Preferred SH3 Domain Partners of ADAM Metalloproteases Include Shared and ADAM-Specific SH3 Interactions

PubMed Central

Kleino, Iivari; Järviluoma, Annika; Hepojoki, Jussi; Huovila, Ari Pekka; Saksela, Kalle

2015-01-01

A disintegrin and metalloproteinases (ADAMs) constitute a protein family essential for extracellular signaling and regulation of cell adhesion. Catalytic activity of ADAMs and their predicted potential for Src-homology 3 (SH3) domain binding show a strong correlation. Here we present a comprehensive characterization of SH3 binding capacity and preferences of the catalytically active ADAMs 8, 9, 10, 12, 15, 17, and 19. Our results revealed several novel interactions, and also confirmed many previously reported ones. Many of the identified SH3 interaction partners were shared by several ADAMs, whereas some were ADAM-specific. Most of the ADAM-interacting SH3 proteins were adapter proteins or kinases, typically associated with sorting and endocytosis. Novel SH3 interactions revealed in this study include TOCA1 and CIP4 as preferred partners of ADAM8, and RIMBP1 as a partner of ADAM19. Our results suggest that common as well as distinct mechanisms are involved in regulation and execution of ADAM signaling, and provide a useful framework for addressing the pathways that connect ADAMs to normal and aberrant cell behavior. PMID:25825872

The ADAMS interactive interpreter

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

Rietscha, E.R.

1990-12-17

The ADAMS (Advanced DAta Management System) project is exploring next generation database technology. Database management does not follow the usual programming paradigm. Instead, the database dictionary provides an additional name space environment that should be interactively created and tested before writing application code. This document describes the implementation and operation of the ADAMS Interpreter, an interactive interface to the ADAMS data dictionary and runtime system. The Interpreter executes individual statements of the ADAMS Interface Language, providing a fast, interactive mechanism to define and access persistent databases. 5 refs.

Electromagnetic guided couch and multileaf collimator tracking on a TrueBeam accelerator

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

Hansen, Rune; Ravkilde, Thomas; Worm, Esben Schjødt

2016-05-15

Purpose: Couch and MLC tracking are two promising methods for real-time motion compensation during radiation therapy. So far, couch and MLC tracking experiments have mainly been performed by different research groups, and no direct comparison of couch and MLC tracking of volumetric modulated arc therapy (VMAT) plans has been published. The Varian TrueBeam 2.0 accelerator includes a prototype tracking system with selectable couch or MLC compensation. This study provides a direct comparison of the two tracking types with an otherwise identical setup. Methods: Several experiments were performed to characterize the geometric and dosimetric performance of electromagnetic guided couch and MLCmore » tracking on a TrueBeam accelerator equipped with a Millennium MLC. The tracking system latency was determined without motion prediction as the time lag between sinusoidal target motion and the compensating motion of the couch or MLC as recorded by continuous MV portal imaging. The geometric and dosimetric tracking accuracies were measured in tracking experiments with motion phantoms that reproduced four prostate and four lung tumor trajectories. The geometric tracking error in beam’s eye view was determined as the distance between an embedded gold marker and a circular MLC aperture in continuous MV images. The dosimetric tracking error was quantified as the measured 2%/2 mm gamma failure rate of a low and a high modulation VMAT plan delivered with the eight motion trajectories using a static dose distribution as reference. Results: The MLC tracking latency was approximately 146 ms for all sinusoidal period lengths while the couch tracking latency increased from 187 to 246 ms with decreasing period length due to limitations in the couch acceleration. The mean root-mean-square geometric error was 0.80 mm (couch tracking), 0.52 mm (MLC tracking), and 2.75 mm (no tracking) parallel to the MLC leaves and 0.66 mm (couch), 1.14 mm (MLC), and 2.41 mm (no tracking) perpendicular to

Adam: a Unix Desktop Application Manager

NASA Astrophysics Data System (ADS)

LiÉBana, M.; Marquina, M.; Ramos, R.

ADAM stands for Affordable Desktop Application Manager. It is a GUI developed at CERN with the aim to ease access to applications. The motivation to develop ADAM came from the unavailability of environments like COSE/CDE and their heavy resource consumption. ADAM has proven to be user friendly: new users are able to customize it to their needs in few minutes. Groups of users may share through ADAM a common application environment. ADAM also integrates the Unix and the PC world. PC users can access Unix applications in the same way as their usual Windows applications. This paper describes all the ADAM features, how they are used at CERN Public Services, and the future plans for ADAM.

On Murray Jackson's 1961 'Chair, couch and countertransference'.

PubMed

Connolly, Angela

2015-09-01

One of the problems facing psychoanalysts of all schools is that theory has evolved at a much faster pace than practice. Whereas there has been an explosion of theory, practice has remained, at least officially, static and unchanging. It is in this sense that Murray Jackson's 1961 paper is still relevant today. Despite the rise of the new relational and intersubjective paradigms, most psychoanalysts, and not a few Jungian analysts, still seem to feel that the couch is an essential component of the analytical setting and process. If the use of the couch is usually justified by the argument that it favours regression, facilitates analytical reverie and protects the patient from the influence of the analyst, over time many important psychoanalysts have come to challenge this position. Increasingly these analysts suggest that the use of the couch may actually be incompatible with the newer theoretical models. This contention is strengthened by some of the findings coming from the neurosciences and infant research. This underlines the necessity of empirical research to verify the clinical effectiveness of these different positions, couch or face-to-face, but it is exactly this type of research that is lacking. © 2015, The Society of Analytical Psychology.

Ansel Adams: early works

NASA Astrophysics Data System (ADS)

Throckmorton, Jodi

2010-02-01

Ansel Adams (1902-1984), photographer, musician, naturalist, explorer, critic, and teacher, was a giant in the field of landscape photography. In his images of the unspoiled Western landscape, he strove to capture the sublime: the transcendentalist concept that nature can generate the experience of awe for the viewer. Many viewers are familiar with the heroic, high-contrast prints on high-gloss paper that Adams made to order beginning in the 1970s; much less well known are the intimate prints that the artist crafted earlier in his career. This exhibition focuses on these masterful small prints from the 1920s into the 1950s. During this time period, Adams's printing style changed dramatically. The painterly, soft-focus, warm-toned style of the Parmelian Prints of the High Sierras from the 1920s evolved into the sharp-focus style of the f/64 school of photography that Adams co-founded in the 1930s with Edward Weston and Imogen Cunningham. After World War II, Adams opted for a cooler, higher-contrast look for his prints. Throughout the various styles in which he chose to work, Adams explored the power of nature and succeeded in establishing landscape photography as a legitimate form of modern art.

The analytic setting today: using the couch or the chair?

PubMed

Wiener, Jan

2015-09-01

This paper re-visits Murray Jackson's 1961 paper in the Journal of Analytical Psychology, 'Chair, couch and countertransference', with the aim of exploring the role of the couch for Jungian analysts in clinical practice today. Within the Society of Analytical Psychology (SAP) and some other London-based societies, there has been an evolution of practice from face-to-face sessions with the patient in the chair, as was Jung's preference, to a mode of practice where patients use the couch with the analyst sitting to the side rather than behind, as has been the tradition in psychoanalysis. Fordham was the founding member of the SAP and it was because of his liaison with psychoanalysis and psychoanalysts that this cultural shift came about. Using clinical examples, the author explores the couch/chair question in terms of her own practice and the internal setting as a structure in her mind. With reference to Bleger's (2013) paper 'Psychoanalysis of the psychoanalytic setting', the author discusses how the analytic setting, including use of the couch or the chair, can act as a silent container for the most primitive aspects of the patient's psyche which will only emerge in analysis when the setting changes or is breached. © 2015, The Society of Analytical Psychology.

ADAM -- Unix Version

NASA Astrophysics Data System (ADS)

Chipperfield, A. J.

This document describes the use of the Starlink Software Environment, ADAM, on Unix. It is primarily of use to programmers but the early sections contain information useful to any user. It is assumed that the reader is familiar with the concepts of ADAM programming and that the Starlink software is installed in the standard way.

Real-time intra-fraction-motion tracking using the treatment couch: a feasibility study

NASA Astrophysics Data System (ADS)

D'Souza, Warren D.; Naqvi, Shahid A.; Yu, Cedric X.

2005-09-01

Significant differences between planned and delivered treatments may occur due to respiration-induced tumour motion, leading to underdosing of parts of the tumour and overdosing of parts of the surrounding critical structures. Existing methods proposed to counter tumour motion include breath-holds, gating and MLC-based tracking. Breath-holds and gating techniques increase treatment time considerably, whereas MLC-based tracking is limited to two dimensions. We present an alternative solution in which a robotic couch moves in real time in response to organ motion. To demonstrate proof-of-principle, we constructed a miniature adaptive couch model consisting of two movable platforms that simulate tumour motion and couch motion, respectively. These platforms were connected via an electronic feedback loop so that the bottom platform responded to the motion of the top platform. We tested our model with a seven-field step-and-shoot delivery case in which we performed three film-based experiments: (1) static geometry, (2) phantom-only motion and (3) phantom motion with simulated couch motion. Our measurements demonstrate that the miniature couch was able to compensate for phantom motion to the extent that the dose distributions were practically indistinguishable from those in static geometry. Motivated by this initial success, we investigated a real-time couch compensation system consisting of a stereoscopic infra-red camera system interfaced to a robotic couch known as the Hexapod™, which responds in real time to any change in position detected by the cameras. Optical reflectors placed on a solid water phantom were used as surrogates for motion. We tested the effectiveness of couch-based motion compensation for fixed fields and a dynamic arc delivery cases. Due to hardware limitations, we performed film-based experiments (1), (2) and (3), with the robotic couch at a phantom motion period and dose rate of 16 s and 100 MU min-1, respectively. Analysis of film measurements

Modeling treatment couches in the Pinnacle treatment planning system: Especially important for arc therapy

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

Duggar, William Neil, E-mail: wduggar@umc.edu; Nguyen, Alex; Stanford, Jason

This study is to demonstrate the importance and a method of properly modeling the treatment couch for dose calculation in patient treatment using arc therapy. The 2 treatment couch tops—Aktina AK550 and Elekta iBEAM evo—of Elekta LINACs were scanned using Philips Brilliance Big Bore CT Simulator. Various parts of the couch tops were contoured, and their densities were measured and recorded on the Pinnacle treatment planning system (TPS) using the established computed tomography density table. These contours were saved as organ models to be placed beneath the patient during planning. Relative attenuation measurements were performed following procedures outlined by TG-176more » as well as absolute dose comparison of static fields of 10 × 10 cm{sup 2} that were delivered through the couch tops with that calculated in the TPS with the couch models. A total of 10 random arc therapy treatment plans (5 volumetric-modulated arc therapy [VMAT] and 5 stereotactic body radiation therapy [SBRT]), using 24 beams, were selected for this study. All selected plans were calculated with and without couch modeling. Each beam was evaluated using the Delta{sup 4} dosimetry system (Delta{sup 4}). The Student t-test was used to determine statistical significance. Independent reviews were exploited as per the Imaging and Radiation Oncology Core head and neck credentialing phantom. The selected plans were calculated on the actual patient anatomies with and without couch modeling to determine potential clinical effects. Large relative beam attenuations were noted dependent on which part of the couch top beams were passing through. Substantial improvements were also noted for static fields both calculated with the TPS and delivered physically when the couch models were included in the calculation. A statistically significant increase in agreement was noted for dose difference, distance to agreement, and γ-analysis with the Delta{sup 4} on VMAT and SBRT plans. A credentialing review

ADAMS: AIRLAB data management system user's guide

NASA Technical Reports Server (NTRS)

Conrad, C. L.; Ingogly, W. F.; Lauterbach, L. A.

1986-01-01

The AIRLAB Data Management System (ADAMS) is an online environment that supports research at NASA's AIRLAB. ADAMS provides an easy to use interactive interface that eases the task of documenting and managing information about experiments and improves communication among project members. Data managed by ADAMS includes information about experiments, data sets produced, software and hardware available in AIRLAB as well as that used in a particular experiment, and an on-line engineer's notebook. The User's Guide provides an overview of the ADAMS system as well as details of the operations available within ADAMS. A tutorial section takes the user step-by-step through a typical ADAMS session. ADAMS runs under the VAX/VMS operating system and uses the ORACLE database management system and DEC/FMS (the Forms Management System). ADAMS can be run from any VAX connected via DECnet to the ORACLE host VAX. The ADAMS system is designed for simplicity, so interactions within the underlying data management system and communications network are hidden from the user.

Was Adam a Real Person?

ERIC Educational Resources Information Center

Lamoureux, Denis O.

2011-01-01

Belief in the historicity of Adam has been held firmly throughout the history of the church. In the light of modern biblical criticism and the evolutionary sciences, some conservative Christians are now questioning whether or not Adam was a real person. This paper argues that the existence of Adam in the opening chapters of scripture reflects an…

Quality control procedures for dynamic treatment delivery techniques involving couch motion.

PubMed

Yu, Victoria Y; Fahimian, Benjamin P; Xing, Lei; Hristov, Dimitre H

2014-08-01

In this study, the authors introduce and demonstrate quality control procedures for evaluating the geometric and dosimetric fidelity of dynamic treatment delivery techniques involving treatment couch motion synchronous with gantry and multileaf collimator (MLC). Tests were designed to evaluate positional accuracy, velocity constancy and accuracy for dynamic couch motion under a realistic weight load. A test evaluating the geometric accuracy of the system in delivering treatments over complex dynamic trajectories was also devised. Custom XML scripts that control the Varian TrueBeam™ STx (Serial #3) axes in Developer Mode were written to implement the delivery sequences for the tests. Delivered dose patterns were captured with radiographic film or the electronic portal imaging device. The couch translational accuracy in dynamic treatment mode was 0.01 cm. Rotational accuracy was within 0.3°, with 0.04 cm displacement of the rotational axis. Dose intensity profiles capturing the velocity constancy and accuracy for translations and rotation exhibited standard deviation and maximum deviations below 3%. For complex delivery involving MLC and couch motions, the overall translational accuracy for reproducing programmed patterns was within 0.06 cm. The authors conclude that in Developer Mode, TrueBeam™ is capable of delivering dynamic treatment delivery techniques involving couch motion with good geometric and dosimetric fidelity.

Social Networking Sites' Influence on Travelers' Authentic Experience a Case Study of Couch Surfing

ERIC Educational Resources Information Center

Liu, Xiao

2013-01-01

This study explored travelers' experiences in the era of network hospitality 2.0 using CouchSurfing.org as a case study. The following research questions guided this study: 1) what experience does CouchSurfing create for travelers before, during and after their travel? 2) how does couch surfers' experience relate to authenticity in context of…

Impact of radiation attenuation by a carbon fiber couch on patient dose verification

NASA Astrophysics Data System (ADS)

Yu, Chun-Yen; Chou, Wen-Tsae; Liao, Yi-Jen; Lee, Jeng-Hung; Liang, Ji-An; Hsu, Shih-Ming

2017-02-01

The aim of this study was to understand the difference between the measured and calculated irradiation attenuations obtained using two algorithms and to identify the influence of couch attenuation on patient dose verification. We performed eight tests of couch attenuation with two photon energies, two longitudinal couch positions, and two rail positions. The couch attenuation was determined using a radiation treatment planning system. The measured and calculated attenuations were compared. We also performed 12 verifications of head-and-neck and rectum cases by using a Delta phantom. The dose deviation (DD), distance to agreement (DTA), and gamma index of pencil-beam convolution (PBC) verifications were nearly the same. The agreement was least consistent for the anisotropic analytical algorithm (AAA) without the couch for the head-and-neck case, in which the DD, DTA, and gamma index were 74.4%, 99.3%, and 89%, respectively; for the rectum case, the corresponding values were 56.2%, 95.1%, and 92.4%. We suggest that dose verification should be performed using the following three metrics simultaneously: DD, DTA, and the gamma index.

Utilization of optical tracking to validate a software-driven isocentric approach to robotic couch movements for proton radiotherapy.

PubMed

Hsi, Wen C; Law, Aaron; Schreuder, Andreas N; Zeidan, Omar A

2014-08-01

An optical tracking and positioning system (OTPS) was developed to validate the software-driven isocentric (SDI) approach to control the six-degrees-of-freedom movement of a robotic couch. The SDI approach to movements rotating around a predefined isocenter, referred to as a GeoIso, instead of a mechanical pivot point was developed by the robot automation industry. With robotic couch-sag corrections for weight load in a traditional SDI approach, movements could be accurately executed for a GeoIso located within a 500 mm cubic volume on the couch for treatments. The accuracy of SDI movement was investigated using the OTPS. The GeoIso was assumed to align with the proton beam isocenter (RadIso) for gantry at the reference angle. However, the misalignment between GeoIso and RadIso was quantitatively investigated by measuring the displacements at various couch angles for a target placed at the RadIso at an initial couch angle. When circular target displacements occur on a plane, a relative isocenter shift (RIS) correction could be applied in the SDI movement to minimize target displacements. Target displacements at a fixed gantry angle without and with RIS correction were measured for 12 robotic couches. Target displacements for various gantry angles were performed on three couches in gantry rooms to study the gantry-induced RadIso shift. The RIS correction can also be applied for the RadIso shift. A new SDI approach incorporating the RIS correction with the couch sag is described in this study. In parallel, the accuracy of SDI translation movements for various weight loads of patients on the couch was investigated during positioning of patients for proton prostate treatments. For a fixed gantry angle, measured target displacements without RIS correction for couch rotations in the horizontal plane varied from 4 to 20 mm. However, measured displacements perpendicular to couch rotation plane were about 2 mm for all couches. Extracted misalignments of GeoIso and RadIso in

Utilization of optical tracking to validate a software-driven isocentric approach to robotic couch movements for proton radiotherapy

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

Hsi, Wen C., E-mail: Wen.Hsi@Mclaren.org, E-mail: Wenchien.hsi@sphic.org.cn; Zeidan, Omar A., E-mail: omar.zeidan@orlandohealth.com; Law, Aaron

Purpose: An optical tracking and positioning system (OTPS) was developed to validate the software-driven isocentric (SDI) approach to control the six-degrees-of-freedom movement of a robotic couch. Methods: The SDI approach to movements rotating around a predefined isocenter, referred to as a GeoIso, instead of a mechanical pivot point was developed by the robot automation industry. With robotic couch-sag corrections for weight load in a traditional SDI approach, movements could be accurately executed for a GeoIso located within a 500 mm cubic volume on the couch for treatments. The accuracy of SDI movement was investigated using the OTPS. The GeoIso wasmore » assumed to align with the proton beam isocenter (RadIso) for gantry at the reference angle. However, the misalignment between GeoIso and RadIso was quantitatively investigated by measuring the displacements at various couch angles for a target placed at the RadIso at an initial couch angle. When circular target displacements occur on a plane, a relative isocenter shift (RIS) correction could be applied in the SDI movement to minimize target displacements. Target displacements at a fixed gantry angle without and with RIS correction were measured for 12 robotic couches. Target displacements for various gantry angles were performed on three couches in gantry rooms to study the gantry-induced RadIso shift. The RIS correction can also be applied for the RadIso shift. A new SDI approach incorporating the RIS correction with the couch sag is described in this study. In parallel, the accuracy of SDI translation movements for various weight loads of patients on the couch was investigated during positioning of patients for proton prostate treatments. Results: For a fixed gantry angle, measured target displacements without RIS correction for couch rotations in the horizontal plane varied from 4 to 20 mm. However, measured displacements perpendicular to couch rotation plane were about 2 mm for all couches. Extracted

Helping Eve overcome ADAM: G-quadruplexes in the ADAM-15 promoter as new molecular targets for breast cancer therapeutics.

PubMed

Brown, Robert V; Gaerig, Vanessa C; Simmons, Taesha; Brooks, Tracy A

2013-12-05

ADAM-15, with known zymogen, secretase, and disintegrin activities, is a catalytically active member of the ADAM family normally expressed in early embryonic development and aberrantly expressed in various cancers, including breast, prostate and lung. ADAM-15 promotes extracellular shedding of E-cadherin, a soluble ligand for the HER2/neu receptor, leading to activation, increased motility, and proliferation. Targeted downregulation of both ADAM-15 and HER2/neu function synergistically kills breast cancer cells, but to date there are no therapeutic options for decreasing ADAM-15 function or expression. In this vein, we have examined a unique string of guanine-rich DNA within the critical core promoter of ADAM-15. This region of DNA consists of seven contiguous runs of three or more consecutive guanines, which, under superhelical stress, can relax from duplex DNA to form an intrastrand secondary G-quadruplex (G4) structure. Using biophysical and biological techniques, we have examined the G4 formation within the entire and various truncated regions of the ADAM-15 promoter, and demonstrate strong intrastrand G4 formation serving to function as a biological silencer element. Characterization of the predominant G4 species formed within the ADAM-15 promoter will allow for specific drug targeting and stabilization, and the further development of novel, targeted therapeutics.

Apollo couch energy absorbers

NASA Technical Reports Server (NTRS)

Wesselski, C. J.; Drexel, R. E.

1972-01-01

Load attenuators for the Apollo spacecraft crew couch and its potential applications are described. Energy absorption is achieved through friction and cyclic deformation of material. In one concept, energy absorption is accomplished by rolling a compressed ring of metal between two surfaces. In another concept, energy is absorbed by forcing a plastically deformed washer along a rod. Among the design problems that had to be solved were material selection, fatigue life, ring slippage, lubrication, and friction loading.

NASA Dryden test pilot Michael J. Adams

NASA Image and Video Library

1967-03-22

Air Force test pilot Maj. Michael J. Adams stands beside X-15 ship number one. Adams was selected for the X-15 program in 1966 and made his first flight on Oct. 6, 1966. On Nov. 15, 1967, Adams made his seventh and final X-15 flight. The X-15 launched from the B-52, but during the ascent an electrical problem affected the X-15's control system. The aircraft crashed northwest of Cuddeback Lake, California, causing the death of Adams. He was posthumously awarded Air Force astronaut wings because his final flight exceeded 50 miles in altitude. Adams was the only pilot lost in the 199-flight X-15 program.

SU-F-T-298: The Impact of Modeling the Treatment Couch On Patient Specific VMAT QA

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

Gelover, E; Dalhart, A; Hyer, D

2016-06-15

Purpose: The aim of this work is to quantify the impact of modeling the treatment couch on the passing rate of ion chamber measurements during VMAT quality assurance. Methods: For the initial characterization, attenuation and surface dose measurements were performed following the guidelines of TG-176 for the Civco Universal couch top using an Elekta VersaHD accelerator at an energy of 6 MV. A simulation CT was performed to aid in the creation of contours for representing the shape and size of the couch top in the treatment planning system (TPS). A uniform value of density for the couch wall wasmore » determined by comparing the ratios of ion chamber measurements made in a 30×30×11 cm3 water phantom with the TPS dose values of a plan with the same geometry. At our institution, patient specific quality assurance is performed using a Sun Nuclear ArcCheck with a multi-plug for chamber measurements, a 0.125cc PTW TN31010 chamber, and a Sun Nuclear 1010 electrometer. Ten VMAT plans were transferred into the phantom geometry created in the TPS with two settings: with and without the couch. The chamber measurements were compared to both treatment plans. Results: A maximum attenuation of 3.6% was observed when the gantry angle was set to 120 and 240 degrees, passing obliquely through the couch. A uniform density of 0.6 g/cm3 for the couch wall was determined in the TPS by comparison with measured data. The VMAT ion chamber measurement/plan ratios systematically improved by 1.79% ±0.53% for all patients when the couch was included in the calculation. Conclusion: The attenuation and surface dose changes produced by the Civco couch can generate observable dose difference in VMAT plans. Including a couch model in the phantom plan used for patient specific VMAT QA can improve the ionization chamber agreement by up to ∼2%.« less

SU-E-T-570: New Quality Assurance Method Using Motion Tracking for 6D Robotic Couches

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

Cheon, W; Cho, J; Ahn, S

Purpose: To accommodate geometrically accurate patient positioning, a robotic couch that is capable of 6-degrees of freedom has been introduced. However, conventional couch QA methods are not sufficient to enable the necessary accuracy of tests. Therefore, we have developed a camera based motion detection and geometry calibration system for couch QA. Methods: Employing a Visual-Tracking System (VTS, BonitaB10, Vicon, UK) which tracks infrared reflective(IR) markers, camera calibration was conducted using a 5.7 × 5.7 × 5.7 cm{sup 3} cube attached with IR markers at each corner. After positioning a robotic-couch at the origin with the cube on the table top,more » 3D coordinates of the cube’s eight corners were acquired by VTS in the VTS coordinate system. Next, positions in reference coordinates (roomcoordinates) were assigned using the known relation between each point. Finally, camera calibration was completed by finding a transformation matrix between VTS and reference coordinate systems and by applying a pseudo inverse matrix method. After the calibration, the accuracy of linear and rotational motions as well as couch sagging could be measured by analyzing the continuously acquired data of the cube while the couch moves to a designated position. Accuracy of the developed software was verified through comparison with measurement data when using a Laser tracker (FARO, Lake Mary, USA) for a robotic-couch installed for proton therapy. Results: VTS system could track couch motion accurately and measured position in room-coordinates. The VTS measurements and Laser tracker data agreed within 1% of difference for linear and rotational motions. Also because the program analyzes motion in 3-Dimension, it can compute couch sagging. Conclusion: Developed QA system provides submillimeter/ degree accuracy which fulfills the high-end couch QA. This work was supported by the National Research Foundation of Korea funded by Ministry of Science, ICT & Future Planning. (2013M2

Dynamic trajectory-based couch motion for improvement of radiation therapy trajectories in cranial SRT

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

MacDonald, R. Lee; Thomas, Christopher G., E-mail: Chris.Thomas@cdha.nshealth.ca; Department of Medical Physics, Nova Scotia Cancer Centre, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia B3H 1V7

2015-05-15

Purpose: To investigate potential improvement in external beam stereotactic radiation therapy plan quality for cranial cases using an optimized dynamic gantry and patient support couch motion trajectory, which could minimize exposure to sensitive healthy tissue. Methods: Anonymized patient anatomy and treatment plans of cranial cancer patients were used to quantify the geometric overlap between planning target volumes and organs-at-risk (OARs) based on their two-dimensional projection from source to a plane at isocenter as a function of gantry and couch angle. Published dose constraints were then used as weighting factors for the OARs to generate a map of couch-gantry coordinate space,more » indicating degree of overlap at each point in space. A couch-gantry collision space was generated by direct measurement on a linear accelerator and couch using an anthropomorphic solid-water phantom. A dynamic, fully customizable algorithm was written to generate a navigable ideal trajectory for the patient specific couch-gantry space. The advanced algorithm can be used to balance the implementation of absolute minimum values of overlap with the clinical practicality of large-scale couch motion and delivery time. Optimized cranial cancer treatment trajectories were compared to conventional treatment trajectories. Results: Comparison of optimized treatment trajectories with conventional treatment trajectories indicated an average decrease in mean dose to the OARs of 19% and an average decrease in maximum dose to the OARs of 12%. Degradation was seen for homogeneity index (6.14% ± 0.67%–5.48% ± 0.76%) and conformation number (0.82 ± 0.02–0.79 ± 0.02), but neither was statistically significant. Removal of OAR constraints from volumetric modulated arc therapy optimization reveals that reduction in dose to OARs is almost exclusively due to the optimized trajectory and not the OAR constraints. Conclusions: The authors’ study indicated that simultaneous couch and gantry

Assessing the image quality of pelvic MR images acquired with a flat couch for radiotherapy treatment planning.

PubMed

McJury, M; O'Neill, A; Lawson, M; McGrath, C; Grey, A; Page, W; O'Sullivan, J M

2011-08-01

To improve the integration of MRI with radiotherapy treatment planning, our department fabricated a flat couch top for our MR scanner. Setting up using this couch top meant that the patients were physically higher up in the scanner and, posteriorly, a gap was introduced between the patient and radiofrequency coil. Phantom measurements were performed to assess the quantitative impact on image quality. A phantom was set up with and without the flat couch insert in place, and measurements of image uniformity and signal to noise were made. To assess clinical impact, six patients with pelvic cancer were recruited and scanned on both couch types. The image quality of pairs of scans was assessed by two consultant radiologists. The use of the flat couch insert led to a drop in image signal to noise of approximately 14%. Uniformity in the anteroposterior direction was affected the most, with little change in right-to-left and feet-to-head directions. All six patients were successfully scanned on the flat couch, although one patient had to be positioned with their arms by their sides. The image quality scores showed no statistically significant change between scans with and without the flat couch in place. Although the quantitative performance of the coil is affected by the integration of a flat couch top, there is no discernible deterioration of diagnostic image quality, as assessed by two consultant radiologists. Although the flat couch insert moved patients higher in the bore of the scanner, all patients in the study were successfully scanned.

IL-5-stimulated eosinophils adherent to periostin undergo stereotypic morphological changes and ADAM8-dependent migration.

PubMed

Johansson, M W; Khanna, M; Bortnov, V; Annis, D S; Nguyen, C L; Mosher, D F

2017-10-01

on periostin-rich extracellular matrix in the asthmatic airway in an ADAM8-dependent manner, making ADAM8 a possible therapeutic target. © 2017 John Wiley & Sons Ltd.

Adam Bratis, Ph.D. | NREL

Science.gov Websites

Sciences & Technology Adam.Bratis@nrel.gov | 303-384-7852 Areas of Expertise Adam Bratis joined the managerial oversight in the areas of biochemical conversion, thermochemical conversion, algal biofuels with 11 years of experience with ExxonMobil in the areas of research and development, corporate

Development and evaluation of a prototype tracking system using the treatment couch

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

Lang, Stephanie, E-mail: stephanie.lang@usz.ch; Riesterer, Oliver; Klöck, Stephan

2014-02-15

Purpose: Tumor motion increases safety margins around the clinical target volume and leads to an increased dose to the surrounding healthy tissue. The authors have developed and evaluated a one-dimensional treatment couch tracking system to counter steer respiratory tumor motion. Three different motion detection sensors with different lag times were evaluated. Methods: The couch tracking system consists of a motion detection sensor, which can be the topometrical system Topos (Cyber Technologies, Germany), the respiratory gating system RPM (Varian Medical Systems) or a laser triangulation system (Micro Epsilon), and the Protura treatment couch (Civco Medical Systems). The control of the treatmentmore » couch was implemented in the block diagram environment Simulink (MathWorks). To achieve real time performance, the Simulink models were executed on a real time engine, provided by Real-Time Windows Target (MathWorks). A proportional-integral control system was implemented. The lag time of the couch tracking system using the three different motion detection sensors was measured. The geometrical accuracy of the system was evaluated by measuring the mean absolute deviation from the reference (static position) during motion tracking. This deviation was compared to the mean absolute deviation without tracking and a reduction factor was defined. A hexapod system was moving according to seven respiration patterns previously acquired with the RPM system as well as according to a sin{sup 6} function with two different frequencies (0.33 and 0.17 Hz) and the treatment table compensated the motion. Results: A prototype system for treatment couch tracking of respiratory motion was developed. The laser based tracking system with a small lag time of 57 ms reduced the residual motion by a factor of 11.9 ± 5.5 (mean value ± standard deviation). An increase in delay time from 57 to 130 ms (RPM based system) resulted in a reduction by a factor of 4.7 ± 2.6. The Topos based tracking

Poster - Thur Eve - 38: Review of couch parameters using an FMEA.

PubMed

Larouche, R; Doucet, R; Rémy, E; Filion, A; Poirier, L

2012-07-01

To improve patient safety during positioning, we undertook a systematic review of the processes used by our center to obtain couch positions. We used a Failure Mode and Effects Analysis (FMEA) framework and fifteen different possible failures were identified and rated. The three major failures were 1) Loss of planned couch position and bias from the previous day's couch position, 2) DICOM origin or isocenter is different between two plans (imaging or treatment), and 3) Patient shift in opposite direction than intended. The main effect of these failures was to cause an override of couch parameters. Based on these results, we modified our processes, introduced new QA and software checks and developed new tolerance tables so as to improve system robustness and increase our success rate at catching failures before they can affect the patient. It has been a year since we made these modifications. Based on our results, we have reduced the number of overrides at our center from a maximum of 20.5% to a maximum of 6.3%, with an average at 4% of daily treatments. Our results suggest that FMEA is an effective tool in improving treatment quality that could be used in other centers. © 2012 American Association of Physicists in Medicine.

Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain

NASA Astrophysics Data System (ADS)

Miller, Miles A.; Moss, Marcia L.; Powell, Gary; Petrovich, Robert; Edwards, Lori; Meyer, Aaron S.; Griffith, Linda G.; Lauffenburger, Douglas A.

2015-10-01

Dysregulation of ErbB-family signaling underlies numerous pathologies and has been therapeutically targeted through inhibiting ErbB-receptors themselves or their cognate ligands. For the latter, “decoy” antibodies have been developed to sequester ligands including heparin-binding epidermal growth factor (HB-EGF); however, demonstrating sufficient efficacy has been difficult. Here, we hypothesized that this strategy depends on properties such as ligand-receptor binding affinity, which varies widely across the known ErbB-family ligands. Guided by computational modeling, we found that high-affinity ligands such as HB-EGF are more difficult to target with decoy antibodies compared to low-affinity ligands such as amphiregulin (AREG). To address this issue, we developed an alternative method for inhibiting HB-EGF activity by targeting its cleavage from the cell surface. In a model of the invasive disease endometriosis, we identified A Disintegrin and Metalloproteinase 12 (ADAM12) as a protease implicated in HB-EGF shedding. We designed a specific inhibitor of ADAM12 based on its recombinant prodomain (PA12), which selectively inhibits ADAM12 but not ADAM10 or ADAM17. In endometriotic cells, PA12 significantly reduced HB-EGF shedding and resultant cellular migration. Overall, specific inhibition of ligand shedding represents a possible alternative to decoy antibodies, especially for ligands such as HB-EGF that exhibit high binding affinity and localized signaling.

ADAM-17: The Enzyme That Does It All

PubMed Central

Gooz, Monika

2010-01-01

This review focuses on the role of ADAM-17 in disease. Since its debut as the tumor necrosis factor converting enzyme or TACE, ADAM-17 has been reported to be an indispensible regulator of almost every cellular event from proliferation to migration. The central role of ADAM-17 in cell regulation is rooted in its diverse array of substrates: cytokines, growth factors, and their receptors as well as adhesion molecules are activated or inactivated by their cleavage with ADAM-17. It is therefore not surprising that ADAM-17 is implicated in numerous human diseases including cancer, heart disease, diabetes, rheumatoid arthritis, kidney fibrosis, Alzheimer’s disease, and is a promising target for future treatments. The specific role of ADAM-17 in the pathophysiology of these diseases is very complex and depends on the cellular context. To exploit the therapeutic potential of ADAM-17, it is important to understand how its activity is regulated and how specific organs and cells can be targeted to inactivate or activate the enzyme. PMID:20184396

Structural Characterization of the Ectodomain of a Disintegrin and Metalloproteinase-22 (ADAM22), a Neural Adhesion Receptor Instead of Metalloproteinase INSIGHTS ON ADAM FUNCTION

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

Liu, Heli; Shim, Ann H.R.; He, Xiaolin

2009-12-01

ADAMs (adisintegrin and metalloproteinases) are a family of multidomain transmembrane glycoproteins with diverse roles in physiology and diseases, with several members being drug targets for cancer and inflammation therapies. The spatial organization of the ADAM extracellular segment and its influence on the function of ADAMs have been unclear. Although most members of the ADAM family are active zinc metalloproteinases, 8 of 21 ADAMs lack functional metalloproteinase domains and are implicated in protein-protein interactions instead of membrane protein ectodomain shedding. One of such non-proteinase ADAMs, ADAM22, acts as a receptor on the surface of the postsynaptic neuron to regulate synaptic signalmore » transmission. The crystal structure of the full ectodomain of mature human ADAM22 shows that it is a compact four-leaf clover with the metalloproteinase-like domain held in the concave face of a rigid module formed by the disintegrin, cysteine-rich, and epidermal growth factor-like domains. The loss of metalloproteinase activity is ensured by the absence of critical catalytic residues, the filling of the substrate groove, and the steric hindrance by the cysteine-rich domain. The structure, combined with calorimetric experiments, suggests distinct roles of three putative calcium ions bound to ADAM22, with one in the metalloproteinase-like domain being regulatory and two in the disintegrin domain being structural. The metalloproteinase-like domain contacts the rest of ADAM22 with discontinuous, hydrophilic, and poorly complemented interactions, suggesting the possibility of modular movement of ADAM22 and other ADAMs. The ADAM22 structure provides a framework for understanding how different ADAMs exert their adhesive function and shedding activities.« less

New Mathematical Dimensions: Adam's Story

ERIC Educational Resources Information Center

Manizade, Agida

2009-01-01

Adam, an 11th grader, was identified as gifted and accepted into a two week summer enrichment program. He signed up for "Geometry with Flash Programming." He had no prior programming experience but had a strong and healthy self-image as mathematics student. Although Adam had a positive attitude toward mathematics and saw himself as a successful…

SU-E-T-315: Dosimetric Effects of Couch Top Shift On VMAT Delivery in Absence of Indexing

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

Islam, M; Jin, H; Ferguson, S

2015-06-15

Purpose: To investigate dosimetric effects of couch top shift for volumetric-modulated arc therapy (VMAT) in absence of indexing of immobilization devices. Methods: A total of twelve VMAT treatment plans were selected from three regions (lung, abdomen, and pelvis) to account for the variation of the patient position relative to the couch top. The treatment plans were generated using the Varian Eclipse system. A pinpoint ionization chamber (PTW TN31014) was placed at the center of 16-cm solid water phantom and the dose was delivered using the Varian TrueBeam STx with BrainLAB ExacTrac couch top. To simulate the day-to-day variation of themore » patient position relative to couch top, the couch top was laterally shifted up to 50 mm, with an increment of 5 mm from 0 to 20 mm; and of 10 mm afterwards, and the phantom was moved back to 0 cm shift for measurement. The dose was also delivered using a Varian tennis racket grid insert at 0 cm shift to simulate the absence of couch top. The treatment plans were delivered with 6, 10, and 15 MV photons using the same leaf sequencing to investigate the energy dependence of couch top shift. The dose difference was normalized to 0 cm shift for the regular couch top for comparison. Results: The percent difference of dose was found to increase with lateral shift for all energies; however, the average differences were close to 0% and the maximum difference was within 1% along the lateral shifts. The differences with the absence of couch top were 2.2±0.5% (6MV), 1.7±0.3% (10MV), and 1.6±0.2% (15MV), respectively. Conclusion: The inclusion of couch top is recommended in treatment planning to minimize the dosimetric uncertainty between calculated and delivered dose even in absence of indexing of immobilization devices in VMAT delivery.« less

ADAM9 is involved in pathological retinal neovascularization.

PubMed

Guaiquil, Victor; Swendeman, Steven; Yoshida, Tsunehiko; Chavala, Sai; Campochiaro, Peter A; Blobel, Carl P

2009-05-01

Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9(-/-) mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9(-/-) mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer.

SU-C-207-04: Reconstruction Artifact Reduction in X-Ray Cone Beam CT Using a Treatment Couch Model

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

Lasio, G; Hu, E; Zhou, J

2015-06-15

Purpose: to mitigate artifacts induced by the presence of the RT treatment couch in on-board CBCT and improve image quality Methods: a model of a Varian IGRT couch is constructed using a CBCT scan of the couch in air. The model is used to generate a set of forward projections (FP) of the treatment couch at specified gantry angles. The model couch forward projections are then used to process CBCT scan projections which contain the couch in addition to the scan object (Catphan phantom), in order to remove the attenuation component of the couch at any given gantry angle. Priormore » to pre-processing with the model FP, the Catphan projection data is normalized to an air scan with bowtie filter. The filtered Catphan projections are used to reconstruct the CBCT with an in-house FDK algorithm. The artifact reduction in the processed CBCT scan is assessed visually, and the image quality improvement is measured with the CNR over a few selected ROIs of the Catphan modules. Results: Sufficient match between the forward projected data and the x-ray projections is achieved to allow filtering in attenuation space. Visual improvement of the couch induced artifacts is achieved, with a moderate expense of CNR. Conclusion: Couch model-based correction of CBCT projection data has a potential for qualitative improvement of clinical CBCT scans, without requiring position specific correction data. The technique could be used to produce models of other artifact inducing devices, such as immobilization boards, and reduce their impact on patient CBCT images.« less

AMS -- The Unix ADAM Message System

NASA Astrophysics Data System (ADS)

Kelly, B. D.; Chipperfield, A. J.

The ADAM Message System (AMS) library, which implements the ADAM inter-task communications protocol under Unix, is described, along with its Fortran-callable interface (FAMS). The description of AMS is distinguished from the current implementation which uses the Message System Primitives (MSP).

RefPrimeCouch—a reference gene primer CouchApp

PubMed Central

Silbermann, Jascha; Wernicke, Catrin; Pospisil, Heike; Frohme, Marcus

2013-01-01

To support a quantitative real-time polymerase chain reaction standardization project, a new reference gene database application was required. The new database application was built with the explicit goal of simplifying not only the development process but also making the user interface more responsive and intuitive. To this end, CouchDB was used as the backend with a lightweight dynamic user interface implemented client-side as a one-page web application. Data entry and curation processes were streamlined using an OpenRefine-based workflow. The new RefPrimeCouch database application provides its data online under an Open Database License. Database URL: http://hpclife.th-wildau.de:5984/rpc/_design/rpc/view.html PMID:24368831

"Couch-potatoeism" and childhood obesity: The inverse causality hypothesis.

PubMed

Fröberg, Andreas

2015-04-01

The bulk of cross-sectional studies suggests that lower levels of physical activity are associated with childhood obesity. Although this has led to the general understanding that "couch-potatoes" are fat on account of their inactive lifestyles, cross-sectional studies do not imply causality. On the contrary, the contribution of physical activity to obesity during childhood is currently unclear, and lately, studies have suggested that "couch-potatoeism" could be the result of obesity rather than its cause. Coupled with evidence suggesting that interventions have had little effect on children's physical activity levels as well as on obesity, this inverse causality challenges the role of physical activity in childhood obesity prevention strategies. Copyright © 2015 Elsevier Inc. All rights reserved.

ADAM9 Is Involved in Pathological Retinal Neovascularization▿

PubMed Central

Guaiquil, Victor; Swendeman, Steven; Yoshida, Tsunehiko; Chavala, Sai; Campochiaro, Peter A.; Blobel, Carl P.

2009-01-01

Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9−/− mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9−/− mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer. PMID:19273593

Connective tissue growth factor is a substrate of ADAM28

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

Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki

2010-11-26

Research highlights: {yields} The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. {yields} ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF{sub 165} complex. {yields} CTGF digestion by ADAM28 releases biologically active VEGF{sub 165} from the complex. {yields} ADAM28, CTGF and VEGF{sub 165} are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. {yields} These suggest that ADAM28 promotes VEGF{sub 165}-induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF{sub 165} complex. -- Abstract: ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinomamore » cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala{sup 181}-Tyr{sup 182} and Asp{sup 191}-Pro{sup 192} bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor{sub 165} (VEGF{sub 165}), releasing biologically active VEGF{sub 165} from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF{sub 165}-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF{sub 165} complex.« less

Maternal serum ADAM12s as a marker of rare aneuploidies in the first or second trimester of pregnancy.

PubMed

Spencer, Kevin; Cowans, Nicholas J; Stamatopoulou, Anastasia

2007-12-01

To assess whether the maternal serum ADAM12s concentrations are altered in the first and second trimester of pregnancies complicated by rare aneuploides. ADAM12s was measured by a semi-automated time-resolved immunofluorometric assay in a series of 60 first-trimester cases with trisomy 13, 78 first-trimester cases with Turner's syndrome, 38 first-trimester cases with triploidy and 24 first-trimester cases with sex aneuploidy-the cases were compared with the data from 389 first-trimester controls. In the second trimester, a smaller number of 6, 7, 2 and 13 cases, respectively, were compared with the data from 341 controls. All data were expressed as multiple of the median (MoM) and corrected for maternal weight. Correlation with previously analysed markers (PAPP-A, free beta-hCG and delta NT) was performed. The first-trimester median MoM ADAM12s was significantly lower than 1.0 in all types of rare aneuploidy with the possible exception of triploidy type II. A significant positive correlation with gestational age was reported for trisomy 13 and Turner's syndrome. ADAM12s was not significantly correlated with any other first-trimester marker. In the second trimester, ADAM12s values were marginally increased in these rare aneuploidies. ADAM12s has already been shown to be a possible early first- and second-trimester marker of trisomies 21 and 18. Our data also show the possibility of levels of this marker being altered in the first and second trimester of pregnancies with rare aneuploidies. This may be a useful addition to screening strategies in the future. Copyright (c) 2007 John Wiley & Sons, Ltd.

The cysteine-rich domain regulates ADAM protease function in vivo.

PubMed

Smith, Katherine M; Gaultier, Alban; Cousin, Helene; Alfandari, Dominique; White, Judith M; DeSimone, Douglas W

2002-12-09

ADAMs are membrane-anchored proteases that regulate cell behavior by proteolytically modifying the cell surface and ECM. Like other membrane-anchored proteases, ADAMs contain candidate "adhesive" domains downstream of their metalloprotease domains. The mechanism by which membrane-anchored cell surface proteases utilize these putative adhesive domains to regulate protease function in vivo is not well understood. We address this important question by analyzing the relative contributions of downstream extracellular domains (disintegrin, cysteine rich, and EGF-like repeat) of the ADAM13 metalloprotease during Xenopus laevis development. When expressed in embryos, ADAM13 induces hyperplasia of the cement gland, whereas ADAM10 does not. Using chimeric constructs, we find that the metalloprotease domain of ADAM10 can substitute for that of ADAM13, but that specificity for cement gland expansion requires a downstream extracellular domain of ADAM13. Analysis of finer resolution chimeras indicates an essential role for the cysteine-rich domain and a supporting role for the disintegrin domain. These and other results reveal that the cysteine-rich domain of ADAM13 cooperates intramolecularly with the ADAM13 metalloprotease domain to regulate its function in vivo. Our findings thus provide the first evidence that a downstream extracellular adhesive domain plays an active role in regulating ADAM protease function in vivo. These findings are likely relevant to other membrane-anchored cell surface proteases.

Autophagy regulates cisplatin-induced stemness and chemoresistance via the upregulation of CD44, ABCB1 and ADAM17 in oral squamous cell carcinoma.

PubMed

Naik, Prajna Paramita; Mukhopadhyay, Subhadip; Panda, Prashanta Kumar; Sinha, Niharika; Das, Chandan Kanta; Mishra, Rajakishore; Patil, Shankargouda; Bhutia, Sujit Kumar

2018-02-01

We inspected the relevance of CD44, ABCB1 and ADAM17 in OSCC stemness and deciphered the role of autophagy/mitophagy in regulating stemness and chemoresistance. A retrospective analysis of CD44, ABCB1 and ADAM17 with respect to the various clinico-pathological factors and their correlation was analysed in sixty OSCC samples. Furthermore, the stemness and chemoresistance were studied in resistant oral cancer cells using sphere formation assay, flow cytometry and florescence microscopy. The role of autophagy/mitophagy was investigated by transient transfection of siATG14, GFP-LC3, tF-LC3, mKeima-Red-Mito7 and Western blot analysis of autophagic and mitochondrial proteins. In OSCC, high CD44, ABCB1 and ADAM17 expressions were correlated with higher tumour grades and poor differentiation and show significant correlation in their co-expression. In vitro and OSCC tissue double labelling confirmed that CD44 + cells co-expresses ABCB1 and ADAM17. Further, cisplatin (CDDP)-resistant FaDu cells displayed stem-like features and higher CD44, ABCB1 and ADAM17 expression. Higher autophagic flux and mitophagy were observed in resistant FaDu cells as compared to parental cells, and inhibition of autophagy led to the decrease in stemness, restoration of mitochondrial proteins and reduced expression of CD44, ABCB1 and ADAM17. The CD44 + /ABCB1 + /ADAM17 + expression in OSCC is associated with stemness and chemoresistance. Further, this study highlights the involvement of mitophagy in chemoresistance and autophagic regulation of stemness in OSCC. © 2017 John Wiley & Sons Ltd.

Potential Role for ADAM15 in Pathological Neovascularization in Mice

PubMed Central

Horiuchi, Keisuke; Weskamp, Gisela; Lum, Lawrence; Hammes, Hans-Peter; Cai, Hui; Brodie, Thomas A.; Ludwig, Thomas; Chiusaroli, Riccardo; Baron, Roland; Preissner, Klaus T.; Manova, Katia; Blobel, Carl P.

2003-01-01

ADAM15 (named for a disintegrin and metalloprotease 15, metargidin) is a membrane-anchored glycoprotein that has been implicated in cell-cell or cell-matrix interactions and in the proteolysis of molecules on the cell surface or extracellular matrix. To characterize the potential roles of ADAM15 during development and in adult mice, we analyzed its expression pattern by mRNA in situ hybridization and generated mice carrying a targeted deletion of ADAM15 (adam15−/− mice). A high level of expression of ADAM15 was found in vascular cells, the endocardium, hypertrophic cells in developing bone, and specific areas of the hippocampus and cerebellum. However, despite the pronounced expression of ADAM15 in these tissues, no major developmental defects or pathological phenotypes were evident in adam15−/− mice. The elevated levels of ADAM15 in endothelial cells prompted an evaluation of its role in neovascularization. In a mouse model for retinopathy of prematurity, adam15−/− mice had a major reduction in neovascularization compared to wild-type controls. Furthermore, the size of tumors resulting from implanted B16F0 mouse melanoma cells was significantly smaller in adam15−/− mice than in wild-type controls. Since ADAM15 does not appear to be required for developmental angiogenesis or for adult homeostasis, it may represent a novel target for the design of inhibitors of pathological neovascularization. PMID:12897135

Effects of ADAM10 and ADAM17 Inhibitors on Natural Killer Cell Expansion and Antibody-dependent Cellular Cytotoxicity Against Breast Cancer Cells In Vitro.

PubMed

Pham, Dang-Huan; Kim, Ju-Sun; Kim, Sang-Ki; Shin, Dong-Jun; Uong, Nguyen-Thanh-Tung; Hyun, Hoon; Yoon, Mee Sun; Kang, Sin Jae; Ryu, Young Jae; Cho, Jin Seong; Yoon, Jung Han; Lee, Ji Shin; Cho, Duck; Lee, Soo-Hyeon; Park, Min Ho

2017-10-01

The inhibition of a disintegrin and metalloproteinase (ADAM) has the potential to become a novel approach for natural killer (NK) cell-based cancer immunotherapy. Thus, the aim of this study was to investigate the influence of ADAM10 and ADAM17 inhibitors on expanded NK cell to enhance antibody-dependent cellular cytotoxicity (ADCC) in breast cancer cell lines. NK cells were expanded in medium supplemented with an ADAM10 or ADAM17 inhibitor to prevent the shedding of soluble CD16/FcγRIII. The expression level of CD16 and production of interferon-gamma (IFN-γ) was detected by flow cytometry using specific antibodies. ADCC activity of expanded NK cells was estimated in trastuzumab treated breast cancer cell lines such as MCF-7, MDA-MB-231, SKBR3, and BT-474 cells. The ADAM17 inhibitor increased the purity of expanded NK cells to 90% after 14 days at 5 and 10 μM in vitro (p=0.043). However, the expansion rate of NK cells was decreased at 10 μM of the ADAM 17 inhibitor (p=0.043). Inhibition of ADAM10 suppressed the expansion of NK cells, although the NK purity was increased at 1 μM of the inhibitor. The expression of CD16 was significantly increased at 1 and 5 μM of the ADAM17 inhibitor (p=0.046, 0.028, respectively) during the culturing period. Inhibition of ADAM10 reduced the expression of CD16 on NK cells. The cytotoxic activity of the ADAM17 inhibitor treated NK cells against MCF-7 (p=0.039) and BT-474 (p=0.027) cells was significantly elevated. The ADCC activity of NK cells treated with 5 μM of ADAM17 inhibitor was significantly increased against SKBR-3 and BT-474 (p=0.027). Inhibition of ADAM17 increased the production of IFN-γ in expanded NK cells. The inhibition of ADAM17 enhanced the purity of expanded NK cells and the ADCC activity of these cells against trastuzumab treated breast cancer cell lines. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Technical Note: Dosimetric effects of couch position variability on treatment plan quality with an MRI-guided Co-60 radiation therapy machine

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

Chow, Phillip E., E-mail: pechow@mednet.ucla.edu

2016-08-15

Purpose: Magnetic resonance imaging (MRI) guidance in radiation therapy brings real-time imaging and adaptive planning into the treatment vault where it can account for interfraction and intrafraction movement of soft tissue. The only commercially available MRI-guided radiation therapy device is a three-head {sup 60}Co and MRI system with an integrated treatment planning system (TPS). Couch attenuation of the beam of up to 20% is well modeled in the TPS. Variations in the patient’s day-to-day position introduce discrepancies in the actual couch attenuation as modeled in the treatment plan. For this reason, the authors’ institution avoids plans with beams that passmore » through or near the couch edges. This study investigates the effects of differential beam attenuation by the couch due to couch shifts in order to determine whether couch edge avoidance restrictions can be lifted. Couch shifts were simulated using a Monte Carlo treatment planning system and ion chamber measurements performed for validation. Methods: A total of 27 plans from 23 patients were investigated. Couch shifts of 1 and 2 cm were introduced in combinations of lateral and vertical directions to simulate patient position variations giving 16 shifted plans per reference plan. The 1 and 2 cm shifts were based on shifts recorded in 320 treatment fractions. Results: Following TG176 recommendations for measurement methods, couch attenuation measurements agreed with TPS modeled attenuation to within 2.1%. Planning target volume D95 changed less than 1% for 1 and 2 cm couch shifts in only the x-direction and less than 3% for all directions. Conclusions: Dosimetry of all plans tested was robust to couch shifts up to ±2 cm. In general, couch shifts resulted in clinically insignificant dosimetric deviations. It is conceivable that in certain cases with large systematic couch shifts and plans that are particularly sensitive to shifts, dosimetric changes might rise to a clinically significant level.« less

ADAM15 expression is downregulated in melanoma metastasis compared to primary melanoma

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

Ungerer, Christopher; Doberstein, Kai; Buerger, Claudia

2010-10-22

Research highlights: {yields} Strong ADAM15 expression is found in normal melanocytes. {yields} ADAM15 expression is significantly downregulated in patients with melanoma metastasis. {yields} TGF-{beta} can downregulate ADAM15 expression in melanoma cells. {yields} Overexpression of ADAM15 in melanoma cells inhibits migration, proliferation and invasion of melanoma cells. {yields} Conclusion: ADAM15 represents an tumor suppressor protein in melanoma. -- Abstract: In a mouse melanoma metastasis model it has been recently shown that ADAM15 overexpression in melanoma cells significantly reduced the number of metastatic nodules on the lung. Unfortunately, the expression of ADAM15 in human melanoma tissue has not been determined so far.more » In our study, we characterized the expression of ADAM15 in tissue micro-arrays of patients with primary melanoma with melanoma metastasis. ADAM15 was expressed in melanocytes and endothelial cells of benign nevi and melanoma tissue. Importantly, ADAM15 was significantly downregulated in melanoma metastasis compared to primary melanoma. We further demonstrate that IFN-{gamma} and TGF-{beta} downregulate ADAM15 protein levels in melanoma cells. To investigate the role of ADAM15 in melanoma progression, we overexpressed ADAM15 in melanoma cells. Importantly, overexpression of ADAM15 in melanoma cells reduced the migration, invasion and the anchorage dependent and independent cell growth of melanoma cells. In summary, the downregulation of ADAM15 plays an important role in melanoma progression and ADAM15 act as a tumorsuppressor in melanoma.« less

Adam8 Limits the Development of Allergic Airway Inflammation in Mice

PubMed Central

Knolle, Martin D.; Nakajima, Takahiro; Hergrueter, Anja; Gupta, Kushagra; Polverino, Francesca; Craig, Vanessa J.; Fyfe, Susanne E.; Zahid, Muhammad; Permaul, Perdita; Cernadas, Manuela; Montano, Gilbert; Tesfaigzi, Yohannes; Sholl, Lynette; Kobzik, Lester; Israel, Elliot; Owen, Caroline A.

2013-01-01

To determine whether a disintegrin and a metalloproteinase-8 (Adam8) regulates allergic airway inflammation (AAI) and airway hyper-responsiveness (AHR), we compared AAI and AHR in wild type (WT) versus Adam8−/− mice in different genetic backgrounds sensitized and challenged with ovalbumin (OVA) or house dust mite protein extract (HDM). OVA- and HDM-treated Adam8−/− mice had higher lung leukocyte counts, more airway mucus metaplasia, greater lung levels of some TH2 cytokines, and higher methacholine-induced increases in central airway resistance than allergen-treated WT mice. Studies of OVA-treated Adam8 bone marrow chimeric mice confirmed that leukocyte-derived Adam8 predominantly mediated Adam8’s anti-inflammatory activities in murine airways. Airway eosinophils and macrophages both expressed Adam8 in WT mice with AAI. Adam8 limited AAI and AHR in mice by reducing leukocyte survival because: 1) Adam8−/− mice with AAI had fewer apoptotic eosinophils and macrophages in their airways than WT mice with AAI; and 2) Adam8−/− macrophages and eosinophils had reduced rates of apoptosis compared with WT leukocytes when the intrinsic (but not the extrinsic) apoptosis pathway was triggered in the cells in vitro. ADAM8 was robustly expressed by airway granulocytes in lung sections from human asthma patients but, surprisingly, airway macrophages had less ADAM8 staining than airway eosinophils. Thus, ADAM8 has anti-inflammatory activities during AAI in mice by activating the intrinsic apoptosis pathway in myeloid leukocytes. Strategies that increase ADAM8 levels in myeloid leukocytes may have therapeutic efficacy in asthma. PMID:23670189

WE-G-213CD-06: Implementation of Real-Time Tumor Tracking Using Robotic Couch.

PubMed

Buzurovic, I; Yu, Y; Podder, T

2012-06-01

The purpose of this study was to present a novel method for real- time tumor tracking using a commercially available robotic treatment couch, and to evaluate tumor tracking accuracy. Commercially available robotic couches are capable of positioning patients with high level of accuracy; however, currently there is no provision for compensating tumor motion using these systems. Elekta's existing commercial couch (PreciseTM Table) was used without changing its design. To establish the real-time couch motion for tracking, a novel control system was developed and implemented. The tabletop could be moved in horizontal plane (laterally and longitudinally) using two Maxon-24V motors with gearbox combination. Vertical motion was obtained using robust 70V-Rockwell Automation motor. For vertical motor position sensing, we used Model 755A-Accu- Coder encoder. Two Baumer-ITD_01_4mm shaft encoders were used for the lateral and longitudinal motions of the couch. Motors were connected to the Advance Motion Controls (AMC) amplifiers: for the vertical motion, motor AMC-20A20-INV amplifier was used, and two AMC-Z6A8 amplifiers were applied for the lateral and longitudinal couch motions. The Galil DMC-4133 controller was connected to standard PC computer using USB port. The system had two independent power supplies: Galil PSR-12- 24-12A, 24vdc power supply with diodes for controller and 24vdc motors and amplifiers, and Galil-PS300W72 72vdc power supply for vertical motion. Control algorithms were developed for position and velocity adjustment. The system was tested for real-time tracking in the range of 50mm in all 3 directions (superior-inferior, lateral, anterior- posterior). Accuracies were 0.15, 0.20, and 0.18mm, respectively. Repeatability of the desired motion was within ± 0.2mm. Experimental results of couch tracking show feasibility of real-time tumor tracking with high level of accuracy (within sub-millimeter range). This tracking technique potentially offers a simple and

Poster — Thur Eve — 33: The Influence of a Modeled Treatment Couch on Dose Distributions During IMRT and RapidArc Treatment Delivery

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

Aldosary, Ghada; Nobah, Ahmad; Al-Zorkani, Faisal

2014-08-15

Treatment couches have been known to perturb dose delivery in patients. This effect is most pronounced in techniques such as IMRT and RapidArc. Although modern treatment planning systems (TPS) include data for a “default” treatment couch, actual couches are not manufactured identically. Thus, variations in their Hounsfield Unit (HU) values may exist. This study demonstrates a practical and simple method of acquiring reliable HU data for any treatment couch. We also investigate the effects of both the default and modeled treatment couches on absorbed dose. Experimental verifications show that by neglecting to incorporate the treatment couch in the TPS, dosemore » differences of up to 9.5% and 7.3% were present for 4 MV and 10 MV photon beams, respectively. Furthermore, a clinical study based on a cohort of 20 RapidArc and IMRT (brain, pelvis and abdominal) cases is performed. 2D dose distributions show that without the couch in the planning phase, differences ≤ 4.6% and 5.9% for RapidArc and IMRT cases are present for the same cases that the default couch was added to. Additionally, in comparison to the default couch, employing the modeled couch in the calculation process influences dose distributions by ≤ 2.7% and 8% for RapidArc and IMRT cases, respectively. This result was found to be site specific; where an accurate couch proves to be preferable for IMRT brain plans. As such, adding the couch during dose calculation decreases dose calculation errors, and a precisely modeled treatment couch offers higher dose delivery accuracy for brain treatment using IMRT.« less

The ADAM workshops and meeting summary

NASA Astrophysics Data System (ADS)

Chipperfield, Alan J.

1990-01-01

ADAM is now a major software project; it provides a fully integrated environment for both data reduction and data acquisition. It is being used in Hawaii, Australia and the Canary Islands, as well as the UK, and has been adopted by Starlink as the environment in which Starlink data reduction software should run. One of the most remarkable things about ADAM is that it has been developed as a co-operative effort between groups that are spread across the world. Although the initial system came out of RGO, and ROE provided by far the major effort in designing and implementing the VAX version, various parts of what is now regarded as 'ADAM' have also come from other establishments. Co-ordinating a project being developed in this way is not an easy job, but the somewhat varied parentage of ADAM - although sometimes an administrative nightmare - is also one of its strengths; it is not a system developed in one place to serve the specific needs of that one place. One way in which this development is co-ordinated is by a series of workshops. These have taken place at about 18 month intervals since the first one in late 1985. The workshops are attended by people actively developing and/or making extensive use of ADAM, and provide a forum for detailed discussion of the problems in the current system and plans for its extension. The 1989 ADAM Workshop was held at Cosener's House, Abingdon from 3rd to 7th July 1989. An 'Open Meeting' was held on Friday 30th June at RAL to enable members of the Starlink community to provide input to the Workshop discussions. Before the previous workshop, in Hawaii, a trend had started to emerge for different establishments to plug the gaps in ADAM (which at the time was missing a number of important facilities) with local solutions. The Hawaii Workshop consolidated these local extensions, adopting some and rejecting others. As a result, ADAM, as reviewed by this third workshop, was a much more complete and uniform system, and it was possible to

Proceedings of the 1989 ADAM Workshop

NASA Astrophysics Data System (ADS)

Chipperfield, Alan

ADAM is now a major software project; it provides a fully integrated environment for both data reduction and data acquisition. It is being used in Hawaii, Australia and the Canary Islands, as well as the UK, and has been adopted by Starlink as the environment in which Starlink data reduction software should run. One of the most remarkable things about ADAM is that it has been developed as a co-operative effort between groups that are spread across the world. Although the initial system came out of RGO, and ROE provided by far the major effort in designing and implementing the VAX version, various parts of what is now regarded as 'ADAM' have also come from other establishments. Co-ordinating a project being developed in this way is not an easy job, but the somewhat varied parentage of ADAM - although sometimes an administrative nightmare - is also one of its strengths; it is not a system developed in one place to serve the specific needs of that one place. One way in which this development is co-ordinated is by a series of workshops. These have taken place at about 18 month intervals since the first one in late 1985. The workshops are attended by people actively developing and/or making extensive use of ADAM, and provide a forum for detailed discussion of the problems in the current system and plans for its extension. The 1989 ADAM Workshop was held at Cosener's House, Abingdon from 3rd to 7th July 1989. An 'Open Meeting' was held on Friday 30th June at RAL to enable members of the Starlink community to provide input to the Workshop discussions. Before the previous workshop, in Hawaii, a trend had started to emerge for different establishments to plug the gaps in ADAM (which at the time was missing a number of important facilities) with local solutions. The Hawaii Workshop consolidated these local extensions, adopting some and rejecting others. As a result, ADAM, as reviewed by this third workshop, was a much more complete and uniform system, and it was possible to

SU-F-J-125: Effects of Couch Position Variability On Dosimetric Accuracy with An MRI-Guided Co-60 Radiation Therapy Machine

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

Chow, P; Thomas, D; Agazaryan, N

2016-06-15

Purpose: Magnetic resonance imaging (MRI) guidance in radiation therapy brings real-time imaging and adaptive planning into the treatment vault where it can account for interfraction and intrafraction movement of soft tissue. The only commercially-available MRI-guided radiation therapy device is a three-head 60Co and MRI system with an integrated treatment planning system (TPS). An up to 20% attenuation of the beam by the couch is well modeled in the TPS. However, variations in the patient’s day-to-day position introduce discrepancies in the actual couch position relative its location as modeled in the treatment plan. For this reason, our institution avoids plans withmore » beams that pass through or near the couch edges. This study looks at plans without restriction on beam angles and investigates the effects of couch shift by simulating shifts of the couch relative to the patient, in order to determine whether couch edge avoidance restrictions can be lifted. Methods: A total of 27 plans from 23 patients were investigated. Couch shifts of 1 and 2 cm were introduced in combinations of lateral and vertical direction to simulate variations in patient positioning on the couch giving 16 shifted plans per reference plan. The shift values of 1 and 2 cm were based on shifts recorded in 320 treatment fractions. Results: Measured couch attenuation versus TPS modeled agreed within 2.1%. Planning Target Volume (PTV) D95 changed less than 1% for 1 and 2 cm couch shifts in only the x-direction and less than 3% for all directions. Conclusion: The dosimetry of all plans with shifts up to ±2 cm was within reasonable clinical tolerances. Robustness of a plan to couch shifts can be tested in the TPS. Inclusion of beams traversing the couch edges should be considered if an improvement in plan quality or delivery time can be achieved.« less

Adam and Bessie Arnet Residence, overall view from rocks above, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Adam and Bessie Arnet Residence, overall view from rocks above, looking southeast. - Adam & Bessie Arnet Homestead, Adam & Bessie Arnet Residence, 18 feet west of Generator House, Model, Las Animas County, CO

Conservation and divergence of ADAM family proteins in the Xenopus genome

PubMed Central

2010-01-01

Background Members of the disintegrin metalloproteinase (ADAM) family play important roles in cellular and developmental processes through their functions as proteases and/or binding partners for other proteins. The amphibian Xenopus has long been used as a model for early vertebrate development, but genome-wide analyses for large gene families were not possible until the recent completion of the X. tropicalis genome sequence and the availability of large scale expression sequence tag (EST) databases. In this study we carried out a systematic analysis of the X. tropicalis genome and uncovered several interesting features of ADAM genes in this species. Results Based on the X. tropicalis genome sequence and EST databases, we identified Xenopus orthologues of mammalian ADAMs and obtained full-length cDNA clones for these genes. The deduced protein sequences, synteny and exon-intron boundaries are conserved between most human and X. tropicalis orthologues. The alternative splicing patterns of certain Xenopus ADAM genes, such as adams 22 and 28, are similar to those of their mammalian orthologues. However, we were unable to identify an orthologue for ADAM7 or 8. The Xenopus orthologue of ADAM15, an active metalloproteinase in mammals, does not contain the conserved zinc-binding motif and is hence considered proteolytically inactive. We also found evidence for gain of ADAM genes in Xenopus as compared to other species. There is a homologue of ADAM10 in Xenopus that is missing in most mammals. Furthermore, a single scaffold of X. tropicalis genome contains four genes encoding ADAM28 homologues, suggesting genome duplication in this region. Conclusions Our genome-wide analysis of ADAM genes in X. tropicalis revealed both conservation and evolutionary divergence of these genes in this amphibian species. On the one hand, all ADAMs implicated in normal development and health in other species are conserved in X. tropicalis. On the other hand, some ADAM genes and ADAM protease

Adam and Bessie Arnet Residence, interior detail of jacal wall ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Adam and Bessie Arnet Residence, interior detail of jacal wall construction in west jacal room - Adam & Bessie Arnet Homestead, Adam & Bessie Arnet Residence, 18 feet west of Generator House, Model, Las Animas County, CO

[Method for evaluating the positional accuracy of a six-degrees-of-freedom radiotherapy couch using high definition digital cameras].

PubMed

Takemura, Akihiro; Ueda, Shinichi; Noto, Kimiya; Kurata, Yuichi; Shoji, Saori

2011-01-01

In this study, we proposed and evaluated a positional accuracy assessment method with two high-resolution digital cameras for add-on six-degrees-of-freedom radiotherapy (6D) couches. Two high resolution digital cameras (D5000, Nikon Co.) were used in this accuracy assessment method. These cameras were placed on two orthogonal axes of a linear accelerator (LINAC) coordinate system and focused on the isocenter of the LINAC. Pictures of a needle that was fixed on the 6D couch were taken by the cameras during couch motions of translation and rotation of each axis. The coordinates of the needle in the pictures were obtained using manual measurement, and the coordinate error of the needle was calculated. The accuracy of a HexaPOD evo (Elekta AB, Sweden) was evaluated using this method. All of the mean values of the X, Y, and Z coordinate errors in the translation tests were within ±0.1 mm. However, the standard deviation of the Z coordinate errors in the Z translation test was 0.24 mm, which is higher than the others. In the X rotation test, we found that the X coordinate of the rotational origin of the 6D couch was shifted. We proposed an accuracy assessment method for a 6D couch. The method was able to evaluate the accuracy of the motion of only the 6D couch and revealed the deviation of the origin of the couch rotation. This accuracy assessment method is effective for evaluating add-on 6D couch positioning.

ADAM10 regulates Notch function in intestinal stem cells of mice.

PubMed

Tsai, Yu-Hwai; VanDussen, Kelli L; Sawey, Eric T; Wade, Alex W; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C; Samuelson, Linda C; Dempsey, Peter J

2014-10-01

A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is a cell surface sheddase that regulates physiologic processes, including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types, but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10(f/f) mice) and conditional (Vil-CreER;Adam10(f/f) and Leucine-rich repeat-containing GPCR5 [Lgr5]-CreER;Adam10(f/f) mice) deletion of ADAM10. We performed cell lineage-tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26(NICD)), or mice with intestine-specific disruption of Notch (Rosa26(DN-MAML)), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26(NICD) and Rosa26(DN-MAML) mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage-tracing experiments showed that ADAM10 is required for survival of Lgr5(+) crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

ADAM10 Regulates Notch Function in Intestinal Stem Cells of Mice

PubMed Central

Tsai, Yu-Hwai; VanDussen, Kelli L.; Sawey, Eric T.; Wade, Alex W.; Kasper, Chelsea; Rakshit, Sabita; Bhatt, Riha G.; Stoeck, Alex; Maillard, Ivan; Crawford, Howard C.; Samuelson, Linda C.; Dempsey, Peter J.

2014-01-01

BACKGROUND & AIMS ADAM10 is a cell surface sheddase that regulates physiological processes including Notch signaling. ADAM10 is expressed in all intestinal epithelial cell types but the requirement for ADAM10 signaling in crypt homeostasis is not well defined. METHODS We analyzed intestinal tissues from mice with constitutive (Vil-Cre;Adam10f/f mice) and conditional (Vil-CreER;Adam10f/f and Lgr5-CreER;Adam10f/f mice) deletion of ADAM10. We performed cell lineage tracing experiments in mice that expressed a gain-of-function allele of Notch in the intestine (Rosa26NICD) or mice with intestine-specific disruption of Notch (Rosa26DN-MAML), to examine the effects of ADAM10 deletion on cell fate specification and intestinal stem cell maintenance. RESULTS Loss of ADAM10 from developing and adult intestine caused lethality associated with altered intestinal morphology, reduced progenitor cell proliferation, and increased secretory cell differentiation. ADAM10 deletion led to the replacement of intestinal cell progenitors with 2 distinct, post-mitotic, secretory cell lineages: intermediate-like (Paneth/goblet) and enteroendocrine cells. Based on analysis of Rosa26NICD and Rosa26DN-MAML mice, we determined that ADAM10 controls these cell fate decisions by regulating Notch signaling. Cell lineage tracing experiments showed that ADAM10 is required for survival of Lgr5+ crypt-based columnar cells. Our findings indicate that Notch-activated stem cells have a competitive advantage for occupation of the stem cell niche. CONCLUSIONS ADAM10 acts in a cell autonomous manner within the intestinal crypt compartment to regulate Notch signaling. This process is required for progenitor cell lineage specification and crypt-based columnar cell maintenance. PMID:25038433

CONTOUR COUCH - MERCURY-ATLAS (MA)-9 PRELAUNCH ACTIVITIES - CAPE

NASA Image and Video Library

1963-02-01

S63-03968 (1963) --- Astronaut L. Gordon Cooper Jr., prime pilot for the Mercury-Atlas 9 (MA-9) mission; Joe Trammel, MAC technician; A. Rochford, NASA suit technician; and C.R. Coyle, MAC technician, look over spacecraft couch. Photo credit: NASA

VIEW OF MORTARED ROCK AND CONCRETE INLET TO COUCH LATERAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

VIEW OF MORTARED ROCK AND CONCRETE INLET TO COUCH LATERAL CANAL, UPSTREAM OF COLLINS ROAD. LOOKING NORTH/NORTHEAST - Tumalo Irrigation District, Tumalo Project, West of Deschutes River, Tumalo, Deschutes County, OR

Couch height–based patient setup for abdominal radiation therapy

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

Ohira, Shingo; Department of Medical Physics and Engineering, Osaka University Graduate School of Medicine, Suita; Ueda, Yoshihiro

2016-04-01

There are 2 methods commonly used for patient positioning in the anterior-posterior (A-P) direction: one is the skin mark patient setup method (SMPS) and the other is the couch height–based patient setup method (CHPS). This study compared the setup accuracy of these 2 methods for abdominal radiation therapy. The enrollment for this study comprised 23 patients with pancreatic cancer. For treatments (539 sessions), patients were set up by using isocenter skin marks and thereafter treatment couch was shifted so that the distance between the isocenter and the upper side of the treatment couch was equal to that indicated on themore » computed tomographic (CT) image. Setup deviation in the A-P direction for CHPS was measured by matching the spine of the digitally reconstructed radiograph (DRR) of a lateral beam at simulation with that of the corresponding time-integrated electronic portal image. For SMPS with no correction (SMPS/NC), setup deviation was calculated based on the couch-level difference between SMPS and CHPS. SMPS/NC was corrected using 2 off-line correction protocols: no action level (SMPS/NAL) and extended NAL (SMPS/eNAL) protocols. Margins to compensate for deviations were calculated using the Stroom formula. A-P deviation > 5 mm was observed in 17% of SMPS/NC, 4% of SMPS/NAL, and 4% of SMPS/eNAL sessions but only in one CHPS session. For SMPS/NC, 7 patients (30%) showed deviations at an increasing rate of > 0.1 mm/fraction, but for CHPS, no such trend was observed. The standard deviations (SDs) of systematic error (Σ) were 2.6, 1.4, 0.6, and 0.8 mm and the root mean squares of random error (σ) were 2.1, 2.6, 2.7, and 0.9 mm for SMPS/NC, SMPS/NAL, SMPS/eNAL, and CHPS, respectively. Margins to compensate for the deviations were wide for SMPS/NC (6.7 mm), smaller for SMPS/NAL (4.6 mm) and SMPS/eNAL (3.1 mm), and smallest for CHPS (2.2 mm). Achieving better setup with smaller margins, CHPS appears to be a reproducible method for abdominal patient setup.« less

Disintegrin and metalloproteinases (ADAMs) expression in gastroesophageal reflux disease and in esophageal adenocarcinoma.

PubMed

Kauttu, T; Mustonen, H; Vainionpää, S; Krogerus, L; Ilonen, I; Räsänen, J; Salo, J; Puolakkainen, P

2017-01-01

Clinically useful marker molecules for the progression of gastroesophageal reflux disease and Barrett's esophagus (BE) to esophageal adenocarcinoma (EAC) are lacking. Many adenocarcinomas and inflammatory conditions exhibit increased expression of ADAMs, 'a disintegrin and metalloproteinases'. We assessed the expression of five ADAMs (9, 10, 12, 17, 19) in three esophageal cell lines (Het-1A, OE19, OE33) by RT-PCR and Western blotting, and in human samples of normal esophagus, esophagitis, BE, Barrett's dysplasia, and EAC by RT-PCR, and in selected samples by immunohistochemistry. EAC patients showed increased mRNA expression of ADAMs 9, 12, 17 and 19, as compared to controls. At immunohistochemistry, ADAM9 and ADAM10 proteins were increased in EAC. Patient samples also showed increased mRNA expression of ADAM12 in esophagitis, of ADAM9 in BE, and of ADAMs 9, 12 and 19 in Barrett's dysplasia, as compared to controls. Two EAC cell lines showed increased ADAM9 mRNA. ADAM9 expression is increased in EAC. Its predecessors show increased ADAM9 mRNA expression. The importance of the alterations in ADAM expression for the development of EAC, and their use as marker molecules, warrant further studies.

Some matters relating to the documentary evidence of the discovery of Neptune

NASA Astrophysics Data System (ADS)

Foster, N.

2014-04-01

The discovery of the planet Neptune was regarded as one of the greatest discoveries of the nineteenth century. Its existence was first detected, not by eye or with telescope, but by the mathematical analysis of the orbit of the planet Uranus. The perturbations of Uranus were under investigation by John Couch Adams (1819-92) in Cambridge, and Urban Le Verrier (1811-77) in Paris. Both these astronomers believed that the irregularities in the motion of Uranus could only be attributed to the action of an unknown planet of the Solar System. However, the circumstances of the discovery have once again become a matter of dispute and contention by some recent historians. My aim is to review the essential facts and the interpretation placed on them and to examine the conspiracy theories that have arisen from an examination of the documentary evidence. These conspiracy theories have detracted from Adams, the true merit of his early researches and his place in the history of the discovery. There has also been speculative allegations made of the character of Adams based on selected documentary evidence, which I believe is not necessarily a true representation of the facts. In presenting a fair portrayal of Adams's researches, I have reconstructed his 1845 October solution in a way that has not been done before.

Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis.

PubMed

De Savi, Chris; Pape, Andrew; Sawyer, Yvonne; Milne, David; Davies, Chris; Cumming, John G; Ting, Attilla; Lamont, Scott; Smith, Peter D; Tart, Jonathon; Page, Ken; Moore, Peter

2011-06-01

A new achiral class of N-hydroxyformamide inhibitor of both ADAM-TS4 and ADAM-TS5, 2 has been discovered through modification of the complex P1 group present in historical inhibitors 1. This structural change improved the DMPK properties and greatly simplified the synthesis whilst maintaining excellent cross-MMP selectivity profiles. Investigation of structure-activity and structure-property relationships in the P1 group resulted in both ADAM-TS4 selective and mixed ADAM-TS4/5 inhibitors. This led to the identification of a pre-clinical candidate with excellent bioavailability across three species and predicting once daily dosing kinetics. Copyright © 2011 Elsevier Ltd. All rights reserved.

A survey on table tolerances and couch overrides in radiotherapy

PubMed Central

Chinsky, Bonnie; Patel, Rakesh; Panfil, Joshua; Surucu, Murat

2016-01-01

The purpose of this study was to survey current departmental policies on treatment couch overrides and the values of table tolerances used clinically. A 25‐question electronic survey on couch overrides and tolerances was sent to full members of the American Association of Physicists in Medicine (AAPM). The first part of the survey asked participants if table overrides were allowed at their institution, who was allowed to perform these overrides, and if imaging was required with overrides. The second part of the survey asked individuals to provide table tolerance data for the following treatment sites: brain/head and neck (H&N), lung, breast, abdomen/pelvis and prostate. Each site was further divided into IMRT/VMAT and 3D conformal techniques. Spaces for free‐text were provided, allowing respondents to enter any table tolerance data they were unable to specify under the treatment sites listed. A total of 361 individuals responded, of which approximately half participated in the couch tolerances portion of the survey. Overall, 86% of respondents’ institutions allow couch tolerance overrides at treatment. Therapists were the most common staff members permitted to perform overrides, followed by physicists, dosimetrists, and physicians, respectively. Of the institutions allowing overrides, 34% reported overriding daily. More than half of the centers document the override and/or require a setup image to radiographically verify the treatment site. With respect to table tolerances, SRS/SBRT table tolerances were the tightest, while clinical setup table tolerances were the largest. There were minimal statistically significant differences between IMRT/VMAT and 3D conformal table tolerances. Our results demonstrated that table overrides are relatively common in radiotherapy despite being a potential safety concern. Institutions should review their override policy and table tolerance values in light of the practices of other institutions. Careful attention to these

SU-F-J-37: Commissioning a Six Degree of Freedom Couch

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

Roberts, D; Lam, K; Bredfeldt, J

2016-06-15

Purpose: The proper operation of a six degree of freedom couch (6DOFC) to position a patient for treatment requires that a number systems on the treatment unit work together correctly. Commissioning a 6DOFC requires not only the commissioning of each separate system but also commissioning the interactions between the systems. Methods: To commission a 6DOFC, we tested the resolvers that readout the linear and angular positions; the orthogonality of the axes of the laser positioning system, the imaging system, the gantry and the couch as well as their relationship to each other. An automated Winston-Lutz test was used verify themore » coincidence of the origins of the laser system, imaging system and treatment unit. The IsoCal phantom was used to verify the consistency of axes orientations between systems. The operation of the couch and imaging system was verified under simulated load conditions and an end to end test was performed to verify correct operation of the system. Results: The tests on the couch resolvers, orthogonality and coincidence of the axes of each system were successfully completed and showed excellent agreement. The automated Winston-Lutz test showed that the maximum displacement of the center of the radiation field with respect to the isocenter was <0.6 mm (radius) at isocenter. The analysis of the IsoCal phantom showed that the maximum variation of the radiation field with respect to known locations in the phantom was ∼0.9 mm for all the BBs in the phantom. Load tests showed maximum errors of 1 mm. Conclusion: We tested all system associated with the 6DOFC and found the uncertainty due to imaging was <.9mm and the uncertainty due to loading ∼1 mm, resulting in a total error of ∼1.4 mm.« less

Adams National Historical Park expanded transit service evaluation

DOT National Transportation Integrated Search

2009-12-01

In 2005 and 2006, Adams National Historical Park piloted expanded shuttle service, with the aim of promoting car-free access for its visitors. This report evaluates the 2006 season of operation. Adams National Historical Park (NHP) is located approxi...

Roles of ADAM13-regulated Wnt activity in early Xenopus eye development

PubMed Central

Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; Nakayama, Takuya; Shah, Anoop; Grainger, Robert M.; White, Judith M.; DeSimone, Douglas W.

2012-01-01

Pericellular proteolysis by ADAM family metalloproteinases has been widely implicated in cell signaling and development. We recently found that Xenopus ADAM13, an ADAM metalloproteinase, is required for activation of canonical Wnt signaling during cranial neural crest (CNC) induction by regulating a novel crosstalk between Wnt and ephrin B (EfnB) signaling pathways (Wei et al., 2010b). In the present study we show that the metalloproteinase activity of ADAM13 also plays important roles in eye development in X. tropicalis. Knockdown of ADAM13 results in reduced expression of eye field markers pax6 and rx1, as well as that of the pan-neural marker sox2. Activation of canonical Wnt signaling or inhibition of forward EfnB signaling rescues the eye defects caused by loss of ADAM13, suggesting that ADAM13 functions through regulation of the EfnB-Wnt pathway interaction. Downstream of Wnt, the head inducer Cerberus was identified as an effector that mediates ADAM13 function in early eye field formation. Furthermore, ectopic expression of the Wnt target gene snail2 restores cerberus expression and rescues the eye defects caused by ADAM13 knockdown. Together these data suggest an important role of ADAM13-regulated Wnt activity in eye development in Xenopus. PMID:22227340

Dose perturbations by two carbon fiber treatment couches and the ability of a commercial treatment planning system to predict these effects.

PubMed

Gerig, L H; Niedbala, M; Nyiri, B J

2010-01-01

To measure the effect of the treatment couch on dose distributions and to investigate the ability of a modern planning system to accurately model these effects. This work measured the dose perturbation at depth and in the dose buildup region when one of two treatment couches, CIVCO (formerly MED-TEC) or Medical Intelligence, was placed between a photon beam source (6, 10, and 18 MV) and the phantom. Beam attenuation was measured in the center of a cylindrical acrylic phantom with a Farmer type ion chamber at multiple gantry angles. Dose buildup was measured in Solid Water with plane parallel ion chambers (NACP-02 and PTW Markus) with the beam normal to both the phantom and couch surfaces. The effective point of measurement method as described [M. R. McEwen et al. "The effective point of measurement of ionization chambers and the build-up anomaly in MV x-ray beams," Med. Phys. 35(3), 950-958 (2008)] was employed to calculate dose in the buildup region. Both experiments were modeled in XiO. Images of the treatment couches were merged with images of the phantoms such that they were included as part of the "patient" image. Dose distributions calculated with superposition and fast superposition algorithms were compared to measurement. The two treatment couches have different radiological signatures and dissimilar water equivalent thicknesses (4.2 vs 6.3 mm.) Maximum attenuation was 7%. Both couches caused significant loss of skin sparing, the worst case showing an increase in surface dose from 17% (no couch) to 88% (with couch). The TPS accurately predicted the surface dose (+/-3%) and the attenuation at depth when the phantom was in contact with the couch. For the open beam the TPS was less successful in the buildup region. The treatment couch is not radio-transparent. Its presence between the patient and beam source significantly alters dose in the patient. For the most part, a modern treatment planning system can adequately predict the altered dose distribution.

Marguerite Arnet Residence, exterior door detail, looking north. Adam ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Marguerite Arnet Residence, exterior door detail, looking north. - Adam & Bessie Arnet Homestead, Marguerite Arnet Residence, 560 feet northeast of Adam & Bessie Arnet Residence, Model, Las Animas County, CO

Marguerite Arnet Residence, exterior window detail, looking north. Adam ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Marguerite Arnet Residence, exterior window detail, looking north. - Adam & Bessie Arnet Homestead, Marguerite Arnet Residence, 560 feet northeast of Adam & Bessie Arnet Residence, Model, Las Animas County, CO

SU-E-T-66: A Prototype for Couch Based Real-Time Dosimetry in External Beam Radiotherapy

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

Ramachandran, P

Purpose: The main purpose of this study is to design a prototype for couch-based based real time dosimetry system in external beam radiotherapy Methods: A prototype of 100 ionization chambers was designed on a printed circuit board by etching the copper layer and each ionization chamber was wired to a 50 pin connector. The signals from the two 50 pin connectors collected from the ionization chambers were then transferred to a PXI module from National Instruments. The PXI module houses a current amplifier that amplifies the charge collected from the ionization chamber. The amplified signal is then sent to amore » digital multimeter module for converting the analog signal to digital signal. A software was designed in labview to read and display the signals obtained from the PXI module. A couch attachment frame was designed to house the 100 ionization chamber module. The frame was fixed underneath the treatment couch for measuring the dose during treatment. Resutls: The ionization chamber based prototype dosimetry was tested for simple radiotherapy treatment fields and found to be a useful device for measuring real time dosimetry at the treatment couch plane. This information could be used to assess the delivered dose to a patient during radiotherapy. It could be used as an invivo dosimeter during radiotherapy. Conclusion: In this study, a prototype for couch based real time dosimetry system was designed and tested. The prototype forms a basis for the development of large scale couch based real time dosimetry system that could be used to perform morning QA prior to treatment, assess real time doses delivered to patient and as a device to monitor the output of the treatment beam. Peter MacCallum Cancer Foundation.« less

Selective Modulation of Integrin-mediated Cell Migration by Distinct ADAM Family MembersV⃞

PubMed Central

Huang, Jing; Bridges, Lance C.; White, Judith M.

2005-01-01

A disintegrin and a metalloprotease (ADAM) family members have been implicated in many biological processes. Although it is recognized that recombinant ADAM disintegrin domains can interact with integrins, little is known about ADAM-integrin interactions in cellular context. Here, we tested whether ADAMs can selectively regulate integrin-mediated cell migration. ADAMs were expressed in Chinese hamster ovary cells that express defined integrins (α4β1, α5β1, or both), and cell migration on full-length fibronectin or on its α4β1 or α5β1 binding fragments was studied. We found that ADAMs inhibit integrin-mediated cell migration in patterns dictated by the integrin binding profiles of their isolated disintegrin domains. ADAM12 inhibited cell migration mediated by the α4β1 but not the α5β1 integrin. ADAM17 had the reciprocal effect; it inhibited α5β1- but not α4β1-mediated cell migration. ADAM19 and ADAM33 inhibited migration mediated by both α4β1 and α5β1 integrins. A point mutation in the ADAM12 disintegrin loop partially reduced the inhibitory effect of ADAM12 on cell migration on the α4β1 binding fragment of fibronectin, whereas mutations that block metalloprotease activity had no effect. Our results indicate that distinct ADAMs can modulate cell migration mediated by specific integrins in a pattern dictated, at least in part, by their disintegrin domains. PMID:16079176

Identification of ADAM 31: a protein expressed in Leydig cells and specialized epithelia.

PubMed

Liu, L; Smith, J W

2000-06-01

A family of proteins containing a disintegrin and metalloproteinase domain (ADAMs) has been identified recently. Here, we report the identification of a novel member of the ADAM protein family from mouse. This protein is designated ADAM 31. The complementary DNA sequence of ADAM 31 predicts a transmembrane protein with metalloproteinase, disintegrin, cysteine-rich, and cytoplasmic domains. Messenger RNA encoding ADAM 31 was most abundant in testes, but was also detected in many other tissues. More significantly, the antibodies raised against ADAM 31 reveal that the protein has a unique and restricted expression pattern. ADAM 31 is expressed in Leydig cells of the testes, but unlike many other ADAMs, it is not found on developing sperm. Furthermore, ADAM 31 is highly expressed on four types of specialized epithelia: the cauda epididymidis, the vas deferens, the convoluted tubules of the kidney, and the parietal cells of the stomach.

The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity.

PubMed

Abbruzzese, Genevieve; Gorny, Anne-Kathrin; Kaufmann, Lilian T; Cousin, Hélène; Kleino, Iivari; Steinbeisser, Herbert; Alfandari, Dominique

2015-03-15

Cranial neural crest (CNC) cells are a transient population of stem cells that originate at the border of the neural plate and the epidermis, and migrate ventrally to contribute to most of the facial structures including bones, cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is essential for CNC cell migration. Here, we show in Xenopus laevis embryos that the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4 function also inhibits CNC cell migration and induces a reduction of mature ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is known to translocate into the nucleus to regulate gene expression. We propose that Fz4 associates with ADAM13 during its transport to the plasma membrane to regulate its proteolytic activity. © 2015. Published by The Company of Biologists Ltd.

The Wnt receptor Frizzled-4 modulates ADAM13 metalloprotease activity

PubMed Central

Abbruzzese, Genevieve; Gorny, Anne-Kathrin; Kaufmann, Lilian T.; Cousin, Hélène; Kleino, Iivari; Steinbeisser, Herbert; Alfandari, Dominique

2015-01-01

ABSTRACT Cranial neural crest (CNC) cells are a transient population of stem cells that originate at the border of the neural plate and the epidermis, and migrate ventrally to contribute to most of the facial structures including bones, cartilage, muscles and ganglia. ADAM13 is a cell surface metalloprotease that is essential for CNC cell migration. Here, we show in Xenopus laevis embryos that the Wnt receptor Fz4 binds to the cysteine-rich domain of ADAM13 and negatively regulates its proteolytic activity in vivo. Gain of Fz4 function inhibits CNC cell migration and can be rescued by gain of ADAM13 function. Loss of Fz4 function also inhibits CNC cell migration and induces a reduction of mature ADAM13, together with an increase in the ADAM13 cytoplasmic fragment that is known to translocate into the nucleus to regulate gene expression. We propose that Fz4 associates with ADAM13 during its transport to the plasma membrane to regulate its proteolytic activity. PMID:25616895

Characterization of a novel ADAM protease expressed by Pneumocystis carinii.

PubMed

Kennedy, Cassie C; Kottom, Theodore J; Limper, Andrew H

2009-08-01

Pneumocystis species are opportunistic fungal pathogens that cause severe pneumonia in immunocompromised hosts. Recent evidence has suggested that unidentified proteases are involved in Pneumocystis life cycle regulation. Proteolytically active ADAM (named for "a disintegrin and metalloprotease") family molecules have been identified in some fungal organisms, such as Aspergillus fumigatus and Schizosaccharomyces pombe, and some have been shown to participate in life cycle regulation. Accordingly, we sought to characterize ADAM-like molecules in the fungal opportunistic pathogen, Pneumocystis carinii (PcADAM). After an in silico search of the P. carinii genomic sequencing project identified a 329-bp partial sequence with homology to known ADAM proteins, the full-length PcADAM sequence was obtained by PCR extension cloning, yielding a final coding sequence of 1,650 bp. Sequence analysis detected the presence of a typical ADAM catalytic active site (HEXXHXXGXXHD). Expression of PcADAM over the Pneumocystis life cycle was analyzed by Northern blot. Southern and contour-clamped homogenous electronic field blot analysis demonstrated its presence in the P. carinii genome. Expression of PcADAM was observed to be increased in Pneumocystis cysts compared to trophic forms. The full-length gene was subsequently cloned and heterologously expressed in Saccharomyces cerevisiae. Purified PcADAMp protein was proteolytically active in casein zymography, requiring divalent zinc. Furthermore, native PcADAMp extracted directly from freshly isolated Pneumocystis organisms also exhibited protease activity. This is the first report of protease activity attributable to a specific, characterized protein in the clinically important opportunistic fungal pathogen Pneumocystis.

Chimpanzee 'Ham' In Biopack Couch

NASA Technical Reports Server (NTRS)

1961-01-01

A three-year-old chimpanzee, named Ham, in the biopack couch for the MR-2 suborbital test flight. On January 31, 1961, a Mercury-Redstone launch from Cape Canaveral carried the chimpanzee 'Ham' over 640 kilometers down range in an arching trajectory that reached a peak of 254 kilometers above the Earth. The mission was successful and Ham performed his lever-pulling task well in response to the flashing light. NASA used chimpanzees and other primates to test the Mercury Capsule before launching the first American astronaut Alan Shepard in May 1961. The successful flight and recovery confirmed the soundness of the Mercury-Redstone systems.

Altered cell-matrix associated ADAM proteins in Alzheimer disease.

PubMed

Gerst, J L; Raina, A K; Pirim, I; McShea, A; Harris, P L; Siedlak, S L; Takeda, A; Petersen, R B; Smith, M A

2000-03-01

Alterations in cell-matrix 'contact' are often related to a disruption of cell cycle regulation and, as such, occur variously in neoplasia. Given the recent findings showing cell cycle alterations in Alzheimer disease, we undertook a study of ADAM-1 and 2 (A Disintegrin And Metalloprotease), developmentally-regulated, integrin-binding, membrane-bound metalloproteases. Our results show that whereas ADAM-1 and 2 are found in susceptible hippocampal neurons in Alzheimer disease, these proteins were not generally increased in similar neuronal populations in younger or age-matched controls except in association with age-related neurofibrillary alterations. This increase in both ADAM-1 and 2 in cases of Alzheimer disease was verified by immunoblot analysis (P < 0.05). An ADAM-induced loss of matrix integration would effectively "reset" the mitotic clock and thereby stimulate re-entry into the cell cycle in neurons in Alzheimer disease. Furthermore, given the importance of integrins in maintaining short-term memory, alterations in ADAM proteins or their proteolytic activity could also play a proximal role in the clinico-pathological manifestations of Alzheimer disease. Copyright 2000 Wiley-Liss, Inc.

ADAMS executive and operating system

NASA Technical Reports Server (NTRS)

Pittman, W. D.

1981-01-01

The ADAMS Executive and Operating System, a multitasking environment under which a variety of data reduction, display and utility programs are executed, a system which provides a high level of isolation between programs allowing them to be developed and modified independently, is described. The Airborne Data Analysis/Monitor System (ADAMS) was developed to provide a real time data monitoring and analysis capability onboard Boeing commercial airplanes during flight testing. It inputs sensor data from an airplane performance data by applying transforms to the collected sensor data, and presents this data to test personnel via various display media. Current utilization and future development are addressed.

Alpha-Secretase ADAM10 Regulation: Insights into Alzheimer’s Disease Treatment

PubMed Central

Peron, Rafaela; Vatanabe, Izabela Pereira; Manzine, Patricia Regina; Camins, Antoni

2018-01-01

ADAM (a disintegrin and metalloproteinase) is a family of widely expressed, transmembrane and secreted proteins of approximately 750 amino acids in length with functions in cell adhesion and proteolytic processing of the ectodomains of diverse cell-surface receptors and signaling molecules. ADAM10 is the main α-secretase that cleaves APP (amyloid precursor protein) in the non-amyloidogenic pathway inhibiting the formation of β-amyloid peptide, whose accumulation and aggregation leads to neuronal degeneration in Alzheimer’s disease (AD). ADAM10 is a membrane-anchored metalloprotease that sheds, besides APP, the ectodomain of a large variety of cell-surface proteins including cytokines, adhesion molecules and notch. APP cleavage by ADAM10 results in the production of an APP-derived fragment, sAPPα, which is neuroprotective. As increased ADAM10 activity protects the brain from β-amyloid deposition in AD, this strategy has been proved to be effective in treating neurodegenerative diseases, including AD. Here, we describe the physiological mechanisms regulating ADAM10 expression at different levels, aiming to propose strategies for AD treatment. We report in this review on the physiological regulation of ADAM10 at the transcriptional level, by epigenetic factors, miRNAs and/or translational and post-translational levels. In addition, we describe the conditions that can change ADAM10 expression in vitro and in vivo, and discuss how this knowledge may help in AD treatment. Regulation of ADAM10 is achieved by multiple mechanisms that include transcriptional, translational and post-translational strategies, which we will summarize in this review. PMID:29382156

Statistical process control and verifying positional accuracy of a cobra motion couch using step-wedge quality assurance tool.

PubMed

Binny, Diana; Lancaster, Craig M; Trapp, Jamie V; Crowe, Scott B

2017-09-01

This study utilizes process control techniques to identify action limits for TomoTherapy couch positioning quality assurance tests. A test was introduced to monitor accuracy of the applied couch offset detection in the TomoTherapy Hi-Art treatment system using the TQA "Step-Wedge Helical" module and MVCT detector. Individual X-charts, process capability (cp), probability (P), and acceptability (cpk) indices were used to monitor a 4-year couch IEC offset data to detect systematic and random errors in the couch positional accuracy for different action levels. Process capability tests were also performed on the retrospective data to define tolerances based on user-specified levels. A second study was carried out whereby physical couch offsets were applied using the TQA module and the MVCT detector was used to detect the observed variations. Random and systematic variations were observed for the SPC-based upper and lower control limits, and investigations were carried out to maintain the ongoing stability of the process for a 4-year and a three-monthly period. Local trend analysis showed mean variations up to ±0.5 mm in the three-monthly analysis period for all IEC offset measurements. Variations were also observed in the detected versus applied offsets using the MVCT detector in the second study largely in the vertical direction, and actions were taken to remediate this error. Based on the results, it was recommended that imaging shifts in each coordinate direction be only applied after assessing the machine for applied versus detected test results using the step helical module. User-specified tolerance levels of at least ±2 mm were recommended for a test frequency of once every 3 months to improve couch positional accuracy. SPC enables detection of systematic variations prior to reaching machine tolerance levels. Couch encoding system recalibrations reduced variations to user-specified levels and a monitoring period of 3 months using SPC facilitated in detecting

Joseph Adams (1756-1818).

PubMed

Emery, A E

1989-02-01

Joseph Adams was eclectic in his interests and wrote on a variety of medical subjects. His last book published in 1814 was on hereditary disease and based on a lifetime's careful clinical observations. In it he distinguished between what would now be defined as dominant and recessive disorders; defined the term congenital; emphasised the role of inbreeding in producing clustering of certain inherited disorders; introduced concepts now known as founder effect, incomplete penetrance, and variable age at onset; emphasised the importance of environmental factors in precipitating disease in certain genetic disorders; and, finally, recommended the establishment of registers for the purpose of preventing genetic disease. But because he proposed no scientific explanation for these various ideas, they were largely ignored by his contemporaries. Nevertheless, it would seem right to regard Joseph Adams as perhaps the first clinical geneticist.

SU-F-T-424: Mitigation of Increased Surface Dose When Treating Through A Carbon Fiber Couch Top

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

Johnson, E; Misgina, F

Purpose: To study the effect of the Varian carbon fiber couch top on surface dose for patients being treated using single PA beams in the supine position and to identify simple methods for surface dose reduction. Methods: Measurements of surface dose were obtained in Solid Water phantoms using both a parallel plate ionization chamber (PTW Advanced Markus) and EBT2 Radiochromic films for both 6 and 10MV photons. All measurements were referenced to a depth considered a typical for PA Spine fields. Techniques used to reduce the surface dose included introducing an air standoff using Styrofoam sheets to suspend the phantommore » surface above the couch top and by adding a thin high Z scattering foil on the table surface. Surface doses were evaluated for typical field sizes, standoff heights, and various scattering materials. Comparisons were made to the surface dose obtainable when treating through a Varian Mylar covered tennis racket style couch top. Results: Dependence on typical spine field sizes was relatively minor. Dependence on air gap was much more significant. Surface doses decreased exponentially with increases in air standoff distance. Surface doses were reduced by approximately 50% for an air gap of 10cm and 40% for a 15cm air gap. Surface doses were reduced by an additional 15% by the addition of a 1mm Tin scattering foil. Conclusion: Using simple techniques, it is possible to reduce the surface dose when treating single PA fields through the Varian carbon fiber couch top. Surface doses can be reduced to levels observed when treating though transparent Mylar tops by adding about 15 cm of air gap. Further reductions are possible by adding thin scattering foils, such as Tin or Lead, on the couch surface. This is a low cost approach to reduce surface dose when using the Varian carbon fiber couch top.« less

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis

PubMed Central

Luzius, Anne; Saggau, Carina; Ruder, Barbara; Bolik, Julia; Schmidt-Arras, Dirk; Linkermann, Andreas; Becker, Christoph; Rosenstiel, Philip; Rose-John, Stefan; Adam, Dieter

2018-01-01

The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17ex/ex) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation in vivo by crossing ADAM17ex/ex mice with mice that lack the necroptotic core protein RIPK3. Despite the loss of RIPK3, ADAM17ex/ex/RIPK3−/− mice showed the same increased susceptibility as ADAM17ex/ex mice in both acute and chronic models of DSS-induced colitis. Mice of both genotypes revealed comparable results with regard to weight loss, disease activity index and colitis-associated changes of inner organs. Histopathological analyses confirmed similar tissue destruction, loss of barrier integrity, immune cell infiltration, and cell death; serum analyses revealed similar levels of the pro-inflammatory cytokine KC. Resolving these unexpected findings, ADAM17ex/ex mice did not show phosphorylation of RIPK3 and its necroptotic interaction partner MLKL during DSS-induced colitis, although both proteins were clearly expressed. Consistent with these findings, murine embryonic fibroblasts derived from ADAM17ex/ex mice were protected from tumor necrosis factor (TNF)-induced necroptosis and failed to show phosphorylation of MLKL and RIPK3 after induction of necroptosis by TNF, revealing a novel, undescribed role of the protease ADAM17 in necroptosis. PMID:29560122

The enhanced susceptibility of ADAM-17 hypomorphic mice to DSS-induced colitis is not ameliorated by loss of RIPK3, revealing an unexpected function of ADAM-17 in necroptosis.

PubMed

Fuchslocher Chico, Johaiber; Falk-Paulsen, Maren; Luzius, Anne; Saggau, Carina; Ruder, Barbara; Bolik, Julia; Schmidt-Arras, Dirk; Linkermann, Andreas; Becker, Christoph; Rosenstiel, Philip; Rose-John, Stefan; Adam, Dieter

2018-02-27

The disintegrin metalloprotease ADAM17 has a critical role in intestinal inflammation and regeneration in mice, as illustrated by the dramatically increased susceptibility of ADAM17 hypomorphic (ADAM17 ex/ex ) mice to dextran sulfate sodium (DSS)-induced colitis. Similarly, necroptosis has been implicated in inflammatory responses in the intestine. In this study, we have investigated the contribution of necroptosis to ADAM17-regulated intestinal inflammation in vivo by crossing ADAM17 ex/ex mice with mice that lack the necroptotic core protein RIPK3. Despite the loss of RIPK3, ADAM17 ex/ex /RIPK3 -/- mice showed the same increased susceptibility as ADAM17 ex/ex mice in both acute and chronic models of DSS-induced colitis. Mice of both genotypes revealed comparable results with regard to weight loss, disease activity index and colitis-associated changes of inner organs. Histopathological analyses confirmed similar tissue destruction, loss of barrier integrity, immune cell infiltration, and cell death; serum analyses revealed similar levels of the pro-inflammatory cytokine KC. Resolving these unexpected findings, ADAM17 ex/ex mice did not show phosphorylation of RIPK3 and its necroptotic interaction partner MLKL during DSS-induced colitis, although both proteins were clearly expressed. Consistent with these findings, murine embryonic fibroblasts derived from ADAM17 ex/ex mice were protected from tumor necrosis factor (TNF)-induced necroptosis and failed to show phosphorylation of MLKL and RIPK3 after induction of necroptosis by TNF, revealing a novel, undescribed role of the protease ADAM17 in necroptosis.

Improved synthesis of ADAM10 inhibitor GI254023X.

PubMed

Hoettecke, Nicole; Ludwig, Andreas; Foro, Sabine; Schmidt, Boris

2010-01-01

The metalloproteinases ADAM10 and ADAM17 are involved in various diseases: neurodegeneration, cancer and inflammation. The inhibition of these proteases is a promising target in the treatment of inflammation and cancer. In this study, we present an improved synthesis of the ADAM10 reference inhibitor GI254023X with a higher overall yield, enhanced detection ability and increased acid stability, providing easier handling. This upscaled synthesis, free of diastereomeric intermediates, ensures single-batch identity, thus warranting its reproducibility in further biological investigations. 2010 S. Karger AG, Basel.

MO-D-213-05: Sensitivity of Routine IMRT QA Metrics to Couch and Collimator Rotations

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

Alaei, P

Purpose: To assess the sensitivity of gamma index and other IMRT QA metrics to couch and collimator rotations. Methods: Two brain IMRT plans with couch and/or collimator rotations in one or more of the fields were evaluated using the IBA MatriXX ion chamber array and its associated software (OmniPro-I’mRT). The plans were subjected to routine QA by 1) Creating a composite planar dose in the treatment planning system (TPS) with the couch/collimator rotations and 2) Creating the planar dose after “zeroing” the rotations. Plan deliveries to MatriXX were performed with all rotations set to zero on a Varian 21ex linearmore » accelerator. This in effect created TPS-created planar doses with an induced rotation error. Point dose measurements for the delivered plans were also performed in a solid water phantom. Results: The IMRT QA of the plans with couch and collimator rotations showed clear discrepancies in the planar dose and 2D dose profile overlays. The gamma analysis, however, did pass with the criteria of 3%/3mm (for 95% of the points), albeit with a lower percentage pass rate, when one or two of the fields had a rotation. Similar results were obtained with tighter criteria of 2%/2mm. Other QA metrics such as percentage difference or distance-to-agreement (DTA) histograms produced similar results. The point dose measurements did not obviously indicate the error due to location of dose measurement (on the central axis) and the size of the ion chamber used (0.6 cc). Conclusion: Relying on Gamma analysis, percentage difference, or DTA to determine the passing of an IMRT QA may miss critical errors in the plan delivery due to couch/collimator rotations. A combination of analyses for composite QA plans, or per-beam analysis, would detect these errors.« less

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development

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

Tan, Yu, E-mail: tanyu2048@163.com; Fu, Runqing, E-mail: furunqing@sjtu.edu.cn; Liu, Jiaqiang, E-mail: liujqmj@163.com

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of themore » craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. -- Highlights: •We firstly reported that ADAM10 was essentially involved in maxillofacial bone development. •ADAM10 cKO mice present craniofacial dysmorphia and bone defects. •Impaired osteoblast differentiation,proliferation and apoptosis underlie the bone deformity.« less

Informatics in radiology: use of CouchDB for document-based storage of DICOM objects.

PubMed

Rascovsky, Simón J; Delgado, Jorge A; Sanz, Alexander; Calvo, Víctor D; Castrillón, Gabriel

2012-01-01

Picture archiving and communication systems traditionally have depended on schema-based Structured Query Language (SQL) databases for imaging data management. To optimize database size and performance, many such systems store a reduced set of Digital Imaging and Communications in Medicine (DICOM) metadata, discarding informational content that might be needed in the future. As an alternative to traditional database systems, document-based key-value stores recently have gained popularity. These systems store documents containing key-value pairs that facilitate data searches without predefined schemas. Document-based key-value stores are especially suited to archive DICOM objects because DICOM metadata are highly heterogeneous collections of tag-value pairs conveying specific information about imaging modalities, acquisition protocols, and vendor-supported postprocessing options. The authors used an open-source document-based database management system (Apache CouchDB) to create and test two such databases; CouchDB was selected for its overall ease of use, capability for managing attachments, and reliance on HTTP and Representational State Transfer standards for accessing and retrieving data. A large database was created first in which the DICOM metadata from 5880 anonymized magnetic resonance imaging studies (1,949,753 images) were loaded by using a Ruby script. To provide the usual DICOM query functionality, several predefined "views" (standard queries) were created by using JavaScript. For performance comparison, the same queries were executed in both the CouchDB database and a SQL-based DICOM archive. The capabilities of CouchDB for attachment management and database replication were separately assessed in tests of a similar, smaller database. Results showed that CouchDB allowed efficient storage and interrogation of all DICOM objects; with the use of information retrieval algorithms such as map-reduce, all the DICOM metadata stored in the large database were

High ADAM8 expression is associated with poor prognosis in patients with hepatocellular carcinoma.

PubMed

Zhang, Yun; Tan, Yong-Fei; Jiang, Chao; Zhang, Kai; Zha, Tian-Zhou; Zhang, Miao

2013-01-01

In this study,we investigated the ADAM8 expression in hepatocellular carcinoma (HCC) and its correlation with clinicopathologic features,including the survival of patients with HCC. Furthermore,we examined the biological processes regulated by ADAM8 during the development of using HepG2 cell line as a model system. We used immunohistochemistry to compare ADAM8 protein expression in HCC and normal liver tissues and further analyze the ADAM8 protein expression in clinicopathologically characterized 105 HCC cases.We stably knocked down the endogenous expression level of ADAM8 in HepG2 cells with specific shRNA-expressing lentiviral vector. Following the successful establishment of stable cells,we examined in vitro cell growth by MTT assay,anchorage-independent growth by soft-agar colony formation assay and cell migration/invasion by transwell and boyden chamber assay. And in addition,we also investigated the in vivo tumor growth by xenograft transplantation of HepG2 cells into nude mice. Protein expression level of ADAM8 was markedly higher in HCC tissues than that in the normal liver tissues (P = 0.0058).In addition,high expression of ADAM8 protein was positively correlated with serum AFP elevation,tumor size,histological differentiation,tumor recurrence,tumor metastasis,and tumor stage. Patients with higher ADAM8 expression showed a significantly shorter overall survival time than patients with low ADAM8 expression. Multivariate analysis suggested that ADAM8 expression might be an independent prognostic indicator (p = 0.016) for the survival of patients with HCC. ADAM8-specific shRNA (shADAM8) successfully knocked down its endogenous expression in HepG2 cells. Compared to the parental and control shRNA-transfected (shCtrl) HepG2 cells,the shADAM8 cells exhibited significantly reduced in vitro cell growth,anchorage-independent growth,cell migration and invasion (p < 0.05).In vivo,the xenograft transplants from shADAM8 cells gave rise to much smaller

Taking Charge: Walter Sydney Adams and the Mount Wilson Observatory

NASA Astrophysics Data System (ADS)

Brashear, R.

2004-12-01

The growing preeminence of American observational astronomy in the first half of the 20th century is a well-known story and much credit is given to George Ellery Hale and his skill as an observatory-building entrepreneur. But a key figure who has yet to be discussed in great detail is Walter Sydney Adams (1876-1956), Hale's Assistant Director at Mount Wilson Observatory. Due to Hale's illnesses, Adams was Acting Director for much of Hale's tenure, and he became the second Director of Mount Wilson from 1923 to 1946. Behind his New England reserve Adams was instrumental in the growth of Mount Wilson and thus American astronomy in general. Adams was hand-picked by Hale to take charge of stellar spectroscopy work at Yerkes and Mount Wilson and the younger astronomer showed tremendous loyalty to Hale and Hale's vision throughout his career. As Adams assumed the leadership role at Mount Wilson he concentrated on making the observatory a place where researchers worked with great freedom but maintain a high level of cooperation. This paper will concentrate on Adams's early years and look at his growing relationship with Hale and how he came to be the central figure in the early history of Mount Wilson as both a solar and stellar observatory. His education, his years at Dartmouth and Yerkes (including his unfortunate encounter with epsilon Leonis), and his formative years on Mount Wilson are all important in learning how he shaped the direction of Mount Wilson and the development of American astronomy in the first half of the 20th century. This latter history cannot be complete until we bring Adams into better focus.

SAP97-mediated ADAM10 trafficking from Golgi outposts depends on PKC phosphorylation

PubMed Central

Saraceno, C; Marcello, E; Di Marino, D; Borroni, B; Claeysen, S; Perroy, J; Padovani, A; Tramontano, A; Gardoni, F; Di Luca, M

2014-01-01

A disintegrin and metalloproteinase 10 (ADAM10) is the major α-secretase that catalyzes the amyloid precursor protein (APP) ectodomain shedding in the brain and prevents amyloid formation. Its activity depends on correct intracellular trafficking and on synaptic membrane insertion. Here, we describe that in hippocampal neurons the synapse-associated protein-97 (SAP97), an excitatory synapse scaffolding element, governs ADAM10 trafficking from dendritic Golgi outposts to synaptic membranes. This process is mediated by a previously uncharacterized protein kinase C phosphosite in SAP97 SRC homology 3 domain that modulates SAP97 association with ADAM10. Such mechanism is essential for ADAM10 trafficking from the Golgi outposts to the synapse, but does not affect ADAM10 transport from the endoplasmic reticulum. Notably, this process is altered in Alzheimer's disease brains. These results help in understanding the mechanism responsible for the modulation of ADAM10 intracellular path, and can constitute an innovative therapeutic strategy to finely tune ADAM10 shedding activity towards APP. PMID:25429624

ADAM-17 regulates endothelial cell morphology, proliferation, and in vitro angiogenesis

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

Goeoz, Pal; Goeoz, Monika; Baldys, Aleksander

2009-02-27

Modulation of angiogenesis is a promising approach for treating a wide variety of human diseases including ischemic heart disease and cancer. In this study, we show that ADAM-17 is an important regulator of several key steps during angiogenesis. Knocking down ADAM-17 expression using lentivirus-delivered siRNA in HUVECs inhibited cell proliferation and the ability of cells to form close contact in two-dimensional cultures. Similarly, ADAM-17 depletion inhibited the ability of HUVECs to form capillary-like networks on top of three-dimensional Matrigel as well as in co-culture with fibroblasts within a three-dimensional scaffold. In mechanistic studies, both baseline and VEGF-induced MMP-2 activation andmore » Matrigel invasion were inhibited by ADAM-17 depletion. Based on our findings we propose that ADAM-17 is part of a novel pro-angiogenic pathway leading to MMP-2 activation and vessel formation.« less

Primate Ham - Fitted Suit - Couch - Mercury-Redstone (MR)-2 - Capsule #5

NASA Image and Video Library

1961-01-23

S63-20801 (23 Jan. 1961) --- Primate chimpanzee ?Ham?, in his spacesuit, is fitted into the couch of the Mercury-Redstone 2 (MR-2) capsule #5 prior to its test flight which was conducted on Jan. 31, 1961. Photo credit: NASA

Adams-Based Rover Terramechanics and Mobility Simulator - ARTEMIS

NASA Technical Reports Server (NTRS)

Trease, Brian P.; Lindeman, Randel A.; Arvidson, Raymond E.; Bennett, Keith; VanDyke, Lauren P.; Zhou, Feng; Iagnemma, Karl; Senatore, Carmine

2013-01-01

The Mars Exploration Rovers (MERs), Spirit and Opportunity, far exceeded their original drive distance expectations and have traveled, at the time of this reporting, a combined 29 kilometers across the surface of Mars. The Rover Sequencing and Visualization Program (RSVP), the current program used to plan drives for MERs, is only a kinematic simulator of rover movement. Therefore, rover response to various terrains and soil types cannot be modeled. Although sandbox experiments attempt to model rover-terrain interaction, these experiments are time-intensive and costly, and they cannot be used within the tactical timeline of rover driving. Imaging techniques and hazard avoidance features on MER help to prevent the rover from traveling over dangerous terrains, but mobility issues have shown that these methods are not always sufficient. ARTEMIS, a dynamic modeling tool for MER, allows planned drives to be simulated before commands are sent to the rover. The deformable soils component of this model allows rover-terrain interactions to be simulated to determine if a particular drive path would take the rover over terrain that would induce hazardous levels of slip or sink. When used in the rover drive planning process, dynamic modeling reduces the likelihood of future mobility issues because high-risk areas could be identified before drive commands are sent to the rover, and drives planned over these areas could be rerouted. The ARTEMIS software consists of several components. These include a preprocessor, Digital Elevation Models (DEMs), Adams rover model, wheel and soil parameter files, MSC Adams GUI (commercial), MSC Adams dynamics solver (commercial), terramechanics subroutines (FORTRAN), a contact detection engine, a soil modification engine, and output DEMs of deformed soil. The preprocessor is used to define the terrain (from a DEM) and define the soil parameters for the terrain file. The Adams rover model is placed in this terrain. Wheel and soil parameter files

Laryngoscopy

MedlinePlus

... may need anesthesia. Images Laryngoscope Laryngoscopy - series References King EF, Couch ME. History, physical examination, and the ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

Ear examination

MedlinePlus

... ear anatomy Otoscopic exam of the ear References King EF, Couch ME. History, physical examination, and the ... commercial use must be authorized in writing by ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer ...

Poster — Thur Eve — 38: Feasibility of a Table-Top Total Body Irradiation Technique using Robotic Couch Motion

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

Chin, Erika; Otto, Karl; Hoppe, Richard

Purpose: To develop and test the feasibility of a table-top implementation for total body irradiation (TBI) via robotic couch motion and coordinated monitor unit modulation on a standard C-arm linac geometry. Methods: To allow for collision free delivery and to maximize the effective field size, the couch was rotated to 270° IEC and dropped to 150 cm from the vertical radiation source. The robotic delivery was programmed using the TrueBeam STx Developer Mode using custom XML scripting. To assess the dosimetry of a sliding 30×20 cm{sup 2} field, irradiation on a solid water phantom of varying thickness was analyzed usingmore » EDR2 radiographic film and OSLDs. Beam modulation was achieved by dividing the couch path into multiple segments of varying dose rates and couch speeds in order to deliver 120 cGy to the midline. Results: The programmed irradiation in conjunction with coordinated couch motion was successfully delivered on a TrueBeam linac. When no beam modulation was employed, the dose difference between two different phantom sections was 17.0%. With simple beam modulation via changing dose rates and couch speeds, the desired prescription dose can be achieved at the centre of each phantom section within 1.9%. However, dose deviation at the junction was 9.2% due to the nonphysical change in the phantom thickness. Conclusions: The feasibility of robotic table-top TBI on a C-arm linac geometry was experimentally demonstrated. To achieve a more uniform dose distribution, inverse-planning allowing for a combination of dose rate modulation, jaw tracking and MLC motion is under investigation.« less

A Disintegrin and Metalloproteases (ADAMs) in Cardiovascular, Metabolic and Inflammatory Diseases: Aspects for Theranostic Approaches.

PubMed

van der Vorst, Emiel P C; Weber, Christian; Donners, Marjo M P C

2018-06-06

A disintegrin and metalloproteases (ADAMs) are membrane-bound enzymes responsible for the shedding or cleavage of various cell surface molecules, such as adhesion molecules, cytokines/chemokines and growth factors. This shedding can result in the release of soluble proteins that can exert agonistic or antagonistic functions. Additionally, ADAM-mediated cleavage can render these membrane proteins inactive. This review will describe the role and association of ADAMs in various pathologies with a main focus on ADAM10 and ADAM17 in atherosclerosis, including a brief overview of atherosclerosis-related ADAM substrates. Furthermore, ADAMs involvement in other metabolic and inflammatory diseases like diabetes, sepsis, Alzheimer's disease and rheumatoid arthritis will be highlighted. Subsequently, we will briefly discuss an interesting emerging field of research, i.e. the potential implications of ADAM expression in extracellular vesicles. Finally, several ADAM-based therapeutic and diagnostic (theranostic) opportunities will be discussed, while focusing on key questions about the required specificity and selectivity. Schattauer GmbH Stuttgart.

SU-E-J-258: Inter- and Intra-Fraction Setup Stability and Couch Change Tolerance for Image Guided Radiation Therapy

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

Teboh, Forbang R; Agee, M; Rowe, L

2014-06-01

Purpose: Immobilization devices combine rigid patient fixation as well as comfort and play a key role providing the stability required for accurate radiation delivery. In the setup step, couch re-positioning needed to align the patient is derived via registration of acquired versus reference image. For subsequent fractions, replicating the initial setup should yield identical alignment errors when compared to the reference. This is not always the case and further couch re-positioning can be needed. An important quality assurance measure is to set couch tolerances beyond which additional investigations are needed. The purpose of this work was to study the inter-fractionmore » couch changes needed to re-align the patient and the intra-fraction stability of the alignment as a guide to establish the couch tolerances. Methods: Data from twelve patients treated on the Accuray CyberKnife (CK) system for fractionated intracranial radiotherapy and immobilized with Aquaplast RT, U-frame, F-Head-Support (Qfix, PA, USA) was used. Each fraction involved image acquisitions and registration with the reference to re-align the patient. The absolute couch position corresponding to the approved setup alignment was recorded per fraction. Intra-fraction set-up corrections were recorded throughout the treatment. Results: The average approved setup alignment was 0.03±0.28mm, 0.15±0.22mm, 0.06±0.31mm in the L/R, A/P, S/I directions respectively and 0.00±0.35degrees, 0.03±0.32degrees, 0.08±0.45degrees for roll, pitch and yaw respectively. The inter-fraction reproducibility of the couch position was 6.65mm, 10.55mm, and 4.77mm in the L/R, A/P and S/I directions respectively and 0.82degrees, 0.71degrees for roll and pitch respectively. Intra-fraction monitoring showed small average errors of 0.21±0.21mm, 0.00±0.08mm, 0.23±0.22mm in the L/R, A/P, S/I directions respectively and 0.03±0.12degrees, 0.04±0.25degrees, and 0.13±0.15degrees in the roll, pitch and yaw respectively

ADAM10 is essential for cranial neural crest-derived maxillofacial bone development.

PubMed

Tan, Yu; Fu, Runqing; Liu, Jiaqiang; Wu, Yong; Wang, Bo; Jiang, Ning; Nie, Ping; Cao, Haifeng; Yang, Zhi; Fang, Bing

2016-07-08

Growth disorders of the craniofacial bones may lead to craniofacial deformities. The majority of maxillofacial bones are derived from cranial neural crest cells via intramembranous bone formation. Any interruption of the craniofacial skeleton development process might lead to craniofacial malformation. A disintegrin and metalloprotease (ADAM)10 plays an essential role in organ development and tissue integrity in different organs. However, little is known about its function in craniofacial bone formation. Therefore, we investigated the role of ADAM10 in the developing craniofacial skeleton, particularly during typical mandibular bone development. First, we showed that ADAM10 was expressed in a specific area of the craniofacial bone and that the expression pattern dynamically changed during normal mouse craniofacial development. Then, we crossed wnt1-cre transgenic mice with adam10-flox mice to generate ADAM10 conditional knockout mice. The stereomicroscopic, radiographic, and von Kossa staining results showed that conditional knockout of ADAM10 in cranial neural crest cells led to embryonic death, craniofacial dysmorphia and bone defects. Furthermore, we demonstrated that impaired mineralization could be triggered by decreased osteoblast differentiation, increased cell death. Overall, these findings show that ADAM10 plays an essential role in craniofacial bone development. Copyright © 2016 Elsevier Inc. All rights reserved.

ADAM10 Missense Mutations Potentiate β-Amyloid Accumulation by Impairing Prodomain Chaperone Function

PubMed Central

Suh, Jaehong; Choi, Se Hoon; Romano, Donna M.; Gannon, Moira A.; Lesinski, Andrea N.; Kim, Doo Yeon; Tanzi, Rudolph E.

2014-01-01

SUMMARY The generation of Aβ, the main component of senile plaques in Alzheimer’s disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that co-segregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated α-secretase activity of ADAM10 and shifted APP processing toward β-secretase-mediated cleavage, while enhancing Aβ plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished α-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. PMID:24055016

ADAM10 missense mutations potentiate β-amyloid accumulation by impairing prodomain chaperone function.

PubMed

Suh, Jaehong; Choi, Se Hoon; Romano, Donna M; Gannon, Moira A; Lesinski, Andrea N; Kim, Doo Yeon; Tanzi, Rudolph E

2013-10-16

The generation of Aβ, the main component of senile plaques in Alzheimer's disease (AD), is precluded by α-secretase cleavage within the Aβ domain of the amyloid precursor protein (APP). We identified two rare mutations (Q170H and R181G) in the prodomain of the metalloprotease, ADAM10, that cosegregate with late-onset AD (LOAD). Here, we addressed the pathogenicity of these mutations in transgenic mice expressing human ADAM10 in brain. In Tg2576 AD mice, both mutations attenuated α-secretase activity of ADAM10 and shifted APP processing toward β-secretase-mediated cleavage, while enhancing Aβ plaque load and reactive gliosis. We also demonstrated ADAM10 expression potentiates adult hippocampal neurogenesis, which is reduced by the LOAD mutations. Mechanistically, both LOAD mutations impaired the molecular chaperone activity of ADAM10 prodomain. Collectively, these findings suggest that diminished α-secretase activity, owing to LOAD ADAM10 prodomain mutations, leads to AD-related pathology, strongly supporting ADAM10 as a promising therapeutic target for this devastating disease. Copyright © 2013 Elsevier Inc. All rights reserved.

Nuclear trafficking of the HIV-1 pre-integration complex depends on the ADAM10 intracellular domain

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

Endsley, Mark A., E-mail: maendsle@utmb.edu; Somasunderam, Anoma D., E-mail: asomasun@utmb.edu; Li, Guangyu, E-mail: LIG001@mail.etsu.edu

Previously, we showed that ADAM10 is necessary for HIV-1 replication in primary human macrophages and immortalized cell lines. Silencing ADAM10 expression interrupted the HIV-1 life cycle prior to nuclear translocation of viral cDNA. Furthermore, our data indicated that HIV-1 replication depends on the expression of ADAM15 and γ-secretase, which proteolytically processes ADAM10. Silencing ADAM15 or γ-secretase expression inhibits HIV-1 replication between reverse transcription and nuclear entry. Here, we show that ADAM10 expression also supports replication in CD4{sup +} T lymphocytes. The intracellular domain (ICD) of ADAM10 associates with the HIV-1 pre-integration complex (PIC) in the cytoplasm and immunoprecipitates and co-localizesmore » with HIV-1 integrase, a key component of PIC. Taken together, our data support a model whereby ADAM15/γ-secretase processing of ADAM10 releases the ICD, which then incorporates into HIV-1 PIC to facilitate nuclear trafficking. Thus, these studies suggest ADAM10 as a novel therapeutic target for inhibiting HIV-1 prior to nuclear entry. - Highlights: • Nuclear trafficking of the HIV-1 pre-integration complex depends on ADAM10. • ADAM10 associates with HIV-1 integrase in the pre-integration complex. • HIV-1 replication depends on the expression of ADAM15 and γ-secretase. • Silencing ADAM15 or γ-secretase expression inhibits nuclear import of viral cDNA. • ADAM10 is important for HIV-1 replication in human macrophages and CD4{sup +} T lymphocytes.« less

Erbb2 up-regulation of ADAM12 expression accelerates skin cancer progression.

PubMed

Rao, Velidi H; Vogel, Kristen; Yanagida, Jodi K; Marwaha, Nitin; Kandel, Amrit; Trempus, Carol; Repertinger, Susan K; Hansen, Laura A

2015-10-01

Solar ultraviolet (UV) radiation can cause severe damage to the skin and is the primary cause of most skin cancer. UV radiation causes DNA damage leading to mutations and also activates the Erbb2/HER2 receptor through indirect mechanisms involving reactive oxygen species. We hypothesized that Erbb2 activation accelerates the malignant progression of UV-induced skin cancer. Following the induction of benign squamous papillomas by UV exposure of v-ras(Ha) transgenic Tg.AC mice, mice were treated topically with the Erbb2 inhibitor AG825 and tumor progression monitored. AG825 treatment reduced tumor volume, increased tumor regression, and delayed the development of malignant squamous cell carcinoma (SCC). Progression to malignancy was associated with increased Erbb2 and ADAM12 (A Disintegin And Metalloproteinase 12) transcripts and protein, while inhibition of Erbb2 blocked the increase in ADAM12 message upon malignant progression. Similarly, human SCC and SCC cell lines had increased ADAM12 protein and transcripts when compared to normal controls. To determine whether Erbb2 up-regulation of ADAM12 contributed to malignant progression of skin cancer, Erbb2 expression was modulated in cultured SCC cells using forced over-expression or siRNA targeting, demonstrating up-regulation of ADAM12 by Erbb2. Furthermore, ADAM12 transfection or siRNA targeting revealed that ADAM12 increased both the migration and invasion of cutaneous SCC cells. Collectively, these results suggest Erbb2 up-regulation of ADAM12 as a novel mechanism contributing to the malignant progression of UV-induced skin cancer. Inhibition of Erbb2/HER2 reduced tumor burden, increased tumor regression, and delayed the progression of benign skin tumors to malignant SCC in UV-exposed mice. Inhibition of Erbb2 suppressed the increase in metalloproteinase ADAM12 expression in skin tumors, which in turn increased migration and tumor cell invasiveness. © 2014 Wiley Periodicals, Inc.

The expression of ADAM12 (meltrin alpha) in human giant cell tumours of bone.

PubMed

Tian, B L; Wen, J M; Zhang, M; Xie, D; Xu, R B; Luo, C J

2002-12-01

To examine the expression of ADAM12 (meltrin alpha), a member of the disintegrin and metalloprotease (ADAM) family, in human giant cell tumours of the bone, skeletal muscle tissue from human embryos, and human adult skeletal muscle tissue. ADAM12 mRNA was detected by reverse transcription polymerase chain reaction and in situ hybridisation. ADAM12 mRNA was detected in 14 of the 20 giant cell tumours of bone and in three of the six tumour cell cultures. The expression of ADAM12 in cells cultured from the tumour was linked to the presence of multinucleated giant cells. ADAM12 mRNA could not be detected in the five adult skeletal muscle tissue samples, although it was found in the two embryonic skeletal muscle tissue samples. ADAM12 mRNA was localised to the cytoplasm of multinucleated giant cells and some mononuclear stromal cells. These results indicate that multinucleated giant cells are formed by the cell fusion of mononuclear stromal cells in giant cell tumours of bone and that ADAM12 is involved in the cell fusion process.

The ADaptation and Anticipation Model (ADAM) of sensorimotor synchronization

PubMed Central

van der Steen, M. C. (Marieke); Keller, Peter E.

2013-01-01

A constantly changing environment requires precise yet flexible timing of movements. Sensorimotor synchronization (SMS)—the temporal coordination of an action with events in a predictable external rhythm—is a fundamental human skill that contributes to optimal sensory-motor control in daily life. A large body of research related to SMS has focused on adaptive error correction mechanisms that support the synchronization of periodic movements (e.g., finger taps) with events in regular pacing sequences. The results of recent studies additionally highlight the importance of anticipatory mechanisms that support temporal prediction in the context of SMS with sequences that contain tempo changes. To investigate the role of adaptation and anticipatory mechanisms in SMS we introduce ADAM: an ADaptation and Anticipation Model. ADAM combines reactive error correction processes (adaptation) with predictive temporal extrapolation processes (anticipation) inspired by the computational neuroscience concept of internal models. The combination of simulations and experimental manipulations based on ADAM creates a novel and promising approach for exploring adaptation and anticipation in SMS. The current paper describes the conceptual basis and architecture of ADAM. PMID:23772211

First-trimester ADAM12 and PAPP-A as markers for intrauterine fetal growth restriction through their roles in the insulin-like growth factor system.

PubMed

Cowans, Nicholas J; Spencer, Kevin

2007-03-01

development by breaking down IGF binding proteins and causing the release of free IGF for uptake into cells to promote growth. In those cases that eventually result in poor fetal growth, levels of PAPP-A and ADAM12 at 11-14 weeks are significantly lower than normal-in this instance, lowered PAPP-A and ADAM12 would result in less free IGF being available for cell uptake and growth stimulation. Further studies may elucidate if screening using such modalities can lead to new potential treatments for poorly growing fetuses. Copyright (c) 2007 John Wiley & Sons, Ltd.

ADAM10 mediates trastuzumab resistance and is correlated with survival in HER2 positive breast cancer

PubMed Central

Feldinger, Katharina; Generali, Daniele; Kramer-Marek, Gabriela; Gijsen, Merel; Ng, Tzi Bun; Wong, Jack Ho; Strina, Carla; Cappelletti, Mariarosa; Andreis, Daniele; Li, Ji-Liang; Bridges, Esther; Turley, Helen; Leek, Russell; Roxanis, Ioannis; Capala, Jacek; Murphy, Gillian; Harris, Adrian L.; Kong, Anthony

2014-01-01

Trastuzumab prolongs survival in HER2 positive breast cancer patients. However, resistance remains a challenge. We have previously shown that ADAM17 plays a key role in maintaining HER2 phosphorylation during trastuzumab treatment. Beside ADAM17, ADAM10 is the other well characterized ADAM protease responsible for HER ligand shedding. Therefore, we studied the role of ADAM10 in relation to trastuzumab treatment and resistance in HER2 positive breast cancer. ADAM10 expression was assessed in HER2 positive breast cancer cell lines and xenograft mice treated with trastuzumab. Trastuzumab treatment increased ADAM10 levels in HER2 positive breast cancer cells (p≤0.001 in BT474; p≤0.01 in SKBR3) and in vivo (p≤0.0001) compared to control, correlating with a decrease in PKB phosphorylation. ADAM10 inhibition or knockdown enhanced trastuzumab response in naïve and trastuzumab resistant breast cancer cells. Trastuzumab monotherapy upregulated ADAM10 (p≤0.05); and higher pre-treatment ADAM10 levels correlated with decreased clinical response (p≤0.05) at day 21 in HER2 positive breast cancer patients undergoing a trastuzumab treatment window study. Higher ADAM10 levels correlated with poorer relapse-free survival (p≤0.01) in a cohort of HER2 positive breast cancer patients. Our studies implicate a role of ADAM10 in acquired resistance to trastuzumab and establish ADAM10 as a therapeutic target and a potential biomarker for HER2 positive breast cancer patients. PMID:24952873

Structural Basis for Regulated Proteolysis by the α-Secretase ADAM10.

PubMed

Seegar, Tom C M; Killingsworth, Lauren B; Saha, Nayanendu; Meyer, Peter A; Patra, Dhabaleswar; Zimmerman, Brandon; Janes, Peter W; Rubinstein, Eric; Nikolov, Dimitar B; Skiniotis, Georgios; Kruse, Andrew C; Blacklow, Stephen C

2017-12-14

Cleavage of membrane-anchored proteins by ADAM (a disintegrin and metalloproteinase) endopeptidases plays a key role in a wide variety of biological signal transduction and protein turnover processes. Among ADAM family members, ADAM10 stands out as particularly important because it is both responsible for regulated proteolysis of Notch receptors and catalyzes the non-amyloidogenic α-secretase cleavage of the Alzheimer's precursor protein (APP). We present here the X-ray crystal structure of the ADAM10 ectodomain, which, together with biochemical and cellular studies, reveals how access to the enzyme active site is regulated. The enzyme adopts an unanticipated architecture in which the C-terminal cysteine-rich domain partially occludes the enzyme active site, preventing unfettered substrate access. Binding of a modulatory antibody to the cysteine-rich domain liberates the catalytic domain from autoinhibition, enhancing enzymatic activity toward a peptide substrate. Together, these studies reveal a mechanism for regulation of ADAM activity and offer a roadmap for its modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Synthesis and immunostimulating properties of novel adamant-1-yl tripeptides.

PubMed

Ribić, Rosana; Habjanec, Lidija; Vranešić, Branka; Frkanec, Ruža; Tomić, Srđanka

2012-04-01

The aim of this work was to prepare L- and D-(adamant-1-yl)-Gly-L-Ala-D-isoGln peptides in order to study their adjuvant (immunostimulating) activities. Adjuvant activity of adamant-1-yl tripeptides was tested in the mouse model using ovalbumin as an antigen and in comparison to the peptidoglycan monomer (PGM; β-D-GlcNAc-(1→4)-D-MurNAc-L-Ala-D-isoGln-mesoDAP(εNH(2) )-D-Ala-D-Ala) and structurally related adamant-2-yl tripeptides. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

Thioredoxin-1 Negatively Modulates ADAM17 Activity Through Direct Binding and Indirect Reductive Activity.

PubMed

Granato, Daniela C; E Costa, Rute A P; Kawahara, Rebeca; Yokoo, Sami; Aragão, Annelize Z; Domingues, Romênia R; Pauletti, Bianca A; Honorato, Rodrigo V; Fattori, Juliana; Figueira, Ana Carolina M; Oliveira, Paulo S L; Consonni, Silvio R; Fernandes, Denise; Laurindo, Francisco; Hansen, Hinrich P; Paes Leme, Adriana F

2018-02-27

A disintegrin and metalloprotease 17 (ADAM17) modulates signaling events by releasing surface protein ectodomains such as TNFa and the EGFR-ligands. We have previously characterized cytoplasmic thioredoxin-1 (Trx-1) as a partner of ADAM17 cytoplasmic domain. Still, the mechanism of ADAM17 regulation by Trx-1 is unknown, and it has become of paramount importance to assess the degree of influence that Trx-1 has on metalloproteinase ADAM17. Combining discovery and targeted proteomic approaches, we uncovered that Trx-1 negatively regulates ADAM17 by direct and indirect effect. We performed cell-based assays with synthetic peptides and site-directed mutagenesis, and we demonstrated that the interaction interface of Trx-1 and ADAM17 is important for the negative regulation of ADAM17 activity. However, both Trx-1 K72A and catalytic site mutant Trx-1 C32/35S rescued ADAM17 activity, although the interaction with Trx-1 C32/35S was unaffected, suggesting an indirect effect of Trx-1. We confirmed that the Trx-1 C32/35S mutant showed diminished reductive capacity, explaining this indirect effect on increasing ADAM17 activity through oxidant levels. Interestingly, Trx-1 K72A mutant showed similar oxidant levels to Trx-1 C32/35S , even though its catalytic site was preserved. We further demonstrated that the general reactive oxygen species inhibitor, Nacetylcysteine (NAC), maintained the regulation of ADAM17 dependent of Trx-1 reductase activity levels; whereas the electron transport chain modulator, rotenone, abolished Trx-1 effect on ADAM17 activity. We show for the first time that the mechanism of ADAM17 regulation, Trx-1 dependent, can be by direct interaction and indirect effect, bringing new insights into the cross-talk between isomerases and mammalian metalloproteinases. This unexpected Trx-1 K72A behavior was due to more dimer formation and, consequently, the reduction of its Trx-1 reductase activity, evaluated through dimer verification, by gel filtration and mass

A new gene for asthma: would you ADAM and Eve it?

PubMed

Cookson, William

2003-04-01

Recently, a novel gene was reported to underlie asthma. Linkage to the short arm of chromosome 20 in a genome screen was followed by positive tests of association that centre on the gene for a membrane-anchored zinc-dependent metalloproteinase known as ADAM33. The domain structure of the ADAM33 protein gives capabilities of proteolysis, adhesion, cell fusion and intracellular signalling. Although its function is at present unknown, these potential actions of ADAM33 provide many possibilities for further research.

EMMPRIN and ADAM12 in prostate cancer: preliminary results of a prospective study.

PubMed

Bilgin Doğru, Elif; Dizdar, Yavuz; Akşit, Ece; Ural, Feyyaz; Şanlı, Öner; Yasasever, Vildan

2014-11-01

Extracellular metalloproteinase inducer (EMMPRIN) and a disintegrin and metalloproteinase (ADAM12) play a major role in cancer invasion and metastasis owing to the fact that they are directly related to the cell microenvironment and extracellular matrix (ECM) degradation. The aim of this study was to search for an answer to the question "whether the determination of EMMPRIN and ADAM12 values especially in urine may be helpful for the early diagnosis of prostate cancer without employing invasive methods" and also to check whether they may be useful for the determination of the patients with high metastasis risk. Peripheral blood and urine from 66 prostate cancer patients (40 local, 20 locally advanced, 6 metastatic) and 14 healthy controls were evaluated by enzyme-linked immunosorbent assay (ELISA) method. Serum EMMPRIN and ADAM12 values of the patients were seen to be statistically higher than the serum EMMPRIN and ADAM12 values of the healthy controls (p=0.01 and p=0.001, respectively). The urine ADAM12 levels were significantly higher in patients (p=0.013). No significant relationships were found between urine EMMPRIN values of the patients and the healthy controls (p>0.05). Positive correlation between urine EMMPRIN-urine ADAM12 tests was found in total patients group (r=0.683, p=0.001). Our preliminary results revealed that serum EMMPRIN and ADAM12 values and urine ADAM12 values may be useful markers in prostate cancer therapy. Due to the high correlation between these two tests, we are of the opinion that the use of urine ADAM12 in clinic may be sufficient and favorable together with prostate-specific antigen (PSA) for treatment.

The Role of ADAM9 in Tumor-Stromal Interactions in Breast Cancer

DTIC Science & Technology

2010-04-01

Tumor-Stromal Interactions in Breast Cancer PRINCIPAL INVESTIGATOR: Jessica L. Fry...The Role of ADAM9 in Tumor-Stromal Interactions in Breast Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-06-1-0460 5c...ADAM9, the development of a model system to investigate the isoforms of ADAM-9 in breast cancer cell migration, and the use of this model system to

Adam10 Mediates the Choice between Principal Cells and Intercalated Cells in the Kidney

PubMed Central

Guo, Qiusha; Wang, Yinqiu; Tripathi, Piyush; Manda, Kalyan R.; Mukherjee, Malini; Chaklader, Malay; Austin, Paul F.

2015-01-01

A disintegrin and metalloproteinase domain 10 (Adam10), a member of the ADAM family of cell membrane–anchored proteins, has been linked to the regulation of the Notch, EGF, E-cadherin, and other signaling pathways. However, it is unclear what role Adam10 has in the kidney in vivo. In this study, we showed that Adam10 deficiency in ureteric bud (UB) derivatives leads to a decrease in urinary concentrating ability, polyuria, and hydronephrosis in mice. Furthermore, Adam10 deficiency led to a reduction in the percentage of aquaporin 2 (Aqp2)+ principal cells (PCs) in the collecting ducts that was accompanied by a proportional increase in the percentage of intercalated cells (ICs). This increase was more prominent in type A ICs than in type B ICs. Foxi1, a transcription factor important for the differentiation of ICs, was upregulated in the Adam10 mutants. The observed reduction of Notch activity in Adam10 mutant collecting duct epithelium and the similar reduction of PC/IC ratios in the collecting ducts in mice deficient for mindbomb E3 ubiquitin protein ligase 1, a key regulator of the Notch and Wnt/receptor-like tyrosine kinase signaling pathways, suggest that Adam10 regulates cell fate determination through the activation of Notch signaling, probably through the regulation of Foxi1 expression. However, phenotypic differences between the Adam10 mutants, the Mib1 mutants, and the Foxi1 mutants suggest that the functions of Adam10 in determining the fate of collecting duct cells are more complex than those of a simple upstream factor in a linear pathway involving Notch and Foxi1. PMID:24904084

ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7

PubMed Central

Bridges, Lance C.; Sheppard, Dean; Bowditch, Ron D.

2004-01-01

The ADAM (a disintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin α4β1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins α4β1, α4β7 and α9β1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported α4β1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not. The lymphocyte integrin α4β7 was also found to recognize both disintegrin domains of ADAM7 and ADAM28, but not of ADAM33. This is the first demonstration that mammalian disintegrins are capable of interacting with α4β7. All three disintegrin domains supported α9β1-dependent cell adhesion. Recognition by both α4β1 and α4β7 of ADAM7 and ADAM28 was activation-dependent, requiring either the presence of Mn2+ or an activating monoclonal antibody for cell attachment. Charge-to-alanine mutagenesis experiments revealed that the same residues within an individual ADAM disintegrin domain function in recognizing multiple integrins. However, the residues within a specific region of each ADAM disintegrin-like domain required for integrin binding were distinct. These results establish that ADAM7 and ADAM28 are recognized by the leucocyte integrins α4β1, α4β7 and α9β1. ADAM33 exclusively supported only α9β1-dependent adhesion. PMID:15504110

Improvement of VMAT plan quality for head and neck cancer with high resolution fluences generated by couch shift between arcs.

PubMed

Park, Jong Min; Park, So-Yeon; Wu, Hong-Gyun; Kim, Jung-In

2018-02-01

To investigate the changes in quality of the volumetric modulated arc therapy (VMAT) plans with couch-shift between arcs by half of a multi-leaf collimator (MLC) leaf width. A total of 22 patients with head-and-neck cancer were retrospectively selected. Since the smallest MLC leaf width was 5 mm in this study, the couch was shifted by 2.5 mm in the longitudinal-direction between arcs to increase the resolution of fluence map. A total of three types of VMAT plans were generated for each patient; the three types of plans were a two-full-arc plan without couch-shift (NS plan), a two-half-arc-pair plan with couch-shift (HAS plan), and a two-full-arc pair plan with couch-shift (FAS plan). Changes in the dose-volumetric parameters were investigated. The FAS plan showed the best plan quality for the target volumes and organs at risk compared to the NS and HAS plans. However, the magnitudes of differences among the three types of plans were minimal, and every plan was clinically acceptable. The average integral doses of the NS, HAS, and FAS plans were 160,549 ± 37,600 Gy-cc, 147,828 ± 33,343 Gy-cc, and 156,030 ± 36,263 Gy-cc, respectively. The average monitor unit of the NS, HAS, and FAS plans were 717 ± 120 MU, 648 ± 100 MU, and 763 ± 158 MU, respectively. The HAS plan was better than the others in terms of normal tissue sparing and plan efficiency. By shifting the couch by half of the MLC leaf width in the longitudinal direction between arcs, the VMAT plan quality could be improved. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Traditional couching is not an effective alternative procedure for cataract surgery in Mali.

PubMed

Schémann, J F; Bakayoko, S; Coulibaly, S

2000-12-01

In Mali, more cataract patients receive sight-restoring surgery using a traditional "couching" procedure (the lens inside the vitreous body) than by modern cataract surgery. In order to evaluate the relative effectiveness and other outcomes of the traditional procedure compared to the modern surgical intervention, we conducted a population-based survey in a rural district of Mali in 1996. A total of 99,800 persons from 160 villages were eligible to be included in the sample. All individuals operated for cataract by a modern procedure were checked for visual acuity and questioned regarding their clinical history, the cost of the surgery and their satisfaction with the surgery immediately following the operation and presently. Each patient was paired with one person operated by a traditional cataract surgical procedure. From a total population of 99,800 we found 85 individuals (0.085%) who had been operated by intracapsular extraction (ICCE) without lens implantation and we paired these with 82 individuals operated by the traditional method and by a local healer. In both groups, males were predominant (74.4% in the modern group and 61.3% in the traditional) and the median age was 65 and 68 years, respectively. Men with a higher social status (defined as administrative or religious authority) were slightly more common among those operated by ICCE (18.9%) than among those operated by the traditional healer (4.4%). Nearly half (47.6%) of the patients operated by couching did not know that a modern alternative existed. The mean cost to the patient of the two procedures was similar; with traditional couching costing on average US$ 42.10 and modern surgery (including transport and drugs) costing US$ 52.40. The traditional healer was often paid partially in kind and the price paid varied according to the patient's ability to pay. The clinical results differed greatly between the two methods. After aphakic correction of eyes operated by ICCE, 5.3% had good vision (33/18), 76

Compensating for Tumor Motion by a 6-Degree-of-Freedom Treatment Couch: Is Patient Tolerance an Issue?

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

Sweeney, Reinhart A.; Arnold, Winfried; Steixner, Eva

2009-05-01

Purpose: To determine whether patients could tolerate the motion of a robotic couch that compensates for breathing-induced tumor motion. Methods and Materials: A total of 10 healthy subjects and 23 radio-oncology patients underwent simulated extracranial stereotactic radiotherapy (two 30-min sessions) on a robotic couch programmed to follow a fictitious tumor trajectory of 20x5x5 mm (cranio-caudal, left-right, and anterior-posterior directions, respectively) while rotating 2 deg. around a cranio-caudal axis at a frequency of 5 seconds per loop. Results: No session had to be interrupted and no nausea was induced. However, one patient refused the second session due to general deterioration andmore » not all patients could keep their arms elevated for the entire session. Conclusions: Our findings showed that most patients tolerated compensatory couch motion and that motion sickness should not pose a problem in the investigation of this tumor-tracking method.« less

ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma.

PubMed

Xu, Qin; Ying, Mingang; Chen, Guilin; Lin, Ang; Xie, Yunqing; Ohara, Noriyuki; Zhou, Dongmei

2014-08-01

Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P < 0.05). Strong expression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P < 0.05). Overexpression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P < 0.05). Multivariate analysis suggested that lymph node metastasis, parametrium invasion, and ADAM17 expression were independent prognostic indicators for cervical cancer. ADAM17 RNAi decreased EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a

Dissecting the role of ADAM10 as a mediator of Staphylococcus aureus α-toxin action.

PubMed

von Hoven, Gisela; Rivas, Amable J; Neukirch, Claudia; Klein, Stefan; Hamm, Christian; Qin, Qianqian; Meyenburg, Martina; Füser, Sabine; Saftig, Paul; Hellmann, Nadja; Postina, Rolf; Husmann, Matthias

2016-07-01

Staphylococcus aureus is a leading cause of bacterial infections in humans, including life-threatening diseases such as pneumonia and sepsis. Its small membrane-pore-forming α-toxin is considered an important virulence factor. By destroying cell-cell contacts through cleavage of cadherins, the metalloproteinase ADAM10 (a disintegrin and metalloproteinase 10) critically contributes to α-toxin-dependent pathology of experimental S. aureus infections in mice. Moreover, ADAM10 was proposed to be a receptor for α-toxin. However, it is unclear whether the catalytic activity or specific domains of ADAM10 are involved in mediating binding and/or subsequent cytotoxicity of α-toxin. Also, it is not known how α-toxin triggers ADAM10's enzymatic activity, and whether ADAM10 is invariably required for all α-toxin action on cells. In the present study, we show that efficient cleavage of the ADAM10 substrate epithelial cadherin (E-cadherin) requires supra-cytotoxic concentrations of α-toxin, leading to significant increases in intracellular [Ca(2+)]; the fall in cellular ATP levels, typically following membrane perforation, became observable at far lower concentrations. Surprisingly, ADAM10 was dispensable for α-toxin-dependent xenophagic targeting of S. aureus, whereas a role for α-toxin attack on the plasma membrane was confirmed. The catalytic site of ADAM10, furin cleavage site, cysteine switch and intracellular domain of ADAM10 were not required for α-toxin binding and subsequent cytotoxicity. In contrast, an essential role for the disintegrin domain and the prodomain emerged. Thus, co-expression of the prodomain with prodomain-deficient ADAM10 reconstituted binding of α-toxin and susceptibility of ADAM10-deficient cells. The results of the present study may help to inform structural analyses of α-toxin-ADAM10 interactions and to design novel strategies to counteract S. aureus α-toxin action. © 2016 The Author(s). published by Portland Press Limited on behalf

From Adam Swift to Adam Smith: How the "Invisible Hand" Overcomes Middle Class Hypocrisy

ERIC Educational Resources Information Center

Tooley, James

2007-01-01

This paper challenges Richard Pring's suggestion that parents using private education may be undermining the desire for social justice and equality, using recent arguments of Adam Swift as a springboard. Swift's position on the banning of private schools, which uses a Rawlsian "veil of ignorance" argument, is explored, and it is suggested that, if…

Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

PubMed Central

Kuhn, Peer-Hendrik; Colombo, Alessio Vittorio; Schusser, Benjamin; Dreymueller, Daniela; Wetzel, Sebastian; Schepers, Ute; Herber, Julia; Ludwig, Andreas; Kremmer, Elisabeth; Montag, Dirk; Müller, Ulrike; Schweizer, Michaela; Saftig, Paul; Bräse, Stefan; Lichtenthaler, Stefan F

2016-01-01

Metzincin metalloproteases have major roles in intercellular communication by modulating the function of membrane proteins. One of the proteases is the a-disintegrin-and-metalloprotease 10 (ADAM10) which acts as alpha-secretase of the Alzheimer's disease amyloid precursor protein. ADAM10 is also required for neuronal network functions in murine brain, but neuronal ADAM10 substrates are only partly known. With a proteomic analysis of Adam10-deficient neurons we identified 91, mostly novel ADAM10 substrate candidates, making ADAM10 a major protease for membrane proteins in the nervous system. Several novel substrates, including the neuronal cell adhesion protein NrCAM, are involved in brain development. Indeed, we detected mistargeted axons in the olfactory bulb of conditional ADAM10-/- mice, which correlate with reduced cleavage of NrCAM, NCAM and other ADAM10 substrates. In summary, the novel ADAM10 substrates provide a molecular basis for neuronal network dysfunctions in conditional ADAM10-/- mice and demonstrate a fundamental function of ADAM10 in the brain. DOI: http://dx.doi.org/10.7554/eLife.12748.001 PMID:26802628

Relax with CouchDB - Into the non-relational DBMS era of Bioinformatics

PubMed Central

Manyam, Ganiraju; Payton, Michelle A.; Roth, Jack A.; Abruzzo, Lynne V.; Coombes, Kevin R.

2012-01-01

With the proliferation of high-throughput technologies, genome-level data analysis has become common in molecular biology. Bioinformaticians are developing extensive resources to annotate and mine biological features from high-throughput data. The underlying database management systems for most bioinformatics software are based on a relational model. Modern non-relational databases offer an alternative that has flexibility, scalability, and a non-rigid design schema. Moreover, with an accelerated development pace, non-relational databases like CouchDB can be ideal tools to construct bioinformatics utilities. We describe CouchDB by presenting three new bioinformatics resources: (a) geneSmash, which collates data from bioinformatics resources and provides automated gene-centric annotations, (b) drugBase, a database of drug-target interactions with a web interface powered by geneSmash, and (c) HapMap-CN, which provides a web interface to query copy number variations from three SNP-chip HapMap datasets. In addition to the web sites, all three systems can be accessed programmatically via web services. PMID:22609849

Identification of novel interaction between ADAM17 (a disintegrin and metalloprotease 17) and thioredoxin-1.

PubMed

Aragão, Annelize Z B; Nogueira, Maria Luiza C; Granato, Daniela C; Simabuco, Fernando M; Honorato, Rodrigo V; Hoffman, Zaira; Yokoo, Sami; Laurindo, Francisco R M; Squina, Fabio M; Zeri, Ana Carolina M; Oliveira, Paulo S L; Sherman, Nicholas E; Paes Leme, Adriana F

2012-12-14

ADAM17, which is also known as TNFα-converting enzyme, is the major sheddase for the EGF receptor ligands and is considered to be one of the main proteases responsible for the ectodomain shedding of surface proteins. How a membrane-anchored proteinase with an extracellular catalytic domain can be activated by inside-out regulation is not completely understood. We characterized thioredoxin-1 (Trx-1) as a partner of the ADAM17 cytoplasmic domain that could be involved in the regulation of ADAM17 activity. We induced the overexpression of the ADAM17 cytoplasmic domain in HEK293 cells, and ligands able to bind this domain were identified by MS after protein immunoprecipitation. Trx-1 was also validated as a ligand of the ADAM17 cytoplasmic domain and full-length ADAM17 recombinant proteins by immunoblotting, immunolocalization, and solid phase binding assay. In addition, using nuclear magnetic resonance, it was shown in vitro that the titration of the ADAM17 cytoplasmic domain promotes changes in the conformation of Trx-1. The MS analysis of the cross-linked complexes showed cross-linking between the two proteins by lysine residues. To further evaluate the functional role of Trx-1, we used a heparin-binding EGF shedding cell model and observed that the overexpression of Trx-1 in HEK293 cells could decrease the activity of ADAM17, activated by either phorbol 12-myristate 13-acetate or EGF. This study identifies Trx-1 as a novel interaction partner of the ADAM17 cytoplasmic domain and suggests that Trx-1 is a potential candidate that could be involved in ADAM17 activity regulation.

Accuracy evaluation of a six-degree-of-freedom couch using cone beam CT and IsoCal phantom with an in-house algorithm.

PubMed

Zhang, Qinghui; Driewer, Joseph; Wang, Shuo; Li, Sicong; Zhu, Xiaofeng; Zheng, Dandan; Cao, Yijian; Zhang, Jiaju; Jamshidi, Abolghassem; Cox, Brett W; Knisely, Jonathan P S; Potters, Louis; Klein, Eric E

2017-08-01

The accuracy of a six degree of freedom (6DoF) couch was evaluated using a novel method. Cone beam CT (CBCT) images of a 3D phantom (IsoCal) were acquired with different, known combinations of couch pitch and roll angles. Pitch and roll angles between the maximum allowable values of 357 and 3 degrees were tested in one degree increments. A total of 49 combinations were tested at 0 degrees of yaw (couch rotation angle). The 3D positions of 16 tungsten carbide ball bearings (BBs), each 4 mm in diameter and arranged in a known geometry within the IsoCal phantom, were determined in the 49 image sets with in-house software. The BB positions at different rotation angles were determined using a rotation matrix from the original BB positions at zero pitch and roll angles. A linear least squares fit method estimated the rotation angles and differences between detected and nominal rotation angles were calculated. This study was conducted for the case with and without extra weight on the couch. Couch walk shifts for the system were investigated using eight combinations of rotation, roll and pitch. A total of 49 CBCT images with voxel sizes 0.5 × 0.5 × 1.0 mm 3 were taken for the case without extra weight on the couch. The 16 BBs were determined to evaluate the isocenter translation and rotation differences between the calculated and nominal couch values. Among all 49 calculations, the maximum rotation angle differences were 0.10 degrees for pitch, 0.15 degrees for roll and 0.09 degrees for yaw. The corresponding mean and standard deviation values were 0.028 ± 0.032, -0.043 ± 0.058, and -0.009 ± 0.033 degrees. The maximum translation differences were 0.3 mm in the left-right direction, 0.5 mm in the anterior-posterior direction and 0.4 mm in the superior-inferior direction. The mean values and corresponding standard deviations were 0.07 ± 0.12, -0.05 ± 0.25, and -0.12±0.14 mm for the planes described above. With an 80 kg phantom on the couch, the

GSK3 and Polo-like kinase regulate ADAM13 function during cranial neural crest cell migration

PubMed Central

Abbruzzese, Genevieve; Cousin, Hélène; Salicioni, Ana Maria; Alfandari, Dominique

2014-01-01

ADAMs are cell surface metalloproteases that control multiple biological processes by cleaving signaling and adhesion molecules. ADAM13 controls cranial neural crest (CNC) cell migration both by cleaving cadherin-11 to release a promigratory extracellular fragment and by controlling expression of multiple genes via its cytoplasmic domain. The latter activity is regulated by γ-secretase cleavage and the translocation of the cytoplasmic domain into the nucleus. One of the genes regulated by ADAM13, the protease calpain8, is essential for CNC migration. Although the nuclear function of ADAM13 is evolutionarily conserved, it is unclear whether the transcriptional regulation is also performed by other ADAMs and how this process may be regulated. We show that ADAM13 function to promote CNC migration is regulated by two phosphorylation events involving GSK3 and Polo-like kinase (Plk). We further show that inhibition of either kinase blocks CNC migration and that the respective phosphomimetic forms of ADAM13 can rescue these inhibitions. However, these phosphorylations are not required for ADAM13 proteolysis of its substrates, γ-secretase cleavage, or nuclear translocation of its cytoplasmic domain. Of significance, migration of the CNC can be restored in the absence of Plk phosphorylation by expression of calpain-8a, pointing to impaired nuclear activity of ADAM13. PMID:25298404

Technical Note: Direct measurement of continuous TMR data with a 1D tank and automated couch movements.

PubMed

Knutson, Nels C; Schmidt, Matthew C; Belley, Matthew D; Nguyen, Ngoc B; Li, H Harold; Sajo, Erno; Price, Michael J

2017-07-01

Real-time dynamic control of the linear accelerator, couch, and imaging parameters during radiation delivery was investigated as a novel technique for acquiring tissue maximum ratio (TMR) data. TrueBeam Developer Mode (Varian Medical Systems, Palo Alto, CA, USA) was used to control the linear accelerator using the Extensible Markup Language (XML). A single XML file was used to dynamically manipulate the machine, couch, and imaging parameters during radiation delivery. A TG-51 compliant 1D water tank was placed on the treatment couch, and used to position a detector at isocenter at a depth of 24.5 cm. A depth scan was performed towards the water surface. Via XML control, the treatment couch vertical position was simultaneously lowered at the same rate, maintaining the detector position at isocenter, allowing for the collection of TMR data. To ensure the detector remained at isocenter during the delivery, the in-room camera was used to monitor the detector. Continuous kV fluoroscopic images during 10 test runs further confirmed this result. TMR data at multiple Source to Detector Distances (SDD) and scan speeds were acquired to investigate their impact on the TMR data. Percentage depth dose (PDD) scans (for conversion to TMR) along with traditional discrete TMR data were acquired as a standard for comparison. More than 99.8% of the measured points had a gamma value (1%/1 mm) < 1 when compared with discrete or PDD converted TMR data. Fluoroscopic images showed that the concurrent couch and tank movements resulted in SDD errors < 1 mm. TMRs acquired at SDDs of 99, 100, and 101 cm showed differences less than 0.004. TrueBeam Developer Mode was used to collect continuous TMR data with the same accuracy as traditionally collected discrete data, but yielded higher sampled resolution and reduced acquisition time. This novel method does not require the modification of any equipment and does not use a 3D tank or reservoir. © 2017 American Association of Physicists in

Increased abundance of ADAM9 transcripts in the blood is associated with tissue damage

PubMed Central

Rinchai, Darawan; Kewcharoenwong, Chidchamai; Kessler, Bianca; Lertmemongkolchai, Ganjana; Chaussabel, Damien

2016-01-01

Background: Members of the ADAM (a disintegrin and metalloprotease domain) family have emerged as critical regulators of cell-cell signaling during development and homeostasis. ADAM9 is consistently overexpressed in various human cancers, and has been shown to play an important role in tumorigenesis. However, little is known about the involvement of ADAM9 during immune-mediated processes. Results: Mining of an extensive compendium of transcriptomic datasets identified important gaps in knowledge regarding the possible role of ADAM9 in immunological homeostasis and inflammation: 1) The abundance of ADAM9 transcripts in the blood was increased in patients with acute infection but, 2) changed very little after in vitro exposure to a wide range of pathogen-associated molecular patterns (PAMPs). 3) Furthermore it was found to increase significantly in subjects as a result of tissue injury or tissue remodeling, in absence of infectious processes. Conclusions: Our findings indicate that ADAM9 may constitute a valuable biomarker for the assessment of tissue damage, especially in clinical situations where other inflammatory markers are confounded by infectious processes. PMID:27990250

α-Lipoic acid reduces neurogenic hypertension by blunting oxidative stress-mediated increase in ADAM17

PubMed Central

de Queiroz, Thyago M.; Xia, Huijing; Filipeanu, Catalin M.; Braga, Valdir A.

2015-01-01

We previously reported that type 2 angiotensin-converting enzyme (ACE2) compensatory activity is impaired by the disintegrin and metalloprotease 17 (ADAM17), and lack of ACE2 is associated with oxidative stress in neurogenic hypertension. To investigate the relationship between ADAM17 and oxidative stress, Neuro2A cells were treated with ANG II (100 nM) 24 h after vehicle or α-lipoic acid (LA, 500 μM). ADAM17 expression was increased by ANG II (120.5 ± 9.1 vs. 100.2 ± 0.8%, P < 0.05) and decreased after LA (69.0 ± 0.3 vs. 120.5 ± 9.1%, P < 0.05). In another set of experiments, LA reduced ADAM17 (92.9 ± 5.3 vs. 100.0 ± 11.2%, P < 0.05) following its overexpression. Moreover, ADAM17 activity was reduced by LA in ADAM17-overexpressing cells [109.5 ± 19.8 vs. 158.0 ± 20.0 fluorescence units (FU)·min−1·μg protein−1, P < 0.05], in which ADAM17 overexpression increased oxidative stress (114.1 ± 2.5 vs. 101.0 ± 1.0%, P < 0.05). Conversely, LA-treated cells attenuated ADAM17 overexpression-induced oxidative stress (76.0 ± 9.1 vs. 114.1 ± 2.5%, P < 0.05). In deoxycorticosterone acetate (DOCA)-salt hypertensive mice, a model in which ADAM17 expression and activity are increased, hypertension was blunted by pretreatment with LA (119.0 ± 2.4 vs. 131.4 ± 2.2 mmHg, P < 0.05). In addition, LA improved dysautonomia and baroreflex sensitivity. Furthermore, LA blunted the increase in NADPH oxidase subunit expression, as well as the increase in ADAM17 and decrease in ACE2 activity in the hypothalamus of DOCA-salt hypertensive mice. Taken together, these data suggest that LA might preserve ACE2 compensatory activity by breaking the feedforward cycle between ADAM17 and oxidative stress, resulting in a reduction of neurogenic hypertension. PMID:26254330

Genetics Home Reference: Adams-Oliver syndrome

MedlinePlus

... Baveja R, Silva ES, Dixon J, Leon EL, Solomon BD, Glusman G, Niederhuber JE, Roach JC, Patel MS. Mutations in NOTCH1 cause Adams-Oliver syndrome. Am J Hum Genet. 2014 Sep 4;95(3):275-84. doi: 10.1016/j. ...

Effect of a new marker, ADAM12, on Down risk figures in first trimester screening.

PubMed

Valinen, Yrtti; Laitinen, Paivi; Ranta, Jenni; Ignatius, Jaakko; Jarvela, Ilkka; Ryynänen, Markku

2009-07-01

To investigate whether incorporating the measurement of ADAM12 in the risk calculation program LifeCycle, can improve Down screening in the first trimester. In a retrospective case control study, maternal serum ADAM12 concentrations were measured and compared in Down syndrome cases (n = 53) and in controls (n = 226) obtained from first trimester (9-12 weeks) screening samples in Oulu and Kuopio University Hospitals. Median concentration ( microg/l), observed and regressed (weight corrected) MoMs of ADAM12 were calculated. There was a significant difference in ADAM12 levels between Downs and controls during the pregnancy weeks 9 + 0 to 10 + 6, but not thereafter. By adding ADAM12 to the marker set used in the risk calculation program, one screening false negative Down syndrome case occurred in the affected population, which did not alter false positive rate. Adding ADAM12 as a parameter in Down screening did not cause radical changes in the risk value. The test might be useful at 9 and 10 weeks in which it might have the potential to improve the performance of the risk assessment especially for women receiving a result close to the high-risk cut-off. The real influence of ADAM12 remains to be elucidated in larger studies incorporating ADAM12 to the risk calculation program.

TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

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

Ebi, Masahide; Kataoka, Hiromi, E-mail: hkataoka@med.nagoya-cu.ac.jp; Shimura, Takaya

2010-11-19

Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cellmore » growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

Neurons on the couch.

PubMed

Marić, Nadja P; Jašović-Gašić, Miroslava

2010-12-01

A hundred years after psychoanalysis was introduced, neuroscience has taken a giant step forward. It seems nowadays that effects of psychotherapy could be monitored and measured by state-of-the art brain imaging techniques. Today, the psychotherapy is considered as a strategic and purposeful environmental influence intended to enhance learning. Since gene expression is regulated by environmental influences throughout life and these processes create brain architecture and influence the strength of synaptic connections, psychotherapy (as a kind of learning) should be explored in the context of aforementioned paradigm. In other words, when placing a client on the couch, therapist actually placed client's neuronal network; while listening and talking, expressing and analyzing, experiencing transference and counter transference, therapist tends to stabilize synaptic connections and influence dendritic growth by regulating gene-transcriptional activity. Therefore, we strongly believe that, in the near future, an increasing knowledge on cellular and molecular interactions and mechanisms of action of different psycho- and pharmaco-therapeutic procedures will enable us to tailor a sophisticated therapeutic approach toward a person, by combining major therapeutic strategies in psychiatry on the basis of rational goals and evidence-based therapeutic expectations.

Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat

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

Duan, Yiyuan; Long, Jiaoyue; Chen, Jun

A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a susceptibility gene for asthma, but details of the causality are not fully understood. We hypothesize that soluble ADAM33 (sADAM33) overexpression can alter the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of the cell's contractile phenotype, and thus contributes to airway hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either overexpressed or knocked down the sADAM33 in rat ASMCs by transfecting the cells with sADAM33 coding sequence or a small interfering RNA (siRNA) that specifically targets the ADAM33 disintegrin domain, and subsequently assessed the cells formore » stiffness, contractility and traction force, together with the expression level of contractile and proliferative phenotype markers. We also investigated whether these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in the absence or presence of ROCK inhibitor (H1152). The results showed that the ASMCs with sADAM33 overexpression were stiffer and more contractile, generated greater traction force, exhibited increased expression levels of contractile phenotype markers and markedly enhanced Rho activation. Furthermore these changes were largely attenuated when the cells were cultured in the presence of H-1152. However, the knock-down of ADAM33 seemed insufficient to influence majority of the mechanical behaviors of the ASMCs. Taken together, we demonstrated that sADAM33 overexpression altered the mechanical behaviors of ASMCs in vitro, which was most likely by promoting a hypercontractile phenotype transition of ASMCs through Rho/ROCK pathway. This revelation may establish the previously missing link between ADAM33 expression and AHR, and also provide useful insight for targeting sADAM33 in asthma prevention and therapy. - Highlights: • sADAM33 overexpression enhances the stiffness, traction force and contractility of ASMCs. • sADAM33 overexpression

Relax with CouchDB--into the non-relational DBMS era of bioinformatics.

PubMed

Manyam, Ganiraju; Payton, Michelle A; Roth, Jack A; Abruzzo, Lynne V; Coombes, Kevin R

2012-07-01

With the proliferation of high-throughput technologies, genome-level data analysis has become common in molecular biology. Bioinformaticians are developing extensive resources to annotate and mine biological features from high-throughput data. The underlying database management systems for most bioinformatics software are based on a relational model. Modern non-relational databases offer an alternative that has flexibility, scalability, and a non-rigid design schema. Moreover, with an accelerated development pace, non-relational databases like CouchDB can be ideal tools to construct bioinformatics utilities. We describe CouchDB by presenting three new bioinformatics resources: (a) geneSmash, which collates data from bioinformatics resources and provides automated gene-centric annotations, (b) drugBase, a database of drug-target interactions with a web interface powered by geneSmash, and (c) HapMap-CN, which provides a web interface to query copy number variations from three SNP-chip HapMap datasets. In addition to the web sites, all three systems can be accessed programmatically via web services. Copyright © 2012 Elsevier Inc. All rights reserved.

SU-F-T-515: Increased Skin Dose in Supine Craniospinal Irradiation Due to Carbon Fiber Couch and Vacuum Bag Immobilization Device

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

Robertson, D; Zhao, Z; Wang, X

2016-06-15

Purpose: To measure the surface dose for supine craniospinal irradiation employing posterior beams, treating through an imaging couch and BlueBag immobilization device. Methods: The percentage depth dose (PDD) in the buildup region of a clinical 6 MV photon beam was measured using an Advanced Markus parallel plate ionization chamber in a solid water phantom. The PDD from a 10×10 cm{sup 2} anterior beam was measured at 100 cm SSD, simulating a traditional prone craniospinal technique. The measurements were compared to commissioning and treatment planning system data. The PDD was also measured in a posterior setup with the phantom surface layingmore » directly on the Brainlab carbon fiber imaging couch, with the phantom surface 100 cm from the source, simulating a supine craniospinal setup. The posterior measurements were repeated with a BlueBag vacuum immobilization device between the couch and phantom, with thicknesses of 1.7 cm and 5 cm. The PDD from a 10×10 cm{sup 2} field and a typical 6×30 cm{sup 2} craniospinal field were also compared. The PDDs were normalized at 5 cm to reflect typical craniospinal prescription dose normalization. Results: The measured PDD curve from the anterior setup agreed well with commissioning and treatment planning data, with surface doses of 19.9%, 28.8% and 27.7%, respectively. The surface doses of the 10×10 cm{sup 2} and 6×30 cm{sup 2} fields delivered through the imaging couch were both 122.4%. The supine setup yielded surface doses of 122.4%, 121.6%, and 119.6% for the couch only, 1.7 cm bag, and 5 cm bag setups, respectively. Conclusion: Delivering craniospinal irradiation through a carbon fiber couch removes the majority of skin sparing. The addition of a vacuum bag immobilization device restores some skin sparing, but the magnitude of this effect is negligible.« less

ADAM, a hands-on patient simulator for teaching principles of drug disposition and compartmental pharmacokinetics.

PubMed

Zuna, Ines; Holt, Andrew

2017-11-01

To design, construct and validate a pharmacokinetics simulator that offers students hands-on opportunities to participate in the design, administration and analysis of oral and intravenous dosing regimens. The Alberta Drug Administration Modeller (ADAM) is a mechanical patient in which peristaltic circulation of water through a network of silicone tubing and glass bottles creates a representation of the outcomes of drug absorption, distribution, metabolism and elimination. Changing peristaltic pump rates and volumes in bottles allows values for pharmacokinetic constants to be varied, thereby simulating differences in drug properties and in patient physiologies and pathologies. Following administration of methylene blue dye by oral or intravenous routes, plasma and/or urine samples are collected and drug concentrations are determined spectrophotometrically. The effectiveness of the simulator in enhancing student competence and confidence was assessed in two undergraduate laboratory classes. The simulator effectively models one- and two-compartment drug behaviour in a mathematically-robust and realistic manner. Data allow calculation of numerous pharmacokinetic constants, by traditional graphing methods or with curve-fitting software. Students' competence in solving pharmacokinetic problems involving calculations and graphing improved significantly, while an increase in confidence and understanding was reported. The ADAM is relatively inexpensive and straightforward to construct, and offers a realistic, hands-on pharmacokinetics learning opportunity for students that effectively complements didactic lectures. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Cardiomyocyte A Disintegrin And Metalloproteinase 17 (ADAM17) Is Essential in Post-Myocardial Infarction Repair by Regulating Angiogenesis.

PubMed

Fan, Dong; Takawale, Abhijit; Shen, Mengcheng; Wang, Wang; Wang, Xiuhua; Basu, Ratnadeep; Oudit, Gavin Y; Kassiri, Zamaneh

2015-09-01

A disintegrin and metalloproteinase 17 (ADAM17) is a membrane-bound enzyme that mediates shedding of many membrane-bound molecules, thereby regulating multiple cellular responses. We investigated the role of cardiomyocyte ADAM17 in myocardial infarction (MI). Cardiomyocyte-specific ADAM17 knockdown mice (ADAM17(flox/flox)/α-MHC-Cre; f/f/Cre) and parallel controls (ADAM17(flox/flox); f/f) were subjected to MI by ligation of the left anterior descending artery. Post MI, f/f/Cre mice showed compromised survival, higher rates of cardiac rupture, more severe left ventricular dilation, and suppressed ejection fraction compared with parallel f/f-MI mice. Ex vivo ischemic injury (isolated hearts) resulted in comparable recovery in both genotypes. Myocardial vascular density (fluorescent-labeled lectin perfusion and CD31 immunofluorescence staining) was significantly lower in the infarct areas of f/f/Cre-MI compared with f/f-MI mice. Activation of vascular endothelial growth factor receptor 2 (VEGFR2), its mRNA, and total protein levels were reduced in infarcted myocardium in ADAM17 knockdown mice. Transcriptional regulation of VEGFR2 by ADAM17 was confirmed in cocultured cardiomyocyte-fibroblast as ischemia-induced VEGFR2 expression was blocked by ADAM17-siRNA. Meanwhile, ADAM17-siRNA did not alter VEGFA bioavailability in the conditioned media. ADAM17 knockdown mice (f/f/Cre-MI) exhibited reduced nuclear factor-κB activation (DNA binding) in the infarcted myocardium, which could underlie the suppressed VEGFR2 expression in these hearts. Post MI, inflammatory response was not altered by ADAM17 downregulation. This study highlights the key role of cardiomyocyte ADAM17 in post-MI recovery by regulating VEGFR2 transcription and angiogenesis, thereby limiting left ventricular dilation and dysfunction. Therefore, ADAM17 upregulation, within the physiological range, could provide protective effects in ischemic cardiomyopathy. © 2015 American Heart Association, Inc.

Extraction and Separation Modeling of Orion Test Vehicles with ADAMS Simulation

NASA Technical Reports Server (NTRS)

Fraire, Usbaldo, Jr.; Anderson, Keith; Cuthbert, Peter A.

2013-01-01

The Capsule Parachute Assembly System (CPAS) project has increased efforts to demonstrate the performance of fully integrated parachute systems at both higher dynamic pressures and in the presence of wake fields using a Parachute Compartment Drop Test Vehicle (PCDTV) and a Parachute Test Vehicle (PTV), respectively. Modeling the extraction and separation events has proven challenging and an understanding of the physics is required to reduce the risk of separation malfunctions. The need for extraction and separation modeling is critical to a successful CPAS test campaign. Current PTV-alone simulations, such as Decelerator System Simulation (DSS), require accurate initial conditions (ICs) drawn from a separation model. Automatic Dynamic Analysis of Mechanical Systems (ADAMS), a Commercial off the Shelf (COTS) tool, was employed to provide insight into the multi-body six degree of freedom (DOF) interaction between parachute test hardware and external and internal forces. Components of the model include a composite extraction parachute, primary vehicle (PTV or PCDTV), platform cradle, a release mechanism, aircraft ramp, and a programmer parachute with attach points. Independent aerodynamic forces were applied to the mated test vehicle/platform cradle and the separated test vehicle and platform cradle. The aero coefficients were determined from real time lookup tables which were functions of both angle of attack ( ) and sideslip ( ). The atmospheric properties were also determined from a real time lookup table characteristic of the Yuma Proving Grounds (YPG) atmosphere relative to the planned test month. Representative geometries were constructed in ADAMS with measured mass properties generated for each independent vehicle. Derived smart separation parameters were included in ADAMS as sensors with defined pitch and pitch rate criteria used to refine inputs to analogous avionics systems for optimal separation conditions. Key design variables were dispersed in a Monte

ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1.

PubMed

Jiao, Xiaodong; Yu, Wenlong; Qian, Jianxin; Chen, Ying; Wei, Peilian; Fang, Wenzheng; Yu, Guanzhen

2018-05-18

A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, - 17, - 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro. ADAM-10, - 17, and - 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, - 17, and - 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens. The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.

The Return of the Freudian Couch®: Managing Affectivity through Technologies of Comfort

ERIC Educational Resources Information Center

Juelskjaer, Malou; Staunaes, Dorthe; Ratner, Helene

2013-01-01

This article explores how the affective "set-up" of Freud's legendary couch has been exported into modern education relations. The so-called psy-sciences from pedagogy, psychology, and psychiatry have informed self-management in school. Managing self-management has a material-affective dimension. Through affective encounters with the…

ADAM17 limits the expression of CSF1R on murine hematopoietic progenitors

PubMed Central

Becker, Amy M.; Walcheck, Bruce; Bhattacharya, Deepta

2014-01-01

All-lymphoid progenitors (ALPs) yield few myeloid cells in vivo, but readily generate such cells in vitro. The basis for this difference remains unknown. We hypothesized that ALPs limit responsiveness to in vivo concentrations of myeloid-promoting cytokines by reducing expression of the corresponding receptors, potentially through post-transcriptional mechanisms. Consistent with such a mechanism, ALPs express higher levels of Csf1r transcripts than their upstream precursors, yet show limited cell surface protein expression of CSF1R. ALPs and other hematopoietic progenitors deficient in ADAM17, a metalloprotease that can cleave CSF1R, display elevated cell surface CSF1R expression. Adam17−/− ALPs, however, fail to yield myeloid cells upon transplantation into irradiated recipients. Moreover, Adam17−/− ALPs yield fewer macrophages in vitro than control ALPs at high concentrations of M-CSF. Mice with hematopoietic-specific deletion of Adam17 have grossly normal numbers of myeloid and lymphoid progenitors and mature cells in vivo. These data demonstrate that ADAM17 limits CSF1R protein expression on hematopoietic progenitors, but that compensatory mechanisms prevent elevated CSF1R levels from altering lymphoid progenitor potential. PMID:25308957

DEVELOPMENT OF THE HUMAN LUNG MEASURED BY AEROSOL-DERIVED AIRWAY MORPHEMETRY (ADAM).

EPA Science Inventory

We measured, in vivo, the airspace calibers of the small airways and alveoli by ADAM in the lungs of children of ages 6 to 18 years and adults aged 18 to 80 years. ADAM utilizes the gravitational settling time of inhaled monodisperse particles to infer the vertical distance to th...

Association between ADAM metallopeptidase domain 33 gene polymorphism and risk of childhood asthma: a meta-analysis.

PubMed

Sun, F J; Zou, L Y; Tong, D M; Lu, X Y; Li, J; Deng, C B

2017-08-31

This study aimed to investigate the association between ADAM metallopeptidase domain 33 (ADAM33) gene polymorphisms and the risk of childhood asthma. The relevant studies about the relationship between ADAM33 gene polymorphisms and childhood asthma were searched from electronic databases and the deadline of retrieval was May 2016. The single nucleotide polymorphisms (SNPs) of ADAM33 (rs511898, rs2280092, rs3918396, rs528557, rs2853209, rs44707, rs2280091 and rs2280089) were analyzed based on several models including the allele, codominant, recessive and dominant models. The results showed that the ADAM33 rs2280091 polymorphism in all four genetic models was associated with an increased risk of childhood asthma. Positive associations were also found between the polymorphisms rs2280090, rs2787094, rs44707 and rs528557 and childhood asthma in some genetic models. This meta-analysis suggested that ADAM33 polymorphisms rs2280091, rs2280090, rs2787094, rs44707 and rs528557 were significantly associated with a high risk of childhood asthma.

Rhesus Monkey - Miss Sam - Fiberglass Couch - Little Joe (LJ)-1B Flight - Prep

NASA Image and Video Library

1959-12-04

B59-00828 (21 Jan. 1959) --- The test subject, a rhesus monkey named Miss Sam, is seen encased in a model of the Mercury fiberglass contour couch. She is being placed in a container for the Little Joe 1B suborbital test flight of the Mercury Capsule. Photo credit: NASA

77 FR 5291 - The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-02

... DEPARTMENT OF STATE [Public Notice: 7783] The Designation of Monir Chouka, also Known as Mounir Chouka, Also Known as Abu Adam, Also Known as Abu Adam From Germany, also Known as Abu Adam aus... Chouka, also known as Abu Adam from Germany, also known as Abu Adam aus Deutschland, committed, or poses...

ADAM10 as a therapeutic target for brain diseases: from developmental disorders to Alzheimer's disease.

PubMed

Marcello, Elena; Borroni, Barbara; Pelucchi, Silvia; Gardoni, Fabrizio; Di Luca, Monica

2017-11-01

In the central nervous system a disintegrin and metalloproteinase 10 (ADAM10) controls several functions such as neurodevelopment, synaptic plasticity and dendritic spine morphology thanks to its activity towards a high number of substrates, including the synaptic cell adhesion molecules as the Amyloid Precursor Protein, N-cadherin, Notch and Ephrins. In particular, ADAM10 plays a key role in the modulation of the molecular mechanisms responsible for dendritic spine formation, maturation and stabilization and in the regulation of the molecular organization of the glutamatergic synapse. Consequently, an alteration of ADAM10 activity is strictly correlated to the onset of different types of synaptopathies, ranging from neurodevelopmental disorders, i.e. autism spectrum disorders, to neurodegenerative diseases, i.e. Alzheimer's Disease. Areas covered: We describe the most recent discoveries in understanding of the role of ADAM10 activity at the glutamatergic excitatory synapse and its involvement in the onset of neurodevelopmental and neurodegenerative disorders. Expert opinion: A progress in the understanding of the molecular mechanisms driving ADAM10 activity at synapses and its alterations in brain disorders is the first step before designing a specific drug able to modulate ADAM10 activity.

The Adam language: Ada extended with support for multiway activities

NASA Technical Reports Server (NTRS)

Charlesworth, Arthur

1993-01-01

The Adam language is an extension of Ada that supports multiway activities, which are cooperative activities involving two or more processes. This support is provided by three new constructs: diva procedures, meet statements, and multiway accept statements. Diva procedures are recursive generic procedures having a particular restrictive syntax that facilitates translation for parallel computers. Meet statements and multiway accept statements provide two ways to express a multiway rendezvous, which is an n-way rendezvous generalizing Ada's 2-way rendezvous. While meet statements tend to have simpler rules than multiway accept statements, the latter approach is a more straightforward extension of Ada. The only nonnull statements permitted within meet statements and multiway accept statements are calls on instantiated diva procedures. A call on an instantiated diva procedure is also permitted outside a multiway rendezvous; thus sequential Adam programs using diva procedures can be written. Adam programs are translated into Ada programs appropriate for use on parallel computers.

The sixteenth presentation of the John Adam Fleming medal to Thomas M. Donahue

NASA Astrophysics Data System (ADS)

Nagy, Andrew F.; Donahue, Thomas M.

Citations are supposed to begin with a statement of the sort ‘It is an honor and a pleasure for me to introduce…’ however, in the case of Tom Donahue I do not think that I have to introduce him, since most everyone here this evening already knows him. His 30-plus-year career spans a very broad field of scientific endeavors as well as numerous institutions. We at Michigan are lucky to have had him with us since 1974. He has made his lasting mark in the field of aeronomy through his publications, which number over 140, his many graduate students, postdocs, and colleagues who have had the good fortune to have worked with him. Sydney Chapman must have been thinking of someone like Tom Donahue when he coined the word aeronomy. Tom was born in Oklahoma, receive his B.A. from Rockhurst College in Kansas City and his Ph.D. from The Johns Hopkins University in 1947. Perhaps it is appropriate that he is now receiving the Fleming Award here in Baltimore, where his professional career began. His deep lifelong involvement in solar system studies really began when he moved to The University of Pittsburgh in 1951, and he has been going full steam ever since.

A Conversation with Adam Heller.

PubMed

Heller, Adam; Cairns, Elton J

2015-01-01

Adam Heller, Ernest Cockrell Sr. Chair in Engineering Emeritus of the John J. McKetta Department of Chemical Engineering at The University of Texas at Austin, recalls his childhood in the Holocaust and his contributions to science and technology that earned him the US National Medal of Technology and Innovation in a conversation with Elton J. Cairns, Professor of Chemical and Biomolecular Engineering at the University of California, Berkeley. Dr. Heller, born in 1933, describes the enslavement of his father by Hungarians in 1942; the confiscation of his family's home, business, and all its belongings in 1944; and his incarceration in a brick factory with 18,000 Jews who were shipped by the Hungarians to be gassed by Germans in Auschwitz. Dr. Heller and his immediate family survived the Holocaust and arrived in Israel in 1945. He studied under Ernst David Bergmann at the Hebrew University, and then worked at Bell Laboratories and GTE Laboratories, where he headed Bell Lab's Electronic Materials Research Department. At GTE Laboratories, he built in 1966 the first neodymium liquid lasers and in 1973 with Jim Auborn conceived and engineered the lithium thionyl chloride battery, one of the first to be manufactured lithium batteries, which is still in use. After joining the faculty of engineering of The University of Texas at Austin, he cofounded with his son Ephraim Heller TheraSense, now a major part of Abbott Diabetes Care, which produced a microcoulometer that made the monitoring of glucose painless by accurately measuring the blood glucose concentration in 300 nL of blood. He also describes the electrical wiring of enzymes, the basis for Abbott's state-of-the-art continuous glucose monitoring system. He discusses his perspective of reducing the risk of catastrophic global warming in a wealth-accumulating, more-energy-consuming world and provides advice for students entering careers in science or engineering.

The Adams formulas for numerical integration of differential equations from 1st to 20th order

NASA Technical Reports Server (NTRS)

Kirkpatrick, J. C.

1976-01-01

The Adams Bashforth predictor coefficients and the Adams Moulton corrector coefficients for the integration of differential equations are presented for methods of 1st to 20th order. The order of the method as presented refers to the highest order difference formula used in Newton's backward difference interpolation formula, on which the Adams method is based. The Adams method is a polynomial approximation method derived from Newton's backward difference interpolation formula. The Newton formula is derived and expanded to 20th order. The Adams predictor and corrector formulas are derived and expressed in terms of differences of the derivatives, as well as in terms of the derivatives themselves. All coefficients are given to 18 significant digits. For the difference formula only, the ratio coefficients are given to 10th order.

Serotoninergic antidepressants positively affect platelet ADAM10 expression in patients with Alzheimer's disease.

PubMed

Bianco, Otávio Augusto Fernandes Marques; Manzine, Patrícia Regina; Nascimento, Carla Manuela Crispim; Vale, Francisco Assis Carvalho; Pavarini, Sofia Cristina Iost; Cominetti, Márcia Regina

2016-06-01

Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (βA) formation. Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using β-actin as endogenous control. Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication. More studies on the positive effects of serotonergic antidepressants on ADAM10 platelet expression should be performed in order to understand its biological mechanisms and to verify whether these effects are reflected in the central nervous system. This work represents an important advance for the study of AD biomarkers, as well as for more effective pharmacological treatment of patients with AD and associated depression.

ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A.

PubMed

Romi, Erez; Gokhman, Irena; Wong, Eitan; Antonovsky, Niv; Ludwig, Andreas; Sagi, Irit; Saftig, Paul; Tessier-Lavigne, Marc; Yaron, Avraham

2014-06-05

During embryonic development, axons can gain and lose sensitivity to guidance cues, and this flexibility is essential for the correct wiring of the nervous system. Yet, the underlying molecular mechanisms are largely unknown. Here we show that receptor cleavage by ADAM (A Disintegrin And Metalloprotease) metalloproteases promotes murine sensory axons loss of responsiveness to the chemorepellant Sema3A. Genetic ablation of ADAM10 and ADAM17 disrupts the developmental downregulation of Neuropilin-1 (Nrp1), the receptor for Sema3A, in sensory axons. Moreover, this is correlated with gain of repulsive response to Sema3A. Overexpression of Nrp1 in neurons reverses axonal desensitization to Sema3A, but this is hampered in a mutant Nrp1 with high susceptibility to cleavage. Lastly, we detect guidance errors of proprioceptive axons in ADAM knockouts that are consistent with enhanced response to Sema3A. Our results provide the first evidence for involvement of ADAMs in regulating developmental switch in responsiveness to axonal guidance cues.

Selective arylsulfonamide inhibitors of ADAM-17: hit optimization and activity in ovarian cancer cell models.

PubMed

Nuti, Elisa; Casalini, Francesca; Santamaria, Salvatore; Fabbi, Marina; Carbotti, Grazia; Ferrini, Silvano; Marinelli, Luciana; La Pietra, Valeria; Novellino, Ettore; Camodeca, Caterina; Orlandini, Elisabetta; Nencetti, Susanna; Rossello, Armando

2013-10-24

Activated leukocyte cell adhesion molecule (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a soluble form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addition, ADAM-17 plays a key role in EGFR signaling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previously identified inhibitor 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biological activity of the newly synthesized compounds was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compound 21, which showed an IC50 of 1.9 nM on ADAM-17 with greatly increased selectivity. This compound maintained good inhibitory properties on sALCAM shedding in several in vitro assays.

ADAM10 is essential for Notch2-dependent marginal zone B cell development and CD23 cleavage in vivo

PubMed Central

Gibb, David R.; El Shikh, Mohey; Kang, Dae-Joong; Rowe, Warren J.; El Sayed, Rania; Cichy, Joanna; Yagita, Hideo; Tew, John G.; Dempsey, Peter J.; Crawford, Howard C.

2010-01-01

The proteolytic activity of a disintegrin and metalloproteinase 10 (ADAM10) regulates cell-fate decisions in Drosophila and mouse embryos. However, in utero lethality of ADAM10−/− mice has prevented examination of ADAM10 cleavage events in lymphocytes. To investigate their role in B cell development, we generated B cell–specific ADAM10 knockout mice. Intriguingly, deletion of ADAM10 prevented development of the entire marginal zone B cell (MZB) lineage. Additionally, cleavage of the low affinity IgE receptor, CD23, was profoundly impaired, but subsequent experiments demonstrated that ADAM10 regulates CD23 cleavage and MZB development by independent mechanisms. Development of MZBs is dependent on Notch2 signaling, which requires proteolysis of the Notch2 receptor by a previously unidentified proteinase. Further experiments revealed that Notch2 signaling is severely impaired in ADAM10-null B cells. Thus, ADAM10 critically regulates MZB development by initiating Notch2 signaling. This study identifies ADAM10 as the in vivo CD23 sheddase and an important regulator of B cell development. Moreover, it has important implications for the treatment of numerous CD23- and Notch-mediated pathologies, ranging from allergy to cancer. PMID:20156974

Caractérisations structurale et morphologique des couches minces de CuInS2 et d'In-S "airless spray"

NASA Astrophysics Data System (ADS)

Kamoun, N.; Belgacem, S.; Amlouk, M.; Bennaceur, R.; Abdelmoula, K.; Belhadj Amara, A.

1994-03-01

We have prepared CuInS2 thin layers by airless spray "S.P.A." in order to use them as an absorber in a photovoltaic cell. The X-ray diffraction analysis has showed that these layers are well crystallized with a privileged (112) principal orientation for a ratio of the concentrations in the pulverized solution x=frac[Cu^I][In^{III]}=1.1. After heat treatment under vacuum the crystallization have been clearly improved. The structural analysis of the thin CuInS2 layers have revealed that a secondary phases of In2S3 and In6S7 are present. Thus we have realized by the same technique thin In-S layers whose structural and morphological properties have been studied. This analysis has showed that the In-S layers are well crystallized for a ratio y=frac[In^{3+]}[S^{2-]}=0.6 in the spray solution. The In-S layers are essentially formed by a β-In2S3 material. Although the In6S7 phase appears to the detriment of β-In2S3 phase for y= 0.75. Nous avons préparé des couches minces de CuInS2, par pulvérisation chimique réactive sans air "P.S.A.", en vue de leur utilisation en tant qu'absorbeur dans un dispositif photovoltaïque. L'analyse par diffraction X a montré que ces couches sont bien cristallisées et que l'orientation principale (112) est privilégiée pour un rapport de concentrations x=frac[Cu^I]{[In^{III}]}=1,1 dans la solution à pulvériser. Après le traitement thermique sous vide la cristallisation est nettement améliorée. L'analyse structurale des couches minces de CuInS2 a révélé que ces couches renferment des phases secondaires d'In2S3 et d'In6S7. Ainsi nous avons réalisé par la même technique "P.S.A.", des couches minces d'In-S dont nous avons étudié les propriétés structurales et morphologiques, Cette analyse a montré que les couches d'In-S sont bien cristallisées. Pour un rapport de concentrations en solution de pulvérisation y=frac[In^{3+]}[S^{2-]}=0,6 les couches d'In-S sont surtout formées du matériau β-In2S3. Alors que la phase In6S7

Dysregulation of the ADAM17/Notch signalling pathways in endometriosis: from oxidative stress to fibrosis.

PubMed

González-Foruria, Iñaki; Santulli, Pietro; Chouzenoux, Sandrine; Carmona, Francisco; Chapron, Charles; Batteux, Frédéric

2017-07-01

Is oxidative stress associated with the A disintegrin and metalloproteases (ADAM) metallopeptidase domain 17 (ADAM17)/Notch signalling pathway and fibrosis in the development of endometriosis? Oxidative stress is correlated with hyperactivation of the ADAM17/Notch signalling pathway and a consequent increase in fibrosis in patients with endometriosis. It is nowadays accepted that oxidative stress plays an important role in the onset and progression of endometriosis. Oxidative stress is able to induce the synthesis of some members of the 'ADAM' family, such as ADAM17. ADAM17/Notch signalling is dysregulated in other profibrotic and inflammatory diseases. This was a prospective laboratory study conducted in a tertiary-care university hospital between January 2011 and April 2013. We investigated non-pregnant, younger than 42-year-old patients (n = 202) during surgery for a benign gynaecological condition. After complete surgical exploration of the abdominopelvic cavity, 121 women with histologically proven endometriosis and 81 endometriosis-free control women were enrolled. Peritoneal fluid (PF) samples were obtained from all the study participants during surgery in order to detect advanced oxidation protein products (AOPPs) and metalloproteinase activity of ADAM17. Stromal cells from endometrial specimens (n = 8) were obtained from endometrium of control patients (Cs), and from eutopic (Es) and ectopic (Ps) endometrium of patients with deep infiltrating endometriosis (DIE) (n = 8). ADAM17, Notch and the fibrosis markers α-smooth muscle actin (α-SMA) and type-I collagen were assessed using immunoblotting in all the endometrial samples obtained. Additionally, fibrosis was assessed after using Notch cleavage inhibitors (DAPT and FLI-06). Notch and fibrosis were also evaluated after stimulation of stromal endometrial cells with ADAM17 purified protein, increasing concentrations of H2O2 and primary cell culture supernatants. Patients with DIE presented higher PF AOPP

SU-E-T-777: Use of Tennis Racket and Air Gap Between the Body and Carbon Fiber Couch for Skin Sparing in Radiation Therapy of Prone Breast

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

Lief, E

2015-06-15

Purpose: To reduce the skin dose from the carbon fiber couch scatter in radiation treatment of breast cancer in the prone position. If this issue is not addressed, the prone breast touching the solid carbon fiber couch can absorb significant dose to the skin and cause the skin reaction. Methods: 1. Use of “tennis racket” instead of the solid couch. To check this hypothesis, we measured the dose at the depth of 5 mm in solid water phantom placed on the couch, using a Farmer chamber. A plan for a patient with 6MV beams, gantry angles of 113 and 286more » degrees Varian scale was used. It was found that treatment with “tennis racket” instead of the solid carbon fiber couch reduces the surface dose by 5–7%, depending on the beam direction. 2. Use of the air gap between the couch and the body was analyzed using radiochromic film on the surface of the solid water phantom 10 cm thick. Initially the phantom was placed on the couch with the film sandwiched in between. Two fields at the angles of 135 and 315 degrees were used. The measurements were repeated for the air gap of 2 and 5 cm and 6 and 15 MV beams. Results: It was found that a 2-cm gap decreased the surface dose by 3% for a 6 MV beam and by 5.5% for a 15 MV beam. A 5-cm gap reduced the dose by 9% for 6 MV and 13.5% for 15 MV. Conclusion: Use of both methods (combined if possible) can significantly reduce the surface dose in radiation therapy of the prone breast and possible skin reaction. We plan to explore dependence of the dose reduction upon the angle of incidence.« less

Dr Adam Zamenhof (1888-1940) and his insight into ophthalmology.

PubMed

Wincewicz, Andrzej; Sulkowska, Mariola; Lieberman, E James; Bakunowicz-Lazarczyk, Alina; Sulkowski, Stanislaw

2009-02-01

Adam Zamenhof was greatly influenced by his father, Ludwik Zamenhof, who designed the international language Esperanto. Like his father, he became an ophthalmologist and joined the Esperanto movement. He published in the field of ophthalmology and was soon chosen as head of an ophthalmology department. He subsequently became Chief of the Orthodox Jewish Hospital at Czystem in Warsaw. He was active in the leadership of the Bialystok-Warsaw Chamber of Medical Doctors. He perished in the Nazi Holocaust (Shoah) but all Zamenhof's ideals that Adam served as a doctor and social activist remain still alive.

ADAM-12 as a Diagnostic Marker for the Proliferation, Migration and Invasion in Patients with Small Cell Lung Cancer

PubMed Central

Shao, Shuhong; Li, Zunling; Gao, Wei; Yu, Guohua; Liu, Dexiang; Pan, Fang

2014-01-01

Small cell lung cancer (SCLC) is highly aggressive and is characterized by malignant metastasis. Approximately 90% of patients die due to extensive metastasis. The extracellular matrix (ECM) is a natural barrier that can prevent cellular invasion and metastasis. Therefore, degradation of the ECM must take place in order for extensive metastasis to occur. A disintegrin and metalloprotease (ADAM) is a multi-domain protease that plays an important role in tumorigenesis, as well as tumor development, invasion and metastasis. However, there have been few reports on the expression and role of ADAMs in SCLC. In the current study, the expression and role of ADAMs in SCLC proliferation, invasion and metastasis was investigated. A total of 150 SCLC tissue samples were examined by immunohistochemistry for ADAMs expression. ADAM-12 was found to be abundantly expressed in 72.67% samples and other ADAMs were found to be expressed in 10% to 40% of samples. ADAM-12 levels in serum and urine, from 70 SCLC patients and 40 normal controls, were also measured using ELISA. ADAM-12 expression was significantly higher in SCLC patients than in healthy controls and in patients with extensive disease compared to those with more limited disease. Silencing the expression of ADAM-12 in H1688 cells through the use of specific siRNA significantly reduced cellular proliferation, invasion and metastasis. Supplementing the expression of ADAM-12-L or -S in H345 cells, significantly enhanced cellular proliferation, invasion and metastasis. Animal models with metastatic SCLC also exhibited increased expression of ADAM-12 along with enhanced invasion and metastasis. In brief, ADAM-12 is an independent prognostic factor and diagnostic marker, and is involved in the proliferation, invasion and metastasis of SCLC. PMID:24465799

ADAM10-mediated ephrin-B2 shedding promotes myofibroblast activation and organ fibrosis

PubMed Central

Lagares, David; Ghassemi-Kakroodi, Parisa; Tremblay, Caroline; Santos, Alba; Probst, Clemens K.; Franklin, Alicia; Santos, Daniela M.; Grasberger, Paula; Ahluwalia, Neil; Montesi, Sydney B.; Shea, Barry S.; Black, Katharine E.; Knipe, Rachel; Blati, Meryem; Baron, Murray; Wu, Brian; Fahmi, Hassan; Gandhi, Rajiv; Pardo, Annie; Selman, Moisés; Wu, Jiangping; Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Tager, Andrew M.; Kapoor, Mohit

2017-01-01

Maladaptive wound healing responses to chronic tissue injury result in organ fibrosis. Fibrosis, which entails excessive extracellular matrix (ECM) deposition and tissue remodelling by activated myofibroblasts, leads to loss of proper tissue architecture and organ function; however the molecular mediators of myofibroblast activation remain to be fully identified. Here we identify soluble ephrin-B2 as a novel pro-fibrotic mediator in lung and skin fibrosis. We provide molecular, functional and translational evidence that the ectodomain of membrane-bound ephrin-B2 is shed from fibroblasts into the alveolar airspace after lung injury. Shedding of soluble ephrin-B2 (sEphrin-B2) promotes fibroblast chemotaxis and activation via EphB3/EphB4 receptor signaling. We found that mice lacking ephrin-B2 in fibroblasts are protected from skin and lung fibrosis and that a distintegrin and metalloproteinase 10 (ADAM10) is the major ephrin-B2 sheddase in fibroblasts. ADAM10 is induced by transforming growth factor-β1 (TGF-β1), and ADAM10-mediated sEphrin-B2 generation is required for TGF-β1–induced myofibroblast activation. Pharmacological inhibition of ADAM10 reduces sEphrin-B2 levels in bronchoalveolar lavage and prevents lung fibrosis in mice. Consistent with the mouse data, ADAM10/sEphrin-B2 signaling is upregulated in fibroblasts from human subjects with idiopathic pulmonary fibrosis. These results uncover a new molecular mechanism of tissue fibrogenesis and identify sEphrin-B2, its receptors Eph3/Eph4, and ADAM10 as potential therapeutic targets in the treatment of fibrotic diseases. PMID:29058717

ADAM12 induction by Twist1 promotes tumor invasion and metastasis via regulation of invadopodia and focal adhesions

PubMed Central

Eckert, Mark A.; Santiago-Medina, Miguel; Lwin, Thinzar M.; Kim, Jihoon; Courtneidge, Sara A.

2017-01-01

ABSTRACT The Twist1 transcription factor promotes tumor invasion and metastasis by inducing epithelial–mesenchymal transition (EMT) and invadopodia-mediated extracellular matrix (ECM) degradation. The critical transcription targets of Twist1 for mediating these events remain to be uncovered. Here, we report that Twist1 strongly induces expression of a disintegrin and metalloproteinase 12 (ADAM12). We observed that the expression levels of Twist1 mRNA and ADAM12 mRNA are tightly correlated in human breast tumors. Knocking down ADAM12 blocked cell invasion in a 3D mammary organoid culture. Suppression of ADAM12 also inhibited Twist1-induced tumor invasion and metastasis in human breast tumor xenografts, without affecting primary tumor formation. Mechanistically, knockdown of ADAM12 in breast cancer cells significantly reduced invadopodia formation and matrix degradation, and simultaneously increased overall cell adhesion to the ECM. Live-imaging analysis showed that knockdown of ADAM12 significantly inhibited focal adhesion turnover. Mechanistically, both the disintegrin and metalloproteinase domains of ADAM12 are required for its function at invadopodia, whereas the metalloproteinase domain is dispensable for its function at focal adhesions. Taken together, these data suggest that ADAM12 plays a crucial role in tumor invasion and metastasis by regulating both invadopodia and focal adhesions. PMID:28468988

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth

PubMed Central

Saha, Nayanendu; Eissman, Moritz F.; Xu, Kai; Llerena, Carmen; Kusebauch, Ulrike; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M.; Nikolov, Dimitar B.; Lackmann, Martin

2016-01-01

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. PMID:27503072

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth.

PubMed

Atapattu, Lakmali; Saha, Nayanendu; Chheang, Chanly; Eissman, Moritz F; Xu, Kai; Vail, Mary E; Hii, Linda; Llerena, Carmen; Liu, Zhanqi; Horvay, Katja; Abud, Helen E; Kusebauch, Ulrike; Moritz, Robert L; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M; Nikolov, Dimitar B; Lackmann, Martin; Janes, Peter W

2016-08-22

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. © 2016 Atapattu et al.

Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity.

PubMed

Kim, Minji; Suh, Jaehong; Romano, Donna; Truong, Mimy H; Mullin, Kristina; Hooli, Basavaraj; Norton, David; Tesco, Giuseppina; Elliott, Kathy; Wagner, Steven L; Moir, Robert D; Becker, K David; Tanzi, Rudolph E

2009-10-15

ADAM10, a member of a disintegrin and metalloprotease family, is an alpha-secretase capable of anti-amyloidogenic proteolysis of the amyloid precursor protein. Here, we present evidence for genetic association of ADAM10 with Alzheimer's disease (AD) as well as two rare potentially disease-associated non-synonymous mutations, Q170H and R181G, in the ADAM10 prodomain. These mutations were found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset AD families. Each mutation was also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuated alpha-secretase activity of ADAM10 (>70% decrease), and elevated Abeta levels (1.5-3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD.

The couch and the chador.

PubMed

Movahedi, Siamak; Homayounpour, Gohar

2012-12-01

The authors present a clinical discussion of the psychic functions of the chador, a veil-like outer garment worn in public by some Iranian women. Drawing on Anzieu's theoretical concept of the skin ego, the authors suggest that the chador does not just cover the body; it may also envelop the psyche and function as a second skin for the ego. The maternal function of a holding environment is symbolically displaced on any clothing that 'hides,''covers,''veils,' or 'dresses' the body. The skin's containing functions are extended through sensory and metonymic mediations to clothes, thus providing an imaginary maternal sack for the person. The clinical vignettes presented here suggest that for some Iranian women the chador may work, on one hand, as a second skin ego and a shield against a perceived intrusive world. On the other hand, it may work as a punitive maternal superego, a 'holding cell' in a jail that paralyses the separation/individuation process. Operating in the service of the patient's resistance and defense, the chador may also function as a psychic refuge and a place to hide on the couch. Copyright © 2012 Institute of Psychoanalysis.

MicroRNA-126 inhibits proliferation and metastasis in prostate cancer via regulation of ADAM9

PubMed Central

Hua, Yibo; Liang, Chao; Miao, Chenkui; Wang, Shangqian; Su, Shifeng; Shao, Pengfei; Liu, Bianjiang; Bao, Meiling; Zhu, Jundong; Xu, Aiming; Zhang, Jianzhong; Li, Jie; Wang, Zengjun

2018-01-01

The aberrant expression of microRNAs (miRs) has been identified to serve a crucial role in tumor progression. The present study aimed to evaluate the role of miR-126 in human prostate cancer (PCa). Firstly, miR-126 expression in prostate cancer tissues and cell lines was analyzed. A luciferase reporter assay and a rescue assay were performed, which identified ADAM metalloproteinase domain 9 (ADAM9) as the target gene of miR-126. Subsequently, Kaplan-Meier and log-rank analyses were used to investigate the association between ADAM9 expression and PCa prognosis. The results revealed that miR-126 expression was significantly downregulated in PCa tissues and cell lines. miR-126 overexpression was demonstrated to reduce PCa cell proliferation and metastasis, and to reverse the epithelial-mesenchymal transition process in vitro. In addition, as the target gene of miR-126, the upregulation of ADAM9 reestablished cell functions, including cell proliferation, migration and invasion. Patients with high ADAM9 expression levels exhibited a shorter biochemical recurrence-free survival time. In summary, miR-126 serves a role in the proliferation and metastasis of PCa cells, indicating that miR-126 and ADAM9 may represent potential biomarkers in the progression of advanced PCa, in addition to therapeutic targets. PMID:29805636

Trajectory modulated prone breast irradiation: a LINAC-based technique combining intensity modulated delivery and motion of the couch.

PubMed

Fahimian, Benjamin; Yu, Victoria; Horst, Kathleen; Xing, Lei; Hristov, Dimitre

2013-12-01

External beam radiation therapy (EBRT) provides a non-invasive treatment alternative for accelerated partial breast irradiation (APBI), however, limitations in achievable dose conformity of current EBRT techniques have been correlated to reported toxicity. To enhance the conformity of EBRT APBI, a technique for conventional LINACs is developed, which through combined motion of the couch, intensity modulated delivery, and a prone breast setup, enables wide-angular coronal arc irradiation of the ipsilateral breast without irradiating through the thorax and contralateral breast. A couch trajectory optimization technique was developed to determine the trajectories that concurrently avoid collision with the LINAC and maintain the target within the MLC apertures. Inverse treatment planning was performed along the derived trajectory. The technique was experimentally implemented by programming the Varian TrueBeam™ STx in Developer Mode. The dosimetric accuracy of the delivery was evaluated by ion chamber and film measurements in phantom. The resulting optimized trajectory was shown to be necessarily non-isocentric, and contain both translation and rotations of the couch. Film measurements resulted in 93% of the points in the measured two-dimensional dose maps passing the 3%/3mm Gamma criterion. Preliminary treatment plan comparison to 5-field 3D-conformal, IMRT, and VMAT demonstrated enhancement in conformity, and reduction of the normal tissue V50% and V100% parameters that have been correlated with EBRT toxicity. The feasibility of wide-angular intensity modulated partial breast irradiation using motion of the couch has been demonstrated experimentally on a standard LINAC for the first time. For patients eligible for a prone setup, the technique may enable improvement of dose conformity and associated dose-volume parameters correlated with toxicity. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Characterization of Oxygen-Induced Retinopathy in Mice Carrying an Inactivating Point Mutation in the Catalytic Site of ADAM15

PubMed Central

Maretzky, Thorsten; Blobel, Carl P.; Guaiquil, Victor

2014-01-01

Purpose. Retinal neovascularization is found in diseases such as macular degeneration, diabetic retinopathy, or retinopathy of prematurity and is usually caused by alterations in oxygen supply. We have previously described that mice lacking the membrane-anchored metalloproteinase ADAM15 (a Disintegrin and Metalloprotease 15) have decreased pathological neovascularization of the retina in the oxygen-induced retinopathy (OIR) model. The main purpose of the present study was to determine the contribution of the catalytic activity of ADAM15 to OIR. Methods. To address this question, we generated knock-in mice carrying an inactivating Glutamate to Alanine (E>A) point mutation in the catalytic site of ADAM15 (Adam15E>A mice) and subjected these animals to the OIR model and a heterotopic tumor model. Moreover, we used cell-based assays to determine whether ADAM15 can process cell surface receptors involved in angiogenesis. Results. We found that pathological neovascularization in the OIR model in Adam15E>A mice was comparable to that observed in wild type mice, but tumor implantation by heterotopically injected melanoma cells was reduced. In cell-based assays, overexpressed ADAM15 could process the FGFR2iiib, but was unable to process several receptors with roles in angiogenesis. Conclusions. Collectively, these results suggest that the catalytic activity of ADAM15 is not crucial for its function in promoting pathological neovascularization in the mouse OIR model, most likely because of the very limited substrate repertoire of ADAM15. Instead, other noncatalytic functions of ADAM15 must be important for its role in the OIR model. PMID:25249606

Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate α-secretase activity

PubMed Central

Kim, Minji; Suh, Jaehong; Romano, Donna; Truong, Mimy H.; Mullin, Kristina; Hooli, Basavaraj; Norton, David; Tesco, Giuseppina; Elliott, Kathy; Wagner, Steven L.; Moir, Robert D.; Becker, K. David; Tanzi, Rudolph E.

2009-01-01

ADAM10, a member of a disintegrin and metalloprotease family, is an α-secretase capable of anti-amyloidogenic proteolysis of the amyloid precursor protein. Here, we present evidence for genetic association of ADAM10 with Alzheimer's disease (AD) as well as two rare potentially disease-associated non-synonymous mutations, Q170H and R181G, in the ADAM10 prodomain. These mutations were found in 11 of 16 affected individuals (average onset age 69.5 years) from seven late-onset AD families. Each mutation was also found in one unaffected subject implying incomplete penetrance. Functionally, both mutations significantly attenuated α-secretase activity of ADAM10 (>70% decrease), and elevated Aβ levels (1.5–3.5-fold) in cell-based studies. In summary, we provide the first evidence of ADAM10 as a candidate AD susceptibility gene, and report two potentially pathogenic mutations with incomplete penetrance for late-onset familial AD. PMID:19608551

ADAM13 Induces Cranial Neural Crest by Cleaving Class B Ephrins and Regulating Wnt Signaling

PubMed Central

Wei, Shuo; Xu, Guofeng; Bridges, Lance C.; Williams, Phoebe; White, Judith M.; DeSimone, Douglas W.

2010-01-01

SUMMARY The cranial neural crest (CNC) are multipotent embryonic cells that contribute to craniofacial structures and other cells and tissues of the vertebrate head. During embryogenesis, CNC is induced at the neural plate boundary through the interplay of several major signaling pathways. Here we report that the metalloproteinase activity of ADAM13 is required for early induction of CNC in Xenopus. In both cultured cells and X. tropicalis embryos, membrane-bound Ephrins (Efns) B1 and B2 were identified as substrates for ADAM13. ADAM13 upregulates canonical Wnt signaling and early expression of the transcription factor snail2, whereas EfnB1 inhibits the canonical Wnt pathway and snail2 expression. We propose that by cleaving class B Efns, ADAM13 promotes canonical Wnt signaling and early CNC induction. PMID:20708595

SU-F-T-621: Impact of Vacuum and Treatment Couch On Surface Dose in Stereotactic Body Radiation Therapy With and Without a Flattening Filter

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

Lan, HT; Lu, SH; Kuo, SH

2016-06-15

Purpose: When treating lung cancer patients with stereotactic body radiation therapy (SBRT), better immobilization is needed for accurate delivery of high-dose radiation. However, using a treatment couch (TrueBeamTM) and vacuum bag (BlueBAGTM) may increase the surface dose and skin toxicity. This study investigated the influence of couch and vacuum bag on the surface dose. Methods: The relative surface dose (D{sub 0}/DMAX) was measured in an ion-chamber (Markus-type PTW, 0.05cm{sup 3}) with a solid water phantom and SSD to 100 cm. A comprehensive comparison of different parameter settings, including the different energies (6MV-FFF, 10MV-FF, and 10MV-FFF), field sizes (3 X 3more » cm{sup 2}, 5 × 5 cm{sup 2}, 8 × x cm{sup 2} , 10 × 10 cm{sup 2}, and 15 × 15 cm{sup 2}), thickness of the vacuum bag (5mm, 15mm, 30mm, 39mm and 55mm), and couch (with and without), was performed. Results: The FFF increases the surface dose as compared to FF mode. In a similar setting with field of 10 × 10 cm{sup 2}, FFF mode increases the surface dose from 26.0% to 32.8% for 6 MV, and 17.4% to 21.5% for 10 MV. When the beam passes through the couch, the surface dose increases to 3.6, 4.6, 2.9, and 3.7 times for 6 MV-FF, 10 MV-FF, 6 MV-FFF, and 10 MV-FFF, respectively. At the same energy, the surface dose increases to 3.93, 4.11, 4.23, 4.16 and 4.24 times at 5 mm, 15 mm, 30 mm, 39 mm and 55 mm thickness of the vacuum, respectively. Conclusion: Using a couch and vacuum significantly increases the surface dose. For SBRT with a superficial target close to the couch and immobilization vacuum, reduction of vacuum thickness and careful attention to skin dose in planning would be helpful in avoiding severe skin toxicity.« less

SU-E-T-84: A Survey On Radiotherapy Table Tolerances and Couch Overrides of Over 350 Institutions

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

Chinsky, B; Patel, R; Panfil, J

Purpose: Table overrides are relatively common in radiotherapy, yet are a potential safety concern. The goal of this study was to survey current departmental policies on treatment couch overrides and table tolerance values used clinically. Methods: A 25 question electronic survey on couch overrides and tolerances was sent to full members of the AAPM. In the first part of the survey, participants were asked: if table overrides were allowed at their institution, who was allowed to perform these overrides, and if imaging was required with overrides. In the second part of the survey, individuals were asked to provide table tolerancemore » data for the following sites: brain/head & neck, lung, breast, abdomen/pelvis and prostate. Each site was further divided into IMRT/VMAT and 3D conformal techniques. Free-text spaces were provided, allowing respondents to enter any table tolerance data they were unable to specify under the treatment sites listed. Results: A total of 361 individuals responded, of which approximately half participated in the couch tolerances portion of the survey. Overall, 86% of respondents’ institutions allow couch tolerance overrides at treatment. Therapists were the most common staff members permitted to perform overrides, followed by physicists, dosimetrists, and physicians, respectively. Of the institutions allowing overrides, 34% reported overriding daily. More than half of the centers require documentation of the override and/or a setup image (acquired after override) to radiographically verify the treatment site. With respect to table tolerances, groups resulting from the free-text responses were at the two extremes; SRS/SBRT were the tightest, while clinical setup/mets/extremities were the most generous. There was no qualitative difference between IMRT/VMAT and 3D conformal table tolerances. Conclusion: This work is intended to stimulate a discussion within the radiotherapy community. This discussion, supplemented by the survey results

Adam Smith, Religion, and Tuition Tax Credits.

ERIC Educational Resources Information Center

Alexander, Kern

1983-01-01

Examines tuition tax credit programs in framework of Adam Smith's ideas on the economic impact of established churches. Finds that tuition tax credits would amount to state expenditures to relieve the financial burden of parochial school parents and would allow churches to invest commercially to maintain their charitable functions. (JW)

Over-expression of two different forms of the alpha-secretase ADAM10 affects learning and memory in mice.

PubMed

Schmitt, Ulrich; Hiemke, Christoph; Fahrenholz, Falk; Schroeder, Anja

2006-12-15

Members of the ADAM family (adisintegrin and metalloprotease) are the main candidates for physiologically relevant alpha-secretases. The alpha-secretase cleaves in the non-amyloidogenic pathway the amyloid precursor protein within the region of the Abeta peptides preventing their aggregation in the brain. The increase of alpha-secretase activity in the brain provides a plausible strategy to prevent Abeta formation. Concerning this possibility two transgenic mouse lines (FVB/N) have been created: mice over-expressing the bovine form of the alpha-secretase (ADAM10) and mice over-expressing an inactive form of the alpha-secretase (ADAM10-E348A-HA; ADAM10-dn). For behavioral examination a F1 generation of transgenic mice (C57Bl/6 x FVB/N (tg)) was generated and compared to wild type F1 generation (C57Bl/6 x FVB/N). Behavior was characterized in the following tasks: standard open field, enriched open field, elevated plus-maze, and the Morris water maze hidden platform task. Concerning basal activity, exploration, and anxiety, transgenic mice behaved similar to controls. With respect to learning and memory both transgenic lines showed a significant deficit compared to controls. ADAM10 mice however, showed thigmotaxis with passive floating behavior in the Morris water maze indicating differences in motivation, whereas, ADAM10-dn mice displayed an inconspicuous but limited goal-directed search pattern. Thus variation of the enzymatic activity of alpha-secretase ADAM10 alters learning and memory differentially. Nevertheless, it could be concluded that both, ADAM10 and ADAM10-dn mice are suitable control mice for the assessment of alpha-secretase-related effects in animal models of Alzheimer's disease.

Upregulation of ADAM12 contributes to accelerated cell proliferation and cell adhesion-mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphoma.

PubMed

Yin, Haibing; Zhong, Fei; Ouyang, Yu; Wang, Qiru; Ding, Linlin; He, Song

2017-10-01

ADAM12 is a member of a disintegrin and metalloproteinase family and has been reported to participate in the development of variety of tumors. However, the role of ADAM12 in Non-Hodgkin Lymphoma (NHL) has not been investigated. The present study was undertaken to determine the expression and biologic function of ADAM12 in human NHL. First, we constructed a model of cell adhesion in NHL, the mRNA, and protein level of ADAM12 in suspension and the adhesion model was analyzed by RT-PCR and western blot. Then, flow cytometry assay and western blot were used to investigate the mechanism of ADAM12 in the proliferation of NHL cells. In vitro, after using siRNA interfering ADAM12 expression, we performed adhesion assay and cell viability assay to determine the effect of ADAM12 on adhesive rate and drug sensitivity. ADAM12 was lowly expressed in suspended cells and highly expressed in adherent NHL cells. In addition, ADAM12 was positively correlated with the proliferation and apoptosis of NHL cells by regulating the expression of p-AKT and p-GSK-3β. Furthermore, ADAM12 promoted cell adhesion-mediated drug resistance (CAM-DR) in DLBCL via AKT signaling pathway. Our data support a role for ADAM12 in NHL cell proliferation, adhesion, and drug resistance, and it may pave the way for a novel therapeutic approach for CAM-DR in NHL.

Adam Smith and the Rhetoric of Style.

ERIC Educational Resources Information Center

Moran, Michael G.

Historians of rhetoric have generally accepted the view that Adam Smith rejected the principles of classical rhetoric. However, while there can be no doubt that Smith greatly truncated the five classical arts of rhetoric (invention, arrangement, style, memory, and delivery) by reducing his concerns largely to style and arrangement, he did not…

Automatic Dynamic Aircraft Modeler (ADAM) for the Computer Program NASTRAN

NASA Technical Reports Server (NTRS)

Griffis, H.

1985-01-01

Large general purpose finite element programs require users to develop large quantities of input data. General purpose pre-processors are used to decrease the effort required to develop structural models. Further reduction of effort can be achieved by specific application pre-processors. Automatic Dynamic Aircraft Modeler (ADAM) is one such application specific pre-processor. General purpose pre-processors use points, lines and surfaces to describe geometric shapes. Specifying that ADAM is used only for aircraft structures allows generic structural sections, wing boxes and bodies, to be pre-defined. Hence with only gross dimensions, thicknesses, material properties and pre-defined boundary conditions a complete model of an aircraft can be created.

ADAM17 targets MMP-2 and MMP-9 via EGFR-MEK-ERK pathway activation to promote prostate cancer cell invasion.

PubMed

Xiao, Li-Jie; Lin, Ping; Lin, Feng; Liu, Xin; Qin, Wei; Zou, Hai-Feng; Guo, Liang; Liu, Wei; Wang, Shu-Juan; Yu, Xiao-Guang

2012-05-01

ADAM17, also known as tumor necrosis factor-α converting enzyme (TACE), is involved in proteolytic ectodomain shedding of cell surface molecules and cytokines. Although aberrant expression of ADAM17 has been shown in various malignancies, the function of ADAM17 in prostate cancer has not been clarified. In the present study, we sought to elucidate whether ADAM17 contributes to prostate cancer cell invasion, as well as the mechanism involved in the process. The expression pattern of ADAM17 was investigated in human prostate cancer cells. The results showed that ADAM17 expression levels are correlated with the invasive ability of androgen-independent prostate cancer cell lines. Further, ADAM17 was overexpressed in cells showing high invasion characteristics, activation of the EGFR-MEK-ERK pathway, up-regulation of MMP-2, MMP-9, and an increased TGF-α release into the supernatant. However, AG1478, PD98059 and antibody against TGF-α deactivating the EGFR-MEK-ERK signaling pathway, abolished up-regulation of MMP-2, MMP-9 and prevented cell invasion. In addition, cells with knockdown of ADAM17 by siRNA exhibited low invasive ability, deactivated EGFR-MEK-ERK signaling pathway, reduced TGF-α released and down-regulation of MMP-2, MMP-9. However, these effects could be reversed by simultaneous addition of TGF-α. These data demonstrated that ADAM17 contributes to androgen-independent prostate cancer cell invasion by shedding of EGFR ligand TGF-α, which subsequently activates the EGFR-MEK-ERK signaling pathway, leading finally to overexpression of MMP-2 and MMP-9. This study suggests that the ADAM17 expression level may be a new predictive biomarker of invasion and metastasis of prostate cancer, and ADAM17 could provide a target for treating metastatic PCa.

MiR-153 inhibits migration and invasion of human non-small-cell lung cancer by targeting ADAM19

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

Shan, Nianxi; Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan 410008; Shen, Liangfang

Highlights: • Decreased miR-153 and up-regulated ADAM19 are correlated with NSCLC pathology. • MiR-153 inhibits the proliferation and migration and invasion of NSCLC cells in vitro. • ADAM19 is a direct target of miR-153. • ADAM19 is involved in miR-153-suppressed migration and invasion of NSCLC cells. - Abstract: MiR-153 was reported to be dysregulated in some human cancers. However, the function and mechanism of miR-153 in lung cancer cells remains unknown. In this study, we investigated the role of miR-153 in human non-small-cell lung cancer (NSCLC). Using qRT-PCR, we demonstrated that miR-153 was significantly decreased in clinical NSCLC tissues andmore » cell lines, and downregulation of miR-153 was significantly correlated with lymph node status. We further found that ectopic expression of miR-153 significantly inhibited the proliferation and migration and invasion of NSCLC cells in vitro, suggesting that miR-153 may be a novel tumor suppressor in NSCLC. Further integrated analysis revealed that ADAM19 is as a direct and functional target of miR-153. Luciferase reporter assay demonstrated that miR-153 directly targeted 3′UTR of ADAM19, and correlation analysis revealed an inverse correlation between miR-153 and ADAM19 mRNA levels in clinical NSCLC tissues. Knockdown of ADAM19 inhibited migration and invasion of NSCLC cells which was similar with effects of overexpression of miR-153, while overexpression of ADAM19 attenuated the function of miR-153 in NSCLC cells. Taken together, our results highlight the significance of miR-153 and ADAM19 in the development and progression of NSCLC.« less

Soluble Axl Is Generated by ADAM10-Dependent Cleavage and Associates with Gas6 in Mouse Serum†

PubMed Central

Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Duitman, Erwin; Brandt, Katja; Ludwig, Andreas; Hartmann, Dieter; Lemke, Greg; Saftig, Paul; Bulfone-Paus, Silvia

2005-01-01

Axl receptor tyrosine kinase exists as a transmembrane protein and as a soluble molecule. We show that constitutive and phorbol 12-myristate 13-acetate-induced generation of soluble Axl (sAxl) involves the activity of disintegrin-like metalloproteinase 10 (ADAM10). Spontaneous and inducible Axl cleavage was inhibited by the broad-spectrum metalloproteinase inhibitor GM6001 and by hydroxamate GW280264X, which is capable of blocking ADAM10 and ADAM17. Furthermore, murine fibroblasts deficient in ADAM10 expression exhibited a significant reduction in constitutive and inducible Axl shedding, whereas reconstitution of ADAM10 restored sAxl production, suggesting that ADAM10-mediated proteolysis constitutes a major mechanism for sAxl generation in mice. Partially overlapping 14-amino-acid stretch deletions in the membrane-proximal region of Axl dramatically affected sAxl generation, indicating that these regions are involved in regulating the access of the protease to the cleavage site. Importantly, relatively high circulating levels of sAxl are present in mouse sera in a heterocomplex with Axl ligand Gas6. Conversely, two other family members, Tyro3 and Mer, were not detected in mouse sera and conditioned medium. sAxl is constitutively released by murine primary cells such as dendritic and transformed cell lines. Upon immobilization, sAxl promoted cell migration and induced the phosphorylation of Axl and phosphatidylinositol 3-kinase. Thus, ADAM10-mediated generation of sAxl might play an important role in diverse biological processes. PMID:16227584

Inhibition of ADAM-17 more effectively down-regulates the Notch pathway than that of γ-secretase in renal carcinoma.

PubMed

Guo, Zhen; Jin, Xunbo; Jia, Haiyan

2013-05-09

Our study is to research the effect of inhibited ADAM-17 expression through the Notch pathway in renal carcinoma. Immunohistochemistry and western blot were used to examine the expression of ADAM-17 protein in renal cancer tissues. Proliferation and cell invasion of 786-o cells, as well as OS-RC-2 cells, after treatment with two different inhibitors of the Notch pathway, were examined by CCK-8 assay and Transwell assay, respectively. 786-o cell apoptosis was measured using the FCM test. ADAM-17 was highly expressed in RCC tissues. Compared with blocking γ-secretase, a known mechanism of impairing Notch, blockade of ADAM-17 more effectively down-regulated the expressions of Notch1 and HES-1 proteins. Similarly, we found that the ADAM-17 inhibitor, Marimastat, could more efficiently reduce renal cell proliferation and invasive capacity in comparison with the γ-secretase inhibitor DAPT when used at the same dose. Similar results were obtained when apoptosis of 786-o was measured. Compared with γ-secretase, inhibition of ADAM-17 expression more effectively inhibits Notch pathway-mediated renal cancer cell proliferation and invasion. ADAM-17 may be a new target for future treatment of renal carcinoma.

Lysophosphatidic acid-induced ADAM12 expression mediates human adipose tissue-derived mesenchymal stem cell-stimulated tumor growth.

PubMed

Do, Eun Kyoung; Kim, Young Mi; Heo, Soon Chul; Kwon, Yang Woo; Shin, Sang Hun; Suh, Dong-Soo; Kim, Ki-Hyung; Yoon, Man-Soo; Kim, Jae Ho

2012-11-01

Lysophosphatidic acid (LPA) is involved in mesenchymal stem cell-stimulated tumor growth in vivo. However, the molecular mechanism by which mesenchymal stem cells promote tumorigenesis remains elusive. In the present study, we demonstrate that conditioned medium from A549 human lung adenocarcinoma cells (A549 CM) induced the expression of ADAM12, a disintegrin and metalloproteases family member, in human adipose tissue-derived mesenchymal stem cells (hASCs). A549 CM-stimulated ADAM12 expression was abrogated by pretreatment of hASCs with the LPA receptor 1 inhibitor Ki16425 or by small interfering RNA-mediated silencing of LPA receptor 1, suggesting a key role for the LPA-LPA receptor 1 signaling axis in A549 CM-stimulated ADAM12 expression. Silencing of ADAM12 expression using small interfering RNA or short hairpin RNA abrogated LPA-induced expression of both α-smooth muscle actin, a marker of carcinoma-associated fibroblasts, and ADAM12 in hASCs. Using a xenograft transplantation model of A549 cells, we demonstrated that silencing of ADAM12 inhibited the hASC-stimulated in vivo growth of A549 xenograft tumors and the differentiation of transplanted hASCs to α-smooth muscle actin-positive carcinoma-associated fibroblasts. LPA-conditioned medium from hASCs induced the adhesion of A549 cells and silencing of ADAM12 inhibited LPA-induced expression of extracellular matrix proteins, periostin and βig-h3, in hASCs and LPA-conditioned medium-stimulated adhesion of A549 cells. These results suggest a pivotal role for LPA-stimulated ADAM12 expression in tumor growth and the differentiation of hASCs to carcinoma-associated fibroblasts expressing α-smooth muscle actin, periostin, and βig-h3. Copyright © 2012 Elsevier Ltd. All rights reserved.

Springs, streams, and gas vent on and near Mount Adams volcano, Washington

USGS Publications Warehouse

Nathenson, Manuel; Mariner, Robert H.

2013-01-01

Springs and some streams on Mount Adams volcano have been sampled for chemistry and light stable isotopes of water. Spring temperatures are generally cooler than air temperatures from weather stations at the same elevation. Spring chemistry generally reflects weathering of volcanic rock from dissolved carbon dioxide. Water in some springs and streams has either dissolved hydrothermal minerals or has reacted with them to add sulfate to the water. Some samples appear to have obtained their sulfate from dissolution of gypsum while some probably involve reaction with sulfide minerals such as pyrite. Light stable isotope data for water from springs follow a local meteoric water line, and the variation of isotopes with elevation indicate that some springs have very local recharge and others have water from elevations a few hundred meters higher. No evidence was found for thermal or slightly thermal springs on Mount Adams. A sample from a seeping gas vent on Mount Adams was at ambient temperature, but the gas is similar to that found on other Cascade volcanoes. Helium isotopes are 4.4 times the value in air, indicating that there is a significant component of mantle helium. The lack of fumaroles on Mount Adams and the ambient temperature of the gas indicates that the gas is from a hydrothermal system that is no longer active.

Comparison Virtual Landing Gear Drop Test for Commuter Aircraft Utilize MSC ADAMS And Solidworks Motion Analysis

NASA Astrophysics Data System (ADS)

Hidayat, Dony; Istiyanto, Jos; Agus Sumarsono, Danardono

2018-04-01

Loads at main landing gear while touchdown impact is function of aircraft weight and ground reaction load factor. In regulation states ground reaction load factor at Vsink = 3.05 m/s is below 3. Contact/impact force from simulation using MSC ADAMS is 94680 N, while using Solidworks Motion Analysis is 97691 N. The difference between MSC ADAMS and Solidworks Motion Analysis is 3.08%. The ground reaction load factor in MSC ADAMS is 2.78 while in Solidworks Motion Analysis is 2.87.

77 FR 60004 - Culturally Significant Object Imported for Exhibition Determinations: “Wtewael's Adam and Eve”

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-01

... Determinations: ``Wtewael's Adam and Eve'' SUMMARY: Notice is hereby given of the following determinations... April 15, 2003), I hereby determine that the object to be included in the exhibition ``Wtewael's Adam and Eve,'' imported from abroad for temporary exhibition within the United States, is of cultural...

Reiter conducts a fit check of the Kazbek couches in the Soyuz TMA-8/12S

NASA Image and Video Library

2006-07-26

ISS013-E-60768 (26 July 2006) --- Attired in a Russian Sokol launch and entry suit, European Space Agency (ESA) astronaut Thomas Reiter, Expedition 13 flight engineer, participates in a Kazbek couch fit check in the TMA-8 Soyuz spacecraft docked to the International Space Station.

Geologic map and geothermal assessment of the Mount Adams volcanic field, Cascade Range of southern Washington

USGS Publications Warehouse

Hildreth, Wes; Fierstein, Judy

1990-01-01

More than 60 Quaternary vents make up the basalt-to-rhyodacite Mount Adams volcanic field and have erupted scoriae and lavas with a total volume of >370 km3. The Mount Adams andesite-dacite stratocone itself is a compound edifice that includes the high cone above 2300 m (20-10 ka), remnants of at least two earlier andesite-dacite cones as old as 0.5 Ma, and 7 Holocene flank vents. Four other Holocene vents and tens of vents contemporaneous with Mount Adams are peripheral to the stratocone. All of these vents, including Mount Adams, lie within a N-S eruptive zone 55 km long and 5 km wide. The age of all known Mount Adams silicic products (>100 ka) and the heterogeneous mafic compositions of the summit cone and Holocene lavas make it unlikely that the stratocone is underlain by an upper-crustal reservoir. Rather, the stratocone at the focus is built up of fractionated hybrid magmas that rise from MASH zones (melting-assimilation-storage-homogenization). The pyroclastic core of breccia and scoria at Mount Adams has undergone acid-sulfate leaching and deposition of alunite, kaolinite, silica, gypsum, sulfur, and Fe-oxides and has been a constant source of avalanches and debris flows. Most heat supplied from depth to the fumarolically altered core is dispersed by the high precipitation rate and high permeability of the rubbly lava flows so that a hydrothermal convection pattern is not maintained. Summit-restricted fumaroles are weak and diffuse.

ADAM13 function is required in the 3 dimensional context of the embryo during cranial neural crest cell migration in Xenopus laevis

PubMed Central

Cousin, Hélène; Abbruzzese, Genevieve; McCusker, Catherine; Alfandari, Dominique

2012-01-01

The cranial neural crest (CNC) is a population of cells that arises from the lateral part of the developing brain, migrates ventrally and coordinates the entire craniofacial development of vertebrates. Many molecules are involved in CNC migration including the transmembrane metalloproteases ADAM13 and 19. We have previously shown that these ADAMs cleave a number of extracellular proteins and modify the transcription of a number of genes, and that both of these activities are important for cell migration. Here we show that the knock down of ADAM13 inhibits CNC migration in vivo but not in vitro, indicating that ADAM13 function is required in the 3-dimentional context of the embryo. We further show that the migration of CNC that do not express ADAM13 and ADAM19 can be rescued in vivo by co-grafting wild type CNC. Furthermore, the migration of CNC lacking ADAM13 can be rescued by mechanically separating the CNC from the surrounding ectoderm and mesoderm. Finally, we show that ADAM13 function is autonomous to CNC tissue, as the migration of morphant CNC can only be rescued by ADAM13 expression in the CNC and not the surrounding tissues. Together our results suggest that ADAM13 changes CNC interaction with the extracellular environment and that this change is necessary for their migration in vivo. PMID:22683825

Dr. Lytle Adams' incendiary "bat bomb" of World War II.

PubMed

Christen, Arden G; Christen, Joan A

2004-11-01

On December 7, 1941, a 60-year old dentist from Irwin, Pennsylvania, Dr. Lytle S. Adams, was driving home from a vacation at Carlsbad Caverns in New Mexico. Hours earlier, he had been gripped with amazement as he witnessed millions of bats exiting the caves of Carlsbad. Listening to his car radio on his return trip, he was shocked to hear that Japan had just attacked Pearl Harbor. Dr. Adams, outraged over this travesty, began to mentally construct a plan for U.S. retaliation. As his thoughts returned to the countless bats that had awed him, he formed a tentative plan: millions of these small, flying mammals could be connected to tiny, time-fused incendiary bombs, and then released to land on the flimsily constructed structures which dotted the cities of Japan. Within a few minutes, the bombs would explode and enflame the entire urban areas. He postulated that these immeasurable numbers of fires, spreading their devastation over such vast areas within Japanese cities would result in the enemy's speedy surrender. This article documents the futile efforts of Dr. Adams, his team and the U.S. government to develop and employ an effective, incendiary bat bomb. The recently developed atom bomb, a far more deadly weapon was used in its place.

ADAM28 is expressed by epithelial cells in human normal tissues and protects from C1q-induced cell death.

PubMed

Miyamae, Yuka; Mochizuki, Satsuki; Shimoda, Masayuki; Ohara, Kentaro; Abe, Hitoshi; Yamashita, Shuji; Kazuno, Saiko; Ohtsuka, Takashi; Ochiai, Hiroki; Kitagawa, Yuko; Okada, Yasunori

2016-05-01

ADAM28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte-specific, is over-expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM28, ADAM28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT-PCR, immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM28-binding protein from a human lung cDNA library by yeast two-hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS-2B and NHBE cells, both of which showed low-level expression of ADAM28, caused apoptosis through activation of p38 and caspase-3, and cell death with autophagy through accumulation of LC3-II and autophagosomes, respectively. C1q-induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM28 prior to addition to culture media reduced C1q-induced cell death, and knockdown of ADAM28 using siRNAs increased cell death. These data demonstrate that ADAM28 is expressed by epithelial cells of several normal organs, and suggest that ADAM28 plays a role in cell survival by suppression of C1q-induced cytotoxicity in bronchial epithelial cells. © 2016 Federation of European Biochemical Societies.

The induction of C/EBPβ contributes to vitamin D inhibition of ADAM17 expression and parathyroid hyperplasia in kidney disease.

PubMed

Arcidiacono, Maria Vittoria; Yang, Jing; Fernandez, Elvira; Dusso, Adriana

2015-03-01

In secondary hyperparathyroidism (SHPT), enhanced parathyroid levels of transforming growth factor-α (TGFα) increase EGF receptor (EGFR) activation causing parathyroid hyperplasia, high parathyroid hormone (PTH) and also reductions in vitamin D receptor (VDR) that limit vitamin D suppression of SHPT. Since anti-EGFR therapy is not an option in human SHPT, we evaluated ADAM17 as a therapeutic target to suppress parathyroid hyperplasia because ADAM17 is required to release mature TGFα, the most potent EGFR-activating ligand. Computer analysis of the ADAM17 promoter identified TGFα and C/EBPβ as potential regulators of the ADAM17 gene. Their regulation of ADAM17 expression, TGFα/EGFR-driven growth and parathyroid gland (PTG) enlargement were assessed in promoter-reporter assays in A431 cells and corroborated in rat and human SHPT, using erlotinib as anti-EGFR therapy to suppress TGFα signals, active vitamin D to induce C/EBPβ or the combination. While TGFα induced ADAM17-promoter activity by 2.2-fold exacerbating TGFα/EGFR-driven growth, ectopic C/EBPβ expression completely prevented this vicious synergy. Accordingly, in advanced human SHPT, parathyroid ADAM17 levels correlated directly with TGFα and inversely with C/EBPβ. Furthermore, combined erlotinib + calcitriol treatment suppressed TGFα/EGFR-cell growth and PTG enlargement more potently than erlotinib in part through calcitriol induction of C/EBPβ to inhibit ADAM17-promoter activity, mRNA and protein. Importantly, in rat SHPT, the correction of vitamin D deficiency effectively reversed the resistance to paricalcitol induction of C/EBPβ to suppress ADAM17 expression and PTG enlargement, reducing PTH by 50%. In SHPT, correction of vitamin D and calcitriol deficiency induces parathyroid C/EBPβ to efficaciously attenuate the severe ADAM17/TGFα synergy, which drives PTG enlargement and high PTH. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Réalisation de couches minces magnétiques d'hexaferrite de baryum en vue de concevoir un isolateur coplanaire passif

NASA Astrophysics Data System (ADS)

Capraro, S.; Nader, C.; Chatelon, J. P.; Le Berre, M.; Rouiller, T.; Bayard, B.; Joisten, H.; Barbier, D.; Rousseau, J. J.

2005-05-01

Le développement des dispositifs intégrés employant un ferrite est un objectif majeur pour des applications électroniques dans la gamme hyperfréquence (circulateurs et isolateurs). Les ferrites hexagonaux, tel que l'hexaferrite de baryum (BaFe{12}O{19} ou BaM), présentent un grand intérêt pour de tels dispositifs en raison de leurs grandes résistivités et de leurs perméabilités élevées aux hautes fréquences. Dans cette étude, les couches minces de BaM, sont déposées et optimisées par pulvérisation cathodique RF sur des substrats d'alumine et de silicium. Après dépôt, les films sont amorphes et un recuit thermique à 800° C est nécessaire pour que les couches de BaM cristallisent et présentent des propriétés magnétiques. Les propriétés magnétiques des couches minces de BaM ont été déterminées par VSM, et on constate que le champ coercitif et l'aimantation à saturation atteignent respectivement 330 kA/m et 500 mT. Des isolateurs sont réalisés par dépôt d'une couche conductrice d'or en utilisant la technique du lift-off qui permet la mise en place du ruban signal ainsi que des plans de masse. Les premiers résultats de mesure en transmission ont montré un effet non réciproque qui atteint 8 dB/cm à 50 GHz.

In silico approaches and proportional odds model towards identifying selective ADAM17 inhibitors from anti-inflammatory natural molecules.

PubMed

Borah, Pallab Kumar; Chakraborty, Sourav; Jha, Anupam N; Rajkhowa, Sanchaita; Duary, Raj Kumar

2016-11-01

ADAM metallopeptidase domain 17 (ADAM17) is an attractive target for the development of new anti-inflammatory drugs. We aimed to identify selective inhibitors of ADAM17 against matrix metalloproteinase enzymes (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-13, and MMP-16) which have substantial structural similarity. Target proteins were docked with 29 anti-inflammatory natural molecule ligands and a known selective inhibitor IK682. The ligands were screened based on Lipinski rules, interaction with the ADAM17 active site cavity, and then ranked using the proportional odds model multinomial logistic regression. Silymarin was the most selective inhibitor of ADAM17 exhibiting H-bonding with Glu 406, Gly 349, Glu 398, Asn 447, Tyr 433, and Lys 432. Molecular dynamics simulations were carried out for 10ns. The root mean square deviation (RMSD), root mean squared fluctuations (RMSF), radius of gyration (Rg), solvent accessible surface area (SASA), and H-bonding indicated the induced metastability. A comparison of the principal component analysis revealed that the silymarin complex also explored lesser region compared to IK682 complex. A control study on ADAM17 protein (2OI0) is included. These observations present silymarin (widely present in plants such as milk thistle (Silybum maianum), wild artichokes (Cynara cardunculus), turmeric (Curcuma longa) roots, coriander (Coriandrum sativum) seeds, etc.) as a promising natural template for development of ADAM17 selective drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

ADAM-17 and TIMP3 protein and mRNA expression in spinal cord white matter of rats with acute experimental autoimmune encephalomyelitis.

PubMed

Plumb, Jonnie; Cross, Alison K; Surr, Jessica; Haddock, Gail; Smith, Terence; Bunning, Rowena A D; Woodroofe, M Nicola

2005-07-01

Tumour necrosis factor (TNF) is a major immunomodulatory and proinflammatory cytokine implicated in the pathogenesis of multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE). ADAM-17 cleaves membrane-bound TNF into its soluble form. The distribution and level of ADAM-17 expression within spinal cords of Lewis rats with EAE was investigated. ADAM-17 was associated with endothelial cells in the naïve and pre-disease spinal cords. In peak disease astrocytic and inflammatory cells expressed ADAM-17. Upregulation of ADAM-17 mRNA expression was coupled with a decrease in mRNA levels of its inhibitor TIMP3 suggesting a role for ADAM-17 in EAE pathogenesis.

[The importance of ADAM family proteins in malignant tumors].

PubMed

Walkiewicz, Katarzyna; Gętek, Monika; Muc-Wierzgoń, Małgorzata; Kokot, Teresa; Nowakowska-Zajdel, Ewa

2016-02-11

Increasing numbers of reports about the role of adamalysins (ADAM) in malignant tumors are being published. To date, more than 30 representatives of this group, out of which about 20 occur in humans, have been described. The ADAM family is a homogeneous group of proteins which regulate, from the stage of embryogenesis, a series of processes such as cell migration, adhesion, and cell fusion. Half of them have proteolytic activity and are involved in the degradation of the extracellular matrix and the disintegration of certain protein complexes, thereby regulating the bioavailability of various growth factors. Many of these functions have a direct role in the processes of carcinogenesis and promoting the growth of tumor, which affect some signaling pathways, including those related to insulin-like growth factors (IGF1, IGF2), vascular growth factor (VEGF), tumor necrosis factor α (TNFα) and the EGFR/HER pathway. Another branch of studies is the evaluation of the possibility of using members of ADAM family proteins in the diagnosis, especially in breast, colon and non- small cell lung cancer. The detection of concentrations of adamalysin in serum, urine and pleural aspirates might contribute to the development of methods of early diagnosis of cancer and monitoring the therapy. However, both the role of adamalysins in the development and progression of tumors and their importance as a diagnostic and predictive further research still need to be checked on large groups of patients.

Kivelson Receives 2005 John Adam Fleming Medal

NASA Astrophysics Data System (ADS)

Singer, Howard J.; Kivelson, Margaret G.

2006-01-01

Margaret G. Kivelson was awarded the Fleming Medal at the AGU Fall Meeting Honors Ceremony, which was held on 7 December 2005, in San Francisco, Calif. The medal recognizes original research and technical leadership in geomagnetism, atmospheric electricity, aeronomy, space physics, and related sciences. After a Ph.D. in theoretical physics (with Nobel Prize winner Julian Schwinger) and part-time work at the RAND Corporation during her children's early childhood, Margaret Kivelson entered geophysics in the 1960s. Since then, Margaret has led a remarkable career in the fields of solar-terrestrial physics, heliospheric and planetary science, and, in particular, planetary magnetism. Her achievementsinclude the following.

John Glenn Prepares for a Test in the Multi-Axis Space Test Inertia Facility

NASA Image and Video Library

1960-02-21

Mercury astronaut John Glenn prepares for a test in the Multi-Axis Space Test Inertia Facility (MASTIF) inside the Altitude Wind Tunnel at the National Aeronautics and Space Administration (NASA) Lewis Research Center. The MASTIF was a three-axis test rig with a pilot’s chair mounted in the center. The device was designed to train Project Mercury pilots to bring a spinning spacecraft under control. An astronaut was secured in a foam couch in the center of the rig. The rig was then spun on three axes from 2 to 50 rotations per minute. Small nitrogen gas thrusters were used by the astronauts to bring the MASTIF under control. In February and March 1960, the seven Project Mercury astronauts traveled to Cleveland to train on the MASTIF. Warren North and a team of air force physicians were on hand to monitor their health. After being briefed by Lewis pilot Joe Algranti and researcher James Useller, the rider would climb into the rig and be secured in the chair, as seen in this photograph. A Lewis engineer would then slowly set the MASTIF in motion. It was the astronaut’s job to bring it under control. Each individual was required to accumulate 4.5 to 5 hours of MASTIF time. Glenn became the first American to orbit the earth on February 20, 1962 in the Friendship 7 Mercury capsule. In March 1999, the Lewis Research Center was renamed the John H. Glenn Research Center at Lewis Field.

Isotopic and trace element constraints on the petrogenesis of lavas from the Mount Adams volcanic field, Washington

USGS Publications Warehouse

Jicha, B.R.; Hart, G.L.; Johnson, C.M.; Hildreth, Wes; Beard, B.L.; Shirey, S.B.; Valley, J.W.

2009-01-01

Strontium, Nd, Pb, Hf, Os, and O isotope compositions for 30 Quaternary lava flows from the Mount Adams stratovolcano and its basaltic periphery in the Cascade arc, southern Washington, USA indicate a major component from intraplate mantle sources, a relatively small subduction component, and interaction with young mafic crust at depth. Major- and trace-element patterns for Mount Adams lavas are distinct from the rear-arc Simcoe volcanic field and other nearby volcanic centers in the Cascade arc such as Mount St. Helens. Radiogenic isotope (Sr, Nd, Pb, and Hf) compositions do not correlate with geochemical indicators of slab-fluids such as (Sr/P)n and Ba/Nb. Mass-balance modeling calculations, coupled with trace-element and isotopic data, indicate that although the mantle source for the calc-alkaline Adams basalts has been modified with a fluid derived from subducted sediment, the extent of modification is significantly less than what is documented in the southern Cascades. The isotopic and trace-element compositions of most Mount Adams lavas require the presence of enriched and depleted mantle sources, and based on volume-weighted chemical and isotopic compositions for Mount Adams lavas through time, an intraplate mantle source contributed the major magmatic mass of the system. Generation of basaltic andesites to dacites at Mount Adams occurred by assimilation and fractional crystallization in the lower crust, but wholesale crustal melting did not occur. Most lavas have Tb/Yb ratios that are significantly higher than those of MORB, which is consistent with partial melting of the mantle in the presence of residual garnet. ??18O values for olivine phenocrysts in Mount Adams lavas are within the range of typical upper mantle peridotites, precluding involvement of upper crustal sedimentary material or accreted terrane during magma ascent. The restricted Nd and Hf isotope compositions of Mount Adams lavas indicate that these isotope systems are insensitive to crustal

Adam Smith and the Teaching of English Literature.

ERIC Educational Resources Information Center

Court, Franklin E.

1985-01-01

Adam Smith used selections from English literature in his classroom during the eighteenth century because he believed that vernacular literature could provide a ready context for the teaching of ideological, social, and moral lessons. He believed that higher education should prepare students for the real business of the real world. (RM)

The TspanC8 Subgroup of Tetraspanins Interacts with A Disintegrin and Metalloprotease 10 (ADAM10) and Regulates Its Maturation and Cell Surface Expression*

PubMed Central

Haining, Elizabeth J.; Yang, Jing; Bailey, Rebecca L.; Khan, Kabir; Collier, Richard; Tsai, Schickwann; Watson, Steve P.; Frampton, Jon; Garcia, Paloma; Tomlinson, Michael G.

2012-01-01

A disintegrin and metalloprotease 10 (ADAM10) is a ubiquitous transmembrane metalloprotease that cleaves the extracellular regions from over 40 different transmembrane target proteins, including Notch and amyloid precursor protein. ADAM10 is essential for embryonic development and is also important in inflammation, cancer, and Alzheimer disease. However, ADAM10 regulation remains poorly understood. ADAM10 is compartmentalized into membrane microdomains formed by tetraspanins, which are a superfamily of 33 transmembrane proteins in humans that regulate clustering and trafficking of certain other transmembrane “partner” proteins. This is achieved by specific tetraspanin-partner interactions, but it is not clear which tetraspanins specifically interact with ADAM10. The aims of this study were to identify which tetraspanins interact with ADAM10 and how they regulate this metalloprotease. Co-immunoprecipitation identified specific ADAM10 interactions with Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, and Tspan33/Penumbra. These are members of the largely unstudied TspanC8 subgroup of tetraspanins, all six of which promoted ADAM10 maturation. Different cell types express distinct repertoires of TspanC8 tetraspanins. Human umbilical vein endothelial cells express relatively high levels of Tspan14, the knockdown of which reduced ADAM10 surface expression and activity. Mouse erythrocytes express predominantly Tspan33, and ADAM10 expression was substantially reduced in the absence of this tetraspanin. In contrast, ADAM10 expression was normal on Tspan33-deficient mouse platelets in which Tspan14 is the major TspanC8 tetraspanin. These results define TspanC8 tetraspanins as essential regulators of ADAM10 maturation and trafficking to the cell surface. This finding has therapeutic implications because focusing on specific TspanC8-ADAM10 complexes may allow cell type- and/or substrate-specific ADAM10 targeting. PMID:23035126

George Adams Junior and his 1789 book An essay on vision.

PubMed

Goss, David A

2009-04-01

English instrument maker George Adams Junior (1750-1795) published An Essay on Vision in 1789, with a second edition appearing in 1792. The 153 page book (157 pages in the second edition) presented material on structure of the eye and the basic nature of vision and vision conditions, with an emphasis on the proper use and choice of spectacles for the "long sighted" and the "short-sighted." A brief biographical sketch of Adams is given, and the contents of the book are discussed, with presentation of excerpts relating to general optometric principles. The excerpts can serve to illustrate the state of optometric knowledge in the late eighteenth century.

A score including ADAM17 substrates correlates to recurring cardiovascular event in subjects with atherosclerosis.

PubMed

Rizza, Stefano; Copetti, Massimiliano; Cardellini, Marina; Menghini, Rossella; Pecchioli, Chiara; Luzi, Alessio; Di Cola, Giovanni; Porzio, Ottavia; Ippoliti, Arnaldo; Romeo, Franco; Pellegrini, Fabio; Federici, Massimo

2015-04-01

Atherosclerosis disease is a leading cause for mortality and morbidity. The narrowing/rupture of a vulnerable atherosclerotic plaque is accountable for acute cardiovascular events. However, despite of an intensive research, a reliable clinical method which may disclose a vulnerable patient is still unavailable. We tested the association of ADAM17 (A Disintegrin and Metallo Protease Domain 17) circulating substrates (sICAM-1, sVCAM-1, sIL6R and sTNFR1) with a second major cardiovascular events [MACEs] (cardiovascular death, peripheral artery surgeries, non-fatal myocardial infarction and non-fatal stroke) in 298 patients belonging to the Vascular Diabetes (AVD) study. To evaluate ADAM17 activity we create ADAM17 score through a RECPAM model. Finally we tested the discrimination ability and the reclassification of clinical models. At follow-up (mean 47 months, range 1-118 months), 55 MACEs occurred (14 nonfatal MI, 14 nonfatal strokes, 17 peripheral artery procedures and 10 cardiovascular deaths) (incidence = 7.8% person-years). An increased risk for incident events was observed among the high ADAM17 score individuals both in univariable (HR 19.20, 95% CI 15.82-63.36, p < 0.001) and multivariable analysis (HR 3.42, 95% CI 1.55-7.54, p < 0.001). Finally we found that ADAM17 score significantly increases the prediction accuracy of the Framingham Recurring-Coronary-Heart-Disease-Score, with a significant improvement in discrimination (integrated discrimination improvement = 9%, p = 0.012) and correctly reclassifying 10% of events and 41% of non-events resulting in a cNRI = 0.51 (p = 0.005). We demonstrated a positive role of ADAM17 activity to predicting CV events. We think that an approach that targets strategies beyond classic cardiovascular risk factors control is necessary in individuals with an established vascular atherosclerosis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A Mechanism of Male Germ Cell Apoptosis Induced by Bisphenol-A and Nonylphenol Involving ADAM17 and p38 MAPK Activation

PubMed Central

Moreno, Ricardo D.

2014-01-01

Germ cell apoptosis regulation is pivotal in order to maintain proper daily sperm production. Several reports have shown that endocrine disruptors such as Bisphenol-A (BPA) and Nonylphenol (NP) induce germ cell apoptosis along with a decrease in sperm production. Given their ubiquitous distribution in plastic products used by humans it is important to clarify their mechanism of action. TACE/ADAM17 is a widely distributed extracellular metalloprotease and participates in the physiological apoptosis of germ cells during spermatogenesis. The aims of this work were: 1) to determine whether BPA and NP induce ADAM17 activation; and 2) to study whether ADAM17 and/or ADAM10 are involved in germ cell apoptosis induced by BPA and NP in the pubertal rat testis. A single dose of BPA or NP (50 mg/kg) induces germ cell apoptosis in 21-day-old male rats, which was prevented by a pharmacological inhibitor of ADAM17, but not by an inhibitor of ADAM10. In vitro, we showed that BPA and NP, at similar concentrations to those found in human samples, induce the shedding of exogenous and endogenous (TNF-α) ADAM17 substrates in primary rat Sertoli cell cultures and TM4 cell line. In addition, pharmacological inhibitors of metalloproteases and genetic silencing of ADAM17 prevent the shedding induced in vitro by BPA and NP. Finally, we showed that in vivo BPA and NP induced early activation (phosphorylation) of p38 MAPK and translocation of ADAM17 to the cell surface. Interestingly, the inhibition of p38 MAPK prevents germ cell apoptosis and translocation of ADAM17 to the cell surface. These results show for the first time that xenoestrogens can induce activation of ADAM17 at concentrations similar to those found in human samples, suggesting a mechanism by which they could imbalance para/juxtacrine cell-to-cell-communication and induce germ cell apoptosis. PMID:25474107

Technical Note: Unified imaging and robotic couch quality assurance.

PubMed

Cook, Molly C; Roper, Justin; Elder, Eric S; Schreibmann, Eduard

2016-09-01

To introduce a simplified quality assurance (QA) procedure that integrates tests for the linac's imaging components and the robotic couch. Current QA procedures for evaluating the alignment of the imaging system and linac require careful positioning of a phantom at isocenter before image acquisition and analysis. A complementary procedure for the robotic couch requires an initial displacement of the phantom and then evaluates the accuracy of repositioning the phantom at isocenter. We propose a two-in-one procedure that introduces a custom software module and incorporates both checks into one motion for increased efficiency. The phantom was manually set with random translational and rotational shifts, imaged with the in-room imaging system, and then registered to the isocenter using a custom software module. The software measured positioning accuracy by comparing the location of the repositioned phantom with a CAD model of the phantom at isocenter, which is physically verified using the MV port graticule. Repeatability of the custom software was tested by an assessment of internal marker location extraction on a series of scans taken over differing kV and CBCT acquisition parameters. The proposed method was able to correctly position the phantom at isocenter within acceptable 1 mm and 1° SRS tolerances, verified by both physical inspection and the custom software. Residual errors for mechanical accuracy were 0.26 mm vertically, 0.21 mm longitudinally, 0.55 mm laterally, 0.21° in pitch, 0.1° in roll, and 0.67° in yaw. The software module was shown to be robust across various scan acquisition parameters, detecting markers within 0.15 mm translationally in kV acquisitions and within 0.5 mm translationally and 0.3° rotationally across CBCT acquisitions with significant variations in voxel size. Agreement with vendor registration methods was well within 0.5 mm; differences were not statistically significant. As compared to the current two-step approach, the proposed

Adams National Historic Park Trolley Vehicle Replacement Selection Analysis

DOT National Transportation Integrated Search

2017-12-01

Adams NHP owns three trolley vehicles that were purchased in the early 2000s and, while their accrued mileage remains low, they have reached the end of their useful lives due in large part to vehicle parts becoming unavailable. Both the original trol...

The dehydration stress of couch grass is associated with its lipid metabolism, the induction of transporters and the re-programming of development coordinated by ABA.

PubMed

Janská, Anna; Svoboda, Pavel; Spiwok, Vojtěch; Kučera, Ladislav; Ovesná, Jaroslava

2018-05-02

The wild relatives of crop species represent a potentially valuable source of novel genetic variation, particularly in the context of improving the crop's level of tolerance to abiotic stress. The mechanistic basis of these tolerances remains largely unexplored. Here, the focus was to characterize the transcriptomic response of the nodes (meristematic tissue) of couch grass (a relative of barley) to dehydration stress, and to compare it to that of the barley crown formed by both a drought tolerant and a drought sensitive barley cultivar. Many of the genes up-regulated in the nodes by the stress were homologs of genes known to be mediated by abscisic acid during the response to drought, or were linked to either development or lipid metabolism. Transporters also featured prominently, as did genes acting on root architecture. The resilience of the couch grass node arise from both their capacity to develop an altered, more effective root architecture, but also from their formation of a lipid barrier on their outer surface and their ability to modify both their lipid metabolism and transporter activity when challenged by dehydration stress. Our analysis revealed the nature of dehydration stress response in couch grass. We suggested the tolerance is associated with lipid metabolism, the induction of transporters and the re-programming of development coordinated by ABA. We also proved the applicability of barley microarray for couch grass stress-response analysis.

Henry Adams’s Life of George Cabot Lodge: A Portrait of the Artist as an Alienated Man

DTIC Science & Technology

1994-07-20

literary tradition, especially as had been handed down from Adams’s Puritan forebears. My aim is to present the most complete critical study of this...several critics have pointed to this book as evidence of Adams’s diminished talents--when a careful study of the book in fact demonstrates otherwise...critical studies have given more than cursory attention to the Life of Lodge: J. C. Levenson, The Mind and Art of Henry Adams (1957); George Hochfield

Targeting ADAM17 inhibits human colorectal adenocarcinoma progression and tumor-initiating cell frequency.

PubMed

Dosch, Joseph; Ziemke, Elizabeth; Wan, Shanshan; Luker, Kathryn; Welling, Theodore; Hardiman, Karin; Fearon, Eric; Thomas, Suneetha; Flynn, Matthew; Rios-Doria, Jonathan; Hollingsworth, Robert; Herbst, Ronald; Hurt, Elaine; Sebolt-Leopold, Judith

2017-09-12

ADAM17 (a disintegrin and metalloproteinase 17)/TACE (TNFα converting enzyme) has emerged as a potential therapeutic target in colorectal cancer (CRC) and other cancers, due in part to its role in regulating various tumor cell surface proteins and growth factors and cytokines in the tumor microenvironment. The emergence of MEDI3622, a highly potent and specific antibody-based ADAM17 inhibitor, has allowed testing of the concept that targeting ADAM17 may be an important new therapeutic approach for CRC patients. We demonstrate that MEDI3622 is highly efficacious on tumor growth in multiple human CRC PDX models, resulting in improved survival of animals bearing tumor xenografts. MEDI3622 was further found to impact Notch pathway activity and tumor-initiating cells. The promising preclinical activity seen here supports further clinical investigation of this treatment approach to improve therapeutic outcome for patients diagnosed with metastatic CRC, including patients with KRAS-mutant tumors for whom other therapeutic options are currently limited.

7. Historic American Buildings Survey, C. C. Adams, Photographer August ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. Historic American Buildings Survey, C. C. Adams, Photographer August 1931, SEED PACKING ROOM, Gift of New York State Department of Education. - Shaker North Family Washhouse (first), Shaker Road, New Lebanon, Columbia County, NY

Welfare effects of reduced milk production associated with Johne's disease on Johne's-positive versus Johne's-negative dairy operations.

PubMed

Losinger, Willard C

2006-08-01

An examination of the economic impacts of reduced milk production associated with Johne's disease on Johne's-positive and Johne's-negative dairy operations indicated that, if Johne's disease had not existed in US dairy cows in 1996, then the economic surplus of Johne's-negative operations would have been $600 million+/-$530 million lower, while the economic surplus of Johne's-positive operations would have been higher by $28 million+/-$79 million, which was not significantly different from zero. The data available for projecting changes in surplus were not sufficiently precise to allow an exact statement on whether Johne's-positive operations would have been better or worse off economically, in terms of the value received for producing more milk if they had not been affected by Johne's disease. The changes in producer surplus, based upon eliminating specific epidemiological risk factors for Johne's disease, were disaggregated between Johne's-positive dairy operations exposed to the risk factor and all other US dairy operations. Eliminating the risk factor of having any cows not born on the operation would have had a significant positive effect on the economic surplus of Johne's-positive operations that had any cows not born on the operation.

ADAM: An Axisymmetric Duct Aeroacoustic Modeling system. [aircraft turbofan engines

NASA Technical Reports Server (NTRS)

Abrahamson, A. L.

1983-01-01

An interconnected system of computer programs for analyzing the propagation and attenuation of sound in aeroengine ducts containing realistic compressible subsonic mean flows, ADAM was developed primarily for research directed towards the reduction of noise emitted from turbofan aircraft engines. The two basic components are a streamtube curvature program for determination of the mean flow, and a finite element code for solution of the acoustic propagation problem. The system, which has been specifically tailored for ease of use, is presently installed at NASA Langley Reseach Center on a Control Data Cyber 175 Computer under the NOS Operating system employing a Tektronix terminal for interactive graphics. The scope and organization of the ADAM system is described. A users guide, examples of input data, and results for selected cases are included.

System Verification of MSL Skycrane Using an Integrated ADAMS Simulation

NASA Technical Reports Server (NTRS)

White, Christopher; Antoun, George; Brugarolas, Paul; Lih, Shyh-Shiuh; Peng, Chia-Yen; Phan, Linh; San Martin, Alejandro; Sell, Steven

2012-01-01

Mars Science Laboratory (MSL) will use the Skycrane architecture to execute final descent and landing maneuvers. The Skycrane phase uses closed-loop feedback control throughout the entire phase, starting with rover separation, through mobility deploy, and through touchdown, ending only when the bridles have completely slacked. The integrated ADAMS simulation described in this paper couples complex dynamical models created by the mechanical subsystem with actual GNC flight software algorithms that have been compiled and linked into ADAMS. These integrated simulations provide the project with the best means to verify key Skycrane requirements which have a tightly coupled GNC-Mechanical aspect to them. It also provides the best opportunity to validate the design of the algorithm that determines when to cut the bridles. The results of the simulations show the excellent performance of the Skycrane system.

Novel and high volume use flame retardants in US couches reflective of the 2005 PentaBDE phase out.

PubMed

Stapleton, Heather M; Sharma, Smriti; Getzinger, Gordon; Ferguson, P Lee; Gabriel, Michelle; Webster, Thomas F; Blum, Arlene

2012-12-18

California's furniture flammability standard Technical Bulletin 117 (TB 117) is believed to be a major driver of chemical flame retardant (FR) use in residential furniture in the United States. With the phase-out of the polybrominated diphenyl ether (PBDE) FR mixture PentaBDE in 2005, alternative FRs are increasingly being used to meet TB 117; however, it was unclear which chemicals were being used and how frequently. To address this data gap, we collected and analyzed 102 samples of polyurethane foam from residential couches purchased in the United States from 1985 to 2010. Overall, we detected chemical flame retardants in 85% of the couches. In samples purchased prior to 2005 (n = 41) PBDEs associated with the PentaBDE mixture including BDEs 47, 99, and 100 (PentaBDE) were the most common FR detected (39%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCPP; 24%), which is a suspected human carcinogen. In samples purchased in 2005 or later (n = 61) the most common FRs detected were TDCPP (52%) and components associated with the Firemaster550 (FM 550) mixture (18%). Since the 2005 phase-out of PentaBDE, the use of TDCPP increased significantly. In addition, a mixture of nonhalogenated organophosphate FRs that included triphenyl phosphate (TPP), tris(4-butylphenyl) phosphate (TBPP), and a mix of butylphenyl phosphate isomers were observed in 13% of the couch samples purchased in 2005 or later. Overall the prevalence of flame retardants (and PentaBDE) was higher in couches bought in California compared to elsewhere, although the difference was not quite significant (p = 0.054 for PentaBDE). The difference was greater before 2005 than after, suggesting that TB 117 is becoming a de facto standard across the U.S. We determined that the presence of a TB 117 label did predict the presence of a FR; however, lack of a label did not predict the absence of a flame retardant. Following the PentaBDE phase out, we also found an increased number of flame retardants on the

Novel and High Volume Use Flame Retardants in US Couches Reflective of the 2005 PentaBDE Phase Out

PubMed Central

2012-01-01

California’s furniture flammability standard Technical Bulletin 117 (TB 117) is believed to be a major driver of chemical flame retardant (FR) use in residential furniture in the United States. With the phase-out of the polybrominated diphenyl ether (PBDE) FR mixture PentaBDE in 2005, alternative FRs are increasingly being used to meet TB 117; however, it was unclear which chemicals were being used and how frequently. To address this data gap, we collected and analyzed 102 samples of polyurethane foam from residential couches purchased in the United States from 1985 to 2010. Overall, we detected chemical flame retardants in 85% of the couches. In samples purchased prior to 2005 (n = 41) PBDEs associated with the PentaBDE mixture including BDEs 47, 99, and 100 (PentaBDE) were the most common FR detected (39%), followed by tris(1,3-dichloroisopropyl) phosphate (TDCPP; 24%), which is a suspected human carcinogen. In samples purchased in 2005 or later (n = 61) the most common FRs detected were TDCPP (52%) and components associated with the Firemaster550 (FM 550) mixture (18%). Since the 2005 phase-out of PentaBDE, the use of TDCPP increased significantly. In addition, a mixture of nonhalogenated organophosphate FRs that included triphenyl phosphate (TPP), tris(4-butylphenyl) phosphate (TBPP), and a mix of butylphenyl phosphate isomers were observed in 13% of the couch samples purchased in 2005 or later. Overall the prevalence of flame retardants (and PentaBDE) was higher in couches bought in California compared to elsewhere, although the difference was not quite significant (p = 0.054 for PentaBDE). The difference was greater before 2005 than after, suggesting that TB 117 is becoming a de facto standard across the U.S. We determined that the presence of a TB 117 label did predict the presence of a FR; however, lack of a label did not predict the absence of a flame retardant. Following the PentaBDE phase out, we also found an increased number of flame retardants on

Ectodomain Shedding by ADAM17: Its Role in Neutrophil Recruitment and the Impairment of This Process during Sepsis.

PubMed

Mishra, Hemant K; Ma, Jing; Walcheck, Bruce

2017-01-01

Neutrophils are specialized at killing bacteria and are recruited from the blood in a rapid and robust manner during infection. A cascade of adhesion events direct their attachment to the vascular endothelium and migration into the underlying tissue. A disintegrin and metalloproteinase 17 (ADAM17) functions in the cell membrane of neutrophils and endothelial cells by cleaving its substrates, typically in a cis manner, at an extracellular site proximal to the cell membrane. This process is referred to as ectodomain shedding and it results in the downregulation of various adhesion molecules and receptors, and the release of immune regulating factors. ADAM17 sheddase activity is induced upon cell activation and rapidly modulates intravascular adhesion events in response to diverse environmental stimuli. During sepsis, an excessive systemic inflammatory response against infection, neutrophil migration becomes severely impaired. This involves ADAM17 as indicated by increased levels of its cleaved substrates in the blood of septic patients, and that ADAM17 inactivation improves neutrophil recruitment and bacterial clearance in animal models of sepsis. Excessive ADAM17 sheddase activity during sepsis thus appears to undermine in a direct and indirect manner the necessary balance between intravascular adhesion and de-adhesion events that regulate neutrophil migration into sites of infection. This review provides an overview of ADAM17 function and regulation and its potential contribution to neutrophil dysfunction during sepsis.

Host status of barley to Puccinia coronata from couch grass and P. striiformis from wheat and brome

USDA-ARS?s Scientific Manuscript database

The pathogenicity and identity of a field sample (PcE) of crown rust fungus Puccinia coronata collected in Hungary on wild couch grass (Elytrigia repens) and of a field sample (Psb) of stripe rust (P. striiformis) collected in the Netherlands on California brome (Bromus carinatus) was studied. We fo...

The Oculist's Eye: Connections between Cataract Couching, Anatomy, and Visual Theory in the Renaissance.

PubMed

Baker, Tawrin

2017-01-01

We now know that cataract couching involves depressing an occluded crystalline lens to the bottom of the vitreous chamber, but from the time of Galen until the seventeenth-century cataracts were thought to be separate concretions arising between the crystalline lens and the pupil. From Antiquity through the Renaissance, the combination of visual theory in which the crystalline humor is the author of vision, and surgical experience—that couching cataracts restored some degree of sight—resulted in anatomists depicting a large space between the crystalline lens and the pupil. In the Renaissance, oculists—surgical specialists with little higher education or connections to learned surgery or medicine—overwhelmingly performed eye surgeries. This article examines how the experience and knowledge of oculists, of barber-surgeons, and of learned surgeons influenced one another on questions of anatomy, visual theory, and surgical experience. By analyzing the writings of the oculist George Bartisch (c. 1535–1607), the barber-surgeon Ambroise Paré (1510–1590), and the learned surgeon Hieronymus Fabricius ab Aquapendente (1533–1619), we see that the oculists’ understanding of the eye—an eye constructed out of the probing, tactile experience of eye surgery—slowly lost currency among the learned toward the beginning of the seventeenth century.

Trajectory optimization for dynamic couch rotation during volumetric modulated arc radiotherapy

NASA Astrophysics Data System (ADS)

Smyth, Gregory; Bamber, Jeffrey C.; Evans, Philip M.; Bedford, James L.

2013-11-01

Non-coplanar radiation beams are often used in three-dimensional conformal and intensity modulated radiotherapy to reduce dose to organs at risk (OAR) by geometric avoidance. In volumetric modulated arc radiotherapy (VMAT) non-coplanar geometries are generally achieved by applying patient couch rotations to single or multiple full or partial arcs. This paper presents a trajectory optimization method for a non-coplanar technique, dynamic couch rotation during VMAT (DCR-VMAT), which combines ray tracing with a graph search algorithm. Four clinical test cases (partial breast, brain, prostate only, and prostate and pelvic nodes) were used to evaluate the potential OAR sparing for trajectory-optimized DCR-VMAT plans, compared with standard coplanar VMAT. In each case, ray tracing was performed and a cost map reflecting the number of OAR voxels intersected for each potential source position was generated. The least-cost path through the cost map, corresponding to an optimal DCR-VMAT trajectory, was determined using Dijkstra’s algorithm. Results show that trajectory optimization can reduce dose to specified OARs for plans otherwise comparable to conventional coplanar VMAT techniques. For the partial breast case, the mean heart dose was reduced by 53%. In the brain case, the maximum lens doses were reduced by 61% (left) and 77% (right) and the globes by 37% (left) and 40% (right). Bowel mean dose was reduced by 15% in the prostate only case. For the prostate and pelvic nodes case, the bowel V50 Gy and V60 Gy were reduced by 9% and 45% respectively. Future work will involve further development of the algorithm and assessment of its performance over a larger number of cases in site-specific cohorts.

Comparative gene expression profiling of ADAMs, MMPs, TIMPs, EMMPRIN, EGF-R and VEGFA in low grade meningioma.

PubMed

Rooprai, Harcharan K; Martin, Andrew J; King, Andrew; Appadu, Usha D; Jones, Huw; Selway, Richard P; Gullan, Richard W; Pilkington, Geoffrey J

2016-12-01

MMPs (matrix metalloproteinases), ADAMs (a disintegrin and metalloproteinase) and TIMPs (tissue inhibitors of metalloproteinases) are implicated in invasion and angiogenesis: both are tissue remodeling processes involving regulated proteolysis of the extracellular matrix, growth factors and their receptors. The expression of these three groups and their correlations with clinical behaviour has been reported in gliomas but a similar comprehensive study in meningiomas is lacking. In this study, we aimed to evaluate the patterns of expression of 23 MMPs, 4 TIMPs, 8 ADAMs, selective growth factors and their receptors in 17 benign meningiomas using a quantitative real-time polymerase chain reaction (qPCR). Results indicated very high gene expression of 13 proteases, inhibitors and growth factors studied: MMP2 and MMP14, TIMP-1, -2 and -3, ADAM9, 10, 12, 15 and 17, EGF-R, EMMPRIN and VEGF-A, in almost every meningioma. Expression pattern analysis showed several positive correlations between MMPs, ADAMs, TIMPs and growth factors. Furthermore, our findings suggest that expression of MMP14, ADAM9, 10, 12, 15 and 17, TIMP-2, EGF-R and EMMPRIN reflects histological subtype of meningioma such that fibroblastic subtype had the highest mRNA expression, transitional subtype was intermediate and meningothelial type had the lowest expression. In conclusion, this is the first comprehensive study characterizing gene expression of 8 ADAMs in meningiomas. These neoplasms, although by histological definition benign, have invasive potential. Taken together, the selected elevated gene expression pattern may serve to identify targets for therapeutic intervention or indicators of biological progression and recurrence.

Lightweight robotic mobility: template-based modeling for dynamics and controls using ADAMS/car and MATLAB

NASA Astrophysics Data System (ADS)

Adamczyk, Peter G.; Gorsich, David J.; Hudas, Greg R.; Overholt, James

2003-09-01

The U.S. Army is seeking to develop autonomous off-road mobile robots to perform tasks in the field such as supply delivery and reconnaissance in dangerous territory. A key problem to be solved with these robots is off-road mobility, to ensure that the robots can accomplish their tasks without loss or damage. We have developed a computer model of one such concept robot, the small-scale "T-1" omnidirectional vehicle (ODV), to study the effects of different control strategies on the robot's mobility in off-road settings. We built the dynamic model in ADAMS/Car and the control system in Matlab/Simulink. This paper presents the template-based method used to construct the ADAMS model of the T-1 ODV. It discusses the strengths and weaknesses of ADAMS/Car software in such an application, and describes the benefits and challenges of the approach as a whole. The paper also addresses effective linking of ADAMS/Car and Matlab for complete control system development. Finally, this paper includes a section describing the extension of the T-1 templates to other similar ODV concepts for rapid development.

ADAM15 is involved in MICB shedding and mediates the effects of gemcitabine on MICB shedding in PANC-1 pancreatic cancer cells.

PubMed

Duan, Xiaohui; Mao, Xianhai; Sun, Weijia

2013-03-01

The aim of this study was to investigate the role of ADAM15 in MHC class I polypeptide-related sequence B (MICB) protein ectodomain shedding and observe whether or not gemcitabine affects MICB shedding from PANC-1 cells. In this study, immunohistochemistry of MICB and ADAM15 were performed on tumor samples obtained from 93 patients with pancreatic ductal adenocarcinoma (PDAC). The expression of MICB and ADAM15 in the PDAC tissues was significantly higher compared with that in the normal tissues of the pancreas. Statistical analysis showed a significant correlation between the expression of MICB and certain classic clinicopathological characteristics (i.e., histological grade and TNM stage). ADAM15 expression was found to correlate with lymph node metastasis and TNM stage. The Spearman's rank test suggested that the expression of MICB was inversely correlated with that of ADAM15 in PDAC tissues. Knockdown of ADAM15 in PANC-1 cells clearly upregulated MICB expression on the cellular surface and downregulated soluble MICB (sMICB) levels in the culture supernatants. A non-toxic dose of 0.5 µmol/l gemcitabine suppresses ADAM15 expression leading, at the same time, to an increase in MICB expression and a decrease in sMICB production in PANC-1 cells. The mRNA levels of MICB did not change following PANC-1 exposure to gemcitabine. Further study suggests that the suppressive effect of gemcitabine on MICB shedding in PANC-1 cells is mediated by ADAM15 downregulation. In conclusion, the results of the present study support the hypothesis that ADAM15 is involved in MICB shedding of PANC-1 cells and that gemcitabine inhibits MICB ectodomain shedding through the suppression of ADAM15.

Cytoskeletal confinement of CX3CL1 limits its susceptibility to proteolytic cleavage by ADAM10

PubMed Central

Wong, Harikesh S.; Jaumouillé, Valentin; Heit, Bryan; Doodnauth, Sasha A.; Patel, Sajedabanu; Huang, Yi-Wei; Grinstein, Sergio; Robinson, Lisa A.

2014-01-01

CX3CL1 is a unique chemokine that acts both as a transmembrane endothelial adhesion molecule and, upon proteolytic cleavage, a soluble chemoattractant for circulating leukocytes. The constitutive release of soluble CX3CL1 requires the interaction of its transmembrane species with the integral membrane metalloprotease ADAM10, yet the mechanisms governing this process remain elusive. Using single-particle tracking and subdiffraction imaging, we studied how ADAM10 interacts with CX3CL1. We observed that the majority of cell surface CX3CL1 diffused within restricted confinement regions structured by the cortical actin cytoskeleton. These confinement regions sequestered CX3CL1 from ADAM10, precluding their association. Disruption of the actin cytoskeleton reduced CX3CL1 confinement and increased CX3CL1–ADAM10 interactions, promoting the release of soluble chemokine. Our results demonstrate a novel role for the cytoskeleton in limiting membrane protein proteolysis, thereby regulating both cell surface levels and the release of soluble ligand. PMID:25253723

GLASS VISCOSITY AS A FUNCTION OF TEMPERATURE AND COMPOSITION: A MODEL BASED ON ADAM-GIBBS EQUATION

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

Hrma, Pavel R.

2008-07-01

Within the temperature range and composition region of processing and product forming, the viscosity of commercial and waste glasses spans over 12 orders of magnitude. This paper shows that a generalized Adam-Gibbs relationship reasonably approximates the real behavior of glasses with four temperature-independent parameters of which two are linear functions of the composition vector. The equation is subjected to two constraints, one requiring that the viscosity-temperature relationship approaches the Arrhenius function at high temperatures with a composition-independent pre-exponential factor and the other that the viscosity value is independent of composition at the glass-transition temperature. Several sets of constant coefficients weremore » obtained by fitting the generalized Adam-Gibbs equation to data of two glass families: float glass and Hanford waste glass. Other equations (the Vogel-Fulcher-Tammann equation, original and modified, the Avramov equation, and the Douglass-Doremus equation) were fitted to float glass data series and compared with the Adam-Gibbs equation, showing that Adam-Gibbs glass appears an excellent approximation of real glasses even as compared with other candidate constitutive relations.« less

EGF promotes the shedding of soluble E-cadherin in an ADAM10-dependent manner in prostate epithelial cells.

PubMed

Grabowska, Magdalena M; Sandhu, Brindar; Day, Mark L

2012-02-01

During the progression of prostate cancer, the epithelial adhesion molecule E-cadherin is cleaved from the cell surface by ADAM15 proteolytic processing, generating an extracellular 80kDa fragment referred to as soluble E-cadherin (sE-cad). Contrary to observations in cancer, the generation of sE-cad appears to correlate with ADAM10 activity in benign prostatic epithelium. The ADAM10-specific inhibitor INCB8765 and the ADAM10 prodomain inhibit the generation of sE-cad, as well as downstream signaling and cell proliferation. Addition of EGF or amphiregulin (AREG) to these untransformed cell lines increases the amount of sE-cad shed into the conditioned media, as well as sE-cad bound to EGFR. EGF-associated shedding appears to be mediated by ADAM10 as shRNA knockdown of ADAM10 results in reduced shedding of sE-cad. To examine the physiologic role of sE-cad on benign prostatic epithelium, we treated BPH-1 and large T immortalized prostate epithelial cells (PrEC) with an sE-cad chimera comprised of the human Fc domain of IgG(1), fused to the extracellular domains of E-cadherin (Fc-Ecad). The treatment of untransformed prostate epithelial cells with Fc-Ecad resulted in phosphorylation of EGFR and downstream signaling through ERK and increased cell proliferation. Pre-treating BPH-1 and PrEC cells with cetuximab, a therapeutic monoclonal antibody against EGFR, decreased the ability of Fc-Ecad to induce EGFR phosphorylation, downstream signaling, and proliferation. These data suggest that ADAM10-generated sE-cad may have a role in EGFR signaling independent of traditional EGFR ligands. Copyright © 2011 Elsevier Inc. All rights reserved.

Ectodomain shedding of Limbic System-Associated Membrane Protein (LSAMP) by ADAM Metallopeptidases promotes neurite outgrowth in DRG neurons.

PubMed

Sanz, Ricardo L; Ferraro, Gino B; Girouard, Marie-Pier; Fournier, Alyson E

2017-08-11

IgLONs are members of the immunoglobulin superfamily of cell adhesion proteins implicated in the process of neuronal outgrowth, cell adhesion and subdomain target recognition. IgLONs form homophilic and heterophilic complexes on the cell surface that repress or promote growth depending on the neuronal population, the developmental stage and surface repertoire of IgLON family members. In the present study, we identified a metalloproteinase-dependent mechanism necessary to promote growth in embryonic dorsal root ganglion cells (DRGs). Treatment of embryonic DRG neurons with pan-metalloproteinase inhibitors, tissue inhibitor of metalloproteinase-3, or an inhibitor of ADAM Metallopeptidase Domain 10 (ADAM10) reduces outgrowth from DRG neurons indicating that metalloproteinase activity is important for outgrowth. The IgLON family members Neurotrimin (NTM) and Limbic System-Associated Membrane Protein (LSAMP) were identified as ADAM10 substrates that are shed from the cell surface of DRG neurons. Overexpression of LSAMP and NTM suppresses outgrowth from DRG neurons. Furthermore, LSAMP loss of function decreases the outgrowth sensitivity to an ADAM10 inhibitor. Together our findings support a role for ADAM-dependent shedding of cell surface LSAMP in promoting outgrowth from DRG neurons.

SU-F-T-430: Validation of IBEAM Evo Couch Top for Different Relative Electron Density (RED) Combination During Photon Beam Dose Calculation in Monaco− Treatment Planning System

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

Manigandan, D; Kumar, M; Mohandas, P

Purpose: Validation of iBEAM™ evo couch-top for different relative electron density (RED) combination during photon beam dose calculation in Monaco− TPS. Methods: The iBEAM™ evo couch-top has two layers:outer carbon fiber (CF) and inner foam core (FC). To study the beam intensity attenuation of couch-top, measured doses were compared with doses calculated for different REDs. Measurements were performed in solid water phantom with PTW-0.125cc ion-chamber positioned at center of the phantom with 5.3cm thickness slabs placed above and below the chamber. Similarly, in TPS, iBEAM™ evo couch-top was simulated and doses were calculated for different RED combinations (0.2CF-0.2FC, 0.4CF-0.2FC, 0.6CF-0.2FC,more » 0.8CF-0.2FC, and 1.0CF-0.2FC) by using Monte Carlo dose calculation algorithm in Monaco TPS (V5.1). Doses were measured for every 10 degree gantry angle separation, 10×10cm{sup 2} field size and 6MV photons. Then, attenuation is defined as the ratio of output at posterior gantry angle to output of its opposed anterior gantry angle (e.g.225°/45°). output fluctuation with different gantry angle was within ±0.21%. To confirm above results, dose-planes were measured for five pelvic VMAT plans (360°arc) in PTW two-dimensional array and compared with different calculated dose-planes of above-mentioned couch REDs. Gamma pass rates<1.00) were analyzed for 3%/2mm criteria. Results: Measured and calculated attenuation was in good agreement for the RED combination of 0.2CF-0.2FC and difference was within ±0.515%. However, other density combination showed difference of ±0.9841%, ±1.667%, ±2.9241% and ±2.8832% for 0.4CF-0.2FC, 0.6CF-0.2FC, 0.8CF-0.2FC, and 1.0CF-0.2FC, respectively. Maximum couch-top attenuation was observed at 110°–120° and 240°–250° and decreases linearly as the gantry angle approaches 180°. Moreover, gamma pass rate confirmed the above results and showed maximum pass rate of 96.23% for 0.2CF-0.2FC, whereas others were 95.72%, 95

ADAM binding protein Eve-1 is required for ectodomain shedding of epidermal growth factor receptor ligands.

PubMed

Tanaka, Motonari; Nanba, Daisuke; Mori, Seiji; Shiba, Fumio; Ishiguro, Hiroshi; Yoshino, Koichiro; Matsuura, Nariaki; Higashiyama, Shigeki

2004-10-01

A disintegrin and metalloproteases (ADAMs) are implicated in the ectodomain shedding of epidermal growth factor receptor (EGFR) ligands in EGFR transactivation. However, the activation mechanisms of ADAMs remain elusive. To analyze the regulatory mechanisms of ADAM activation, we performed yeast two-hybrid screening using the cytoplasmic domain of ADAM12 as bait, and identified a protein that we designated Eve-1. Two cDNAs were cloned and characterized. They encode alternatively spliced isoforms of Eve-1, called Eve-1a and Eve-1b, that have four and five tandem Src homology 3 (SH3) domains in the carboxyl-terminal region, respectively, and seven proline-rich SH3 domain binding motifs in the amino-terminal region. The short forms of Eve-1, Eve-1c and Eve-1d, translated at Met-371 are human counterparts of mouse Sh3d19. Northern blot analysis demonstrated that Eve-1 is abundantly expressed in skeletal muscle and heart. Western blot analysis revealed the dominant production of Eve-1c in human cancer cell lines. Knockdown of Eve-1 by small interfering RNA in HT1080 cells reduced the shedding of proHB-EGF induced by angiotensin II and 12-O-tetradecanoylphorbol-13-acetate, as well as the shedding of pro-transforming growth factor-alpha, promphiregulin, and proepiregulin by 12-O-tetradecanoylphorbol-13-acetate, suggesting that Eve-1 plays a role in positively regulating the activity of ADAMs in the signaling of EGFR-ligand shedding.

Trestle #1, deck from above. Note Adams Ranch and Thiokol ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Trestle #1, deck from above. Note Adams Ranch and Thiokol (upper right). View to northeast - Promontory Route Railroad Trestles, S.P. Trestle 779.91, One mile southwest of junction of State Highway 83 and Blue Creek, Corinne, Box Elder County, UT

An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin.

PubMed

Lo Sardo, Valentina; Zuccato, Chiara; Gaudenzi, Germano; Vitali, Barbara; Ramos, Catarina; Tartari, Marzia; Myre, Michael A; Walker, James A; Pistocchi, Anna; Conti, Luciano; Valenza, Marta; Drung, Binia; Schmidt, Boris; Gusella, James; Zeitlin, Scott; Cotelli, Franco; Cattaneo, Elena

2012-05-01

The Huntington's disease gene product, huntingtin, is indispensable for neural tube formation, but its role is obscure. We studied neurulation in htt-null embryonic stem cells and htt-morpholino zebrafish embryos and found a previously unknown, evolutionarily recent function for this ancient protein. We found that htt was essential for homotypic interactions between neuroepithelial cells; it permitted neurulation and rosette formation by regulating metalloprotease ADAM10 activity and Ncadherin cleavage. This function was embedded in the N terminus of htt and was phenocopied by treatment of htt knockdown zebrafish with an ADAM10 inhibitor. Notably, in htt-null cells, reversion of the rosetteless phenotype occurred only with expression of evolutionarily recent htt heterologues from deuterostome organisms. Conversely, all of the heterologues that we tested, including htt from Drosophila melanogaster and Dictyostelium discoideum, exhibited anti-apoptotic activity. Thus, anti-apoptosis may have been one of htt’s ancestral function(s), but, in deuterostomes, htt evolved to acquire a unique regulatory activity for controlling neural adhesion via ADAM10-Ncadherin, with implications for brain evolution and development.

Analysis of Survivor Benefit Plan - Acceptance and Comparison with Private Sector

DTIC Science & Technology

1989-01-01

I COPY AIU WAR COLLEGE ,.SEARCH REPORT ,YSIS OF SURVIVOR BENEFIT PLAN-__CCEPTANCE ’-U AND COMPARISON WITH PRIVATE SECTOR LIEUENNT COLONEL JOHN R...AAA AIR WAR COLLEGE AIR UNIVERSITY ANALYSIS OF SURVIVOR BENEFIT PLAN--ACCEPTANCE AND COMPARISON WITH PRIVATE SECTOR by John R. Adams Lieutenant...Survivor Benefit Plan (SBP)--Acceptance and Comparison With Private Sector . AUTHORS: John R. Adams, Lieutenant Colonel, USAF; Daniel 3. Kohn

Toward Understanding Trust: A Response to Adams and Miskell

ERIC Educational Resources Information Center

Romero, Lisa S.; Mitchell, Douglas E.

2018-01-01

Purpose: Trust is a key component of successful schools. Although scholars widely agree that trust is multifaceted, there is less agreement about the number and nature of these factors. In the October 2016 issue of "Educational Administration Quarterly," C. M. Adams and Miskell (see EJ1112413) argued that their Teacher Trust of District…

The Retention of Minorities in Colorado Public Institutions of Higher Education: Fort Lewis and Adams State Colleges.

ERIC Educational Resources Information Center

Colorado State Advisory Committee to the U.S. Commission on Civil Rights, Denver.

Based on background research, interviews, and a public hearing held in Durango (Colorado) in March 1993, this report addresses issues regarding minority retention at Fort Lewis College in Durango and, to a lesser extent, at Adams State College in Alamosa. Due to limited information about Adams State College, none of the recommendations address…

Adam M. Reid: APA/APAGS Award for Distinguished Graduate Student in Professional Psychology.

PubMed

2015-11-01

The APA/APAGS Award for Distinguished Graduate Student in Professional Psychology is awarded on an annual basis by the APA Board of Professional Affairs (BPA) and the American Psychological Association of Graduate Students (APAGS) to a graduate student who has demonstrated outstanding practice and application of psychology. One of the 2015 award winners is Adam M. Reid, who received this award "for his community service, in which he has integrated the highest standards of professional psychological clinical practice and science." Adam's award citation, biography, and a selected bibliography are presented here. (c) 2015 APA, all rights reserved).

Empathy's purity, sympathy's complexities; De Waal, Darwin and Adam Smith.

PubMed

van der Weele, Cor

2011-07-01

Frans de Waal's view that empathy is at the basis of morality directly seems to build on Darwin, who considered sympathy as the crucial instinct. Yet when we look closer, their understanding of the central social instinct differs considerably. De Waal sees our deeply ingrained tendency to sympathize (or rather: empathize) with others as the good side of our morally dualistic nature. For Darwin, sympathizing was not the whole story of the "workings of sympathy"; the (selfish) need to receive sympathy played just as central a role in the complex roads from sympathy to morality. Darwin's understanding of sympathy stems from Adam Smith, who argued that the presence of morally impure motives should not be a reason for cynicism about morality. I suggest that De Waal's approach could benefit from a more thorough alignment with the analysis of the workings of sympathy in the work of Darwin and Adam Smith.

ADAM: analysis of discrete models of biological systems using computer algebra.

PubMed

Hinkelmann, Franziska; Brandon, Madison; Guang, Bonny; McNeill, Rustin; Blekherman, Grigoriy; Veliz-Cuba, Alan; Laubenbacher, Reinhard

2011-07-20

Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web

ADAM: Analysis of Discrete Models of Biological Systems Using Computer Algebra

PubMed Central

2011-01-01

Background Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed. Results We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second. Conclusions Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on

Conserved binding of GCAC motifs by MEC-8, couch potato, and the RBPMS protein family

PubMed Central

Soufari, Heddy

2017-01-01

Precise regulation of mRNA processing, translation, localization, and stability relies on specific interactions with RNA-binding proteins whose biological function and target preference are dictated by their preferred RNA motifs. The RBPMS family of RNA-binding proteins is defined by a conserved RNA recognition motif (RRM) domain found in metazoan RBPMS/Hermes and RBPMS2, Drosophila couch potato, and MEC-8 from Caenorhabditis elegans. In order to determine the parameters of RNA sequence recognition by the RBPMS family, we have first used the N-terminal domain from MEC-8 in binding assays and have demonstrated a preference for two GCAC motifs optimally separated by >6 nucleotides (nt). We have also determined the crystal structure of the dimeric N-terminal RRM domain from MEC-8 in the unbound form, and in complex with an oligonucleotide harboring two copies of the optimal GCAC motif. The atomic details reveal the molecular network that provides specificity to all four bases in the motif, including multiple hydrogen bonds to the initial guanine. Further studies with human RBPMS, as well as Drosophila couch potato, confirm a general preference for this double GCAC motif by other members of the protein family and the presence of this motif in known targets. PMID:28003515

Constant Aims, Changing Technologies: Photostat and Microfilm Publishing at the Massachusetts Historical Society.

ERIC Educational Resources Information Center

Wright, Conrad Edick

1995-01-01

Discusses the Massachusetts Historical Society's various photostat and microfilming projects and describes how they grew out of the philosophy of the society's founder, the Reverend Jeremy Belknap. Topics include the preservation of the papers of presidents John Adams and John Quincy Adams, and collaboration with other repositories. (Author/JKP)

Intellectual Couch Potato?

NASA Astrophysics Data System (ADS)

Mason, Diana S.

2002-08-01

What does this say for where we've been and where we're going? The Information Age has brought us closer together. I know more about more people and events than I have ever known. I see this as a good thing. It is easy to keep in touch with friends. It is easy to buy and sell over the Internet, to seek answers on various questions, to gather facts, to improve your mind, etc. However, Joshua Benton of The Dallas Morning News1 cites a U.S. Department of Education report as stating, "Too many teachers make it into American classrooms without knowing the material they're teaching...". This concerns me greatly. With all the advantages afforded to us in an affluent society, then how/why can this be true? Other things in the report mentioned by Benton include (1) criticism of the states for setting low standards for new teachers; (2) colleges of education spending too much time on classroom management and teaching techniques and not enough on subject area content in mathematics, literature, and science; and (3) a call to the states to make it easier for professionals to switch careers into teaching through alternative programs. On the other side of the debate, how can 3 4 months of training in an alternative program bring successful teaching practices into the classroom? Yes, we need more teachers, especially in mathematics and science. Getting the content to these prospective teachers is not a problem. There is the Web, there are many online courses available (more on the way) both in subject areas and pedagogy, and the number of conferences and workshops offered abound. The following pages go into great depth regarding all the wonderful talks, workshops, and entertaining events that you can attend at the Fall 2002, ACS National Meeting, August 18 20. However, you've got to get off the couch and attend! The High School Program is Monday, August 19, from 8:30 until 3:00 at the Park Plaza Hotel. Preregistration is $30. Mahatma Gandhi said, "Live as if you were to die

Poor interoperability of the Adams-Harbertson method for analysis of anthocyanins: comparison with AOAC pH differential method.

PubMed

Brooks, Larry M; Kuhlman, Benjamin J; McKesson, Doug W; McCloskey, Leo

2013-01-01

The poor interoperability of anthocyanin glycosides measurements by two pH differential methods is documented. Adams-Harbertson, which was proposed for commercial winemaking, was compared to AOAC Official Method 2005.02 for wine. California bottled wines (Pinot Noir, Merlot, and Cabernet Sauvignon) were assayed in a collaborative study (n=105), which found mean precision of Adams-Harbertson winery versus reference measurements to be 77 +/- 20%. Maximum error is expected to be 48% for Pinot Noir, 42% for Merlot, and 34% for Cabernet Sauvignon from reproducibility RSD. Range of measurements was actually 30 to 91% for Pinot Noir. An interoperability study (n=30) found Adams-Harbertson produces measurements that are nominally 150% of the AOAC pH differential method. Large analytical chemistry differences are: AOAC method uses Beer-Lambert equation and measures absorbance at pH 1.0 and 4.5, proposed a priori by Flueki and Francis; whereas Adams-Harbertson uses "universal" standard curve and measures absorbance ad hoc at pH 1.8 and 4.9 to reduce the effects of so-called co-pigmentation. Errors relative to AOAC are produced by Adams-Harbertson standard curve over Beer-Lambert and pH 1.8 over pH 1.0. The study recommends using AOAC Official Method 2005.02 for analysis of wine anthocyanin glycosides.

Consumer leather exposure: an unrecognized cause of cobalt sensitization.

PubMed

Thyssen, Jacob P; Johansen, Jeanne D; Jellesen, Morten S; Møller, Per; Sloth, Jens J; Zachariae, Claus; Menné, Torkil

2013-11-01

A patient who had suffered from persistent generalized dermatitis for 7 years was diagnosed with cobalt sensitization, and his leather couch was suspected as the culprit, owing to the clinical presentation mimicking allergic chromium dermatitis resulting from leather furniture exposure. The cobalt spot test, X-ray fluorescence, inductively coupled plasma mass spectrometry and scanning electron microscopy were used to determine cobalt content and release from the leather couch that caused the dermatitis and from 14 randomly collected samples of furniture leather. The sample from the patient's leather couch, but none of the 14 random leather samples, released cobalt in high concentrations. Dermatitis cleared when the patient stopped using his couch. Cobalt is used in the so-called pre-metallized dyeing of leather products. Repeated studies have found high levels of cobalt sensitization, but not nickel sensitization, in patients with foot dermatitis. We raise the possibility that cobalt may be widely released from leather items, and advise dermatologists to consider this in patients with positive cobalt patch test reactions. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Decks of Trestle #2 (foreground) and Trestle #1. Note Adams ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

Decks of Trestle #2 (foreground) and Trestle #1. Note Adams Ranch and Thiokol (upper right). View to northeast - Promontory Route Railroad Trestles, S.P. Trestle 779.91, One mile southwest of junction of State Highway 83 and Blue Creek, Corinne, Box Elder County, UT

Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain-8 expression and cranial neural crest cell migration

PubMed Central

Cousin, Hélène; Abbruzzese, Genevieve; Kerdavid, Erin; Gaultier, Alban; Alfandari, Dominique

2011-01-01

Summary ADAMs are transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. The cytoplasmic domain of ADAMs can regulate the proteolytic activity by controlling the subcellular localization and/or the activation of the protease domain. Here we show that the cytoplasmic domain of ADAM13 is cleaved and translocates into the nucleus. Preventing this translocation renders the protein incapable of promoting cranial neural crest (CNC) cell migration in vivo, without affecting its proteolytic activity. In addition, the cytoplasmic domain of ADAM13 regulates the expression of multiple genes in CNC, including the protease Calpain8-a. Restoring the expression of Calpain8-a is sufficient to rescue CNC migration in the absence of the ADAM13 cytoplasmic domain. This study shows that the cytoplasmic domain of ADAM metalloproteases can perform essential functions in the nucleus of cells and may contribute substantially to the overall function of the protein. PMID:21316592

Sensitization of cerebral tissue in nude mice with photodynamic therapy induces ADAM17/TACE and promotes glioma cell invasion

PubMed Central

Zheng, Xuguang; Jiang, Feng; Katakowski, Mark; Zhang, Xuepeng; Jiang, Hao; Zhang, Zheng Gang; Chopp, Michael

2008-01-01

In the present study, we tested the hypothesis that a mild cerebral tissue injury promotes subsequent glioma invasion via activation of the ADAM17-EGFR-PI3K-Akt pathway. Mild injury was induced by Photodynamic therapy (PDT), which employs tissue-penetrating laser light exposure following systemic administration of a tumor-localizing photosensitizer. Athymic nude mice were treated with sublethal PDT (80J/cm2 with 2mg/kg Photofrin). Hypoxic stress and ADAM17-EGFR-PI3K-Akt were measured using Western blot and immunostaining. Additional groups with/without pro-sublethal PDT were subsequently implanted with U87 glioma tumor cell. Tumor invasion and ADAM17-EGFR-PI3K-Akt pathway in tumor area were measured. After a sublethal dose of PDT, HIF-1α expression was increased by a factor of three in PDT-treated normal brain tissue compared to contralateral control brain tissue. PDT-treated brain tissue exhibited a significant increase in ADAM17, p-EGFR, p-Akt expression compared to non-treated tissue. ADAM17 positive area significantly increased from 1.78% to 10.89%. The percentage of p-EGFR and p-Akt positive cells significantly increased from 9.50% and 14.50% to 21.31% and 32.29%,respectively, PDT treatment significantly increased subsequent implanted U87 glioma cell invasion by 3.68-fold and increased ADAM17, EGFR, p-EGFR, Akt, p-Akt expression by 178%, 43.9%,152.7%, 89.6%,and 164.2%, respectively, compared to control group. Our data showed that a sublethal sensitization of cerebral tissue with PDT significantly increased U87 cell invasion in nude mice, and that glioma cell invasion is highly correlated with activation of the ADAM17-EGFR-PI3K-Akt pathway (r=0.928, 0.775, 0.870, 0.872, and 0.883, respectively), most likely via HIF-1α. PMID:18358600

'The chearful haunts': John Armstrong (1709-1779), physician, poet, satirist and leveller of medical knowledge.

PubMed

Bryan, Charles S; Scott, Patrick

2015-11-01

John Armstrong, the first honours graduate of the University of Edinburgh School of Medicine, was famous in his day for a lengthy didactic poem entitled The Art of Preserving Health (1744). He is now obscure except to scholars specializing in the 18th century and, when discussed at all, often dismissed as a failed physician who wrote mediocre poetry in a quest for money and fame. A new exegesis by Adam Budd exhumes Armstrong as an original voice who offered timely and reassuring advice to Britons as they braced for another epidemic of plague; who depicted illness through the lens of a vulnerable and sympathetic physician, and who was perhaps above all else a leveller of medical knowledge. Elaborating on Budd's thesis, it would seem that Armstrong, a complicated man, has frequently been misread and was in some ways ahead of his time. © The Author(s) 2014.

Problems with McAdams and Pals's (2006) Proposal of a Framework for an Integrative Theory of Personality

ERIC Educational Resources Information Center

Epstein, Seymour

2007-01-01

Comments on the original article "A New Big Five: Fundamental Principles for an Integrative Science of Personality," by Dan P. McAdams and Jennifer L. Pals (see record 2006-03947-002). Here, the current author begins with a critique of McAdams and Pals's (April 2006) five principles for a framework for an integrative theory of personality. The…

An ADAM12 and FAK positive feedback loop amplifies the interaction signal of tumor cells with extracellular matrix to promote esophageal cancer metastasis.

PubMed

Luo, Man-Li; Zhou, Zhuan; Sun, Lichao; Yu, Long; Sun, Lixin; Liu, Jun; Yang, Zhihua; Ran, Yuliang; Yao, Yandan; Hu, Hai

2018-05-28

Esophageal squamous cell carcinomas (ESCCs) have a poor prognosis mostly due to early metastasis. To explore the early event of metastasis in ESCC, we established an in vitro selection model to mimic the interaction of tumor cells with extracellular matrix, through which a sub-line of ESCC cells with high invasive ability was generated. By comparing the gene expression profile of the highly invasive sub-line to that of the parental cells, ADAM12-L was identified as a candidate gene promoting ESCC cell invasion. Immunohistochemistry revealed that the ADAM12-L was overexpressed in human ESCC tissues, especially at cancer invasive edge, and ADAM12-L overexpression tightly correlated with increased metastasis and poor outcome of ESCC patients. Indeed, ADAM12-L knockdown reduced the invasion and metastasis of ESCC cells both in vitro and in vivo. Furthermore, we demonstrated that ADAM12-L participated in focal adhesion turnover and promoted the activation of focal adhesion kinase (FAK), which in turn increased ADAM12-L transcription through FAK/JNK/c-Jun axis. Therefore, a loop initiated from the cancer cell upon the engagement with extracellular matrix through FAK and c-Jun to enhance ADAM12-L expression is established, leading to the positive feedback of further FAK activation and prompting metastasis. Our study indicates that overexpression of ADAM12-L can serve as a precision marker to determine the activation of this loop. Targeting ADAM12-L to disrupt this positive feedback loop represents a promising strategy to treat the metastasis of esophageal cancers. Copyright © 2018 Elsevier B.V. All rights reserved.

Branding campaign: Emory Healthcare, Adam Arkin, promote hospital as destination.

PubMed

2006-01-01

Popular actor Adam Arkin (Chicago Hope, Commander in Chief) teamed up with Emory Healthcare-an 800-bed, three-hospital health system located in Atlanta-to promote the hospital's cardiology and oncology services, and to brand the facility as a destination hospital that's free of stress and hassle.

A Chimpanzee, 'Ham,' in the Biopack Couch for the MR-2 Flight

NASA Technical Reports Server (NTRS)

1961-01-01

A three-year-old chimpanzee, named Ham, in the biopack couch for the MR-2 suborbital test flight. On January 31, 1961, a Mercury-Redstone launch from Cape Canaveral carried the chimpanzee 'Ham' over 640 kilometers down range in an arching trajectory that reached a peak of 254 kilometers above the Earth. The mission was successful and Ham performed his lever-pulling task well in response to the flashing light. NASA used chimpanzees and other primates to test the Mercury Capsule before launching the first American astronaut Alan Shepard in May 1961. The successful flight and recovery confirmed the soundness of the Mercury-Redstone systems.

Endothelial deletion of ADAM17 in mice results in defective remodeling of the semilunar valves and cardiac dysfunction in adults.

PubMed

Wilson, Carole L; Gough, Peter J; Chang, Cindy A; Chan, Christina K; Frey, Jeremy M; Liu, Yonggang; Braun, Kathleen R; Chin, Michael T; Wight, Thomas N; Raines, Elaine W

2013-01-01

Global inactivation of the metalloproteinase ADAM17 during mouse development results in perinatal lethality and abnormalities of the heart, including late embryonic cardiomegaly and thickened semilunar and atrioventricular valves. These defects have been attributed in part to a lack of ADAM17-mediated processing of HB-EGF, as absence of soluble HB-EGF results in similar phenotypes. Because valvular mesenchymal cells are largely derived from cardiac endothelial cells, we generated mice with a floxed Adam17 allele and crossed these animals with Tie2-Cre transgenics to focus on the role of endothelial ADAM17 in valvulogenesis. We find that although hearts from late-stage embryos with ablation of endothelial ADAM17 appear normal, an increase in valve size and cell number is evident, but only in the semilunar cusps. Unlike Hbegf(-/-) valves, ADAM17-null semilunar valves do not differ from controls in acute cell proliferation at embryonic day 14.5 (E14.5), suggesting compensatory processing of HB-EGF. However, levels of the proteoglycan versican are significantly reduced in mutant hearts early in valve remodeling (E12.5). After birth, aortic valve cusps from mutants are not only hyperplastic but also show expansion of the glycosaminoglycan-rich component, with the majority of adults exhibiting aberrant compartmentalization of versican and increased deposition of collagen. The inability of mutant outflow valve precursors to transition into fully mature cusps is associated with decreased postnatal viability, progressive cardiomegaly, and systolic dysfunction. Together, our data indicate that ADAM17 is required in valvular endothelial cells for regulating cell content as well as extracellular matrix composition and organization in semilunar valve remodeling and homeostasis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Congressional Oversight: The New Mortal Enemy of Military Justice

DTIC Science & Technology

2000-04-01

Ansell , supra note 18, at 3-4. In 1776, after drafting the new Articles of War, John Adams supported his nearly verbatim adoption of the British Articles...martial process by requiring reporting of all court-martial sentences to, and approval by, the Commander-in-Chief, the 18 See S.T. Ansell , Military...supra note 30, at 21. 32 See THE WORKS OF JOHN ADAMS (Charles Francis Adams , ed., 1850-1856), quoted in LINDLEY, supra note 15, at 42-43, n. 100. 33

Application of the ADAMS program to deployable space truss structures

NASA Technical Reports Server (NTRS)

Calleson, R. E.

1985-01-01

The need for a computer program to perform kinematic and dynamic analyses of large truss structures while deploying from a packaged configuration in space led to the evaluation of several existing programs. ADAMS (automatic dynamic analysis of mechanical systems), a generalized program from performing the dynamic simulation of mechanical systems undergoing large displacements, is applied to two concepts of deployable space antenna units. One concept is a one cube folding unit of Martin Marietta's Box Truss Antenna and the other is a tetrahedral truss unit of a Tetrahedral Truss Antenna. Adequate evaluation of dynamic forces during member latch-up into the deployed configuration is not yet available from the present version of ADAMS since it is limited to the assembly of rigid bodies. Included is a method for estimating the maximum bending stress in a surface member at latch-up. Results include member displacement and velocity responses during extension and an example of member bending stresses at latch-up.

3. Aerial view southeast, State Route 92 bottom left, Adams ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. Aerial view southeast, State Route 92 bottom left, Adams Dam Road center, Brandywine Creek State Park and J. Chandler Farm in center left, duck pond bottom right and reservoir bottom left. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

An Informal Report on Collegiate Successes with "The Adams Chronicles."

ERIC Educational Resources Information Center

Goldsberry, Gary G.

In the spring of 1976, "The Adams Chronicles", a bicentennial television course developed by Coast Community College District and the University of California at San Diego, was distributed to colleges nationwide at no charge with the understanding that each college would return information regarding promotion, enrollment, and form of…

Cost-effectiveness of Project ADAM: a project to prevent sudden cardiac death in high school students.

PubMed

Berger, S; Whitstone, B N; Frisbee, S J; Miner, J T; Dhala, A; Pirrallo, R G; Utech, L M; Sachdeva, R C

2004-01-01

Public access defibrillation (PAD) in the adult population is thought to be both efficacious and cost-effective. Similar programs aimed at children and adolescents have not been evaluated for their cost-effectiveness. This study evaluates the potential cost-effectiveness of implementing Project ADAM, a program targeting children and adolescents in high schools in the Milwaukee Public School System. Project ADAM provides education about cardiopulmonary resuscitation (CPR) and the warning signs of sudden cardiac death (SCD) and training in the use and placement of automated external defibrillators (AEDs) in high schools. We developed decision analysis models to evaluate the cost-effectiveness of the decision to implement Project ADAM in public high schools in Milwaukee. We examined clinical model and public policy applications. Data on costs included estimates of hospital-based charges derived from a pediatric medical center where a series of patients were treated for SCD, educational programming, and the direct costs of one AED and training for 15 personnel per school. We performed sensitivity analyses to assess the variation in outputs with respect to changes to input data. The main outcome measures were Life years saved and incremental cost-effectiveness ratios. At an arbitrary societal willingness to pay $100,000 per life year saved, the policy to implement Project ADAM in schools is a cost-effective strategy at a threshold of approximately 5 patients over 5 years for the clinical model and approximately 8 patients over 5 years for the public policy model. Implementation of Project ADAM in high schools in the United States is potentially associated with an incremental cost-effectiveness ratio that is favorable.

Deficiency of a Disintegrin and Metalloproteinase 10 (ADAM10) on dendritic cells prevents the development of type 2 immunity and IgE production

USDA-ARS?s Scientific Manuscript database

Mice in which dendritic cells (DCs)lack ADAM10 (ADAM10DC-/-) were found to have a dramatic decrease in TH2 immunity and IgE production, as measured by both lung inflammation to house dust mite (HDM) and active systemic anaphylaxis models (ASA). With HDM, the ADAM10DC-/- had significantly less airway...

SU-E-J-46: Evaluation of the Accuracy of a Six Degree of Freedom Robotic Couch Using ConeBeam CT Images of the Isocal Phantom

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

Zhang, Q; Driewer, J; Wang, S

Purpose The accuracy of Varian PerfectPitch six degree of freedom (DOF) robotic couch was examined using Varian Isocal phantom and cone-beam CT (CBCT) system. Methods CBCT images of the Isocal phantom were taken at different pitch and roll angles. The pitch and roll angles were varied from 357 to 3 degrees in one degree increments by input from service console, generating a total of 49 combinations with couch angle (yaw) zero. The center positions of the 16 tungsten carbide BBs contained in the Isocal were determined with in-house image processing software. Expected BBs positions at different rotation angles were determinedmore » mathematically by applying a combined translation/rotation operator to BB positions at zero pitch and roll values. A least square method was used to minimize the difference between the expected BB positions and their measured positions. In this way rotation angles were obtained and compared with input values from the console. Results A total of 49 CBCT images with voxel sizes 0.51 mm × 0.51 mm × 1 mm were used in analysis. Among the 49 calculations, the maximum rotation angle differences were 0.1 degree, 0.15 degree, and 0.09 degree, for pitch, roll, and couch rotation, respectively. The mean ± standard-deviation angle differences were 0.028±0.001 degree, −0.043±0.003 degree, and −0.009±0.001 degree, for pitch, roll, and couch rotation, respectively. The maximum isocenter shifts were 0.3 mm, 0.5 mm, 0.4 mm in x, y, z direction respectively following IEC6127 convention. The mean isocenter shifts were 0.07±0.02 mm, −0.05±0.06 mm, and −0.12±0.02 mm in x, y and z directions. Conclusion The accuracy of the Varian PerfectPitch six DOF couch was studied with CBCTs of the Isocal phantom. The rotational errors were less than 0.15 degree and isocenter shifts were less than 0.5 mm in any direction. This accuracy is sufficient for stereotactic radiotherapy clinical applications.« less

Eating at the table, on the couch and in bed: An exploration of different locus of commensality in the discourses of Brazilian working mothers.

PubMed

Scagliusi, Fernanda Baeza; da Rocha Pereira, Patrícia; Unsain, Ramiro Fernandez; de Morais Sato, Priscila

2016-08-01

Commensality is a remarkable human act, and tends to be more present among families. Nevertheless, it is possible that eating at the table is being taking for granted when one refers to family meals. Thus, this paper aims to analyze working mothers' discourses about family meals eaten at the table, on the couch and in the bed/bedroom. The participants were thirty mothers working in public universities of the Brazilian region called Baixada Santista. A qualitative study was conducted, using semi-structured interviews. In the transcripts the words "table", "couch", "bed", "bedroom" were located and the excerpts containing them were extracted and analyzed according to a classical and exploratory content analysis. The table is a significant component of meals that unite the family. While for some the meal at the table is an enjoyable moment, it is a stiff moment for others. Indeed, manners and the notion of hierarchy appeared only for the table. Regarding the couch, it seems that the family chose to eat there, because it is a more casual and relaxed setting. Eating in the bed was related to precarity, intimacy and casualness. In the three settings, watching television was a common practice, replacing or being added to talking. Commensality is such an important practice that appears in different settings and even in precarity contexts. The table emerged as the maximal cornerstone of commensality. However, when it was not present, new arrangements were made. Especially the couch seems to be a new commensal space, less formal and rigid, but able to allow some collective conviviality. Eating in the bed was a less common practice. Finally, the significant role that television assumed in meals is highlighted. Copyright © 2016 Elsevier Ltd. All rights reserved.

AVS as a GUI for ADAM

NASA Astrophysics Data System (ADS)

Terrett, D. L.

The basis of this report is 2 days spent with an AVS expert from DEC's CERN project office attempting to convert an ADAM application into an AVS module. The experiment was successful in that we succeeded in running a KAPPA application (ADD) as a module in an AVS network without modifying the applications program code in any way. We took many short cuts and it became clear that doing the job properly would be a major exercise, but we learned enough to know that the job is feasible and gained a clear idea of what the final system would look like and what it would be capable of.

"Adam of the Road" by Elizabeth Janet Gray. Literature Unit.

ERIC Educational Resources Information Center

Robbins, Mari Lu

Intended as an aid to classroom teachers, this 48-page handbook presents a literature unit based on the children's book, "Adam of the Road" by Elizabeth Janet Gray. It begins with sample lesson plans, pre-reading activities, author information, a book summary, and vocabulary lists and suggested vocabulary activities. Next, chapters of…

5. Aerial view west, Adams Dam Road bottom center, State ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. Aerial view west, Adams Dam Road bottom center, State Route 100 center, duck pond and reservoir center, State Route 100 center right, State Route 92 below center right, Brandywine Creek State Park center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

John Twysden and John Palmer: 17th-century Northamptonshire astronomers

NASA Astrophysics Data System (ADS)

Frost, M. A.

2008-01-01

John Twysden (1607-1688) and John Palmer (1612-1679) were two astronomers in the circle of Samuel Foster (circa 1600-1652), the subject of a recent paper in this journal. John Twysden qualified in law and medicine and led a peripatetic life around England and Europe. John Palmer was Rector of Ecton, Northamptonshire and later Archdeacon of Northampton. The two astronomers catalogued observations made from Northamptonshire from the 1640s to the 1670s. In their later years Twysden and Palmer published works on a variety of topics, often astronomical. Palmer engaged in correspondence with Henry Oldenburg, the first secretary of the Royal Society, on topics in astronomy and mathematics.

Adam M. Grant: Award for Distinguished Scientific Early Career Contributions to Psychology.

PubMed

2011-11-01

Presents Adam M. Grant, the 2011 winner of the American Psychological Association Award for Distinguished Scientific Early Career Contributions to Psychology. "For extensive, elegant, and programmatic research on the power of relational job design in enhancing employee motivation, productivity, and satisfaction; for creative and rigorous studies documenting the profound and surprising effects of connecting employees to their impact on others; for highlighting prosocial motivation, not only extrinsic and intrinsic motivations, as a key force behind employee behavior; and for demonstrating by example the feasibility and benefits of conducting field experiments, yielding studies rich in internal validity, external validity, and practical impact. In addition to his accomplishments, Adam M. Grant is known for his generosity as a scholar, teacher, and colleague." (PsycINFO Database Record (c) 2011 APA, all rights reserved). 2011 APA, all rights reserved

Efficacy and workload analysis of a fixed vertical couch position technique and a fixed‐action–level protocol in whole‐breast radiotherapy

PubMed Central

Verhoeven, Karolien; Weltens, Caroline; Van den Heuvel, Frank

2015-01-01

Quantification of the setup errors is vital to define appropriate setup margins preventing geographical misses. The no‐action–level (NAL) correction protocol reduces the systematic setup errors and, hence, the setup margins. The manual entry of the setup corrections in the record‐and‐verify software, however, increases the susceptibility of the NAL protocol to human errors. Moreover, the impact of the skin mobility on the anteroposterior patient setup reproducibility in whole‐breast radiotherapy (WBRT) is unknown. In this study, we therefore investigated the potential of fixed vertical couch position‐based patient setup in WBRT. The possibility to introduce a threshold for correction of the systematic setup errors was also explored. We measured the anteroposterior, mediolateral, and superior–inferior setup errors during fractions 1–12 and weekly thereafter with tangential angled single modality paired imaging. These setup data were used to simulate the residual setup errors of the NAL protocol, the fixed vertical couch position protocol, and the fixed‐action–level protocol with different correction thresholds. Population statistics of the setup errors of 20 breast cancer patients and 20 breast cancer patients with additional regional lymph node (LN) irradiation were calculated to determine the setup margins of each off‐line correction protocol. Our data showed the potential of the fixed vertical couch position protocol to restrict the systematic and random anteroposterior residual setup errors to 1.8 mm and 2.2 mm, respectively. Compared to the NAL protocol, a correction threshold of 2.5 mm reduced the frequency of mediolateral and superior–inferior setup corrections with 40% and 63%, respectively. The implementation of the correction threshold did not deteriorate the accuracy of the off‐line setup correction compared to the NAL protocol. The combination of the fixed vertical couch position protocol, for correction of the anteroposterior

Two Rival Conceptions of Vocational Education: Adam Smith and Friedrich List.

ERIC Educational Resources Information Center

Winch, Christopher

1998-01-01

Examines and discusses two views of political economy: (1) the classical model of Adam Smith; and (2) the social capitalist model associated with Friedrich List. Explores two varieties of vocational education and training that emerge from a comparison of Smith's and List's ideas. (CMK)

EGFR and ADAMs Cooperate to Regulate Shedding and Endocytic Trafficking of the Desmosomal Cadherin Desmoglein 2

PubMed Central

Klessner, Jodi L.; Desai, Bhushan V.; Amargo, Evangeline V.; Getsios, Spiro

2009-01-01

Regulation of classic cadherins plays a critical role in tissue remodeling during development and cancer; however, less attention has been paid to the importance of desmosomal cadherins. We previously showed that EGFR inhibition results in accumulation of the desmosomal cadherin, desmoglein 2 (Dsg2), at cell–cell interfaces accompanied by inhibition of matrix metalloprotease (MMP)-dependent shedding of the Dsg2 ectodomain and tyrosine phosphorylation of its cytoplasmic domain. Here, we show that EGFR inhibition stabilizes Dsg2 at intercellular junctions by interfering with its accumulation in an internalized cytoplasmic pool. Furthermore, MMP inhibition and ADAM17 RNAi, blocked shedding and depleted internalized Dsg2, but less so E-cadherin, in highly invasive SCC68 cells. ADAM9 and 15 silencing also impaired Dsg2 processing, supporting the idea that this desmosomal cadherin can be regulated by multiple ADAM family members. In contrast, ADAM10 siRNA enhanced accumulation of a 100-kDa Dsg2 cleavage product and internalized pool of Dsg2. Although both MMP and EGFR inhibition increased intercellular adhesive strength in control cells, the response to MMP-inhibition was Dsg2-dependent. These data support a role for endocytic trafficking in regulating desmosomal cadherin turnover and function and raise the possibility that internalization and regulation of desmosomal and classic cadherin function can be uncoupled mechanistically. PMID:18987342

Cytoskeletal confinement of CX3CL1 limits its susceptibility to proteolytic cleavage by ADAM10.

PubMed

Wong, Harikesh S; Jaumouillé, Valentin; Heit, Bryan; Doodnauth, Sasha A; Patel, Sajedabanu; Huang, Yi-Wei; Grinstein, Sergio; Robinson, Lisa A

2014-12-01

CX3CL1 is a unique chemokine that acts both as a transmembrane endothelial adhesion molecule and, upon proteolytic cleavage, a soluble chemoattractant for circulating leukocytes. The constitutive release of soluble CX3CL1 requires the interaction of its transmembrane species with the integral membrane metalloprotease ADAM10, yet the mechanisms governing this process remain elusive. Using single-particle tracking and subdiffraction imaging, we studied how ADAM10 interacts with CX3CL1. We observed that the majority of cell surface CX3CL1 diffused within restricted confinement regions structured by the cortical actin cytoskeleton. These confinement regions sequestered CX3CL1 from ADAM10, precluding their association. Disruption of the actin cytoskeleton reduced CX3CL1 confinement and increased CX3CL1-ADAM10 interactions, promoting the release of soluble chemokine. Our results demonstrate a novel role for the cytoskeleton in limiting membrane protein proteolysis, thereby regulating both cell surface levels and the release of soluble ligand. © 2014 Wong et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Adam Smith and the Moral Economy of the Classroom System.

ERIC Educational Resources Information Center

Hamilton, D.

1980-01-01

Traces the development of mass schooling to its origins in 19th-century Glasgow. Its importance as an intellectual and economic center enabled Glasgow to invent a solution to the problem of urban schooling, while the association of scholars like Adam Smith with Glasgow University made Scottish educational theories acceptable around the world. (DB)

4. Aerial view southwest, Adams Dam Road bottom left, State ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

4. Aerial view southwest, Adams Dam Road bottom left, State Route 100 center, back gates to Winterthur and Wilmington Country Club upper center, duck pond and reservoir bottom right and center, and State Route 92 center bottom. - Winterthur Farms, Intersection State Routes 92 & 100, Intersection State Routes 92 & 100, Winterthur, New Castle County, DE

iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function

PubMed Central

Brooke, Matthew A.; Etheridge, Sarah L.; Kaplan, Nihal; Simpson, Charlotte; O'Toole, Edel A.; Ishida-Yamamoto, Akemi; Marches, Olivier; Getsios, Spiro; Kelsell, David P.

2014-01-01

iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation. PMID:24643277

Father Knows Best: Using Adam Smith to Teach Transactions Costs

ERIC Educational Resources Information Center

Dupont, Brandon

2014-01-01

Adam Smith's moral philosophy can be used to introduce economics students to the important idea of transactions costs. The author provides a brief background in this article to Smith's moral philosophy and connects it to the costs of transacting in a way that fits easily into the standard principles of microeconomics classroom. By doing…

SuperADAM: Upgraded polarized neutron reflectometer at the Institut Laue-Langevin

NASA Astrophysics Data System (ADS)

Devishvili, A.; Zhernenkov, K.; Dennison, A. J. C.; Toperverg, B. P.; Wolff, M.; Hjörvarsson, B.; Zabel, H.

2013-02-01

A new neutron reflectometer SuperADAM has recently been built and commissioned at the Institut Laue-Langevin, Grenoble, France. It replaces the previous neutron reflectometer ADAM. The new instrument uses a solid state polarizer/wavelength filter providing a highly polarized (up to 98.6%) monochromatic neutron flux of 8 × 104 n cm-2 s-1 with monochromatization Δλ/λ = 0.7% and angular divergence Δα = 0.2 mrad. The instrument includes both single and position sensitive detectors. The position sensitive detector allows simultaneous measurement of specular reflection and off-specular scattering. Polarization analysis for both specular reflection and off-specular scattering is achieved using either mirror analyzers or a 3He spin filter cell. High efficiency detectors, low background, and high flux provides a dynamic range of up to seven decades in reflectivity. Detailed specifications and the instrument capabilities are illustrated with examples of recently collected data in the fields of thin film magnetism and thin polymer films.

Influence of mannosylation on immunostimulating activity of adamant-1-yl tripeptide.

PubMed

Ribić, Rosana; Habjanec, Lidija; Frkanec, Ruža; Vranešić, Branka; Tomić, Srđanka

2012-07-01

The mannosylated derivative of adamant-1-yl tripeptide (D-(Ad-1-yl)Gly-L-Ala-D-isoGln) was prepared to study the effects of mannosylation on adjuvant (immunostimulating) activity. Mannosylated adamant-1-yl tripeptide (Man-OCH(2) CH(Me)CO-D-(Ad-1-yl)Gly-L-Ala-D-isoGln) is a non-pyrogenic, H(2) O-soluble, and non-toxic compound. Adjuvant activity of mannosylated adamantyl tripeptide was tested in the mouse model with ovalbumin as an antigen and in comparison to the parent tripeptide and peptidoglycan monomer (PGM, β-D-GlcNAc-(1→4)-D-MurNAc-L-Ala-D-isoGln-mesoDAP(εNH(2) )-D-Ala-D-Ala), a well-known effective adjuvant. The mannosylation of adamantyl tripeptide caused the amplification of its immunostimulating activity in such a way that it was comparable to that of PGM. Copyright © 2012 Verlag Helvetica Chimica Acta AG, Zürich.

SuperADAM: upgraded polarized neutron reflectometer at the Institut Laue-Langevin.

PubMed

Devishvili, A; Zhernenkov, K; Dennison, A J C; Toperverg, B P; Wolff, M; Hjörvarsson, B; Zabel, H

2013-02-01

A new neutron reflectometer SuperADAM has recently been built and commissioned at the Institut Laue-Langevin, Grenoble, France. It replaces the previous neutron reflectometer ADAM. The new instrument uses a solid state polarizer/wavelength filter providing a highly polarized (up to 98.6%) monochromatic neutron flux of 8 × 10(4) n cm(-2) s(-1) with monochromatization Δλ∕λ = 0.7% and angular divergence Δα = 0.2 mrad. The instrument includes both single and position sensitive detectors. The position sensitive detector allows simultaneous measurement of specular reflection and off-specular scattering. Polarization analysis for both specular reflection and off-specular scattering is achieved using either mirror analyzers or a (3)He spin filter cell. High efficiency detectors, low background, and high flux provides a dynamic range of up to seven decades in reflectivity. Detailed specifications and the instrument capabilities are illustrated with examples of recently collected data in the fields of thin film magnetism and thin polymer films.

John Lewis | NREL

Science.gov Websites

Lewis John Lewis John Lewis Researcher IV-Chemical Engineering John.Lewis@nrel.gov | 303-275-3021 Education Ph.D. Chemical Engineering, California Institute of Technology, Pasadena, CA, 1996 M.S. Chemical Engineering, California Institute of Technology, Pasadena, CA, 1993 B.S. Chemical Engineering, Texas A&M

Elevated serum CXCL16 is an independent predictor of poor survival in ovarian cancer and may reflect pro-metastatic ADAM protease activity

PubMed Central

Gooden, M J M; Wiersma, V R; Boerma, A; Leffers, N; Boezen, H M; ten Hoor, K A; Hollema, H; Walenkamp, A M E; Daemen, T; Nijman, H W; Bremer, E

2014-01-01

Background: In certain cancers, expression of CXCL16 and its receptor CXCR6 associate with lymphocyte infiltration, possibly aiding anti-tumour immune response. In other cancers, CXCL16 and CXCR6 associate with pro-metastatic activity. In the current study, we aimed to characterise the role of CXCL16, sCXCL16, and CXCR6 in ovarian cancer (OC). Methods: CXCL16/CXCR6 expression was analysed on tissue microarray containing 306 OC patient samples. Pre-treatment serum sCXCL16 was determined in 118 patients using ELISA. In vitro, (primary) OC cells were treated with an ADAM-10/ADAM-17 inhibitor (TAPI-2) and an ADAM-10-specific inhibitor (GI254023x), whereupon CXCL16 levels were evaluated on the cell membrane (immunofluorescent analysis, western blots) and in culture supernatants (ELISA). In addition, cell migration was assessed using scratch assays. Results: sCXCL16 independently predicted for poor survival (hazard ratio=2.28, 95% confidence interval=1.29–4.02, P=0.005), whereas neither CXCL16 nor CXCR6 expression correlated with survival. Further, CXCL16/CXCR6 expression and serum sCXCL16 levels did not associate with lymphocyte infiltration. In vitro inhibition of both ADAM-17 and ADAM-10, but especially the latter, decreased CXCL16 membrane shedding and strongly reduced cell migration of A2780 and cultured primary OC-derived malignant cells. Conclusions: High serum sCXCL16 is a prognostic marker for poor survival of OC patients, possibly reflecting ADAM-10 and ADAM-17 pro-metastatic activity. Therefore, serum sCXCL16 levels may be a pseudomarker that identifies patients with highly metastatic tumours. PMID:24518602

Comparing Adam Smith's Wealth of Nations to James Madison's Federalist #10.

ERIC Educational Resources Information Center

Mundell, Jean

1987-01-01

Presents a lesson which calls upon students to compare Adam Smith's WEALTH OF NATIONS to James Madison's FEDERALIST #10 to see how the ancient concept of individual rights and liberties was used to describe both economic and governmental systems. Presents questions to provide the basis for comparison. (GEA)

ADAM33 polymorphisms are associated with asthma and a distinctive palm dermatoglyphic pattern

PubMed Central

XUE, WEILIN; HAN, WEI; ZHOU, ZHAO-SHAN

2013-01-01

A close correlation between asthma and palm dermatoglyphic patterns has been observed in previous studies, but the underlying genetic mechanisms have not been investigated. A disintegrin and metalloprotein-33 (ADAM33) polymorphisms are important in the development of asthma and other atopic diseases. To investigate the underlying mechanisms of the association between asthma and distinctive palm dermatoglyphic patterns, thirteen ADAM33 single-nucleotide polymorphisms (SNPs) were analyzed for the association between asthma and palm dermatoglyphic patterns in a population of 400 asthmatic patients and 200 healthy controls. Based on the results, five SNPs, rs44707 (codominant model, P=0.031; log-additive model, P=0.0084), rs2787094 (overdominant model, P=0.049), rs678881 (codominant model, P=0.028; overdominant model, P=0.0083), rs677044 (codominant model, P=0.013; log-additive model, P=0.0033) and rs512625 (dominant model, P=0.033), were associated with asthma in this population. Two SNPs, rs44707 (dominant model, P=0.042) and rs2787094 (codominant model, P=0.014; recessive model, P=0.0038), were observed in the asthma patients with the distinctive palm pattern. As rs44707 and rs2787094 are associated with asthma and a distinctive palm pattern, the data suggest that ADAM33 polymorphisms are correlated with asthma and may be the underlying genetic basis of the association between asthma and palm dermatoglyphic patterns. PMID:24141861

Expression of ADAM10, Fas, FasL and Soluble FasL in Patients with Oral Squamous Cell Carcinoma (OSCC) and their Association with Clinical-Pathological Parameters.

PubMed

Zepeda-Nuño, José Sergio; Guerrero-Velázquez, Celia; Del Toro-Arreola, Susana; Vega-Magaña, Natali; Ángeles-Sánchez, Julián; Haramati, Jesse; Pereira-Suárez, Ana L; Bueno-Topete, Miriam R

2017-04-01

ADAM10 has been implicated in the progression of various solid tumors. ADAM10 regulates the cleavage of the FasL ectodomain from the plasma membrane of different cell types, generating the soluble FasL fragment (sFasL). Currently, there are few studies in oral squamous cell carcinoma (OSCC) that correlate levels of ADAM10 and FasL in the tumor microenvironment with clinical parameters of the disease. To determine the expression of ADAM10, Fas, FasL and sFasL in patients with OSCC and its association with TNM stage. Twenty-five patients with OSCC and 25 healthy controls were included. Biopsies of tumor tissue from patients with OSCC and buccal mucosa in controls were obtained. ADAM10, Fas, and FasL were analyzed by Western blotting. sFasL was quantified by ELISA. ADAM10 and Fas decreased significantly in OSCC compared with controls. Relatedly, within the OSCC group, Fas and ADAM10 decreased in accordance with tumor disease stage; in stages I/II, as well as in tumors of smaller diameter (T1-T2), ADAM10 showed higher levels when compared to patients with T3-T4 tumors and in stage III-IV. FasL in the tumor microenvironment and serum FasL showed no significant differences between both groups. Levels of complete FasL and cleaved FasL were positively correlated in controls; this correlation is preserved in patients with tumors in early stages (I-II), but is lost in later stage (III-IV). The dysregulation of ADAM10, Fas and FasL could be useful indicators of the progression and severity of OSCC.

Extraction-Separation Performance and Dynamic Modeling of Orion Test Vehicles with Adams Simulation: 3rd Edition

NASA Technical Reports Server (NTRS)

Varela, Jose G.; Reddy, Satish; Moeller, Enrique; Anderson, Keith

2017-01-01

NASA's Orion Capsule Parachute Assembly System (CPAS) Project is now in the qualification phase of testing, and the Adams simulation has continued to evolve to model the complex dynamics experienced during the test article extraction and separation phases of flight. The ability to initiate tests near the upper altitude limit of the Orion parachute deployment envelope requires extractions from the aircraft at 35,000 ft-MSL. Engineering development phase testing of the Parachute Test Vehicle (PTV) carried by the Carriage Platform Separation System (CPSS) at altitude resulted in test support equipment hardware failures due to increased energy caused by higher true airspeeds. As a result, hardware modifications became a necessity requiring ground static testing of the textile components to be conducted and a new ground dynamic test of the extraction system to be devised. Force-displacement curves from static tests were incorporated into the Adams simulations, allowing prediction of loads, velocities and margins encountered during both flight and ground dynamic tests. The Adams simulation was then further refined by fine tuning the damping terms to match the peak loads recorded in the ground dynamic tests. The failure observed in flight testing was successfully replicated in ground testing and true safety margins of the textile components were revealed. A multi-loop energy modulator was then incorporated into the system level Adams simulation model and the effect on improving test margins be properly evaluated leading to high confidence ground verification testing of the final design solution.

Music for Elementary Teachers, Competency-Based Approach. Adams State College.

ERIC Educational Resources Information Center

Stokes, Cloyce; And Others

This is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The goals of this module package are listed as follows: a) to introduce the intern to music for elementary school children; b) to enable interns to develop knowledge and skills of an elementary level in music; c) to enable interns to…

Back to Beginnings: Credentialism, Productivity, and Adam Smith's Division of Labour.

ERIC Educational Resources Information Center

Davis, Denis J.

1981-01-01

The foundation of factional pressures for upgrading educational credentials in the labor market is examined through a review of human capital and screening theories. The writings of Adam Smith are referenced to show that the claims of the beneficial effects of educational upgrading have been questioned for 200 years. (Author/MLW)

Helicopter magnetic and electromagnetic surveys at Mounts Adams, Baker and Rainier, Washington: implications for debris flow hazards and volcano hydrology

USGS Publications Warehouse

Finn, Carol A.; Deszcz-Pan, Maria

2011-01-01

High‐resolution helicopter magnetic and electromagnetic (HEM) data flown over the rugged, ice‐covered Mt. Adams, Mt. Baker and Mt. Rainier volcanoes (Washington), reveal the distribution of alteration, water and ice thickness essential to evaluating volcanic landslide hazards. These data, combined with geological mapping and rock property measurements, indicate the presence of appreciable thicknesses (>500 m) of water‐saturated hydrothermally altered rock west of the modern summit of Mount Rainier in the Sunset Amphitheater region and in the central core of Mount Adams north of the summit. Alteration at Mount Baker is restricted to thinner (<300 m) zones beneath Sherman Crater and the Dorr Fumarole Fields. The EM data identified water‐saturated rocks from the surface to the detection limit (100–200 m) in discreet zones at Mt. Rainier and Mt Adams and over the entire summit region at Mt. Baker. The best estimates for ice thickness are obtained over relatively low resistivity (<800 ohm‐m) ground for the main ice cap on Mt. Adams and over most of the summit of Mt. Baker. The modeled distribution of alteration, pore fluids and partial ice volumes on the volcanoes helps identify likely sources for future alteration‐related debris flows, including the Sunset Amphitheater region at Mt. Rainier, steep cliffs at the western edge of the central altered zone at Mount Adams and eastern flanks of Mt. Baker.

Development of an advanced system identification technique for comparing ADAMS analytical results with modal test data for a MICON 65/13 wind turbine

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

Bialasiewicz, J.T.

1995-07-01

This work uses the theory developed in NREL/TP--442-7110 to analyze simulated data from an ADAMS (Automated Dynamic Analysis of Mechanical Systems) model of the MICON 65/13 wind turbine. The Observer/Kalman Filter identification approach is expanded to use input-output time histories from ADAMS simulations or structural test data. A step by step outline is offered on how the tools developed in this research, can be used for validation of the ADAMS model.

[11C]SMe-ADAM, an imaging agent for the brain serotonin transporter: synthesis, pharmacological characterization and microPET studies in rats.

PubMed

Zessin, Jörg; Deuther-Conrad, Winnie; Kretzschmar, Marion; Wüst, Frank; Pawelke, Beate; Brust, Peter; Steinbach, Jörg; Bergmann, Ralf

2006-01-01

N,N-Dimethyl-2-(2-amino-4-methylthiophenylthio)benzylamine (SMe-ADAM, 1) is a highly potent and selective inhibitor of the serotonin transporter (SERT). This compound was labeled with carbon-11 by methylation of the S-desmethyl precursor 10 with [(11)C]methyl iodide to obtain the potential positron emission tomography (PET) radioligand [(11)C]SMe-ADAM. The radiochemical yield was 27 +/- 5%, and the specific radioactivity was 26-40 GBq/micromol at the end of synthesis. Ex vivo and in vivo biodistribution experiments in rats demonstrated a rapid accumulation of the radiotracer in brain regions known to be rich in SERT, such as the thalamus/hypothalamus region (3.59 +/- 0.41%ID/g at 5 min after injection). The specific uptake reached a thalamus to cerebellum ratio of 6.74 +/- 0.95 at 60 min postinjection. The [(11)C]SMe-ADAM uptake in the thalamus was significantly decreased by pretreatment with fluoxetine to 38 +/- 11% of the control value. Furthermore, no metabolites of [(11)C]SMe-ADAM could be detected in the SERT-rich regions of the rat brain. It is concluded that [(11)C]SMe-ADAM may be a suitable PET ligand for SERT imaging in the living brain.

Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

NASA Technical Reports Server (NTRS)

Humphreys, B. T.; Thompson, W. K.; Lewandowski, B. E.; Cadwell, E. E.; Newby, N. J.; Fincke, R. S.; Sheehan, C.; Mulugeta, L.

2012-01-01

NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the

SU-F-T-642: Sub Millimeter Accurate Setup of More Than Three Vertebrae in Spinal SBRT with 6D Couch

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

Wang, X; Zhao, Z; Yang, J

Purpose: To assess the initial setup accuracy in treating more than 3 vertebral body levels in spinal SBRT using a 6D couch. Methods: We retrospectively analyzed last 20 spinal SBRT patients (4 cervical, 9 thoracic, 7 lumbar/sacrum) treated in our clinic. These patients in customized immobilization device were treated in 1 or 3 fractions. Initial setup used ExacTrac and Brainlab 6D couch to align target within 1 mm and 1 degree, following by a cone beam CT (CBCT) for verification. Our current standard practice allows treating a maximum of three continuous vertebrae. Here we assess the possibility to achieve submore » millimeter setup accuracy for more than three vertebrae by examining the residual error in every slice of CBCT. The CBCT had a range of 17.5 cm, which covered 5 to 9 continuous vertebrae depending on the patient and target location. In the study, CBCT from the 1st fraction treatment was rigidly registered with the planning CT in Pinnacle. The residual setup error of a vertebra was determined by expanding the vertebra contour on the planning CT to be large enough to enclose the corresponding vertebra on CBCT. The margin of the expansion was considered as setup error. Results: Out of the 20 patients analyzed, initial setup accuracy can be achieved within 1 mm for a span of 5 or more vertebrae starting from T2 vertebra to inferior vertebra levels. 2 cervical and 2 upper thoracic patients showed the cervical spine was difficult to achieve sub millimeter accuracy for multi levels without a customized immobilization headrest. Conclusion: If the curvature of spinal columns can be reproduced in customized immobilization device during treatment as simulation, multiple continuous vertebrae can be setup within 1 mm with the use of a 6D couch.« less

Reliability evaluation of I-123 ADAM SPECT imaging using SPM software and AAL ROI methods

NASA Astrophysics Data System (ADS)

Yang, Bang-Hung; Tsai, Sung-Yi; Wang, Shyh-Jen; Su, Tung-Ping; Chou, Yuan-Hwa; Chen, Chia-Chieh; Chen, Jyh-Cheng

2011-08-01

The level of serotonin was regulated by serotonin transporter (SERT), which is a decisive protein in regulation of serotonin neurotransmission system. Many psychiatric disorders and therapies were also related to concentration of cerebral serotonin. I-123 ADAM was the novel radiopharmaceutical to image SERT in brain. The aim of this study was to measure reliability of SERT densities of healthy volunteers by automated anatomical labeling (AAL) method. Furthermore, we also used statistic parametric mapping (SPM) on a voxel by voxel analysis to find difference of cortex between test and retest of I-123 ADAM single photon emission computed tomography (SPECT) images.Twenty-one healthy volunteers were scanned twice with SPECT at 4 h after intravenous administration of 185 MBq of 123I-ADAM. The image matrix size was 128×128 and pixel size was 3.9 mm. All images were obtained through filtered back-projection (FBP) reconstruction algorithm. Region of interest (ROI) definition was performed based on the AAL brain template in PMOD version 2.95 software package. ROI demarcations were placed on midbrain, pons, striatum, and cerebellum. All images were spatially normalized to the SPECT MNI (Montreal Neurological Institute) templates supplied with SPM2. And each image was transformed into standard stereotactic space, which was matched to the Talairach and Tournoux atlas. Then differences across scans were statistically estimated on a voxel by voxel analysis using paired t-test (population main effect: 2 cond's, 1 scan/cond.), which was applied to compare concentration of SERT between the test and retest cerebral scans.The average of specific uptake ratio (SUR: target/cerebellum-1) of 123I-ADAM binding to SERT in midbrain was 1.78±0.27, pons was 1.21±0.53, and striatum was 0.79±0.13. The cronbach's α of intra-class correlation coefficient (ICC) was 0.92. Besides, there was also no significant statistical finding in cerebral area using SPM2 analysis. This finding might help us

ADAM: An Accident Diagnostic,Analysis and Management System - Applications to Severe Accident Simulation and Management

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

Zavisca, M.J.; Khatib-Rahbar, M.; Esmaili, H.

2002-07-01

The Accident Diagnostic, Analysis and Management (ADAM) computer code has been developed as a tool for on-line applications to accident diagnostics, simulation, management and training. ADAM's severe accident simulation capabilities incorporate a balance of mechanistic, phenomenologically based models with simple parametric approaches for elements including (but not limited to) thermal hydraulics; heat transfer; fuel heatup, meltdown, and relocation; fission product release and transport; combustible gas generation and combustion; and core-concrete interaction. The overall model is defined by a relatively coarse spatial nodalization of the reactor coolant and containment systems and is advanced explicitly in time. The result is to enablemore » much faster than real time (i.e., 100 to 1000 times faster than real time on a personal computer) applications to on-line investigations and/or accident management training. Other features of the simulation module include provision for activation of water injection, including the Engineered Safety Features, as well as other mechanisms for the assessment of accident management and recovery strategies and the evaluation of PSA success criteria. The accident diagnostics module of ADAM uses on-line access to selected plant parameters (as measured by plant sensors) to compute the thermodynamic state of the plant, and to predict various margins to safety (e.g., times to pressure vessel saturation and steam generator dryout). Rule-based logic is employed to classify the measured data as belonging to one of a number of likely scenarios based on symptoms, and a number of 'alarms' are generated to signal the state of the reactor and containment. This paper will address the features and limitations of ADAM with particular focus on accident simulation and management. (authors)« less

ADAM10 controls collagen signaling and cell migration on collagen by shedding the ectodomain of discoidin domain receptor 1 (DDR1)

PubMed Central

Shitomi, Yasuyuki; Thøgersen, Ida B.; Ito, Noriko; Leitinger, Birgit; Enghild, Jan J.; Itoh, Yoshifumi

2015-01-01

Discoidin domain receptor 1 (DDR1) is a receptor tyrosine kinase that binds and transmits signals from various collagens in epithelial cells. However, how DDR1–dependent signaling is regulated has not been understood. Here we report that collagen binding induces ADAM10-dependent ectodomain shedding of DDR1. DDR1 shedding is not a result of an activation of its signaling pathway, since DDR1 mutants defective in signaling were shed in an efficient manner. DDR1 and ADAM10 were found to be in a complex on the cell surface, but shedding did not occur unless collagen bound to DDR1. Using a shedding-resistant DDR1 mutant, we found that ADAM10-dependent DDR1 shedding regulates the half-life of collagen-induced phosphorylation of the receptor. Our data also revealed that ADAM10 plays an important role in regulating DDR1-mediated cell adhesion to achieve efficient cell migration on collagen matrices. PMID:25540428

The Adam Williams initiative: collaborating with community resources to improve care for traumatic brain injury.

PubMed

Bader, Mary Kay; Stutzman, Sonja E; Palmer, Sylvain; Nwagwu, Chiedozie I; Goodman, Gary; Whittaker, Margie; Olson, Daiwai M

2014-12-01

The Brain Trauma Foundation has developed treatment guidelines for the care of patients with acute traumatic brain injury. However, a method to provide broad acceptance and application of these guidelines has not been published. To describe methods for the development, funding, and continued educational efforts of the Adam Williams Initiative; the experiences from the first 10 years may serve as a template for hospitals and nurses that seek to engage in long-term quality improvement collaborations with foundations and/or industry. In 2004, the nonprofit Adam Williams Initiative was established with the goal of providing education and resources that would encourage hospitals across the United States to incorporate the Brain Trauma Foundation's guidelines into practice. Between 2004 and 2014, 37 hospitals have been funded by the Adam Williams Initiative and have had staff members participate in an immersion experience at Mission Hospital (Mission Viejo, California) during which team members received both didactic and hands-on education in the care of traumatic brain injury. Carefully cultivated relationships and relentless teamwork have contributed to successful implementation of the Brain Trauma Foundation's guidelines in US hospitals. ©2014 American Association of Critical-Care Nurses.

iRHOM2-dependent regulation of ADAM17 in cutaneous disease and epidermal barrier function.

PubMed

Brooke, Matthew A; Etheridge, Sarah L; Kaplan, Nihal; Simpson, Charlotte; O'Toole, Edel A; Ishida-Yamamoto, Akemi; Marches, Olivier; Getsios, Spiro; Kelsell, David P

2014-08-01

iRHOM2 is a highly conserved, catalytically inactive member of the Rhomboid family, which has recently been shown to regulate the maturation of the multi-substrate ectodomain sheddase enzyme ADAM17 (TACE) in macrophages. Dominant iRHOM2 mutations are the cause of the inherited cutaneous and oesophageal cancer-susceptibility syndrome tylosis with oesophageal cancer (TOC), suggesting a role for this protein in epithelial cells. Here, using tissues derived from TOC patients, we demonstrate that TOC-associated mutations in iRHOM2 cause an increase in the maturation and activity of ADAM17 in epidermal keratinocytes, resulting in significantly upregulated shedding of ADAM17 substrates, including EGF-family growth factors and pro-inflammatory cytokines. This activity is accompanied by increased EGFR activity, increased desmosome processing and the presence of immature epidermal desmosomes, upregulated epidermal transglutaminase activity and heightened resistance to Staphylococcal infection in TOC keratinocytes. Many of these features are consistent with the presence of a constitutive wound-healing-like phenotype in TOC epidermis, which may shed light on a novel pathway in skin repair, regeneration and inflammation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Automation of TL brick dating by ADAM-1

NASA Astrophysics Data System (ADS)

Čechák, T.; Gerndt, J.; Hiršl, P.; Jiroušek, P.; Kanaval, J.; Kubelík, M.; Musílek, L.

2001-06-01

A specially adapted machine ADAM-1 for the thermoluminescence fine grain dating of bricks was constructed in an interdisciplinary research project, undertaken by a team recruited from three faculties of the Czech Technical University in Prague. This TL-reader is able to measure and evaluate automatically numerous samples. The sample holder has 60 sample positions, which allow the irradiation and evaluation of samples taken from two locations. All procedures of alpha and beta irradiation by varying doses and the TL-signal measurement as also the age evaluation and error assessment are programmable and fully automated.

Deletion of admB gene encoding a fungal ADAM affects cell wall construction in Aspergillus oryzae.

PubMed

Kobayashi, Takuji; Maeda, Hiroshi; Takeuchi, Michio; Yamagata, Youhei

2017-05-01

Mammals possess a unique signaling system based on the proteolytic mechanism of a disintegrin and metalloproteinases (ADAMs) on the cell surface. We found two genes encoding ADAMs in Aspergillus oryzae and named them admA and admB. We produced admA and admB deletion strains to elucidate their biological function and clarify whether fungal ADAMs play a similar role as in mammals. The ∆admA∆admB and ∆admB strains were sensitive to cell wall-perturbing agents, congo red, and calcofluor white. Moreover, the two strains showed significantly increased weights of total alkali-soluble fractions from the mycelial cell wall compared to the control strain. Furthermore, ∆admB showed MpkA phosphorylation at lower concentration of congo red stimulation than the control strain. However, the MpkA phosphorylation level was not different between ∆admB and the control strain without the stimulation. The results indicated that A. oryzae AdmB involved in the cell wall integrity without going through the MpkA pathway.

Commemorating John Dyson

NASA Astrophysics Data System (ADS)

Pittard, Julian M.

2015-03-01

John Dyson was born on the 7th January 1941 in Meltham Mills, West Yorkshire, England, and later grew up in Harrogate and Leeds. The proudest moment of John's early life was meeting Freddie Trueman, who became one of the greatest fast bowlers of English cricket. John used a state scholarship to study at Kings College London, after hearing a radio lecture by D. M. McKay. He received a first class BSc Special Honours Degree in Physics in 1962, and began a Ph.D. at the University of Manchester Department of Astronomy after being attracted to astronomy by an article of Zdenek Kopal in the semi-popular journal New Scientist. John soon started work with Franz Kahn, and studied the possibility that the broad emission lines seen from the Orion Nebula were due to flows driven by the photoevaporation of neutral globules embedded in a HII region. John's thesis was entitled ``The Age and Dynamics of the Orion Nebula`` and he passed his oral examination on 28th February 1966.

Detector system dose verification comparisons for arc therapy: couch vs. gantry mount

PubMed Central

Manikandan, Arjunan; Nandy, Maitreyee; Sureka, Chandra Sekaran; Gossman, Michael S.; Sujatha, Nadendla; Rajendran, Vivek Thirupathur

2014-01-01

The aim of this study was to assess the performance of a gantry‐mounted detector system and a couch set detector system using a systematic multileaf collimator positional error manually introduced for volumetric‐modulated arc therapy. Four head and neck and esophagus VMAT plans were evaluated by measurement using an electronic portal imaging device and an ion chamber array. Each plan was copied and duplicated with a 1 mm systematic MLC positional error in the left leaf bank. Direct comparison of measurements for plans with and without the error permitted observational characteristics for quality assurance performance between detectors. A total of 48 different plans were evaluated for this testing. The mean percentage planar dose differences required to satisfy a 95% match between plans with and without the MLCPE were 5.2% ± 0.5% for the chamber array with gantry motion, 8.12% ± 1.04% for the chamber array with a static gantry at 0°, and 10.9% ± 1.4% for the EPID with gantry motion. It was observed that the EPID was less accurate due to overresponse of the MLCPE in the left leaf bank. The EPID always images bank‐A on the ipsilateral side of the detector, whereas for a chamber array or for a patient, that bank changes as it crosses the ‐90° or +90° position. A couch set detector system can reproduce the TPS calculated values most consistently. We recommend it as the most reliable patient specific QA system for MLC position error testing. This research is highlighted by the finding of up to 12.7% dose variation for H/N and esophagus cases for VMAT delivery, where the mere source of error was the stated clinically acceptability of 1 mm MLC position deviation of TG‐142. PACS numbers: 87.56.‐v, 87.55.‐x, 07.57.KP, 29.40.‐n, 85.25.Pb PMID:24892330

Fractalkine shedding is mediated by p38 and the ADAM10 protease under pro-inflammatory conditions in human astrocytes.

PubMed

O'Sullivan, Sinead A; Gasparini, Fabrizio; Mir, Anis K; Dev, Kumlesh K

2016-08-22

The fractalkine (CX3CR1) ligand is expressed in astrocytes and reported to be neuroprotective. When cleaved from the membrane, soluble fractalkine (sCX3CL1) activates the receptor CX3CR1. Although somewhat controversial, CX3CR1 is reported to be expressed in neurons and microglia. The membrane-bound form of CX3CL1 additionally acts as an adhesion molecule for microglia and infiltrating white blood cells. Much research has been done on the role of fractalkine in neuronal cells; however, little is known about the regulation of the CX3CL1 ligand in astrocytes. The mechanisms involved in the up-regulation and cleavage of CX3CL1 from human astrocytes were investigated using immunocytochemistry, Q-PCR and ELISA. All statistical analysis was performed using GraphPad Prism 5. A combination of ADAM17 (TACE) and ADAM10 protease inhibitors was found to attenuate IL-1β-, TNF-α- and IFN-γ-induced sCX3CL1 levels in astrocytes. A specific ADAM10 (but not ADAM17) inhibitor also attenuated these effects, suggesting ADAM10 proteases induce release of sCX3CL1 from stimulated human astrocytes. A p38 MAPK inhibitor also attenuated the levels of sCX3CL1 upon treatment with IL-1β, TNF-α or IFN-γ. In addition, an IKKβ inhibitor significantly reduced the levels of sCX3CL1 induced by IL-1β or TNF-α in a concentration-dependent manner, suggesting a role for the NF-kB pathway. In conclusion, this study shows that the release of soluble astrocytic fractalkine is regulated by ADAM10 proteases with p38 MAPK also playing a role in the fractalkine shedding event. These findings are important for understanding the role of CX3CL1 in healthy and stimulated astrocytes and may benefit our understanding of this pathway in neuro-inflammatory and neurodegenerative diseases.

Séchage d'un enduit pigmenté avec application à l'étude d'une couche papetière

NASA Astrophysics Data System (ADS)

Bernada, P.; Bruneau, D.

1996-07-01

Paper color coating drying is investigated from several experimental view points which include drying kinetics and time evolution of moisture content profiles, pore size distribution in the dried coating, and natural binder (starch) distribution in the dried coating. A study of the effects of drying conditions on those experimental parameters is carried out. Furthermore, gelification and consolidation characteristic moisture contents of the coating are determined using a graphical approach. Le séchage d'un enduit pigmenté à l'usage d'une couche papetière est absorbé sous diverts aspects : cinétiques de séchage et évolution temporelle des profils de teneur en eau, profils de répartition de la taille des pores dans la couche séchée, et répartition finale d'un liant hydrophile de la sauce de couchage (amidon). Les conséquences des conditions de séchage sur ces paramètres expérimentaux sont mises en évidence. De plus, les teneurs en eau caractéristiques de gélification et consolidation de la sauce de couchage sont obtenues par une approche graphique.

SuperADAM: Upgraded polarized neutron reflectometer at the Institut Laue-Langevin

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

Devishvili, A.; Zhernenkov, K.; Institut Laue-Langevin, BP 156, 38042 Grenoble

2013-02-15

A new neutron reflectometer SuperADAM has recently been built and commissioned at the Institut Laue-Langevin, Grenoble, France. It replaces the previous neutron reflectometer ADAM. The new instrument uses a solid state polarizer/wavelength filter providing a highly polarized (up to 98.6%) monochromatic neutron flux of 8 Multiplication-Sign 10{sup 4} n cm{sup -2} s{sup -1} with monochromatization {Delta}{lambda}/{lambda}= 0.7% and angular divergence {Delta}{alpha}= 0.2 mrad. The instrument includes both single and position sensitive detectors. The position sensitive detector allows simultaneous measurement of specular reflection and off-specular scattering. Polarization analysis for both specular reflection and off-specular scattering is achieved using either mirror analyzersmore » or a {sup 3}He spin filter cell. High efficiency detectors, low background, and high flux provides a dynamic range of up to seven decades in reflectivity. Detailed specifications and the instrument capabilities are illustrated with examples of recently collected data in the fields of thin film magnetism and thin polymer films.« less

Award for Distinguished Scientific Early Career Contributions to Psychology: Adam K. Anderson

ERIC Educational Resources Information Center

American Psychologist, 2009

2009-01-01

Adam K. Anderson, recipient of the Award for Distinguished Scientific Early Career Contributions to Psychology, is cited for his outstanding contribution to understanding the representation of emotion and its influence on cognition. By combining psychological and neuroscience techniques with rigorous and creative experimental designs, Anderson has…

Adam Smith and the Educative Critique: A Response to My Commentators

ERIC Educational Resources Information Center

Weinstein, Jack Russell

2015-01-01

This paper is both a response to the four reviewers in a special symposium on my book Adam Smith's Pluralism and a substantive discussion of philosophy of education. In it, I introduce what I call "the educative critique," a mode of analysis similar to Marxist, feminist, or postcolonial critiques, but focusing on the educative role of a…

Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17.

PubMed

Ren, Jing; Nie, Yunzhong; Lv, Mingming; Shen, Sunan; Tang, Ruijing; Xu, Yujun; Hou, Yayi; Zhao, Shuli; Wang, Tingting

2015-11-01

Estrogen is involved in promoting lung cancer cell division and metastasis. MICA and MICB function as ligands for NKG2D, an important immunoreceptor expressed on natural killer (NK) cells. However, whether estrogen regulates MICA/B expression and affects tumor immune escape remains unknown. In this study, we measured the mRNA levels of MICA, MICB and ADAM17in non-small cell lung cancer (NSCLC) cell lines treated with estrogen. Surface expression of MICA/B on LTEP-a2 and A549 was detected using flow cytometry. We demonstrate that both mRNA and secretory protein levels of MICA/B in lung adenocarcinoma cell lines were upregulated by estradiol. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. This secretion of MICA/B downregulated the NKG2D receptor on the surface of NK92 cells and impaired the cytotoxic activity of NK cells. Estradiol enhanced the expression of ADAM17, which was associated with the secretion of MICA/B. Furthermore, a significant correlation between the concentration of estradiol and the expression of MICA was found in tumor tissues of NSCLC patients. Therefore, we conclude that estrogen can regulate the expression and secretion of MICA/B through ADAM17, which helps lung cancer cells escape NKG2D-mediated immune surveillance.

Expression of FAP, ADAM12, WISP1, and SOX11 is heterogeneous in aggressive fibromatosis and spatially relates to the histologic features of tumor activity.

PubMed

Misemer, Benjamin S; Skubitz, Amy P N; Carlos Manivel, J; Schmechel, Stephen C; Cheng, Edward Y; Henriksen, Jonathan C; Koopmeiners, Joseph S; Corless, Christopher L; Skubitz, Keith M

2014-02-01

Aggressive fibromatosis (AF) represents a group of tumors with a variable and unpredictable clinical course, characterized by a monoclonal proliferation of myofibroblastic cells. The optimal treatment for AF remains unclear. Identification and validation of genes whose expression patterns are associated with AF may elucidate biological mechanisms in AF, and aid treatment selection. This study was designed to examine the protein expression by immunohistochemistry (IHC) of four genes, ADAM12, FAP, SOX11, and WISP1, that were found in an earlier study to be uniquely overexpressed in AF compared with normal tissues. Digital image analysis was performed to evaluate inter- and intratumor heterogeneity, and correlate protein expression with histologic features, including a histopathologic assessment of tumor activity, defined by nuclear chromatin density ratio (CDR). AF tumors exhibited marked inter- and intratumor histologic heterogeneity. Pathologic assessment of tumor activity and digital assessment of average nuclear size and CDR were all significantly correlated. IHC revealed protein expression of all four genes. IHC staining for ADAM12, FAP, and WISP1 correlated with CDR and was higher, whereas SOX11 staining was lower in tumors with earlier recurrence following excision. All four proteins were expressed, and the regional variation in tumor activity within and among AF cases was demonstrated. A spatial correlation between protein expression and nuclear morphology was observed. IHC also correlated with the probability of recurrence following excision. These proteins may be involved in AF pathogenesis and the corresponding pathways could serve as potential targets of therapy. © 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

The Efficiency of First-Trimester Uterine Artery Doppler, ADAM12, PAPP-A and Maternal Characteristics in the Prediction of Pre-Eclampsia

PubMed Central

GOETZINGER, Katherine R.; ZHONG, Yan; CAHILL, Alison G.; ODIBO, Linda; MACONES, George A.; ODIBO, Anthony O.

2014-01-01

Objective To estimate the efficiency of first-trimester uterine artery Doppler, A-disintegrin and metalloprotease 12 (ADAM12), pregnancy-associated plasma protein A (PAPP-A) and maternal characteristics in the prediction of pre-eclampsia. Methods This is a prospective cohort study of patients presenting for first-trimester aneuploidy screening between 11-14 weeks’ gestation. Maternal serum ADAM12 and PAPP-A levels were measured by immunoassay, and mean uterine artery Doppler pulsatility indices (PI) were calculated. Outcomes of interest included pre-eclampsia, early pre-eclampsia, defined as requiring delivery at <34 weeks’ gestation, and gestational hypertension. Logistic regression analysis was used to model the prediction of pre-eclampsia using ADAM12 multiples of the median (MoM), PAPP-A MoM, and uterine artery Doppler PI MoM, either individually or in combination. Sensitivity, specificity, and area under the receiver-operating characteristic curves (AUC) were used to compare the screening efficiency of the models using non-parametric U-statistics. Results Of 578 patients with complete outcome data, there were 54 (9.3%) cases of preeclampsia and 13 (2.2%) cases of early pre-eclampsia. Median ADAM12 levels were significantly lower in patients who developed pre-eclampsia compared to those who did not. (0.81 v. 1.01 MoMs; p<0.04) For a fixed false positive rate (FPR) of 10%, ADAM12, PAPP-A, and uterine artery Doppler in combination with maternal characteristics identified 50%, 48%, and 52% of patients who developed pre-eclampsia, respectively. Combining these first-trimester parameters did not improve the predictive efficiency of the models. Conclusion First-trimester ADAM12, PAPP-A, and uterine artery Doppler are not sufficiently predictive of pre-eclampsia. Combinations of these parameters do not further improve their screening efficiency. PMID:23980220

The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis.

PubMed

De Savi, Chris; Pape, Andrew; Cumming, John G; Ting, Attilla; Smith, Peter D; Burrows, Jeremy N; Mills, Mark; Davies, Chris; Lamont, Scott; Milne, David; Cook, Calum; Moore, Peter; Sawyer, Yvonne; Gerhardt, Stefan

2011-03-01

Two series of N-hydroxyformamide inhibitors of ADAM-TS4 were identified from screening compounds previously synthesised as inhibitors of matrix metalloproteinase-13 (collagenase-3). Understanding of the binding mode of this class of compound using ADAM-TS1 as a structural surrogate has led to the discovery of potent and very selective inhibitors with favourable DMPK properties. Synthesis, structure-activity relationships, and strategies to improve selectivity and lower in vivo metabolic clearance are described. Copyright © 2011 Elsevier Ltd. All rights reserved.

PAR -- Interface to the ADAM Parameter System

NASA Astrophysics Data System (ADS)

Currie, Malcolm J.; Chipperfield, Alan J.

PAR is a library of Fortran subroutines that provides convenient mechanisms for applications to exchange information with the outside world, through input-output channels called parameters. Parameters enable a user to control an application's behaviour. PAR supports numeric, character, and logical parameters, and is currently implemented only on top of the ADAM parameter system. The PAR library permits parameter values to be obtained, without or with a variety of constraints. Results may be put into parameters to be passed onto other applications. Other facilities include setting a prompt string, and suggested defaults. This document also introduces a preliminary C interface for the PAR library -- this may be subject to change in the light of experience.

Adam Smith and dependency.

PubMed

Ozler, Sule

2012-06-01

The focus of this paper is the works and life of Adam Smith, who is widely recognized as the father and founder of contemporary economics. Latent content analysis is applied to his seminal text in economics, An Inquiry into the Nature and Causes of the Wealth of Nations (1776). The results reveal that Smith considers dependence on others a problem and sees the solution to this problem in impersonalized interdependence. In addition, his views on social dependency and personal dependency, reflected in his Lectures on Jurisprudence (1963) and The Theory of Moral Sentiments (1759), are analyzed. This analysis suggests a central tension between dependence and independence in Smith's writings. The personal dependency patterns he exhibited in his life, which also suggest a tension between dependence and independence, are identified through a reading of his biographies. Based on insights from psychoanalytic literature, this paper proposes that developing the ideas in the Wealth of Nations was part of Smith's creative solution to this tension. In particular, his solution to one individual's dependence on another was through a system of impersonalized interdependence. In other words, Smith defended against his personal dependence through his economic theorizing.

Adam Smith on population.

PubMed

Spengler, J J

1970-11-01

Abstract Adam Smith dealt with questions of population mainly in his Wealth of Nations. His discussion falls roughly under five heads and reflects in considerable measure his image of the English economy. (1) A country's population capacity, given the average level of consumption, was conditioned by the stock of land, the skill with which it was cultivated, and the degree to which division of labour could be increased and thereby augment output for domestic use and sale in external markets. (2) Growth of population was essentially in response to growth of the demand for labour and served to increase division of labour. (3) The social mechanisms underlying elevation of the scale of living are touched upon, and in an optimistic spirit. (4) The distribution of a country's population responded to its progress in opulence, with the rate of this progress conditioned by the degree to which inappropriate (e.g. mercantilist) policies were avoided. (5) Smith dealt briefly with such matters as colonies, education, size of economy, environmental influences, and public policy, all of which he recognized as significant for the quantity and quality of a country's numbers.

Serendipity in the Theater: Maude Adams as James M. Barrie's American Muse.

ERIC Educational Resources Information Center

Diaz de Chumaceiro, Cora L.

2003-01-01

This essay discusses how Maude Adams influenced James M. Barrie's creative process and became his inspiration. Set change theory is underscored as a cognitive explanation for Barrie's illumination. The psychoanalytic theory of transference is proposed as an underlying mechanism for facilitating the change of mental set during the incubation stage.…

[Improvement and the mechanism of cardiac function by knockdown of ADAM10 in adriamycin-induced cardiomyopathy rats].

PubMed

Li, Xiaoou; Xie, Lili; He, Bing; Huang, Wei

2018-01-01

Objective To study the role of a disintegrin and metalloproteinase10 (ADAM10) in shedding neural cadherin (N-cadherin) and develop an approach to interfere the process of ventricular remodeling in adriamycin-induced cardiomyopathy (ACM) rats. Methods In a rat model of ACM, the effects of intraperitoneal injection of the lentiviral RNAi vector of ADAM10 on the morphology of cardiomyocytes and contractile function were observed by HE staining and color Doppler echocardiography. The expressions of N-cadherin and C-terminal fragment 1 (CTF1) were detected by Western blotting and immunohistochemistry. Results In the in vivo experiment, a large amount of fluorescence was seen in the isolated primary cardiomyocytes, which indicated that the transfection in the rat model was successful. In the treatment group, the morphology of cardiomyocytes and function of the heart were evidently improved, N-cadherin protein expression was remarkably up-regulated and CTF1 protein was obviously down-regulated compared with the model group. Conclusion Knock-down of ADAM10 increases N-cadherin expression and decreases CTF1 expression, thus improves cardiac function in the rat model of ACM.

The Adam and Eve Robot Scientists for the Automated Discovery of Scientific Knowledge

NASA Astrophysics Data System (ADS)

King, Ross

A Robot Scientist is a physically implemented robotic system that applies techniques from artificial intelligence to execute cycles of automated scientific experimentation. A Robot Scientist can automatically execute cycles of hypothesis formation, selection of efficient experiments to discriminate between hypotheses, execution of experiments using laboratory automation equipment, and analysis of results. The motivation for developing Robot Scientists is to better understand science, and to make scientific research more efficient. The Robot Scientist `Adam' was the first machine to autonomously discover scientific knowledge: both form and experimentally confirm novel hypotheses. Adam worked in the domain of yeast functional genomics. The Robot Scientist `Eve' was originally developed to automate early-stage drug development, with specific application to neglected tropical disease such as malaria, African sleeping sickness, etc. We are now adapting Eve to work with on cancer. We are also teaching Eve to autonomously extract information from the scientific literature.

Evaluation of ADAM/1 model for advanced coal extraction concepts

NASA Technical Reports Server (NTRS)

Deshpande, G. K.; Gangal, M. D.

1982-01-01

Several existing computer programs for estimating life cycle cost of mining systems were evaluated. A commercially available program, ADAM/1 was found to be satisfactory in relation to the needs of the advanced coal extraction project. Two test cases were run to confirm the ability of the program to handle nonconventional mining equipment and procedures. The results were satisfactory. The model, therefore, is recommended to the project team for evaluation of their conceptual designs.

DARPA ADAMS Project

DTIC Science & Technology

2015-05-11

it means that Mary distrusts John. We showed that it is possible to analyze such trust- distrust relationships within signed social networks in... relationship problems) − Professional Problems (negative changes at workplace, interpersonal conflicts) Furthermore, we encode in 2nd degree variables...a social media forum data. • Processed initial set of Vegas metrics data (clustering coefficient, # similar users, # skip levels) through time

The Dosimetric Importance of Six Degree of Freedom Couch End to End Quality Assurance for SRS/SBRT Treatments when Comparing Intensity Modulated Radiation Therapy to Volumetric Modulated Arc Therapy

NASA Astrophysics Data System (ADS)

Ulizio, Vincent Michael

With the advancement of technology there is an increasing ability for lesions to be treated with higher radiation doses each fraction. This also allows for low fractionated treatments. Because the patient is receiving a higher dose of radiation per fraction and because of the fast dose falloff in these targets there must be extreme accuracy in the delivery. The 6 DOF couch allows for extra rotational corrections and for a more accurate set-up. The movement of the couch needs to be verified to be accurate and because of this, end to end quality assurance tests for the couch have been made. After the set-up is known to be accurate then different treatment techniques can be studied. SBRT of the Spine has a very fast dose falloff near the spinal cord and was typically treated with IMRT. Treatment plans generated using this technique tend to have streaks of low dose radiation, so VMAT is being studied to determine if this treatment technique can reduce the low dose radiation volume as well as improve OAR sparing. For the 6 DOF couch QA, graph paper is placed on the anterior and right lateral sides of the VisionRT OSMS Cube Phantom. Each rotational shift is then applied individually, with a 3 degree shift in the positive and negative directions for pitch and roll. A mark is drawn on the paper to record each shift. A CBCT is then taken of the Cube and known shifts are applied and then an additional CBCT is taken to return the Cube to isocenter. The original IMRT plans for SBRT of the Spine are evaluated and then a plan is made utilizing VMAT. These plans are then compared for low dose radiation, OAR sparing, and conformity. If the original IMRT plan is determined to be an inferior treatment to what is acceptable, then this will be re-planned and compared to the VMAT plan. The 6 DOF couch QA tests have proven to be accurate and reproducible. The average deviations in the 3 degree and -3 degree pitch and roll directions were 0.197, 0.068, 0.091, and 0.110 degrees

Towards the "Informed Use" of Information and Communication Technology in Education: A Response to Adams' "Powerpoint, Habits of Mind, and Classroom Culture"

ERIC Educational Resources Information Center

Vallance, Michael; Towndrow, Phillip A.

2007-01-01

PowerPoint, the widely-used slide-show software package, is finding increasing currency in lecture halls and classrooms as the preferred method of communicating and presenting information. But, as Adams [Adams, C. (2006) "PowerPoint, habits of mind, and classroom culture." "Journal of Curriculum Studies," 38(4), 389-411] attempts to show, users…

Rhetorical Studies: A Reassessment of Adam Smith's Lectures on Rhetoric and Belles Lettres.

ERIC Educational Resources Information Center

Purcell, William M.

1986-01-01

Offers a dissenting interpretation of Adam Smith's Lectures on Rhetoric and Belles Lettres and a more conservative perspective on Smith's significance to the history of rhetorical theory. Views the lectures as an historical commentary on literature and rhetoric from the perspective of an eighteenth-century lecturer. (JD)

Genetic variants of ADAM33 are associated with asthma susceptibility in the Punjabi population of Pakistan.

PubMed

Sabar, Muhammad Farooq; Ghani, Muhammad Usman; Shahid, Mariam; Sumrin, Aleena; Ali, Amjad; Akram, Muhammad; Tariq, Muhammad Akram; Bano, Iqbal

2016-01-01

A disintegrin and metalloproteinase 33 (ADAM33) gene has been considered as an asthma susceptibility gene due to its possible role in airway remodeling, abnormal cell proliferation, and differentiation. Association of this gene with asthma has been reported in several genetic studies on various populations. The current study aims to evaluate the association of ADAM33 gene polymorphisms with the risk of asthma in the Punjabi population of Pakistan. A total of 101 asthma patients and 102 age-matched healthy controls from Lahore, a city in Punjab, were recruited. ADAM33 single nucleotide polymorphisms (SNPs) T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 5[rs597980], ST + 4[rs44707], S2[rs528557], Q - 1[rs612709], and F + 1[rs511898] were genotyped in both patients and controls using single base extension and capillary electrophoresis-based genetic analyzer. The basic allelic and genotypic model was analyzed for association of the SNPs with asthma using SHEsis software. Haploview software was used to calculate pairwise linkage disequilibrium (LD) among six of the genotyped SNPs. Of the 8 SNPs genotyped, only S2[rs528557] showed significant association with asthma (Allele p = 0.0189, Genotype p = 0.021). SNPs T + 1[rs2280089], T2[rs2280090], T1[rs2280091], ST + 4[rs44707], S2[rs528557], and Q - 1[rs612709] were found to be in moderate to strong LD. The significantly higher frequency of haplotype "AAGTCG" in healthy controls suggests a protective effect against asthma risk in the studied population (p = 0.0059). These findings suggest that genetic variants of ADAM33 gene may play important roles in asthma susceptibility in the Punjabi population of Pakistan.

Who was this Man, George Adams

DTIC Science & Technology

1988-03-30

Henry. Smith , John. Steel, Thomas. Strephan, William. Stubbs, Robert. Sutton, David. Tea, John. Terman, Henry. Ward, Matthias. Wilkinson, Will Williams...1778 - General Lachlan McIntosh succeeds Hand. May 19, 1791 - Major Isarc Craig reports Fort Pitt in a ruinous condition - built Fort Lafayette. 1...Quick Step. (Champlain) The Roast Beef. The Rogues March. The Scotch. Slow March. (General Brown’s March) Slow March. (General Scott’s March) Smiths

Modeled inundation limits of potential lahars from Mount Adams in the White Salmon River Valley, Washington

USGS Publications Warehouse

Griswold, Julia P.; Pierson, Thomas C.; Bard, Joseph A.

2018-05-09

Lahars large enough to reach populated areas are a hazard at Mount Adams, a massive volcano in the southern Cascade Range of Washington State (fig. 1). It is considered to be still active and has the potential to erupt again. By definition, lahars are gravity-driven flows of water-saturated mixtures of mud and rock (plus or minus ice, wood, and other debris), which originate from volcanoes and have a variety of potential triggering mechanisms (Vallance, 2000; Vallance and Iverson, 2015). Flowing mixtures can range in fluid consistency from something like a milkshake to something more like wet concrete, and they behave like flash floods, in that they can appear suddenly in river channels with little warning and commonly have boulder- or log-choked flow fronts. Lahars are hazardous because they can flow rapidly in confined valleys (commonly 20–35 miles per hour [mph] or 9–16 meters per second [m/s]), can travel more than 100 miles (mi) (161 kilometers [km]) from a source volcano, and can move with incredible destructive force, carrying multi-ton boulders and logs that can act as battering rams (Pierson, 1998). The biggest threats from lahars to downstream communities are present during eruptive activity, and impacts to communities can be dire. For example, a very large eruption-triggered lahar in Colombia in 1985 surprised and killed more than 20,000 people in a large town located about 45 mi (72 km) downstream and out of sight of the volcano that produced it (Pierson and others, 1990).Mount Adams, one of the largest volcanoes in the Cascade Range, is a composite stratocone composed primarily of andesite lava flows. It has been the most continuously active volcano within the 480-mi2 Mount Adams volcanic field—a region covering parts of Klickitat, Skamania, Yakima, andLewis Counties and part of the Yakama Nation Reservation in Washington State (Hildreth and Fierstein,1995, 1997). About 500,000 years in age, Mount Adams reached its present size by about 15

Inducible expression of A Disintegrin and Metalloproteinase 8 in chronic periodontitis and gingival epithelial cells.

PubMed

Aung, W P P; Chotjumlong, P; Pata, S; Montreekachon, P; Supanchart, C; Khongkhunthian, S; Sastraruji, T; Krisanaprakornkit, S

2017-06-01

The expression of A Disintegrin and Metalloproteinase 8 (ADAM8) is associated with several inflammatory diseases. Elevated ADAM8 levels have been shown in gingival crevicular fluid of patients with chronic periodontitis. The objective of this study was to investigate ADAM8 expression in chronic periodontitis tissues compared with that in normal tissues. ADAM8 expression and its inductive mechanism were examined in human gingival epithelial cells (HGECs) and human gingival fibroblasts. Total RNA and protein were extracted from gingival biopsies of 33 patients with chronic periodontitis and those of 23 healthy volunteers. ADAM8 mRNA and protein expression was analyzed by real-time polymerase chain reaction, immunoblotting and immunohistochemistry. ADAM8 expression in control and stimulated cells in the presence or absence of specific inhibitors for mitogen-activated protein kinase pathways was assayed by real-time polymerase chain reaction, immunoblotting, flow cytometry and immunofluorescence. ADAM8 mRNA and protein expression in chronic periodontitis tissues was significantly greater than that in normal tissues (p < 0.01). Significantly increased ADAM8 expression was detected in the gingival epithelium of chronic periodontitis tissues (p < 0.001). ADAM8 mRNA expression in HGECs, but not in human gingival fibroblasts, was significantly induced by stimulation with Fusobacterium nucleatum (p < 0.05), partially via the p44/42 mitogen-activated protein kinase pathway. ADAM8 expression in the cell lysates and on the surface of HGECs was induced by stimulation with F. nucleatum. ADAM8 expression is increased in inflamed chronic periodontitis tissues and localized within gingival epithelium, consistent with an upregulation of ADAM8 expression in F. nucleatum-stimulated HGECs, suggesting a possible role of ADAM8 in innate immunity of periodontal tissue. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Expression of L1-CAM and ADAM10 in human colon cancer cells induces metastasis.

PubMed

Gavert, Nancy; Sheffer, Michal; Raveh, Shani; Spaderna, Simone; Shtutman, Michael; Brabletz, Thomas; Barany, Francis; Paty, Phillip; Notterman, Daniel; Domany, Eytan; Ben-Ze'ev, Avri

2007-08-15

L1-CAM, a neuronal cell adhesion receptor, is also expressed in a variety of cancer cells. Recent studies identified L1-CAM as a target gene of beta-catenin-T-cell factor (TCF) signaling expressed at the invasive front of human colon cancer tissue. We found that L1-CAM expression in colon cancer cells lacking L1-CAM confers metastatic capacity, and mice injected in their spleen with such cells form liver metastases. We identified ADAM10, a metalloproteinase that cleaves the L1-CAM extracellular domain, as a novel target gene of beta-catenin-TCF signaling. ADAM10 overexpression in colon cancer cells displaying endogenous L1-CAM enhanced L1-CAM cleavage and induced liver metastasis, and ADAM10 also enhanced metastasis in colon cancer cells stably transfected with L1-CAM. DNA microarray analysis of genes induced by L1-CAM in colon cancer cells identified a cluster of genes also elevated in a large set of human colon carcinoma tissue samples. Expression of these genes in normal colon epithelium was low. These results indicate that there is a gene program induced by L1-CAM in colon cancer cells that is also present in colorectal cancer tissue and suggest that L1-CAM can serve as target for colon cancer therapy.

Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand–dependent terminal keratinocyte differentiation

PubMed Central

Cobzaru, Cristina; Triantafyllopoulou, Antigoni; Löffek, Stefanie; Horiuchi, Keisuke; Threadgill, David W.; Kurz, Thomas; van Rooijen, Nico; Bruckner-Tuderman, Leena

2012-01-01

ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17ΔKC) have a normal epidermal barrier and skin architecture at birth but develop pronounced defects in epidermal barrier integrity soon after birth and develop chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 d after birth, followed by reduced transglutaminase (TGM) activity, transepidermal water loss, up-regulation of the proinflammatory cytokine IL-36α, and inflammatory immune cell infiltration. Activation of the EGFR was strongly reduced in A17ΔKC skin, and topical treatment of A17ΔKC mice with recombinant TGF-α significantly improved TGM activity and decreased skin inflammation. Finally, we show that mice lacking the EGFR in keratinocytes (EgfrΔKC) closely resembled A17ΔKC mice. Collectively, these results identify a previously unappreciated critical role of the ADAM17–EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier and suggest that this pathway could represent a good target for treatment of epidermal barrier defects. PMID:22565824

Music for Elementary Teachers; Self-Help Guide (MUS 370). Adams State College.

ERIC Educational Resources Information Center

Stokes, Cloyce

This self-help guide for the music teacher is one of a series of eight Teacher Education Modules developed by Adams State College Teacher Corps Program. The guide itself consists of 11 modules, the first five of which focus on the mathematical and scientific aspects of music--pitch, tempo, furation, time, and key. These five modules are…

Sequence-specific interaction between the disintegrin domain of mouse ADAM 3 and murine eggs: role of beta1 integrin-associated proteins CD9, CD81, and CD98.

PubMed

Takahashi, Y; Bigler, D; Ito, Y; White, J M

2001-04-01

ADAM 3 is a sperm surface glycoprotein that has been implicated in sperm-egg adhesion. Because little is known about the adhesive activity of ADAMs, we investigated the interaction of ADAM 3 disintegrin domains, made in bacteria and in insect cells, with murine eggs. Both recombinant proteins inhibited sperm-egg binding and fusion with potencies similar to that which we recently reported for the ADAM 2 disintegrin domain. Alanine scanning mutagenesis revealed a critical importance for the glutamine at position 7 of the disintegrin loop. Fluorescent beads coated with the ADAM 3 disintegrin domain bound to the egg surface. Bead binding was inhibited by an authentic, but not by a scrambled, peptide analog of the disintegrin loop. Bead binding was also inhibited by the function-blocking anti-alpha6 monoclonal antibody (mAb) GoH3, but not by a nonfunction blocking anti-alpha6 mAb, or by mAbs against either the alphav or beta3 integrin subunits. We also present evidence that in addition to the tetraspanin CD9, two other beta1-integrin-associated proteins, the tetraspanin CD81 as well as the single pass transmembrane protein CD98 are expressed on murine eggs. Antibodies to CD9 and CD98 inhibited in vitro fertilization and binding of the ADAM 3 disintegrin domain. Our findings are discussed in terms of the involvement of multiple sperm ADAMs and multiple egg beta1 integrin-associated proteins in sperm-egg binding and fusion. We propose that an egg surface "tetraspan web" facilitates fertilization and that it may do so by fostering ADAM-integrin interactions.

ADAM10 and γ-secretase regulate sensory regeneration in the avian vestibular organs.

PubMed

Warchol, Mark E; Stone, Jennifer; Barton, Matthew; Ku, Jeffrey; Veile, Rose; Daudet, Nicolas; Lovett, Michael

2017-08-01

The loss of sensory hair cells from the inner ear is a leading cause of hearing and balance disorders. The mammalian ear has a very limited ability to replace lost hair cells, but the inner ears of non-mammalian vertebrates can spontaneously regenerate hair cells after injury. Prior studies have shown that replacement hair cells are derived from epithelial supporting cells and that the differentiation of new hair cells is regulated by the Notch signaling pathway. The present study examined molecular influences on regeneration in the avian utricle, which has a particularly robust regenerative ability. Chicken utricles were placed in organotypic culture and hair cells were lesioned by application of the ototoxic antibiotic streptomycin. Cultures were then allowed to regenerate in vitro for seven days. Some specimens were treated with small molecule inhibitors of γ-secretase or ADAM10, proteases which are essential for transmission of Notch signaling. As expected, treatment with both inhibitors led to increased numbers of replacement hair cells. However, we also found that inhibition of both proteases resulted in increased regenerative proliferation. Subsequent experiments showed that inhibition of γ-secretase or ADAM10 could also trigger proliferation in undamaged utricles. To better understand these phenomena, we used RNA-Seq profiling to characterize changes in gene expression following γ-secretase inhibition. We observed expression patterns that were consistent with Notch pathway inhibition, but we also found that the utricular sensory epithelium contains numerous γ-secretase substrates that might regulate cell cycle entry and possibly supporting cell-to-hair cell conversion. Together, our data suggest multiple roles for γ-secretase and ADAM10 in vestibular hair cell regeneration. Copyright © 2017. Published by Elsevier Inc.

The LGI1–ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function

PubMed Central

Lovero, Kathryn L.; Fukata, Yuko; Granger, Adam J.; Fukata, Masaki; Nicoll, Roger A.

2015-01-01

Synapse development is coordinated by a number of transmembrane and secreted proteins that come together to form synaptic organizing complexes. Whereas a variety of synaptogenic proteins have been characterized, much less is understood about the molecular networks that support the maintenance and functional maturation of nascent synapses. Here, we demonstrate that leucine-rich, glioma-inactivated protein 1 (LGI1), a secreted protein previously shown to modulate synaptic AMPA receptors, is a paracrine signal released from pre- and postsynaptic neurons that acts specifically through a disintegrin and metalloproteinase protein 22 (ADAM22) to set postsynaptic strength. We go on to describe a novel role for ADAM22 in maintaining excitatory synapses through PSD-95/Dlg1/zo-1 (PDZ) domain interactions. Finally, we show that in the absence of LGI1, the mature synapse scaffolding protein PSD-95, but not the immature synapse scaffolding protein SAP102, is unable to modulate synaptic transmission. These results indicate that LGI1 and ADAM22 form an essential synaptic organizing complex that coordinates the maturation of excitatory synapses by regulating the functional incorporation of PSD-95. PMID:26178195

[Professor Adam Nowosławski (1925-2012)--founder of the Polish School of Immunopathology].

PubMed

Madaliński, Kazimierz

2012-01-01

Professor dr med. Adam Nowosławski, has died at age of 87, on February 3, 2012, the founder of the Polish school of immunopathology, member of Polish Academy of Sciences and of Polish Academy of Art and Sciences. Professor was born on April 30, 1925 in Rzeszów (SE Poland). During the Second World War he took part in the anti-nazi resistance movement; he was the soldier of the 'Baszta' regiment of the Home Army. Subsequently, he was imprisoned in the Pawiak and concentration camps: Majdanek and Buchenwald. The medical studies he has completed at Warsaw Medical Academy between 1946-1951. The degree of doctor of medicine Prof. Adam Nowosławski has obtained in 1963, habilitation degree in the field of immunopathology--in 1966; the title of Professor he has obtained in 1980. His scientific achievements consist of 170 publications, including 101 original papers. His publications were quoted in several American books for students and physicians. Topics of his early papers concerned the immunopatogenesis ofPneumocystis carinii--induced pneumonia in premature babies, immunopatogenesis of rheumatoid arthritis, and the origin of rheumatoid factor. The enormous role in the field of hepatology played research on the virus of hepatitis B. These studies dealt with the discovery of HB core antigen which had the cellular localization different from HB surface antigen and with the parameters of the immune response to infection. Papers published on this topic were the mostly quoted in the literature and earned him national awards. The activity of Prof. Adam Nowosławski in the field of HIV/AIDS prevention was honored by the special prize of the Minister of Health. Professor was the honorary member of the two Societies: Polish Society of Pathologists and Polish Society of Hepatology. He was also the member of International Association for the Study of the Liver and International Academy of Pathology. Prof. Adam Nowosławski received the national medals: Polonia Restituta Crosses

Foreword: Sir John Pendry FRS Sir John Pendry FRS

NASA Astrophysics Data System (ADS)

Inglesfield, John; Echenique, Pedro

2008-07-01

John Pendry John Inglesfield and Pedro Echenique write: John Pendry's 65th birthday is on 4 July 2008, and this issue of the Journal of Physics: Condensed Matter is dedicated to him, with articles by friends, colleagues, and former students. By any standards, John Pendry is a great scientist, who has made—and continues to make—an enormous contribution to physics; the wide range of his interests is reflected in the scope of these articles. Not many scientists can establish a completely new and unexpected area of research, but this has been John's achievement in the last few years in the field of metamaterials, materials whose electromagnetic properties depend on their structure rather than the materials of which the structure is built. In this way, structures with effectively negative electrical permittivity and negative magnetic permeability can be constructed, demonstrating negative refraction; through metamaterials scientists now have access to properties not found in nature, and never previously explored experimentally. Never a week goes by without a potential new application of metamaterials, whether it is perfect lensing, or the cloak of invisibility. This has certainly led to tremendous visibility for John himself, with guest lectures all over the world, and radio and television appearances. John Pendry's first paper was published exactly 40 years ago, 'Analytic properties of pseudopotentials' [1], and since then he has published 310 articles at the latest count. But this first paper already reflected something of the way John works. His PhD project, with Volker Heine at the Cavendish Laboratory, was to interpret the scattering of low energy electrons from surfaces, the technique of LEED which was to become the method of choice for determining surface structure. Although the energy of the electrons in LEED is relatively low—say 50 eV—it is much higher than the energy of the conduction electrons, for which pseudopotentials had been devised, and John

Impact of treatment planning with deformable image registration on dose distribution for carbon-ion beam lung treatment using a fixed irradiation port and rotating couch.

PubMed

Kumagai, M; Mori, S; Yamamoto, N

2015-06-01

When using a fixed irradiation port, treatment couch rotation is necessary to increase beam angle selection. We evaluated dose variations associated with positional morphological changes to organs. We retrospectively chose the data sets of ten patients with lung cancer who underwent respiratory-gated CT at three different couch rotation angles (0°, 20° and -20°). The respective CT data sets are referred to as CT0, CT20 and CT-20. Three treatment plans were generated as follows: in Plan 1, all compensating bolus designs and dose distributions were calculated using CT0. To evaluate the rotation effect without considering morphology changes, in Plan 2, the compensating boli designed using CT0 were applied to the CT±20 images. Plan 3 involved compensating boli designed using the CT±20 images. The accumulated dose distributions were calculated using deformable image registration (DIR). A sufficient prescribed dose was calculated for the planning target volume (PTV) in Plan 1 [minimum dose received by a volume ≥95% (D95) > 95.8%]. By contrast, Plan 2 showed degraded dose conformation to the PTV (D95 > 90%) owing to mismatch of the bolus design to the morphological positional changes in the respective CT. The dose assessment results of Plan 3 were very close to those of Plan 1. Dose distribution is significantly affected by whether or not positional organ morphology changes are factored into dose planning. In treatment planning using multiple CT scans with different couch positions, it is mandatory to calculate the accumulated dose using DIR.

N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)-benzylamine (4-(18)F-ADAM): an improved PET radioligand for serotonin transporters.

PubMed

Shiue, Grace G; Choi, Seok-Rye; Fang, Ping; Hou, Catherine; Acton, Paul D; Cardi, Chris; Saffer, Janet R; Greenberg, Joel H; Karp, Joel S; Kung, Hank F; Shiue, Chyng-Yann

2003-12-01

There has been considerable interest in the development of PET radioligands that are useful for imaging serotonin transporter (SERT) in the living human brain. For the last decade, (11)C-(+)McN5652 has been the most promising PET agent for studying SERT in humans. However, this agent has some limitations. Recently, a new promising SERT PET radioligand, 3-(11)C-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile, has been reported. We recently reported the synthesis of a new (18)F-labeled SERT PET radioligand, N,N-dimethyl-2-(2-amino-4-(18)F-fluorophenylthio)benzylamine (4-(18)F-ADAM), which may have advantages over (11)C-labeled radioligands. The purpose of this study was to evaluate this newly developed (18)F-labeled PET radioligand as a promising agent for studying SERT in the living human brain. This agent was evaluated by studying its in vitro binding to different monoamine transporters, its in vivo biodistributions in rats, its integrity and pharmacologic profiles in rat brain, and its distribution in a female baboon brain. In vitro binding assays showed that 4-F-ADAM displayed high affinity to SERT sites (inhibition constant = 0.081 nmol/L, using membrane preparations of LLC-PK1 cells expressing the specific transporter) and showed more than 1,000- and 28,000-fold selectivity for SERT over norepinephrine transporter and dopamine transporter, respectively. Biodistribution of 4-(18)F-ADAM in rats showed a high initial uptake and slow clearance in the brain (2.13%, 1.90%, and 0.95% injected dose per organ at 2, 30, and 60 min after intravenous injection, respectively), with the specific binding peaking at 2 h after injection (hypothalamus/cerebellum = 12.49). The uptake in blood, muscle, lung, kidney, and liver was also initially high but cleared rapidly. The radioactivity in the femur increases with time for 4-(18)F-ADAM, indicating that in vivo defluorination may occur. In vivo metabolism studies in rats showed that 4-(18)F-ADAM was not metabolized in

St. John's Wort (image)

MedlinePlus

The herb St. John's Wort is believed to be helpful in relieving mild to moderate depression, but should only be taken under a physician's supervision. St. John's Wort may clash with other medications or ...

TACE/ADAM17 is essential for oligodendrocyte development and CNS myelination.

PubMed

Palazuelos, Javier; Crawford, Howard C; Klingener, Michael; Sun, Bingru; Karelis, Jason; Raines, Elaine W; Aguirre, Adan

2014-09-03

Several studies have elucidated the significance of a disintegrin and metalloproteinase proteins (ADAMs) in PNS myelination, but there is no evidence if they also play a role in oligodendrogenesis and CNS myelination. Our study identifies ADAM17, also called tumor necrosis factor-α converting enzyme (TACE), as a novel key modulator of oligodendrocyte (OL) development and CNS myelination. Genetic deletion of TACE in oligodendrocyte progenitor cells (OPs) induces premature cell cycle exit and reduces OL cell survival during postnatal myelination of the subcortical white matter (SCWM). These cellular and molecular changes lead to deficits in SCWM myelination and motor behavior. Mechanistically, TACE regulates oligodendrogenesis by modulating the shedding of EGFR ligands TGFα and HB-EGF and, consequently, EGFR signaling activation in OL lineage cells. Constitutive TACE depletion in OPs in vivo leads to similar alterations in CNS myelination and motor behavior as to what is observed in the EGFR hypofunctional mouse line EgfrWa2. EGFR overexpression in TACE-deficient OPs restores OL survival and development. Our study reveals an essential function of TACE in oligodendrogenesis, and demonstrates how this molecule modulates EGFR signaling activation to regulate postnatal CNS myelination. Copyright © 2014 the authors 0270-6474/14/3411884-13$15.00/0.

SU-E-T-234: Daily Quality Assurance for a Six Degrees of Freedom Couch Using a Novel Phantom

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

Woods, K; Woollard, J; Ayan, A

2015-06-15

Purpose: To test the accuracy and reproducibility of both translational and rotational movements for a couch with six degrees of freedom (6DoF) using a novel phantom design Methods: An end-to-end test was carried out using two different phantoms. A 6 cm3 cube with a central fiducial BB (WL-QA Sun Nuclear) and a custom fabricated rectangular prism (31 cm x 8 cm x 8 cm), placed on a baseplate with known angular offsets for pitch, roll and yaw with a central fiducial BB and unique surface structures for registration purposes, were used. The end-to-end test included an initial CT simulation formore » a reference study, setup to an offset mark on each phantom, registration of the reference CT to the acquired cone-beam CT, and final Winston-Lutz delivery at four cardinal gantry angles. Results for both translational and rotational movements were recorded and compared for both phantoms. Results: Translational and rotational measurements were performed with a PerfectPitch (Varian) couch for 10 trials for both phantoms. Distinct translational shifts were [−5.372±0.384mm, −10.183±0.137mm, 14.028±0.155mm] for the cube and [7.520±0.159mm, −9.117±0.101mm, 16.273±0.115mm] for the prototype phantom for lateral, longitudinal, and vertical shifts, respectively. Distinct rotational adjustments were [1.121±0.102o, −1.067±0.235o, −2.662±0.380o] for the cube and [2.534±0.059o, 1.994±0.025o, 2.094±0.076o] for the prototype for pitch, roll, and yaw, respectively. Winston-Lutz test results performed after 6DoF couch correction from each cardinal gantry angle ranged from 0.26–0.72mm for the cube and 0.55–0.86mm for the prototype. Conclusion: The prototype phantom is more precise for both translational and rotational adjustments compared to a commercial phantom. The design of the prototype phantom allows for a more discernible visual confirmation of correct translational and rotational adjustments with the prototype phantom. Winston-Lutz results are more accurate

Rival ecologies of global commerce: Adam Smith and the natural historians.

PubMed

Jonsson, Fredrik Albritton

2010-01-01

This essay explores how the defense of global commerce pioneered in the Enlightenment was tied to the improvement of the natural order. Two rival ecologies, one made by natural historians and the other developed by Adam Smith and his liberal successors, vied for intellectual precedence as well as for practical application in the metropole and the colonies. Together they constitute the beginnings of an ongoing quarrel over the environmental foundation of capitalism.

The Sargassum Frogfish (Histrio histrio Linnaeus) observed in mangroves in St. John, US Virgin Islands

USGS Publications Warehouse

Rogers, C.S.; Pietsch, T.W.; Randall, J.E.; Arnold, R.J.

2010-01-01

The Sargassum Frogfish (Histrio histrio), the only pelagic member of the frogfish family Antennariidae, is considered an obligate associate of floating mats of the brown algae Sargassum natans and S. fluitans (Adams 1960; Dooley 1972; Pietsch and Grobecker 1987). Between February and April 2010, 20 of these fish were observed in three mangrove-fringed bays in Virgin Islands Coral Reef National Monument, St. John, US Virgin Islands. All of them were clinging to clumps of the red alga Acanthophora spicifera growing on the submerged prop roots of red mangrove trees (Rhizophora mangle) distributed along an estimated total of 2,160 mof shoreline (Fig. 1). All of the fish were at a depth of less than 0.5 meters. Two individuals were seen on one prop root, but the other 18 were solitary. Their estimated standard lengths ranged from about 20 to 100 mm. Littler and Littler (2000, p. 295) published a photograph of one individual in blades of the green alga Ulva lactuca growing on a prop root in Belize. This is the first report of the Sargassum Frogfish living in association with attached algae.

Detrital zircon geochronology of the Adams Argillite and Nation River Formation, east-central Alaska, U.S.A

USGS Publications Warehouse

Gehrels, G.E.; Johnsson, M.J.; Howell, D.G.

1999-01-01

The Cambrian Adams Argillite and the Devonian Nation River Formation are two sandstone-bearing units within a remarkably complete Paleozoic stratigraphic section in east-central Alaska. These strata, now foreshortened and fault-bounded, were originally contiguous with miogeoclinal strata to the east that formed as a passive-margin sequence along the northwestern margin of the North American continent. Seventy-five detrital zircon grains from the Adams Argillite and the Nation River Formation were analyzed in an effort to provide constraints on the original sources of the grains, and to generate a detrital zircon reference for miogeoclinal strata in the northern Cordillera. Thirty-five single zircon grains from a quartzite in the Adams Argillite yield dominant age clusters of 1047-1094 (n = 6), 1801-1868 (n = 10), and 2564-2687 (n = 5) Ma. Forty zircons extracted from a sandstone in the Nation River Formation yield clusters primarily of 424-434 (n = 6), 1815-1838 (n = 6), 1874-1921 (n = 7), and 2653-2771 (n = 4) Ma. The Early Proterozoic and Archean grains in both units probably originated in basement rocks in a broad region of the Canadian Shield. In contrast, the original igneous sources for mid-Protcrozoic grains in the Adams Argillite and ??? 430 Ma grains in the Nation River Formation are more difficult to identify. Possible original sources for the mid-Proterozoic grains include: (1) the Grenville Province of eastern Laurentia, (2) the Pearya terrane along the Arctic margin, and (3) mid-Proterozoic igneous rocks that may have been widespread along or outboard of the Cordilleran margin. The ??? 430 Ma grains may have originated in: (1) arc-type sources along the Cordilleran margin, (2) the Caledonian orogen, or (3) a landmass, such as Pearya, Siberia, or crustal fragments now in northern Asia, that resided outboard of the Innuitian orogen during mid-Paleozoic time. Copyright ?? 1999, SEPM (Society for Sedimentary Geology).

Mt, St. Helens, Mt. Adams, and Mt. Rainier, WA, USA

NASA Technical Reports Server (NTRS)

1992-01-01

This view of Mt. St. Helens (46.5N, 122.0W), taken 12 years after the volcanic eruption on 18 May 1980, in which the top 1300 ft. of the 9,677 ft. mountain was blown away, shows the rapid vegetation recovery within the blast area. Many fir trees have grown to heights of 20 ft. within the 150 square mile devastated area. Mt. Adams, an extinct volcano is just to the west and Mt. Rainier is to the north. Checkerboard logging can be seen throughout.

Jasper Johns' Painted Words.

ERIC Educational Resources Information Center

Levinger, Esther

1989-01-01

States that the painted words in Jasper Johns' art act in two different capacities: concealed words partake in the artist's interrogation of visual perception; and visible painted words question classical representation. Argues that words are Johns' means of critiquing modernism. (RS)

Mid-trimester maternal ADAM12 levels differ according to fetal gender in pregnancies complicated by preeclampsia.

PubMed

Myers, Jenny E; Thomas, Grégoire; Tuytten, Robin; Van Herrewege, Yven; Djiokep, Raoul O; Roberts, Claire T; Kenny, Louise C; Simpson, Nigel A B; North, Robyn A; Baker, Philip N

2015-02-01

An overrepresentation of adverse pregnancy outcomes has been observed in pregnancies associated with a male fetus. We investigated the association between fetal gender and candidate biomarkers for preeclampsia. Proteins were quantified in samples taken at 20 weeks from women recruited to the SCreening fOr Pregnancy Endpoints (SCOPE) study (preeclampsia n = 150; no preeclampsia n = 450). In contrast to placental growth factor, soluble endoglin, and insulin-like growth factor acid labile subunit, levels of metallopeptidase domain 12 (ADAM12) at 20 weeks were dependent on fetal gender in pregnancies complicated by preeclampsia, for male (n = 73) fetuses the multiples of the median (MoM; interquartile range [IQR] 1.1-1.5) was 1.3, whereas for female fetuses (n = 75) MoM was 1.1 (1.0-1.3); P < .01. Prediction of preeclampsia using ADAM12 levels was improved for pregnancies associated with a male fetus (area under receiver-operator curve [AUC] 0.73 [95% confidence interval [CI] 0.67-0.80]) than that of a female fetus (AUC 0.62 [0.55-0.70]); P = .03. The data presented here fit a contemporary hypothesis that there is a difference between the genders in response to an adverse maternal environment and suggest that an alteration in ADAM12 may reflect an altered placental response in pregnancies subsequently complicated by preeclampsia. © The Author(s) 2014.

Cocaine use and syphilis trends: findings from the arrestee drug abuse monitoring (ADAM) program and syphilis epidemiology in Houston.

PubMed

Ross, Michael W; Risser, Jan; Peters, Ronald J; Johnson, Regina J

2006-01-01

There has been speculation that trends in syphilis have been fueled by crack cocaine use. This study examined the data on syphilis notifications and arrestee drug abuse monitoring (ADAM) to ascertain the relationships between syphilis and cocaine use trends in three racial/ethnic groups. Syphilis notifications and data from the ADAM project were compared in Houston/Harris County, Texas, from 1991-1998 using a linear regression equation. Data indicated significant relationships between the data for cocaine use and syphilis in African Americans but not Hispanics or non-Hispanic whites. For African Americans, 58% of the variance between cocaine use and syphilis was explained. When data limited to jail syphilis notifications and ADAM cocaine in African Americans were examined, the association was stronger for males than for females. For African Americans, cocaine (probably crack cocaine) use trends were significantly associated with syphilis trends in this population. These data suggest that control of crack cocaine may have an impact on syphilis rates and that there may be close relationships between some STDs and drug abuse.

Critical Role of the Disintegrin Metalloprotease ADAM-like Decysin-1 [ADAMDEC1] for Intestinal Immunity and Inflammation.

PubMed

O'Shea, Nuala R; Chew, Thean S; Dunne, Jenny; Marnane, Rebecca; Nedjat-Shokouhi, Bahman; Smith, Philip J; Bloom, Stuart L; Smith, Andrew M; Segal, Anthony W

2016-12-01

ADAM [A Disintegrin And Metalloproteinase] is a family of peptidase proteins which have diverse roles in tissue homeostasis and immunity. Here, we study ADAM-like DECysin-1 [ADAMDEC1] a unique member of the ADAM family. ADAMDEC1 expression is restricted to the macrophage/dendritic cell populations of the gastrointestinal tract and secondary lymphoid tissue. The biological function of ADAMDEC1 is unknown but it has been hypothesised to play a role in immunity. The identification of reduced ADAMDEC1 expression in Crohn's disease patients has provided evidence of a potential role in bowel inflammation. Adamdec1 -/- mice were exposed to dextran sodium sulphate or infected orally with Citrobacter rodentium or Salmonella typhimurium. The clinical response was monitored. The loss of Adamdec1 rendered mice more susceptible to the induction of bacterial and chemical induced colitis, as evidenced by increased neutrophil infiltration, greater IL-6 and IL-1β secretion, more weight loss and increased mortality. In the absence of Adamdec1, greater numbers of Citrobacter rodentium were found in the spleen, suggestive of a breakdown in mucosal immunity which resulted in bacteraemia. In summary, ADAMDEC1 protects the bowel from chemical and bacterial insults, failure of which may predispose to Crohn's disease. © European Crohn’s and Colitis Organisation 2016.

The futility of utility: how market dynamics marginalize Adam Smith

NASA Astrophysics Data System (ADS)

McCauley, Joseph L.

2000-10-01

Economic theorizing is based on the postulated, nonempiric notion of utility. Economists assume that prices, dynamics, and market equilibria are supposed to be derived from utility. The results are supposed to represent mathematically the stabilizing action of Adam Smith's invisible hand. In deterministic excess demand dynamics I show the following. A utility function generally does not exist mathematically due to nonintegrable dynamics when production/investment are accounted for, resolving Mirowski's thesis. Price as a function of demand does not exist mathematically either. All equilibria are unstable. I then explain how deterministic chaos can be distinguished from random noise at short times. In the generalization to liquid markets and finance theory described by stochastic excess demand dynamics, I also show the following. Market price distributions cannot be rescaled to describe price movements as ‘equilibrium’ fluctuations about a systematic drift in price. Utility maximization does not describe equilibrium. Maximization of the Gibbs entropy of the observed price distribution of an asset would describe equilibrium, if equilibrium could be achieved, but equilibrium does not describe real, liquid markets (stocks, bonds, foreign exchange). There are three inconsistent definitions of equilibrium used in economics and finance, only one of which is correct. Prices in unregulated free markets are unstable against both noise and rising or falling expectations: Adam Smith's stabilizing invisible hand does not exist, either in mathematical models of liquid market data, or in real market data.

The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin β and ADAM10.

PubMed

Jefferson, Tamara; Auf dem Keller, Ulrich; Bellac, Caroline; Metz, Verena V; Broder, Claudia; Hedrich, Jana; Ohler, Anke; Maier, Wladislaw; Magdolen, Viktor; Sterchi, Erwin; Bond, Judith S; Jayakumar, Arumugam; Traupe, Heiko; Chalaris, Athena; Rose-John, Stefan; Pietrzik, Claus U; Postina, Rolf; Overall, Christopher M; Becker-Pauly, Christoph

2013-01-01

The in vivo roles of meprin metalloproteases in pathophysiological conditions remain elusive. Substrates define protease roles. Therefore, to identify natural substrates for human meprin α and β we employed TAILS (terminal amine isotopic labeling of substrates), a proteomics approach that enriches for N-terminal peptides of proteins and cleavage fragments. Of the 151 new extracellular substrates we identified, it was notable that ADAM10 (a disintegrin and metalloprotease domain-containing protein 10)-the constitutive α-secretase-is activated by meprin β through cleavage of the propeptide. To validate this cleavage event, we expressed recombinant proADAM10 and after preincubation with meprin β, this resulted in significantly elevated ADAM10 activity. Cellular expression in murine primary fibroblasts confirmed activation. Other novel substrates including extracellular matrix proteins, growth factors and inhibitors were validated by western analyses and enzyme activity assays with Edman sequencing confirming the exact cleavage sites identified by TAILS. Cleavages in vivo were confirmed by comparing wild-type and meprin(-/-) mice. Our finding of cystatin C, elafin and fetuin-A as substrates and natural inhibitors for meprins reveal new mechanisms in the regulation of protease activity important for understanding pathophysiological processes.

Working for the People? Mrs Bridges Adams and the London School Board, 1897-1904.

ERIC Educational Resources Information Center

Martin, Jane

2000-01-01

Focuses on Mrs. Bridges Adams who was a supporter of state maintenance committed to educational opportunity for workers' children. Focuses on her political recruitment, her contribution to the work of the London School Board (England), and her role in the struggle to save the school board system. (CMK)

Sequence-Specific Interaction between the Disintegrin Domain of Mouse ADAM 3 and Murine Eggs: Role of β1 Integrin-associated Proteins CD9, CD81, and CD98

PubMed Central

Takahashi, Yuji; Bigler, Dora; Ito, Yasuhiko; White, Judith M.

2001-01-01

ADAM 3 is a sperm surface glycoprotein that has been implicated in sperm-egg adhesion. Because little is known about the adhesive activity of ADAMs, we investigated the interaction of ADAM 3 disintegrin domains, made in bacteria and in insect cells, with murine eggs. Both recombinant proteins inhibited sperm-egg binding and fusion with potencies similar to that which we recently reported for the ADAM 2 disintegrin domain. Alanine scanning mutagenesis revealed a critical importance for the glutamine at position 7 of the disintegrin loop. Fluorescent beads coated with the ADAM 3 disintegrin domain bound to the egg surface. Bead binding was inhibited by an authentic, but not by a scrambled, peptide analog of the disintegrin loop. Bead binding was also inhibited by the function-blocking anti-α6 monoclonal antibody (mAb) GoH3, but not by a nonfunction blocking anti-α6 mAb, or by mAbs against either the αv or β3 integrin subunits. We also present evidence that in addition to the tetraspanin CD9, two other β1-integrin-associated proteins, the tetraspanin CD81 as well as the single pass transmembrane protein CD98 are expressed on murine eggs. Antibodies to CD9 and CD98 inhibited in vitro fertilization and binding of the ADAM 3 disintegrin domain. Our findings are discussed in terms of the involvement of multiple sperm ADAMs and multiple egg β1 integrin-associated proteins in sperm-egg binding and fusion. We propose that an egg surface “tetraspan web” facilitates fertilization and that it may do so by fostering ADAM–integrin interactions. PMID:11294888

Functional and molecular evidence for expression of the renin angiotensin system and ADAM17-mediated ACE2 shedding in COS7 cells

PubMed Central

Grobe, Nadja; Di Fulvio, Mauricio; Kashkari, Nada; Chodavarapu, Harshita; Somineni, Hari K.; Singh, Richa

2015-01-01

The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal functions. COS7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aims of this study were to 1) demonstrate the presence of an endogenous and functional RAS in COS7, and 2) investigate the role of a disintegrin and metalloproteinase-17 (ADAM17) in the ectodomain shedding of angiotensin converting enzyme-2 (ACE2). Reverse transcription coupled to gene-specific polymerase chain reaction demonstrated expression of ACE, ACE2, angiotensin II type 1 receptor (AT1R), and renin at the transcript levels in total RNA cell extracts. Western blot and immunohistochemistry identified ACE (60 kDa), ACE2 (75 kDa), AT1R (43 kDa), renin (41 kDa), and ADAM17 (130 kDa) in COS7. At the functional level, a sensitive and selective mass spectrometric approach detected endogenous renin, ACE, and ACE2 activities. ANG-(1–7) formation (m/z 899) from the natural substrate ANG II (m/z 1,046) was detected in lysates and media. COS7 cells stably expressing shRNA constructs directed against endogenous ADAM17 showed reduced ACE2 shedding into the media. This is the first study demonstrating endogenous expression of the RAS and ADAM17 in the widely used COS7 cell line and its utility to study ectodomain shedding of ACE2 mediated by ADAM17 in vitro. The transfectable nature of this cell line makes it an attractive cell model for studying the molecular, functional, and pharmacological properties of the renal RAS. PMID:25740155

How To Survive in Postindustrial Environments: Adam Smith's Advice for Today's Colleges and Universities.

ERIC Educational Resources Information Center

Ortmann, Andreas

1997-01-01

Adam Smith's discussion of the payment modes of teachers and resulting consequences for the quality of teaching and process of curricular innovation are reviewed through the conceptual lens of modern agency theory. Smith's analysis of higher education in his day (eighteenth century) sheds light on faculty incentive and assessment problems that…

Maniac Talk - John Mather

NASA Image and Video Library

2014-11-19

John Mather Maniac Lecture, November 19, 2014 Nobel Laureate John Mather presented a Maniac Talk entitled "Creating the Future: Building JWST, what it may find, and what comes next?" In this lecture, John takes a rear view look at how James Webb Space Telescope was started, what it can see and what it might discover. He describes the hardware, what it was designed to observe, and speculate about the surprises it might uncover. He also outlines a possible future of space observatories: what astronomers want to build, what we need to invent, and what they might find, even the chance of discovering life on planets around other stars.

Making Socialists: Mary Bridges Adams and the Fight for Knowledge and Power, 1855-1939

ERIC Educational Resources Information Center

Weiler, Kathleen

2012-01-01

This article presents a review of "Making socialists: Mary Bridges Adams and the fight for knowledge and power, 1855-1939," by Jane Martin. Jane Martin has explored the history of late-nineteenth-century and early-twentieth century-British women educational activists in numerous publications over the past two decades. Her first book,…

Why Did the Founding Fathers Write the Constitution of the United States?

ERIC Educational Resources Information Center

Singer, Alan

1987-01-01

Presents a mock dialogue among Thomas Jefferson, John Adams, James Madison, Alexander Hamilton, and Abigail Adams that questions whether the Founding Fathers wrote the U.S. Constitution as defenders of hard-won liberty or as self-serving aristocrats whose sole interest was in preserving their own economic and political positions. (BSR)

An overview of Airborne Data for Assessing Models (ADAM): a web development effort to effectively disseminate airborne data products

NASA Astrophysics Data System (ADS)

Mangosing, D. C.; Chen, G.; Kusterer, J.; Rinsland, P.; Perez, J.; Sorlie, S.; Parker, L.

2011-12-01

One of the objectives of the NASA Langley Research Center's MEaSURES project, "Creating a Unified Airborne Database for Model Assessment", is the development of airborne Earth System Data Records (ESDR) for the regional and global model assessment and validation activities performed by the tropospheric chemistry and climate modeling communities. The ongoing development of ADAM, a web site designed to access a unified, standardized and relational ESDR database, meets this objective. The ESDR database is derived from publically available data sets, from NASA airborne field studies to airborne and in-situ studies sponsored by NOAA, NSF, and numerous international partners. The ADAM web development activities provide an opportunity to highlight a growing synergy between the Airborne Science Data for Atmospheric Composition (ASD-AC) group at NASA Langley and the NASA Langley's Atmospheric Sciences Data Center (ASDC). These teams will collaborate on the ADAM web application by leveraging the state-of-the-art service and message-oriented data distribution architecture developed and implemented by ASDC and using a web-based tool provided by the ASD-AC group whose user interface accommodates the nuanced perspective of science users in the atmospheric chemistry and composition and climate modeling communities.

Neptune's Discovery: Le Verrier, Adams, and the Assignment of Credit

NASA Astrophysics Data System (ADS)

Sheehan, William

2011-01-01

As one of the most significant achievements of 19th century astronomy, the discovery of Neptune has been the subject of a vast literature. A large part of this literature--beginning with the period immediately after the optical discovery in Berlin--has been the obsession with assigning credit to the two men who attempted to calculate the planet's position (and initially this played out against the international rivalry between France and England). Le Verrier and Adams occupied much different positions in the Scientific Establishments of their respective countries; had markedly different personalities; and approached the investigation using different methods. A psychiatrist and historian of astronomy tries to provide some new contexts to the familiar story of the discovery of Neptune, and argues that the personalities of these two men played crucial roles in their approaches to the problem they set themselves and the way others reacted to their stimuli. Adams had features of high-functioning autism, while Le Verrier's domineering, obsessive, orderly personality--though it allowed him to be immensely productive--eventually led to serious difficulties with his peers (and an outright revolt). Though it took extraordinary smarts to calculate the position of Neptune, the discovery required social skills that these men lacked--and thus the process to discovery was more bumbling and adventitious than it might have been. The discovery of Neptune occurred at a moment when astronomy was changing from that of heroic individuals to team collaborations involving multiple experts, and remains an object lesson in the sociological aspects of scientific endeavor.

John Dewey, an Appreciation

ERIC Educational Resources Information Center

Clopton, Robert W.

2015-01-01

The subject of the annual Presidential address of Phi Kappa Phi, presented on May 8, 1962, was John Dewey. Dewey is identified in the public mind chiefly as an educational philosopher. In this address, the author describes the life and work of John Dewey as an indefatigable student of life whose interests ranged, like those of Aristotle, over the…

"ADAM' or "EVE'?--a toxicological conundrum.

PubMed

Cox, D E; Williams, K R

1996-01-12

The 3,4-methylenedioxy ring-substituted amphetamines, including "ADAM' and "EVE', are currently popular drugs of abuse. Adverse reactions are reported in the clinical literature but few fatal cases are documented and little toxicological data is available to guide those determining the cause or manner of death in such cases. We report two deaths presenting in a similar manner and with similar clinical features. Various body fluid samples were analysed for amphetamines by gas chromatography/mass spectrometry. In one case, amphetamine alone was detected at levels of 1.54 mg/l and 1.47 mg/l in postmortem blood and admission serum, respectively. The other involved several 3,4-methylenedioxy ring-substituted amphetamines, namely MDA, MDMA and MDEA, at levels of 0.25 mg/l, 0.43 mg/l and 0.3 mg/l, respectively in postmortem femoral blood and 0.24 mg/l, 0.55 mg/l and 0.49 mg/l in admission blood. The interpretation of these toxicological results and some novel legal issues are discussed.

Big huckleberry abundance as related to environment and associated vegetation near Mount Adams, Washington.

Treesearch

Don Minore; Michael E. Dubrasich

1978-01-01

Big huckleberry abundance was correlated with associated vegetation and soil pH in a 625-square-kilometer (241-square-mile) area southwest of Mount Adams, Washington. Annual berry production appeared to be influenced by weather more than by site factors in this area. Douglas-fir site index was not correlated with either Vaccinium membranaceum...

A Global Education Program for the High Schools of Adams County, Ohio. Applied Project.

ERIC Educational Resources Information Center

Yunker, Jonel Jones

This project sought to develop a global education curriculum at the secondary level by developing a rationale and support for a global education curriculum; surveying teachers at North Adams High School as to what they would like to include in the course of study that related to global education; contacting various state departments of education…

Conceptions of Childhood in the Educational Philosophies of John Locke and John Dewey

ERIC Educational Resources Information Center

Bynum, Gregory Lewis

2015-01-01

This article compares progressive conceptions of childhood in the educational philosophies of John Locke and John Dewey. Although the lives of the two philosophers were separated by an ocean and two centuries of history, they had in common the following things: (1) a relatively high level of experience working with, and observing, children that is…

T1 polymorphism in a disintegrin and metalloproteinase 33 (ADAM33) gene may contribute to the risk of childhood asthma in Asians.

PubMed

Deng, Rui; Zhao, Fengyan; Zhong, Xiaoyun

2017-05-01

Polymorphisms in ADAM33 gene have been implicated in susceptibility to the risk of childhood asthma. However, the results remain controversial. We performed meta-analyses to clarify the relationship between them. Relevant articles were searched in PubMed, Embase, Wanfang, and China National Knowledge Infrastructure. The Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the associations. Fourteen studies with five ADAM33 polymorphisms (F + 1, T1, T2, S2, and V4) were identified, involving 2687 cases and 2996 controls. ADAM33 F + 1, T2, and T1 polymorphisms showed significant associations with asthma risks in the overall and Caucasian children, Asian children, and Caucasian and Chinese children, respectively; however, these significant results were unstable in sensitivity analysis. T1 revealed significant and stable associations with asthma risks among Asian children in the dominant (OR = 2.00, 95% CI = 1.40-2.87, P = 0.0002) and codominant (OR = 3.06, 95% CI = 1.71-5.50, P = 0.0002) models; in cumulative meta-analyses, these significant results were robust. Concerning S2 or V4 polymorphism, no significant associations were observed. These findings demonstrate that ADAM33 T1 polymorphism might be a potential susceptible predictor of asthma for Asian children. Further functional studies between this polymorphism and asthma risks are warranted.

Areca nut components stimulate ADAM17, IL-1α, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling.

PubMed

Chang, Mei-Chi; Chan, Chiu-Po; Chen, Yi-Jane; Hsien, Hsiang-Chi; Chang, Ya-Ching; Yeung, Sin-Yuet; Jeng, Po-Yuan; Cheng, Ru-Hsiu; Hahn, Liang-Jiunn; Jeng, Jiiang-Huei

2016-03-29

Betel quid (BQ) chewing is an etiologic factor of oral submucous fibrosis (OSF) and oral cancer. There are 600 million BQ chewers worldwide. The mechanisms for the toxic and inflammatory responses of BQ are unclear. In this study, both areca nut (AN) extract (ANE) and arecoline stimulated epidermal growth factor (EGF) and interleukin-1α (IL-1α) production of gingival keratinocytes (GKs), whereas only ANE can stimulate a disintegrin and metalloproteinase 17 (ADAM17), prostaglandin E2 (PGE2) and 8-isoprostane production. ANE-induced EGF production was inhibited by catalase. Addition of anti-EGF neutralizing antibody attenuated ANE-induced cyclooxygenase-2 (COX-2), mature ADAM9 expression and PGE2 and 8-isoprostane production. ANE-induced IL-1α production was inhibited by catalase, anti-EGF antibody, PD153035 (EGF receptor antagonist) and U0126 (MEK inhibitor) but not by α-naphthoflavone (cytochrome p450-1A1 inhibitor). ANE-induced ADAM17 production was inhibited by pp2 (Src inhibitor), U0126, α-naphthoflavone and aspirin. AG490 (JAK inhibitor) prevented ANE-stimulated ADAM17, IL-1α, PGE2 production, COX-2 expression, ADAM9 maturation, and the ANE-induced decline in keratin 5 and 14, but showed little effect on cdc2 expression and EGF production. Moreover, ANE-induced 8-isoprostane production by GKs was inhibited by catalase, anti-EGF antibody, AG490, pp2, U0126, α-naphthoflavone, Zinc protoporphyrin (ZnPP) and aspirin. These results indicate that AN components may involve in BQ-induced oral cancer by induction of reactive oxygen species, EGF/EGFR, IL-1α, ADAMs, JAK, Src, MEK/ERK, CYP1A1, and COX signaling pathways, and the aberration of cell cycle and differentiation. Various blockers against ROS, EGF, IL-1α, ADAM, JAK, Src, MEK, CYP1A1, and COX can be used for prevention or treatment of BQ chewing-related diseases.

ADAM17_i33708A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the Genetics of Lipid Lowering Drugs and Diet Network study

PubMed Central

Junyent, Mireia; Parnell, Laurence D.; Lai, Chao-Qiang; Arnett, Donna K.; Tsai, Michael Y.; Kabagambe, Edmond K.; Straka, Robert J.; Province, Michael; An, Ping; Smith, Caren E.; Lee, Yu-Chi; Borecki, Ingrid; Ordovás, Jose M.

2015-01-01

Background and aims The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes. Importantly, elevated levels of ADAM17 expression have been linked to obesity and insulin resistance. Therefore, the aim of this study was to evaluate the association of six ADAM17 single nucleotide polymorphisms (SNPs) (m1254A>G, i14121C>A, i33708A>G, i48827A>C, i53440C>T, and i62781G>T) with insulin-resistance phenotypes and obesity risk, and their potential interactions with dietary polyunsaturated fatty acids (PUFA). Methods and results ADAM17 SNPs were genotyped in 936 subjects (448 men/488 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Anthropometrical and biochemical measurements were determined by standard procedures. PUFA intake was estimated using a validated questionnaire. G allele carriers at the ADAM17_m1254A>G polymorphism exhibited significantly higher risk of obesity (P=0.003), were shorter (P=0.017), had higher insulin (P=0.016), and lower HDL-C concentrations (P=0.027) than AA subjects. For the ADAM17_i33708A>G SNP, homozygotes for the A allele displayed higher risk of obesity (P=0.001), were heavier (P=0.011), had higher BMI (P=0.005), and higher waist measurements (P=0.023) than GG subjects. A significant gene-diet interaction was found (P=0.030), in which the deleterious association of the i33708A allele with obesity was observed in subjects with low intakes from (n-6) PUFA (P<0.001), whereas no differences in obesity risk were seen among subjects with high (n-6) PUFA intake (P>0.5) Conclusion These findings support that ADAM17 (m1254A>G and i33708A>G) SNPs may contribute to obesity risk. For the ADAM17_i33708A>G SNP, this risk may be further modulated by (n-6) PUFA intake. PMID:19819120

ADAM17_i33708A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the Genetics of Lipid Lowering Drugs and Diet Network study.

PubMed

Junyent, M; Parnell, L D; Lai, C-Q; Arnett, D K; Tsai, M Y; Kabagambe, E K; Straka, R J; Province, M; An, P; Smith, C E; Lee, Y-C; Borecki, I; Ordovás, J M

2010-12-01

The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes. Importantly, elevated levels of ADAM17 expression have been linked to obesity and insulin resistance. Therefore, the aim of this study was to evaluate the association of six ADAM17 single nucleotide polymorphisms (SNPs) (m1254A>G, i14121C>A, i33708A>G, i48827A>C, i53440C>T, and i62781G>T) with insulin-resistance phenotypes and obesity risk, and their potential interactions with dietary polyunsaturated fatty acids (PUFA). ADAM17 SNPs were genotyped in 936 subjects (448 men/488 women) who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Anthropometrical and biochemical measurements were determined by standard procedures. PUFA intake was estimated using a validated questionnaire. G allele carriers at the ADAM17_m1254A>G polymorphism exhibited significantly higher risk of obesity (P=0.003), were shorter (P=0.017), had higher insulin (P=0.016), and lower HDL-C concentrations (P=0.027) than AA subjects. For the ADAM17_i33708A>G SNP, homozygotes for the A allele displayed higher risk of obesity (P=0.001), were heavier (P=0.011), had higher BMI (P=0.005), and higher waist measurements (P=0.023) than GG subjects. A significant gene-diet interaction was found (P=0.030), in which the deleterious association of the i33708A allele with obesity was observed in subjects with low intakes from (n-6) PUFA (P<0.001), whereas no differences in obesity risk were seen among subjects with high (n-6) PUFA intake (P>0.5) These findings support that ADAM17 (m1254A>G and i33708A>G) SNPs may contribute to obesity risk. For the ADAM17_i33708A>G SNP, this risk may be further modulated by (n-6) PUFA intake. Copyright © 2009 Elsevier B.V. All rights reserved.

Celebrating John Glenn’s Legacy

NASA Image and Video Library

2012-03-02

Sen. John Glenn, left, shakes hands with former Astronaut Steve Lindsey as NASA Administrator Charles Bolden smiles at an event celebrating John Glenn's legacy and 50 years of americans in orbit held at the Cleveland State University Wolstein Center on Friday, March 3, 2012 in Cleveland, Ohio. In 1998 Lindsey flew onboard the space shuttle Discovery along with then 77 year-old Sen. John Glenn for the STS-95 mission. Glenn became the first American to orbit Earth in 1962. Photo Credit: (NASA/Bill Ingalls)

Of weekend warriors and couch potatoes: Socio-economic determinants of physical activity in Swiss middle-aged adults.

PubMed

Gubelmann, Cédric; Vollenweider, Peter; Marques-Vidal, Pedro

2017-12-01

Determinants of the interplay between physical activity (PA) and sedentary (SE) status are poorly known. We assessed the socio-economic determinants of PA and SE behaviours and patterns in a population-based study (The CoLaus study, Lausanne, Switzerland, 2014-2017). 2229 adults (51.8% women, age range 45-86 years) had PA and SE levels measured for 14 days using a wrist-worn accelerometer. Four activity behaviours: (1) 'Couch potato': low PA & high SE; (2) 'Light mover': low PA & low SE; (3) 'Sedentary exerciser': high PA & high SE, and (4) 'Busy bee': high PA & low SE; and three activity patterns: (1) 'Inactive', (2) 'Weekend warrior', and (3) 'Regularly active' were defined. Employment, household income and educational level were collected by questionnaire. For activity behaviours, relative to 'Couch potatoes', multivariate analysis showed that being employed and having a low educational level were positively associated with 'Light movers': relative risk ratios and (95% confidence interval): 1.54 (1.00-2.37) and 1.73 (1.11-2.69), respectively, and also with 'Busy bees': 1.49 (1.09-2.04) and 1.71 (1.26-2.32), respectively. High household income was negatively associated with 'Light movers': 0.58 (0.34-0.97) and positively with 'Sedentary exercisers': 1.85 (1.10-3.10). For activity patterns, relative to 'Inactives', being employed and having a high household income were positively associated with 'Weekend warriors': 1.78 (1.26-2.50) and 1.59 (1.07-2.36), respectively, while having a low educational level was positively associated with 'Regularly actives': 1.76 (1.32-2.34). Employment, educational level and household income are significantly but differently associated with activity behaviours and patterns. Copyright © 2017 Elsevier Inc. All rights reserved.

Blood-induced bone loss in murine hemophilic arthropathy is prevented by blocking the iRhom2/ADAM17/TNFα pathway.

PubMed

Haxaire, Coline; Hakobyan, Narine; Pannellini, Tania; Carballo, Camila; McIlwain, David; Mak, Tak W; Rodeo, Scott; Acharya, Suchitra; Li, Daniel; Szymonifka, Jackie; Song, Xiangqian; Monette, Sébastien; Srivastava, Alok; Salmon, Jane E; Blobel, Carl P

2018-05-18

Hemophilic arthropathy (HA) is a debilitating degenerative joint disease that is a major manifestation of the bleeding disorder Hemophilia A. HA typically begins with hemophilic synovitis (HS) that resembles inflammatory arthritides such as rheumatoid arthritis (RA) and frequently results in bone loss in patients. A major cause of RA is inappropriate release of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) by the TNFα convertase (TACE, also referred to as ADAM17) and its regulator, iRhom2. Therefore, we hypothesized that iRhom2/ADAM17-dependent shedding of TNFα also has a pivotal role in mediating HA. Here, we show that addition of blood or its components to macrophages activates iRhom2/ADAM17-dependent TNFα shedding, providing the premise to study the activation of this pathway by blood in the joint in vivo. For this, we turned to hemophilic FVIII-deficient mice (F8-/- mice), which develop a hemarthrosis following needle puncture injury with synovial inflammation and significant osteopenia adjacent to the affected joint. We found that needle puncture-induced bleeding leads to increased TNFα levels in the affected joint of F8-/- mice. Moreover, inactivation of TNFα or iRhom2 in F8-/- mice reduced the osteopenia and synovial inflammation that develops in this mouse model for HA. Taken together, our results suggest that blood entering the joint activates the iRhom2/ADAM17/TNFα pathway, thereby contributing to osteopenia and synovitis in mice. Therefore, this pro-inflammatory signaling pathway could emerge as an attractive new target to prevent osteoporosis and joint damage in HA patients. Copyright © 2018 American Society of Hematology.

Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a.

PubMed

Khedgikar, Vikram; Abbruzzese, Genevieve; Mathavan, Ketan; Szydlo, Hannah; Cousin, Helene; Alfandari, Dominique

2017-08-22

Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration.

Fisetin suppresses ADAM9 expression and inhibits invasion of glioma cancer cells through increased phosphorylation of ERK1/2.

PubMed

Chen, Chien-Min; Hsieh, Yi-Hsien; Hwang, Jin-Ming; Jan, Hsun-Jin; Hsieh, Shu-Ching; Lin, Shin-Huey; Lai, Chung-Yu

2015-05-01

Fisetin (3,3',4',7-tetrahydroxyflavone) is a naturally occurring flavonoid which is widely distributed in plants. It has been reported to possess some anticancer and anti-invasive capabilities. We set out to explore the effects of fisetin on antimetastatic and its mechanism of action in GBM8401 cells. The results indicated that fisetin exhibited effective inhibition of cell migration and inhibited the invasion of GBM8401 cells under non-cytotoxic concentrations. To identify the potential targets of fisetin, human proteinase antibody array analysis was performed, and the results indicated that the fisetin treatment inhibited the expression of ADAM9 protein and mRNA, which are known to contribute to the progression of glioma cancer. Our results showed that fisetin phosphorylated ERK1/2 in a sustained way that contributed to the inhibited ADAM9 protein and mRNA expression determined by Western blot and RT-PCR. Moreover, inhibition of ERK1/2 by U0126 or transfection with the siERK plasmid significantly abolished the fisetin-inhibited migration and invasion through activation of the ERK1/2 pathway. In summary, our results suggest that fisetin might be a potential therapeutic agent against human glioma cells based on its capacity to activate ERK1/2 and to inhibit ADAM9 expression.

Influences on my clinical practice and identity. Jungian analysis on the couch-what and where is the truth of it?

PubMed

Schmidt, Martin

2014-11-01

The author considers the various influences that have shaped his clinical practice and particular identity as a Jungian analyst. It is hoped that the sharing of these observations will, like a shard of a hologram, reflect aspects of the Jungian community as a whole. The author also attempts to put Jungian analysis 'on the couch' by looking at the current debate in the Journal between traditional and relational psychoanalysis. This is compared to the discourse that philosophy has been struggling with for centuries concerning the nature of truth. © 2014, The Society of Analytical Psychology.

Tuberculous spondylitis in Haji Adam Malik hospital, Medan

NASA Astrophysics Data System (ADS)

Dharmajaya, R.

2018-03-01

Ankylosing tuberculosis is an infection caused by Mycobacterium tuberculosis in one or more components of the vertebrae; it is Pott disease or tuberculous spondylitis. It might become a potential cause of morbidity, including neurological deficits and permanent deformity of the spine. Management of TB Spondylitis, in general, is chemotherapy with antituberculosis drugs (ATG), immobilization, and spine surgical interventions. A retrospective study was conducted to analyze the patients of TB Spondylitis who had undergone surgery at Haji Adam Malik hospital from June 2015 to June 2017. The most common location is thoracal (10%), lumbal (3%), and thoracolumbal junction (3%). Decompression laminectomy with fusion (18%) is the most suitable option for surgical management. The majority, pre- operation ASIA scale is D (8%), and post operation is E (8%). It means that surgical plays an important role in themanagement of tuberculous spondylitis.

The "delivery" of Adam: a medical interpretation of Michelangelo.

PubMed

Di Bella, Stefano; Taglietti, Fabrizio; Iacobuzio, Andrea; Johnson, Emma; Baiocchini, Andrea; Petrosillo, Nicola

2015-04-01

This article describes what we believe to be the key to interpreting the concept represented by Michelangelo's painting the Creation of Adam. This fresco, one of his most famous masterpieces, is situated in the heart of the Sistine Chapel and is viewed by millions of people every year. A man of many talents, Michelangelo's proficiency in anatomical dissection is reflected in his artwork. As such, analyses of hidden meanings in this fresco have been ascribed, including the concept of the "Brain-God." However, we see a postpartum uterus and adjacent anatomy, justifying our interpretation that Michelangelo was depicting something far more fundamental: the birth of mankind. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Positioning accuracy during VMAT of gynecologic malignancies and the resulting dosimetric impact by a 6-degree-of-freedom couch in combination with daily kilovoltage cone beam computed tomography.

PubMed

Yao, Lihong; Zhu, Lihong; Wang, Junjie; Liu, Lu; Zhou, Shun; Jiang, ShuKun; Cao, Qianqian; Qu, Ang; Tian, Suqing

2015-04-26

To improve the delivery of radiotherapy in gynecologic malignancies and to minimize the irradiation of unaffected tissues by using daily kilovoltage cone beam computed tomography (kV-CBCT) to reduce setup errors. Thirteen patients with gynecologic cancers were treated with postoperative volumetric-modulated arc therapy (VMAT). All patients had a planning CT scan and daily CBCT during treatment. Automatic bone anatomy matching was used to determine initial inter-fraction positioning error. Positional correction on a six-degrees-of-freedom (6DoF) couch was followed by a second scan to calculate the residual inter-fraction error, and a post-treatment scan assessed intra-fraction motion. The margins of the planning target volume (MPTV) were calculated from these setup variations and the effect of margin size on normal tissue sparing was evaluated. In total, 573 CBCT scans were acquired. Mean absolute pre-/post-correction errors were obtained in all six planes. With 6DoF couch correction, the MPTV accounting for intra-fraction errors was reduced by 3.8-5.6 mm. This permitted a reduction in the maximum dose to the small intestine, bladder and femoral head (P=0.001, 0.035 and 0.032, respectively), the average dose to the rectum, small intestine, bladder and pelvic marrow (P=0.003, 0.000, 0.001 and 0.000, respectively) and markedly reduced irradiated normal tissue volumes. A 6DoF couch in combination with daily kV-CBCT can considerably improve positioning accuracy during VMAT treatment in gynecologic malignancies, reducing the MPTV. The reduced margin size permits improved normal tissue sparing and a smaller total irradiated volume.

Control of a HexaPOD treatment couch for robot-assisted radiotherapy.

PubMed

Hermann, Christian; Ma, Lei; Wilbert, Jürgen; Baier, Kurt; Schilling, Klaus

2012-10-01

Moving tumors, for example in the vicinity of the lungs, pose a challenging problem in radiotherapy, as healthy tissue should not be irradiated. Apart from gating approaches, one standard method is to irradiate the complete volume within which a tumor moves plus a safety margin containing a considerable volume of healthy tissue. This work deals with a system for tumor motion compensation using the HexaPOD® robotic treatment couch (Medical Intelligence GmbH, Schwabmünchen, Germany). The HexaPOD, carrying the patient during treatment, is instructed to perform translational movements such that the tumor motion, from the beams-eye view of the linear accelerator, is eliminated. The dynamics of the HexaPOD are characterized by time delays, saturations, and other non-linearities that make the design of control a challenging task. The focus of this work lies on two control methods for the HexaPOD that can be used for reference tracking. The first method uses a model predictive controller based on a model gained through system identification methods, and the second method uses a position control scheme useful for reference tracking. We compared the tracking performance of both methods in various experiments with real hardware using ideal reference trajectories, prerecorded patient trajectories, and human volunteers whose breathing motion was compensated by the system.

Modeling and analysis of dynamic characteristics of carrier system of machining center in MSC.Adams

NASA Astrophysics Data System (ADS)

Grinek, A. V.; Rybina, A. V.; Boychuk, I. P.; Dantsevich, I. M.; Hurtasenko, A. V.

2018-03-01

The simulation model with the help of vibration analysis was developed in MSC.Adams/Vibration and experimental research of the dynamic characteristics of a five-axis machining center was carried out. The amplitude-frequency characteristics, resonant frequencies in various directions are investigated. Dynamic and static rigidity, damping intensity and the coefficient of dynamism of the center are determined.

Dual control of pcdh8l/PCNS expression and function in Xenopus laevis neural crest cells by adam13/33 via the transcription factors tfap2α and arid3a

PubMed Central

Khedgikar, Vikram; Abbruzzese, Genevieve; Mathavan, Ketan; Szydlo, Hannah; Cousin, Helene

2017-01-01

Adam13/33 is a cell surface metalloprotease critical for cranial neural crest (CNC) cell migration. It can cleave multiple substrates including itself, fibronectin, ephrinB, cadherin-11, pcdh8 and pcdh8l (this work). Cleavage of cadherin-11 produces an extracellular fragment that promotes CNC migration. In addition, the adam13 cytoplasmic domain is cleaved by gamma secretase, translocates into the nucleus and regulates multiple genes. Here, we show that adam13 interacts with the arid3a/dril1/Bright transcription factor. This interaction promotes a proteolytic cleavage of arid3a and its translocation to the nucleus where it regulates another transcription factor: tfap2α. Tfap2α in turn activates multiple genes including the protocadherin pcdh8l (PCNS). The proteolytic activity of adam13 is critical for the release of arid3a from the plasma membrane while the cytoplasmic domain appears critical for the cleavage of arid3a. In addition to this transcriptional control of pcdh8l, adam13 cleaves pcdh8l generating an extracellular fragment that also regulates cell migration. PMID:28829038

Paricalcitol modulates ACE2 shedding and renal ADAM17 in NOD mice beyond proteinuria.

PubMed

Riera, Marta; Anguiano, Lidia; Clotet, Sergi; Roca-Ho, Heleia; Rebull, Marta; Pascual, Julio; Soler, Maria Jose

2016-03-15

Circulating and renal activity of angiotensin-converting enzyme 2 (ACE2) is increased in non-obese diabetic (NOD) mice. Because paricalcitol has been reported to protect against diabetic nephropathy, we investigated the role of paricalcitol in modulating ACE2 in these mice. In addition, renal ADAM17, a metalloprotease implied in ACE2 shedding, was assessed. NOD female and non-diabetic control mice were studied for 21 days after diabetes onset and divided into various treatment groups. Diabetic animals received either vehicle; 0.4 or 0.8 μg/kg paricalcitol, aliskiren, or a combination of paricalcitol and aliskiren. We then studied the effect of paricalcitol on ACE2 expression in proximal tubular epithelial cells. Paricalcitol alone or in combination with aliskiren resulted in significantly reduced circulating ACE2 activity in NOD mice but there were no changes in urinary albumin excretion. Serum renin activity was significantly decreased in mice that received aliskiren but no effect was found when paricalcitol was used alone. Renal content of ADAM17 was significantly decreased in animals that received a high dose of paricalcitol. Renal and circulating oxidative stress (quantified by plasma H2O2 levels and immunolocalization of nitrotyrosine) were reduced in high-dose paricalcitol-treated mice compared with non-treated diabetic mice. In culture, paricalcitol incubation resulted in a significant increase in ACE2 expression compared with nontreated cells. In NOD mice with type 1 diabetes, paricalcitol modulates ACE2 activity, ADAM17, and oxidative stress renal content independently from the glycemic profile and urinary albumin excretion. In tubular cells, paricalcitol may modulate ACE2 by blocking its shedding. In the early stage of diabetic nephropathy, paricalcitol treatment counterbalances the effect of diabetes on circulating ACE2 activity. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard

Human colonic myocytes are involved in postischemic inflammation through ADAM17-dependent TNFα production

PubMed Central

Jarry, Anne; Bach-Ngohou, Kalyane; Masson, Damien; Dejoie, Thomas; Lehur, Paul-Antoine; Mosnier, Jean-François; Denis, Marc G; Laboisse, Christian L

2005-01-01

The aim of this study was to identify human colonic resident cells able to initiate an inflammatory response in postischemic injury. Postischemic colonic injury, a condition relevant to various clinical settings, involves an inflammatory cascade in intestinal tissues through the recruitment of circulating inflammatory cells. However, there is no information on the nature of resident cells of the different intestinal layers able to initiate a postischemic inflammatory response. It is however an important issue in the context of a pharmacological approach of the early phase of intestinal ischemia. We reasoned that maintaining the different colonic layers as explant cultures in an oxygenated medium immediately after colonic resection, that is, after an ischemic period, would allow one to identify the resident cells able to initiate an inflammatory cascade, without interference of recruited inflammatory/immune cells. To this end, we designed an explant culture system that operationally defines three compartments in surgical specimens of the human colon, based on the microdissected layers, that is, mucosa, submucosa (containing muscularis mucosae) and muscularis propria. To validate the results obtained in explant cultures in the clinical setting of ischemic colitis, eight cases of sigmoid volvulus were examined. Only the myocytes-containing explants produced tumor necrosis factor alpha (TNFα), via an ADAM17 (a disintegrin and metalloproteinase-17)-dependent pathway, as shown by the abrogation of TNFα production by the inhibitor Tapi-2. Immunofluorescence studies identified nonvascular and vascular myocytes as resident cells coexpressing TNFα and ADAM17, both in our postischemic explant system and in surgical specimens from ischemic colitis patients. Finally, time-course experiments on explanted tissues showed that TNFα production by myocytes was an early event triggered by a postischemic oxidative stress involving nuclear factor kappa B (NF-κB). In conclusion

John Butcher and hybrid methods

NASA Astrophysics Data System (ADS)

Mehdiyeva, Galina; Imanova, Mehriban; Ibrahimov, Vagif

2017-07-01

As is known there are the mainly two classes of the numerical methods for solving ODE, which is commonly called a one and multistep methods. Each of these methods has certain advantages and disadvantages. It is obvious that the method which has better properties of these methods should be constructed at the junction of them. In the middle of the XX century, Butcher and Gear has constructed at the junction of the methods of Runge-Kutta and Adams, which is called hybrid method. Here considers the construction of certain generalizations of hybrid methods, with the high order of accuracy and to explore their application to solving the Ordinary Differential, Volterra Integral and Integro-Differential equations. Also have constructed some specific hybrid methods with the degree p ≤ 10.

ADAM17_i33780A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the genetics of lipid lowering drugs and diet network study

USDA-ARS?s Scientific Manuscript database

The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes, and elevated levels of expression have been linked to obesity and insulin resistance. This study evaluated the association of six ADAM17 single nucleotide polymorphi...

John Bahcall and the Solar Neutrino Problem

NASA Astrophysics Data System (ADS)

Bahcall, Neta

2016-03-01

``I feel like dancing'', cheered John Bahcall upon hearing the exciting news from the SNO experiment in 2001. The results confirmed, with remarkable accuracy, John's 40-year effort to predict the rate of neutrinos from the Sun based on sophisticated Solar models. What began in 1962 by John Bahcall and Ray Davis as a pioneering project to test and confirm how the Sun shines, quickly turned into a four-decade-long mystery of the `Solar Neutrino Problem': John's models predicted a higher rate of neutrinos than detected by Davis and follow-up experiments. Was the theory of the Sun wrong? Were John's calculations in error? Were the neutrino experiments wrong? John worked tirelessly to understand the physics behind the Solar Neutrino Problem; he led the efforts to greatly increase the accurately of the solar model, to understand its seismology and neutrino fluxes, to use the neutrino fluxes as a test for new physics, and to advocate for important new experiments. It slowly became clear that none of the then discussed possibilities --- error in the Solar model or neutrino experiments --- was the culprit. The SNO results revealed that John's calculations, and hence the theory of the Solar model, have been correct all along. Comparison of the data with John's theory demanded new physics --- neutrino oscillations. The Solar Neutrino saga is one of the most amazing scientific stories of the century: exploring a simple question of `How the Sun Shines?' led to the discovery of new physics. John's theoretical calculations are an integral part of this journey; they provide the foundation for the Solar Neutrino Problem, for confirming how the Sun shines, and for the need of neutrino oscillations. His tenacious persistence, dedication, enthusiasm and love for the project, and his leadership and advocacy of neutrino physics over many decades are a remarkable story of scientific triumph. I know John is smiling today.

Econophysical visualization of Adam Smith’s invisible hand

NASA Astrophysics Data System (ADS)

Cohen, Morrel H.; Eliazar, Iddo I.

2013-02-01

Consider a complex system whose macrostate is statistically observable, but yet whose operating mechanism is an unknown black-box. In this paper we address the problem of inferring, from the system’s macrostate statistics, the system’s intrinsic force yielding the observed statistics. The inference is established via two diametrically opposite approaches which result in the very same intrinsic force: a top-down approach based on the notion of entropy, and a bottom-up approach based on the notion of Langevin dynamics. The general results established are applied to the problem of visualizing the intrinsic socioeconomic force-Adam Smith’s invisible hand-shaping the distribution of wealth in human societies. Our analysis yields quantitative econophysical representations of figurative socioeconomic forces, quantitative definitions of “poor” and “rich”, and a quantitative characterization of the “poor-get-poorer” and the “rich-get-richer” phenomena.

Oligodendrocyte Regeneration and CNS Remyelination Require TACE/ADAM17.

PubMed

Palazuelos, Javier; Klingener, Michael; Raines, Elaine W; Crawford, Howard C; Aguirre, Adan

2015-09-02

The identification of the molecular network that supports oligodendrocyte (OL) regeneration under demyelinating conditions has been a primary goal for regenerative medicine in demyelinating disorders. We recently described an essential function for TACE/ADAM17 in regulating oligodendrogenesis during postnatal myelination, but it is unknown whether this protein also plays a role in OL regeneration and remyelination under demyelinating conditions. By using genetic mouse models to achieve selective gain- or loss-of-function of TACE or EGFR in OL lineage cells in vivo, we found that TACE is critical for EGFR activation in OLs following demyelination, and therefore, for sustaining OL regeneration and CNS remyelination. TACE deficiency in oligodendrocyte progenitor cells following demyelination disturbs OL lineage cell expansion and survival, leading to a delay in the remyelination process. EGFR overexpression in TACE deficient OLs in vivo restores OL development and postnatal CNS myelination, but also OL regeneration and CNS remyelination following demyelination. Our study reveals an essential function of TACE in supporting OL regeneration and CNS remyelination that may contribute to the design of new strategies for therapeutic intervention in demyelinating disorders by promoting oligodendrocyte regeneration and myelin repair. Oligodendrocyte (OL) regeneration has emerged as a promising new approach for the treatment of demyelinating disorders. By using genetic mouse models to selectively delete TACE expression in oligodendrocyte progenitors cells (OPs), we found that TACE/ADAM17 is required for supporting OL regeneration following demyelination. TACE genetic depletion in OPs abrogates EGFR activation in OL lineage cells, and perturbs cell expansion and survival, blunting the process of CNS remyelination. Moreover, EGFR overexpression in TACE-deficient OPs in vivo overcomes the defects in OL development during postnatal development but also OL regeneration during CNS

Harvey Cushing at Johns Hopkins.

PubMed

Long, D M

1999-11-01

Harvey Cushing began surgical training with William Halsted at Johns Hopkins in 1896. Cushing joined the Johns Hopkins faculty in 1900 and spent 1 year in Europe in the laboratory of Theodore Kocher. He returned to Johns Hopkins, where he founded neurosurgery as an independent specialty, established the concept of the clinician scientist, discovered the hormonal properties of the pituitary gland and founded endocrinology, introduced intraoperative x-rays into surgical practice, introduced blood pressure monitoring into the operating room, and wrote the first definitive text on neurosurgery. Although there have been many pioneers in our field, Cushing, more than anyone else, developed neurosurgery as a specialty and left a legacy of talented neurosurgeons to develop and expand the field.

Obituary: John Louis Perdrix, 1926-2005

NASA Astrophysics Data System (ADS)

Orchiston, D. Wayne

2006-12-01

John Perdrix, astronomical historian and co-founder of the Journal of Astronomical History and Heritage, died on 27 June 2005. John Louis Perdrix was born in Adelaide, Australia, on 30 June 1926. After studying chemistry at Melbourne Technical College and working in industry, he joined the Commonwealth Scientific and Industrial Research Organisation's Division of Minerals and Geochemistry. In 1974 the Division relocated to the Western Australian capital, Perth, and John spent the rest of his working life there involved in geochemical research. From his teenage years John had a passion for astronomy, which he fine-tuned through the Astronomical Society of Victoria and the Victorian Branch of the British Astronomical Association. He was very active in both groups, serving as President of the former and Secretary/Treasurer of the latter. He was also an FRAS, and a member of the AAS, the BAA parent body, and the IAU (Commission 41)?no mean feat for an Australian amateur astronomer. Throughout his life, he was a strong advocate of close amateur-professional relations. John's main research interest was history of astronomy, and over the years he wrote a succession of research papers, mainly about aspects of Australian astronomy. His well-researched and neatly-illustrated papers on the Melbourne Observatory and the Great Melbourne Telescope are classics, and when the Observatory's future was in the balance they played a key role in the State Government's decision to convert this unique facility into a museum precinct. To support his research activities, John built up an amazing library that developed its own distinctive personality and quickly took over his house and garage before invading commercial storage facilities! Apart from writing papers, John had an even greater passion for editing and publishing. From 1985 to 1997 he produced the Australian Journal of Astronomy, and in 1998 this was replaced by the Journal of Astronomical History and Heritage (JAH2). Both

TACE (ADAM17) inhibits Schwann cell myelination

PubMed Central

Marca, Rosa La; Cerri, Federica; Horiuchi, Keisuke; Bachi, Angela; Feltri, M Laura; Wrabetz, Lawrence; Blobel, Carl P; Quattrini, Angelo; Salzer, James L; Taveggia, Carla

2012-01-01

Tumor necrosis factor-α–converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves neuregulin-1 (NRG1) type III in the epidermal growth factor domain, probably inactivating it (as assessed by deficient activation of the phosphatidylinositol-3-OH kinase pathway), and thereby negatively regulating peripheral nervous system (PNS) myelination. Lentivirus-mediated knockdown of TACE in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hypermyelination. In agreement, motor neurons of conditional knockout mice lacking TACE specifically in these cells are significantly hypermyelinated, and small-caliber fibers are aberrantly myelinated. Further, reduced TACE activity rescues hypomyelination in NRG1 type III haploinsufficient mice in vivo. We also show that the inhibitory effect of TACE is neuron-autonomous, as Schwann cells lacking TACE elaborate myelin of normal thickness. Thus, TACE is a modulator of NRG1 type III activity and is a negative regulator of myelination in the PNS. PMID:21666671

Marcel Breuer at Saint John's

ERIC Educational Resources Information Center

Carlson, Scott

2008-01-01

A visitor to Saint John's University and Saint John's Abbey, in north-central Minnesota, sees something of Gothic heritage while standing in front of the abbey church, designed and built around 1960. The church's 112-foot campanile--a trapezoidal slab made of 2,500 tons of steel and concrete--stands boldly in front of a huge concrete honeycomb…

Demythologizing John Dewey

ERIC Educational Resources Information Center

Bhattacharya, N. C.

1974-01-01

This article takes a brief but critical look at John Dewey's version of pragmatism, his contribution to philosophical scholarship generally as well as his theory and practice of liberalism. (Author/RK)

The 'Dollond' Versus 'Dolland' Controversy

NASA Astrophysics Data System (ADS)

Breyer, Walter H.

Discussion of the Dollond and Dolland (a forgery) telescopes. Mentioned are telescope makers, opticians, ...: Chester Moore [1703-1771]; Gordon Bass; Edward Scarlett; James Mann; John Dollond; Peter Dollond; Robert Rew; Benjamin Martin [1714-1782]; George Adams; Henry Pyefinch; John Bevis [1693-1771]; and Charles Tulley.

Museum Quality: A New Museum and Recharged College Bring Creative Energy to North Adams, Massachusetts

ERIC Educational Resources Information Center

Grant, Mary

2005-01-01

Nestled in the valley between the Berkshire hills and the Taconic range, North Adams, Massachusetts, in many ways is typical of old New England mill towns working hard to create a new identity in the global economy. When Sprague Electric left town in 1985, the city of 16,000 reeled from the loss of 4,000 blue-collar jobs. This article describes…

An ADAM33 polymorphism associates with progression of preschool wheeze into childhood asthma: a prospective case-control study with replication in a birth cohort study.

PubMed

Klaassen, Ester M M; Penders, John; Jöbsis, Quirijn; van de Kant, Kim D G; Thijs, Carel; Mommers, Monique; van Schayck, Constant P; van Eys, Guillaume; Koppelman, Gerard H; Dompeling, Edward

2015-01-01

The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined. To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma. In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis). In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze. Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma.

An ADAM33 Polymorphism Associates with Progression of Preschool Wheeze into Childhood Asthma: A Prospective Case-Control Study with Replication in a Birth Cohort Study

PubMed Central

Klaassen, Ester M. M.; Penders, John; Jöbsis, Quirijn; van de Kant, Kim D. G.; Thijs, Carel; Mommers, Monique; van Schayck, Constant P.; van Eys, Guillaume; Koppelman, Gerard H.; Dompeling, Edward

2015-01-01

Background The influence of asthma candidate genes on the development from wheeze to asthma in young children still needs to be defined. Objective To link genetic variants in asthma candidate genes to progression of wheeze to persistent wheeze into childhood asthma. Materials and Methods In a prospective study, children with recurrent wheeze from the ADEM (Asthma DEtection and Monitoring) study were followed until the age of six. At that age a classification (transient wheeze or asthma) was based on symptoms, lung function and medication use. In 198 children the relationship between this classification and 30 polymorphisms in 16 asthma candidate genes was assessed by logistic regression. In case of an association based on a p<0.10, replication analysis was performed in an independent birth cohort study (KOALA study, n = 248 included for the present analysis). Results In the ADEM study, the minor alleles of ADAM33 rs511898 and rs528557 and the ORMDL3/GSDMB rs7216389 polymorphisms were negatively associated, whereas the minor alleles of IL4 rs2243250 and rs2070874 polymorphisms were positively associated with childhood asthma. When replicated in the KOALA study, ADAM33 rs528557 showed a negative association of the CG/GG-genotype with progression of recurrent wheeze into childhood asthma (0.50 (0.26-0.97) p = 0.04) and no association with preschool wheeze. Conclusion Polymorphisms in ADAM33, ORMDL3/GSDMB and IL4 were associated with childhood asthma in a group of children with recurrent wheeze. The replication of the negative association of the CG/GG-genotype of rs528557 ADAM33 with childhood asthma in an independent birth cohort study confirms that a compromised ADAM33 gene may be implicated in the progression of wheeze into childhood asthma. PMID:25768087

Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus-related hepatocellular carcinoma metastasis through the upregulation of ADAM9.

PubMed

Xiang, Le-Yang; Ou, Huo-Hui; Liu, Xin-Cheng; Chen, Zhan-Jun; Li, Xiang-Hong; Huang, Yu; Yang, Ding-Hua

2017-06-01

Hepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, baseline miR-126 expression levels in hepatitis B virus-related hepatocellular carcinoma patients who did not undergo pre-operational treatment remains unknown since hepatitis B virus infection and pre-operational transcatheter arterial chemoembolization were shown to upregulate miR-126 expression. Here, we demonstrated that miR-126 is generally downregulated in a homogeneous population of pre-operational treatment-naïve hepatitis B virus-related hepatocellular carcinoma patients (84.0%, 84/100), and its expression is significantly associated with pre-operational alpha-fetoprotein levels ( p < 0.05), microvascular invasion ( p < 0.05), tumor metastasis ( p < 0.05), as well as early recurrence (12 months after surgery; p < 0.01). Furthermore, the results of our study revealed that miR-126 is negatively correlated with ADAM9 expression in hepatitis B virus-related hepatocellular carcinoma patients. Overexpression of miR-126 was shown to attenuate ADAM9 expression in hepatocellular carcinoma cells, which subsequently inhibits cell migration and invasion in vitro. In addition, Cox proportional hazards regression model analysis showed that ADAM9 levels, tumor number, microvascular invasion, and tumor metastasis rate represent independent prognostic factors for shorter recurrence-free survival. In conclusion, we demonstrated that the loss of tumor suppressor miR-126 in hepatitis B virus-related hepatocellular carcinoma cells contributes to the development of metastases through the upregulated expression of its target gene, ADAM9. MiR-126-ADAM9 pathway-based therapeutic targeting may represent a novel approach for the inhibition of hepatitis B virus

A dual inhibitor of matrix metalloproteinases and a disintegrin and metalloproteinases, [¹⁸F]FB-ML5, as a molecular probe for non-invasive MMP/ADAM-targeted imaging.

PubMed

Matusiak, Nathalie; Castelli, Riccardo; Tuin, Adriaan W; Overkleeft, Herman S; Wisastra, Rosalina; Dekker, Frank J; Prély, Laurette M; Bischoff, Rainer; Bischoff, Rainer P M; van Waarde, Aren; Dierckx, Rudi A J O; Elsinga, Philip H

2015-01-01

Numerous clinical studies have shown a correlation between increased matrix metalloproteinase (MMP)/a disintegrin and metalloproteinase (ADAM) activity and poor outcome of cancer. Various MMP inhibitors (MMPIs) have been developed for therapeutic purposes in oncology. In addition, molecular imaging of MMP/ADAM levels in vivo would allow the diagnosis of tumors. We selected the dual inhibitor of MMPs and ADAMs, ML5, which is a hydroxamate-based inhibitor with affinities for many MMPs and ADAMs. ML5 was radiolabelled with (18)F and the newly obtained radiolabelled inhibitor was evaluated in vitro and in vivo. ML5 was radiolabelled by direct acylation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB) for PET (positron emission tomography). The resulting radiotracer [(18)F]FB-ML5 was evaluated in vitro in human bronchial epithelium 16HBE cells and breast cancer MCF-7 cells. The non-radioactive probe FB-ML5 and native ML5 were tested in a fluorogenic inhibition assay against MMP-2, -9, -12 and ADAM-17. The in vivo kinetics of [(18)F]FB-ML5 were examined in a HT1080 tumor-bearing mouse model. Specificity of probe binding was examined by co-injection of 0 or 2.5mg/kg ML5. ML5 and FB-ML5 showed high affinity for MMP-2, -9, -12 and ADAM-17; indeed IC50 values were respectively 7.4 ± 2.0, 19.5 ± 2.8, 2.0 ± 0.2 and 5.7 ± 2.2 nM and 12.5 ± 3.1, 31.5 ± 13.7, 138.0 ± 10.9 and 24.7 ± 2.8 nM. Radiochemical yield of HPLC-purified [(18)F]FB-ML5 was 13-16% (corrected for decay). Cellular binding of [(18)F]FB-ML5 was reduced by 36.6% and 27.5% in MCF-7 and 16 HBE cells, respectively, after co-incubation with 10 μM of ML5. In microPET scans, HT1080 tumors exhibited a low and homogeneous uptake of the tracer. Tumors of mice injected with [(18)F]FB-ML5 showed a SUVmean of 0.145 ± 0.064 (n=6) which decreased to 0.041 ± 0.027 (n=6) after target blocking (p<0.05). Ex vivo biodistribution showed a rapid excretion through the kidneys and the liver. Metabolite assays

John Leask Lumley: Whither Turbulence?

NASA Astrophysics Data System (ADS)

Leibovich, Sidney; Warhaft, Zellman

2018-01-01

John Lumley's contributions to the theory, modeling, and experiments on turbulent flows played a seminal role in the advancement of our understanding of this subject in the second half of the twentieth century. We discuss John's career and his personal style, including his love and deep knowledge of vintage wine and vintage cars. His intellectual contributions range from abstract theory to applied engineering. Here we discuss some of his major advances, focusing on second-order modeling, proper orthogonal decomposition, path-breaking experiments, research on geophysical turbulence, and important contributions to the understanding of drag reduction. John Lumley was also an influential teacher whose books and films have molded generations of students. These and other aspects of his professional career are described.

Microarray identifies ADAM family members as key responders to TGF-beta1 in alveolar epithelial cells.

PubMed

Keating, Dominic T; Sadlier, Denise M; Patricelli, Andrea; Smith, Sinead M; Walls, Dermot; Egan, Jim J; Doran, Peter P

2006-09-01

The molecular mechanisms of Idiopathic Pulmonary Fibrosis (IPF) remain elusive. Transforming Growth Factor beta 1(TGF-beta1) is a key effector cytokine in the development of lung fibrosis. We used microarray and computational biology strategies to identify genes whose expression is significantly altered in alveolar epithelial cells (A549) in response to TGF-beta1, IL-4 and IL-13 and Epstein Barr virus. A549 cells were exposed to 10 ng/ml TGF-beta1, IL-4 and IL-13 at serial time points. Total RNA was used for hybridisation to Affymetrix Human Genome U133A microarrays. Each in vitro time-point was studied in duplicate and an average RMA value computed. Expression data for each time point was compared to control and a signal log ratio of 0.6 or greater taken to identify significant differential regulation. Using normalised RMA values and unsupervised Average Linkage Hierarchical Cluster Analysis, a list of 312 extracellular matrix (ECM) proteins or modulators of matrix turnover was curated via Onto-Compare and Gene-Ontology (GO) databases for baited cluster analysis of ECM associated genes. Interrogation of the dataset using ontological classification focused cluster analysis revealed coordinate differential expression of a large cohort of extracellular matrix associated genes. Of this grouping members of the ADAM (A disintegrin and Metalloproteinase domain containing) family of genes were differentially expressed. ADAM gene expression was also identified in EBV infected A549 cells as well as IL-13 and IL-4 stimulated cells. We probed pathologenomic activities (activation and functional activity) of ADAM19 and ADAMTS9 using siRNA and collagen assays. Knockdown of these genes resulted in diminished production of collagen in A549 cells exposed to TGF-beta1, suggesting a potential role for these molecules in ECM accumulation in IPF.

Frailty profile for geriatric patients in outpatient clinic of RSUP H. Adam Malik Medan

NASA Astrophysics Data System (ADS)

Permatasari, T. D.; Sihombing, B.; Arianto, P.

2018-03-01

Frailty is a circumstance of increased vulnerability to bad resolution of homeostasis after a stressor occasion, which increases the risk of adverse outcomes. Early detection of frailty in elderly patients is a must but is rarely in the Geriatric Outpatient settings. We conducted a study to see the frailty profile for geriatric patients in the outpatient clinic of RSUP H. Adam Malik Medan. A cross-sectional research with a descriptive method was in the Geriatric Outpatient Clinic of Adam Malik Hospital from July-September 2016. The population of this study was patients from the Geriatric Outpatient Clinic, and sampling was by using consecutive methods. Samples were by questionnaires assessing (FRAIL Scale).This study was140 patients. Based on age, the age group of 81-90 years was dominantly frail (53.8%). Most of the subjects worked as government employees (109 subjects), and most of them were robust (42.2%). Based on income, both groups were dominated by robust (38.3% and 41.3%, respectively). Based on BMI, most were robust with underweight 33.5%, normoweight 37.8%, and obese 44.7%. Among the 140 patients, frailty was in the 27.1% of the subjects and the contributing factors were Age, Gender, and Obesity.

The Adam and Eve story as exemplar of an early-life variant of the oedipus complex.

PubMed

Osman, M P

2000-01-01

The Adam and Eve story is construed as having an organizing function that facilitates the analytic understanding of certain patients. In this interpretation, the story epitomizes a psychodynamic in which progressive growth, with separation and individuation, of the young is experienced as perilous--not only to them, but also correspondingly to their procreators. In the myth, the increasing psychic and physical maturation of Adam and Eve produced a crisis. Not only was divine authority flouted, but also apprehensions were aroused that God might be humbled or diminished. This threatened him, evoking his wrath and leading to the punishment by abandonment of his youthful wards. It is suggested that the story depicts an emotional complex of widespread application and is an archaic version of the oedipus complex, continuous with the oedipus complex proper, but from an earlier stage of development. This archaic complex is delineated with clinical vignettes, and a clinical explication of its various components is provided. Clinical management is considered, particularly with reference to the challenge that a closed-system perspective (Fairbairn 1958) presents to a patient's development.

Logos Announced the Light of Salvation: Interpreting How John Presented His Message in John 1:1-18, According to Functional Grammar

ERIC Educational Resources Information Center

Pollinger, Seth

2014-01-01

This study of John 1:1-18 describes how John (the speaker) presented his message to his audience within their activity of verbal communication. By focusing on verbal meaning, this interpretation analyzes how John presented and expressed his meanings through language by interpreting this text based on the seamless interrelation between John's…

Obituary: John W. Firor (1927-2007)

NASA Astrophysics Data System (ADS)

Gilman, Peter A.

2009-12-01

John W. Firor, a former Director of the High Altitude Observatory and the National Center for Atmospheric Research, and a founder of the Solar Physics Division of the American Astronomical Society, died of Alzheimer's disease in Pullman, Washington on November 5, 2007, he was 80. He was born in Athens Georgia on October 18, 1927, where his father was a professor of agricultural economics. John had an unusually diverse scientific career. His interest in physics and astrophysics began while serving in the army, during which time he was assigned to the Los Alamos National Laboratory, where he guarded highly radioactive materials (many have heard him describe how informal the protections were compared to later times). After his service he returned to college and graduated in physics from Georgia Tech in 1949. He received his Ph.D. from the University of Chicago in 1954, writing his thesis on cosmic rays under John Simpson. John Firor would later remark that: "If you needed cosmic rays to actually do anything, you are sunk." That thought, partly in jest, may help explain his motivation for moving to so many new scientific and management pursuits. John moved from cosmic ray physics to radio astronomy (particularly of the Sun) when he began work at the Carnegie Institution of Washington's Department of Terrestrial Magnetism, where he remained until 1961. During this time, he met Walter Orr Roberts, then the Director of the High Altitude Observatory (HAO) in Boulder, Colorado. HAO was then affiliated with the University of Colorado. In 1959, a movement began to upgrade the atmospheric sciences in the United States by establishing a National Center, where the largest, most important atmospheric research problems could be addressed. Roberts became the first Director of NCAR, as well as the first president of the University Corporation for Atmospheric Research (UCAR), the consortium of universities that was commissioned to manage and staff the new Center. HAO became a

An accuracy assessment of different rigid body image registration methods and robotic couch positional corrections using a novel phantom

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

Arumugam, Sankar; Xing Aitang; Jameson, Michael G.

2013-03-15

Purpose: Image guided radiotherapy (IGRT) using cone beam computed tomography (CBCT) images greatly reduces interfractional patient positional uncertainties. An understanding of uncertainties in the IGRT process itself is essential to ensure appropriate use of this technology. The purpose of this study was to develop a phantom capable of assessing the accuracy of IGRT hardware and software including a 6 degrees of freedom patient positioning system and to investigate the accuracy of the Elekta XVI system in combination with the HexaPOD robotic treatment couch top. Methods: The constructed phantom enabled verification of the three automatic rigid body registrations (gray value, bone,more » seed) available in the Elekta XVI software and includes an adjustable mount that introduces known rotational offsets to the phantom from its reference position. Repeated positioning of the phantom was undertaken to assess phantom rotational accuracy. Using this phantom the accuracy of the XVI registration algorithms was assessed considering CBCT hardware factors and image resolution together with the residual error in the overall image guidance process when positional corrections were performed through the HexaPOD couch system. Results: The phantom positioning was found to be within 0.04 ({sigma}= 0.12) Degree-Sign , 0.02 ({sigma}= 0.13) Degree-Sign , and -0.03 ({sigma}= 0.06) Degree-Sign in X, Y, and Z directions, respectively, enabling assessment of IGRT with a 6 degrees of freedom patient positioning system. The gray value registration algorithm showed the least error in calculated offsets with maximum mean difference of -0.2({sigma}= 0.4) mm in translational and -0.1({sigma}= 0.1) Degree-Sign in rotational directions for all image resolutions. Bone and seed registration were found to be sensitive to CBCT image resolution. Seed registration was found to be most sensitive demonstrating a maximum mean error of -0.3({sigma}= 0.9) mm and -1.4({sigma}= 1.7) Degree-Sign in

Exceptional Scholarship and Democratic Agendas: Interviews with John Goodlad, John Hoyle, Joseph Murphy, and Thomas Sergiovanni

ERIC Educational Resources Information Center

Mullen, Carol A.

2006-01-01

This portraiture study of four exceptional scholars in education--John Goodlad, John Hoyle, Joseph Murphy, and Thomas Sergiovanni--provides insight into their scholarly work and life habits, direction and aspirations, assessment and analysis of major trends in the profession, and advice for aspiring leaders and academics. Telephone interviews with…

Exceptional Scholarship and Democratic Agendas: Interviews with John Goodlad, John Hoyle, Joseph Murphy, and Thomas Sergiovanni

ERIC Educational Resources Information Center

Mullen, Carol A.

2009-01-01

This portraiture study of four exceptional scholars in education--John Goodlad, John Hoyle, Joseph Murphy, and Thomas Sergiovanni--provides insight into their scholarly work and life habits, direction and aspirations, assessment and analysis of major trends in the profession, and advice for aspiring leaders and academics. Telephone interviews with…

Geochemical survey of the Adams Gap and Shinbone Creek Roadless Areas, Clay County, Alabama

USGS Publications Warehouse

Robinson, G.R.; Klein, T.L.; Lesure, F.G.; Hanley, J.T.

1984-01-01

Reports covering the mineral resources of Clay County and vicinity include Brewer (1896) and Adams (1930) on gold, Prouty (1923) on graphite, and Heinrich and Olson (1953) on mica. The mineral resources of the Talladega National Forest were evaluated by Gilbert and Smith (1973). The mineral resource potential of the two roadless areas is detailed in Robinson and others (1983) and an accompanying geologic report is given in Robinson and others (in press).

Inferential modeling and predictive feedback control in real-time motion compensation using the treatment couch during radiotherapy

NASA Astrophysics Data System (ADS)

Qiu, Peng; D'Souza, Warren D.; McAvoy, Thomas J.; Liu, K. J. Ray

2007-09-01

Tumor motion induced by respiration presents a challenge to the reliable delivery of conformal radiation treatments. Real-time motion compensation represents the technologically most challenging clinical solution but has the potential to overcome the limitations of existing methods. The performance of a real-time couch-based motion compensation system is mainly dependent on two aspects: the ability to infer the internal anatomical position and the performance of the feedback control system. In this paper, we propose two novel methods for the two aspects respectively, and then combine the proposed methods into one system. To accurately estimate the internal tumor position, we present partial-least squares (PLS) regression to predict the position of the diaphragm using skin-based motion surrogates. Four radio-opaque markers were placed on the abdomen of patients who underwent fluoroscopic imaging of the diaphragm. The coordinates of the markers served as input variables and the position of the diaphragm served as the output variable. PLS resulted in lower prediction errors compared with standard multiple linear regression (MLR). The performance of the feedback control system depends on the system dynamics and dead time (delay between the initiation and execution of the control action). While the dynamics of the system can be inverted in a feedback control system, the dead time cannot be inverted. To overcome the dead time of the system, we propose a predictive feedback control system by incorporating forward prediction using least-mean-square (LMS) and recursive least square (RLS) filtering into the couch-based control system. Motion data were obtained using a skin-based marker. The proposed predictive feedback control system was benchmarked against pure feedback control (no forward prediction) and resulted in a significant performance gain. Finally, we combined the PLS inference model and the predictive feedback control to evaluate the overall performance of the

Celebrating John Glenn’s Legacy

NASA Image and Video Library

2012-03-02

Former NASA Astronaut Steve Lindsey gives remarks at an event celebrating John Glenn's legacy and 50 years of americans in orbit held at the Cleveland State University Wolstein Center on Friday, March 3, 2012 in Cleveland, Ohio. In 1998 Lindsey flew onboard the space shuttle Discovery along with then 77 year-old Sen. John Glenn for the STS-95 mission. Glenn became the first American to orbit Earth in 1962. Photo Credit: (NASA/Bill Ingalls)

Celebrating John Glenn’s Legacy

NASA Image and Video Library

2012-03-02

Wife of former astronaut and Senator John Glenn, Annie Glenn, listens intently to Cleveland State University Master of Music Major James Binion Jr. as he sings a musical tribute during an event celebrating John Glenn's legacy and 50 years of americans in orbit held at the university's Wolstein Center on Friday, March 3, 2012 in Cleveland, Ohio. Glenn became the first American to orbit Earth in 1962. Photo Credit: (NASA/Bill Ingalls)

Performance evaluation of the Arkray Adams HA-8160 HbA1c analyser.

PubMed

Thevarajah, T Malathi; Nani, Nordin; Chew, Y Y

2008-12-01

HbA1c measurement is currently routinely used to predict long term outcome of diabetes, thus playing a fundamental role in the management of diabetes. The relationship between HbA1c value and long term diabetic complications has been established by a randomised control Diabetes Control and Complications Trial (DCCT) which used high performance liquid chromatography (HPLC) as a reference method for HbA1c assay. To ensure that HbA1c results from a variety HbA1c assay methods are similar to the DCCT values, the American Diabetes Association (ADA) recommended that all laboratories should use methods certified by the National Glycohemoglobin Standardization Programme (NGSP) with interassay coefficient variation (CV) of < 5% (ideally < 3%). The International Federation of Clinical Chemistry (IFCC) working group on HbA1c standardisation has set a CV < 2.5% as a criteria for its reference laboratories. To evaluate the performance of Arkray Adams HA-8160 HbA1c analyser which uses a cation exchange HPLC method and its correlation to HbA1c assay on Cobas Integra 800 which is an immunoturbidimetric method. For the imprecision study, patient samples and control material of two levels were analysed on HA-8160 analyser 20 times in a single run (within-run imprecision) and twice a day on five consecutive days (between-run imprecision). For the recovery study, two samples each with high and low values were selected and mixed in ratios of 1:3, 1:1 and 3:1, and were analysed by HA-8160. Sixty samples were analysed by both Cobas Integra 800 and HA-8160 for method comparison study. Ten uraemic samples and ten thalassaemic samples were assayed on Cobas Integra 800 and HA 8160 for interference study. Within-run CVs were 0.6% and 0.7% for medium and high value samples respectively, 0.6% and 0.7% for low and high level controls respectively. Between-run CVs were 0.5% and 0.4% for medium and high value samples respectively, 0.5% and 0.6% for low and high level controls respectively. The

78 FR 37791 - In the Matter of: Jose Guadalupe Reyes-Martinez, Inmate Number #85993-279, CI Adams County...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... DEPARTMENT OF COMMERCE Bureau of Industry and Security In the Matter of: Jose Guadalupe Reyes-Martinez, Inmate Number 85993-279, CI Adams County, Correctional Institution, P.O. Box 1600, Washington, MS 39190; Order Denying Export Privileges On November 21, 2011, in the U.S. District Court, Southern...

Ophthalmology in North America: Early Stories (1491-1801)

PubMed Central

Leffler, Christopher T; Schwartz, Stephen G; Wainsztein, Ricardo D; Pflugrath, Adam; Peterson, Eric

2017-01-01

New World plants, such as tobacco, tomato, and chili, were held to have beneficial effects on the eyes. Indigenous healers rubbed or scraped the eyes or eyelids to treat inflammation, corneal opacities, and even eye irritation from smoke. European settlers used harsh treatments, such as bleeding and blistering, when the eyes were inflamed or had loss of vision with a normal appearance (gutta serena). In New Spain, surgery for corneal opacity was performed in 1601 and cataract couching in 1611. North American physicians knew of contralateral loss of vision after trauma or surgery (sympathetic ophthalmia), which they called “sympathy.” To date, the earliest identified cataract couching by a surgeon trained in the New World was performed in 1769 by John Bartlett of Rhode Island. The American Revolution negatively affected ophthalmology, as loyalist surgeons were expelled and others were consumed with wartime activities. After the war, cataract extraction was imported to America in earnest and academic development resumed. Charles F Bartlett, the son of John, performed cataract extraction but was also a “rapacious privateer.” In 1801, a doctor in the frontier territory of Kentucky observed anticholinergic poisoning by Datura stramonium (Jimsonweed) and suggested that this agent be applied topically to dilate the pupil before cataract extraction. John Warren at Harvard preferred couching in the 1790s, but, after his son returned from European training, recommended treating angle closure glaucoma by lens extraction. Other eye procedures described or advertised in America before the 19th century included enucleation, resection of conjunctival lesions or periocular tumors, treatment of lacrimal fistula, and fitting of prosthetic eyes. PMID:28804247

Obituary: John Leroy Climenhaga, 1916-2008

NASA Astrophysics Data System (ADS)

Scarfe, Colin

2009-01-01

John Leroy Climenhaga was born on 7 November 1916 on a farm some 10 km from Delisle, a small town on the Canadian prairies, located about 50 km south-west of Saskatoon, Saskatchewan, and died at his home in Victoria, British Columbia, on 27 May 2008. His parents, Reuben and Elizabeth (nee Bert) Climenhaga, were farming folk, and he carried their honest and open attitude to the world throughout his life. John was the seventh born, and last to die, of their ten children. His father also served as an ordained minister of the Brethren in Christ. In early adulthood, John worked on his father's farm, but then attended the University of Saskatchewan, obtaining a B.A. with Honors in Mathematics and Physics and an M.A. in Physics, in 1945 and 1949 respectively. Between these events he worked as a Physics Instructor at Regina College from 1946 to 1948. In 1949 Climenhaga joined the faculty of Victoria College, as one of only two physicists in a small institution that was then part of the University of British Columbia. He remained in Victoria for the rest of his career, playing a major role in the College's growth into a full-fledged university, complete with thriving graduate programs in physics and astronomy as well as in many other fields. He served as Head of the Physics Department during the 1960s, a period which saw the College become the University of Victoria, with a full undergraduate program in Physics, and campaigned successfully for the establishment of a program in Astronomy, which began in 1965. From 1969 until 1972 he held the position of Dean of Arts and Science, and championed the university's participation in the Tri-University Meson Facility, whose high-current medium-energy beam was ideal for the production and study of mesons and their physics. That period was a turbulent one in the university's history, but John's integrity and his balanced and fair-minded approach to conflicts were of immeasurable importance in steering the young institution through it

John N Bahcall (1934 2005)

NASA Astrophysics Data System (ADS)

Bergström, Lars; Botner, Olga; Carlson, Per; Hulth, Per Olof; Ohlsson, Tommy

2005-01-01

John Norris Bahcall, passed away on August 17, 2005, in NewYork City, USA. He was born on December 30, 1934, in Shreveport, Louisiana, USA. He was Richard Black Professor of Astrophysics in the School of Natural Sciences at the Institute forAdvanced Study (IAS) in Princeton, New Jersey, USA and a recipient of the National Medal of Science. In addition, he was President of the American Astronomical Society, President-Elect of the American Physical Society, and a prominent leader of the astrophysics community. John had a long and prolific career in astronomy and astrophysics, spanning five decades and the publication of more than five hundred technical articles, books, and popular papers. John's most recognized scientific contribution was the novel proposal in 1964, together with Raymond Davis Jr, that scientific mysteries of our Sun `how it shines, how old it is, how hot it is' could be examined by measuring the number of neutrinos arriving on Earth from the Sun. Measuring the properties of these neutrinos tests both our understanding of how stars shine and our understanding of fundamental particle physics. However, in the 1960s and 1970s, the observations by Raymond Davis Jr showed a clear discrepancy between John's theoretical predictions, based on standard solar and particle physics models, and what was experimentally measured. This discrepancy, known as the `Solar Neutrino Problem', was examined by hundreds of physicists, chemists, and astronomers over the subsequent three decades. In the late 1990s through 2002, new large-scale neutrino experiments in Japan, Canada, Italy, and Russia culminated in the conclusion that the discrepancy between John's theoretical predictions and the experimental results required a modification of our understanding of particle physics: neutrinos must have a mass and `oscillate' among different particle states. In addition to neutrino astrophysics, John contributed to many areas of astrophysics including the study of dark matter in

SU-F-BRE-10: Methods to Simulate and Measure the Attenuation for Modeling a Couch Top with Rails for FFF Treatment Delivery On the Varian Edge Linac

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

Gulam, M; Gardner, S; Zhao, B

2014-06-15

Purpose: To measure attenuation for modelling of the KVue Couchtop for 6X and 10X FFF SRS/SBRT treatment Methods: Treatment planning simulation studies were done using 6X FFF beams to estimate the dosimetric impact of KVue couchtops (including the Q-Fix IGRT [carbon fiber] and Calypso [nonconductive Kevlar material]) with a structure model obtained from a research workstation (Eclipse, advanced planning interface (API) v13). Prior to installation on the Varian Edge linac, the couchtop along with (Kevlar) rails were CT scanned with the rails at various positions. An additional scan with the couchtop 15cm above the CT table top was obtained withmore » 20cm solid water to facilitate precised/indexed data acquisition. Measurements for attenuation were obtained for field sizes of 2, 4 and 10 cm{sup 2} at 42 gantry angles including 6 pairs of opposing fields and other angles for oblique delivery where the beams traversed the couchtop and or rails. The delivery was fully automated with xml scripts running in developer mode. The results were then used to determine an accurate structure model for AAA (Eclipse v11) planning of IMRT and RapidArc delivery. Results: The planning simulation relative dose attenuation for oblique entry was not significantly different than the Exact IGRT or BrainLab iBeam couch except that the rails added 6% additional attenuation. The relative attenuation measurements for PA, PA (rails: inner position), oblique, oblique (rails: outer position), oblique (rails: inner position) were: −2.0%, −2.5%, −15.6%, −2.5%, −5.0% for 6X FFF and −1.4%, −1.5%, −12.2%, − 2.5%, −5.0% for 10X FFF with slight decrease in attenuation versus field size. A Couch structure model (with HU values) was developed. Calculation compared to measurement showed good agreement except for oblique (rails: outer position) where differences approached a magnitude of 6%. Conclusion: A model of the couch structures has been developed accounting for attenuation for

Obituary: John Louis Africano III, 1951-2006

NASA Astrophysics Data System (ADS)

Barker, Edwin, S.

2007-12-01

The orbital debris, space surveillance, and astronomical communities lost a valued and beloved friend when John L. Africano passed away on July 27, 2006, at the young age of 55. John passed away in Honolulu, Hawaii, from complications following a heart attack suffered while playing racquetball, which was his avocation in life. Born on February 8, 1951, in Saint Louis, Missouri, John graduated with a B.S. in Physics from the University of Missouri at Saint Louis in 1973, and received a Master's degree in Astronomy from Vanderbilt University in 1974. John had a real love for astronomical observing and for conveying his many years of experience to others. He encouraged many young astronomers and mentored them in the basics of photometry and astronomical instrumentation. John was author or co-author on nearly one-hundred refereed publications ranging from analyses of cool stars to the timing of occultations to space surveillance. He was honored for his contributions to minor planet research when the Jet Propulsion Laboratory named Minor Planet 6391 (Africano) after him. John held operational staff positions at several major observatories including McDonald Observatory in Texas, Kitt Peak National Observatory in Arizona, and the Cloudcroft Telescope Facility in New Mexico. He observed at numerous observatories worldwide, including Cerro Tololo Inter-American Observatory (CTIO) in Chile, developing a world-wide network of friends and colleagues. John's ability to build diverse teams through his managerial and technical skills, not to mention his smiling personality, resulted in numerous successes in the observational astronomy and space surveillance arenas. As an astronomer for Boeing LTS Inc., he worked for many years at the Advanced Maui Optical and Space Surveillance site (AMOS) on Maui, Hawaii, where he contributed his operational and instrumental expertise to both the astronomy and space surveillance communities. He was also the co-organizer of the annual AMOS

John locke on personal identity.

PubMed

Nimbalkar, Namita

2011-01-01

John Locke speaks of personal identity and survival of consciousness after death. A criterion of personal identity through time is given. Such a criterion specifies, insofar as that is possible, the necessary and sufficient conditions for the survival of persons. John Locke holds that personal identity is a matter of psychological continuity. He considered personal identity (or the self) to be founded on consciousness (viz. memory), and not on the substance of either the soul or the body.

Obituary: John Sulston (1942-2018).

PubMed

White, John

2018-05-08

John Sulston, a pioneer in the developmental studies of the nematode C. elegans who went on to spearhead the sequencing of the genome of this organism and ultimately the human genome, died on 6th March 2018, shortly after being diagnosed with stomach cancer. Here, I reflect on John's life and work, with a particular focus on his time working on the developmental genetics and lineage of C. elegans . © 2018. Published by The Company of Biologists Ltd.

ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and release in cigarette smoke-exposed primary bronchial epithelial cells from patients with chronic obstructive pulmonary disease (COPD).

PubMed

Stolarczyk, Marta; Amatngalim, Gimano D; Yu, Xiao; Veltman, Mieke; Hiemstra, Pieter S; Scholte, Bob J

2016-08-01

Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as TACE, and epidermal growth factor receptor (EGFR) has been suggested to contribute to chronic obstructive pulmonary disease (COPD) development and progression. The aim of this study was to investigate the role of these proteins in activation of primary bronchial epithelial cells differentiated at the air-liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells from COPD patients with non-COPD CS exposure of ALI-PBEC enhanced ADAM17-mediated shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) toward the basolateral compartment, which was more pronounced in cells from COPD patients than in non-COPD controls. CS transiently increased IL6R and AREG mRNA in ALI-PBEC to a similar extent in cultures from both groups, suggesting that posttranslational events determine differential shedding between COPD and non-COPD cultures. We show for the first time by in situ proximity ligation (PLA) that CS strongly enhances interactions of phosphorylated ADAM17 with AREG and IL-6R in an intracellular compartment, suggesting that CS-induced intracellular trafficking events precede shedding to the extracellular compartment. Both EGFR and ADAM17 activity contribute to CS-induced IL-6R and AREG protein shedding and to mRNA expression, as demonstrated using selective inhibitors (AG1478 and TMI-2). Our data are consistent with an autocrine-positive feedback mechanism in which CS triggers shedding of EGFR agonists evoking EGFR activation, in ADAM17-dependent manner, and subsequently transduce paracrine signaling toward myeloid cells and connective tissue. Reducing ADAM17 and EGFR activity could therefore be a therapeutic approach for the tissue remodeling and inflammation observed in COPD. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

SETI group let by Barney Oliver, John Wolfe and John Billingham (in middle standing) lead a 1976

NASA Technical Reports Server (NTRS)

1976-01-01

SETI group let by Barney Oliver, John Wolfe and John Billingham (in middle standing) lead a 1976 discussion on the best strategies in the Search for Extraterrestrial Intelligence. Joining the discussion are L-R; Charles Seeger, Dario Black, Mary Connors, (Oliver, Wolfe, Billingham) and Larry Lesyna, (seated) Mark Stull.

Protein levels of ADAM10, BACE1, and PSEN1 in platelets and leukocytes of Alzheimer's disease patients.

PubMed

Bram, Jessyka Maria de França; Talib, Leda Leme; Joaquim, Helena Passarelli Giroud; Sarno, Tamires Alves; Gattaz, Wagner Farid; Forlenza, Orestes Vicente

2018-05-29

The clinical diagnosis of Alzheimer's disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process. Abnormalities in amyloid-beta precursor protein (APP) metabolism and in the level of APP secretases have been demonstrated in platelets, and to a lesser extent in leukocytes, of AD patients, with conflicting results. The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls. The protein levels of all APP secretases were significantly higher in platelets compared to leukocytes. We found statistically a significant decrease in ADAM10 (52.5%, p < 0.0001) and PSEN1 (32%, p = 0.02) in platelets from AD patients compared to controls, but not in leukocytes. Combining all three secretases to generate receiver-operating characteristic (ROC) curves, we found a good discriminatory effect (AD vs. controls) when using platelets (the area under the curve-AUC-0.90, sensitivity 88.9%, specificity 66.7%, p = 0.003), but not in leukocytes (AUC 0.65, sensitivity 77.8%, specificity 50.0%, p = 0.2). Our findings indicate that platelets represent a better biological matrix than leukocytes to address the peripheral level of APP secretases. In addition, combining the protein level of ADAM10, BACE1, and PSEN1 in platelets, yielded a good accuracy to discriminate AD from controls.

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site.

PubMed

Abbruzzese, Genevieve; Becker, Sarah F; Kashef, Jubin; Alfandari, Dominique

2016-07-15

The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell-cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. Copyright © 2015. Published by Elsevier Inc.

ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site

PubMed Central

Kashef, Jubin; Alfandari, Dominique

2015-01-01

The cranial neural crest (CNC) is a highly motile population of cells that is responsible for forming the face and jaw in all vertebrates and perturbing their migration can lead to craniofacial birth defects. Cell motility requires a dynamic modification of cell–cell and cell-matrix adhesion. In the CNC, cleavage of the cell adhesion molecule cadherin-11 by ADAM13 is essential for cell migration. This cleavage generates a shed extracellular fragment of cadherin-11 (EC1-3) that possesses pro-migratory activity via an unknown mechanism. Cadherin-11 plays an important role in modulating contact inhibition of locomotion (CIL) in the CNC to regulate directional cell migration. Here, we show that while the integral cadherin-11 requires the homophilic binding site to promote CNC migration in vivo, the EC1-3 fragment does not. In addition, we show that increased ADAM13 activity or expression of the EC1-3 fragment increases CNC invasiveness in vitro and blocks the repulsive CIL response in colliding cells. This activity requires the presence of an intact homophilic binding site on the EC1-3 suggesting that the cleavage fragment may function as a competitive inhibitor of cadherin-11 adhesion in CIL but not to promote cell migration in vivo. PMID:26206614

The Elsevier Trophoblast Research Award Lecture: Importance of metzincin proteases in trophoblast biology and placental development: a focus on ADAM12.

PubMed

Aghababaei, Mahroo; Beristain, Alexander G

2015-04-01

Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentiate into diverse trophoblast subsets is a fundamental process in placental development. Differentiation of trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential for uterine arterial remodeling and placental function. Inadequate placentation, characterized by defects in trophoblast differentiation, may underlie the earliest cellular events driving pregnancy disorders such as preeclampsia and fetal growth restriction. Molecularly, invasive trophoblasts acquire characteristics defined by profound alterations in cell-cell and cell-matrix adhesion, cytoskeletal reorganization and production of proteolytic factors. To date, most studies have investigated the importance of the matrix metalloproteinases (MMPs) and their ability to efficiently remodel components of the extracellular matrix (ECM). However, it is now becoming clear that besides MMPs, other related proteases regulate trophoblast invasion via mechanisms other than ECM turnover. In this review, we will summarize the current knowledge on the regulation of trophoblast invasion by members of the metzincin family of metalloproteinases. Specifically, we will discuss the emerging roles that A Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a particular focus on the ADAM subtype, ADAM12. Copyright © 2015 Elsevier Ltd. All rights reserved.

Celebrating John Glenn’s Legacy

NASA Image and Video Library

2012-03-02

Cleveland State University Master of Music Major James Binion Jr. sings a musical tribute during an event celebrating John Glenn's legacy and 50 years of americans in orbit held at the university's Wolstein Center on Friday, March 3, 2012 in Cleveland, Ohio. In 1998 Lindsey flew onboard the space shuttle Discovery along with then 77 year-old Sen. John Glenn for the STS-95 mission. Glenn became the first American to orbit Earth in 1962. Photo Credit: (NASA/Bill Ingalls)

A to Z with Jasper Johns

ERIC Educational Resources Information Center

Kirker, Sara Schmickle

2008-01-01

One contemporary artist that kindergarten students can easily relate to is Jasper Johns. In this article, the author discusses how she introduced John's numeric and alphabetic paintings to her kindergarten students. The young artists were amazed that art can be created from the familiar symbols that they are learning to make in their regular…

Hydroquinone-induced FOXP3-ADAM17-Lyn-Akt-p21 signaling axis promotes malignant progression of human leukemia U937 cells.

PubMed

Chen, Ying-Jung; Liu, Wen-Hsin; Chang, Long-Sen

2017-02-01

Hydroquinone (1,4-benzenediol; HQ), a major marrow metabolite of the leukemogen benzene, has been proven to evoke benzene-related hematological disorders and myelotoxicity in vitro and in vivo. The goal of the present study was to explore the role of FOXP3 in HQ-induced malignant progression of U937 human leukemia cells. U937 cells were treated with 5 μM HQ for 24 h, and the cells were re-suspended in serum-containing medium without HQ for 2 days. The same procedure was repeated three times, and the resulting U937/HQ cells were maintained in cultured medium containing 5 μM HQ. Proliferation and colony formation of U937/HQ cells were notably higher than those of U937 cells. Ten-eleven translocation methylcytosine dioxygenase-mediated demethylation of the Treg-specific demethylated region in FOXP3 gene resulted in higher FOXP3 expression in U937/HQ cells than in U937 cells. FOXP3-induced miR-183 expression reduced β-TrCP mRNA stability and suppressed β-TrCP-mediated Sp1 degradation, leading to up-regulation of Sp1 expression in U937/HQ cells. Sp1 up-regulation further increased ADAM17 and Lyn expression, and ADAM17 up-regulation stimulated Lyn activation in U937/HQ cells. Moreover, U937/HQ cells showed higher Lyn-mediated Akt activation and cytoplasmic p21 expression than U937 cells did. Abolishment of Akt activation decreased cytoplasmic p21 expression in U937/HQ cells. Suppression of FOXP3, ADAM17, and Lyn expression, as well as Akt inactivation, repressed proliferation and clonogenicity of U937/HQ cells. Together with the finding that cytoplasmic p21 shows anti-apoptotic and oncogenic activities in cancer cells, the present data suggest a role of FOXP3/ADAM17/Lyn/Akt/p21 signaling axis in HQ-induced hematological disorders.

John Henry--The Steel Driving Man

ERIC Educational Resources Information Center

Murphy, David E.; Gulley, Laura L.

2005-01-01

The story of John Henry provided the setting for sixth-grade class to participate in a John Henry Day of mathematics experiments. The students collected data from experiments where students competed against machines and technology. The student analyzed the data by comparing two box plots, a box plot of human data, and a box plot of machine or…

John C. Mather, the Big Bang, and the COBE

Science.gov Websites

Additional Information * Videos John C. Mather Courtesy of NASA "Dr. John C. Mather of NASA's Goddard excerpt from NASA Scientist Shares Nobel Prize for Physics 2Edited excerpt from John Mather: The Path to a Spacecraft Courtesy of Lawrence Berkeley National Laboratory Additional Web Pages: Dr. John C Mather, NASA

The Co-simulation of Humanoid Robot Based on Solidworks, ADAMS and Simulink

NASA Astrophysics Data System (ADS)

Song, Dalei; Zheng, Lidan; Wang, Li; Qi, Weiwei; Li, Yanli

A simulation method of adaptive controller is proposed for the humanoid robot system based on co-simulation of Solidworks, ADAMS and Simulink. A complex mathematical modeling process is avoided by this method, and the real time dynamic simulating function of Simulink would be exerted adequately. This method could be generalized to other complicated control system. This method is adopted to build and analyse the model of humanoid robot. The trajectory tracking and adaptive controller design also proceed based on it. The effect of trajectory tracking is evaluated by fitting-curve theory of least squares method. The anti-interference capability of the robot is improved a lot through comparative analysis.

A.D.A.M. test (Antibiofilm Dressing's Activity Measurement) - Simple method for evaluating anti-biofilm activity of drug-saturated dressings against wound pathogens.

PubMed

Junka, Adam F; Żywicka, Anna; Szymczyk, Patrycja; Dziadas, Mariusz; Bartoszewicz, Marzena; Fijałkowski, Karol

2017-12-01

In the present article, we propose a simple Antibiofilm Dressing's Activity Measurement (A.D.A.M.) test that allows to check in vitro a dressing's suitability against biofilm-related wound infections. To perform the test, three agar discs are covered with biofilm formed by the tested pathogen after which they are assembled one over another in the form of an agar plug and placed in the well of a 24-well plate. The top disc is covered with the analyzed dressing and the entire set is incubated for 24h. During this time, the investigated antimicrobial substance is released from the dressing and penetrates to subsequent biofilm-covered agar discs. Biofilm reduction is measured using 2,3,5-triphenyl-2H-tetrazolium chloride (TTC) spectrometric assay and the results are compared to untreated control samples (agar plug covered with biofilm and without the dressing/or with a passive dressing placed on the top disc). Furthermore, in order to standardize the differences in penetrability of the drugs released from active dressings the results can be expressed as a dimensionless value referred to as the Penetrability Index. In summary, A.D.A.M. test is simple, cheap, can be performed practically in every clinical laboratory and takes no more time than routine microbiological diagnostics. Apart from measuring the released drug's activity, the A.D.A.M. test allows to assess drug penetrability (across three agar discs), reflecting real wound conditions, where microbes are frequently hidden under the necrotic tissue or cloth. In conclusion, the A.D.A.M. test produces a high volume of data that, when analyzed, can provide a researcher with a valuable hint concerning the applicability of active dressings against specific biofilm pathogens in a particular setting. Copyright © 2017 Elsevier B.V. All rights reserved.

33 CFR 110.183 - St. Johns River, Florida.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false St. Johns River, Florida. 110.183... ANCHORAGE REGULATIONS Anchorage Grounds § 110.183 St. Johns River, Florida. (a) The anchorage grounds—(1... anchor in the St. Johns River, as depicted on NOAA chart 11491, between the entrance buoy (STJ) and the...

33 CFR 110.73 - St. Johns River, Fla.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false St. Johns River, Fla. 110.73... ANCHORAGE REGULATIONS Special Anchorage Areas § 110.73 St. Johns River, Fla. (a) Area A. The waters lying within an area bounded by a line beginning at a point located at the west bank of St. Johns River at...

Apixaban and dalteparin in active malignancy associated venous thromboembolism. The ADAM VTE Trial.

PubMed

McBane Ii, Robert; Loprinzi, Charles L; Ashrani, Aneel; Perez-Botero, Juliana; Leon Ferre, Roberto A; Henkin, Stanislav; Lenz, Charles J; Le-Rademacher, Jennifer G; Wysokinski, Waldemar E

2017-10-05

Currently, low molecular weight heparin (LMWH) is the guideline endorsed treatment of patients with cancer associated venous thromboembolism (VTE). While apixaban is approved for the treatment of acute VTE, there are limited data supporting its use in cancer patients. The rationale and design of this investigator initiated Phase IV, multicenter, randomized, open label, superiority trial assessing the safety of apixaban versus dalteparin for cancer associated VTE is provided (ADAM-VTE; NCT02585713). The main aim of the ADAM-VTE trial is to test the hypothesis that apixaban is associated with a significantly lower rate of major bleeding compared to dalteparin in the treatment of cancer patients with acute VTE. The primary safety outcome is rate of major bleeding. Secondary efficacy objective is to assess the rates of recurrent VTE or arterial thromboembolism. Cancer patients with acute VTE (n=300) are randomized to receive apixaban (10 mg twice daily for 7 days followed by 5 mg twice daily thereafter) or dalteparin (200 IU/Kg daily for 30 days followed by 150 IU/kg daily thereafter) for 6 months. Stratification factors used for randomization include cancer stage and cancer specific risk of venous thromboembolism using the Khorana score. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium comprised of 90 oncology practices in the United States and Canada. Based on the hypothesis to be tested, we anticipate that these trial results will provide evidence supporting apixaban as an effective treatment of cancer associated VTE at lower rates of major bleeding compared to LMWH.

Defenses and morality: Adam Smith, Sigmund Freud, and contemporary psychoanalysis.

PubMed

Gabrinetti, Paul A; Özler, Sule

2014-10-01

In this paper we follow the development and transmission of moral learning from Adam Smith's impartial spectator to Sigmund Freud's superego and then to contemporary psychoanalysis. We argue that defenses are an integral component in the acquisition of any moral system. Elaborating on this argument, we assert that there is a progression from defensive systems that are "closed" to defensive systems that are "open," as defined in a recent work by Novick and Novick. The former system is "static, avoids reality, and is characterized by power dynamics, sadomasochism, and omnipotent defense." The latter, on the other hand, is a system that allows for "joy, creativity, spontaneity, love and it is attuned to reality." Furthermore, while Smith and Freud's systems are more one-person systems of defense, contemporary psychoanalysis has moved to more of a two-person system.

DebrisLV Hypervelocity Impact Post-Shot Physical Results Summary

DTIC Science & Technology

2015-02-27

Sheaffer1, Paul M. Adams2, Naoki Hemmi3, Christopher Hartney1 1Space Science Applications Laboratory Physical Sciences Laboratories 2Space Materials...PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Patti M. Sheaffer, Paul M. Adams, Naoki Hemmi, Christopher Hartney 5d. PROJECT NUMBER 5e. TASK NUMBER 5f...this document could not have been acquired without the active help and support of NASA (J.-C. Liou, Robert Markowicz); Jacobs Technologies ( John Opiela

Suppression of Akt/Foxp3-mediated miR-183 expression blocks Sp1-mediated ADAM17 expression and TNFα-mediated NFκB activation in piceatannol-treated human leukemia U937 cells.

PubMed

Liu, Wen-Hsin; Chang, Long-Sen

2012-09-01

To address the mechanism of piceatannol in inhibiting TNFα-mediated pathway, studies on piceatannol-treated human leukemia U937 cells were conducted. Piceatannol treatment reduced TNFα shedding and NFκB activation and decreased the release of soluble TNFα into the culture medium of U937 cells. Moreover, ADAM17 expression was down-regulated in piceatannol-treated cells. Over-expression of ADAM17 abrogated the ability of piceatannol to suppress TNFα-mediated NFκB activation. Piceatannol-evoked β-TrCP up-regulation promoted Sp1 degradation, thus reducing transcriptional level of ADAM17 gene in U937 cells. Piceatannol treatment induced p38 MAPK phosphorylation but inactivation of Akt and ERK. In contrast to p38 MAPK inhibitor or restoration of ERK activation, transfection of constitutive active Akt abolished the effect of piceatannol on β-TrCP, Sp1 and ADAM17 expression. Piceatannol-elicited down-regulation of miR-183 expression was found to cause β-TrCP up-regulation. Inactivation of Akt resulted in Foxp3 down-regulation and reduced miR-183 expression in piceatannol-treated cells. Knock-down of Foxp3 and chromatin immunoprecipitating revealed that Foxp3 genetically regulated transcription of miR-183 gene. Taken together, our data indicate that suppression of Akt/Foxp3-mediated miR-183 expression blocks Sp1-mediated ADAM17 expression in piceatannol-treated U937 cells. Consequently, piceatannol suppresses TNFα shedding, leading to inhibition of TNFα/NFκB pathway. Copyright © 2012 Elsevier Inc. All rights reserved.

46 CFR 7.90 - St. Johns River, FL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false St. Johns River, FL. 7.90 Section 7.90 Shipping COAST... § 7.90 St. Johns River, FL. A line drawn from the southeasternmost extremity of Little Talbot (Spike) Island to latitude 30°23.8′ N. longitude 81°20.3′ W. (St. Johns Lighted Whistle Buoy “2 STJ”); thence to...

St. John's wort: a new alternative for depression?

PubMed

Josey, E S; Tackett, R L

1999-03-01

The primary purpose of this article is to review the existing literature concerning the therapeutic uses, adverse effects, and possible drug interactions of St. John's wort (Hypericum perforatum) as compared to other antidepressant medications. Reference material was obtained through database searches with time restrictions of 1985 to the present. Studies selected were those written in the English language which compared the role of St. John's wort, tricyclic antidepressants, monoamine oxidase inhibitors, and serotonin-selective reuptake inhibitors in the treatment of depression. Other studies were selected based on their evaluation of the safety and efficacy of St. John's wort as an antidepressant for a minimum of four weeks. A review of existing literature recognized nine clinical trials that reported the efficacy of St. John's wort as compared to placebo and to other antidepressant medications. Of these nine, four controlled studies were chosen based upon their large patient populations and their consistency in brand and dosage of St. John's wort used. These four studies demonstrated that St. John's wort was as effective as other antidepressant medications and more effective than placebo, as the clinical symptoms of depression greatly decreased upon administration of H. perforatum. The side-effect profile of H. perforatum at this time appears to be superior to any current U.S.-approved antidepressant medication. From the existing literature, St. John's wort appears to be a safe and effective alternative in the treatment of depression. Tricylic antidepressants and monoamine oxidase inhibitors can produce serious cardiac side-effects, such as tachycardia and postural hypotension, and many unwanted anticholinergic side-effects, including dry mouth and constipation. St. John's wort has proven to be free of any cardiac, as well as anticholinergic, side-effects normally seen with antidepressant medications. Based upon limited studies, St. John's wort appears to be an

ADAM, a hands‐on patient simulator for teaching principles of drug disposition and compartmental pharmacokinetics

PubMed Central

Zuna, Ines

2017-01-01

Aims To design, construct and validate a pharmacokinetics simulator that offers students hands‐on opportunities to participate in the design, administration and analysis of oral and intravenous dosing regimens. Methods The Alberta Drug Administration Modeller (ADAM) is a mechanical patient in which peristaltic circulation of water through a network of silicone tubing and glass bottles creates a representation of the outcomes of drug absorption, distribution, metabolism and elimination. Changing peristaltic pump rates and volumes in bottles allows values for pharmacokinetic constants to be varied, thereby simulating differences in drug properties and in patient physiologies and pathologies. Following administration of methylene blue dye by oral or intravenous routes, plasma and/or urine samples are collected and drug concentrations are determined spectrophotometrically. The effectiveness of the simulator in enhancing student competence and confidence was assessed in two undergraduate laboratory classes. Results The simulator effectively models one‐ and two‐compartment drug behaviour in a mathematically‐robust and realistic manner. Data allow calculation of numerous pharmacokinetic constants, by traditional graphing methods or with curve‐fitting software. Students' competence in solving pharmacokinetic problems involving calculations and graphing improved significantly, while an increase in confidence and understanding was reported. Conclusions The ADAM is relatively inexpensive and straightforward to construct, and offers a realistic, hands‐on pharmacokinetics learning opportunity for students that effectively complements didactic lectures. PMID:28666308

John Carroll University

ERIC Educational Resources Information Center

Dean, Kathleen Lis; Rombalski, Patrick; O'Dell, Kyle

2009-01-01

John Carroll University (JCU) is a Jesuit Catholic institution located in University Heights, approximately 10 miles east of Cleveland, Ohio. Founded in 1888, the university has a population of 3,400 undergraduates and 800 graduate students. The Division of Student Affairs at JCU comprises 11 units. The mission of the division is the same as that…

Adams' Closed-Loop Concept of Learning and Motor Performance: It's Application in Behavioural Kinesiology and Patients Education in Rehabilitation.

ERIC Educational Resources Information Center

Olaogun, Matthew O. B.

1986-01-01

J. Adams' application of the closed-loop theory (involving feedback and correction) on human learning and motor performance is described. The theory's applicability to behavioral kinesiology (the science of human movement) is discussed in the context of physical therapy, stressing the importance of knowledge of results as a motivating factor.…

Ideas of the Founders on Constitutional Government: Resources for Teachers of History and Government.

ERIC Educational Resources Information Center

Patrick, John J., Ed.

The political ideas of John Adams, Alexander Hamilton, John Jay, Thomas Jefferson, James Madison, and other Founders of the United States have been a rich civic legacy for successive generations of citizens. An important means of ensuring that these ideas on constitutional government continue to inspire and guide people in the 21st century lies in…

Liberty for All? A History of US: Book Five.

ERIC Educational Resources Information Center

Hakim, Joy

This volume is book 5 in a 10 part series on U.S. history for children. The book tells the story of the Antebellum era--especially the story of children from a variety of backgrounds. Some of the characters depicted in this volume include Jedediah Smith, Davy Crockett, John Quincy Adams, Emily Dickinson, Sojourner Truth, John James Audubon, and…

33 CFR 117.325 - St. Johns River.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false St. Johns River. 117.325 Section 117.325 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Florida § 117.325 St. Johns River. (a) The drawspan...

Camp Upshur, Marine Corps Base Quantico, VA Architectural Survey

DTIC Science & Technology

2009-08-01

MIPR) M9301509MPFE007, dated 21 November 2008. The MCB Quantico technical monitor was John Haynes, Archeologist. The work was performed by the...Manager was Adam Smith. Dr. Christopher White is Chief, CN-C, and Dr. John Bandy is Chief, CN. The Deputy Director of CERL is Dr. Kirankumar V...Previous work reported in “Historical Resource Survey and Evaluation, Marine Corps Base Quantico, Virginia” John Milner Associates, 2008 and on

Obituary: John J. Hillman, 1938-2006

NASA Astrophysics Data System (ADS)

Chanover, Nancy

2007-12-01

John J. Hillman, a dedicated NASA civil servant, spectroscopist, astrophysicist, planetary scientist, and mentor, died on February 12, 2006 of ocular melanoma at his home in Columbia, Maryland. His professional and personal interests were wide-reaching and varied, and he devoted his career to the advancement of our understanding of the beauty and wonder in the world around us. His love of nature, art, and science made him a true Renaissance man. John was born in Fort Jay, New York, on November 22, 1938, and was raised in Washington, D.C. He received his B.S., M.S., and Ph.D. degrees in Physics from American University in 1967, 1970, and 1975, respectively. He began working at NASA's Goddard Space Flight Center, then in its infancy, in 1969, juggling a full-time position as a Research Physicist, the completion of his M.S. and Ph.D. degrees, and a young family. His background in molecular spectroscopy enabled him to apply his skills to numerous disciplines within NASA: infrared and radio astronomy; electronic, vibrational, and rotational structure of interstellar molecules; solar and stellar atmospheres; and planetary atmospheres. He published more than 70 journal papers in these disciplines. He was a frequent contributor to the Ohio State University International Symposium on Molecular Spectroscopy, and possessed a rare ability to bridge the gap between laboratory and remote sensing spectroscopy, bringing scientists from different disciplines together to understand our Universe. The last fifteen years of John's career were devoted to the development of acousto-optic tunable filter (AOTF) cameras. He championed this technology as a low-cost, low-power alternative to traditional imaging cameras for in situ or remotely sensed planetary exploration. It was within this context that I got to know John, and eventually worked closely with him on the demonstration and application of this technology for planetary science using ground-based telescopes in New Mexico, California

Effets de l'interaction avec l'oxygène sur le comportement de couches semi-conductrices de ZnO, SnO{2} et CdSe

NASA Astrophysics Data System (ADS)

Ain-Souya, A.; Ghers, M.; Haddad, A.; Tebib, W.; Rehamnia, R.; Messsalhi, A.; Bounouala, M.; Djouama, M. C.

2005-05-01

Les propriétés superficielles des matériaux solides diffèrent de celles du volume. A la surface, des défauts de différentes natures peuvent être présents. Ils permettent à la surface d'être interactive avec le milieu ambiant. Les multiples interactions entre les états de surface et des éléments du milieu extérieur peuvent modifier les propriétés superficielles. Ce travail étudie la régénération de couches semi-conductrices après adsorption isotherme d'oxygène à différentes températures effectuées entre 20 ° C et 300 ° C. Les matériaux qui ont servi à l'étude sont des couches de ZnO, SnO{2} et CdSe. Celles de CdSe ont été obtenues par co-évaporation, sous vide, de cadmium et de sélénium. Les échantillons de ZnO et SnO{2} ont été élaborés par oxydation, à des températures respectives de 450 ° C et 200 ° , de Zn et Sn déposés par électrolyse et par évaporation sous vide. Les matériaux évaporés ont été déposés sur des plaquettes en verre, les autres ont été électrodéposés sur des substrats métalliques. Les variations des propriétés électriques des couches ont été suivies par mesure de leur résistance électrique superficielle R. Les courbes LogR = f (103 /T (K)), relevées sous vide à différentes températures, sont caractéristiques d'un comportement de semi-conducteur. Des essais d'adsorption d'O{2} à différentes températures montrent des variations considérables de R. En effet, la chimisorption forte d'un gaz par une surface semi-conductrice est telle que l'échange électronique entre adsorbant et adsorbat provoque la formation d'une zone de charge d'espace modifiant la conduction superficielle. Les résultats mettent en évidence des domaines de température de plus haute sensibilité à l'oxygène. Pour le CdSe, certaines désorptions isothermes ont été suffisantes pour une régénération totale des échantillons. Les couches de ZnO ont souvent nécessité des désorptions programm

In memoriam - John M. Young (1942-2013)

USDA-ARS?s Scientific Manuscript database

It is with sadness that friends and colleagues of John Young learnt of his death at home in Auckland, New Zealand on 30th September 2013. John began his scientific career at the Plant Diseases Division (PDD) of the Department of Scientific and Industrial Research (DSIR), New Zealand after completing...

Jonction Josephson en couche épaisse d'oxydes supraconducteurs

NASA Astrophysics Data System (ADS)

Gunther, C.; Monfort, Y.; Sing, M. Lam Chok; Bloyet, D.; Brousse, T.; Provost, J.; Raveau, B.

1992-02-01

Constrictions engraved in YBaCuO thick films fabricated by screen printing on YSZ substrate (J_c>3 000 A/cm^2 at 77 K) have been studied. Microwave irradiation of the devices at LN2 showed distinct Shapiro steps demonstrating the presence intrinsic Josephson junctions. The latter have an I_c(T) dependence fitting (1-T/T_c)^2 characteristic of SNS junctions. Furthermore, dc SQUID effects have also been observed with a peak-to-peak response simeq 0.2 μV and with a magnetic field periodicity extending through several hundred of φ_0. An energy resolution close to 3× 10^{-29} J/Hz is estimated for our constriction operating in the white noise frequency range (f>50 Hz) at 77 K. This sensitivity is adequate to use this flux sensor in many applications : geomagnetism, magnetocardiology, ... Nous avons étudié des constrictions gravées dans des couches épaisses d'YBaCuO déposées sur substrat de YSZ (J_c>3 000 A/cm^2 à 77 K). L'observation de marches de Shapiro lors d'irradiations des échantillons à 77 K par un champ HF met clairement en évidence la présence de jonctions Josephson intrinsèques de type SNS, leur dépendance en température du courant critique étant en (1-T/T_c)^2. De plus, nous avons obtenu des réponses en champ magnétique, caractéristiques des SQUIDs dc, d'amplitude 0,2 μVcc et dont la périodicité s'étend sur plusieurs centaines de φ_0. La résolution en énergie est de l'ordre de 3× 10^{-29} J/Hz en zone de bruit blanc (f>50 Hz) à 77 K. Cette sensibilité est suffisante pour envisager son utilisation dans des applications telles que : géomagnétisme, magnétocardiologie, ...

Modeling and simulation research on electromagnetic and energy-recycled damper based on Adams

NASA Astrophysics Data System (ADS)

Zhou, C. F.; Zhang, K.; Zhang, Pengfei

2018-05-01

In order to study the voltage and power output characteristics of the electromagnetic and energy-recycled damper which consists of gear, rack and generator, the Adams model of this damper and the Simulink model of generator are established, and the co-simulation is accomplished with these two models. The output indexes such as the gear speed and power of generator are obtained by the simulation, and the simulation results demonstrate that the voltage peak of the damper is 25 V; the maximum output power of the damper is 8 W. The above research provides a basis for the prototype development of electromagnetic and energy-recycled damper with gear and rack.

The Utilitarians Revisited.

ERIC Educational Resources Information Center

Camic, Charles

1979-01-01

Investigates the social theories of the major utilitarians (David Hume, Adam Smith, Jeremy Bentham, and John Stewart Mill), and outlines the historical process whereby the prevailing mythology concerning utilitarianism developed. (Author/KC)

[Kurschmann-Steinert myotonic dystrophia and Adams-Stoke attacks. Successful treatment of arrhythmia by means of pacemaker implantation].

PubMed

Bieler, M; Sefidpar, M; Engel, U R; Reutter, F W

1976-11-20

The case is reported of a 39-year-old male with Steinert's dystrophia myotonica complicated by cardiac arrhythmias manifested by high-degree a-v block with Stokes-Adams attacks. Implantation of a demand-type cardiac pacemaker brought prompt relief from cardiac symptoms and the patient was able to resume work. The pathologico-anatomical findings in dystrophia myotonica are discussed, together with their possible connection with the type of arrhythmias described.

John Kotter on Leadership, Management and Change.

ERIC Educational Resources Information Center

Bencivenga, Jim

2002-01-01

Excerpts from interview with John Kotter, Konosuke Matsushita Professor of Leadership at the Harvard Business School, about his thoughts on the role of the superintendent as leader and manager. Describes his recent book "John P. Kotter on What Leaders Really Do," 1999. Lists eight-step change process from his book "Leading Change," 1996. (PKP)

Struggle for the Soul: John Lawrence Childs

ERIC Educational Resources Information Center

Stallones, Jared

2010-01-01

John Lawrence Childs was born in Eau Claire, Wisconsin on January 11, 1889, the second child of John Nelson Childs and Helen Janette (Nettie) Smith. In childhood Childs absorbed the values of industry, democracy, and a traditional, but socially conscious, religion. Childs was a Methodist and an intensely private person not given to talking about…

In memoriam: John Warren Aldrich, 1906-1995

USGS Publications Warehouse

Banks, Richard C.

1997-01-01

John Aldrich was born in Providence, Rhode Island, on 23 February 1906, and went to the Providence public schools. He developed a broad interest in natural history at an early age, being stimulated by his mother, a kindergarten teacher, who introduced him to nature books. His interest was strengthened by Harold L. Madison, Director of the Park Museum in Providence, an Associate ( = member) of the AOU. As a high school student, John taught nature study at the Rhode Island Boy Scout Camp in summers. John was President of his class at Classical High School, and manager of the school's football team in his senior year. Also in that year, 1923, John published his first paper, a note in Bird-Lore on the occurrence of the Mockingbird in Rhode Island. That paper is a literary gem, showing that his skill in writing developed as early as his knowledge of birds. His early interest in football continued as well; he was a devoted fan of the Washington Redskins in his later years.

Dedication: John Reuben Clark.

USDA-ARS?s Scientific Manuscript database

Volume 40 of Horticultural reviews is dedicated to John Reuben Clark (University of Arkansas) for his outstanding contributions to horticulture. While known particularly for his impact on blackberry, blueberry, table grape, and peach cultivar development, he has also been a strong and enthusiastic v...

Connecting the Edge: Mobile Ad-Hoc Networks (MANETs) for Network Centric Warfare

DTIC Science & Technology

2007-04-01

Cebrowski and Mr. John Garstka are generally credited with introducing the concept and origins of NCW.8 They described the military’s evolution from...www.sdrforum.org/pages/aboutTheForum/faqs.asp Adams, James. The Next World War. New York, NY: Simon & Schuster, 1998. Alberts, David S., John J. Garstka, and...Joint Tactical Radio System – Reloaded.” CHIPS, July-September 2006: 6-9. Arquilla, John , and David Ronfeldt. In Athena’s Camp. Santa Monica, CA