is most environmentally beneficial among all. Catalytic treatment using carbon-supported Re-Pd has a higher (ca. 4600 times) impact than others, but is within 0.9-30 times the impact of IX with a newly developed ligand-complexed Re-Pd catalyst formulation. This suggests catalytic reduction can be competitive with increased activity. Our assessment shows that while IX is an environmentally competitive, emerging technologies also show great promise from an environmental sustainability perspective.

Inhibition of Carbonic Anhydrase IX by Ureidosulfonamide Inhibitor U104 Reduces Prostate Cancer Cell Growth, But Does Not Modulate Daunorubicin or Cisplatin Cytotoxicity.

PubMed

Riemann, Anne; Güttler, Antje; Haupt, Verena; Wichmann, Henri; Reime, Sarah; Bache, Matthias; Vordermark, Dirk; Thews, Oliver

2018-03-05

Carbonic anhydrase (CA) IX has emerged as a promising target for cancer therapy. It is highly upregulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment, which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells with regard to potential therapeutic implications. CA IX was upregulated by hypoxia as well as acidosis in prostate cancer cells. This induction did not modulate intracellular pH but led to extracellular acidification. Pharmacological inhibition of CA IX activity by U104 (SLC-0111) resulted in a reduction in tumor cell growth and an increase in apoptotic cell death. Intracellular pH was reduced under normoxic and even more so under hypoxic conditions when CA IX level was high. However, although intracellular pH regulation was disturbed, targeting CA IX in combination with daunorubicin or cisplatin did not intensify apoptotic tumor cell death. Hence, targeting CA IX in prostate cancer cells can lead to intracellular pH dysregulation and, consequently, can reduce cellular growth and elevate apoptotic cell death. Attenuation of extracellular acidification by blocking CA IX might additionally impede tumor progression and metastasis. However, no beneficial effect was seen when targeting CA IX in combination with chemotherapeutic drugs.

Cyclooxygenase-2/carbonic anhydrase-IX up-regulation promotes invasive potential and hypoxia survival in colorectal cancer cells

PubMed Central

Sansone, Pasquale; Piazzi, Giulia; Paterini, Paola; Strillacci, Antonio; Ceccarelli, Claudio; Minni, Francesco; Biasco, Guido; Chieco, Pasquale; Bonafè, Massimiliano

2009-01-01

Inflammation promotes colorectal carcinogenesis. Tumour growth often generates a hypoxic environment in the inner tumour mass. We here report that, in colon cancer cells, the expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2) associates with that of the hypoxia response gene carbonic anhydrase-IX (CA-IX). The COX-2 knockdown, achieved by the stable infection of a COX-2 specific short harpin RNA interference (shCOX-2), down-regulates CA-IX gene expression. In colorectal cancer (CRC) cells, PGE2, the main COX-2 gene products, promotes CA-IX gene expression by ERK1/2 activation. In normoxic environment, shCOX-2 infected/CA-IX siRNA transfected CRC cells show a reduced level of active metalloproteinase-2 (MMP-2) that associates with a decreased extracellular matrix invasion capacity. In presence of hypoxia, COX-2 gene expression and PGE2 production increase. The knockdown of COX-2/CA-IX blunts the survival capability of CRC cells in hypoxia. At a high cell density, a culture condition that creates a mild pericellular hypoxic environment, the expression of COX-2/CA-IX genes is increased and triggers the invasive potential of colon cancer cells. In human colon cancer tissues, COX-2/CA-IX protein expression levels, assessed by Western blot and immunohistochemistry, correlate each other and increase with tumour stage. In conclusion, these data indicate that COX-2/CA-IX interplay promotes the aggressive behaviour of CRC cells. PMID:19017360

In vitro characterization of high purity factor IX concentrates for the treatment of hemophilia B.

PubMed

Limentani, S A; Gowell, K P; Deitcher, S R

1995-04-01

This study employed sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis and immunoblotting to assess the purity of seven high purity factor IX concentrates: Aimafix (Aima), AlphaNine-SD (Alpha Therapeutic), Factor IX VHP (Biotransfusion), Immunine (Immuno), Mononine (Armour Pharmaceutical), Nanotiv (Kabi Pharmacia), and 9MC (Blood Products Laboratory). The mean specific activity of these products ranged from 68 U factor IX/mg (Aimafix) to 246 U factor IX/mg (Mononine). SDS-PAGE analysis showed that the highest purity product, Mononine, had a single contaminating band under non-reducing conditions. Two additional bands were detected when this product was analyzed under reducing conditions. All other products had multiple contaminating bands that were more apparent under reducing than non-reducing conditions. The immunoblot for factor IX showed a dominant factor IX band for all products. In addition, visible light chain of factor IX was detected for AlphaNine-SD, Factor IX VHP, Immunine, Mononine, Nanotiv, and 9MC, suggesting that the factor IX in these products had undergone partial activation to factor IXa. Another contaminating band was visible at 49,500 for all of the products except 9MC. In addition to this band, high molecular weight contaminants were apparent for some products, most notably AlphaNine-SD. The identity of these bands is unknown. Immunoblotting failed to demonstrate factor VII as a contaminant of any of the high purity products, although factor VIIa could be detected in some lots of Immunine, Nanotiv, and 9MC by a clot-based assay. Factor X contaminated Aimafix, AlphaNine-SD, Factor IX VHP, Immunine, Nanotiv, and 9MC, but activation products of factor X were not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma: qualitative and quantitative measurements in vivo.

PubMed

Valdes, Pablo A; Bekelis, Kimon; Harris, Brent T; Wilson, Brian C; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E; Erkmen, Kadir; Paulsen, Keith D; Roberts, David W

2014-03-01

The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intraoperative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (cPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher cPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature.

5-Aminolevulinic Acid-Induced Protoporphyrin IX Fluorescence in Meningioma: Qualitative and Quantitative Measurements In Vivo

PubMed Central

Valdes, Pablo A.; Bekelis, Kimon; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Kim, Anthony; Simmons, Nathan E.; Erkmen, Kadir; Paulsen, Keith D.; Roberts, David W.

2014-01-01

BACKGROUND The use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence has shown promise as a surgical adjunct for maximizing the extent of surgical resection in gliomas. To date, the clinical utility of 5-ALA in meningiomas is not fully understood, with most descriptive studies using qualitative approaches to 5-ALA-PpIX. OBJECTIVE To assess the diagnostic performance of 5-ALA-PpIX fluorescence during surgical resection of meningioma. METHODS ALA was administered to 15 patients with meningioma undergoing PpIX fluorescence-guided surgery at our institution. At various points during the procedure, the surgeon performed qualitative, visual assessments of fluorescence by using the surgical microscope, followed by a quantitative fluorescence measurement by using an intra-operative probe. Specimens were collected at each point for subsequent neuropathological analysis. Clustered data analysis of variance was used to ascertain a difference between groups, and receiver operating characteristic analyses were performed to assess diagnostic capabilities. RESULTS Red-pink fluorescence was observed in 80% (12/15) of patients, with visible fluorescence generally demonstrating a strong, homogenous character. Quantitative fluorescence measured diagnostically significant PpIX concentrations (CPpIx) in both visibly and nonvisibly fluorescent tissues, with significantly higher CPpIx in both visibly fluorescent (P < .001) and tumor tissue (P = .002). Receiver operating characteristic analyses also showed diagnostic accuracies up to 90% for differentiating tumor from normal dura. CONCLUSION ALA-induced PpIX fluorescence guidance is a potential and promising adjunct in accurately detecting neoplastic tissue during meningioma resective surgery. These results suggest a broader reach for PpIX as a biomarker for meningiomas than was previously noted in the literature. PMID:23887194

The concomitant prescribing of ethinyl estradiol/drospirenone and potentially interacting drugs.

PubMed

McAdams, Mara; Staffa, Judy A; Dal Pan, Gerald J

2007-10-01

Ethinyl estradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) contains a progestin drospirenone with antimineralocorticoid properties that may cause potassium retention leading to hyperkalemia. We estimated the percentage of EE/DRSP users prescribed concomitant potassium-sparing drugs [nonsteroidal antiinflammatory drugs, diuretics, angiotensin-converting enzyme inhibitors (with diuretics), angiotensin II agonists (with diuretics), and potassium chloride] between January 1, 2002, and March 31, 2005. We analyzed a population-based data set of 62,527 EE/DRSP users (Dimension Rx, Caremark). We compared the fill date and end date for each prescription (Rx) for an interacting drug to the start and end date for each EE/DRSP episode (linked Rxs). If a day of an interacting Rx overlapped with an EE/DRSP episode, concomitant prescribing was recorded. A total of 17.6% of the women concomitantly used EE/DRSP and an interacting drug. Twenty-nine percent of concomitant use occurred within a month of EE/DRSP initiation. Nonsteroidal antiinflammatory drugs and diuretics were most frequently used concomitantly with EE/DRSP. Forty percent of the women with concomitant use were 35 yearsof age or older at EE/DRSP initiation compared with 29% without concomitant use (p<.001). Obstetricians/gynecologists and family practitioners were the most common prescribers of EE/DRSP and potassium-sparing drugs, respectively. Concomitant prescribing of EE/DRSP and potassium-sparing drugs occurred frequently in our study population. As EE/DRSP becomes more widely used, physicians prescribing it should monitor patients for potassium-sparing drug use.

Factor IX assay

MedlinePlus

... factor assay; Serum factor IX; Hemophilic factor B; Plasma thromboplastin component; PTC ... BJ. Factor IX (Christmas factor, hemophilic factor B, plasma thromboplastin component, PTC) - blood. In: Chernecky CC, Berger ...

Title IX: With New Opportunities, Girls' Interest Rises

ERIC Educational Resources Information Center

Toporek, Bryan

2012-01-01

On June 23, 1972, President Richard M. Nixon signed into law Title IX of the Education Amendments of 1972, which prohibits gender discrimination in any federally financed education program or activity. Title IX is far-reaching, but the law is most often associated with school and college athletics. Title IX allows schools to prove their athletic…

Title IX: A Practical Guide to Achieving Sex Equity in Education.

ERIC Educational Resources Information Center

National Coalition for Women and Girls in Education.

Title IX of the Education Amendments of 1972 is the principal federal law which prohibits sex discriminaton in education. This monograph sets forth the extent of Title IX's coverage by subject area, describes the obligations of covered institutions, and explains how victims of discrimination can enforce their Title IX right. While dealing with…

Title IX: Human Rights in School Sport.

ERIC Educational Resources Information Center

Graham, Peter J.

This paper focuses on Title IX, a part of the Federal Education Amendments of 1972, and its effect upon human rights in school sport. The paper is divided into three sections. The first section reviews the purpose of Title IX and the historical developments which led to its establishment. It states that Title IX was enacted to eliminate sexual…

Evaluating the utility of companion animal tick surveillance practices for monitoring spread and occurrence of human Lyme disease in West Virginia, 2014-2016.

PubMed

Hendricks, Brian; Mark-Carew, Miguella; Conley, Jamison

2017-11-13

Domestic dogs and cats are potentially effective sentinel populations for monitoring occurrence and spread of Lyme disease. Few studies have evaluated the public health utility of sentinel programmes using geo-analytic approaches. Confirmed Lyme disease cases diagnosed by physicians and ticks submitted by veterinarians to the West Virginia State Health Department were obtained for 2014-2016. Ticks were identified to species, and only Ixodes scapularis were incorporated in the analysis. Separate ordinary least squares (OLS) and spatial lag regression models were conducted to estimate the association between average numbers of Ix. scapularis collected on pets and human Lyme disease incidence. Regression residuals were visualised using Local Moran's I as a diagnostic tool to identify spatial dependence. Statistically significant associations were identified between average numbers of Ix. scapularis collected from dogs and human Lyme disease in the OLS (β=20.7, P<0.001) and spatial lag (β=12.0, P=0.002) regression. No significant associations were identified for cats in either regression model. Statistically significant (P≤0.05) spatial dependence was identified in all regression models. Local Moran's I maps produced for spatial lag regression residuals indicated a decrease in model over- and under-estimation, but identified a higher number of statistically significant outliers than OLS regression. Results support previous conclusions that dogs are effective sentinel populations for monitoring risk of human exposure to Lyme disease. Findings reinforce the utility of spatial analysis of surveillance data, and highlight West Virginia's unique position within the eastern United States in regards to Lyme disease occurrence.

The H IX galaxy survey - II. H I kinematics of H I eXtreme galaxies

NASA Astrophysics Data System (ADS)

Lutz, K. A.; Kilborn, V. A.; Koribalski, B. S.; Catinella, B.; Józsa, G. I. G.; Wong, O. I.; Stevens, A. R. H.; Obreschkow, D.; Dénes, H.

2018-05-01

By analysing a sample of galaxies selected from the H I Parkes All Sky Survey (HIPASS) to contain more than 2.5 times their expected H I content based on their optical properties, we investigate what drives these H I eXtreme (H IX) galaxies to be so H I-rich. We model the H I kinematics with the Tilted Ring Fitting Code TiRiFiC and compare the observed H IX galaxies to a control sample of galaxies from HIPASS as well as simulated galaxies built with the semi-analytic model DARK SAGE. We find that (1) H I discs in H IX galaxies are more likely to be warped and more likely to host H I arms and tails than in the control galaxies, (2) the average H I and average stellar column density of H IX galaxies is comparable to the control sample, (3) H IX galaxies have higher H I and baryonic specific angular momenta than control galaxies, (4) most H IX galaxies live in higher spin haloes than most control galaxies. These results suggest that H IX galaxies are H I-rich because they can support more H I against gravitational instability due to their high specific angular momentum. The majority of the H IX galaxies inherits their high specific angular momentum from their halo. The H I content of H IX galaxies might be further increased by gas-rich minor mergers. This paper is based on data obtained with the Australia Telescope Compact Array through the large program C 2705.

Gypenoside IX Suppresses p38 MAPK/Akt/NFκB Signaling Pathway Activation and Inflammatory Responses in Astrocytes Stimulated by Proinflammatory Mediators.

PubMed

Wang, Xiaoshuang; Yang, Liu; Yang, Li; Xing, Faping; Yang, Hua; Qin, Liyue; Lan, Yunyi; Wu, Hui; Zhang, Beibei; Shi, Hailian; Lu, Cheng; Huang, Fei; Wu, Xiaojun; Wang, Zhengtao

2017-12-01

Gypenoside IX (GP IX) is a pure compound isolated from Panax notoginseng. Gypenosides have been implicated to benefit the recovery of enormous neurological disorders. By suppressing the activation of astrocytes, gypenosides can improve the cognitive impairment. However, so far, little is known about whether GP IX could restrain the inflammatory responses in astrocytes or reactive astrogliosis. In present study, the anti-inflammatory effects of GP IX were investigated in reactive astrocytes induced by proinflammatory mediators both in vitro and in vivo. GP IX significantly reduced the production of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) at either protein or mRNA level in glial cell line C6 cells stimulated by lipopolysaccharide (LPS)/TNF-α combination. It also alleviated the astrogliosis and decreased the production of inflammatory mediators in brain cortex of LPS-treated mice. Further study disclosed that GP IX inhibited nuclear translocation of nuclear factor kappa B (NFκB) and reduced its transcriptional activity. Meanwhile, GP IX significantly attenuated the phosphorylation of NFκB, inhibitor of kappa B (IκB), Akt, and p38 mitogen-activated protein kinase (MAPK) under inflammatory conditions both in vitro and in vivo. These findings indicated that GP IX might suppress reactive astrogliosis by suppressing Akt/p38 MAPK/NFκB signaling pathways. And GP IX might be a promising drug candidate or prodrug for the therapy of neuroinflammatory disorders characterized with reactive astrogliosis.

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

PubMed

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

2006-03-01

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

Ongoing advances in quantitative PpIX fluorescence guided intracranial tumor resection (Conference Presentation)

NASA Astrophysics Data System (ADS)

Olson, Jonathan D.; Kanick, Stephen C.; Bravo, Jaime J.; Roberts, David W.; Paulsen, Keith D.

2016-03-01

Aminolevulinc-acid induced protoporphyrin IX (ALA-PpIX) is being investigated as a biomarker to guide neurosurgical resection of brain tumors. ALA-PpIX fluorescence can be observed visually in the surgical field; however, raw fluorescence emissions can be distorted by factors other than the fluorophore concentration. Specifically, fluorescence emissions are mixed with autofluorescence and attenuated by background absorption and scattering properties of the tissue. Recent work at Dartmouth has developed advanced fluorescence detection approaches that return quantitative assessments of PpIX concentration, which are independent of background optical properties. The quantitative fluorescence imaging (qFI) approach has increased sensitivity to residual disease within the resection cavity at the end of surgery that was not visible to the naked eye through the operating microscope. This presentation outlines clinical observations made during an ongoing investigation of ALA-PpIX based guidance of tumor resection. PpIX fluorescence measurements made in a wide-field hyperspectral imaging approach are co-registered with point-assessment using a fiber optic probe. Data show variations in the measured PpIX accumulation among different clinical tumor grades (i.e. high grade glioma, low grade glioma), types (i.e. primary tumors. metastases) and normal structures of interest (e.g. normal cortex, hippocampus). These results highlight the contrast enhancement and underscore the potential clinical benefit offered from quantitative measurements of PpIX concentration during resection of intracranial tumors.

Impact of Florida's prescription drug monitoring program and pill mill law on high-risk patients: A comparative interrupted time series analysis.

PubMed

Chang, Hsien-Yen; Murimi, Irene; Faul, Mark; Rutkow, Lainie; Alexander, G Caleb

2018-04-01

We quantified the effects of Florida's prescription drug monitoring program and pill mill law on high-risk patients. We used QuintilesIMS LRx Lifelink data to identify patients receiving prescription opioids in Florida (intervention state, N: 1.13 million) and Georgia (control state, N: 0.54 million). The preintervention, intervention, and postintervention periods were July 2010 to June 2011, July 2011 to September 2011, and October 2011 to September 2012. We identified 3 types of high-risk patients: (1) concomitant users: patients with concomitant use of benzodiazepines and opioids; (2) chronic users: long-term, high-dose, opioid users; and (3) opioid shoppers: patients receiving opioids from multiple sources. We compared changes in opioid prescriptions between Florida and Georgia before and after policy implementation among high-risk/low-risk patients. Our monthly measures included (1) average morphine milligram equivalent per transaction, (2) total opioid volume across all prescriptions, (3) average days supplied per transaction, and (4) total number of opioid prescriptions dispensed. Among opioid-receiving individuals in Florida, 6.62% were concomitant users, 1.96% were chronic users, and 0.46% were opioid shoppers. Following policy implementation, Florida's high-risk patients experienced relative reductions in morphine milligram equivalent (opioid shoppers: -1.08 mg/month, 95% confidence interval [CI] -1.62 to -0.54), total opioid volume (chronic users: -4.58 kg/month, CI -5.41 to -3.76), and number of dispensed opioid prescriptions (concomitant users: -640 prescriptions/month, CI -950 to -340). Low-risk patients generally did not experience statistically significantly relative reductions. Compared with Georgia, Florida's prescription drug monitoring program and pill mill law were associated with large relative reductions in prescription opioid utilization among high-risk patients. Copyright © 2018 John Wiley & Sons, Ltd.

Big Men on Campus: Administrative Response to Title IX and the Development of Women's Sports in the Big Ten Conference, 1972-1982

ERIC Educational Resources Information Center

Ramsey, Jeffrey T.

2014-01-01

Signed into law in 1972, Title IX of the Education Amendments was designed to eliminate gender discrimination throughout the American educational system. Title IX applied to all educational programs at any level of schooling including admissions, financial aid, academic programs, and social organizations. However, Title IX has primarily been…

Core-shell AgSiO2-protoporphyrin IX nanoparticle: Effect of the Ag core on reactive oxygen species generation

NASA Astrophysics Data System (ADS)

Lismont, M.; Pá; ez-Martinez, C.; Dreesen, L.

2015-03-01

Photodynamic therapy (PDT) for cancer is based on the use of a light sensitive molecule to produce, under specific irradiation, toxic reactive oxygen species (ROS). A way to improve the therapy efficiency is to increase the amount of produced ROS near cancer cells. This aim can be achieved by using a metal enhanced process arising when an optically active molecule is located near a metallic nanoparticle (NP). Here, the coupling effect between silver (Ag) NPs and protoporphyrin IX (PpIX) molecules, a clinically approved photosensitizer, is studied compared first, to PpIX fluorescence yield and second, to ROS production efficiency. By applying a modified Stöber process, PpIX was encapsulated into a silica (SiO2) shell, surrounding a 60 nm sized Ag core. We showed that, compared to SiO2-PpIX NPs, Ag coated SiO2-PpIX NPs dramatically decreased PpIX fluorescence together with singlet oxygen production efficiency. However, after incubation time in the dark, the amount of superoxide anions generated by the Ag doped sample was higher than the control sample one.

The efficacy of intraoperative atrial radiofrequency ablation for atrial fibrillation during concomitant cardiac surgery-the Surgical Atrial Fibrillation Suppression (SAFS) Study.

PubMed

Veasey, Rick A; Segal, Oliver R; Large, Janet K; Lewis, Michael E; Trivedi, Uday H; Cohen, Andrew S; Hyde, Jonathan A J; Sulke, A Neil

2011-10-01

Studies assessing radiofrequency ablation (RFA) for atrial fibrillation (AF) performed at the time of concomitant cardiac surgery have reported high success rates. The efficacy of this treatment has primarily been determined by a single electrocardiogram (ECG) or 24-h Holter monitor at follow-up. We sought to assess the true efficacy of this procedure using prolonged cardiac rhythm monitoring. One hundred patients with paroxysmal (n = 47) and persistent AF (n = 53) requiring cardiac surgery were enrolled. Patients were clinically reviewed 6 weeks post-operatively and were monitored with 7-day Holter with full disclosure, 6 months post-surgery. A cohort of 50 patients also underwent 7 day Holter monitoring preoperatively. AF recurrence was defined as >30 s of AF. At 6 months, 75% of patients were in sinus rhythm according to a single ECG. However, only 62% of patients were free from AF on 7-day Holter; all AF episodes in these patients were asymptomatic. The procedure resulted in a significant decrease in AF burden from 56.2% at baseline to 27.5% at 6 months follow-up, (p < 0.001). Predictors of AF recurrence were (1) pre-operative AF duration; (2) persistent compared with paroxysmal AF; (3) increasing left atrial diameter and (4) requirement for mitral valve surgery. Surgical RFA for the treatment of AF, during concomitant cardiac surgery, is a successful procedure and significantly reduces AF burden. However, 13% of patients have asymptomatic AF episodes only identified with continuous monitoring. This has important implications for post-operative anti-arrhythmic and anticoagulant management and for the definition of surgical AF ablation success.

Collagen type IX from human cartilage: a structural profile of intermolecular cross-linking sites.

PubMed Central

Diab, M; Wu, J J; Eyre, D R

1996-01-01

Type IX collagen, a quantitatively minor collagenous component of cartilage, is known to be associated with and covalently cross-linked to type II collagen fibrils in chick and bovine cartilage. Type IX collagen molecules have also been shown to form covalent cross-links with each other in bovine cartilage. In the present study we demonstrate by structural analysis and location of cross-linking sites that, in human cartilage, type IX collagen is covalently cross-linked to type II collagen and to other molecules of type IX collagen. We also present evidence that, if the proteoglycan form of type IX collagen is present in human cartilage, it can only be a minor component of the matrix, similar to findings with bovine cartilage. PMID:8660302

KSC-2009-5954

NASA Image and Video Library

2009-10-28

CAPE CANAVERAL, Fla. - At NASA's Kennedy Space Center in Florida, a post-launch news conference is held in the Press Site auditorium following the successful launch of the Ares I-X test rocket at 11:30 a.m. EDT Oct. 28. Smiling, from left, are Doug Cooke, associate administrator for NASA's Exploration Systems Mission Directorate; Jeff Hanley, Constellation Program manager; Bob Ess, mission manager for the Ares I-X flight test; and Edward Mango, launch director for the Ares I-X flight test. For more information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5955

NASA Image and Video Library

2009-10-28

CAPE CANAVERAL, Fla. - At NASA's Kennedy Space Center in Florida, Constellation Program Manager Jeff Hanley addresses a post-launch news conference in the Press Site auditorium following the successful launch of the Ares I-X test rocket at 11:30 a.m. EDT Oct. 28. From left, are, Doug Cooke, associate administrator for NASA's Exploration Systems Mission Directorate; Hanley; Bob Ess, mission manager for the Ares I-X flight test; and Edward Mango, launch director for the Ares I-X flight test. For more information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

ARES I-X Launch Prep

NASA Image and Video Library

2009-10-26

Mission managers, from left, NASA Constellation Program manager Jeff Hanley, Ares I-X Launch Director Ed Mango, Ares I-X mission manager Bob Ess, Ground Operations Manager Philip "Pepper" Phillips, review the latest data in Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center during the launch countdown of the Ares I-X rocket in Cape Canaveral, Fla., Tuesday, Oct. 27, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

ARES I-X Launch Prep

NASA Image and Video Library

2009-10-26

Mission managers, from left, NASA Ares I-X Assistant Launch Director Pete Nickolenko, Ground Operations Manager Philip "Pepper" Phillips, Ares I-X Launch Director Ed Mango, and Constellation Program manager Jeff Hanley review the latest weather radar from Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center during the launch countdown of the Ares I-X rocket in Cape Canaveral, Fla., Tuesday, Oct. 27, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

ARES I-X Launch

NASA Image and Video Library

2009-10-27

NASA Ares I-X Launch Director Ed Mango, left, laughs as NASA Ares I-X Assistant Launch Director Pete Nickolenko looks out the window of Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center prior to the launch of the Ares I-X rocket from pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Wednesday, Oct. 28, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

Evaluation of factor IX deficiency by interdigitated electrode (IDE)

NASA Astrophysics Data System (ADS)

Gopinath, Subash C. B.; Hashim, Uda; Uda, M. N. A.

2017-03-01

Factor IX deficiency is the main cause of hemophilia A and B. This a severe excessive bleeding disorder that can even kill the patient if not treated with the right prescription of Factor IX hormone to stop the bleeding. The bleeding can be caused by an injury or even a sudden bleeding in some very rare cases. To find the Factor IX effectiveness and to understand the deficiency more carefully for the future of medicine, experiments are conducted to test the Factor IX using the Interdigitated Electrode (IDE) and gold Nanoparticle with the help of Nanoelectrical technology.

Improved muscle-derived expression of human coagulation factor IX from a skeletal actin/CMV hybrid enhancer/promoter.

PubMed

Hagstrom, J N; Couto, L B; Scallan, C; Burton, M; McCleland, M L; Fields, P A; Arruda, V R; Herzog, R W; High, K A

2000-04-15

Hemophilia B is caused by the absence of functional coagulation factor IX (F.IX) and represents an important model for treatment of genetic diseases by gene therapy. Recent studies have shown that intramuscular injection of an adeno-associated viral (AAV) vector into mice and hemophilia B dogs results in vector dose-dependent, long-term expression of biologically active F.IX at therapeutic levels. In this study, we demonstrate that levels of expression of approximately 300 ng/mL (6% of normal human F.IX levels) can be reached by intramuscular injection of mice using a 2- to 4-fold lower vector dose (1 x 10(11) vector genomes/mouse, injected into 4 intramuscular sites) than previously described. This was accomplished through the use of an improved expression cassette that uses the cytomegalovirus (CMV) immediate early enhancer/promoter in combination with a 1.2-kilobase portion of human skeletal actin promoter. These results correlated with enhanced levels of F.IX transcript and secreted F.IX protein in transduced murine C2C12 myotubes. Systemic F.IX expression from constructs containing the CMV enhancer/promoter alone was 120 to 200 ng/mL in mice injected with 1 x 10(11) vector genomes. Muscle-specific promoters performed poorly for F.IX transgene expression in vitro and in vivo. However, the incorporation of a sequence from the alpha-skeletal actin promoter containing at least 1 muscle-specific enhancer and 1 enhancer-like element further improved muscle-derived expression of F.IX from a CMV enhancer/promoter-driven expression cassette over previously published results. These findings will allow the design of a clinical protocol for therapeutic levels of F.IX expression with lower vector doses, thus enhancing efficacy and safety of the protocol. (Blood. 2000;95:2536-2542)

5-Aminolevulinic Acid Induced Fluorescence Is a Powerful Intraoperative Marker for Precise Histopathological Grading of Gliomas with Non-Significant Contrast-Enhancement

PubMed Central

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A.; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Background Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. Methods We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. Results A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Conclusions Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift. PMID:24204718

Evaluation of ALA-induced PpIX as a photosensitizer for PDT in cats

NASA Astrophysics Data System (ADS)

Lucroy, Michael D.; Edwards, Benjamin F.; Peavy, George M.; Krasieva, Tatiana B.; Griffey, Stephen M.; Madewell, Bruce R.

1998-07-01

Given exogenously, ALA defeats intrinsic regulatory feedback mechanisms allowing intracellular accumulation of protoporphyrin IX (PpIX), a highly efficient photosensitizer. In vivo, PpIX synthesis in neoplastic mammary tissues averages 20-fold higher than in normal mammary tissues. PpIX is retained intracellularly, unlike perivascular localization of other photosensitizers, and it is then cleared quickly from the body. In vitro, ALA induced PpIX production in our laboratory in 6 cell lines tested, including an established feline kidney cell line and dermal fibroblasts from primary skin biopsy explant, resulting in photosensitization. Fluorescent microscopy confirmed PpIX production in skin adnexae following ALA administration in a normal cat. To evaluate toxicity, three cats were treated with a single i.v. dose of ALA (either 100, 200, of 400 mg/kg) and followed for 7 days. Cats receiving 100 or 200 mg/kg ALA i.v. had elevated liver enzymes and bilirubin within 24 hours. Histopathology revealed hydropic changes in the liver and renal fibrosis. The cat receiving 400 mg/kg ALA intravenously had cutaneous flush, bradycardia and apnea associated with ALA administration; within 24 hours the cat was lethargic, anorectic and icteric. ALT, AST and bilirubin concentrations had increased significantly. At necropsy the liver had a prominent lobular pattern; histopathology revealed severe periportal hepatitis and splenic necrosis. Systemically administered ALA induces PpIX production, but toxicity may preclude its clinical application in the cat. PpIX levels seem to be more time dependent than those dependent at these three ALA doses and they are well beyond the saturation point for adequate PpIX conversion. The literature is scant regarding toxicity associated with parenteral administration of ALA.

Expanding the versatility of phage display II: improved affinity selection of folded domains on protein VII and IX of the filamentous phage.

PubMed

Løset, Geir Åge; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger

2011-02-24

Phage display is a leading technology for selection of binders with affinity for specific target molecules. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII) or the minor coat protein III (pIII). Whereas pVIII display suffers from drawbacks such as heterogeneity in display levels and polypeptide fusion size limitations, toxicity and infection interference effects have been described for pIII display. Thus, display on other coat proteins such as pVII or pIX might be more attractive. Neither pVII nor pIX display have gained widespread use or been characterized in detail like pIII and pVIII display. Here we present a side-by-side comparison of display on pIII with display on pVII and pIX. Polypeptides of interest (POIs) are fused to pVII or pIX. The N-terminal periplasmic signal sequence, which is required for phage integration of pIII and pVIII and that has been added to pVII and pIX in earlier studies, is omitted altogether. Although the POI display level on pIII is higher than on pVII and pIX, affinity selection with pVII and pIX display libraries is shown to be particularly efficient. Display through pVII and/or pIX represent platforms with characteristics that differ from those of the pIII platform. We have explored this to increase the performance and expand the use of phage display. In the paper, we describe effective affinity selection of folded domains displayed on pVII or pIX. This makes both platforms more attractive alternatives to conventional pIII and pVIII display than they were before.

Photodynamic therapy using hemagglutinating virus of Japan envelope (HVJ-E): a novel therapeutic approach for the treatment of hormone antagonistic prostate cancer

NASA Astrophysics Data System (ADS)

Inai, Mizuho; Yamauchi, Masaya; Honda, Norihiro; Hazama, Hisanao; Tachikawa, Shoji; Nakamura, Hiroyuki; Nishida, Tomoki; Yasuda, Hidehiro; Kaneda, Yasufumi; Awazu, Kunio

2015-03-01

Traditional treatment options for prostate cancer are insufficient to cure advanced drug-resistant prostate cancer. Thus, as an alternative form of cancer therapy, photodynamic therapy (PDT) has become the main subject of intense investigation as a possible treatment modality. In this study, ultraviolet-inactivated viral vector, called hemagglutinating virus of Japan envelope (HVJ-E) was utilized to establish an effective delivery system for photosensitizer. Lipidated protoporphyrin IX (PpIX lipid) was inserted in HVJ-E by centrifugation to create a new drug delivering system that allows selective accumulation of photosensitizers in cancer cells. To study in vitro drug release mechanism of porphyrus envelope, the ultra-high voltage electron microscope tomography was applied. Next, to evaluate the photodynamic efficiency of porphyrus envelope for hormone antagonistic prostate cancer cells (PC-3), uptake of porphyrus envelope derived PpIX lipid and PpIX induced from exogenously administered precursor of 5-aminolevulinic acid hydrochloride (5-ALA) were compared by measuring fluorescence intensity of PpIX. Finally, to evaluate the efficacy of porphyrus envelope-PDT, laser light at a wavelength of 405 nm was irradiated to PC-3 cells. As a result, incorporation of porphyrus envelope-derived PpIX lipid occurred via membrane fusion, giving the highest fluorescence intensity when compared to 5-ALA-induced PpIX. Also, results from PDT experiment revealed the 28.6 × 103-fold and 206-fold increase in therapeutic efficacy when compared to those of PDT using 5-ALA induced PpIX and PpIX lipid, respectively. Our findings suggest how porphyrus envelope can induce efficient accumulation of PpIX lipid, which can enhance the therapeutic efficacy of PDT against hormone antagonistic prostate cancer.

Aminolevulinic acid-mediated protoporphyrin IX and photodynamic therapy for breast cancers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Chen, Bin

2017-02-01

Photodynamic therapy (PDT) involves the combination of a photosensitizer and light of a specific wavelength. Upon light activation in the presence of oxygen, photosensitizer molecules generate reactive oxygen species that cause cytotoxicity by inducing oxidative stress. Aminolevulinic acid (ALA) is a pro-drug used for the diagnosis and PDT treatment of various solid tumors based on endogenous production of heme precursor protoporphyrin IX (PpIX). Although nearly all types of human cells express heme biosynthesis enzymes and produce PpIX, tumor cells are found to have more PpIX production and accumulation than normal cells, allowing for the detection and treatment of solid tumors. The objective of my research is to explore therapeutic approaches to enhance ALA-based tumor detection and therapy. We have found that high ABCG2 transporter activity in triple negative breast cancer cells (TNBC) contributed to reduced PpIX levels in cells, causing them to be more resistant towards ALA-PDT. The administration of an ABCG2 inhibitor, Ko143, was able to reverse cell resistance to ALA-PDT by enhancing PpIX mitochondrial accumulation and sensitizing cancer cells to ALA-PDT. Ko143 treatment had little effect on PpIX production and ALA-PDT in normal and ER- or HER2-positive cells. Furthermore, since some tyrosine kinase inhibitors (TKI) are known to block ABCG2 transporter activity, we screened a panel of tyrosine kinase inhibitors to examine its effect on enhancing PpIX fluorescence and ALA-PDT efficacy. Several TKIs including lapatinib and gefitinib showed effectiveness in increasing ALA-PpIX fluorescence in TNBC leading to increased cell death after PDT administration. These results indicate that inhibiting ABCG2 transporter using TKIs is a promising approach for targeting TNBC with ALA-based modality.

Influence of vector dose on factor IX-specific T and B cell responses in muscle-directed gene therapy.

PubMed

Herzog, Roland W; Fields, Paul A; Arruda, Valder R; Brubaker, Jeff O; Armstrong, Elina; McClintock, Darryl; Bellinger, Dwight A; Couto, Linda B; Nichols, Timothy C; High, Katherine A

2002-07-20

Intramuscular injection of an adeno-associated virus (AAV) vector has resulted in vector dose-dependent, stable expression of canine factor IX (cF.IX) in hemophilia B dogs with an F.IX missense mutation (Herzog et al., Nat. Med. 1999;5:56-63). The use of a species-specific transgene allowed us to study risks and characteristics of antibody formation against the therapeutic transgene product. We analyzed seven dogs that had been injected at a single time point at multiple intramuscular sites with varying vector doses (dose per kilogram, dose per animal, dose per site). Comparison of individual animals suggests an increased likelihood of inhibitory anti-cF.IX (inhibitor) development with increased vector doses, with dose per site showing the strongest correlation with the risk of inhibitor formation. In six of seven animals, such immune responses were either absent or transient, and therefore did not prevent sustained systemic expression of cF.IX. Transient inhibitory/neutralizing anti-cF.IX responses occurred at vector doses of 2 x 10(12)/site, whereas a 6-fold higher dose resulted in a longer lasting, higher titer inhibitor. Anti-cF.IX was efficiently blocked in an eighth animal that was injected with a high vector dose per site, but in addition received transient immune suppression. Inhibitor formation was characterized by synthesis of two IgG subclasses and in vitro proliferation of lymphocytes to cF.IX antigen, indicating a helper T cell-dependent mechanism. Anti-cF.IX formation is likely influenced by the extent of local antigen presentation and may be avoided by limited vector doses or by transient immune modulation.

5-Aminolevulinic acid induced fluorescence is a powerful intraoperative marker for precise histopathological grading of gliomas with non-significant contrast-enhancement.

PubMed

Widhalm, Georg; Kiesel, Barbara; Woehrer, Adelheid; Traub-Weidinger, Tatjana; Preusser, Matthias; Marosi, Christine; Prayer, Daniela; Hainfellner, Johannes A; Knosp, Engelbert; Wolfsberger, Stefan

2013-01-01

Intraoperative identification of anaplastic foci in diffusely infiltrating gliomas (DIG) with non-significant contrast-enhancement on MRI is indispensible to avoid histopathological undergrading and subsequent treatment failure. Recently, we found that 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) fluorescence can visualize areas with increased proliferative and metabolic activity in such gliomas intraoperatively. As treatment of DIG is predominantely based on histopathological World Health Organisation (WHO) parameters, we analyzed whether PpIX fluorescence can detect anaplastic foci according to these criteria. We prospectively included DIG patients with non-significant contrast-enhancement that received 5-ALA prior to resection. Intraoperatively, multiple samples from PpIX positive and negative intratumoral areas were collected using a modified neurosurgical microscope. In all samples, histopathological WHO criteria and proliferation rate were assessed and correlated to the PpIX fluorescence status. A total of 215 tumor specimens were collected in 59 patients. Of 26 WHO grade III gliomas, 23 cases (85%) showed focal PpIX fluorescence, whereas 29 (91%) of 33 WHO grade II gliomas were PpIX negative. In intratumoral areas with focal PpIX fluorescence, mitotic rate, cell density, nuclear pleomorphism, and proliferation rate were significantly higher than in non-fluorescing areas. The positive predictive value of focal PpIX fluorescence for WHO grade III histology was 85%. Our study indicates that 5-ALA induced PpIX fluorescence is a powerful marker for intraoperative identification of anaplastic foci according to the histopathological WHO criteria in DIG with non-significant contrast-enhancement. Therefore, application of 5-ALA optimizes tissue sampling for precise histopathological diagnosis independent of brain-shift.

Modulation of the endogenous production of protoporphyrin IX in a yeast-based model organism

NASA Astrophysics Data System (ADS)

Joniová, Jaroslava; Gerelli, Emmanuel; Wagnières, Georges

2017-02-01

The main aim of this study was to assess conditions at which simple yeast-based model organism produces maximal levels of protoporphyrin IX (PpIX) after an exogenous administration of its precursor, 5-aminolevulinic acid (ALA), and the ferrous-ion chelator 2,2'-bipyridyl. We observed that the fluorescing porphyrin, produced after these administrations, was likely to be PpIX since fluorescence spectroscopy of the porphyrins produced endogenously in yeast cells resembles that of PpIX in DMSO and in vivo in the chick's chorioallantoic membrane model. Also, fluorescence lifetimes of these porphyrins are very similar to that of PpIX in vitro and in vivo. This suggests that PpIX is the main fluorescent compound produced by yeast in our conditions. We found that the conditions at which yeast produces the maximal PpIX were a synchronous administration of 5 μM ALA and 1 mM 2,2'-bipyridyl for yeast incubated in aqueous glucose and 1 mM 2,2'-bipyridyl in the presence of YPD medium. Such a simple model is of high interest to study basic mechanisms involved in the mitochondrial respiration since PpIX, which is produced in this organelle, can be used as an oxygen sensor, or to perform photodynamic therapy and photodiagnosis. Since the absorption and scattering coefficients of this model are much smaller than those of soft tissues over the visible part of the spectrum, a version of this model loaded with appropriated amounts of light absorbing and scattering particles could be designed as a phantom to mimic tumors containing PpIX, a useful tool to optimize certain cancer photodetection set-ups.

Enhancement and optimization of PpIX-based photodynamic therapy of skin cancer: translational studies from bench to clinic

NASA Astrophysics Data System (ADS)

Maytin, Edward V.; Anand, Sanjay; Baran, Christine; Honari, Golara; Lohser, Sara; Kyei, Angela; Bailin, Philip; Pogue, Brian W.

2009-02-01

Nonmelanoma skin carcinomas are the most common of all human cancers. Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) has been used to treat these tumors, but has shown variable results. We are pursuing a multifaceted approach toward optimizing tumor responsiveness. First, a new paradigm is being developed in which tumors are pretreated with differentiation-inducing agents, e.g. methotrexate or Vitamin D, to enhance synthesis of protoporphyrin IX (PpIX) and improve tumor cell killing upon exposure to 635 nm light. This principle was first elucidated in cell culture studies, and has now been shown to hold true for murine skin tumors, and for a human subcutaneous tumor model (A431 cells injected in nude mice). Clinical trials to test methotrexate and Vitamin D as augmenting agents for ALA-PDT of nonmelanoma skin cancer are being designed. Second, better methods to measure PpIX in patients' skin tumors in real time are being developed. In a clinical study to measure PpIX in patients with dysplastic skin lesions, in vivo fluorescence dosimetry was used to measure the accumulation of PpIX over time, and revealed that intralesional PpIX may reach clinically-useful levels earlier than previously thought for the treatment of actinic keratoses. In a second clinical study to examine depth of PpIX production in nonmelanoma skin cancer, the depth of PpIX within BCC tumors was found at relatively deep levels (>1 mm) in some tumor nests, but not in others. Production of PpIX in deep squamous cell carcinoma was very low. In summary, molecular approaches such as differentiation therapy to enhance ALA-PDT for individual patients may ultimately be needed to help to improve skin cancer responses to this modality.

Molecular and electronic structure of thin films of protoporphyrin(IX)Fe(III)Cl

NASA Astrophysics Data System (ADS)

Snyder, Shelly R.; White, Henry S.

1991-11-01

Electrochemical, scanning tunneling microscopy (STM), and tunneling spectroscopy studies of the molecular and electronic properties of thin films of protoporphyrin(IX)Fe(III)Cl (abbreviated as PP(IX)Fe(III)Cl) on highly oriented pyrolytic graphite (HOPG) electrodes are reported. PP(IX)Fe(III)Cl films are prepared by two different methods: (1) adsorption, yielding an electrochemically-active film, and (2) irreversible electrooxidative polymerization, yielding an electrochemically-inactive film. STM images, in conjunction with electro-chemical results, indicate that adsorption of PP(IX)Fe(III)Cl from aqueous solutions onto freshly cleaved HOPG results in a film comprised of molecular aggregates. In contrast, films prepared by irreversible electrooxidative polymerization of PP(IX)Fe(III)Cl have a denser, highly structured morphology, including what appear to be small pinholes (approx. 50A diameter) in an otherwise continuous film.

Intrinsic thermodynamics of inhibitor binding to human carbonic anhydrase IX.

PubMed

Linkuvienė, Vaida; Matulienė, Jurgita; Juozapaitienė, Vaida; Michailovienė, Vilma; Jachno, Jelena; Matulis, Daumantas

2016-04-01

Human carbonic anhydrase 9th isoform (CA IX) is an important marker of numerous cancers and is increasingly interesting as a potential anticancer drug target. Various synthetic aromatic sulfonamide-bearing compounds are being designed as potent inhibitors of CA IX. However, sulfonamide compound binding to CA IX is linked to several reactions, the deprotonation of the sulfonamide amino group and the protonation of the CA active site Zn(II)-bound hydroxide. These linked reactions significantly affect the affinities and other thermodynamic parameters such as enthalpies and entropies of binding. The observed and intrinsic affinities of compound binding to CA IX were determined by the fluorescent thermal shift assay. The enthalpies and entropies of binding were determined by the isothermal titration calorimetry. The pKa of CA IX was determined to be 6.8 and the enthalpy of CA IX-Zn(II)-bound hydroxide protonation was -24 kJ/mol. These values enabled the analysis of intrinsic thermodynamics of a library of compounds binding to CA IX. The most strongly binding compounds exhibited the intrinsic affinity of 0.01 nM and the observed affinity of 2 nM. The intrinsic thermodynamic parameters of compound binding to CA IX helped to draw the compound structure to thermodynamics relationship. It is important to distinguish the intrinsic from observed parameters of any disease target protein interaction with its inhibitors as drug candidates when drawing detailed compound structure to thermodynamics correlations. Copyright © 2016 Elsevier B.V. All rights reserved.

KSC-2009-5956

NASA Image and Video Library

2009-10-28

CAPE CANAVERAL, Fla. - At NASA's Kennedy Space Center in Florida, a post-launch news conference is held in the Press Site auditorium following the successful launch of the Ares I-X test rocket at 11:30 a.m. EDT Oct. 28. Sharing a lighter moment are, from left, Doug Cooke, associate administrator for NASA's Exploration Systems Mission Directorate; Jeff Hanley, Constellation Program manager; Bob Ess, mission manager for the Ares I-X flight test; and Edward Mango, launch director for the Ares I-X flight test. For more information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5848

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights illuminate the pad and the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5849

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights illuminate the pad and the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5850

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights illuminate the pad and the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5859

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As night settles over Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5860

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As night settles over Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5852

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5858

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As night settles over Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5847

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights illuminate the pad and the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5846

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights illuminate the pad and the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5853

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5854

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5855

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5856

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As night settles over Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5851

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As nightfall comes to Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5857

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. - As night settles over Launch Complex 39B at NASA's Kennedy Space Center in Florida, xenon lights reveal the Ares I-X rocket awaiting the approaching liftoff of its flight test. This is the first time since the Apollo Program's Saturn rockets were retired that a vehicle other than the space shuttle has occupied the pad. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

Concentrating Solar Power Projects - Solar Electric Generating Station IX |

Science.gov Websites

Station IX (SEGS IX) Country: United States Location: Harper Dry Lake, California (Mojave Desert) Owner(s : Parabolic trough Status: Operational Country: United States City: Harper Dry Lake State: California County

Cutaneous respirometry by dynamic measurement of mitochondrial oxygen tension for monitoring mitochondrial function in vivo.

PubMed

Harms, Floor A; Voorbeijtel, Wilhelmina J; Bodmer, Sander I A; Raat, Nicolaas J H; Mik, Egbert G

2013-09-01

Progress in diagnosis and treatment of mitochondrial dysfunction in chronic and acute disease could greatly benefit from techniques for monitoring of mitochondrial function in vivo. In this study we demonstrate the feasibility of in vivo respirometry in skin. Mitochondrial oxygen measurements by means of oxygen-dependent delayed fluorescence of protoporphyrin IX are shown to provide a robust basis for measurement of local oxygen disappearance rate (ODR). The fundamental principles behind the technology are described, together with an analysis method for retrievel of respirometry data. The feasibility and reproducibility of this clinically useful approach are demonstrated in a series of rats. Copyright © 2012 Elsevier B.V. All rights reserved.

Application of 1,2-diethyl-3-hydroxypyridin-4-one to enhance tissue selectivity for photodynamic therapy of the bladder

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Porter, John B.; Bown, Stephen G.

1995-03-01

Five-aminolaevulinic acid (ALA) induced protoporphyrin IX (PpIX) has proven to be a useful photosensitizer for photodynamic therapy (PDT). In living cells, the conversion of PpIX to photoinactive haem is catalyzed by ferrochelatase in the presence of tissue iron and inhibition of this final committed step results in increased accumulation of PpIX. The in vivo effect of a new iron chelator, 1,2-diethyl-3-hydroxypyridin-4-one (CP94), on the buildup of PpIX in different bladder layers was evaluated. In CP94 treated rats, 5 - 7 hours after intravesical instillation of ALA solution, the fluorescence intensity of PpIX in the urothelium was doubled whilst in the muscle layer it remained low at a similar level to those seen without the iron chelator. With CP94, further reduction of skin photosensitization is possible as a similar photodynamic effect on the bladder could be achieved at lower ALA concentration. The addition of CP94 seems an effective and convenient way to potentiate ALA induced PpIX tissue selectivity.

Lansoprazole and carbonic anhydrase IX inhibitors sinergize against human melanoma cells.

PubMed

Federici, Cristina; Lugini, Luana; Marino, Maria Lucia; Carta, Fabrizio; Iessi, Elisabetta; Azzarito, Tommaso; Supuran, Claudiu T; Fais, Stefano

2016-01-01

Proton Pump Inhibitors (PPIs) reduce tumor acidity and therefore resistance of tumors to drugs. Carbonic Anhydrase IX (CA IX) inhibitors have proven to be effective against tumors, while tumor acidity might impair their full effectiveness. To analyze the effect of PPI/CA IX inhibitors combined treatment against human melanoma cells. The combination of Lansoprazole (LAN) and CA IX inhibitors (FC9-399A and S4) has been investigated in terms of cell proliferation inhibition and cell death in human melanoma cells. The combination of these inhibitors was more effective than the single treatments in both inhibiting cell proliferation and in inducing cell death in human melanoma cells. These results represent the first successful attempt in combining two different proton exchanger inhibitors. This is the first evidence on the effectiveness of a new approach against tumors based on the combination of PPI and CA IX inhibitors, thus providing an alternative strategy against tumors.

Urothelial conversion of 5-aminolevulinic acid to protoporphyrin IX following oral or intravesical administration

NASA Astrophysics Data System (ADS)

Moore, Ronald B.; Miller, Gerald G.; Brown, Kevin; Bhatnagar, Rakesh; Tulip, John; McPhee, Malcolm S.

1995-03-01

Preferential conversion of 5-aminolevulinic acid (5-ALA) to protoporphyrin-IX (Pp-IX) occurs in malignant tissue, with accumulation to diagnostic and therapeutic levels. Recent studies have suggested selective conversion in epithelial tissue following oral or intravenous administration. Topical application avoids systemic photosensitization. However, the glycosaminoglycan (GAG) layer lining the urinary bladder is believed to be a protective barrier generally limiting mucosal absorption. Our objective was to evaluate uptake and conversion of 5-ALA following intravesical or oral administration. Using a rat model, Pp-IX content within epithelial and muscularis layers was quantitated by fluorescence confocal microscopy. Following intravesical administration, Pp-IX accumulated predominantly in the urothelium; whereas following oral administration, Pp-IX accumulated in both the urothelium and muscularis. Intravesical 5-ALA administration is feasible and may afford selective photosensitization of the urothelium for treatment of carcinoma in situ.

KSC-2009-5542

NASA Image and Video Library

2009-10-20

CAPE CANAVERAL, Fla. - Poised inside Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the Ares I-X rocket's upper stage is adorned with the American flag, NASA logo, and the logos of the Constellation Program, Ares, and Ares I-X. The transfer of the pad from the Space Shuttle Program to the Constellation Program took place May 31. Modifications made to the pad include the removal of shuttle unique subsystems, such as the orbiter access arm and a section of the gaseous oxygen vent arm, along with the installation of three 600-foot lightning towers, access platforms, environmental control systems and a vehicle stabilization system. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

Ares I-X Flight Test Vehicle: Stack 5 Modal Test

NASA Technical Reports Server (NTRS)

Buehrle, Ralph D.; Templeton, Justin D.; Reaves, Mercedes C.; Horta, Lucas G.; Gaspar, James L.; Bartolotta, Paul A.; Parks, Russel A.; Lazor, Danel R.

2010-01-01

Ares I-X was the first flight test vehicle used in the development of NASA's Ares I crew launch vehicle. The Ares I-X used a 4-segment reusable solid rocket booster from the Space Shuttle heritage with mass simulators for the 5th segment, upper stage, crew module and launch abort system. Three modal tests were defined to verify the dynamic finite element model of the Ares I-X flight test vehicle. Test configurations included two partial stacks and the full Ares I-X flight test vehicle on the Mobile Launcher Platform. This report focuses on the first modal test that was performed on the top section of the vehicle referred to as Stack 5, which consisted of the spacecraft adapter, service module, crew module and launch abort system simulators. This report describes the test requirements, constraints, pre-test analysis, test operations and data analysis for the Ares I-X Stack 5 modal test.

Ares I-X Flight Test Vehicle:Stack 1 Modal Test

NASA Technical Reports Server (NTRS)

Buehrle, Ralph D.; Templeton, Justin D.; Reaves, Mercedes C.; Horta, Lucas G.; Gaspar, James L.; Bartolotta, Paul A.; Parks, Russel A.; Lazor, Daniel R.

2010-01-01

Ares I-X was the first flight test vehicle used in the development of NASA s Ares I crew launch vehicle. The Ares I-X used a 4-segment reusable solid rocket booster from the Space Shuttle heritage with mass simulators for the 5th segment, upper stage, crew module and launch abort system. Three modal tests were defined to verify the dynamic finite element model of the Ares I-X flight test vehicle. Test configurations included two partial stacks and the full Ares I-X flight test vehicle on the Mobile Launcher Platform. This report focuses on the second modal test that was performed on the middle section of the vehicle referred to as Stack 1, which consisted of the subassembly from the 5th segment simulator through the interstage. This report describes the test requirements, constraints, pre-test analysis, test operations and data analysis for the Ares I-X Stack 1 modal test.

The scorpion toxin Bot IX is a potent member of the α-like family and has a unique N-terminal sequence extension.

PubMed

Martin-Eauclaire, Marie-France; Salvatierra, Juan; Bosmans, Frank; Bougis, Pierre E

2016-09-01

We report the detailed chemical, immunological and pharmacological characterization of the α-toxin Bot IX from the Moroccan scorpion Buthus occitanus tunetanus venom. Bot IX, which consists of 70 amino acids, is a highly atypical toxin. It carries a unique N-terminal sequence extension and is highly lethal in mice. Voltage clamp recordings on oocytes expressing rat Nav1.2 or insect BgNav1 reveal that, similar to other α-like toxins, Bot IX inhibits fast inactivation of both variants. Moreover, Bot IX belongs to the same structural/immunological group as the α-like toxin Bot I. Remarkably, radioiodinated Bot IX competes efficiently with the classical α-toxin AaH II from Androctonus australis, and displays one of the highest affinities for Nav channels. © 2016 Federation of European Biochemical Societies.

Quantitative fluorescence using 5-aminolevulinic acid–induced protoporphyrin IX biomarker as a surgical adjunct in low-grade glioma surgery

PubMed Central

Valdés, Pablo A.; Jacobs, Valerie; Harris, Brent T.; Wilson, Brian C.; Leblond, Frederic; Paulsen, Keith D.; Roberts, David W.

2015-01-01

OBJECT Previous studies in high-grade gliomas (HGGs) have indicated that protoporphyrin IX (PpIX) accumulates in higher concentrations in tumor tissue, and, when used to guide surgery, it has enabled improved resection leading to increased progression-free survival. Despite the benefits of complete resection and the advances in fluorescence-guided surgery, few studies have investigated the use of PpIX in low-grade gliomas (LGGs). Here, the authors describe their initial experience with 5-aminolevulinic acid (ALA)–induced PpIX fluorescence in a series of patients with LGG. METHODS Twelve patients with presumed LGGs underwent resection of their tumors after receiving 20 μg/kg of ALA approximately 3 hours prior to surgery under an institutional review board–approved protocol. Intraoperative assessments of the resulting PpIX emissions using both qualitative, visible fluorescence and quantitative measurements of PpIX concentration were obtained from tissue locations that were subsequently biopsied and evaluated histopathologically. Mixed models for random effects and receiver operating characteristic curve analysis for diagnostic performance were performed on the fluorescence data relative to the gold-standard histopathology. RESULTS Five of the 12 LGGs (1 ganglioglioma, 1 oligoastrocytoma, 1 pleomorphic xanthoastrocytoma, 1 oligodendroglioma, and 1 ependymoma) demonstrated at least 1 instance of visible fluorescence during surgery. Visible fluorescence evaluated on a specimen-by-specimen basis yielded a diagnostic accuracy of 38.0% (cutoff threshold: visible fluorescence score ≥ 1, area under the curve = 0.514). Quantitative fluorescence yielded a diagnostic accuracy of 67% (for a cutoff threshold of the concentration of PpIX [CPpIX] > 0.0056 μg/ml, area under the curve = 0.66). The authors found that 45% (9/20) of nonvisibly fluorescent tumor specimens, which would have otherwise gone undetected, accumulated diagnostically significant levels of CPpIX that were detected quantitatively. CONCLUSIONS The authors’ initial experience with ALA-induced PpIX fluorescence in LGGs concurs with other literature reports that the resulting visual fluorescence has poor diagnostic accuracy. However, the authors also found that diagnostically significant levels of CPpIX do accumulate in LGGs, and the resulting fluorescence emissions are very often below the detection threshold of current visual fluorescence imaging methods. Indeed, at least in the authors’ initial experience reported here, if quantitative detection methods are deployed, the diagnostic performance of ALA-induced PpIX fluorescence in LGGs approaches the accuracy associated with visual fluorescence in HGGs. PMID:26140489

Development and characterisation of a brain tumour mimicking protoporphyrin IX fluorescence phantom (Conference Presentation)

NASA Astrophysics Data System (ADS)

Xie, Yijing; Tisca, Cristiana; Peveler, William; Noimark, Sacha; Desjardins, Adrien E.; Parkin, Ivan P.; Ourselin, Sebastien; Vercauteren, Tom

2017-02-01

5-ALA-PpIX fluorescence-guided brain tumour resection can increase the accuracy at which cancerous tissue is removed and thereby improve patient outcomes, as compared with standard white light imaging. Novel optical devices that aim to increase the specificity and sensitivity of PpIX detection are typically assessed by measurements in tissue-mimicking optical phantoms of which all optical properties are defined. Current existing optical phantoms specified for PpIX lack consistency in their optical properties, and stability with respect to photobleaching, thus yielding an unstable correspondence between PpIX concentration and the fluorescence intensity. In this study, we developed a set of aqueous-based phantoms with different compositions, using deionised water or PBS buffer as background medium, intralipid as scattering material, bovine haemoglobin as background absorber, and either PpIX dissolved in DMSO or a novel nanoparticle with similar absorption and emission spectrum to PpIX as the fluorophore. We investigated the phantom stability in terms of aggregation and photobleaching by comparing with different background medium and fluorophores, respectively. We characterised the fluorescence intensity of the fluorescent nanoparticle in different concentration of intralipid and haemoglobin and its time-dependent stability, as compared to the PpIX-induced fluorescence. We corroborated that the background medium was essential to prepare a stable aqueous phantom. The novel fluorescent nanoparticle used as surrogate fluorophore of PpIX presented an improved temporal stability and a reliable correspondence between concentration and emission intensity. We proposed an optimised phantom composition and recipe to produce reliable and repeatable phantom for validation of imaging device.

KSC-2009-5953

NASA Image and Video Library

2009-10-28

CAPE CANAVERAL, Fla. - At NASA's Kennedy Space Center in Florida, members of the news media attend a post-launch news conference in the Press Site auditorium following the successful launch of the Ares I-X test rocket at 11:30 a.m. EDT Oct. 28. Onstage, from left, are moderator George Diller, NASA Public Affairs officer; Doug Cooke, associate administrator for NASA's Exploration Systems Mission Directorate; Jeff Hanley, Constellation Program manager; Bob Ess, mission manager for the Ares I-X flight test; and Edward Mango, launch director for the Ares I-X flight test. For more information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5862

NASA Image and Video Library

2009-10-23

CAPE CANAVERAL, Fla. – In the Press Site auditorium at NASA's Kennedy Space Center in Florida, Bob Ess, NASA's mission manager for the Ares I-X flight test, participates in a news conference following the conclusion of the flight test readiness review, or FTRR, for the Ares I-X test rocket. During the meeting, senior NASA and contractor managers assessed the risks associated with the test and determined the rocket, support systems and procedures are ready for launch. The Ares I-X launch date was announced after the FTRR and is officially set for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Jack Pfaller

Compilation of 1991 Annual Reports of the Navy ELF Communications Systems Ecological Monitoring Program

DTIC Science & Technology

1992-08-01

and the conservation benefit of large versus small forests. Biol. Conserv. 30:173-187. 1 Blake, J.G., G.J. Niemi, and J.M. Hanowski. Drought and... health of algal populations. ixI I U Predators - animals that ingest other animals. 3 Relative weight (Wr) - weight at length values calculated from fish...examination of 3 water and wastewater, 15th edition. American Public Health Association. Washington, D. C. 1134 pp. Bormann, F. H. and G. E. Likens. 1979

Ultrasound Tomography by Galerkin or Moment Methods,

DTIC Science & Technology

1983-05-05

in terms of i(x) . Let (31,32) gj~x) - J gji ~ix and G() W i(x) where i(x) is given by (24). Thus, by (25) the coefficients gji an Gqji are givenby...4 yK (mh,nh) y, (mh,nh) gji qji and i(mn)(X) Thus on factoring, we obtain f(S) (f - fu)). 2 (3) i i 4. i 0 ~ ko y,,Qxj)f 0 (,x,)g.. + A qjG bsil. 2

IBM PC/IX operating system evaluation plan

NASA Technical Reports Server (NTRS)

Dominick, Wayne D. (Editor); Granier, Martin; Hall, Philip P.; Triantafyllopoulos, Spiros

1984-01-01

An evaluation plan for the IBM PC/IX Operating System designed for IBM PC/XT computers is discussed. The evaluation plan covers the areas of performance measurement and evaluation, software facilities available, man-machine interface considerations, networking, and the suitability of PC/IX as a development environment within the University of Southwestern Louisiana NASA PC Research and Development project. In order to compare and evaluate the PC/IX system, comparisons with other available UNIX-based systems are also included.

Characterization and standardization of tissue-simulating protoporphyrin IX optical phantoms

NASA Astrophysics Data System (ADS)

Marois, Mikael; Bravo, Jaime; Davis, Scott C.; Kanick, Stephen Chad

2016-03-01

Optical devices for measuring protoporphryin IX (PpIX) fluorescence in tissue are routinely validated by measurements in optical phantoms. Yet there exists limited data to form a consensus on the recipe for phantoms that both mimic the optical properties found in tissue and yield a reliable and stable relationship between PpIX concentration and the fluorescence remission intensity. This study characterizes the influence of multiple phantom components on PpIX fluorescence emission intensity, using Intralipid as the scattering source, bovine whole blood as the background absorber, and Tween as a surfactant to prevent PpIX aggregation. Optical measurements showed a linear proportionality (r>0.99) between fluorescence intensity and PpIX concentration (0.1 to 10 μg/mL) over a range of Intralipid (1 to 2%) and whole blood (0.5 to 3%) for phantoms containing low surfactant (≤0.1%), with fluorescence intensities and scattering and absorption properties stable for 5 h after mixing. The role of surfactant in PpIX phantoms was found to be complex, as aggregation was evident in aqueous nonturbid phantoms with no surfactant (0% Tween), and avoided in phantoms containing Intralipid as the scattering source with no additional or low amounts of added surfactant (≤0.1% Tween). Conversely, phantoms containing higher surfactant content (>0.1% Tween) and whole blood showed interactions that distorted the fluorescence emissions.

Identification of Bisindolylmaleimide IX as a potential agent to treat drug-resistant BCR-ABL positive leukemia

PubMed Central

Liu, Huijuan; Zang, Yi; Azam, Mohammad; Habib, Samy L.; Li, Jia; Ruan, Xinsen; Jia, Hao; Wang, Xueying; Li, Baojie

2016-01-01

Chronic myeloid leukemia (CML) treatment with BCR-ABL inhibitors is often hampered by development of drug resistance. In a screen for novel chemotherapeutic drug candidates with genotoxic activity, we identified a bisindolylmaleimide derivative, IX, as a small molecule compound with therapeutic potential against CML including drug-resistant CML. We show that Bisindolylmaleimide IX inhibits DNA topoisomerase, generates DNA breaks, activates the Atm-p53 and Atm-Chk2 pathways, and induces cell cycle arrest and cell death. Interestingly, Bisindolylmaleimide IX is highly effective in targeting cells positive for BCR-ABL. BCR-ABL positive cells display enhanced DNA damage and increased cell cycle arrest in response to Bisindolylmaleimide IX due to decreased expression of topoisomerases. Cells positive for BCR-ABL or drug-resistant T315I BCR-ABL also display increased cytotoxicity since Bisindolylmaleimide IX inhibits B-Raf and the downstream oncogene addiction pathway. Mouse cancer model experiments showed that Bisindolylmaleimide IX, at doses that show little side effect, was effective in treating leukemia-like disorders induced by BCR-ABL or T315I BCR-ABL, and prolonged the lifespan of these model mice. Thus, Bisindolylmaleimide IX presents a novel drug candidate to treat drug-resistant CML via activating BCR-ABL-dependent genotoxic stress response and inhibiting the oncogene addiction pathway activated by BCR-ABL. PMID:27564101

ALA-induced PpIX fluorescence in epileptogenic tissue

NASA Astrophysics Data System (ADS)

Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

2011-03-01

Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

Expanding the Versatility of Phage Display II: Improved Affinity Selection of Folded Domains on Protein VII and IX of the Filamentous Phage

PubMed Central

Løset, Geir Åge; Roos, Norbert; Bogen, Bjarne; Sandlie, Inger

2011-01-01

Background Phage display is a leading technology for selection of binders with affinity for specific target molecules. Polypeptides are normally displayed as fusions to the major coat protein VIII (pVIII) or the minor coat protein III (pIII). Whereas pVIII display suffers from drawbacks such as heterogeneity in display levels and polypeptide fusion size limitations, toxicity and infection interference effects have been described for pIII display. Thus, display on other coat proteins such as pVII or pIX might be more attractive. Neither pVII nor pIX display have gained widespread use or been characterized in detail like pIII and pVIII display. Methodology/Principal Findings Here we present a side-by-side comparison of display on pIII with display on pVII and pIX. Polypeptides of interest (POIs) are fused to pVII or pIX. The N-terminal periplasmic signal sequence, which is required for phage integration of pIII and pVIII and that has been added to pVII and pIX in earlier studies, is omitted altogether. Although the POI display level on pIII is higher than on pVII and pIX, affinity selection with pVII and pIX display libraries is shown to be particularly efficient. Conclusions/Significance Display through pVII and/or pIX represent platforms with characteristics that differ from those of the pIII platform. We have explored this to increase the performance and expand the use of phage display. In the paper, we describe effective affinity selection of folded domains displayed on pVII or pIX. This makes both platforms more attractive alternatives to conventional pIII and pVIII display than they were before. PMID:21390283

Ares I-X Flight Test Vehicle Similitude to the Ares I Crew Launch Vehicle

NASA Technical Reports Server (NTRS)

Huebner, Lawrence D.; Smith, R. Marshall; Campbell, John R.; Taylor, Terry L.

2009-01-01

The Ares I-X Flight Test Vehicle is the first in a series of flight test vehicles that will take the Ares I Crew Launch Vehicle design from development to operational capability. Ares I-X is scheduled for a 2009 flight date, early enough in the Ares I design and development process so that data obtained from the flight can impact the design of Ares I before its Critical Design Review. Decisions on Ares I-X scope, flight test objectives, and FTV fidelity were made prior to the Ares I systems requirements being baselined. This was necessary in order to achieve a development flight test to impact the Ares I design. Differences between the Ares I-X and the Ares I configurations are artifacts of formulating this experimental project at an early stage and the natural maturation of the Ares I design process. This paper describes the similarities and differences between the Ares I-X Flight Test Vehicle and the Ares I Crew Launch Vehicle. Areas of comparison include the outer mold line geometry, aerosciences, trajectory, structural modes, flight control architecture, separation sequence, and relevant element differences. Most of the outer mold line differences present between Ares I and Ares I-X are minor and will not have a significant effect on overall vehicle performance. The most significant impacts are related to the geometric differences in Orion Crew Exploration Vehicle at the forward end of the stack. These physical differences will cause differences in the flow physics in these areas. Even with these differences, the Ares I-X flight test is poised to meet all five primary objectives and six secondary objectives. Knowledge of what the Ares I-X flight test will provide in similitude to Ares I - as well as what the test will not provide - is important in the continued execution of the Ares I-X mission leading to its flight and the continued design and development of Ares I.

The Regulation of Title IX: Sex Discrimination in Student Affairs

ERIC Educational Resources Information Center

Malloy, Michele

1976-01-01

The aspects of student affairs covered by Title IX and its final regulation are emphasized since that area represents new vistas of sexual equality. The Regulation of Title IX is examined for accomplishments and oversights, effects and exemptions. (Author/LBH)

ARES I-X Launch

NASA Image and Video Library

2009-10-27

NASA Ares I-X Launch Director Ed Mango, 3rd from left, along with other mission managers watches the launch of the Ares I-X rocket from Firing Room One of the Launch Control Center (LCC) at the Kennedy Space Center in Cape Canaveral, Fla., Wednesday, Oct. 28, 2009. The flight test of Ares I-X will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

Ares I-X Flight Test Vehicle Similitude to the Ares I Crew Launch Vehicle

NASA Technical Reports Server (NTRS)

Huebner, Lawrence D.; Smith, R. Marshall; Campbell, John R., Jr.; Taylor, Terry L.

2008-01-01

The Ares I-X Flight Test Vehicle is the first in a series of flight test vehicles that will take the Ares I Crew Launch Vehicle design from development to operational capability. The test flight is scheduled for April 2009, relatively early in the Ares I design process so that data obtained from the flight can impact the design of Ares I before its Critical Design Review. Because of the short time frame (relative to new launch vehicle development) before the Ares I-X flight, decisions about the flight test vehicle design had to be made in order to complete analysis and testing in time to manufacture the Ares I-X vehicle hardware elements. This paper describes the similarities and differences between the Ares I-X Flight Test Vehicle and the Ares I Crew Launch Vehicle. Areas of comparison include the outer mold line geometry, aerosciences, trajectory, structural modes, flight control architecture, separation sequence, and relevant element differences. Most of the outer mold line differences present between Ares I and Ares I-X are minor and will not have a significant effect on overall vehicle performance. The most significant impacts are related to the geometric differences in Orion Crew Exploration Vehicle at the forward end of the stack. These physical differences will cause differences in the flow physics in these areas. Even with these differences, the Ares I-X flight test is poised to meet all five primary objectives and six secondary objectives. Knowledge of what the Ares I-X flight test will provide in similitude to Ares I as well as what the test will not provide is important in the continued execution of the Ares I-X mission leading to its flight and the continued design and development of Ares I.

Expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer.

PubMed

Nakai, Yasushi; Tatsumi, Yoshihiro; Miyake, Makito; Anai, Satoshi; Kuwada, Masaomi; Onishi, Sayuri; Chihara, Yoshitomo; Tanaka, Nobumichi; Hirao, Yoshihiko; Fujimoto, Kiyohide

2016-03-01

The mechanism underlying the increased levels of protoporphyrin IX in bladder cancer remains unclear. Here, we focus on proteins associated with protoporphyrin IX accumulation in bladder cancer cells and investigate the protein that plays a key role in increased protoporphyrin IX accumulation in bladder cancer cells. Western blotting was used to determine the expression of peptide transporter 1, hydroxymethylbilane synthase, ferrochelatase, ATP-binding cassette 2, and heme oxygenase-1 in bladder cancer cell line cells. We evaluated the correlation between the expression of each protein and accumulated protoporphyrin IX in these cells using Pearson's correlation analysis. Immunohistochemistry was used to estimate the expression of the same five proteins in samples from 75 patients who underwent transurethral resection of bladder tumors. The correlation between the expression of each protein in cells from resected bladder specimens and accumulated protoporphyrin IX in bladder cancer cells in voided urine was evaluated using Pearson's correlation analysis. The expression of ferrochelatase showed a significant negative correlation with protoporphyrin IX accumulation in vitro (p=0.04). The expression of peptide transporter 1 (p<0.01, R=0.39), heme oxygenase-1 (p<0.01, R=0.33), and ferrochelatase (p<0.01, R=0.75) in resected bladder specimens by immunohistochemistry was correlated with protoporphyrin IX accumulation in bladder cancer cells in voided urine. On multivariate analysis, the expression of ferrochelatase (p=0.03) was significant factors to predict positive 5-aminolevulinic acid-induced fluorescent cytology. The expression of ferrochelatase has a strong correlation in protoporphyrin IX accumulation with photodynamic detection of bladder cancer. Copyright © 2015 Elsevier B.V. All rights reserved.

Vitamin D as a potential enhancer of aminolevulinate-based photodynamic therapy for nonmelanoma skin cancer

NASA Astrophysics Data System (ADS)

Maytin, Edward V.; Anand, Sanjay; Atanaskova, Natasha; Wilson, Clara

2010-02-01

Vitamin D3 (Vit D3) is a hormone essential for normal bone and cardiovascular health, and may participate in preventing nonmelanoma skin cancers (NMSC). Calcitriol (1,25 dihydroxyD3) is the active form of the hormone. We showed previously that calcitriol is a potent inducer of protoporphyrin IX (PpIX) in skin keratinocytes grown in organotypic cultures. Here, we investigated the ability of Vit D3 to enhance PpIX levels within skin tumors in vivo. Squamous tumors, generated by chemical carcinogenesis in mice, were pretreated for 3 days with topical calcitriol. Then 5-aminolevulinic acid (5-ALA) was applied topically, and PpIX levels were measured by noninvasive fluorimetry and in biopsied tissue. Calcitriol pretreatment resulted in a 3 to 4-fold elevation of PpIX in tumors, relative to no pretreatmen, providing significantly more photosensitizer available for tumor destruction. For deep tumors, topical calcitriol may not penetrate sufficiently. Therefore we explored whether systemic Vit D3, given short-term (3 days), might elevate PpIX within NMSC in a deep tumor model (subcutaneously-implanted A431 human squamous carcinoma cells). Defined amounts of calcitriol were injected into the mice for 3 d, followed by systemic 5-ALA, tissue biopsy, and confocal microscopic measurement of PpIX in frozen tissues. PpIX was clearly elevated after systemically delivered calcitriol. More work is needed, but if the amount of calcitriol required to elevate PpIX levels proves to be small, then the approach may ultimately prove attractive. Since most Americans are currently Vitamin D deficient, a small increase in calcitriol might be possible without risk of hypercalcemia.

KSC-2009-5342

NASA Image and Video Library

2009-10-06

CAPE CANAVERAL, Fla. – A banner inside NASA Kennedy Space Center's Vehicle Assembly Building captures the excitement building at Kennedy in anticipation of the flight test of the Ares I-X rocket, towering above it in High Bay 3. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I, which is the essential core of a space transportation system designed to carry crewed missions back to the moon, on to Mars and out into the solar system. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/mission_pages/constellation/ares/flighttests/aresIx/index.html. Photo credit: NASA/Glenn Benson

KSC-2009-3688

NASA Image and Video Library

2009-06-11

CAPE CANAVERAL, Fla. – In the NASA News Center TV Studio at NASA's Kennedy Space Center in Florida, on view is a 1/12 model of the vehicle stabilization system that will be installed on Launch Pad 39B to hold the Ares I-X rocket for its flight test. Looking at the model are (from left) Roger Lenard, consultant with Lee & Associates, LCC; Jon Cowart, NASA's Ares I-X deputy mission manager; and Eric Mellberg, Ares I-X Vehicle Stabilization Design lead with United Space Alliance Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in August 2009. Photo credit: NASA/Kim Shiflett

Why, What and Where To? Title IX, Educational Amendment of 1972

ERIC Educational Resources Information Center

Perry-Miller, Mitzi

1977-01-01

Discusses the ramifications of Title IX and asserts that access to variety without the limitations of tradition for women, both as students and employees, is the guts of Title IX as it is the heart of the community college movement. (JG)

32 CFR 196.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-07-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

24 CFR 3.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-04-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

45 CFR 2555.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

45 CFR 2555.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

24 CFR 3.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

32 CFR 196.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-07-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

36 CFR 1211.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-07-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

45 CFR 2555.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

10 CFR 5.235 - Statutory amendments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

10 CFR 5.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

24 CFR 3.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-04-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

45 CFR 2555.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

32 CFR 196.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-07-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

24 CFR 3.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-04-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

36 CFR 1211.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-07-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

36 CFR 1211.235 - Statutory amendments.

Code of Federal Regulations, 2012 CFR

2012-07-01

... provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation... organization. (ii) For example, all of the operations of a college, university, or other postsecondary...

Significant performance enhancement of inverted organic light-emitting diodes by using ZnIx as a hole-blocking layer

NASA Astrophysics Data System (ADS)

Cheng, Chuan-Hui; Zhang, Bi-Long; Sun, Chao; Li, Ruo-Xuan; Wang, Yuan; Tian, Wen-Ming; Zhao, Chun-Yi; Jin, Sheng-Ye; Liu, Wei-Feng; Luo, Ying-Min; Du, Guo-Tong; Cong, Shu-Lin

2017-06-01

A highly efficient inverted organic light emitting diode using 1.0 nm-thick ZnIx as a hole-blocking layer is developed. We fabricate devices with the configuration ITO/ZnIx (1.0 nm)/Alq3 (50 nm)/NPB (50 nm)/MoO3 (6.0 nm)/Al (100 nm). The deposition of a ZnIx layer increases the maximum luminance by two orders of magnitude from 13.4 to 3566.1 cd/m2. In addition, the maximum current efficiency and power efficiency are increased by three orders of magnitude, and the turn-on voltage to reach 1 cd/m2 decreases from 13 to 8 V. The results suggest that the electron injection efficiency is not improved by introducing a ZnIx layer. Instead, the improved device performance originates from the strong hole-blocking ability of ZnIx. This work indicates that layered materials may lead to novel applications in optoelectronic devices.

Institutional Transformation 2.5 Building Module Help Manual.

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

Villa, Daniel

The Institutional Transformation (IX) building module is a software tool developed at Sandia National Laboratories to evaluate energy conservation measures (ECMs) on hundreds of DOE-2 building energy models simultaneously. In IX, ECMs can be designed through parameterizing DOE-2 building models and doing further processing via visual basic for applications subroutines. IX provides the functionality to handle multiple building models for different years, which enables incrementally changing a site of hundreds of buildings over time. It also enables evaluation of the effects of changing climate, comparisons between data and modeling results, and energy use of centralized utility buildings (CUBs). IX consistsmore » of a Microsoft Excel(r) user interface, Microsoft Access(r) database, and Microsoft Excel(r) CUB build utility whose functionalities are described in detail in this report. In addition to descriptions of the user interfaces, descriptions of every ECM already designed in IX is included. SAND2016-8983 IX 2.5 Help Manual« less

Expression of hypoxia-inducible carbonic anhydrases in brain tumors

PubMed Central

Proescholdt, Martin A.; Mayer, Christina; Kubitza, Marion; Schubert, Thomas; Liao, Shu-Yuan; Stanbridge, Eric J.; Ivanov, Sergey; Oldfield, Edward H.; Brawanski, Alexander; Merrill, Marsha J.

2005-01-01

Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel–Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1α staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target. PMID:16212811

ARES I-X USS Fracture Analysis Loads Spectra Development

NASA Technical Reports Server (NTRS)

Larsen, Curtis; Mackey, Alden

2008-01-01

This report describes the development of a set of bounding load spectra for the ARES I-X launch vehicle. These load spectra are used in the determination of the critical initial flaw size (CIFS) of the welds in the ARES I-X upper stage simulator (USS).

75 FR 18245 - Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... the meeting is for Business Organizations, Trade Associations, Chambers of Commerce and related... SMALL BUSINESS ADMINISTRATION Public Federal Regulatory Enforcement Fairness Hearing Region IX... hereby given that the U.S. Small Business Administration (SBA) Region IX Regulatory Fairness Board and...

40 CFR 5.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

40 CFR 5.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

14 CFR 1253.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

43 CFR 41.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

31 CFR 28.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-07-01

....235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or... local educational agency (as defined in section 8801 of title 20), system of vocational education, or...

40 CFR 5.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

43 CFR 41.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

31 CFR 28.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-07-01

....235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or... local educational agency (as defined in section 8801 of title 20), system of vocational education, or...

43 CFR 41.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

31 CFR 28.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-07-01

....235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or... local educational agency (as defined in section 8801 of title 20), system of vocational education, or...

14 CFR § 1253.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-01-01

....235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or... local educational agency (as defined in section 8801 of title 20), system of vocational education, or...

Factor Activity Assays for Monitoring Extended Half-Life FVIII and Factor IX Replacement Therapies.

PubMed

Kitchen, Steve; Tiefenbacher, Stefan; Gosselin, Robert

2017-04-01

The advent of modified factor VIII (FVIII) and factor IX (FIX) molecules with extended half-lives (EHLs) compared with native FVIII and FIX represents a major advance in the field of hemophilia care, with the potential to reduce the frequency of prophylactic injections and/or to increase the trough level prior to subsequent injections. Monitoring treatment through laboratory assays will be an important part of ensuring patient safety, including any tailoring of prophylaxis. Several approaches have been used to extend half-lives, including PEGylation, and fusion to albumin or immunoglobulin. Some of these modifications affect factor assays as routinely performed in hemophilia centers; so, laboratories will need to use FVIII and FIX assays which have been shown to be suitable on a product-by-product basis. For some products, there are marked differences between results obtained using one-stage or chromogenic assays and results obtained using different reagents in the one-stage assay. The laboratory should use an assay in which the recovery of the product closely aligns with the assay used by the pharmaceutical company to assign potency to the product, so that the units reported by the laboratory agree with those used to demonstrate efficacy of the product during clinical trials. Reported assay differences in relation to several of the EHL FVIII and FIX molecules will be reviewed in this article. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Title IX: The Half Full, Half Empty Glass.

ERIC Educational Resources Information Center

National Advisory Council on Women's Educational Programs, Washington, DC.

This publication discusses changes in the educational system resulting from Title IX of the 1972 Education Amendments which prohibits sex discrimination in federally assisted education programs and activities. The purpose of the publication is to help people understand and support Title IX. There are nine sections. The first section examines the…

Title IX. Physical Educators for Equity. Module 4.

ERIC Educational Resources Information Center

Uhlir, Ann

This module presents information on the provisions of Public Law 92 318 (Title IX) that affect the teaching of secondary school physical education. Title IX ensures equal educational opportunities for both sexes in any federally assisted educational program. It is designed to enable teachers to identify educational practices inconsistent with the…

41 CFR 101-4.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-07-01

... amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

41 CFR 101-4.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-07-01

... amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

18 CFR 1317.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Coverage § 1317.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not... education; or (B) A local educational agency (as defined in section 8801 of title 20), system of vocational...

38 CFR 23.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Coverage § 23.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or... local educational agency (as defined in section 8801 of title 20), system of vocational education, or...

15 CFR 8a.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

13 CFR 113.235 - Statutory amendments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Coverage § 113.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not... education; or (B) A local educational agency (as defined in section 8801 of title 20), system of vocational...

28 CFR 54.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-07-01

... amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

43 CFR 41.235 - Statutory amendments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

45 CFR 618.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Coverage § 618.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not... education; or (B) A local educational agency (as defined in section 8801 of title 20), system of vocational...

45 CFR 618.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Coverage § 618.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not... education; or (B) A local educational agency (as defined in section 8801 of title 20), system of vocational...

22 CFR 229.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

45 CFR 618.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Coverage § 618.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not... education; or (B) A local educational agency (as defined in section 8801 of title 20), system of vocational...

44 CFR 19.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-10-01

... applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the American... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation...

44 CFR 19.235 - Statutory amendments.

Code of Federal Regulations, 2012 CFR

2012-10-01

... applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the American... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation...

10 CFR 1042.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the... (as defined in section 8801 of title 20), system of vocational education, or other school system; (iii...

36 CFR § 1211.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-07-01

... all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the American Legion... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation...

10 CFR 1042.235 - Statutory amendments.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the... (as defined in section 8801 of title 20), system of vocational education, or other school system; (iii...

44 CFR 19.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-10-01

... applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the American... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation...

44 CFR 19.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the American... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation...

18 CFR 1317.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Coverage § 1317.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not... education; or (B) A local educational agency (as defined in section 8801 of title 20), system of vocational...

10 CFR 1042.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the... (as defined in section 8801 of title 20), system of vocational education, or other school system; (iii...

22 CFR 146.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

29 CFR 36.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-07-01

... applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the American... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation...

49 CFR 25.235 - Statutory amendments.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

29 CFR 36.235 - Statutory amendments.

Code of Federal Regulations, 2012 CFR

2012-07-01

... applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the American... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation...

13 CFR 113.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Coverage § 113.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not... education; or (B) A local educational agency (as defined in section 8801 of title 20), system of vocational...

29 CFR 36.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-07-01

... applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the American... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation...

28 CFR 54.235 - Statutory amendments.

Code of Federal Regulations, 2012 CFR

2012-07-01

... amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

29 CFR 36.235 - Statutory amendments.

Code of Federal Regulations, 2011 CFR

2011-07-01

... applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or activity of the American... of title 20), system of vocational education, or other school system; (iii)(A) An entire corporation...

45 CFR 618.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Coverage § 618.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not... education; or (B) A local educational agency (as defined in section 8801 of title 20), system of vocational...

49 CFR 25.235 - Statutory amendments.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any program or... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

28 CFR 54.235 - Statutory amendments.

Code of Federal Regulations, 2010 CFR

2010-07-01

... amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or preclude: (1) Any... educational agency (as defined in section 8801 of title 20), system of vocational education, or other school...

38 CFR 23.235 - Statutory amendments.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Coverage § 23.235 Statutory amendments. (a) This section, which applies to all provisions of these Title IX regulations, addresses statutory amendments to Title IX. (b) These Title IX regulations shall not apply to or... local educational agency (as defined in section 8801 of title 20), system of vocational education, or...

31 CFR 28.625 - Decisions and notices.

Code of Federal Regulations, 2013 CFR

2013-07-01

... BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Procedures § 28... Title IX regulations with which it is found that the applicant or recipient has failed to comply. (e... Title IX regulations, or to have otherwise failed to comply with these Title IX regulations unless and...

Rape on College Campuses: Reform through Title IX.

ERIC Educational Resources Information Center

Steinberg, Terry Nicole

1991-01-01

This article first, analyzes the growing problem of campus rape; second, evaluates some college rape reduction programs; third, uses case law to demonstrate that rape should be considered sex discrimination under Title IX; and, fourth, suggests an amendment to Title IX, defining rape as sex discrimination. Appropriate implementation measures by…

KSC-2009-1996

NASA Image and Video Library

2009-03-09

CAPE CANAVERAL, Fla. – Media were invited to a showing of the Ares I-X simulator rocket segments at NASA's Kennedy Space Center in Florida. Here, Bob Ess and Jon Cowart discuss the flight test objectives of the Ares I-X targeted for launch in July 2009. Ess is manager of the Ares I-X project. Cowart is Ares I-X deputy mission manager. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I, part of the Constellation Program to return men to the moon and beyond. Ares I is the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Photo credit: NASA/Jack Pfaller

Complete genome analysis of a novel umbravirus-polerovirus combination isolated from Ixeridium dentatum.

PubMed

Yoo, Ran Hee; Lee, Seung-Won; Lim, Seungmo; Zhao, Fumei; Igori, Davaajargal; Baek, Dasom; Hong, Jin-Sung; Lee, Su-Heon; Moon, Jae Sun

2017-12-01

Two novel viruses, isolated in Bonghwa, Republic of Korea, from an Ixeridium dentatum plant with yellowing mottle symptoms, have been provisionally named Ixeridium yellow mottle-associated virus 1 (IxYMaV-1) and Ixeridium yellow mottle-associated virus 2 (IxYMaV-2). IxYMaV-1 has a genome of 6,017 nucleotides sharing a 56.4% sequence identity with that of cucurbit aphid-borne yellows virus (genus Polerovirus). The IxYMaV-2 genome of 4,196 nucleotides has a sequence identity of less than 48.3% with e other species classified within the genus Umbravirus. Genome properties and phylogenetic analysis suggested that IxYMaV-1 and -2 are representative isolates of new species classifiable within the genus Polerovirus and Umbravirus, respectively.

Optical-sectioning microscopy of protoporphyrin IX fluorescence in human gliomas: standardization and quantitative comparison with histology

NASA Astrophysics Data System (ADS)

Wei, Linpeng; Chen, Ye; Yin, Chengbo; Borwege, Sabine; Sanai, Nader; Liu, Jonathan T. C.

2017-04-01

Systemic delivery of 5-aminolevulinic acid leads to enhanced fluorescence image contrast in many tumors due to the increased accumulation of protoporphyrin IX (PpIX), a fluorescent porphyrin that is associated with tumor burden and proliferation. The value of PpIX-guided resection of malignant gliomas has been demonstrated in prospective randomized clinical studies in which a twofold greater extent of resection and improved progression-free survival have been observed. In low-grade gliomas and at the diffuse infiltrative margins of all gliomas, PpIX fluorescence is often too weak to be detected with current low-resolution surgical microscopes that are used in operating rooms. However, it has been demonstrated that high-resolution optical-sectioning microscopes are capable of detecting the sparse and punctate accumulations of PpIX that are undetectable via conventional low-power surgical fluorescence microscopes. To standardize the performance of high-resolution optical-sectioning devices for future clinical use, we have developed an imaging phantom and methods to ensure that the imaging of PpIX-expressing brain tissues can be performed reproducibly. Ex vivo imaging studies with a dual-axis confocal microscope demonstrate that these methods enable the acquisition of images from unsectioned human brain tissues that quantitatively and consistently correlate with images of histologically processed tissue sections.

Early events in photodynamic therapy: chemical and physical changes in a POPC:cholesterol bilayer due to hematoporphyrin IX-mediated photosensitization.

PubMed

Santos, António; Rodrigues, António M; Sobral, Abílio J F N; Monsanto, Paula V; Vaz, Winchil L C; Moreno, Maria João

2009-01-01

We studied the interaction of hematoporphyrin IX (HpIX) with bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) containing cholesterol at a molar fraction between 0 and 0.5. The membrane-associated fraction of HpIX decreases significantly over a period of hours, for porphyrin concentrations in the aqueous phase above 50 nM. This was attributed to self-aggregation of HpIX and was well described by a dimerization process. A model was developed to correct for aggregation and obtain the true partition coefficient which is dependent on the molar fraction of cholesterol with a maximum at 20 mol%. The chemical and physical effects on the lipid bilayer upon irradiation of HpIX were studied for lipid bilayers with POPC:Chol 1:1. Exposure of these bilayers to visible light in the presence of HpIX leads to several cholesterol oxidation products that were identified using GC-MS. A dramatic increase in the membrane leakiness was also observed, even for short irradiation times and small light intensities, as evaluated from the rate of pH equilibration and dithionite permeability. The relevance of these results for the mechanism of photodynamic therapy is discussed.

Perchlorate and nitrate treatment by ion exchange integrated with biological brine treatment.

PubMed

Lehman, S Geno; Badruzzaman, Mohammad; Adham, Samer; Roberts, Deborah J; Clifford, Dennis A

2008-02-01

Groundwater contaminated with perchlorate and nitrate was treated in a pilot plant using a commercially available ion exchange (IX) resin. Regenerant brine concentrate from the IX process, containing high perchlorate and nitrate, was treated biologically and the treated brine was reused in IX resin regeneration. The nitrate concentration of the feed water determined the exhaustion lifetime (i.e., regeneration frequency) of the resin; and the regeneration condition was determined by the perchlorate elution profile from the exhausted resin. The biological brine treatment system, using a salt-tolerant perchlorate- and nitrate-reducing culture, was housed in a sequencing batch reactor (SBR). The biological process consistently reduced perchlorate and nitrate concentrations in the spent brine to below the treatment goals of 500 microg ClO4(-)/L and 0.5mg NO3(-)-N/L determined by equilibrium multicomponent IX modeling. During 20 cycles of regeneration, the system consistently treated the drinking water to below the MCL of nitrate (10 mgNO3(-)-N/L) and the California Department of Health Services (CDHS) notification level of perchlorate (i.e., 6 microg/L). A conceptual cost analysis of the IX process estimated that perchlorate and nitrate treatment using the IX process with biological brine treatment to be approximately 20% less expensive than using the conventional IX with brine disposal.

The utilization of a non-invasive fluorescence imaging system to follow clinical dermatological MAL-PDT

NASA Astrophysics Data System (ADS)

Tyrrell, Jessica; Campbell, Sandra; Curnow, Alison

2009-06-01

This study employed a commercially available, non-invasive, fluorescence imaging system (Dyaderm, Biocam, Germany), to measure protoporphyrin IX (PpIX) concentration at several different stages during clinical dermatological methyl aminolevulinate photodynamic therapy (MAL-PDT). We validated the system prior to use to ensure that the PpIX changes witnessed were accurate and not due to environmental or user induced artifacts. The system was then employed to acquire color (morphological) and fluorescent (physiological) images simultaneously during dermatological PDT. Clinical data was collected from a range of licensed dermatological conditions (actinic keratosis, Bowen's disease and superficial basal cell carcinoma) during initial and subsequent PDT treatment cycles. The initial clinical data indicated that each type of licensed lesion considered responded in a similar manner following the application of Metvix (Galderma, U.K.) and the subsequent light irradiation (Aktilite, Galderma, U.K.). Images acquired three hours after Metvix application showed a significant increase in PpIX concentration within the lesion (P < 0.05), whilst PpIX levels in the surrounding normal tissue remained unaltered. After irradiation, the PpIX concentration was significantly decreased and returned to a level similar to the initial concentration originally observed. Lesions that received subsequent treatment cycles accumulated significantly less PpIX (P < 0.05) prior to irradiation.

Analysis of transcriptional isoforms of collagen types IX, II, and I in the developing avian cornea by competitive polymerase chain reaction.

PubMed

Fitch, J M; Gordon, M K; Gibney, E P; Linsenmayer, T F

1995-01-01

The genes for the alpha 1(IX), alpha 1(II), and alpha 2(I) collagen chains can give rise to different isoforms of mRNA, generated by alternative promotor usage [for alpha 1(IX) and alpha 2(I)] or alternative splicing [for alpha 1(II)]. In this study, we employed competitive reverse transcriptase PCR to quantitate the amounts of transcriptional isoforms for these genes in the embryonic avian cornea from its inception (about 3 1/2 days of development) to 11 days. In order to compare values at different time points, the results were normalized to those obtained for the "housekeeping" enzyme, glycerol-3-phosphate dehydrogenase (G3PDH). These values were compared to those obtained from other tissues (anterior optic cup and cartilage) that synthesize different combinations of the collagen isoforms. We found that, in the cornea, transcripts from the upstream promotor of alpha 1(IX) collagen (termed "long IX") were predominant at stage 18-20 (about 3 1/2 days), but then fell rapidly, and remained at a low level. By 5 days (just before stromal swelling) the major mRNA isoform of alpha 1(IX) was from the downstream promoter (termed "short IX"). The relative amount of transcript for the short form of type IX collagen rose to a peak at about 6 days of development, and then declined. Throughout this period, the predominant transcriptional isoform of the collagen type II gene was IIA (i.e., containing the alternatively spliced exon 2). This indicates that the molecules of type II collagen that are assembled into heterotypic fibrils with type I collagen possess, at least transiently, an amino-terminal globular domain similar to that found in collagen types I, III, and V. For type I, the "bone/tendon" mRNA isoform of the alpha 2(I) collagen gene was predominant; transcripts from the downstream promotor were at basal levels. In other tissues expressing collagen types IX and II, long IX was expressed predominantly with the IIA form in the anterior optic cup at stage 22/23; in 14 1/2 day cartilage, long IX was expressed predominantly along with the IIB form of alpha 1(II). The downstream transcript of the alpha 2(I) gene (Icart) was found at high levels only in cartilage.

Single-shot imaging with higher-dimensional encoding using magnetic field monitoring and concomitant field correction.

PubMed

Testud, Frederik; Gallichan, Daniel; Layton, Kelvin J; Barmet, Christoph; Welz, Anna M; Dewdney, Andrew; Cocosco, Chris A; Pruessmann, Klaas P; Hennig, Jürgen; Zaitsev, Maxim

2015-03-01

PatLoc (Parallel Imaging Technique using Localized Gradients) accelerates imaging and introduces a resolution variation across the field-of-view. Higher-dimensional encoding employs more spatial encoding magnetic fields (SEMs) than the corresponding image dimensionality requires, e.g. by applying two quadratic and two linear spatial encoding magnetic fields to reconstruct a 2D image. Images acquired with higher-dimensional single-shot trajectories can exhibit strong artifacts and geometric distortions. In this work, the source of these artifacts is analyzed and a reliable correction strategy is derived. A dynamic field camera was built for encoding field calibration. Concomitant fields of linear and nonlinear spatial encoding magnetic fields were analyzed. A combined basis consisting of spherical harmonics and concomitant terms was proposed and used for encoding field calibration and image reconstruction. A good agreement between the analytical solution for the concomitant fields and the magnetic field simulations of the custom-built PatLoc SEM coil was observed. Substantial image quality improvements were obtained using a dynamic field camera for encoding field calibration combined with the proposed combined basis. The importance of trajectory calibration for single-shot higher-dimensional encoding is demonstrated using the combined basis including spherical harmonics and concomitant terms, which treats the concomitant fields as an integral part of the encoding. © 2014 Wiley Periodicals, Inc.

Knock-out of the magnesium protoporphyrin IX methyltransferase gene in Arabidopsis. Effects on chloroplast development and on chloroplast-to-nucleus signaling

PubMed Central

Pontier, Dominique; Albrieux, Catherine; Joyard, Jacques; Lagrange, Thierry; Block, Maryse

2007-01-01

Protoporphyrin IX is the last common intermediate between the haem and chlorophyll biosynthesis pathways. The addition of Mg directs this molecule toward chlorophyll biosynthesis. The first step downstream from the branchpoint is catalyzed by the Mg chelatase and is a highly regulated process. The corresponding product, Mg protoporphyrin IX, has been proposed to play an important role as a signaling molecule implicated in plastid-to-nucleus communication. In order to get more information on the chlorophyll biosynthesis pathway and on Mg protoporphyrin IX derivative functions, we have identified an Mg protoporphyrin IX methyltransferase (CHLM) knock-out mutant in Arabidopsis in which the mutation induces a blockage downstream from Mg protoporphyrin IX and an accumulation of this chlorophyll biosynthesis intermediate. Our results demonstrate that the CHLM gene is essential for the formation of chlorophyll and subsequently for the formation of photosystems I and II and cyt b6f complexes. Analysis of gene expression in the chlm mutant provides an independent indication that Mg protoporphyrin IX is a negative effector of nuclear photosynthetic gene expression, as previously reported. Moreover, it suggests the possible implication of Mg protoporphyrin IX methylester, the product of CHLM, in chloroplast-to-nucleus signaling. Finally, post-transcriptional up-regulation of the level of the CHLH subunit of the Mg chelatase has been detected in the chlm mutant and most likely corresponds to specific accumulation of this protein inside plastids. This result suggests that the CHLH subunit might play an important regulatory role when the chlorophyll biosynthetic pathway is disrupted at this particular step. PMID:17135235

Title IX and Pregnancy Discrimination in Higher Education: The New Frontier.

PubMed

Mason, Mary Ann; Younger, Jaclyn

2014-01-01

Pregnancy discrimination is a little known area covered by Title IX. According to the Title IX regulations, areas of prohibited discrimination include: admissions; hiring; coursework accommodations and completion; pregnancy leave policies and status protection upon return from leave; and health insurance coverage. These regulations will soon get more attention as the Obama Administration insists on Title IX dissemination and compliance in an effort to stop the leaky pipeline for women in the STEM fields. Research shows that pregnancy and childbirth are the major reasons why women drop out of research science in much greater numbers than men; this dropout is most likely to occur among graduate students and postdoctoral fellows who are in their peak childbearing years. A similar pattern of dropout can be seen in all fields, including related professional schools. Research also reveals that there are currently few established policies in higher education which adequately address pregnancy and childbirth in formal policies for students. This article will address new efforts by the United States Department of Education and the federal agencies to begin to seek compliance relating to Title IX and pregnancy discrimination in educational institutions. It will discuss the recent successful efforts of the U.S. Department of Education's Office for Civil Rights in investigating and settling pregnancy discrimination claims as well as the lessons learned in private action lawsuits under Title IX. Title IX private action suits have transformed athletics for women, and more recently Title IX has been applied in sexual harassment cases. Pregnancy discrimination is now the new frontier.

Different Duck Species Infected Intramuscularly with Duck-Origin Genotype IX APMV-1 Show Discrepant Mortality and Indicate Another Fatal Genotype APMV-1 to Ducks.

PubMed

Fu, Guanghua; Cheng, Longfei; Fu, Qiuling; Qi, Baomin; Chen, Cuiteng; Shi, Shaohua; Chen, Hongmei; Wan, Chunhe; Liu, Rongchang; Huang, Yu

2017-03-01

Isolations of genotype IX (gIX) avian paramyxovirus type 1 (APMV-1) from various bird species have been more common recently, with isolates showing variable pathogenicity in different species of poultry. Here we sequenced the genome of a Muscovy duck origin gIX virus strain XBT14 and characterized the virulence and pathogenicity of this isolate in chickens and ducks. The genome sequence of strain XBT14 is 15,192 nt in length, containing multiple basic amino acids at the fusion protein cleavage site. The XBT14 strain shared 91.6%-91.9% nucleotide identities with early-genotype viruses (such as genotype III and IV) and shared 85.3%-85.9% nucleotide homologies with later genotype viruses (such as genotype VII). Pathogenicity tests showed that strain XBT14 could cause death in different duck breeds with a mortality rate of 44.4% in Muscovy duck, 25.9% in Sheldrake, and 11.1% in Cherry Valley duck, respectively. Similar mortality discrepancies were also observed in different ducks when infected with chicken-origin gIX virus strain F48E8. These results indicate that XBT14-like velogenic gIX APMV-1 (such as XBT14, F48E8, and GD09-2) could cause fatal infection in duck, and genotype IX is another genotype velogenic to duck as well as genotype VII. Accompanied by genetic differences in the vaccine strains or dominant strains prevailing in poultry, the virulent XBT14-like gIX viruses might become potentially endemic strains in poultry in the future.

Phototoxicity, dark-toxicity, and uptake-kinetics of natural hydrophilic and hydrophobic porphyrins in endothelial cells

NASA Astrophysics Data System (ADS)

Akguen, Nermin; Sailer, Reinhard; Kunzi-Rapp, Karin; Schneckenburger, Herbert; Beck, Gerd C.; Rueck, Angelika C.

1996-01-01

The phototoxicity, darktoxicity and uptake kinetics of three natural porphyrins (Uropoprhyrin III; UP III, Coproporphyrin III; CP III and Protoporphyrin IX; PP IX) were investigated in vitro using the BKEz-7 aorta endothelial cells of the calf. The cells were incubated with the porphyrins in different concentrations (0.5 (mu) M PP IX; 50 (mu) M UP III and CP III). After 24 h incubation they were irradiated in the case of PP IX with an Ar+-dye- laser at 635 nm and in the case of UP III and CP III with a Kr+-laser at 407 nm: While PP IX was phototoxic at low concentrations (0.5 (mu) M) and low energies (10 J/cm2), irradiation of UP III and CP III hardly induced phototoxicity even at higher concentrations. The same could be observed for the darktoxicity. PP IX was darktoxic at relatively low concentrations (1 (mu) M). In addition PP IX was taken up much faster and in greater amounts into the endothelial cells than UP III and CP III. These results could be due to the different structures of the sensitizers and/or to different uptake mechanisms. PP IX is a hydrophobic sensitizer while UP III and CP III are both hydrophilic molecules. A different uptake mechanism and accumulation in endothelial cells is quite probable. This hypothesis was confirmed with video-microscopy. In addition to the experiments in vitro, the cellular uptake and distribution of the sensitizers were observed in an appropriate in vivo model of the Chorioallantoismembrane (CAM).

An open-label, randomized, multicenter study of the safety, tolerability, and immunogenicity of quadrivalent human papillomavirus (types 6/11/16/18) vaccine given concomitantly with diphtheria, tetanus, pertussis, and poliomyelitis vaccine in healthy adolescents 11 to 17 years of age.

PubMed

Vesikari, Timo; Van Damme, Pierre; Lindblad, Niklas; Pfletschinger, Ulrich; Radley, David; Ryan, Desmond; Vuocolo, Scott; Haupt, Richard M; Guris, Dalya

2010-04-01

GARDASIL/SILGARD is a quadrivalent human papillomavirus (HPV) vaccine with activity against HPV 6/11/16/18. In many countries, GARDASIL is recommended for routine use among adolescents at the same age as other vaccines. In this study, we evaluated the immunogenicity and safety of GARDASIL administered concomitantly with REPEVAX (diphtheria, tetanus, acellular pertussis, and poliomyelitis vaccine). This was an open-label, randomized, multicenter study. We enrolled males (n = 260) and females (n = 583) aged 11 to 17 years. All subjects received a 0.5 mL dose of GARDASIL at day 1, month 2, and month 6, and a 0.5 mL dose of REPEVAX either on day 1 (opposite limb from GARDASIL) or at month 1. Antibody levels for all vaccine components were measured. We monitored systemic and injection-site adverse experiences (AEs) and serious adverse experiences. Immune response for all GARDASIL antigens following concomitant administration of the vaccines was demonstrated noninferior to nonconcomitant administration. Seroconversion for HPV 6, 11, 16, and 18 was >99.7% in both concomitant and nonconcomitant vaccination groups. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, and all polio and pertussis antigens. Concomitant administration of the 2 vaccines was generally well-tolerated, although there was a small increase in headache and injection-site swelling in the concomitant group. Overall, concomitant administration of GARDASIL and REPEVAX was generally well-tolerated and did not interfere with the immune response to either vaccine. Concomitant administration of vaccines would minimize the number of visits required to deliver each vaccine individually.

KSC-2009-3690

NASA Image and Video Library

2009-06-12

CAPE CANAVERAL, Fla. – In the Rotation, Processing, and Surge Facility at NASA's Kennedy Space Center in Florida, the Ares I-X aft skirt is mated to the aft segment. The complete Ares I-X will be assembled in the Vehicle Assembly Building. The launch of Ares I-X is targeted for August 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-3692

NASA Image and Video Library

2009-06-12

CAPE CANAVERAL, Fla. – In the Rotation, Processing, and Surge Facility at NASA's Kennedy Space Center in Florida, the Ares I-X aft skirt is mated to the aft segment. The complete Ares I-X will be assembled in the Vehicle Assembly Building. The launch of Ares I-X is targeted for August 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-3691

NASA Image and Video Library

2009-06-12

CAPE CANAVERAL, Fla. – In the Rotation, Processing, and Surge Facility at NASA's Kennedy Space Center in Florida, the Ares I-X aft skirt is mated to the aft segment. The complete Ares I-X will be assembled in the Vehicle Assembly Building. The launch of Ares I-X is targeted for August 2009. Photo credit: NASA/Jack Pfaller

Sex Discrimination Against Students: Implications of Title IX of the Education Amendments of 1972.

ERIC Educational Resources Information Center

Dunkle, Margaret C.; Sandler, Bernice

Title IX of the Education Amendments of 1972 mandates that sex discrimination be eliminated in federally assisted education programs. Title IX has significant implications for a variety of issues including recruiting, admissions, financial aid, student rules and regulations, housing rules, health care and insurance benefits, student employment,…

Physical Education, Part I. Options in Education, Program No. 99.

ERIC Educational Resources Information Center

George Washington Univ., Washington, DC. Inst. for Educational Leadership.

This transcript of a National Public Radio broadcast discusses the impact of Title IX on elementary and secondary physical education. Topics covered include competition, difficulties involved in the sex integration of sports, statements on Title IX by five chief state school officers, the experience of Massachusetts in implementing Title IX, and…

A Place on the Team: The Triumph and Tragedy of Title IX

ERIC Educational Resources Information Center

Suggs, Welch

2006-01-01

"A Place on the Team" is the inside story of how Title IX revolutionized American sports. The federal law guaranteeing women's rights in education, Title IX opened gymnasiums and playing fields to millions of young women previously locked out. Journalist Welch Suggs chronicles both the law's successes and failures-the exciting…

Title IX Compliance at Two-Year Colleges: An Analysis of Perceived Barriers and Strategies

ERIC Educational Resources Information Center

Causby, Cory Scott

2010-01-01

Although Title IX legislation has been in effect since 1972 and has created unprecedented positive change on intercollegiate athletics, educational institutions have still had difficulty meeting the basic requirements set forth by Title IX and ensuring gender equity in their athletic programs. Additionally, specific research has been largely…

KSC-2009-5541

NASA Image and Video Library

2009-10-20

CAPE CANAVERAL, Fla. - Inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the 327-foot-tall Ares I-X rocket stands on its mobile launcher platform. The transfer of the pad from the Space Shuttle Program to the Constellation Program took place May 31. Modifications made to the pad include the removal of shuttle unique subsystems, such as the orbiter access arm and a section of the gaseous oxygen vent arm, along with the installation of three 600-foot lightning towers, access platforms, environmental control systems and a vehicle stabilization system. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

Development of a functionalized UV-emitting nanocomposite for the treatment of cancer using indirect photodynamic therapy.

PubMed

Sengar, Prakhar; Juárez, Patricia; Verdugo-Meza, Andrea; Arellano, Danna L; Jain, Akhil; Chauhan, Kanchan; Hirata, Gustavo A; Fournier, Pierrick G J

2018-02-27

Photodynamic therapy is a promising cancer therapy modality but its application for deep-seated tumor is mainly hindered by the shallow penetration of visible light. X-ray-mediated photodynamic therapy (PDT) has gained a major attention owing to the limitless penetration of X-rays. However, substantial outcomes have still not been achieved due to the low luminescence efficiency of scintillating nanoparticles and weak energy transfer to the photosensitizer. The present work describes the development of Y 2.99 Pr 0.01 Al 5 O 12 -based (YP) mesoporous silica coated nanoparticles, multifunctionalized with protoporphyrin IX (PpIX) and folic acid (YPMS@PpIX@FA) for potential application in targeted deep PDT. A YP nanophosphor core was synthesized using the sol-gel method to be used as X-ray energy transducer and was then covered with a mesoporous silica layer. The luminescence analysis indicated a good spectral overlap between the PpIX and nanoscintillator at the Soret as well as Q-band region. The comparison of the emission spectra with or without PpIX showed signs of energy transfer, a prerequisite for deep PDT. In vitro studies showed the preferential uptake of the nanocomposite in cancer cells expressing the folate receptorFolr1, validating the targeting efficiency. Direct activation of conjugated PpIX with UVA in vitro induced ROS production causing breast and prostate cancer cell death indicating that the PpIX retained its activity after conjugation to the nanocomposite. The in vivo toxicity analysis showed the good biocompatibility and non-immunogenic response of YPMS@PpIX@FA. Our results indicate that YPMS@PpIX@FA nanocomposites are promising candidates for X-ray-mediated PDT of deep-seated tumors. The design of these nanoparticles allows the functionalization with exchangeable targeting ligands thus offering versatility, in order to target various cancer cells, expressing different molecular targets on their surface.

Comparison of protoporphyrin IX content and related gene expression in the tissues of chickens laying brown-shelled eggs.

PubMed

Li, Guangqi; Chen, Sirui; Duan, Zhongyi; Qu, Lujiang; Xu, Guiyun; Yang, Ning

2013-12-01

Protoporphyrin IX (PpIX), an immediate precursor of heme, is the main pigment resulting in the brown coloration of eggshell. The brownness and uniformity of the eggshell are important marketing considerations. In this study, 9 chickens laying darker brown shelled eggs and 9 chickens laying lighter brown shelled eggs were selected from 464 individually caged layers in a Rhode Island Red pureline. The PpIX contents were measured with a Microplate Reader at the wavelength of 412 nm and were compared in different tissues of the 2 groups. Although no significant difference in serum, bile, and excreta was found between the 2 groups, PpIX content in the shell gland and eggshell of the darker group was higher than in those of the lighter group, suggesting that PpIX was synthesized in the shell gland. We further determined the expression levels of 8 genes encoding enzymes involved in the heme synthesis and transport in the liver and shell gland at 6 h postoviposition by quantitative PCR. The results showed that expression of aminolevulinic acid synthase-1 (ALAS1) was higher in the liver of hens laying darker brown shelled eggs, whereas in the shell gland the expression levels of ALAS1, coproporphyrinogen oxidase (CPOX), ATP-binding cassette family members ABCB7 and ABCG2, and receptor for feline leukemia virus, subgroup C (FLVCR) were significantly higher in the hens laying darker brown shelled eggs. Our results demonstrated that hens laying darker brown shelled eggs could deposit more PpIX onto the eggshell and the brownness of the eggshell was dependent on the total quantity of PpIX in the eggshell. More heme was synthesized in the liver and shell gland of hens laying darker brown shelled eggs than those of hens laying lighter brown shelled eggs. High expression level of ABCG2 might facilitate the accumulation of PpIX in the shell gland.

Comparing high-resolution microscopy techniques for potential intraoperative use in guiding low-grade glioma resections.

PubMed

Meza, Daphne; Wang, Danni; Wang, Yu; Borwege, Sabine; Sanai, Nader; Liu, Jonathan T C

2015-04-01

Fluorescence image-guided surgery (FIGS), with contrast provided by 5-ALA-induced PpIX, has been shown to enable a higher extent of resection of high-grade gliomas. However, conventional FIGS with low-power microscopy lacks the sensitivity to aid in low-grade glioma (LGG) resection because PpIX signal is weak and sparse in such tissues. Intraoperative high-resolution microscopy of PpIX fluorescence has been proposed as a method to guide LGG resection, where sub-cellular resolution allows for the visualization of sparse and punctate mitochondrial PpIX production in tumor cells. Here, we assess the performance of three potentially portable high-resolution microscopy techniques that may be used for the intraoperative imaging of human LGG tissue samples with PpIX contrast: high-resolution fiber-optic microscopy (HRFM), high-resolution wide-field microscopy (WFM), and dual-axis confocal (DAC) microscopy. Thick unsectioned human LGG tissue samples (n = 7) with 5-ALA-induced PpIX contrast were imaged using three imaging techniques (HRFM, WFM, DAC). The average signal-to-background ratio (SBR) was then calculated for each imaging modality (5 images per tissue, per modality). HRFM provides the ease of use and portability of a flexible fiber bundle, and is simple and inexpensive to build. However, in most cases (6/7), HRFM is not capable of detecting PpIX signal from LGGs due to high autofluorescence, generated by the fiber bundle under laser illumination at 405 nm, which overwhelms the PpIX signal and impedes its visualization. WFM is a camera-based method possessing high lateral resolution but poor axial resolution, resulting in sub-optimal image contrast. Consistent successful detection of PpIX signal throughout our human LGG tissue samples (n = 7), with an acceptable image contrast (SBR >2), was only achieved using DAC microscopy, which offers superior image resolution and contrast that is comparable to histology, but requires a laser-scanning mechanism to achieve optical sectioning. © 2015 Wiley Periodicals, Inc.

Ares I-X Flight Test--The Future Begins Here

NASA Technical Reports Server (NTRS)

Davis, Stephan R.; Tuma, Margaret L.; Heitzman, Keith

2007-01-01

In less than two years, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will eventually send humans to the Moon, Mars, and beyond. As the countdown to this first Ares mission continues, personnel from across the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for a 2009 launch. This paper will discuss the hardware and programmatic progress of the Ares I-X mission.

KSC-2009-3120

NASA Image and Video Library

2009-05-11

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the framework known as the "birdcage" lowers the Ares I-X simulator crew module-launch abort system, or CM-LAS, onto the simulator service module-service adapter stack. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for August 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-3122

NASA Image and Video Library

2009-05-11

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the framework known as the "birdcage" lowers the Ares I-X simulator crew module-launch abort system, or CM-LAS, onto the simulator service module-service adapter stack. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for August 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-3121

NASA Image and Video Library

2009-05-11

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the framework known as the "birdcage" lowers the Ares I-X simulator crew module-launch abort system, or CM-LAS, onto the simulator service module-service adapter stack. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for August 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-3124

NASA Image and Video Library

2009-05-11

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, a technician checks the mating from the inside of the Ares I-X simulator crew module-launch abort system, or CM-LAS, with the simulator service module-service adapter stack. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for August 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-3123

NASA Image and Video Library

2009-05-11

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the framework known as the "birdcage" lowers the Ares I-X simulator crew module-launch abort system, or CM-LAS, onto the simulator service module-service adapter stack. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for August 2009. Photo credit: NASA/Kim Shiflett

Red-light excitation of protoporphyrin IX fluorescence for subsurface tumor detection.

PubMed

Roberts, David W; Olson, Jonathan D; Evans, Linton T; Kolste, Kolbein K; Kanick, Stephen C; Fan, Xiaoyao; Bravo, Jaime J; Wilson, Brian C; Leblond, Frederic; Marois, Mikael; Paulsen, Keith D

2018-06-01

OBJECTIVE The objective of this study was to detect 5-aminolevulinic acid (ALA)-induced tumor fluorescence from glioma below the surface of the surgical field by using red-light illumination. METHODS To overcome the shallow tissue penetration of blue light, which maximally excites the ALA-induced fluorophore protoporphyrin IX (PpIX) but is also strongly absorbed by hemoglobin and oxyhemoglobin, a system was developed to illuminate the surgical field with red light (620-640 nm) matching a secondary, smaller absorption peak of PpIX and detecting the fluorescence emission through a 650-nm longpass filter. This wide-field spectroscopic imaging system was used in conjunction with conventional blue-light fluorescence for comparison in 29 patients undergoing craniotomy for resection of high-grade glioma, low-grade glioma, meningioma, or metastasis. RESULTS Although, as expected, red-light excitation is less sensitive to PpIX in exposed tumor, it did reveal tumor at a depth up to 5 mm below the resection bed in 22 of 24 patients who also exhibited PpIX fluorescence under blue-light excitation during the course of surgery. CONCLUSIONS Red-light excitation of tumor-associated PpIX fluorescence below the surface of the surgical field can be achieved intraoperatively and enables detection of subsurface tumor that is not visualized under conventional blue-light excitation. Clinical trial registration no.: NCT02191488 (clinicaltrials.gov).

A Perspective on Development Flight Instrumentation and Flight Test Analysis Plans for Ares I-X

NASA Technical Reports Server (NTRS)

Huebner, Lawrence D.; Richards, James S.; Brunty, Joseph A.; Smith, R. Marshall; Trombetta, Dominic R.

2009-01-01

NASA. s Constellation Program will take a significant step toward completion of the Ares I crew launch vehicle with the flight test of Ares I-X and completion of the Ares I-X post-flight evaluation. The Ares I-X flight test vehicle is an ascent development flight test that will acquire flight data early enough to impact the design and development of the Ares I. As the primary customer for flight data from the Ares I-X mission, Ares I has been the major driver in the definition of the Development Flight Instrumentation (DFI). This paper focuses on the DFI development process and the plans for post-flight evaluation of the resulting data to impact the Ares I design. Efforts for determining the DFI for Ares I-X began in the fall of 2005, and significant effort to refine and implement the Ares I-X DFI has been expended since that time. This paper will present a perspective in the development and implementation of the DFI. Emphasis will be placed on the process by which the list was established and changes were made to that list due to imposed constraints. The paper will also discuss the plans for the analysis of the DFI data following the flight and a summary of flight evaluation tasks to be performed in support of tools and models validation for design and development.

In vivo wide-field multispectral dosimeter for use in ALA-PpIX based photodynamic therapy of skin

NASA Astrophysics Data System (ADS)

LaRochelle, Ethan P. M.; Davis, Scott C.; de Souza, Ana Luiza Ribeiro; Pogue, Brian W.

2017-02-01

Photodynamic therapy (PDT) for Actinic Kertoses (AK) using aminoluvelinic acid (ALA) is an FDA-approved treatment, which is generally effective, yet response rates vary. The origin of the variability is not well characterized, but may be related to inter-patient variability in the production of protoporphyrin IX (PpIX). While fiber-based point probe systems provide a method for measuring PpIX production, these measurements have demonstrated large spatial and inter-operator variability. Thus, in an effort to improve patient-specific dosimetry and treatment it is important to develop a robust system that accounts for spatial variability and reduces the chance of operator errors. To address this need, a wide-field multispectral imaging system was developed that is capable of quantifying maps of PpIX in both liquid phantoms and in vivo experiments, focusing on high sensitivity light signals. The system uses both red and blue excitation to elicit a fluorescent response at varying skin depths. A ten-position filter wheel with bandpass filters ranging from 635nm to 710nm are used to capture images along the emission band. A linear least-square spectral fitting algorithm provides the ability to decouple background autofluorescence from PpIX fluorescence, which has improved the system sensitivity by an order of magnitude, detecting nanomolar PpIX concentrations in liquid phantoms in the presence of 2% whole blood and 2% intralipid.

Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-defined glioma stem cells by iron chelation

PubMed Central

Wang, Wenqian; Tabu, Kouichi; Hagiya, Yuichiro; Sugiyama, Yuta; Kokubu, Yasuhiro; Murota, Yoshitaka; Ogura, Shun-ichiro; Taga, Tetsuya

2017-01-01

Cancer stem cells (CSCs) are dominantly responsible for tumor progression and chemo/radio-resistance, resulting in tumor recurrence. 5-aminolevulinic acid (ALA) is metabolized to fluorescent protoporphyrin IX (PpIX) specifically in tumor cells, and therefore clinically used as a reagent for photodynamic diagnosis (PDD) and therapy (PDT) of cancers including gliomas. However, it remains to be clarified whether this method could be effective for CSC detection. Here, using flow cytometry-based analysis, we show that side population (SP)-defined C6 glioma CSCs (GSCs) displayed much less 5-ALA-derived PpIX fluorescence than non-GSCs. Among the C6 GSCs, cells with ultralow PpIX fluorescence exhibited dramatically higher tumorigenicity when transplanted into the immune-deficient mouse brain. We further demonstrated that the low PpIX accumulation in the C6 GSCs was enhanced by deferoxamine (DFO)-mediated iron chelation, not by reserpine-mediated inhibition of PpIX-effluxing ABCG2. Finally, we found that the expression level of the gene for heme oxygenase-1 (HO-1), a heme degradation enzyme, was high in C6 GSCs, which was further up-regulated when treated with 5-ALA. Our results provide important new insights into 5-ALA-based PDD of gliomas, particularly photodetection of SP-defined GSCs by iron chelation based on their ALA-PpIX-Heme metabolism. PMID:28169355

Antipsychotic treatment among youth in foster care.

PubMed

Dosreis, Susan; Yoon, Yesel; Rubin, David M; Riddle, Mark A; Noll, Elizabeth; Rothbard, Aileen

2011-12-01

Despite national concerns over high rates of antipsychotic medication use among youth in foster care, concomitant antipsychotic use has not been examined. In this study, concomitant antipsychotic use among Medicaid-enrolled youth in foster care was compared with disabled or low-income Medicaid-enrolled youth. The sample included 16 969 youths younger than 20 years who were continuously enrolled in a Mid-Atlantic state Medicaid program and had ≥1 claim with a psychiatric diagnosis and ≥1 antipsychotic claim in 2003. Antipsychotic treatment was characterized by days of any use and concomitant use with ≥2 overlapping antipsychotics for >30 days. Medicaid program categories were foster care, disabled (Supplemental Security Income), and Temporary Assistance for Needy Families (TANF). Multicategory involvement for youths in foster care was classified as foster care/Supplemental Security Income, foster care/TANF, and foster care/adoption. We used multivariate analyses, adjusting for demographics, psychiatric comorbidities, and other psychotropic use, to assess associations between Medicaid program category and concomitant antipsychotic use. Average antipsychotic use ranged from 222 ± 110 days in foster care to only 135 ± 101 days in TANF (P < .001). Concomitant use for ≥180 days was 19% in foster care only and 24% in foster care/adoption compared with <15% in the other categories. Conduct disorder and antidepressant or mood-stabilizer use was associated with a higher likelihood of concomitant antipsychotic use (P < .0001). Additional study is needed to assess the clinical rationale, safety, and outcomes of concomitant antipsychotic use and to inform statewide policies for monitoring and oversight of antipsychotic use among youths in the foster care system.

ARES I-X Launch Prep

NASA Image and Video Library

2009-10-25

NASA's Ares I-X rocket is seen on launch pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Monday, Oct. 26, 2009. The flight test of Ares I-X, scheduled for Tuesday, Oct. 27, 2009, will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I.

ARES I-X Launch

NASA Image and Video Library

2009-10-27

NASA Ares I-X mission managers watch as NASA's Ares I-X rocket launches from pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Wednesday, Oct. 28, 2009. The flight test will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

"What Do I Think about Title IX?" Voices from a University Community

ERIC Educational Resources Information Center

Paule-Koba, Amanda L.; Harris, Othello; Freysinger, Valeria J.

2013-01-01

Despite the apparent benefits of Title IX, the implementation of the law remains controversial, and there are divergent beliefs regarding its impact on collegiate sport. The purpose of this study was to examine how members of a university community, whose intercollegiate sport programs have changed, perceive and make sense of Title IX and the…

Not Second-Class: Title IX, Equity, and Girls' High School Sports

ERIC Educational Resources Information Center

Stader, David L.; Surface, Jeanne L.

2014-01-01

Title IX is designed to protect students from discrimination based on sex in any educational institution that receives financial assistance. This article focuses on Title IX as it applies to high school athletic programs by considering the trial of a high school district in California. A federal court found considerable inequalities between boys…

Tilting the Playing Field: Schools, Sports, Sex and Title IX.

ERIC Educational Resources Information Center

Gavora, Jessica

This book suggests that Title IX of the Education Amendments is not creating more female athletes but instead eliminating some of the most prestigious men's sports programs in the name of gender equity. It shows how Title IX has affected every aspect of education, from kindergarten through graduate school, making profound changes in areas as…

A License for Bias: Sex Discrimination, Schools, and Title IX.

ERIC Educational Resources Information Center

Morse, Susan Ed.

This report discusses non-sports-related Title IX complaints filed with the Department of Education's Office for Civil Rights (OCR) from 1993-1997. Its purpose is to dispel the popular belief that Title IX is a sports-equity law and to determine the effectiveness of the legislation. The document examines the kinds of complaints filed, the status…

Multi-spectral wide-field imaging for PplX PDT dosimetry of skin (Conference Presentation)

NASA Astrophysics Data System (ADS)

LaRochelle, Ethan; Chun, Hayden H.; Hasan, Tayyaba; Pogue, Brian W.; Maytin, Edward V.; Chapman, Michael S.; Davis, Scott C.

2016-03-01

Actinic Kertoses (AK) are common pre-cancerous lesions associated with sun-damaged skin. While generally benign, the condition can progress to squamous cell carcinoma (SCC) and is a particular concern for immunosuppressed patients who are susceptible to uncontrolled AK and SCC. Among the FDA-approved treatment options for AK, ALA-based photodynamic therapy is unique in that it is non-scarring and can be repeated on the same area. However, response rates vary widely due to variations in drug and light delivery, PpIX production, and tissue oxygenation. Thus, developing modalities to predict response is critical to enable patient-specific treatment-enhancing interventions. To that end, we have developed a wide-field spectrally-resolved fluorescence imaging system capable of red and blue light excitation. While blue light excites PpIX efficiently, poor photon penetration limits the image content to superficial layers of skin. Red light excitation, on the other hand, can reveal fluorescence information originating from deeper in tissue, which may provide relevant information about PpIX distribution. Our instrument illuminates the skin via a fiber-based ring illuminator, into which is coupled sequentially a white light source, and blue and red laser diodes. Light emitted from the tissue passes through a high-speed filter wheel with filters selected to resolve the PpIX emission spectrum. This configuration enables the use of spectral fitting to decouple PpIX fluorescence from background signal, improving sensitivity to low concentrations of PpIX. Images of tissue-simulating phantoms and animal models confirm a linear response to PpIX, and the ability to image sub-surface PpIX inaccessible with blue light using red excitation.

Differentiation of embryonic stem cells into hepatocytes that coexpress coagulation factors VIII and IX.

PubMed

Cao, Jun; Shang, Chang-zhen; Lü, Li-hong; Qiu, De-chuan; Ren, Meng; Chen, Ya-jin; Min, Jun

2010-11-01

To establish an efficient culture system to support embryonic stem (ES) cell differentiation into hepatocytes that coexpress F-VIII and F-IX. Mouse E14 ES cells were cultured in differentiation medium containing sodium butyrate (SB), basic fibroblast growth factor (bFGF), and/or bone morphogenetic protein 4 (BMP4) to induce the differentiation of endoderm cells and hepatic progenitor cells. Hepatocyte growth factor, oncostatin M, and dexamethasone were then used to induce the maturation of ES cell-derived hepatocytes. The mRNA expression levels of endoderm-specific genes and hepatocyte-specific genes, including the levels of F-VIII and F-IX, were detected by RT-PCR and real-time PCR during various stages of differentiation. Protein expression was examined by immunofluorescence and Western blot. At the final stage of differentiation, flow cytometry was performed to determine the percentage of cells coexpressing F-VIII and F-IX, and ELISA was used to detect the levels of F-VIII and F-IX protein secreted into the culture medium. The expression of endoderm-specific and hepatocyte-specific markers was upregulated to highest level in response to the combination of SB, bFGF, and BMP4. Treatment with the three inducers during hepatic progenitor differentiation significantly enhanced the mRNA and protein levels of F-VIII and F-IX in ES cell-derived hepatocytes. More importantly, F-VIII and F-IX were coexpressed with high efficiency at the final stage of differentiation, and they were also secreted into the culture medium. We have established a novel in vitro differentiation protocol for ES-derived hepatocytes that coexpress F-VIII and F-IX that may provide a foundation for stem cell replacement therapy for hemophilia.

Photocatalytic reduction of nitrate using titanium dioxide for regeneration of ion exchange brine

PubMed Central

Yang, Ting; Doudrick, Kyle; Westerhoff, Paul

2016-01-01

Nitrate is often removed from groundwater by ion exchange (IX) before its use as drinking water. Accumulation of nitrate in IX brine reduces the efficiency of IX regeneration and the useful life of the regeneration brine. For the first time, we present a strategy to photocatalytically reduce nitrate in IX brine, thereby extending the use of the brine. Titanium dioxide (Evonik P90), acting as photocatalyst, reduced nitrate effectively in both synthetic brines and sulfate-removed IX brine when formic acid (FA) was used as the hole scavenger (i.e., electron donor) and the initial FA to nitrate molar ratio (IFNR) was 5.6. Increasing the NaCl level in the synthetic brine slowed the nitrate reduction rate without affecting byproduct selectivity of ammonium and gaseous N species (e.g., N2, N2O). In a non-modified IX brine, nitrate removal was greatly inhibited owing to the presence of sulfate, which competed with nitrate for active surface sites on P90 and induced aggregation of P90 nanoparticles. After removing sulfate through barium sulfate precipitation, nitrate was effectively reduced; approximately 3.6 × 1024 photons were required to reduce each mole of nitrate to 83% N Gases and 17% NH4+. To make optimum use of FA and control the residual FA level in treated brine, the IFNR was varied. High IFNRs (e.g., 4, 5.6) were found to be more efficient for nitrate reduction but left higher residual FA in brine. IX column tests were performed to investigate the impact of residual FA for brine reuse. The residual FA in the brine did not significantly affect the nitrate removal capacity of IX resins, and formate contamination of treated water could be eliminated by rinsing with one bed volume of fresh brine. PMID:23276425

Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker

PubMed Central

Valdés, Pablo A.; Leblond, Frederic; Kim, Anthony; Harris, Brent T.; Wilson, Brian C.; Fan, Xiaoyao; Tosteson, Tor D.; Hartov, Alex; Ji, Songbai; Erkmen, Kadir; Simmons, Nathan E.; Paulsen, Keith D.; Roberts, David W.

2011-01-01

Object Accurate discrimination between tumor and normal tissue is crucial for optimal tumor resection. Qualitative fluorescence of protoporphyrin IX (PpIX), synthesized endogenously following δ-aminolevulinic acid (ALA) administration, has been used for this purpose in high-grade glioma (HGG). The authors show that diagnostically significant but visually imperceptible concentrations of PpIX can be quantitatively measured in vivo and used to discriminate normal from neoplastic brain tissue across a range of tumor histologies. Methods The authors studied 14 patients with diagnoses of low-grade glioma (LGG), HGG, meningioma, and metastasis under an institutional review board–approved protocol for fluorescence-guided resection. The primary aim of the study was to compare the diagnostic capabilities of a highly sensitive, spectrally resolved quantitative fluorescence approach to conventional fluorescence imaging for detection of neoplastic tissue in vivo. Results A significant difference in the quantitative measurements of PpIX concentration occurred in all tumor groups compared with normal brain tissue. Receiver operating characteristic (ROC) curve analysis of PpIX concentration as a diagnostic variable for detection of neoplastic tissue yielded a classification efficiency of 87% (AUC = 0.95, specificity = 92%, sensitivity = 84%) compared with 66% (AUC = 0.73, specificity = 100%, sensitivity = 47%) for conventional fluorescence imaging (p < 0.0001). More than 81% (57 of 70) of the quantitative fluorescence measurements that were below the threshold of the surgeon's visual perception were classified correctly in an analysis of all tumors. Conclusions These findings are clinically profound because they demonstrate that ALA-induced PpIX is a targeting biomarker for a variety of intracranial tumors beyond HGGs. This study is the first to measure quantitative ALA-induced PpIX concentrations in vivo, and the results have broad implications for guidance during resection of intracranial tumors. PMID:21438658

Highly sensitive fluorescence detection of metastatic lymph nodes of gastric cancer with photo-oxidation of protoporphyrin IX.

PubMed

Koizumi, N; Harada, Y; Beika, M; Minamikawa, T; Yamaoka, Y; Dai, P; Murayama, Y; Yanagisawa, A; Otsuji, E; Tanaka, H; Takamatsu, T

2016-08-01

The establishment of a precise and rapid method to detect metastatic lymph nodes (LNs) is essential to perform less invasive surgery with reduced gastrectomy along with reduced lymph node dissection. We herein describe a novel imaging strategy to detect 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence in excised LNs specifically with reduced effects of tissue autofluorescence based on photo-oxidation of PpIX. We applied the method in a clinical setting, and evaluated its feasibility. To reduce the unfavorable effect of autofluorescence, we focused on photo-oxidation of PpIX: Following light irradiation, PpIX changes into another substance, photo-protoporphyrin, via an oxidative process, which has a different spectral peak, at 675 nm, whereas PpIX has its spectral peak at 635 nm. Based on the unique spectral alteration, fluorescence spectral imaging before and after light irradiation and subsequent originally-developed image processing was performed. Following in vitro study, we applied this method to a total of 662 excised LNs obtained from 30 gastric cancer patients administered 5-ALA preoperatively. Specific visualization of PpIX was achieved in in vitro study. The method allowed highly sensitive detection of metastatic LNs, with sensitivity of 91.9% and specificity of 90.8% in the in vivo clinical trial. Receiver operating characteristic analysis indicated high diagnostic accuracy, with the area under the curve of 0.926. We established a highly sensitive and specific 5-ALA-induced fluorescence imaging method applicable in clinical settings. The novel method has a potential to become a useful tool for intraoperative rapid diagnosis of LN metastasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

KSC-2009-5548

NASA Image and Video Library

2009-10-20

CAPE CANAVERAL, Fla. - The Ares I-X rocket heads toward Launch Pad 39B at NASA's Kennedy Space Center in Florida, riding atop a crawler-transporter. The 4.2-mile trip to the pad from the massive Vehicle Assembly Building began at 1:39 a.m. EDT. The transfer of the pad from the Space Shuttle Program to the Constellation Program took place May 31. Modifications made to the pad include the removal of shuttle unique subsystems, such as the orbiter access arm and a section of the gaseous oxygen vent arm, along with the installation of three 600-foot lightning towers, access platforms, environmental control systems and a vehicle stabilization system. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5543

NASA Image and Video Library

2009-10-20

CAPE CANAVERAL, Fla. - With the work platforms retracted, the Ares I-X stands tall inside the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The platforms were retracted in preparation for the rocket's rollout to Launch Pad 39B. The transfer of the pad from the Space Shuttle Program to the Constellation Program took place May 31. Modifications made to the pad include the removal of shuttle unique subsystems, such as the orbiter access arm and a section of the gaseous oxygen vent arm, along with the installation of three 600-foot lightning towers, access platforms, environmental control systems and a vehicle stabilization system. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5546

NASA Image and Video Library

2009-10-20

CAPE CANAVERAL, Fla. - The towering 327-foot-tall Ares I-X rocket rides aboard a crawler-transporter as it exits the massive Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The rocket is bolted to its mobile launcher platform for the move to the launch pad. The transfer of the pad from the Space Shuttle Program to the Constellation Program took place May 31. Modifications made to the pad include the removal of shuttle unique subsystems, such as the orbiter access arm and a section of the gaseous oxygen vent arm, along with the installation of three 600-foot lightning towers, access platforms, environmental control systems and a vehicle stabilization system. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5529

NASA Image and Video Library

2009-10-20

CAPE CANAVERAL, Fla. – Spotlighted against the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the 327-foot-tall Ares I-X rocket begins its slow trek to Launch Pad 39B. The move, known as "rollout," began at 1:39 a.m. EDT. The transfer of the pad from the Space Shuttle Program to the Constellation Program took place May 31. Modifications made to the pad include the removal of shuttle unique subsystems, such as the orbiter access arm and a section of the gaseous oxygen vent arm, along with the installation of three 600-foot lightning towers, access platforms, environmental control systems and a vehicle stabilization system. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Jim Grossmann

Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms.

PubMed Central

Elcombe, C R; Mitchell, A M

1986-01-01

The exposure of cultured rat hepatocytes to mono(2-ethylhexyl)phthalate (MEHP) for 72 hr resulted in marked induction of peroxisomal enzyme activity (beta-oxidation; cyanide-insensitive palmitoyl CoA oxidase) and concomitant increases in the number of peroxisomes. Similar treatment of cultured guinea pig, marmoset, or human hepatocytes revealed little or no effect of MEHP. In order to eliminate possible confounding influences of biotransformation, the proximate peroxisome proliferator(s) derived from MEHP have been identified. Using cultured hepatocytes these agents were found to be metabolite VI [mono(2-ethyl-5-oxohexyl) phthalate] and metabolite IX [mono(2-ethyl-5-hydroxyhexyl) phthalate]. The addition of these "active" metabolites to cultured guinea pig, marmoset, or human hepatocytes again revealed little effect upon peroxisomes or related enzyme activities (peroxisomal beta-oxidation or microsomal lauric acid hydroxylation). These studies demonstrate a marked species difference in the response of hepatocytes to MEHP-elicited peroxisome proliferation. Preliminary studies have also suggested that peroxisome proliferation due to MEHP may be due to an initial biochemical lesion of fatty acid metabolism. Images FIGURE 4. a FIGURE 4. b PMID:3104023

Why, What and Where To? Title IX, Educational Amendment of 1972.

ERIC Educational Resources Information Center

Perry-Miller, Mitzi

Three years after Title IX of the Education Amendments of 1972 became law, the U. S. Department of Health, Education, and Welfare provided regulations for the implementation of Title IX. This report reviews the implications of these regulations as well as several of the court cases in which discrimination on the basis of sex has been declared…

ARES I-X Launch Prep

NASA Image and Video Library

2009-10-25

NASA's Ares I-X rocket is seen on launch pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Monday, Oct. 26, 2009. The flight test of Ares I-X, scheduled for Tuesday, Oct. 27, 2009, will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

An Annotated Summary of the Regulation for Title IX Education Amendments of 1972.

ERIC Educational Resources Information Center

NETWORK, Inc., Andover, MA.

This document is one of a two-part set of publications. Both deal with equal education and provide a concise overview of Title IX and gender equity issues in education and steps to take to ensure nondiscrimination and equal education opportunity for all. Title IX of the Education Amendments of 1972 is the major federal law prohibiting sex…

The Meanings of the Preposition "By" in the IX-XIX Centuries with Their Azerbaijani Equivalents

ERIC Educational Resources Information Center

Anvar Ghizi, Aliyeva Shalalah

2010-01-01

The article deals with the meanings of the English preposition "by" in the IX-XIX centuries and their Azerbaijani equivalents. During that period the preposition "by" had more than 10 variants of writing. From the IX to the XIX centuries the preposition "by" was used in 6 main meanings: the meanings were connected…

The Impact of Implementing Title IX in a Predominantly Black Public University.

ERIC Educational Resources Information Center

Simmons, Gertrude L.

Information on the impact of implementing Title IX of the 1972 Education Amendments at Florida A and M University, a predominantly Black public university, is presented. Title IX assures everyone regardless of sex an equal opportunity to learn a skill, choose a course of study, advance in status, participate in a sport, receive a scholarship, or…

The History, Uses, and Abuses of Title IX. 2016 Bulletin

ERIC Educational Resources Information Center

American Association of University Professors, 2016

2016-01-01

This report, an evaluation of the history and current uses of Title IX, is the result of a joint effort by a subcommittee that included members of the AAUP's Committee A on Academic Freedom and Tenure and the Committee on Women in the Academic Profession. The report identifies tensions between current interpretations of Title IX and the academic…

Hardware and Programmatic Progress on the Ares I-X Flight Test

NASA Technical Reports Server (NTRS)

Davis, Stephan R.

2008-01-01

In less than two years, the National Aeronautics and Space Administration (NASA) will execute the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle; which, together with the Ares V cargo launch vehicle (Figure 1), will eventually send humans to the Moon, Mars, and beyond. As the countdown to this first Ares mission continues, personnel from across the Ares I-X Mission Management Office (MMO) are finalizing designs and, in some cases, already fabricating vehicle hardware in preparation for an April 2009 launch. This paper will discuss the hardware and programmatic progress of the Ares I-X mission.

KSC-2009-1529

NASA Image and Video Library

2009-02-10

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center, the Ares I-X mock-up crew module displays the newly applied window decals. Ares I-X is the test flight for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of full-scale Ares I-X, targeted for July 2009, will be the first in a series of unpiloted rocket launches from Kennedy. When fully developed, the 16-foot diameter crew module will furnish living space and reentry protection for the astronauts. Photo credit: NASA/Tim Jacobs

KSC-2009-2796

NASA Image and Video Library

2009-04-20

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the yellow framework at left, nicknamed the "birdcage," is lifted high above the floor for a fit check with the Crew Module, or CM, and Launch Abort System, or LAS, assembly nearby for the Ares I-X rocket. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for July 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-1528

NASA Image and Video Library

2009-02-10

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center, a worker applies a window decal on the Ares I-X mock-up crew module. Ares I-X is the test flight for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of full-scale Ares I-X, targeted for July 2009, will be the first in a series of unpiloted rocket launches from Kennedy. When fully developed, the 16-foot diameter crew module will furnish living space and reentry protection for the astronauts. Photo credit: NASA/Tim Jacobs

KSC-2009-1896

NASA Image and Video Library

2009-02-26

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, a large overhead crane lowers the Ares I-X service module onto the service adapter. Workers check the precision of the connection. Ares I-X is the test flight for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X, targeted for July 2009, will be the first in a series of unpiloted rocket launches from Kennedy. Photo credit: NASA/Tim Jacobs

KSC-2009-1893

NASA Image and Video Library

2009-02-26

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, a large overhead crane lifts the Ares I-X service module, which will be mated to the service adapter in the bay. Ares I-X is the test flight for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X, targeted for July 2009, will be the first in a series of unpiloted rocket launches from Kennedy. Photo credit: NASA/Tim Jacobs

KSC-2009-3119

NASA Image and Video Library

2009-05-11

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the framework known as the "birdcage" lifts the Ares I-X simulator crew module-launch abort system, or CM-LAS. The CM-LAS stack will be mated with the simulator service module-service adapter stack. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for August 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-2830

NASA Image and Video Library

2009-04-27

CAPE CANAVERAL, Fla. –– The fifth segment simulator segments of the Ares I-X rocket have been moved to the transfer aisle of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The stacking operations with other segments in the VAB in June. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I, which is part of the Constellation Program to return men to the moon and beyond. Launch of the Ares I-X flight test is targeted for August 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-1897

NASA Image and Video Library

2009-02-26

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the installation of the Ares I-X service module onto the service adapter, at right, is complete. At left is the simulator crew module. Ares I-X is the test flight for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X, targeted for July 2009, will be the first in a series of unpiloted rocket launches from Kennedy. Photo credit: NASA/Tim Jacobs

KSC-2009-1892

NASA Image and Video Library

2009-02-26

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, workers attach a large overhead crane to the Ares I-X service module, on the floor. The module will be lifted and mated to the service adapter. Ares I-X is the test flight for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X, targeted for July 2009, will be the first in a series of unpiloted rocket launches from Kennedy. Photo credit: NASA/Tim Jacobs

KSC-2009-1527

NASA Image and Video Library

2009-02-10

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center, a worker applies a window decal on the Ares I-X mock-up crew module. Ares I-X is the test flight for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of full-scale Ares I-X, targeted for July 2009, will be the first in a series of unpiloted rocket launches from Kennedy. When fully developed, the 16-foot diameter crew module will furnish living space and reentry protection for the astronauts. Photo credit: NASA/Tim Jacobs

KSC-2009-2829

NASA Image and Video Library

2009-04-27

CAPE CANAVERAL, Fla. –– The fifth segment simulator segments of the Ares I-X rocket have been moved to the transfer aisle of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. The stacking operations with other segments in the VAB in June. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I, which is part of the Constellation Program to return men to the moon and beyond. Launch of the Ares I-X flight test is targeted for August 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-2795

NASA Image and Video Library

2009-04-20

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the yellow framework at left, nicknamed the "birdcage," is lifted for a fit check with the Crew Module, or CM, and Launch Abort System, or LAS, assembly in the foreground for the Ares I-X rocket. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for July 2009. Photo credit: NASA/Jack Pfaller

Implicit dosimetry of microorganism photodynamic inactivation

NASA Astrophysics Data System (ADS)

Tamošiūnas, Mindaugas; Kuliešienė, Neringa; Daugelavičius, Rimantas

2017-12-01

Photosensitization based antibacterial treatment is efficient against a broad range of pathogens but it utilizes suboptimal dosimetry with an explicit (and very broad range) determination of sensitizer concentration, light dose and fluence rates. In this study we verified the implicit dosimetry approach for pathogen photodynamic treatment, employing protoporphyrin IX (ppIX) photobleaching to assess the killing efficacy against Staphylococcus aureus and Candida albicans cells. The results show that there was an increased kill of S. aureus and C. albicans at higher degree of ppIX fluorescence decay. Therefore ppIX photobleaching can be incorporated into the PDI dose metric offering to predict the pathogen killing efficacy during photodynamic treatment.

Quantitative spatial frequency fluorescence imaging in the sub-diffusive domain for image-guided glioma resection

PubMed Central

Sibai, Mira; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Wilson, Brian C.

2015-01-01

Intraoperative 5- aminolevulinic acid induced-Protoporphyrin IX (PpIX) fluorescence guidance enables maximum safe resection of glioblastomas by providing surgeons with real-time tumor optical contrast. However, visual assessment of PpIX fluorescence is subjective and limited by the distorting effects of light attenuation and tissue autofluorescence. We have previously shown that non-invasive point measurements of absolute PpIX concentration identifies residual tumor that is otherwise non-detectable. Here, we extend this approach to wide-field quantitative fluorescence imaging by implementing spatial frequency domain imaging to recover tissue optical properties across the field-of-view in phantoms and ex vivo tissue. PMID:26713206

Electrophysiology of Cranial Nerve Testing: Cranial Nerves IX and X.

PubMed

Martinez, Alberto R M; Martins, Melina P; Moreira, Ana Lucila; Martins, Carlos R; Kimaid, Paulo A T; França, Marcondes C

2018-01-01

The cranial nerves IX and X emerge from medulla oblongata and have motor, sensory, and parasympathetic functions. Some of these are amenable to neurophysiological assessment. It is often hard to separate the individual contribution of each nerve; in fact, some of the techniques are indeed a composite functional measure of both nerves. The main methods are the evaluation of the swallowing function (combined IX and X), laryngeal electromyogram (predominant motor vagal function), and heart rate variability (predominant parasympathetic vagal function). This review describes, therefore, the techniques that best evaluate the major symptoms presented in IX and X cranial nerve disturbance: dysphagia, dysphonia, and autonomic parasympathetic dysfunction.

Delineating Normal from Diseased Brain by Aminolevulinic Acid-Induced Fluorescence

NASA Astrophysics Data System (ADS)

Stepp, Herbert; Stummer, Walter

5-Aminolevulinic acid (5-ALA) as a precursor of protoporphyrin IX (PpIX) has been established as an orally applied drug to guide surgical resection of malignant brain tumors by exciting the red fluorescence of PpIX. The accumulation of PpIX in glioblastoma multiforme (GBM) is highly selective and provides excellent contrast to normal brain when using surgical microscopes with appropriately filtered light sources and cameras. The positive predictive value of fluorescent tissue is very high, enabling safe gross total resection of GBM and other brain tumors and improving prognosis of patients. Compared to other intraoperative techniques that have been developed with the aim of increasing the rate of safe gross total resections of malignant gliomas, PpIX fluorescence is considerably simpler, more cost effective, and comparably reliable. We present the basics of 5-ALA-based fluorescence-guided resection, and discuss the clinical results obtained for GBM and the experience with the fluorescence staining of other primary brain tumors and metastases as well as the results for spinal cord tumors. The phototoxicity of PpIX, increasingly used for photodynamic therapy of brain tumors, is mentioned briefly in this chapter.

Cell metabolic changes of porphyrins and superoxide anions by anthracene and benzo(a)pyrene.

PubMed

Uribe-Hernández, Raúl; Pérez-Zapata, Aura J; Vega-Barrita, María L; Ramón-Gallegos, Eva; Amezcua-Allieri, Myriam A

2008-09-01

The aim of this work was to evaluate the induction of protoporphyrins IX (PpIX) activity and superoxide anions (SO) in human leukocytes exposed to anthracene (ANT) and benzo(a)pyrene (B(a)P). The leukocyte LC(50)s for both hydrocarbons and the PpIX accumulation and SO overproduction were measured. The LC(50)s were 0.35 and 3.23μM for ANT and B(a)P, respectively. A linear relationship (r=0.97, p<0.01) between PpIX and ANT concentration was obtained. The induced accumulation of PpIX was proportional (r=0.63, p<0.01) to B(a)P concentration. SO overproduction showed a linear relationship (r=0.83, p<0.05) with ANT concentrations. The linear regression analysis of the effect of B(a)P on the superoxide anion overproduction showed a good coefficient (r=0.97, p<0.01), showed that ANT and B(a)P exposure induces PpIX accumulation, probably by disruption of the haem biosynthesis. ANT and B(a)P induce SO overproduction, perhaps through a process of redox cycling. Copyright © 2008 Elsevier B.V. All rights reserved.

Retargeting of adenovirus vectors through genetic fusion of a single-chain or single-domain antibody to capsid protein IX.

PubMed

Poulin, Kathy L; Lanthier, Robert M; Smith, Adam C; Christou, Carin; Risco Quiroz, Milagros; Powell, Karen L; O'Meara, Ryan W; Kothary, Rashmi; Lorimer, Ian A; Parks, Robin J

2010-10-01

Adenovirus (Ad) vectors are the most commonly used system for gene therapy applications, due in part to their ability to infect a wide array of cell types and tissues. However, many therapies would benefit from the ability to target the Ad vector only to specific cells, such as tumor cells for cancer gene therapy. In this study, we investigated the utility of capsid protein IX (pIX) as a platform for the presentation of single-chain variable-fragment antibodies (scFv) and single-domain antibodies (sdAb) for virus retargeting. We show that scFv can be displayed on the capsid through genetic fusion to native pIX but that these molecules fail to retarget the virus, due to improper folding of the scFv. Redirecting expression of the fusion protein to the endoplasmic reticulum (ER) results in correct folding of the scFv and allows it to recognize its epitope; however, ER-targeted pIX-scFv was incorporated into the Ad capsid at a very low level which was not sufficient to retarget virus infection. In contrast, a pIX-sdAb construct was efficiently incorporated into the Ad capsid and enhanced virus infection of cells expressing the targeted receptor. Taken together, our data indicate that pIX is an effective platform for presentation of large targeting polypeptides on the surface of the virus capsid, but the nature of the ligand can significantly affect its association with virions.

Specific Binding of Protoporphyrin IX to a Membrane-Bound 63 Kilodalton Polypeptide in Cucumber Cotyledons Treated with Diphenyl Ether-Type Herbicides.

PubMed

Sato, R; Oshio, H; Koike, H; Inoue, Y; Yoshida, S; Takahashi, N

1991-06-01

Porphyrin accumulation in excised cucumber cotyledons (Cucumis sativus L.) treated with a N-phenylimide S-23142 (N-[4-chloro-2-fluoro-5-propargyloxyphenyl]-3,4,5,6- tetrahydrophthalimide) and a diphenylether acifluorfen-ethyl (ethyl-5-[2-chloro-4-(trifluoromethyl)phenoxy]-2-nitro benzoic acid) was studied. Most of the accumulated porphyrins were found in the membrane fractions of 6,000g and 30,000g pellets, forming a complex with a membrane polypeptide. The complex was solubilized with 1% n-dodecyl beta-d-maltoside and its molecular mass was estimated to be 63,000 and 66,000 daltons by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel permeation high performance liquid chromatography (HPLC), respectively. The polypeptide also existed in untreated cotyledons but had little protoporphyrin IX. The complex was also formed in vitro by mixing the 30,000g pellets from untreated cotyledons and authentic protoporphyrin IX. However, protoporphyrin IX formed the complex specifically with the 63,000 dalton polypeptide and not with the other proteins both in vivo and in vitro. At least four fluorescent porphyrins, including protoporphyrin IX, were found in the acetone extract of the cotyledons by HPLC using a reversed phase column. Protoporphyrin IX was one of the two porphyrins that formed the complex. These results suggest that S-23142 and acifluorfenethyl enhance the accumulation of protoporphyrin IX, which forms the complex with the membrane protein.

ALA-induced PpIX spectroscopy for brain tumor image-guided surgery

NASA Astrophysics Data System (ADS)

Valdes, Pablo A.; Leblond, Frederic; Kim, Anthony; Harris, Brent T.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.

2011-03-01

Maximizing the extent of brain tumor resection correlates with improved survival and quality of life outcomes in patients. Optimal surgical resection requires accurate discrimination between normal and abnormal, cancerous tissue. We present our recent experience using quantitative optical spectroscopy in 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence-guided resection. Exogenous administration of ALA leads to preferential accumulation in tumor tissue of the fluorescent compound, PpIX, which can be used for in vivo surgical guidance. Using the state of the art approach with a fluorescence surgical microscope, we have been able to visualize a subset of brain tumors, but the sensitivity and accuracy of fluorescence detection for tumor tissue with this system are low. To take full advantage of the biological selectivity of PpIX accumulation in brain tumors, we used a quantitative optical spectroscopy system for in vivo measurements of PpIX tissue concentrations. We have shown that, using our quantitative approach for determination of biomarker concentrations, ALA-induced PpIX fluorescence-guidance can achieve accuracies of greater than 90% for most tumor histologies. Here we show multivariate analysis of fluorescence and diffuse reflectance signals in brain tumors with comparable diagnostic performance to our previously reported quantitative approach. These results are promising, since they show that technological improvements in current fluorescence-guided surgical technologies and more biologically relevant approaches are required to take full advantage of fluorescent biomarkers, achieve better tumor identification, increase extent of resection, and subsequently, lead to improve survival and quality of life in patients.

Perceptions of Women's Teams Coaches Regarding Gender Equity and Title IX Compliance in Community Colleges

ERIC Educational Resources Information Center

Kenney, Cynthia A.

2013-01-01

Title IX was enacted over 40 years ago, and although there have been marked increases in the number of girls and women participating in athletics at every level, gender equity in athletics continues to be a concern. This is especially evident at the community college level. Title IX requires equity in the areas of opportunities for participation,…

"To Study the Relationship of Academic Stress and Socio-Economic Status among IX Standard Students of Raipur City"

ERIC Educational Resources Information Center

Khan, Suhail Ahmed; Ayyub, Khan Farhat

2013-01-01

This paper focuses on the relationship between academic stress and socio-economic status among IX standard students. The research was carried out in Raipur City (Chhattisgarh) on a sample of 600 IX standard students of English and Hindi medium schools. Academic Stress was measured by Stress Inventory for School Students prepared by Seema Rani…

Perceptions of Title IX Administrators in Arkansas Institutions of Higher Education on Implementing Office for Civil Rights Guidance: A Qualitative Study

ERIC Educational Resources Information Center

Jones, Arch

2017-01-01

With the significant pressure placed on higher education administrators, and more specifically Title IX Coordinators, to manage compliance of the Office for Civil Rights (OCR) guidance on Title IX, this study has focused on the perceptions of the of individuals tasked with this obligation. To determine from the individuals on the front line of…

Performance and life cycle environmental benefits of recycling spent ion exchange brines by catalytic treatment of nitrate.

PubMed

Choe, Jong Kwon; Bergquist, Allison M; Jeong, Sangjo; Guest, Jeremy S; Werth, Charles J; Strathmann, Timothy J

2015-09-01

Salt used to make brines for regeneration of ion exchange (IX) resins is the dominant economic and environmental liability of IX treatment systems for nitrate-contaminated drinking water sources. To reduce salt usage, the applicability and environmental benefits of using a catalytic reduction technology to treat nitrate in spent IX brines and enable their reuse for IX resin regeneration were evaluated. Hybrid IX/catalyst systems were designed and life cycle assessment of process consumables are used to set performance targets for the catalyst reactor. Nitrate reduction was measured in a typical spent brine (i.e., 5000 mg/L NO3(-) and 70,000 mg/L NaCl) using bimetallic Pd-In hydrogenation catalysts with variable Pd (0.2-2.5 wt%) and In (0.0125-0.25 wt%) loadings on pelletized activated carbon support (Pd-In/C). The highest activity of 50 mgNO3(-)/(min - g(Pd)) was obtained with a 0.5 wt%Pd-0.1 wt%In/C catalyst. Catalyst longevity was demonstrated by observing no decrease in catalyst activity over more than 60 days in a packed-bed reactor. Based on catalyst activity measured in batch and packed-bed reactors, environmental impacts of hybrid IX/catalyst systems were evaluated for both sequencing-batch and continuous-flow packed-bed reactor designs and environmental impacts of the sequencing-batch hybrid system were found to be 38-81% of those of conventional IX. Major environmental impact contributors other than salt consumption include Pd metal, hydrogen (electron donor), and carbon dioxide (pH buffer). Sensitivity of environmental impacts of the sequencing-batch hybrid reactor system to sulfate and bicarbonate anions indicate the hybrid system is more sustainable than conventional IX when influent water contains <80 mg/L sulfate (at any bicarbonate level up to 100 mg/L) or <20 mg/L bicarbonate (at any sulfate level up to 100 mg/L) assuming 15 brine reuse cycles. The study showed that hybrid IX/catalyst reactor systems have potential to reduce resource consumption and improve environmental impacts associated with treating nitrate-contaminated water sources. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Child Survival and Development Revolution?

ERIC Educational Resources Information Center

Halpern, Robert

1986-01-01

Addresses the problems of child survival and development in developing countries by discussing the biomedical causes and the concomitant social determinants of high infant mortality rates. Describes four intervention strategies recommended by UNICEF: growth monitoring, oral rehydration therapy, breast feeding, and immunization. (HOD)

Antipsychotic Treatment Among Youth in Foster Care

PubMed Central

Yoon, Yesel; Rubin, David M.; Riddle, Mark A.; Noll, Elizabeth; Rothbard, Aileen

2011-01-01

OBJECTIVE: Despite national concerns over high rates of antipsychotic medication use among youth in foster care, concomitant antipsychotic use has not been examined. In this study, concomitant antipsychotic use among Medicaid-enrolled youth in foster care was compared with disabled or low-income Medicaid-enrolled youth. PATIENTS AND METHODS: The sample included 16 969 youths younger than 20 years who were continuously enrolled in a Mid-Atlantic state Medicaid program and had ≥1 claim with a psychiatric diagnosis and ≥1 antipsychotic claim in 2003. Antipsychotic treatment was characterized by days of any use and concomitant use with ≥2 overlapping antipsychotics for >30 days. Medicaid program categories were foster care, disabled (Supplemental Security Income), and Temporary Assistance for Needy Families (TANF). Multicategory involvement for youths in foster care was classified as foster care/Supplemental Security Income, foster care/TANF, and foster care/adoption. We used multivariate analyses, adjusting for demographics, psychiatric comorbidities, and other psychotropic use, to assess associations between Medicaid program category and concomitant antipsychotic use. RESULTS: Average antipsychotic use ranged from 222 ± 110 days in foster care to only 135 ± 101 days in TANF (P < .001). Concomitant use for ≥180 days was 19% in foster care only and 24% in foster care/adoption compared with <15% in the other categories. Conduct disorder and antidepressant or mood-stabilizer use was associated with a higher likelihood of concomitant antipsychotic use (P < .0001). CONCLUSIONS: Additional study is needed to assess the clinical rationale, safety, and outcomes of concomitant antipsychotic use and to inform statewide policies for monitoring and oversight of antipsychotic use among youths in the foster care system. PMID:22106072

Labor and delivery in a patient with hemophilia B.

PubMed

Przkora, R; Euliano, T Y; Roussos-Ross, K; Zumberg, M; Robicsek, S A

2011-07-01

Hemophilia B is a rare X-linked disorder that may cause dramatic bleeding. Women account for only 3.2% of those clinically affected. The X-linked inheritance frequently delays the diagnosis in women and may expose the patient to an increased risk of adverse events. There is limited experience with these patients during labor and delivery. A 28-year-old primiparous woman with hemophilia B (bleeding phenotype) delivered a male infant by an unplanned cesarean delivery under general anesthesia following treatment with factor IX and normalization of her coagulation parameters, guided by thromboelastography. Postpartum vaginal bleeding required transfusion of two units of packed red blood cells. Factor IX supplementation continued for one week. Once diagnosed with hemophilia B, a multidisciplinary approach and advanced antenatal planning can increase the likelihood of a safe delivery. Neuraxial approaches and cesarean delivery are recommended only after normalization of the coagulation profile. The male fetus of a hemophilia A or B patient requires special attention. Operative vaginal delivery and invasive fetal monitoring should be avoided. Thromboelastography is an excellent technique to assess parturients with bleeding disorders or peripartum hemorrhage and may be underused. Copyright © 2011 Elsevier Ltd. All rights reserved.

KSC-2009-2794

NASA Image and Video Library

2009-04-20

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the yellow framework at center will undergo a fit check. Nicknamed the "birdcage," it is the lifting fixture that will have the ability to lift the Crew Module, or CM, and Launch Abort System, or LAS, assembly for the Ares I-X rocket. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for July 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-3118

NASA Image and Video Library

2009-05-11

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the framework known as the "birdcage" is placed over the Ares I-X simulator crew module-launch abort system, or CM-LAS. The birdcage will be used to lift the CM-LAS to mate the stack with the simulator service module-service adapter stack. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for August 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-2797

NASA Image and Video Library

2009-04-20

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the yellow framework at top, nicknamed the "birdcage," is lifted high above the floor for a fit check with the Crew Module, or CM, and Launch Abort System, or LAS, assembly at lower left for the Ares I-X rocket. Ares I-X is the flight test for the Ares I. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I. The launch of the 327-foot-tall, full-scale Ares I-X is targeted for July 2009. Photo credit: NASA/Jack Pfaller

KSC-2009-6024

NASA Image and Video Library

2009-10-30

CAPE CANAVERAL, Fla. – The solid rocket booster recovery ship Freedom Star, towing the spent first stage of NASA's Ares I-X rocket, passes through Port Canaveral in Florida. Following the launch of the Ares I-X flight test, the booster splashed down in the Atlantic Ocean and was recovered. Liftoff of the 6-minute flight test was at 11:30 a.m. EDT Oct. 28. This was the first launch from Kennedy's pads of a vehicle other than the space shuttle since the Apollo Program's Saturn rockets were retired. The parts used to make the Ares I-X booster flew on 30 different shuttle missions ranging from STS-29 in 1989 to STS-106 in 2000. The data returned from more than 700 sensors throughout the rocket will be used to refine the design of future launch vehicles and bring NASA one step closer to reaching its exploration goals. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-6027

NASA Image and Video Library

2009-10-30

CAPE CANAVERAL, Fla. – The solid rocket booster recovery ship Freedom Star delivers the spent first stage of NASA's Ares I-X rocket to Hangar AF at Cape Canaveral Air Force Station in Florida. Following the launch of the Ares I-X flight test, the booster splashed down in the Atlantic Ocean and was recovered. Liftoff of the 6-minute flight test was at 11:30 a.m. EDT Oct. 28. This was the first launch from Kennedy's pads of a vehicle other than the space shuttle since the Apollo Program's Saturn rockets were retired. The parts used to make the Ares I-X booster flew on 30 different shuttle missions ranging from STS-29 in 1989 to STS-106 in 2000. The data returned from more than 700 sensors throughout the rocket will be used to refine the design of future launch vehicles and bring NASA one step closer to reaching its exploration goals. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5536

NASA Image and Video Library

2009-10-20

CAPE CANAVERAL, Fla. – The 327-foot-tall Ares I-X rocket clears the door of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, on its way to Launch Pad 39B. The move to the launch pad, known as "rollout," began at 1:39 a.m. EDT. The transfer of the pad from the Space Shuttle Program to the Constellation Program took place May 31. Modifications made to the pad include the removal of shuttle unique subsystems, such as the orbiter access arm and a section of the gaseous oxygen vent arm, along with the installation of three 600-foot lightning towers, access platforms, environmental control systems and a vehicle stabilization system. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Jack Pfaller

Factor IX expression in skeletal muscle of a severe hemophilia B patient 10 years after AAV-mediated gene transfer.

PubMed

Buchlis, George; Podsakoff, Gregory M; Radu, Antonetta; Hawk, Sarah M; Flake, Alan W; Mingozzi, Federico; High, Katherine A

2012-03-29

In previous work we transferred a human factor IX-encoding adeno-associated viral vector (AAV) into skeletal muscle of men with severe hemophilia B. Biopsy of injected muscle up to 1 year after vector injection showed evidence of gene transfer by Southern blot and of protein expression by IHC and immunofluorescent staining. Although the procedure appeared safe, circulating F.IX levels remained subtherapeutic (< 1%). Recently, we obtained muscle tissue from a subject injected 10 years earlier who died of causes unrelated to gene transfer. Using Western blot, IHC, and immunofluorescent staining, we show persistent factor IX expression in injected muscle tissue. F.IX transcripts were detected in injected skeletal muscle using RT-PCR, and isolated whole genomic DNA tested positive for the presence of the transferred AAV vector sequence. This is the longest reported transgene expression to date from a parenterally administered AAV vector, with broad implications for the future of muscle-directed gene transfer.

Protoporphyrin IX fluorescence as potential indicator of psoriasis severity and progression.

PubMed

Wang, Bo; Xu, Yu-Ting; Zhang, Li; Zheng, Jie; Sroka, Ronald; Wang, Hong-Wei; Wang, Xiu-Li

2017-09-01

In psoriatic lesions, fluorescence diagnosis with blue light can detect protoporphyrin IX accumulation, especially after topical 5-aminolaevulinic acid (ALA) application. However, variable fluorescence distributions, interpersonal variations and long incubation time limit its wide application in clinic. This study is aimed to identify a consistent and convenient method to facilitate diagnosis and evaluation of psoriatic lesions. 104 psoriatic lesions from 30 patients were evaluated. Single lesion PSI scoring and fluorescence by macrospectrofluorometry were recorded on each lesion before and after treatment with narrow-band UVB. Punctate red fluorescence, emitted mainly by protoporphyrin IX, is observed in some psoriatic lesions. According to psoriasis severity index, fluorescence-positive lesions are more severe than lesions without fluorescence. We found a significant positive correlation between psoriasis severity and fluorescence intensity from protoporphyrin IX. Protoporphyrin IX-induced red fluorescence can be used as a novel and convenient approach for psoriasis diagnosis and progression evaluation. Copyright © 2017. Published by Elsevier B.V.

Understanding Noncompliance: A Qualitative Content Analysis of Title IX Sexual Misconduct Violations Using the Office for Civil Rights Investigative Findings

ERIC Educational Resources Information Center

Schaffer, Lenore

2017-01-01

On April 4, 2011, the U.S. Department of Education's Office for Civil Rights (OCR) released a Dear Colleague Letter (DCL) reminding higher education institutions (HEIs) of their obligations under Title IX to respond to complaints of sexual misconduct. The 2011 DCL was meant to be a guidance document to assist HEIs in complying with Title IX, but…

KSC-2009-2742

NASA Image and Video Library

2009-04-17

CAPE CANAVERAL, Fla. –– In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, technicians are seen inside the Ares I-X segment installing the roll control system. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

Optical spectroscopy for stereotactic biopsy of brain tumors

NASA Astrophysics Data System (ADS)

Markwardt, Niklas; von Berg, Anna; Fiedler, Sebastian; Goetz, Marcus; Haj-Hosseini, Neda; Polzer, Christoph; Stepp, Herbert; Zelenkov, Petr; Rühm, Adrian

2015-07-01

Stereotactic biopsy procedure is performed to obtain a tissue sample for diagnosis purposes. Currently, a fiber-based mechano-optical device for stereotactic biopsies of brain tumors is developed. Two different fluorophores are employed to improve the safety and reliability of this procedure: The fluorescence of intravenously applied indocyanine green (ICG) facilitates the recognition of blood vessels and thus helps minimize the risk of cerebral hemorrhages. 5- aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence is used to localize vital tumor tissue. ICG fluorescence detection using a 2-fiber probe turned out to be an applicable method to recognize blood vessels about 1.5 mm ahead of the fiber tip during a brain tumor biopsy. Moreover, the suitability of two different PpIX excitation wavelengths regarding practical aspects was investigated: While PpIX excitation in the violet region (at 405 nm) allows for higher sensitivity, red excitation (at 633 nm) is noticeably superior with regard to blood layers obscuring the fluorescence signal. Contact measurements on brain simulating agar phantoms demonstrated that a typical blood coverage of the tumor reduces the PpIX signal to about 75% and nearly 0% for 633 nm and 405 nm excitation, respectively. As a result, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of high-grade gliomas in stereotactic biopsy.

Preclinical evaluation of spatial frequency domain-enabled wide-field quantitative imaging for enhanced glioma resection

NASA Astrophysics Data System (ADS)

Sibai, Mira; Fisher, Carl; Veilleux, Israel; Elliott, Jonathan T.; Leblond, Frederic; Roberts, David W.; Wilson, Brian C.

2017-07-01

5-Aminolevelunic acid-induced protoporphyrin IX (PpIX) fluorescence-guided resection (FGR) enables maximum safe resection of glioma by providing real-time tumor contrast. However, the subjective visual assessment and the variable intrinsic optical attenuation of tissue limit this technique to reliably delineating only high-grade tumors that display strong fluorescence. We have previously shown, using a fiber-optic probe, that quantitative assessment using noninvasive point spectroscopic measurements of the absolute PpIX concentration in tissue further improves the accuracy of FGR, extending it to surgically curable low-grade glioma. More recently, we have shown that implementing spatial frequency domain imaging with a fluorescent-light transport model enables recovery of two-dimensional images of [PpIX], alleviating the need for time-consuming point sampling of the brain surface. We present first results of this technique modified for in vivo imaging on an RG2 rat brain tumor model. Despite the moderate errors in retrieving the absorption and reduced scattering coefficients in the subdiffusive regime of 14% and 19%, respectively, the recovered [PpIX] maps agree within 10% of the point [PpIX] values measured by the fiber-optic probe, validating its potential as an extension or an alternative to point sampling during glioma resection.

Prognostic Relevance of the Expression of CA IX, GLUT-1, and VEGF in Ovarian Epithelial Cancers

PubMed Central

Kim, Kyungbin; Park, Won Young; Kim, Jee Yeon; Sol, Mee Young; Shin, Dong Hun; Park, Do Youn; Lee, Chang Hun; Lee, Jeong Hee

2012-01-01

Background Tumor hypoxia is associated with malignant progression and treatment resistance. Hypoxia-related factors, such as carbonic anhydrase IX (CA IX), glucose transporter-1 (GLUT-1), and vascular endothelial growth factor (VEGF) permit tumor cell adaptation to hypoxia. We attempted to elucidate the correlation of these markers with variable clinicopathological factors and overall prognosis. Methods Immunohistochemistry for CA IX, GLUT-1, and VEGF was performed on formalin-fixed, paraffin-embedded tissues from 125 cases of ovarian epithelial cancer (OEC). Results CA IX expression was significantly associated with an endometrioid and mucinous histology, nuclear grade, tumor necrosis, and mitosis. GLUT-1 expression was associated with tumor necrosis and mitosis. VEGF expression was correlated only with disease recurrence. Expression of each marker was not significant in terms of overall survival in OECs; however, there was a significant correlation between poor overall survival rate and high coexpression of these markers. Conclusions The present study suggests that it is questionable whether CA IX, GLUT-1, or VEGF can be used alone as independent prognostic factors in OECs. Using at least two markers helps to predict patient outcomes in total OECs. Moreover, the inhibition of two target gene combinations might prove to be a novel anticancer therapy. PMID:23323103

Epitope Capsid-Incorporation: New Effective Approach for Vaccine Development for Chagas Disease

PubMed Central

Matthews, Qiana L.; Farrow, Anitra L.; Rachakonda, Girish; Gu, Linlin; Nde, Pius; Krendelchtchikov, Alexandre; Pratap, Siddharth; Sakhare, Shruti S.; Sabbaj, Steffanie; Lima, Maria F.; Villalta, Fernando

2016-01-01

Background Previously we reported that a hexon-modified adenovirus (Ad) vector containing the invasive neutralizing epitope of Trypanosoma cruzi (T. cruzi) trypomastigote gp83 (Ad5-gp83) provided immunoprotection against T. cruzi infection. The purpose of this work was to design an improved vaccine for T. cruzi using a novel epitope capsid incorporation strategy. Thus, we evaluated the immunoprotection raised by co-immunization with Ad5-gp83 and an Ad vector containing an epitope (ASP-M) of the T. cruzi amastigote surface protein 2. Methods Protein IX (pIX)-modified Ad vector (Ad5-pIX-ASP-M) was generated, characterized, and validated. C3H/He mice were immunized with Ad5-pIX-ASP-M and Ad5-gp83 and the cell-mediated responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and intracellular staining. Immunized mice were challenged with T. cruzi to evaluate the vaccine efficacy. Results Our findings indicate that Ad5-pIX-ASP-M was viable. Specific CD8+ T-cell mediated responses prior to the challenge show an increase in IFNγ and TNFα production. A single immunization with Ad5-pIX-ASP-M provided protection from T. cruzi infection, but co-immunizations with Ad5-pIX-ASP-M and Ad5-gp83 provided a higher immunoprotection and increased survival rate of mice. Conclusions Overall, these results suggest that the combination of gp83 and ASP-M specific epitopes onto the capsid-incorporated adenoviruses would provide superior protection against Chagas disease as compared with Ad5-gp83 alone. PMID:27709126

An intraoperative spectroscopic imaging system for quantification of Protoporphyrin IX during glioma surgery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Angulo-Rodríguez, Leticia M.; Laurence, Audrey; Jermyn, Michael; Sheehy, Guillaume; Sibai, Mira; Petrecca, Kevin; Roberts, David W.; Paulsen, Keith D.; Wilson, Brian C.; Leblond, Frédéric

2016-03-01

Cancer tissue often remains after brain tumor resection due to the inability to detect the full extent of cancer during surgery, particularly near tumor boundaries. Commercial systems are available for intra-operative real-time aminolevulenic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence imaging. These are standard white-light neurosurgical microscopes adapted with optical components for fluorescence excitation and detection. However, these instruments lack sensitivity and specificity, which limits the ability to detect low levels of PpIX and distinguish it from tissue auto-fluorescence. Current systems also cannot provide repeatable and un-biased quantitative fluorophore concentration values because of the unknown and highly variable light attenuation by tissue. We present a highly sensitive spectroscopic fluorescence imaging system that is seamlessly integrated onto a neurosurgical microscope. Hardware and software were developed to achieve through-microscope spatially-modulated illumination for 3D profilometry and to use this information to extract tissue optical properties to correct for the effects of tissue light attenuation. This gives pixel-by-pixel quantified fluorescence values and improves detection of low PpIX concentrations. This is achieved using a high-sensitivity Electron Multiplying Charge Coupled Device (EMCCD) with a Liquid Crystal Tunable Filter (LCTF) whereby spectral bands are acquired sequentially; and a snapshot camera system with simultaneous acquisition of all bands is used for profilometry and optical property recovery. Sensitivity and specificity to PpIX is demonstrated using brain tissue phantoms and intraoperative human data acquired in an on-going clinical study using PpIX fluorescence to guide glioma resection.

Infectious bronchitis virus and brown shell colour: Australian strains of infectious bronchitis virus affect brown eggshell colour in commercial laying hens differently.

PubMed

Samiullah, Sami; Roberts, Juliet; Chousalkar, Kapil

2016-10-01

The aim of the current study was to assess any effect of wild and vaccine Australian infectious bronchitis virus (IBV) strains on shell colour in brown-shelled eggs. In Experiment 1, eggs were collected from day 1 to day 13 post-inoculation (p.i.) from unvaccinated laying hens challenged with IBV wild strains T and N1/88 and from a negative control group of hens. In Experiment 2, eggs were collected from 2 to 22 days p.i. from unvaccinated and vaccinated laying hens challenged with either a wild or a vaccine strain of IBV. In Experiment 1, there was a significant effect (P < 0.05) of day p.i. and of viral strain on shell reflectivity, L* and protoporphyrin IX (PP IX) in eggshells, with and without cuticle. The mean PP IX/g of shell with and without cuticle was significantly higher on day 1 p.i. compared to day 7, after which PP IX increased with day p.i. In Experiment 2, shell reflectivity and L* increased and PP IX decreased with increased day p.i. until day 12. Shell reflectivity and L* decreased slightly after day 12 and increased again towards day 22. Shell reflectivity, L* and PP IX were not significantly different for eggshells from unvaccinated and vaccinated laying hens in the intact eggshell, but were significantly different in shells from which cuticle had been removed. In conclusion, the IBV strains reduced the intensity of brown shell colour to different extents with a lower amount of PP IX in eggshells.

Ares I-X Flight Test - On the Fast Track to the Future

NASA Technical Reports Server (NTRS)

Davis, Stephan R.; Robinson, Kimberly F.

2008-01-01

In less than two years, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will send humans to the Moon and beyond. Personnel from the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for an April 2009 launch. Ares I-X will be a suborbital development flight test that will gather critical data about the flight dynamics of the integrated launch vehicle stack; understand how to control its roll during flight; better characterize the severe stage separation environments that the upper stage engine will experience during future flights; and demonstrate the first stage recovery system. NASA also will modify the launch infrastructure and ground and mission operations. The Ares I-X Flight Test Vehicle (FTV) will incorporate flight and mockup hardware similar in mass and weight to the operational vehicle. It will be powered by a four-segment Solid Rocket Booster (SRB), which is currently in Shuttle inventory, and will include a fifth spacer segment and new forward structures to make the booster approximately the same size and weight as the five-segment SRB. The Ares I-X flight profile will closely approximate the flight conditions that the Ares I will experience through Mach 4.5, up to approximately130,OOO feet and through maximum dynamic pressure ("Max Q") of approximately 800 pounds per square foot. Data from the Ares I-X flight will support the Ares I Critical Design Review (CDR), scheduled for 2010. Work continues on Ares I-X design and hardware fabrication. All of the individual elements are undergoing CDRs, followed by an integrated vehicle CDR in March 2008. The various hardware elements are on schedule to begin deliveries to Kennedy Space Center (KSC) in early September 2008.

Photocatalytic reduction of nitrate using titanium dioxide for regeneration of ion exchange brine.

PubMed

Yang, Ting; Doudrick, Kyle; Westerhoff, Paul

2013-03-01

Nitrate is often removed from groundwater by ion exchange (IX) before its use as drinking water. Accumulation of nitrate in IX brine reduces the efficiency of IX regeneration and the useful life of the regeneration brine. For the first time, we present a strategy to photocatalytically reduce nitrate in IX brine, thereby extending the use of the brine. Titanium dioxide (Evonik P90), acting as photocatalyst, reduced nitrate effectively in both synthetic brines and sulfate-removed IX brine when formic acid (FA) was used as the hole scavenger (i.e., electron donor) and the initial FA to nitrate molar ratio (IFNR) was 5.6. Increasing the NaCl level in the synthetic brine slowed the nitrate reduction rate without affecting by-product selectivity of ammonium and gaseous N species (e.g., N(2), N(2)O). In a non-modified IX brine, nitrate removal was greatly inhibited owing to the presence of sulfate, which competed with nitrate for active surface sites on P90 and induced aggregation of P90 nanoparticles. After removing sulfate through barium sulfate precipitation, nitrate was effectively reduced; approximately 3.6 × 10(24) photons were required to reduce each mole of nitrate to 83% N Gases and 17% NH(4)(+). To make optimum use of FA and control the residual FA level in treated brine, the IFNR was varied. High IFNRs (e.g., 4, 5.6) were found to be more efficient for nitrate reduction but left higher residual FA in brine. IX column tests were performed to investigate the impact of residual FA for brine reuse. The residual FA in the brine did not significantly affect the nitrate removal capacity of IX resins, and formate contamination of treated water could be eliminated by rinsing with one bed volume of fresh brine. Copyright © 2012 Elsevier Ltd. All rights reserved.

Helicopter Electro-Optical System Display Requirements. 1. The Effects of CRT Display Size, System Gamma Function, and Terrain Type on Pilots’ Required Display Luminance

DTIC Science & Technology

1980-03-01

full-color terrain model designed to 6 ,. .. ., CINE MA ICiINE h MRO FILM To’ N U Ix v M C CTMIRROR MONITOR FRESNEL REAR- PROJECTION SCREEN Z...ments of NOE flight, recorded on videotape. One segment was filmed at the Hunter-Liggett, Calif., ntilitary reservation, and the other segment was... filmed near Fort Rucker, Ala. The tapes were viewed by each participant pilot on the 13-cm and the 26-cm CRT displays. They could attenuate the display

Vibrationally Excited Ions: Quenching Reaction Enhancement, Lifetimes

DTIC Science & Technology

1991-01-01

affinities in our lad- A,.=Af exp( - AS/IR) = I .IX 10𔄃 cm’ S_ with limits der . Any change it. P.A.(Br), ither due to a change in bet~een 7.Sx l3 9and...8217K P Huber and G Hereberg. C oeto of Drateooc Molecules ( Van "M Tubs’, G JasAay. N D Toeddy. and B. B. Fergusn. Ini J Mass Nostrand-Reinhold. New York...objectives and it seemed possible .aat neut - rals such as N,. Xe and CF, might provide suitable monitor gases for vibra- tionally excited HBr*. For HBr

KSC-2009-2466

NASA Image and Video Library

2009-04-01

CAPE CANAVERAL, Fla. – In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the Ares I-X upper stage simulator service module/service adapter segment has been installed on a stand. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. The Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-3586

NASA Image and Video Library

2009-06-08

CAPE CANAVERAL, Fla. – The Ares I-X aft skirt moves past the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida on its way to the Rotation, Processing and Surge Facility. In the RPSF, it will be stacked with the aft motor to form the aft assembly. The complete Ares I-X will be assembled in the Vehicle Assembly Building. The launch of Ares I-X is targeted for August 2009. Photo credit: NASA/Jim Grossmann

KSC-2009-2896

NASA Image and Video Library

2009-04-29

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, a crane lifts a second roll control system module for installation in an Ares I-X segment. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in August 2009. Photo credit: NASA/Dimitri Gerondidakis

KSC-2009-2899

NASA Image and Video Library

2009-04-29

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, technicians complete installation of a second roll control system module in an Ares I-X segment. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in August 2009. Photo credit: NASA/Dimitri Gerondidakis

KSC-2009-3587

NASA Image and Video Library

2009-06-08

CAPE CANAVERAL, Fla. – The Ares I-X aft skirt moves past the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida on its way to the Rotation, Processing and Surge Facility. In the RPSF, it will be stacked with the aft motor to form the aft assembly. The complete Ares I-X will be assembled in the Vehicle Assembly Building. The launch of Ares I-X is targeted for August 2009. Photo credit: NASA/Jim Grossmann

KSC-2009-2898

NASA Image and Video Library

2009-04-29

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, technicians maneuver a second roll control system module into place for installation in the Ares I-X segment. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in August 2009. Photo credit: NASA/Dimitri Gerondidakis

KSC-2009-2893

NASA Image and Video Library

2009-04-29

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, a second roll control system module is ready to be installed in an Ares I-X segment. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in August 2009. Photo credit: NASA/Dimitri Gerondidakis

ARES I-X Launch Prep

NASA Image and Video Library

2009-10-26

NASA's Ares I-X rocket is seen on launch pad 39b at the Kennedy Space Center in Cape Canaveral, Fla., Tuesday, Oct. 27, 2009 shortly after NASA scrubbed the launch attempt due to weather. The flight test of Ares I-X, now scheduled for Wednesday, Oct. 28, 2009, will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

KSC-2009-2741

NASA Image and Video Library

2009-04-17

CAPE CANAVERAL, Fla. –– In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, at left center, technicians install the roll control system in the Ares I-X segment in the center. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-2739

NASA Image and Video Library

2009-04-17

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, at right, technicians get ready to install the roll control system in the Ares I-X segment at left. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

Inelastic X-ray scattering of RTAl3 (R = La, Ce, T = Cu, Au)

NASA Astrophysics Data System (ADS)

Tsutsui, Satoshi; Kaneko, Koji; Pospisil, Jiri; Haga, Yoshinori

2018-05-01

Inelastic X-ray scattering (IXS) experiments of RTAl3 (R = La Ce, T = Cu, Au) were carried out at 300 and 5.5 K. The spectra between LaCuAl3 and CeCuAl3 (LaAuAl3 and CeAuAl3) are nearly identical at both temperatures except for temperature factors such as temperature dependence of Bose factor in IXS spectra and effect on thermal expansion. This means that no evident temperature dependence of IXS spectra was observed in CeTAl3 (T = Cu, Au). Since the major contribution of scattering cross section in IXS measurements is Thomson scattering, the present results failed to confirm the presence of vibron in these compounds.

Cardiac Sarcoidosis Concomitant with Large-vessel Aortitis Detected by 18F-fluorodeoxyglucose Positron Emission Tomography.

PubMed

Higuchi, Yoshihiro; Kimoto, Yasutaka; Tanoue, Rika; Tokunou, Tomotake; Tomonari, Kenichiro; Maeda, Toyoki; Horiuchi, Takahiko

2018-06-01

We herein report a case of concurrent cardiac sarcoidosis and large-vessel aortitis detected by 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) and followed up during immunosuppressive therapy. After high-dose prednisolone administration (1 mg/kg), serial FDG-PET showed that almost all of the abnormal FDG uptake in the heart and extracardiac region, including the abdominal to bilateral iliac arteries, had been disappeared. During the tapering of prednisolone, additive methotrexate therapy was needed to treat the recurrence of cardiac sarcoidosis. FDG-PET is a useful tool for detecting cardiac sarcoidosis concomitant with large-vessel aortitis and monitoring the effectiveness of immunosuppressive therapy.

Effect of production system and flock age on eggshell and egg internal quality measurements.

PubMed

Samiullah, Sami; Omar, Amal Saleh; Roberts, Juliet; Chousalkar, Kapil

2017-01-01

Egg quality was measured in eggs from different flocks that were reared together and then allocated to different production systems. Eggs were processed for measurements of eggshell and egg internal quality variables, scoring of ultrastructural mammillary layer features, completeness of cuticle cover, and protoporphyrin IX (PP IX) quantification. There was a significant main effect (P < 0.05) of production system on shell reflectivity, egg weight, and egg internal quality and significant effects of flock age on most measurements. The mammillary layer ultrastructural variables showed no clear relationship with production system and flock age. However, there was a significant interaction between production system and flock age for mammillary cap, early and late fusions. Cuticle cover ([Formula: see text]), was significantly higher in barn eggs (19.20), followed by free range (17.57), and cage eggs (15.99). Completeness of cuticle cover was significantly higher in eggs from the 44 week old flock than for 64 week and 73 week old flocks. For eggshells with cuticle intact, there was a significant main effect of both production system and flock age, and significant interaction between the two, for shell reflectivity, L*a*b* values and amount of PP IX. For PP IX, when this difference was calculated for the cuticle alone, there were no statistically significant differences. In 1 g of shell with and without cuticle, there was more PP IX in cage eggs (9.49 × 10 -8 , 7.90 × 10 -8  mM) followed by free range (8.24 × 10 -8 , 6.90 × 10 -8  mM), and barn eggs (8.64 × 10 -8 , 7.28 × 10 -8  mM). Similar trends were recorded for the amount of PP IX in 1 g of cuticle, but the difference was not statistically significant. The amount of PP IX decreased significantly with increasing flock age. Comparing the cage and barn production systems at 68 week of flock age, there was no difference for the amount of PP IX in shell with or without cuticle, or in the cuticle alone. Eggs from the cage production system were darker in color and contained more PP IX mainly within the calcareous part of the shell. For the barn production system, the completeness of cuticle cover was higher and egg weight generally lower. © 2016 Poultry Science Association Inc.

Ares I-X Flight Test--The Future Begins Here

NASA Technical Reports Server (NTRS)

Davis, Stephan R.; Robinson, Kimberly F.

2008-01-01

In less than one year, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will send humans to the Moon and beyond. Personnel from the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for a 2009 launch. Ares I-X will be a suborbital development flight test that will gather critical data about the flight dynamics of the integrated launch vehicle stack; understand how to control its roll during flight; better characterize the severe stage separation environments that the upper stage engine will experience during future flights; and demonstrate the first stage recovery system. NASA also will modify the launch infrastructure and ground and mission operations. The Ares I-X Flight Test Vehicle (FTV) will incorporate flight and mockup hardware similar in mass and weight to the operational vehicle. It will be powered by a four-segment Solid Rocket Booster (SRB), which is currently in Shuttle inventory, and will include a fifth spacer segment and new forward structures to make the booster approximately the same size and weight as the five-segment SRB. The Ares I-X flight profile will closely approximate the flight conditions that the Ares I will experience through Mach 4.5, up to approximately 130,000 feet (39,600 meters (m)) and through maximum dynamic pressure ('Max Q') of approximately 800 pounds per square foot (38.3 kilopascals (kPa)). Data from the Ares I-X flight will support the Ares I Critical Design Review (CDR), scheduled for 2010. Work continues on Ares I-X design and hardware fabrication. All of the individual elements are undergoing CDRs, followed by a two-part integrated vehicle CDR in March and July 2008. The various hardware elements are on schedule to begin deliveries to Kennedy Space Center (KSC) in early September 2008. Ares I-X is the first step in the long journey to the Moon and farther destinations. This suborbital test will be NASA's first flight of a new human-rated launch vehicle in more than a generation. This promises to be an exciting time for NASA and the nation, as we reach for new goals in space exploration. A visual presentation is included.

Improving contrast enhancement in magnetic resonance imaging using 5-aminolevulinic acid-induced protoporphyrin IX for high-grade gliomas.

PubMed

Yamamoto, Junkoh; Kakeda, Shingo; Yoneda, Tetsuya; Ogura, Shun-Ichiro; Shimajiri, Shohei; Tanaka, Tohru; Korogi, Yukunori; Nishizawa, Shigeru

2017-03-01

Magnetic resonance imaging (MRI) with a gadolinium-based contrast agent is the gold standard for high-grade gliomas (HGGs). The compound 5-aminolevulinic acid (5-ALA) undergoes a high rate of cellular uptake, particularly in cancer cells. In addition, fluorescence-guided resection with 5-ALA is widely used for imaging HGGs. 5-ALA is water soluble, while protoporphyrin IX (PpIX) is water insoluble. It was speculated whether converting from 5-ALA to PpIX may relatively increase intracellular water content, and consequently, might enhance the T2 signal intensity in HGG. The aim of the present study was to assess whether 5-ALA-induced PpIX enhances the T2 signal intensity in patients with HGGs. A total of 4 patients who were candidates for HGG surgical treatment were prospectively analyzed with preoperative MRI. Patients received oral doses of 5-ALA (20 mg/kg) 3 h prior to anesthesia. At 2.5 h post-5-ALA administration, T2-weighted images (T2WIs) were obtained from all patients. Subsequently, tumors were evaluated via fluorescence using a modified operating microscope. Fluorescent tumor tissues were obtained to analyze the accumulation of 5-ALA-induced PpIX within the tumors, which was confirmed quantitatively by high-performance liquid chromatography (HPLC) analysis. The MRI T2 signal intensity within the tumors was evaluated prior to and following 5-ALA administration. Three glioblastoma multiformes (GBMs) and 1 anaplastic oligodendroglioma (AO) were included in the analysis. Intraoperatively, all GBMs exhibited strong fluorescence of 5-ALA-induced PpIX, whilst no fluorescence was observed in the AO sample. HPLC analysis indicated a higher accumulation of 5-ALA-induced PpIX in the GBM samples compared with the AO sample. In total, 48 regions of interest were identified within the tumors from T2-WIs. In the GBM group, the relative T2 signal intensity value within the tumors following 5-ALA administration was significantly increased compared with the T2 signal intensity value prior to 5-ALA administration (1.537±0.021 and 1.577±0.023, respectively; P=0.0055). No significant differences were observed in the AO group. These results suggest that the 5-ALA-induced PpIX enhanced the T2 signal intensity in HGG. Therefore, 5-ALA may be a potentially useful MRI contrast reagent for HGG.

Outcomes of pregnancies complicated by liver cirrhosis, portal hypertension, or esophageal varices.

PubMed

Puljic, Anela; Salati, Jennifer; Doss, Amy; Caughey, Aaron B

2016-01-01

To evaluate pregnancy outcomes in women with liver cirrhosis, portal hypertension, or esophageal varices. We analyzed a retrospective cohort of 2,284,218 pregnancies in 2005-2009 recorded in the California Birth Registry database. Utilizing ICD-9 codes we analyzed the following outcomes for liver cirrhosis, portal hypertension, or esophageal varices in pregnancy: preeclampsia (PET), preterm delivery (PTD; <37 weeks), cesarean section, low birth weight (LBW; <2500 g), small for gestational age (SGA; <10th percentile), neonatal death (NND), and postpartum hemorrhage (PPH). Cirrhosis in pregnancy conferred an increased risk of PET, PTD, CS in multiparous women, LBW, and NND. Portal hypertension in pregnancy was associated with PTD, LBW, NND, and PPH. Non-bleeding esophageal varices in pregnancy were not associated with the outcomes assessed in a statistically significant manner. One case of bleeding esophageal varices was observed, resulting in PTD with a LBW infant. There were three cases of concomitant portal hypertension or concomitant esophageal varices with cirrhosis in pregnancy. Pregnancy in women with concomitant liver cirrhosis, portal hypertension, or esophageal varices can be successful. However, pregnancy outcomes are worse and may warrant closer antenatal monitoring and patient counseling. Cirrhosis in pregnancy with concomitant portal hypertension or esophageal varices is rare.

Initial Assessment of the Ares I-X Launch Vehicle Upper Stage to Vibroacoustic Flight Environments

NASA Technical Reports Server (NTRS)

Larko, Jeffrey M.; Hughes, William O.

2008-01-01

The Ares I launch vehicle will be NASA s first new launch vehicle since 1981. Currently in design, it will replace the Space Shuttle in taking astronauts to the International Space Station, and will eventually play a major role in humankind s return to the Moon and eventually to Mars. Prior to any manned flight of this vehicle, unmanned test readiness flights will be flown. The first of these readiness flights, named Ares I-X, is scheduled to be launched in April 2009. The NASA Glenn Research Center is responsible for the design, manufacture, test and analysis of the Ares I-X upper stage simulator (USS) element. As part of the design effort, the structural dynamic response of the Ares I-X launch vehicle to its vibroacoustic flight environments must be analyzed. The launch vehicle will be exposed to extremely high acoustic pressures during its lift-off and aerodynamic stages of flight. This in turn will cause high levels of random vibration on the vehicle's outer surface that will be transmitted to its interior. Critical flight equipment, such as its avionics and flight guidance components are susceptible to damage from this excitation. This study addresses the modelling, analysis and predictions from examining the structural dynamic response of the Ares I-X upper stage to its vibroacoustic excitations. A statistical energy analysis (SEA) model was used to predict the high frequency response of the vehicle at locations of interest. Key to this study was the definition of the excitation fields corresponding to lift off acoustics and the unsteady aerodynamic pressure fluctuations during flight. The predicted results will be used by the Ares I-X Project to verify the flight qualification status of the Ares I-X upper stage components.

Analysis of the in vitro and in vivo effects of photodynamic therapy on prostate cancer by using new photosensitizers, protoporphyrin IX-polyamine derivatives.

PubMed

Fidanzi-Dugas, Chloë; Liagre, Bertrand; Chemin, Guillaume; Perraud, Aurélie; Carrion, Claire; Couquet, Claude-Yves; Granet, Robert; Sol, Vincent; Léger, David Yannick

2017-07-01

Photodynamic therapy, using porphyrins as photosensitizers (PS), has been approved in treatment of several solid tumors. However, commonly used PS induce death but also resistance pathways in cancer cells and an alteration of surrounding normal tissues. Because polyamines (PA) are actively accumulated in cancer cells by the Polyamine Transport System (PTS), they may enable PS to specifically target cancer cells. Here, we investigated whether new protoporphyrin IX-polyamine derivatives were effective PS against prostate cancer and whether PA increased PDT specificity after 630nm irradiation. CHO and CHO-MG cells (differing in their PTS activity) were used to assess efficacy of polyamine vectorization. MTT assays were performed on human prostate non-malignant (RWPE-1) and malignant (PC-3, DU 145 and LNCaP) cell lines to test PS phototoxicity. ROS generation, DNA fragmentation and cell signalling were assessed by ELISA/EIA, western-blots and gel shift assays. Finally, PS effects were studied on tumor growth in nude mice. Our PS were more effective on cancer cells compared to non-malignant cells and more effective than PpIX alone. PpIX-PA generated ROS production involved in induction of apoptotic intrinsic pathways. Different pathways involved in apoptosis resistance were studied: PS inhibited Bcl-2, Akt, and NF-κB but activated p38/COX-2/PGE 2 pathways which were not implicated in apoptosis resistance in our model. In vivo experiments showed PpIX-PA efficacy was greater than results obtained with PpIX. All together, our results showed that PpIX-PA exerted its maximum effects without activating resistance pathways and appears to be a good candidate for prostate cancer PDT treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

The MYStIX Infrared-Excess Source Catalog

NASA Astrophysics Data System (ADS)

Povich, Matthew S.; Kuhn, Michael A.; Getman, Konstantin V.; Busk, Heather A.; Feigelson, Eric D.; Broos, Patrick S.; Townsley, Leisa K.; King, Robert R.; Naylor, Tim

2013-12-01

The Massive Young Star-Forming Complex Study in Infrared and X-rays (MYStIX) project provides a comparative study of 20 Galactic massive star-forming complexes (d = 0.4-3.6 kpc). Probable stellar members in each target complex are identified using X-ray and/or infrared data via two pathways: (1) X-ray detections of young/massive stars with coronal activity/strong winds or (2) infrared excess (IRE) selection of young stellar objects (YSOs) with circumstellar disks and/or protostellar envelopes. We present the methodology for the second pathway using Spitzer/IRAC, 2MASS, and UKIRT imaging and photometry. Although IRE selection of YSOs is well-trodden territory, MYStIX presents unique challenges. The target complexes range from relatively nearby clouds in uncrowded fields located toward the outer Galaxy (e.g., NGC 2264, the Flame Nebula) to more distant, massive complexes situated along complicated, inner Galaxy sightlines (e.g., NGC 6357, M17). We combine IR spectral energy distribution (SED) fitting with IR color cuts and spatial clustering analysis to identify IRE sources and isolate probable YSO members in each MYStIX target field from the myriad types of contaminating sources that can resemble YSOs: extragalactic sources, evolved stars, nebular knots, and even unassociated foreground/background YSOs. Applying our methodology consistently across 18 of the target complexes, we produce the MYStIX IRE Source (MIRES) Catalog comprising 20,719 sources, including 8686 probable stellar members of the MYStIX target complexes. We also classify the SEDs of 9365 IR counterparts to MYStIX X-ray sources to assist the first pathway, the identification of X-ray-detected stellar members. The MIRES Catalog provides a foundation for follow-up studies of diverse phenomena related to massive star cluster formation, including protostellar outflows, circumstellar disks, and sequential star formation triggered by massive star feedback processes.

Harnessing cellular differentiation to improve ALA-based photodynamic therapy in an artificial skin model

NASA Astrophysics Data System (ADS)

Maytin, Edward; Anand, Sanjay; Sato, Nobuyuki; Mack, Judith; Ortel, Bernhard

2005-04-01

During ALA-based photodynamic therapy (PDT), a pro-drug (aminolevulinic acid; ALA) is taken up by tumor cells and metabolically converted to a photosensitizing intermediate (protoporphyrin IX; PpIX). ALA-based PDT, while an emerging treatment modality, remains suboptimal for most cancers (e.g. squamous cell carcinoma of the skin). Many treatment failures may be largely due to insufficient conversion of ALA to PpIX within cells. We discovered a novel way to increase the conversion of ALA to PpIX, by administering agents that can drive terminal differentiation (i.e., accelerate cellular maturation). Terminally-differentiated epithelial cells show higher levels of intracellular PpIX, apparently via increased levels of a rate-limiting enzyme, coproporphyrinogen oxidase (CPO). To study these mechanisms in a three-dimensional tissue, we developed an organotypic model that mimics true epidermal physiology in a majority of respects. A line of rat epidermal keratinocytes (REKs), when grown in raft cultures, displays all the features of a fully-differentiated epidermis. Addition of ALA to the culture medium results in ALA uptake and PpIX synthesis, with subsequent death of keratinocytes upon exposure to blue light. Using this model, we can manipulate cellular differentiation via three different approaches. (1) Vitamin D, a hormone that enhances keratinocyte differentiation; (2) Hoxb13, a nuclear transcription factor that affects the genetically-controlled differentiation program of stratifying cells (3) Hyaluronan, an abundant extracellular matrix molecule that regulates epidermal differentiation. Because the raft cultures contain only a single cell type (no blood, fibroblasts, etc.) the effects of terminal differentiation upon CPO, PpIX, and keratinocyte cell death can be specifically defined.

KSC-2009-2464

NASA Image and Video Library

2009-04-01

CAPE CANAVERAL, Fla. – In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, a large crane lifts the Ares I-X upper stage simulator service module/service adapter segment to move it to a stand. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. The Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-2894

NASA Image and Video Library

2009-04-29

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, technicians maneuver the crane that will lift a second roll control system module for installation in an Ares I-X segment. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in August 2009. Photo credit: NASA/Dimitri Gerondidakis

KSC-2009-5249

NASA Image and Video Library

2009-09-25

CAPE CANAVERAL, Fla. – The Ares I-X rocket stands tall inside NASA Kennedy Space Center's Vehicle Assembly Building Bay 3. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I, which is the essential core of a space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system . The Ares I-X flight test is targeted for Oct. 27. Photo credit: NASA/Kim Shiflett

KSC-2009-2897

NASA Image and Video Library

2009-04-29

CAPE CANAVERAL, Fla. –– In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, technicians are ready to maneuver a second roll control system module into place for installation in the Ares I-X segment. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in August 2009. Photo credit: NASA/Dimitri Gerondidakis

KSC-2009-2740

NASA Image and Video Library

2009-04-17

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, at left center, technicians get ready to install the roll control system in the Ares I-X segment in the center. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

Forecasting Maintenance Shortcomings of a Planned Equipment Density Listing in Support of Expeditionary Missions

DTIC Science & Technology

2017-06-01

importantly, it examines the methodology used to build the class IX block embarked on ship prior to deployment. The class IX block is defined as a repository...compared to historical data to evaluate model and simulation outputs. This thesis provides recommendations on improving the methodology implemented in...improving the level of organic support available to deployed units. More importantly, it examines the methodology used to build the class IX block

Qualitative cosmology - Diagrammatic solutions for Bianchi type IX universes with expansion, rotation, and shear. II.

NASA Technical Reports Server (NTRS)

Ryan, M. P., Jr.

1971-01-01

The investigation of expanding, rotating, shearing Bianchi type IX universes is extended to the most general case possible. Use is made of the techniques of Arnowitt et al. (1962). It is shown that the conclusion reached by Arnowitt et al. regarding the small effect of rotation on the singularity of type IX universes is true in general. The superspace approach to the motion of the universe is discussed in an appendix.

Ares I-X Flight Test - The Future Begins Here

NASA Technical Reports Server (NTRS)

Davis, Stephan R.

2008-01-01

In less than two years, the National Aeronautics and Space Administration (NASA) will launch the Ares I-X mission. This will be the first flight of the Ares I crew launch vehicle, which, together with the Ares V cargo launch vehicle, will eventually send humans to the Moon, Mars, and beyond. As the countdown to this first Ares mission continues, personnel from across the Ares I-X Mission Management Office (MMO) are finalizing designs and fabricating vehicle hardware for an April 2009 launch. This paper will discuss the hardware and programmatic progress of the Ares I-X mission. Like the Apollo program, the Ares launch vehicles will rely upon extensive ground, flight, and orbital testing before sending the Orion crew exploration vehicle into space with humans on board. The first flight of Ares I, designated Ares I-X, will be a suborbital development flight test. Ares I-X gives NASA its first opportunity to gather critical data about the flight dynamics of the integrated launch vehicle stack; understand how to control its roll during flight; better characterize the severe stage separation environments that the upper stage engine will experience during future operational flights; and demonstrate the first stage recovery system. NASA also will begin modifying the launch infrastructure and fine-tuning ground and mission operations, as the agency makes the transition from the Space Shuttle to the Ares/Orion system.

Preparation of poly-L-lysine functionalized magnetic nanoparticles and their influence on viability of cancer cells

NASA Astrophysics Data System (ADS)

Khmara, I.; Koneracka, M.; Kubovcikova, M.; Zavisova, V.; Antal, I.; Csach, K.; Kopcansky, P.; Vidlickova, I.; Csaderova, L.; Pastorekova, S.; Zatovicova, M.

2017-04-01

This study was aimed at development of biocompatible amino-functionalized magnetic nanoparticles as carriers of specific antibodies able to detect and/or target cancer cells. Poly-L-lysine (PLL)-modified magnetic nanoparticle samples with different PLL/Fe3O4 content were prepared and tested to define the optimal PLL/Fe3O4 weight ratio. The samples were characterized for particle size and morphology (SEM, TEM and DLS), and surface properties (zeta potential measurements). The optimal PLL/Fe3O4 weight ratio of 1.0 based on both zeta potential and DLS measurements was in agreement with the UV/VIS measurements. Magnetic nanoparticles with the optimal PLL content were conjugated with antibody specific for the cancer biomarker carbonic anhydrase IX (CA IX), which is induced by hypoxia, a physiologic stress present in solid tumors and linked with aggressive tumor behavior. CA IX is localized on the cell surface with the antibody-binding epitope facing the extracellular space and is therefore suitable for antibody-based targeting of tumor cells. Here we showed that PLL/Fe3O4 magnetic nanoparticles exhibit cytotoxic activities in a cell type-dependent manner and bind to cells expressing CA IX when conjugated with the CA IX-specific antibody. These data support further investigations of the CA IX antibody-conjugated, magnetic field-guided/activated nanoparticles as tools in anticancer strategies.

Topical hexylaminolevulinate and aminolevulinic acid photodynamic therapy: complete arteriole vasoconstriction occurs frequently and depends on protoporphyrin IX concentration in vessel wall.

PubMed

Middelburg, T A; de Bruijn, H S; Tettero, L; van der Ploeg van den Heuvel, A; Neumann, H A M; de Haas, E R M; Robinson, D J

2013-09-05

Vascular responses to photodynamic therapy (PDT) may influence the availability of oxygen during PDT and the extent of tumor destruction after PDT. However, for topical PDT vascular effects are largely unknown. Arteriole and venule diameters were measured before and after hexylaminolevulinate (HAL) and aminolevulinic acid (ALA) PDT and related to the protoporphyrin IX (PpIX) concentration in the vessel wall. A mouse skin fold chamber model and an intravital confocal microscope allowed direct imaging of the subcutaneous vessels underlying the treated area. In both HAL and ALA groups over 60% of arterioles constricted completely, while venules generally did not respond, except for two larger veins that constricted partially. Arteriole vasoconstriction strongly correlated with PpIX fluorescence intensity in the arteriole wall. Total PpIX fluorescence intensity was significantly higher for HAL than ALA for the whole area that was imaged but not for the arteriole walls. In conclusion, complete arteriole vasoconstriction occurs frequently in both HAL and ALA based topical PDT, especially when relatively high PpIX concentrations in arteriole walls are reached. Vasoconstriction will likely influence PDT effect and should be considered in studies on topical HAL and ALA-PDT. Also, our results may redefine the vasculature as a potential secondary target for topical PDT. Copyright © 2013 Elsevier B.V. All rights reserved.

Comparative evaluation of compressive strength, diametral tensile strength and shear bond strength of GIC type IX, chlorhexidine-incorporated GIC and triclosan-incorporated GIC: An in vitro study.

PubMed

Jaidka, Shipra; Somani, Rani; Singh, Deepti J; Shafat, Shazia

2016-04-01

To comparatively evaluate the compressive strength, diametral tensile strength, and shear bond strength of glass ionomer cement type IX, chlorhexidine-incorporated glass ionomer cement, and triclosan-incorporated glass ionomer cement. In this study, glass ionomer cement type IX was used as a control. Chlorhexidine diacetate, and triclosan were added to glass ionomer cement type IX powder, respectively, in order to obtain 0.5, 1.25, and 2.5% concentrations of the respective experimental groups. Compressive strength, diametral tensile strength, and shear bond strength were evaluated after 24 h using Instron Universal Testing Machine. The results obtained were statistically analyzed using the independent t-test, Dunnett test, and Tukey test. There was no statistical difference in the compressive strength, diametral tensile strength, and shear bond strength of glass ionomer cement type IX (control), 0.5% triclosan-glass ionomer cement, and 0.5% chlorhexidine-glass ionomer cement. The present study suggests that the compressive strength, diametral tensile strength, and shear bond strength of 0.5% triclosan-glass ionomer cement and 0.5% chlorhexidine-glass ionomer cement were similar to those of the glass ionomer cement type IX, discernibly signifying that these can be considered as viable options for use in pediatric dentistry with the additional value of antimicrobial property along with physical properties within the higher acceptable range.

White light-informed optical properties improve ultrasound-guided fluorescence tomography of photoactive protoporphyrin IX

NASA Astrophysics Data System (ADS)

Flynn, Brendan P.; DSouza, Alisha V.; Kanick, Stephen C.; Davis, Scott C.; Pogue, Brian W.

2013-04-01

Subsurface fluorescence imaging is desirable for medical applications, including protoporphyrin-IX (PpIX)-based skin tumor diagnosis, surgical guidance, and dosimetry in photodynamic therapy. While tissue optical properties and heterogeneities make true subsurface fluorescence mapping an ill-posed problem, ultrasound-guided fluorescence-tomography (USFT) provides regional fluorescence mapping. Here USFT is implemented with spectroscopic decoupling of fluorescence signals (auto-fluorescence, PpIX, photoproducts), and white light spectroscopy-determined bulk optical properties. Segmented US images provide a priori spatial information for fluorescence reconstruction using region-based, diffuse FT. The method was tested in simulations, tissue homogeneous and inclusion phantoms, and an injected-inclusion animal model. Reconstructed fluorescence yield was linear with PpIX concentration, including the lowest concentration used, 0.025 μg/ml. White light spectroscopy informed optical properties, which improved fluorescence reconstruction accuracy compared to the use of fixed, literature-based optical properties, reduced reconstruction error and reconstructed fluorescence standard deviation by factors of 8.9 and 2.0, respectively. Recovered contrast-to-background error was 25% and 74% for inclusion phantoms without and with a 2-mm skin-like layer, respectively. Preliminary mouse-model imaging demonstrated system feasibility for subsurface fluorescence measurement in vivo. These data suggest that this implementation of USFT is capable of regional PpIX mapping in human skin tumors during photodynamic therapy, to be used in dosimetric evaluations.

Impact of the underlying mutation and the route of vector administration on immune responses to factor IX in gene therapy for hemophilia B.

PubMed

Cao, Ou; Hoffman, Brad E; Moghimi, Babak; Nayak, Sushrusha; Cooper, Mario; Zhou, Shangzhen; Ertl, Hildegund C J; High, Katherine A; Herzog, Roland W

2009-10-01

Immune responses to factor IX (F.IX), a major concern in gene therapy for hemophilia, were analyzed for adeno-associated viral (AAV-2) gene transfer to skeletal muscle and liver as a function of the F9 underlying mutation. Vectors identical to those recently used in clinical trials were administered to four lines of hemophilia B mice on a defined genetic background [C3H/HeJ with deletion of endogenous F9 and transgenic for a range of nonfunctional human F.IX (hF.IX) variants]. The strength of the immune response to AAV-encoded F.IX inversely correlated with the degree of conservation of endogenous coding information and levels of endogenous antigen. Null mutation animals developed T- and B-cell responses in both protocols. However, inhibitor titers were considerably higher upon muscle gene transfer (or protein therapy). Transduced muscles of Null mice had strong infiltrates with CD8+ cells, which were much more limited in the liver and not seen for the other mutations. Sustained expression was achieved with liver transduction in mice with crm(-) nonsense and missense mutations, although they still formed antibodies upon muscle gene transfer. Therefore, endogenous expression prevented T-cell responses more effectively than antibody formation, and immune responses varied substantially depending on the protocol and the underlying mutation.

Investigations on photolon-and porphyrin-doped sol-gel fiberoptic coatings for laser-assisted applications in medicine

NASA Astrophysics Data System (ADS)

Bindig, U.; Ulatowska-Jarza, A.; Kopaczynska, M.; Müller, G.; Podbielska, H.

2008-01-01

In view of laser-assisted medical applications, the construction of silica-based sol-gel fiberoptic sensors based on photolon (Ph) and protoporphyrin IX (PP IX) is discussed. Electron microscopy and AFM were used to characterize the silica sol-gel coatings. AFM measurements indicate a change in the surface porosity. The PP IX-based sensors were constructed as a one-layer optode as well as a multilayered structure. An additional hybrid sensor made up of alternate layers of PP IX-and Ph-doped sol-gel was also constructed and examined. Sol-gel matrices were prepared from silicate precursor tetraethylorthosilicate (TEOS) mixed with ethanol in acid-catalyzed hydrolysis. The carrier matrices of photosensitive dyes were produced with factor R = 20, where R denotes the ratio of solvent moles (ethanol) to the number of TEOS moles. A multilayered coating was built up using the reverse-dipping technique. The overall coating thickness was determined by electron microscopy. Doped sol-gels with different PP IX concentrations were used to produce fiberoptic coatings. The film optodes with a different number of layers were examined by fluorescence spectroscopy. It was found that photolon and protoporphyrin IX entrapped in sol-gel preserve their chemical reactivity and have contact with the external environment. The hybrid sensor demonstrated clear fluorescence and a reversible behavior in gaseous environments.

KSC-2009-6026

NASA Image and Video Library

2009-10-30

CAPE CANAVERAL, Fla. – The solid rocket booster recovery ship Freedom Star, towing the spent first stage of NASA's Ares I-X rocket through the Banana River, delivers the booster to Hangar AF at Cape Canaveral Air Force Station in Florida. Following the launch of the Ares I-X flight test, the booster splashed down in the Atlantic Ocean and was recovered. Liftoff of the 6-minute flight test was at 11:30 a.m. EDT Oct. 28. This was the first launch from Kennedy's pads of a vehicle other than the space shuttle since the Apollo Program's Saturn rockets were retired. The parts used to make the Ares I-X booster flew on 30 different shuttle missions ranging from STS-29 in 1989 to STS-106 in 2000. The data returned from more than 700 sensors throughout the rocket will be used to refine the design of future launch vehicles and bring NASA one step closer to reaching its exploration goals. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5595

NASA Image and Video Library

2009-10-20

CAPE CANAVERAL, Fla. – Workers prepare to close the arms of the vehicle stabilization system around the towering 327-foot-tall Ares I-X rocket, newly arrived on Launch Pad 39B at NASA's Kennedy Space Center in Florida. The test rocket left the Vehicle Assembly Building at 1:39 a.m. EDT on its 4.2-mile trek to the pad and was "hard down" on the pad’s pedestals at 9:17 a.m. The transfer of the pad from the Space Shuttle Program to the Constellation Program took place May 31. Modifications made to the pad include the removal of shuttle unique subsystems, such as the orbiter access arm and a section of the gaseous oxygen vent arm, along with the installation of three 600-foot lightning towers, access platforms, environmental control systems and a vehicle stabilization system. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

KSC-2009-5596

NASA Image and Video Library

2009-10-20

CAPE CANAVERAL, Fla. – The arms of the vehicle stabilization system are closed around the towering 327-foot-tall Ares I-X rocket, newly arrived on Launch Pad 39B at NASA's Kennedy Space Center in Florida. The test rocket left the Vehicle Assembly Building at 1:39 a.m. EDT on its 4.2-mile trek to the pad and was "hard down" on the pad’s pedestals at 9:17 a.m. The transfer of the pad from the Space Shuttle Program to the Constellation Program took place May 31. Modifications made to the pad include the removal of shuttle unique subsystems, such as the orbiter access arm and a section of the gaseous oxygen vent arm, along with the installation of three 600-foot lightning towers, access platforms, environmental control systems and a vehicle stabilization system. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I. The Ares I-X flight test is targeted for Oct. 27. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

[The right to medical rehabilitation according to the 2007 act to strengthen health insurance competition, GKV-WSG].

PubMed

Liebold, D

2008-02-01

Since April 1, 2007 medical rehabilitation is a standard insurance benefit of the statutory health insurance scheme (covered by the SGB V, book 5 of the German social code), with the right of the beneficiary to comply especially with the intentions, the principles and the preconditions of the benefits as stipulated in the SGB IX (book 9 of the German social code covering rehabilitation and participation of persons with disabilities). In claiming benefits the applicable rules primarily are those of the SGB IX, as long as the SGB V does not contain different rules. In light of the demands of the SGB IX, the prevailing case law of the Federal Social Court concerning technical aids and assistive devices cannot persist any longer. The so-called "basic-compensation" is contradictory to the specifications of the SGB IX. Medical rehabilitation does not only consist of complex benefits, but every single benefit pursuant to section sign 26 Abs. 2, Abs. 3 SGB IX is a medical rehabilitation benefit if its priority intention is to achieve the beneficiary's participation in society.

Venous drainage of the dorsal sector of the liver: differences between segments I and IX. A study on corrosion casts of the human liver.

PubMed

Gadzijev, E M; Ravnik, D; Stanisavljevic, D; Trotovsek, B

1997-01-01

The aim of this study was to determine the venous drainage of the dorsal sector of the liver in order to define the differences between segments I and IX and their implications for sectorially and segmentally oriented hepatic surgery. The study was based on corrosion casts of 61 macroscopically healthy livers. The drainage pathways of veins at least 10 mm long and 1 mm wide were evaluated and statistically analysed. On average, 9 veins drained the two segments and three veins from both segments entered the inferior vena cava. In 95% of cases the veins from segment I drained predominantly into the inferior vena cava, whereas in segment IX this pathway was dominant in only 30% of cases. In 64% of cases a vein originating in segment IX entered the right hepatic v. The difference in the venous drainage of the two segments suggests that segment IX partly belongs to the neighbouring segments and may thus be only a paracaval region of the right liver.

Structure of the Type IX Group B Streptococcus Capsular Polysaccharide and Its Evolutionary Relationship with Types V and VII

PubMed Central

Berti, Francesco; Campisi, Edmondo; Toniolo, Chiara; Morelli, Laura; Crotti, Stefano; Rosini, Roberto; Romano, Maria Rosaria; Pinto, Vittoria; Brogioni, Barbara; Torricelli, Giulia; Janulczyk, Robert; Grandi, Guido; Margarit, Immaculada

2014-01-01

The Group B Streptococcus capsular polysaccharide type IX was isolated and purified, and the structure of its repeating unit was determined. Type IX capsule →4)[NeupNAc-α-(2→3)-Galp-β-(1→4)-GlcpNAc-β-(1→6)]-β-GlcpNAc-(1→4)-β-Galp-(1→4)-β-Glcp-(1→ appears most similar to types VII and V, although it contains two GlcpNAc residues. Genetic analysis identified differences in cpsM, cpsO, and cpsI gene sequences as responsible for the differentiation between the three capsular polysaccharide types, leading us to hypothesize that type V emerged from a recombination event in a type IX background. PMID:24990951

Factor IX[sub Madrid 2]: A deletion/insertion in Facotr IX gene which abolishes the sequence of the donor junction at the exon IV-intron d splice site

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

Solera, J.; Magallon, M.; Martin-Villar, J.

1992-02-01

DNA from a patient with severe hemophilia B was evaluated by RFLP analysis, producing results which suggested the existence of a partial deletion within the factor IX gene. The deletion was further localized and characterized by PCR amplification and sequencing. The altered allele has a 4,442-bp deletion which removes both the donor splice site located at the 5[prime] end of intron d and the two last coding nucleotides located at the 3[prime] end of exon IV in the normal factor IX gene; this fragment has been inserted in inverted orientation. Two homologous sequences have been discovered at the ends ofmore » the deleted DNA fragment.« less

Photodynamic diagnosis following intravesical instillation of aminolevulinic acid (ALA): first clinical experiences in urology

NASA Astrophysics Data System (ADS)

Baumgartner, Reinhold; Kriegmair, M.; Stepp, Herbert G.; Lumper, W.; Heil, Peter; Riesenberg, Rainer; Stocker, Susanne; Hofstetter, Alfons G.

1993-06-01

Delta Aminolevulinic acid (ALA), a precursor of Protoporphyrin IX (PP IX) in hem biosynthesis has been topically applied in urinary bladders in order to study its potential as fluorescent tumor marker. Preclinical experiments have been performed on chemically induced tumors in rats, revealing a ratio of PP IX-fluorescence intensity up to 20:1 in tumors as compared to healthy urothelium. Synthesis of PP IX has been stimulated in 56 patients by intravesical instillation of a pH-neutral ALA-solution. After an incubation time of two to four hours strong red fluorescence was endoscopically observed even in tiny superficial tumors. Brightness and contrast allows visualization of early stage urothelial diseases with naked eyes and without the necessity suppressing background fluorescence or violet excitation light.

Intracellular localization analysis of npAu-PpIX in HeLa cells using specific dyes and confocal microscopy

NASA Astrophysics Data System (ADS)

Roblero-Bartolón, Victoria Gabriela; Maldonado-Alvarado, Elizabeth; Galván-Mendoza, José Iván; Ramón-Gallegos, Eva

2012-10-01

Cervical carcinoma (CC) represents the second leading cause of cancer death in Mexican women. No conventional treatments are being developed such as photodynamic therapy (PDT), involving the simultaneous presence of a photosensitizer (Ps), light of a specific wavelength and tissue oxygen. On the other hand, it has seen that the use of gold nanoparticles coupled to protoporphyrin IX increases the effectiveness of PDT. The aim of this study was to determine the site of accumulation of the conjugate npAu-PpIX in cells of cervical cancer by the use of specific dyes and confocal microscopy. The results indicate that the gold nanoparticles coupled to protoporphyrin IX are accumulated in both the cytoplasm and nucleus of HeLa cells.

KSC-2009-2463

NASA Image and Video Library

2009-04-01

CAPE CANAVERAL, Fla. –In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, a large crane is attached to the Ares I-X upper stage simulator service module/service adapter segment to lift and move it to a stand. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. The Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-2465

NASA Image and Video Library

2009-04-01

CAPE CANAVERAL, Fla. – In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, a large crane moves the Ares I-X upper stage simulator service module/service adapter segment toward a stand. Other segments are placed and stacked on the floor around it. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. The Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-5081

NASA Image and Video Library

2009-09-11

CAPE CANAVERAL, Fla. – In NASA Kennedy Space Center's Vehicle Assembly Building High Bay 3, NASA's Ares I-X rocket is ready to undergo its first power-up. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I, which is the essential core of a space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. The Ares I-X flight test is targeted for Oct. 31. Photo credit: NASA/Cory Huston

KSC-2009-2467

NASA Image and Video Library

2009-04-01

CAPE CANAVERAL, Fla. – In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the Ares I-X upper stage simulator service module/service adapter (left, center) has been installed on a stand. Other segments are placed and stacked on the floor around it. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. The Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-3738

NASA Image and Video Library

2009-06-15

CAPE CANAVERAL, Fla. – In the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the Ares I-X fifth segment simulator assembly is lowered through a work platform in High Bay 4. Ares I-X is the flight test vehicle for the Ares I, the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Ares I-X is targeted for launch in August 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-5085

NASA Image and Video Library

2009-09-11

CAPE CANAVERAL, Fla. – In NASA Kennedy Space Center's Vehicle Assembly Building High Bay 3, NASA's Ares I-X rocket undergoes its first power-up. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I, which is the essential core of a space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. The Ares I-X flight test is targeted for Oct. 31. Photo credit: NASA/Cory Huston

Ares I-X: First Flight of a New Generation

NASA Technical Reports Server (NTRS)

Davis, Stephan R.; Askins, Bruce R.

2010-01-01

The Ares I-X suborbital development flight test demonstrated NASA s ability to design, develop, launch and control a new human-rated launch vehicle (Figure 14). This hands-on missions experience will provide the agency with necessary skills and insights regardless of the future direction of space exploration. The Ares I-X team, having executed a successful launch, will now focus on analyzing the flight data and extracting lessons learned that will be used to support the development of future vehicles.

ARES I-X Launch Prep

NASA Image and Video Library

2009-10-25

A launch countdown sign showing one day until launch of the NASA ARES I-X rocket is seen along the road between Cape Canaveral Air Force Base and the NASA Kennedy Space Center in Cape Canaveral, Florida on Monday, Oct. 26, 2009. The flight test of Ares I-X, scheduled for Tuesday, Oct. 27, 2009, will provide NASA with an early opportunity to test and prove flight characteristics, hardware, facilities and ground operations associated with the Ares I. Photo Credit: (NASA/Bill Ingalls)

KSC-2009-2743

NASA Image and Video Library

2009-04-17

CAPE CANAVERAL, Fla. –– In the lower right, the roll control system can be seen installed inside the Ares I-X segment. The work is being done in high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

The Application of Lean Thinking Principles and Kaizen Practices for the Successful Development and Implementation of the Ares I-X Flight Test Rocket and Mission

NASA Technical Reports Server (NTRS)

Askins, B. R.; Davis, S. R.; Heitzman, K. S.; Olsen, R. A.

2011-01-01

On October 28, 2009 the Ares I-X flight test rocket launched from Kennedy Space Center and flew its suborbital trajectory as designed. The mission was successfully completed as data from the test, and associated development activities were analyzed, transferred to stakeholders, and well documented. A positive lesson learned from Ares I-X was that the application of lean thinking principles and kaizen practices was very effective in streamlining development activities. Ares I-X, like other historical rocket development projects, was hampered by technical, cost, and schedule challenges and if not addressed boldly could have resulted in cancellation of the test. The mission management team conducted nine major meetings, referred to as lean events, across its elements to assess plans, procedures, processes, requirements, controls, culture, organization, use of resources, and anything that could be changed to optimize schedule or reduce risk. The preeminent aspect of the lean events was the focus on value added activities and the removal or at least reduction in non-value added activities. Trained Lean Six Sigma facilitators assisted the Ares I-X developers in conducting the lean events. They indirectly helped formulate the mission s own unique methodology for assessing schedule. A core team was selected to lead the events and report to the mission manager. Each activity leveraged specialized participants to analyze the subject matter and its related processes and then recommended alternatives and solutions. Stakeholders were the event champions. They empowered and encouraged the team to succeed. The keys to success were thorough preparation, honest dialog, small groups, adherence to the Ares I-X ground rules, and accountability through disciplined reporting and tracking of actions. This lean event formula was game-changing as demonstrated by Ares I-X. It is highly recommended as a management tool to help develop other complex systems efficiently. The key benefits for Ares I-X were obtaining unambiguous schedule margin, defining enabling options for risk reduction, and most importantly a stronger more unified team.

The Application of Lean Thinking Principles and Kaizen Practices for the Successful Development and Implementation of the Ares I-X Flight Test Rocket and Mission

NASA Technical Reports Server (NTRS)

Askins, B. R.; Davis, S. R.; Heitzman, K. S.; Olsen, R. A.

2011-01-01

On October 28, 2009 the Ares I-X flight test rocket launched from Kennedy Space Center and flew its suborbital trajectory as designed. The mission was successfully completed as data from the test, and associated development activities were analyzed, transferred to stakeholders, and well documented. Positive lessons learned from Ares I-X were that the application of lean thinking principles and kaizen practices are effective in streamlining development activities. Ares I-X, like other historical rocket development projects, was hampered by technical, cost, and schedule challenges and if not addressed boldly could have resulted in cancellation of the test. The mission management team conducted nine major meetings, referred to as lean events, across its elements to assess plans, procedures, processes, requirements, controls, culture, organization, use of resources, and anything that could be changed to optimize schedule or reduce risk. The preeminent aspect of the lean events was the focus on value added activities and the removal or at least reduction in non-value activities. Trained Lean Six Sigma facilitators assisted the Ares I-X developers in conducting the lean events. They indirectly helped formulate the mission s own unique methodology for assessing schedule. A core team was selected to lead the events and report to the mission manager. Each activity leveraged specialized participants to analyze the subject matter and its related processes and then recommended alternatives and solutions. Stakeholders were the event champions. They empowered and encouraged the team to succeed. The keys to success were thorough preparation, honest dialog, small groups, adherence to the Ares I-X ground rules, and accountability through disciplined reporting and tracking of actions. This lean event formula was game-changing as demonstrated by the success of Ares I-X. It is highly recommended as a management tool to help develop other complex systems efficiently. The key benefits for Ares I-X were obtaining unambiguous schedule margin, defining enabling options for risk reduction, and most importantly a stronger more unified team.

Skin permeation and retention of topical bead formulation containing tranexamic acid.

PubMed

Vijayakumar, Ajay; Baskaran, Rengarajan; Yoo, Bong Kyu

2017-02-01

The objective of this study is to develop a topical bead formulation of tranexamic acid (TA) which can be used concomitantly with laser treatment. The bead formulation of TA (TAB) was successfully prepared by fluidized bed drying method. Physicochemical properties of the TAB were evaluated in terms of chemical stability of TA and differential scanning calorimetry. TA in the bead was stable up to six months at 25°C and existed as amorphous state. In vitro skin permeation and in vivo skin retention of TA in the beads were significantly higher compared to a commercial product. When the bead was dissolved into distilled water and applied concomitantly with laser treatment, the amount of TA retained in the skin in the in vivo study was inversely proportional to the energy levels of laser treatment, indicating absorption into subcutaneous tissue and drainage to systemic circulation. Therefore, when laser treatment is used concomitantly with TAB, energy level should be very carefully monitored to avoid possible adverse events associated with systemic side effects of TA.

[CORRECTION OF METABOLIC DISTURBANCES IN PATIENTS WITH PULMONARY TUBERCULOSIS AND CONCOMITANT DISEASES].

PubMed

2010-01-01

Metabolic disturbances were corrected using the oral specialized formula Nutrien-phthisio (ZAO "Company Nutritec", Russia) in 53 patients with pulmonary tuberculosis and concomitant diseases. In the whole group, tuberculosis was first detected in 21 patients; 32 had a chronic process. Chemotherapy was discontinued in all the patients due to the intolerance phenomena caused by comorbidity (erosive gastritis, gastroduodenal peptic ulcer, hepatitis B and C, chronic pyelonephritis) in 24 patients, by adverse reactions in 19, and by a combination of both factors in 10. The criteria for objectively monitoring the efficiency of nutritional support (in combination with specific treatment) were body mass index, general blood analysis, by taking into account the percentage and absolute count of lymphocytes and the protein metabolism from the serum levels of total protein, albumin, and transferrin. The study determined clinical and laboratory indications for the use of Nutrien-phthisio and the favorable impact of nutritional support on the course of a tuberculous process and concomitant diseases.

26. Photocopy of August 1918 photograph. Glass Negative Box IX, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

26. Photocopy of August 1918 photograph. Glass Negative Box IX, Tower Grove, Missouri Botanical Garden. ITALIAN GARDEN, LOOKING SOUTHWEST - Missouri Botanical Garden, 2345 Tower Grove Avenue, Saint Louis, Independent City, MO

KSC-2009-1530

NASA Image and Video Library

2009-02-10

CAPE CANAVERAL, Fla. – The Ares I-X roll control system module, comprising two modules and four thrusters, is being prepared for a fit check on the Ares I-X rocket upper stage simulator. The hardware is in high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center. The system is designed to perform a 90-degree roll after the rocket clears the launch tower, preventing a roll during flight and maintaining the orientation of the rocket until separation of the upper and first stages. The system module will return to earth and splash down; it will not be recovered. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in summer of 2009. Photo credit: NASA/Tim Jacobs

KSC-2009-1531

NASA Image and Video Library

2009-02-10

CAPE CANAVERAL, Fla. – The Ares I-X roll control system module, comprising two modules and four thrusters, is being prepared for a fit check on the Ares I-X rocket upper stage simulator. The hardware is in high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center. The system is designed to perform a 90-degree roll after the rocket clears the launch tower, preventing a roll during flight and maintaining the orientation of the rocket until separation of the upper and first stages. The system module will return to earth and splash down; it will not be recovered. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in summer of 2009. Photo credit: NASA/Tim Jacobs

KSC-2009-1532

NASA Image and Video Library

2009-02-10

CAPE CANAVERAL, Fla. – The Ares I-X roll control system module, comprising two modules and four thrusters, is being prepared for a fit check on the Ares I-X rocket upper stage simulator. The hardware is in high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center. The system is designed to perform a 90-degree roll after the rocket clears the launch tower, preventing a roll during flight and maintaining the orientation of the rocket until separation of the upper and first stages. The system module will return to earth and splash down; it will not be recovered. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I-X is targeted for launch in summer of 2009. Photo credit: NASA/Tim Jacobs

Improved sensitivity to fluorescence for cancer detection in wide-field image-guided neurosurgery

PubMed Central

Jermyn, Michael; Gosselin, Yoann; Valdes, Pablo A.; Sibai, Mira; Kolste, Kolbein; Mercier, Jeanne; Angulo, Leticia; Roberts, David W.; Paulsen, Keith D.; Petrecca, Kevin; Daigle, Olivier; Wilson, Brian C.; Leblond, Frederic

2015-01-01

In glioma surgery, Protoporphyrin IX (PpIX) fluorescence may identify residual tumor that could be resected while minimizing damage to normal brain. We demonstrate that improved sensitivity for wide-field spectroscopic fluorescence imaging is achieved with minimal disruption to the neurosurgical workflow using an electron-multiplying charge-coupled device (EMCCD) relative to a state-of-the-art CMOS system. In phantom experiments the EMCCD system can detect at least two orders-of-magnitude lower PpIX. Ex vivo tissue imaging on a rat glioma model demonstrates improved fluorescence contrast compared with neurosurgical fluorescence microscope technology, and the fluorescence detection is confirmed with measurements from a clinically-validated spectroscopic probe. Greater PpIX sensitivity in wide-field fluorescence imaging may improve the residual tumor detection during surgery with consequent impact on survival. PMID:26713218

Pyrazolylbenzo[d]imidazoles as new potent and selective inhibitors of carbonic anhydrase isoforms hCA IX and XII.

PubMed

Kumar, Satish; Ceruso, Mariangela; Tuccinardi, Tiziano; Supuran, Claudiu T; Sharma, Pawan K

2016-07-01

Novel pyrazolylbenzo[d]imidazole derivatives (2a-2f) were designed, synthesized and evaluated against four human carbonic anhydrase isoforms belonging to α family comprising of two cytosolic isoforms hCA I and II as well as two transmembrane tumor associated isoforms hCA IX and XII. Starting from these derivatives that showed high potency but low selectivity in favor of tumor associated isoforms hCA IX and XII, we investigated the impact of removing the sulfonamide group. Thus, analogs 3a-3f without sulfonamide moiety were synthesized and biological assay revealed a good activity as well as an excellent selectivity as inhibitors for tumor associated hCA IX and hCA XII and the same was analyzed by molecular docking studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice.

PubMed

Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng

2017-09-06

Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. Radiosensitizers can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64 Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64 Cu-AGuIX accumulates to high levels in the HepG2 xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the HepG2 cells. In radiation therapy studies, a decrease in 18 F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic radiosensitizer for PET imaging to guide radiotherapy for liver cancer.

Physiological levels of blood coagulation factors IX and X control coagulation kinetics in an in vitro model of circulating tissue factor

NASA Astrophysics Data System (ADS)

Tormoen, Garth W.; Khader, Ayesha; Gruber, András; McCarty, Owen J. T.

2013-06-01

Thrombosis significantly contributes to cancer morbidity and mortality. The mechanism behind thrombosis in cancer may be circulating tissue factor (TF), as levels of circulating TF are associated with thrombosis. However, circulating TF antigen level alone has failed to predict thrombosis in patients with cancer. We hypothesize that coagulation factor levels regulate the kinetics of circulating TF-induced thrombosis. Coagulation kinetics were measured as a function of individual coagulation factor levels and TF particle concentration. Clotting times increased when pooled plasma was mixed at or above a ratio of 4:6 with PBS. Clotting times increased when pooled plasma was mixed at or above a ratio of 8:2 with factor VII-depleted plasma, 7:3 with factor IX- or factor X-depleted plasmas, or 2:8 with factor II-, V- or VIII-depleted plasmas. Addition of coagulation factors VII, X, IX, V and II to depleted plasmas shortened clotting and enzyme initiation times, and increased enzyme generation rates in a concentration-dependent manner. Only additions of factors IX and X from low-normal to high-normal levels shortened clotting times and increased enzyme generation rates. Our results demonstrate that coagulation kinetics for TF particles are controlled by factor IX and X levels within the normal physiological range. We hypothesize that individual patient factor IX and X levels may be prognostic for susceptibility to circulating TF-induced thrombosis.

Evaluation of Novel 64Cu-Labeled Theranostic Gadolinium-Based Nanoprobes in HepG2 Tumor-Bearing Nude Mice

NASA Astrophysics Data System (ADS)

Hu, Pengcheng; Cheng, Dengfeng; Huang, Tao; Banizs, Anna B.; Xiao, Jie; Liu, Guobing; Chen, Quan; Wang, Yuenan; He, Jiang; Shi, Hongcheng

2017-09-01

Radiation therapy of liver cancer is limited by low tolerance of the liver to radiation. Radiosensitizers can effectively reduce the required radiation dose. AGuIX nanoparticles are small, multifunctional gadolinium-based nanoparticles that can carry radioisotopes or fluorescent markers for single-photon emission computed tomography (SPECT), positron emission tomography (PET), fluorescence imaging, and even multimodality imaging. In addition, due to the high atomic number of gadolinium, it can also serve as a tumor radiation sensitizer. It is critical to define the biodistribution and pharmacokinetics of these gadolinium-based nanoparticles to quantitate the magnitude and duration of their retention within the tumor microenvironment during radiotherapy. Therefore, in this study, we successfully labeled AGuIX with 64Cu through the convenient built-in chelator. The biodistribution studies indicated that the radiotracer 64Cu-AGuIX accumulates to high levels in the HepG2 xenograft of nude mice, suggesting that it would be a potential theranostic nanoprobe for image-guided radiotherapy in HCC. We also used a transmission electron microscope to confirm AGuIX uptake in the HepG2 cells. In radiation therapy studies, a decrease in 18F-FDG uptake was observed in the xenografts of the nude mice irradiated with AGuIX, which was injected 1 h before. These results provide proof-of-concept that AGuIX can be used as a theranostic radiosensitizer for PET imaging to guide radiotherapy for liver cancer.

Ares I-X Flight Data Evaluation: Executive Overview

NASA Technical Reports Server (NTRS)

Huebner, Lawrence D.; Waits, David A.; Lewis, Donny L.; Richards, James S.; Coates, R. H., Jr.; Cruit, Wendy D.; Bolte, Elizabeth J.; Bangham, Michal E.; Askins, Bruce R.; Trausch, Ann N.

2011-01-01

NASA's Constellation Program (CxP) successfully launched the Ares I-X flight test vehicle on October 28, 2009. The Ares I-X flight was a developmental flight test to demonstrate that this very large, long, and slender vehicle could be controlled successfully. The flight offered a unique opportunity for early engineering data to influence the design and development of the Ares I crew launch vehicle. As the primary customer for flight data from the Ares I-X mission, the Ares Projects Office (APO) established a set of 33 flight evaluation tasks to correlate flight results with prospective design assumptions and models. The flight evaluation tasks used Ares I-X data to partially validate tools and methodologies in technical disciplines that will ultimately influence the design and development of Ares I and future launch vehicles. Included within these tasks were direct comparisons of flight data with preflight predictions and post-flight assessments utilizing models and processes being applied to design and develop Ares I. The benefits of early development flight testing were made evident by results from these flight evaluation tasks. This overview provides summary information from assessment of the Ares I-X flight test data and represents a small subset of the detailed technical results. The Ares Projects Office published a 1,600-plus-page detailed technical report that documents the full set of results. This detailed report is subject to the International Traffic in Arms Regulations (ITAR) and is available in the Ares Projects Office archives files.

fMRI activities in the emotional cerebellum: a preference for negative stimuli and goal-directed behavior.

PubMed

Schraa-Tam, Caroline K L; Rietdijk, Willem J R; Verbeke, Willem J M I; Dietvorst, Roeland C; van den Berg, Wouter E; Bagozzi, Richard P; De Zeeuw, Chris I

2012-03-01

Several studies indicate that the cerebellum might play a role in experiencing and/or controlling emphatic emotions, but it remains to be determined whether there is a distinction between positive and negative emotions, and, if so, which specific parts of the cerebellum are involved in these types of emotions. Here, we visualized activations of the cerebellum and extracerebellar regions using high-field fMRI, while we asked participants to observe and imitate images with pictures of human faces expressing different emotional states or with moving geometric shapes as control. The state of the emotions could be positive (happiness and surprise), negative (anger and disgust), or neutral. The positive emotional faces only evoked mild activations of crus 2 in the cerebellum, whereas the negative emotional faces evoked prominent activations in lobules VI and VIIa in its hemispheres and lobules VIII and IX in the vermis. The cerebellar activations associated with negative emotions occurred concomitantly with activations of mirror neuron domains such as the insula and amygdala. These data suggest that the potential role of the cerebellum in control of emotions may be particularly relevant for goal-directed behavior that is required for observing and reacting to another person's (negative) expressions.

KSC-2009-6025

NASA Image and Video Library

2009-10-30

CAPE CANAVERAL, Fla. – The solid rocket booster recovery ship Freedom Star, towing the spent first stage of NASA's Ares I-X rocket, traverses the Banana River along the shore of Cape Canaveral Air Force Station in Florida. Across the river, in the background, is the Vehicle Assembly Building at NASA's Kennedy Space Center. Following the launch of the Ares I-X flight test, the booster splashed down in the Atlantic Ocean and was recovered. Liftoff of the 6-minute flight test was at 11:30 a.m. EDT Oct. 28. This was the first launch from Kennedy's pads of a vehicle other than the space shuttle since the Apollo Program's Saturn rockets were retired. The parts used to make the Ares I-X booster flew on 30 different shuttle missions ranging from STS-29 in 1989 to STS-106 in 2000. The data returned from more than 700 sensors throughout the rocket will be used to refine the design of future launch vehicles and bring NASA one step closer to reaching its exploration goals. For information on the Ares I-X vehicle and flight test, visit http://www.nasa.gov/aresIX. Photo credit: NASA/Kim Shiflett

Biodistribution and photodynamic effect of protoporphyrin IX in rat urinary bladders after intravesical instillation of 5-aminolaevulinic acid

NASA Astrophysics Data System (ADS)

Chang, Shi-Chung; MacRobert, Alexander J.; Bown, Stephen G.

1995-03-01

Photodynamic therapy (PDT) has considerable potential for the treatment of superficial bladder neoplasia. Complications such as scarring of the detrusor muscle and prolonged cutaneous photosensitivity may be reduced by using the new photosensitizer precursor, 5- aminolaevulinic acid (ALA). After instillation of ALA, the concentration, pH, and time of bladder retention of ALA solution were found to be the key factors to a satisfactory PpIX buildup in the mucosa. The optimum PpIX fluorescence intensity ratio between mucosa and muscle layer is 10 to 1 with a pH 5.5, 1% ALA solution retained for 5 hours. Higher concentration resulted in more mucosal PpIX formation, but less selectivity. Unbuffered ALA was unsuitable for bladder instillation. Two days after laser treatment with 25 J/cm2 at 630 nm with optimal sensitization, typical histological findings were urothelial sloughing and lamina propria edema without obvious muscle damage. After 7 days, recovery of the urothelium was almost complete and fibroblast infiltration was minimal. ALA induced PpIX after bladder instillation may be an appropriate photosensitizer for future management of superficial bladder cancer.

Ares I-X Flight Test Vehicle Modal Test

NASA Technical Reports Server (NTRS)

Buehrle, Ralph D.; Templeton, Justin D.; Reaves, Mercedes C.; Horta, Lucas G.; Gaspar, James L.; Bartolotta, Paul A.; Parks, Russel A.; Lazor, Daniel R.

2010-01-01

The first test flight of NASA's Ares I crew launch vehicle, called Ares I-X, was launched on October 28, 2009. Ares I-X used a 4-segment reusable solid rocket booster from the Space Shuttle heritage with mass simulators for the 5th segment, upper stage, crew module and launch abort system. Flight test data will provide important information on ascent loads, vehicle control, separation, and first stage reentry dynamics. As part of hardware verification, a series of modal tests were designed to verify the dynamic finite element model (FEM) used in loads assessments and flight control evaluations. Based on flight control system studies, the critical modes were the first three free-free bending mode pairs. Since a test of the free-free vehicle was not practical within project constraints, modal tests for several configurations during vehicle stacking were defined to calibrate the FEM. Test configurations included two partial stacks and the full Ares I-X flight test vehicle on the Mobile Launcher Platform. This report describes the test requirements, constraints, pre-test analysis, test execution and results for the Ares I-X flight test vehicle modal test on the Mobile Launcher Platform. Initial comparisons between pre-test predictions and test data are also presented.

Wide-field spectrally resolved quantitative fluorescence imaging system: toward neurosurgical guidance in glioma resection

NASA Astrophysics Data System (ADS)

Xie, Yijing; Thom, Maria; Ebner, Michael; Wykes, Victoria; Desjardins, Adrien; Miserocchi, Anna; Ourselin, Sebastien; McEvoy, Andrew W.; Vercauteren, Tom

2017-11-01

In high-grade glioma surgery, tumor resection is often guided by intraoperative fluorescence imaging. 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) provides fluorescent contrast between normal brain tissue and glioma tissue, thus achieving improved tumor delineation and prolonged patient survival compared with conventional white-light-guided resection. However, commercially available fluorescence imaging systems rely solely on visual assessment of fluorescence patterns by the surgeon, which makes the resection more subjective than necessary. We developed a wide-field spectrally resolved fluorescence imaging system utilizing a Generation II scientific CMOS camera and an improved computational model for the precise reconstruction of the PpIX concentration map. In our model, the tissue's optical properties and illumination geometry, which distort the fluorescent emission spectra, are considered. We demonstrate that the CMOS-based system can detect low PpIX concentration at short camera exposure times, while providing high-pixel resolution wide-field images. We show that total variation regularization improves the contrast-to-noise ratio of the reconstructed quantitative concentration map by approximately twofold. Quantitative comparison between the estimated PpIX concentration and tumor histopathology was also investigated to further evaluate the system.

Synthesis and biological evaluation of novel aromatic and heterocyclic bis-sulfonamide Schiff bases as carbonic anhydrase I, II, VII and IX inhibitors.

PubMed

Akocak, Suleyman; Lolak, Nabih; Nocentini, Alessio; Karakoc, Gulcin; Tufan, Anzel; Supuran, Claudiu T

2017-06-15

A series of sixteen novel aromatic and heterocyclic bis-sulfonamide Schiff bases were prepared by conjugation of well known aromatic and heterocyclic aminosulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor pharmacophores with aromatic and heterocyclic bis-aldehydes. The obtained bis-sulfonamide Schiff bases were investigated as inhibitors of four selected human (h) CA isoforms, hCA I, hCA II, hCA VII and hCA IX. Most of the newly synthesized compounds showed a good inhibitory profile against isoforms hCA II and hCA IX, also showing moderate selectivity against hCA I and VII. Several efficient lead compounds were identified among this bis-sulfonamide Schiff bases with low nanomolar to sub-nanomolar activity against hCA II (K i s ranging between 0.4 and 861.1nM) and IX (K i s between 0.5 and 933.6nM). Since hCA II and hCA IX are important drug targets (antiglaucoma and anti-tumor agents), these isoform-selective inhibitors may be considered of interest for various biomedical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fluorescence-Guided Resection of Malignant Glioma with 5-ALA

PubMed Central

Kaneko, Sadahiro

2016-01-01

Malignant gliomas are extremely difficult to treat with no specific curative treatment. On the other hand, photodynamic medicine represents a promising technique for neurosurgeons in the treatment of malignant glioma. The resection rate of malignant glioma has increased from 40% to 80% owing to 5-aminolevulinic acid-photodynamic diagnosis (ALA-PDD). Furthermore, ALA is very useful because it has no serious complications. Based on previous research, it is apparent that protoporphyrin IX (PpIX) accumulates abundantly in malignant glioma tissues after ALA administration. Moreover, it is evident that the mechanism underlying PpIX accumulation in malignant glioma tissues involves an abnormality in porphyrin-heme metabolism, specifically decreased ferrochelatase enzyme activity. During resection surgery, the macroscopic fluorescence of PpIX to the naked eye is more sensitive than magnetic resonance imaging, and the alert real time spectrum of PpIX is the most sensitive method. In the future, chemotherapy with new anticancer agents, immunotherapy, and new methods of radiotherapy and gene therapy will be developed; however, ALA will play a key role in malignant glioma treatment before the development of these new treatments. In this paper, we provide an overview and present the results of our clinical research on ALA-PDD. PMID:27429612

KSC-2009-4134

NASA Image and Video Library

2009-07-15

CAPE CANAVERAL, Fla. – A crane is attached to the Ares I-X forward center assembly in NASA Kennedy Space Center's Vehicle Assembly Building. It will be mated with the aft center assembly. Part of the Constellation Program, the Ares I-X is the test vehicle for the Ares I, which is the essential core of a space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system . The Ares I-X flight test is targeted for no earlier than Aug. 30. Photo credit: NASA/Troy Cryder

KSC-2009-1359

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – In the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the fifth segment simulator of the Ares I-X is on a work stand. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I is the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Ares I-X is targeted for launch in July 2009.

KSC-2009-2462

NASA Image and Video Library

2009-04-01

CAPE CANAVERAL, Fla. – In High Bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, the Ares I-X upper stage simulator service module/service adapter segment (foreground) is being prepared for its move to a stand. Other segments are placed and stacked on the floor around it. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. The Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Kim Shiflett

KSC-2009-3875

NASA Image and Video Library

2009-06-30

CAPE CANAVERAL, Fla. – At NASA's Kennedy Space Center in Florida, Marshall Smith, the Ares I-X Systems Engineering and Integration chief, reviews consensus for stacking and mating of the I-X upper stage segments with the management team. Launch of the Ares I-X flight test is targeted no earlier than Aug. 30 from Launch Pad 39B. Ares I is the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Photo credit: NASA/Dimitri Gerondidakis

Intercollegiate Sports. Hearing on Title IX Impact on Women's Participation in Intercollegiate Athletics and Gender Equity before the Subcommittee on Commerce, Consumer Protection, and Competitiveness of the Committee on Energy and Commerce. House of Representatives, One Hundred Third Congress, First Session.

ERIC Educational Resources Information Center

Congress of the U.S., Washington, DC. House Committee on Energy and Commerce.

The purpose of this hearing was to re-examine the status of women's participation in intercollegiate athletics and the impact of the regulations mandated by Title IX of the Education Amendments of 1972. The chairwoman, Honorable Cardiss Collins, opened the hearing by stating that 20 years after passage of Title IX, men continue to dominate all…

VizieR Online Data Catalog: Atomic data for X-ray lines of FeVIII and FeIX (O'Dwyer+, 2012)

NASA Astrophysics Data System (ADS)

O'Dwyer, B.; Del Zanna, G.; Badnell, N. R.; Mason, H. E.; Storey, P. J.

2012-04-01

The distorted wave extension of the autostructure code has been used to calculate energy levels, radiative transition probabilities and collisional excitation rates of Fe VIII and Fe IX up to n=6 for Fe IX and n=7 for Fe VIII. We have compared some of the data with previous calculations, finding overall agreement for radiative transition rates, but interesting differences for some collisional data. ************************************************************************** * * * Sorry, but the author(s) never supplied the tabular material * * announced in the paper * * * **************************************************************************

Surgical anatomy of the styloid muscles and the extracranial glossopharyngeal nerve.

PubMed

Prades, J M; Gavid, M; Asanau, A; Timoshenko, A P; Richard, C; Martin, C H

2014-03-01

The purpose of the study was to determine the relationships between the extracranial glossopharyngeal (IX) nerve and the muscles of the styloid diaphragm. In humans, the IX nerve is a hidden retrostyloid nerve which plays a critical role notably in swallowing and has to be preserved during infratemporal fossa and parapharyngeal spaces surgical procedures. In ten adult heads from cadavers (20 sides) fixed in formalin, dissection of the extracranial IX nerve was performed under operating microscope with special attention given to the relationships between this nerve and the styloid muscles of the styloid diaphragm. The three styloid muscles delimit three triangular intermuscular intervals which were each thoroughly explored. Different osseous landmarks were investigated for easy nerve location. The styloid process (SP) is the main superior osseous landmark for the three muscles of the styloid diaphragm. The stylohyoid muscle (SHM) is anteromedially located to the posterior belly of the digastric muscle. The styloglossus muscle (SGM) is medial and anterior to the SHM. The stylopharyngeal muscle (SPM) is the most vertical and medial of the three styloid muscles. It courses from the medial surface of the SP in a deep plane hidden between the SHM and the SGM. The extracranial IX nerve turns around the SPM superiorly with a vertical segment posterior to the SPM and inferiorly with a horizontal segment lateral to the SPM. The meeting point of the two segments of the IX nerve is about 10 mm anteriorly located from the transverse process of the atlas. The external carotid artery and some of its branches lie in contact with the lateral side of the IX nerve. Such relationships between the extracranial IX nerve, the styloid muscles and the transverse process of the atlas should be appreciated by clinician who treats patients with stylohyoid complex syndromes and by the surgeon for the parapharyngeal spaces approach.

29. Photocopy of 1921 photograph. Glass Negative Box IX, Tower ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

29. Photocopy of 1921 photograph. Glass Negative Box IX, Tower Grove, Missouri Botanical Garden. ITALIAN GARDEN AND NEW PALM HOUSE (DEMOLISHED), LOOKING NORTHEAST - Missouri Botanical Garden, 2345 Tower Grove Avenue, Saint Louis, Independent City, MO

Spatial frequency domain tomography of protoporphyrin IX fluorescence in preclinical glioma models

PubMed Central

Konecky, Soren D.; Owen, Chris M.; Rice, Tyler; Valdés, Pablo A.; Kolste, Kolbein; Wilson, Brian C.; Leblond, Frederic; Roberts, David W.; Paulsen, Keith D.

2012-01-01

Abstract. Multifrequency (0 to 0.3  mm−1), multiwavelength (633, 680, 720, 800, and 820 nm) spatial frequency domain imaging (SFDI) of 5-aminolevulinic acid-induced protoporphyrin IX (PpIX) was used to recover absorption, scattering, and fluorescence properties of glioblastoma multiforme spheroids in tissue-simulating phantoms and in vivo in a mouse model. Three-dimensional tomographic reconstructions of the frequency-dependent remitted light localized the depths of the spheroids within 500 μm, and the total amount of PpIX in the reconstructed images was constant to within 30% when spheroid depth was varied. In vivo tumor-to-normal contrast was greater than ∼1.5 in reduced scattering coefficient for all wavelengths and was ∼1.3 for the tissue concentration of deoxyhemoglobin (ctHb). The study demonstrates the feasibility of SFDI for providing enhanced image guidance during surgical resection of brain tumors. PMID:22612131

Singlet oxygen and ROS in a new light: low-dose subcellular photodynamic treatment enhances proliferation at the single cell level.

PubMed

Blázquez-Castro, Alfonso; Breitenbach, Thomas; Ogilby, Peter R

2014-09-01

Two-photon excitation of a sensitizer with a focused laser beam was used to create a spatially-localized subcellular population of reactive oxygen species, ROS, in single HeLa cells. The sensitizer used was protoporphyrin IX, PpIX, endogenously derived from 5-aminolevulinic acid delivered to the cells. Although we infer that singlet oxygen, O2(a(1)Δg), is one ROS produced upon irradiation of PpIX under these conditions, it is possible that the superoxide ion, O2(-˙), may also play a role in this system. With a "high" dose of PpIX-sensitized ROS, the expected death of the cell was observed. However, under "low dose" conditions, clear signs of cell proliferation were observed. The present results facilitate studies of ROS-mediated signalling in imaging-based single cell experiments.

Gene therapy in an era of emerging treatment options for hemophilia B.

PubMed

Monahan, P E

2015-06-01

Factor IX deficiency (hemophilia B) is less common than factor VIII deficiency (hemophilia A), and innovations in therapy for hemophilia B have generally lagged behind those for hemophilia A. Recently, the first sustained correction of the hemophilia bleeding phenotype by clotting factor gene therapy has been described using recombinant adeno-associated virus (AAV) to deliver factor IX. Despite this success, many individuals with hemophilia B, including children, men with active hepatitis, and individuals who have pre-existing natural immunity to AAV, are not eligible for the current iteration of hemophilia B gene therapy. In addition, recent advances in recombinant factor IX protein engineering have led some hemophilia treaters to reconsider the urgency of genetic cure. Current clinical and preclinical approaches to advancing AAV-based and alternative approaches to factor IX gene therapy are considered in the context of current demographics and treatment of the hemophilia B population. © 2015 International Society on Thrombosis and Haemostasis.

Ares I-X: First Flight of a New Era

NASA Technical Reports Server (NTRS)

Davis, Stephen R.; Askins, Bruce R.

2010-01-01

Since 2005, NASA s Constellation Program has been designing, building, and testing the next generation of launch and space vehicles to carry humans beyond low-Earth orbit (LEO). The Ares Projects at Marshall Space Flight Center (MSFC) are developing the Ares I crew launch vehicle and Ares V cargo launch vehicle. On October 28, 2009, the first development flight test of the Ares I crew launch vehicle, Ares I-X, lifted off from a launch pad at Kennedy Space Center (KSC) on successful suborbital flight. Basing exploration launch vehicle designs on Ares I-X information puts NASA one step closer to full-up "test as you fly," a best practice in vehicle design. Although the final Constellation Program architecture is under review, the Ares I-X data and experience in vehicle design and operations can be applied to any launch vehicle. This paper presents the mission background as well as results and lessons learned from the flight.

Oral-facial-digital syndrome type IX in a patient with Dandy-Walker malformation.

PubMed Central

Nagai, K; Nagao, M; Nagao, M; Yanai, S; Minagawa, K; Takahashi, Y; Takekoshi, Y; Ishizaka, A; Matsuzono, Y; Kobayashi, O; Itagaki, T

1998-01-01

We report a girl with oral, facial, and digital anomalies including multiple alveolar frenula, lobulated tongue with nodules, a posterior cleft palate, hypertelorism, a prominent forehead with a large anterior fontanelle, and postaxial polydactyly in both hands and the right foot, features compatible with the oral-facial-digital syndrome (OFDS). In addition, she had bilateral microphthalmia, optic disc coloboma, and retinal degeneration with partial detachment, thus establishing a diagnosis of OFDS type IX. Dandy-Walker malformation and retrobulbar cysts were observed on MRI. These additional malformations have not been reported in OFDS type IX. The frequent apnoeic spells which occurred immediately after birth were relieved after cystoperitoneal shunt implantation for hydrocephalus. Considering our case and previous reports of OFDS type IX, including two male sibs, a boy born to consanguineous parents, and three females, inheritance is probably autosomal recessive. Images PMID:9598735

A direct and simultaneous detection of zinc protoporphyrin IX, free protoporphyrin IX, and fluorescent heme degradation product in red blood cell hemolysates.

PubMed

Chen, Qiuying; Hirsch, Rhoda Elison

2006-03-01

Fluorescence emission of free protoporphyrin IX (PPIX, em. approximately 626 nm), zinc protoporphyrin IX (ZPP, em. approximately 594 nm) and fluorescent heme degradation product (FHDP, em. approximately 466 nm) are identified and simultaneously detected in mouse and human red cell hemolysates, when excited at 365 nm. A novel method is established for comparing relative FHDP, PPIX and ZPP levels in hemolysates without performing red cell porphyrin extractions. The ZPP fluorescence directly measured in hemolysates (F(365/594)) correlates with the ZPP fluorescence obtained from acetone/water extraction (R(2) = 0.9515, P < 0.0001). The relative total porphyrin (ZPP and PPIX) fluorescence obtained from direct hemolysate fluorescence measurements also correlates with red blood cell total porphyrins determined by ethyl acetate extraction (Piomelli extraction, R(2) = 0.88, P < 0.0001). These fluorescent species serves as biomarkers for alterations in Hb synthesis and Hb stability.

KSC-2009-1661

NASA Image and Video Library

2009-02-16

CAPE CANAVERAL, Fla. – In high bay 4 of the Vehicle Assembly Building at NASA's Kennedy Space Center, workers lift the Ares I-X crew module mock-up during a fit check with a mock-up of the service module. When fully developed, the 16-foot diameter crew module will furnish living space and reentry protection for future astronauts, and the service module’s main engine will be used to break out of lunar orbit for the return trip to Earth. Ares I-X is the test flight for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. The I-X flight will provide NASA an early opportunity to test and prove hardware, facilities and ground operations associated with Ares I launches. Targeted for the summer of 2009, the launch of the full-scale Ares I-X will be the first in a series of unpiloted rocket launches from Kennedy. Photo credit: NASA/Jack Pfaller

Setting of commercial glass ionomer cement Fuji IX by (27)Al and (19)F MAS-NMR.

PubMed

Munhoz, Tais; Karpukhina, Natalia; Hill, Robert G; Law, Robert V; De Almeida, L H

2010-04-01

To investigate the long term setting reaction in the glass ionomer restorative, Fuji IX, by monitoring the structural evolution of aluminium and fluorine species using (27)Al and (19)F MAS-NMR spectroscopy. Fuji IX cements aged from 5min up to 3 months were prepared according to the manufacturer instructions from the commercial material. The (27)Al and (19)F MAS-NMR studies were carried out on powders made after terminating the setting reaction. (27)Al MAS-NMR results show conversion of aluminium from the glass phase, where it has coordination number four, Al(IV), into the cement matrix where it has a coordination number of six, Al(VI). At least two different Al(VI) species were detected at short ageing time cements. Assignment of these species is discussed and compared with the data from other sources. The possibility for a condensed aluminium species [Al(13)(OH)(24)(H(2)O)(12)](7+) to form is considered. The ratio of aluminium in the cement, Al(VI), to the remaining unreacted in glass has been evaluated by deconvolution of the spectra. Various theoretical ratios of aluminium species in the cement matrix to the unreacted ones remaining in glass have been estimated. The (19)F MAS-NMR spectra are identical for the glass and cements at the early times and contain a dominant signal assigned to Al-F-Sr(n). The data confirms that the conversion of aluminium is a diffusion-controlled process at early stage less than 1h and it is largely complete between 1 and 6h. The comparison with the experimental data shows that the majority of aluminium cations do not form tricarboxylates but are coordinated with one or two carboxylic groups and other ligands. Insufficient amount of water and excess of glass in this cement formulation affect glass degradation mechanism. Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.

Genetic Correction and Hepatic Differentiation of Hemophilia B-specific Human Induced Pluripotent Stem Cells.

PubMed

He, Qiong; Wang, Hui-Hui; Cheng, Tao; Yuan, Wei-Ping; Ma, Yu-Po; Jiang, Yong-Ping; Ren, Zhi-Hua

2017-09-27

Objective To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient. Methods First, the disease-causing mutation was detected by sequencing the encoding area of human coagulation factor IX (F IX) gene. Genomic DNA was extracted from the iPSCs, and the primers were designed to amplify the eight exons of F IX. Next, the point mutation in those iPSCs was genetically corrected using CRISPR/Cas9 technology in the presence of a 129-nucleotide homologous repair template that contained two synonymous mutations. Then, top 8 potential off-target sites were subsequently analyzed using Sanger sequencing. Finally, the corrected clones were differentiated into hepatocyte-like cells, and the secretion of F IX was validated by immunocytochemistry and ELISA assay. Results The cell line bore a missense mutation in the 6 th coding exon (c.676 C>T) of F IX gene. Correction of the point mutation was achieved via CRISPR/Cas9 technology in situ with a high efficacy at about 22% (10/45) and no off-target effects detected in the corrected iPSC clones. F IX secretion, which was further visualized by immunocytochemistry and quantified by ELISA in vitro, reached about 6 ng/ml on day 21 of differentiation procedure. Conclusions Mutations in human disease-specific iPSCs could be precisely corrected by CRISPR/Cas9 technology, and corrected cells still maintained hepatic differentiation capability. Our findings might throw a light on iPSC-based personalized therapies in the clinical application, especially for hemophilia B.

Cellular pH and PI3K signaling as determinants of Protoporphyrin IX conversion and ALA PDT response

NASA Astrophysics Data System (ADS)

Anderson, Michael; El-Hamidi, Hamid; Celli, Jonathan

2018-02-01

ALA PDT is a FDA approved cancer treatment. The general model is that excess exogenous ALA is eventually converted to the active photosensitizer, PpIX, and accumulates PpIX to concentrations well above baseline. This accumulation, however, varies considerable from person to person and even intra-tumorally due to a high number of factors that are involved. Due to this there is an increasing desire to pair ALA PDT with other treatments to enhance the efficacy of PDT. This idea itself isn't new as the labs of Bin Chen and Edward Maytin have a long history of using biology to enhance PpIX accumulation. The PI3K pathway is a long-studied cancer treatment target due to it being one of the most ubiquitous over expressed pathways in cancer and that many treatments have demonstrated enhanced efficacy upon PI3K inhibition. In this paper we show that the PI3K pathway inhibitor, LY294002, alters PpIX accumulation in cells (decreased for A431 and increases for Panc-1 and Panc-1 OR) and significantly increases the efficacy of ALA PDT in every case for both monolayer and spheroid cultures. Additionally, we show that PDT treatments using the nonendogenous photosensitizer, verteporfin, also have enhanced efficacy upon PI3K inhibition. Beyond the treatment synergy of PI3K inhibition and PDT, this work presents a cell pairing model that is perfect to study the previously, to our knowledge, undocumented connection between the PI3K pathway and PpIX accumulation.

Vitamin D Combined with Aminolevulinate (ALA)-Mediated Photodynamic Therapy (PDT) for Human Psoriasis: A Proof-of-Principle Study

PubMed Central

Maytin, Edward V.; Honari, Golara; Khachemoune, Amor; Taylor, Charles R.; Ortel, Bernhard; Pogue, Brian W.; Sznycer-Taub, Nathaniel; Hasan, Tayyaba

2012-01-01

We previously showed that select agents (methotrexate or Vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with Vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation plays a major role, could serve as a useful model to test the effects of pro-differentiating agents upon PpIX levels in a non-neoplastic setting. In particular, Vitamin D, a treatment for psoriasis that restores (increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of 7 patients with bilaterally-matched psoriatic plaques. A regimen in which calcipotriol 0.005% ointment was applied for 3 days prior to ALA-PDT with blue light, led to preferential increases in PpIX (~130%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with Vitamin D and ALA-PDT for psoriasis. PMID:23264699

Legal Forum: Title IX: Does It Apply to Employees?

ERIC Educational Resources Information Center

McCarthy, Martha

1981-01-01

Briefly reviews a number of Federal court cases that have dealt with Title IX, considering the issue of whether the 1974 regulations prohibiting sex discrimination in employment practices accurately reflect the intent of the 1972 law. (GC)

Effects of Bovine Polymerized Hemoglobin in Coagulation in Controlled Hemorrhagic Shock in Swine

DTIC Science & Technology

2005-01-01

continuous blood pressure monitoring. A pulmonary artery catheter was also inserted. To mimic soft tissue injury, the rectus abdominus muscle was crushed in...volume by catheter withdrawal of blood over 15 min (;1.7 mL/kg/min). Time 0 designated initiation of the rectus abdominus crush and concomitant hemorrhage

Serum potassium monitoring for users of ethinyl estradiol/drospirenone taking medications predisposing to hyperkalemia: physician compliance and survey of knowledge and attitudes.

PubMed

Mona Eng, Patricia; Seeger, John D; Loughlin, Jeanne; Oh, Kelly; Walker, Alexander M

2007-02-01

Yasmin-28 [ethinyl estradiol 0.03 mg/drospirenone 3 mg (EE/DRSP)] contains drospirenone, a progestin component that possesses antimineralocorticoid activity with a potassium-sparing diuretic effect similar to that in spironolactone. Product labeling recommends potassium monitoring in the first month of use for women concurrently receiving medication that may increase serum potassium. We evaluated compliance with this recommendation by measuring monitoring around the date of oral contraceptive (OC) initiation in women who received EE/DRSP while being treated with medications predisposing to hyperkalemia and in similar women who received other OCs. Because preliminary analyses indicated incomplete compliance, we surveyed physicians who prescribed EE/DRSP to women receiving drugs predisposing to hyperkalemia on their knowledge and attitudes with regard to the recommendation. We conducted this study using data from the Ingenix Research Datamart, which includes insurance claims for reimbursement for medical services and prescription medications for approximately 8,000,000 members of a large nationally dispersed health plan. We used claims for pharmacy dispensings of prescription medications to identify all women aged 10-59 years old who initiated EE/DRSP or other OCs during the first 3 years of EE/DRSP availability (July 2001 to June 2004). The frequency of potassium monitoring was measured by identifying claims for serum potassium tests. We conducted a telephone survey of 58 physicians who had prescribed EE/DRSP up to June 2003 to women who received concomitant hyperkalemic drugs. Although potassium monitoring was generally more frequent among EE/DRSP initiators receiving concomitant hyperkalemic drugs than among other OC initiators receiving similar medications, only 40% of 466 EE/DRSP initiators with concurrent hyperkalemic treatment had potassium tests. More than 98% of surveyed physicians were aware of the potassium-sparing property of EE/DRSP. Compared with physicians whose patients had potassium tests, physicians of patients without such tests were more likely to disagree with the recommendation for users of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, heparin and nonsteroidal anti-inflammatory drugs. Patient barriers and health plan restrictions were other factors possibly contributing to noncompliance. This study demonstrates incomplete physician compliance with a labeling recommendation of potassium monitoring for initiators of EE/DRSP receiving concomitant therapy predisposing to hyperkalemia. The limited compliance was likely due to a combination of selective physician acceptance of the recommendations and specific patient and health plan barriers to testing.

Addressing Sexual Violence as Student Affairs Work

ERIC Educational Resources Information Center

Landreman, Lisa M.; Williamsen, Kaaren M.

2018-01-01

In this chapter, we outline the challenges campuses face in addressing sexual violence and Title IX compliance. We argue that there are critical roles for student affairs professionals in Title IX work in developing effective campus sexual violence prevention and response strategies.

KSC-2009-1358

NASA Image and Video Library

2009-01-26

CAPE CANAVERAL, Fla. – In the Vehicle Assembly Building at NASA's Kennedy Space Center in Florida, workers begin removing the protective material wrapping the fifth segment simulator of the Ares I-X. Ares I-X is the test vehicle for the Ares I, which is part of the Constellation Program to return men to the moon and beyond. Ares I is the essential core of a safe, reliable, cost-effective space transportation system that eventually will carry crewed missions back to the moon, on to Mars and out into the solar system. Ares I-X is targeted for launch in July 2009. Photo credit: NASA/Tim Jacobs

A Double Selection Approach to Achieve Specific Expression of Toxin Genes for Ovarian Cancer Gene Therapy

DTIC Science & Technology

2005-11-01

biological properties. CAV-1 is known to cause allergic two knobs may in fact be distinct based on our uveitis, called the ’blue eye syndrome ’ and rarely...system - first steps towards gene therapy of Alport syndrome . Gene Ther 3(1), 2 1-7. Hemminki, A., and Alvarez, R. D. 2002. Adenoviruses in oncology: a...Ad-IX- Ad-IX-imRFPI or Ad-IX-tdimer2(12) (10000 viral particles/ tdimer2(12) with plX modifications, and wild-type El/E3 cell) were added to the