Meiosis-Specific Loading of the Centromere-Specific Histone CENH3 in Arabidopsis thaliana

Science.gov (United States)

Ravi, Maruthachalam; Shibata, Fukashi; Ramahi, Joseph S.; Nagaki, Kiyotaka; Chen, Changbin; Murata, Minoru; Chan, Simon W. L.

2011-01-01

Centromere behavior is specialized in meiosis I, so that sister chromatids of homologous chromosomes are pulled toward the same side of the spindle (through kinetochore mono-orientation) and chromosome number is reduced. Factors required for mono-orientation have been identified in yeast. However, comparatively little is known about how meiotic centromere behavior is specialized in animals and plants that typically have large tandem repeat centromeres. Kinetochores are nucleated by the centromere-specific histone CENH3. Unlike conventional histone H3s, CENH3 is rapidly evolving, particularly in its N-terminal tail domain. Here we describe chimeric variants of CENH3 with alterations in the N-terminal tail that are specifically defective in meiosis. Arabidopsis thaliana cenh3 mutants expressing a GFP-tagged chimeric protein containing the H3 N-terminal tail and the CENH3 C-terminus (termed GFP-tailswap) are sterile because of random meiotic chromosome segregation. These defects result from the specific depletion of GFP-tailswap protein from meiotic kinetochores, which contrasts with its normal localization in mitotic cells. Loss of the GFP-tailswap CENH3 variant in meiosis affects recruitment of the essential kinetochore protein MIS12. Our findings suggest that CENH3 loading dynamics might be regulated differently in mitosis and meiosis. As further support for our hypothesis, we show that GFP-tailswap protein is recruited back to centromeres in a subset of pollen grains in GFP-tailswap once they resume haploid mitosis. Meiotic recruitment of the GFP-tailswap CENH3 variant is not restored by removal of the meiosis-specific cohesin subunit REC8. Our results reveal the existence of a specialized loading pathway for CENH3 during meiosis that is likely to involve the hypervariable N-terminal tail. Meiosis-specific CENH3 dynamics may play a role in modulating meiotic centromere behavior. PMID:21695238

PCR specific for Actinobacillus pleuropneumoniae serotype 3

DEFF Research Database (Denmark)

Zhou, L.; Jones, S.C.P.; Angen, Øystein

2008-01-01

, but the method has liminations, for example, cross-reactions between serotypes 3, 6, and 8. This study describes the development of a serotype 3-specific PCR, based on the capsule locus, which can be used in a multiplex format with the organism's specific gene apxIV. The PCR test was evaluated on 266 strains...

Correlation between (3H)dopamine specific uptake and (3H)GBR 12783 specific binding during the maturation of rat striatum

International Nuclear Information System (INIS)

Bonnet, J.J.; Costentin, J.

1989-01-01

The development of the specific uptake of dopamine in the rat striatum during the early postnatal period is compared with the ontogenetic changes of the specific binding of ( 3 H)GBR 12783 to the site of uptake inhibition. During maturation, the increase in the specific binding of ( 3 H)GBR 12783 parallels the increase in the specific uptake of dopamine. ( 3 H)GBR 12783 specific binding sites increase in number from day 1 postpartum until 40 days, when they reach the adult level. In 40 day-old rats, the weight of the striatum represents 80% of adult values. The affinity of ( 3 H)GBR 12783 for the inhibition site is similar in membrane preparations obtained from 6 day-old pups and adults; this results in a same ability of the inhibitor to block the specific uptake of dopamine into synaptosomes obtained from pups or adult rats. These data support the hypothesis of the existence of a single molecular entity including both the inhibition site and the carrier itself

Specific heat of amorphous 3He films and confined liquid 3He

International Nuclear Information System (INIS)

Golov, A.; Pobell, F.

1995-01-01

We have measured the heat capacities of 3 He films and liquid 3 He in porous Vycor glass at 10 to 600 mK. With increasing the film thickness front 1 to 3 atomic layers , the specific heat evolves gradually from that typical to solid to that of liquid 3 He. At about 2 atomic layers, however, its low-temperature part is nearly temperature-independent; we interpret this as a result of gradual freezing of spins in an amorphous solid 3 He film with decreasing the temperature. The contribution of liquid 3 He in the center of the Vycor pores can be described as the specific heat of bulk liquid 3 He at corresponding pressures in the range 0 to 28 bar. The thickness of amorphous solid on the pore walls increases with external pressure roughly linearly. Preplating the walls with 4 He allows to determine the positions of 3 He atoms contributing to the surface specific heat at 10 to 50 mK. In addition, the contribution from the specific heat of 3 He- 4 He mixing at 100 to 600 mK is discussed as a function of pressure and amount of 4 He

3D-printed patient-specific applications in orthopedics

Directory of Open Access Journals (Sweden)

Wong KC

2016-10-01

Full Text Available Kwok Chuen Wong Department of Orthopedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong Abstract: With advances in both medical imaging and computer programming, two-dimensional axial images can be processed into other reformatted views (sagittal and coronal and three-dimensional (3D virtual models that represent a patients’ own anatomy. This processed digital information can be analyzed in detail by orthopedic surgeons to perform patient-specific orthopedic procedures. The use of 3D printing is rising and has become more prevalent in medical applications over the last decade as surgeons and researchers are increasingly utilizing the technology’s flexibility in manufacturing objects. 3D printing is a type of manufacturing process in which materials such as plastic or metal are deposited in layers to create a 3D object from a digital model. This additive manufacturing method has the advantage of fabricating objects with complex freeform geometry, which is impossible using traditional subtractive manufacturing methods. Specifically in surgical applications, the 3D printing techniques can not only generate models that give a better understanding of the complex anatomy and pathology of the patients and aid in education and surgical training, but can also produce patient-specific surgical guides or even custom implants that are tailor-made to the surgical requirements. As the clinical workflow of the 3D printing technology continues to evolve, orthopedic surgeons should embrace the latest knowledge of the technology and incorporate it into their clinical practice for patient-specific orthopedic applications. This paper is written to help orthopedic surgeons stay up-to-date on the emerging 3D technology, starting from the acquisition of clinical imaging to 3D printing for patient-specific applications in orthopedics. It 1 presents the necessary steps to prepare the medical images that are

Conventional patient specific IMRT QA and 3DVH verification of dose distribution for helical tomotherapy

International Nuclear Information System (INIS)

Sharma, Prabhat Krishna; Joshi, Kishore; Epili, D.; Gavake, Umesh; Paul, Siji; Reena, Ph.; Jamema, S.V.

2016-01-01

In recent years, patient-specific IMRT QA has transitioned from point dose measurements by ion chambers to films to 2D array measurements. 3DVH software has taken this transition a step further by estimating the 3D dose delivered to the patient volume from 2D diode measurements using a planned dose perturbation (PDP) algorithm. This algorithm was developed to determine, if the conventional IMRT QA though sensitive at detecting errors, has any predictive power in detecting dose errors of clinical significance related to dose to the target volume and organs at risk (OAR). The aim of this study is to compare the conventional IMRT patient specific QA and 3DVH dose distribution for patients treated with helical tomotherapy (HT)

The role of NLRP3 and AIM2 in inflammasome activation during Brucella abortus infection.

Science.gov (United States)

Marim, Fernanda M; Franco, Miriam M Costa; Gomes, Marco Tulio R; Miraglia, Maria Cruz; Giambartolomei, Guillermo H; Oliveira, Sergio C

2017-02-01

The innate immune system is essential for the detection and elimination of bacterial pathogens. Upon inflammasome activation, caspase-1 cleaves pro-IL-1β and pro-IL-18 to their mature forms IL-1β and IL-18, respectively, and the cell undergoes inflammatory death termed pyroptosis. Here, we reviewed recent findings demonstrating that Brucella abortus ligands activate NLRP3 and AIM2 inflammasomes which lead to control of infection. This protective effect is due to the inflammatory response caused by IL-1β and IL-18 rather than cell death. Brucella DNA is sensed by AIM2 and bacteria-induced mitochondrial reactive oxygen species is detected by NLRP3. However, deregulation of pro-inflammatory cytokine production can lead to immunopathology. Nervous system invasion by bacteria of the genus Brucella results in an inflammatory disorder termed neurobrucellosis. Herein, we discuss the mechanism of caspase-1 activation and IL-1β secretion in glial cells infected with B. abortus. Our results demonstrate that the ASC inflammasome is indispensable for inducing the activation of caspase-1 and secretion of IL-1β upon infection of astrocytes and microglia with Brucella. Moreover, our results demonstrate that secretion of IL-1β by Brucella-infected glial cells depends on NLRP3 and AIM2 and leads to neurobrucellosis. Further, the inhibition of the host cell inflammasome as an immune evasion strategy has been described for bacterial pathogens. We discuss here that the bacterial type IV secretion system VirB is required for inflammasome activation in host cells during infection. Taken together, our results indicate that Brucella is sensed by ASC inflammasomes mainly NLRP3 and AIM2 that collectively orchestrate a robust caspase-1 activation and pro-inflammatory response.

A novel antihuman C3d monoclonal antibody with specificity to the C3d complement split product

DEFF Research Database (Denmark)

Rasmussen, Karina Juhl; Skjødt, Mikkel-Ole; Vitved, Lars

2017-01-01

The complement component C3 and the cleavage products of C3b/iC3b, C3c and C3d are used as biomarkers in clinical diagnostics. Currently, no specific antibodies are able to differentiate C3d from other fragments, although such a distinction could be very valuable considering that they may reflect...... different pathophysiological mechanisms. We have developed a rat antihuman C3d monoclonal antibody with specificity to the end sequence of the N-terminal region of C3d. The antibody can therefore only bind to C3d when it manifests itself as the final end product of cleaved C3. We believe...

Discovery of a Heparan sulfate 3- o -sulfation specific peeling reaction

NARCIS (Netherlands)

Huang, Yu; Mao, Yang; Zong, Chengli; Lin, Cheng; Boons, Geert Jan|info:eu-repo/dai/nl/088245489; Zaia, Joseph

2015-01-01

Heparan sulfate (HS) 3-O-sulfation determines the binding specificity of HS/heparin for antithrombin III and plays a key role in herpes simplex virus (HSV) infection. However, the low natural abundance of HS 3-O-sulfation poses a serious challenge for functional studies other than the two cases

Substrate specificity of Arabidopsis 3-ketoacyl-CoA synthases

International Nuclear Information System (INIS)

Blacklock, Brenda J.; Jaworski, Jan G.

2006-01-01

The very long chain fatty acids (VLCFA) incorporated into plant lipids are derived from the iterative addition of C2 units provided by malonyl-CoA to an acyl-CoA by the 3-ketoacyl-CoA synthase (KCS) component of a fatty acid elongase (FAE) complex. Mining of the Arabidopsis genome sequence database revealed 20 genes with homology to seed-specific FAE1 KCS. Eight of the 20 putative KCSs were cloned, expressed in yeast, and isolated as (His) 6 fusion proteins. Five of the eight (At1g71160, At1g19440, At1g07720, At5g04530, and At4g34250) had little or no activity with C16 to C20 substrates while three demonstrated activity with C16, C18, and C20 saturated acyl-CoA substrates. At1g01120 KCS (KCS1) and At2g26640 KCS had broad substrate specificities when assayed with saturated and mono-unsaturated C16 to C24 acyl-CoAs while At4g34510 KCS was specific for saturated fatty acyl-CoA substrates

Aligning emergency care with the triple aim: Opportunities and future directions after healthcare reform.

Science.gov (United States)

Agrawal, Shantanu; Conway, Patrick H

2014-09-01

The Triple Aim of better health, better care, and lower costs has become a fundamental framework for understanding the need for broad health care reform and describing health care value. While the framework is not specific to any clinical setting, this article focuses on the alignment between the framework and Emergency Department (ED) care. The paper explores where emergency care is naturally aligned with each Aim, as well as current barriers which must be addressed to meet the full vision of the Triple Aim. We propose a vision of EDs serving as a nexus for care coordination optimally consistent with the Triple Aim and the requirements for such a role. These requirements include: (1) substantial integration in coordinated care models; (2) development of reliable and actionable data on ED quality, population health, and cost outcomes; (3) specific initiatives to control and optimize ED utilization; and (4) payment models which preserve surge and disaster response capacity. Published by Elsevier Inc.

IR technology for enhanced force protection by AIM

Science.gov (United States)

Breiter, R.; Ihle, T.; Rode, W.; Wendler, J.; Rühlich, I.; Haiml, M.; Ziegler, J.

2008-04-01

In all recent missions our forces are faced with various types of asymmetric threads like snipers, IEDs, RPGs or MANPADS. 2 nd and 3 rd Gen IR technology is a backbone of modern force protection by providing situational awareness and accurate target engagement at day/night. 3 rd Gen sensors are developed for thread warning capabilities by use of spectral or spatial information. The progress on a dual-color IR module is discussed in a separate paper [1]. A 1024x256 SWIR array with flexure bearing compressor and pulse tube cold finger provides > 50,000h lifetime for space or airborne hyperspectral imaging in pushbroom geometry with 256 spectral channels for improved change detection and remote sensing of IEDs or chemical agents. Similar concepts are pursued in the LWIR with either spectroscopic imaging or a system of LWIR FPA combined with a cooled tunable Laser to do spectroscopy with stimulated absorption of specific wavelengths. AIM introduced the RangIR sight to match the requirements of sniper teams, AGLs and weapon stations, extending the outstanding optronic performance of the fielded HuntIR with position data of a target by a laser range finder (LRF), a 3 axis digital magnetic compass (DMC) and a ballistic computer for accurate engagement of remote targets. A version with flexure bearing cooler with >30,000h life time is being developed for continuous operation in e.g. gunfire detection systems. This paper gives an overview of AIM's technologies for enhanced force protection.

Standard technical specifications: Combustion engineering plants. Volume 3, Revision 1: Bases (Sections 3.4--3.9)

International Nuclear Information System (INIS)

1995-04-01

This report documents the results of the combined effort of the NRC and the industry to produce improved Standard Technical Specifications (STS), Revision 1 for Combustion Engineering Plants. The changes reflected in Revision 1 resulted from the experience gained from license amendment applications to convert to these improved STS or to adopt partial improvements to existing technical specifications. This NUREG is the result of extensive public technical meetings and discussions between the Nuclear Regulatory Commission (NRC) staff and various nuclear power plant licensees, Nuclear Steam Supply System (NSSS) Owners Groups, NSSS vendors, and the Nuclear Energy Institute (NEI). The improved STS were developed based on the criteria in the Final Commission Policy Statement on Technical Specifications Improvements for Nuclear Power Reactors, dated July 22, 1993. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume 1 contains the Specifications for all chapters and sections of the improved STS. Volume 2 contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the improved STS Volume 3 contains the Bases for Sections 3.4--3.9 of the improved STS

The Teacher Is a Learner: Dewey on Aims in Education

Science.gov (United States)

Harðarson, Atli

2018-01-01

In Chapter VIII of "Democracy and Education", Dewey objects to all three of the following propositions: (1) education serves predefined aims; (2) Education serves aims that are external to the process of education; and (3) Education serves aims that are imposed by authority. From the vantage point of policy-makers and authors of…

Production of prostate-specific antigen by a breast cancer cell line, Sk-Br-3

International Nuclear Information System (INIS)

Kamali Sarvestani, E.; Ghaderi, A.

2002-01-01

Prostate-specific antigen is a 33-KDa serine protease that is produced predominantly by prostate epithelium. However, it has been shown that about 30-40% of female breast tumors produce prostate-specific antigen and its production is associated with the presence of estrogen and progesterone receptors. We have now developed a new tissue culture system to study prostate-specific antigen production in breast cancer and its association with prognostic factors such as progesterone receptor and c-erbB-2. For this purpose we investigated the ability of prostate-specific antigen production in five different cell lines, including two breast cancer cell lines, Sk-Br-3 and MDA-MB-453. The prostate-specific antigen in tissue culture supernatant and cytoplasm of the Sk-Br-3 cell line was detected by western blotting and immunoperoxidase, respectively. Furthermore, we found lower expression of c-erbB-2 in Sk-Br-3 than non-prostate-specific antigen producer breast cancer cell line, MDA-MB-453. Progesterone receptor was expressed by both prostate-specific antigen-positive and -negative cell lines and only the intensity of staining and the number of positive cells in Sk-Br-3 population was higher than MDA-MB-453. According to our findings prostate-specific antigen can be considered as a good prognostic factor in breast cancer and we suggest that these two cell lines are a good in vitro model to study the relationship of different breast cancer prognostic factors and their regulations

Substrate Specificity of Na+,Cl-(HCO3-)-ATPase.

Science.gov (United States)

Yurkiv, V A; Melikhov, V I; Shubin, V S

2016-09-01

We studied substrate specificity of Na + ,Cl - (HCO 3 - )-ATPase. In most cases, replacement of ATP for other phosphate-containing substances resulted in not only pronounced suppression of phosphohydrolase reactions, but also dramatic changes of their responsiveness to the stimulating effect of monovalent ions. The data showed that Na + ,Cl - (HCO 3 - )-ATPase is a highly specific enzyme for ATP.

AIM Data Services

Directory of Open Access Journals (Sweden)

Michael Scholz

2016-05-01

Full Text Available AIM Data Services as a virtual facility provides virtual 3D reference tracks for simulation applications in the domain of automotive and railway systems. It offers tools for management and analysis of experiment data and a platform for survey and processing of vehicle data in the public transport domain. Collected spatial data is bundled in a database cluster and published through common web mapping interfaces.

A Patient-Specific Polylactic Acid Bolus Made by a 3D Printer for Breast Cancer Radiation Therapy.

Science.gov (United States)

Park, So-Yeon; Choi, Chang Heon; Park, Jong Min; Chun, MinSoo; Han, Ji Hye; Kim, Jung-In

2016-01-01

The aim of this study was to assess the feasibility and advantages of a patient-specific breast bolus made using a 3D printer technique. We used the anthropomorphic female phantom with breast attachments, which volumes are 200, 300, 400, 500 and 650 cc. We simulated the treatment for a right breast patient using parallel opposed tangential fields. Treatment plans were used to investigate the effect of unwanted air gaps under bolus on the dose distribution of the whole breast. The commercial Super-Flex bolus and 3D-printed polylactic acid (PLA) bolus were applied to investigate the skin dose of the breast with the MOSFET measurement. Two boluses of 3 and 5 mm thicknesses were selected. There was a good agreement between the dose distribution for a virtual bolus generated by the TPS and PLA bolus. The difference in dose distribution between the virtual bolus and Super-Flex bolus was significant within the bolus and breast due to unwanted air gaps. The average differences between calculated and measured doses in a 200 and 300 cc with PLA bolus were not significant, which were -0.7% and -0.6% for 3mm, and -1.1% and -1.1% for 5 mm, respectively. With the Super-Flex bolus, however, significant dose differences were observed (-5.1% and -3.2% for 3mm, and -6.3% and -4.2% for 5 mm). The 3D-printed solid bolus can reduce the uncertainty of the daily setup and help to overcome the dose discrepancy by unwanted air gaps in the breast cancer radiation therapy.

Dissociated effects of distractors on saccades and manual aiming.

Science.gov (United States)

McIntosh, Robert D; Buonocore, Antimo

2012-08-01

The remote distractor effect (RDE) is a robust phenomenon whereby target-directed saccades are delayed by the appearance of a distractor. This effect persists even when the target location is perfectly predictable. The RDE has been studied extensively in the oculomotor domain but it is unknown whether it generalises to other spatially oriented responses. In three experiments, we tested whether the RDE generalises to manual aiming. Experiment 1 required participants to move their hand or eyes to predictable targets presented alone or accompanied by a distractor in the opposite hemifield. The RDE was observed for the eyes but not for the hand. Experiment 2 replicated this dissociation in a more naturalistic task in which eye movements were not constrained during manual aiming. Experiment 3 confirmed the lack of manual RDE across a wider range of distractor delays (0, 50, 100, and 150 ms). Our data imply that the RDE is specific to the oculomotor system, at least for non-foveal distractors. We suggest that the oculomotor RDE reflects competitive interactions between target and distractor representations in the superior colliculus, which are not necessarily shared by manual aiming.

Preparation of high specific activity labelled triiodothyronine (T3) for radioimmunoassay

International Nuclear Information System (INIS)

Pillai, M.R.A.; Nagvekar, U.H.; Desai, C.N.; Mani, R.S.

1981-01-01

A method standardized for the preparation of high specific activity labelled triiodothyronine (T 3 ) is discussed. Iodine-125 labelled T 3 with a specific activity of 3 mCi μg was prepared by iodinating 3,5-diiodothyronine (T 2 ) and purifying it over Sephadex G-25 gel. Radochemical purity and stability evaluations were done by paper chromatography. Specific activity of the labelled T 3 prepared was estimated by the self-displacement method. The use of this high specific activity labelled T 3 in radioimmunoassay increased the sensitivity considerably. The advantage of this procedure is that the specific activity of labelled T 3 formed is independent of reaction yield and labelled T 3 yield. (author)

Standard technical specifications: Babcock and Wilcox plants. Volume 3, Revision 1: Bases (Sections 3.4--3.9)

International Nuclear Information System (INIS)

1995-04-01

This report documents the results of the combined effort of the NRC and the industry to produce improved Standard Technical Specifications (STS), Revision 1 for Babcock and Wilcox Plants. The changes reflected in Revision 1 resulted from the experience gained from license amendment applications to convert to these improved STS or to adopt partial improvements to existing technical specifications. This NUREG is the result of extensive public technical meetings and discussions between the Nuclear Regulatory Commission (NRC) staff and various nuclear power plant licensees, Nuclear Steam Supply System (NSSS) Owners Groups, NSSS vendors, and the Nuclear Energy Institute (NEI). The improved STS were developed based on the criteria in the Final Commission Policy Statement on Technical Specifications Improvements for Nuclear Power Reactors, dated July 22, 1993. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume 1 contains the Specifications for all chapters and sections of the improved STS. Volume 2 contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1--3.3 of the improved STS. Volume 3 contains the Bases for Sections 3.4--3.9 of the improved STS

A Patient-Specific Polylactic Acid Bolus Made by a 3D Printer for Breast Cancer Radiation Therapy.

Directory of Open Access Journals (Sweden)

So-Yeon Park

Full Text Available The aim of this study was to assess the feasibility and advantages of a patient-specific breast bolus made using a 3D printer technique.We used the anthropomorphic female phantom with breast attachments, which volumes are 200, 300, 400, 500 and 650 cc. We simulated the treatment for a right breast patient using parallel opposed tangential fields. Treatment plans were used to investigate the effect of unwanted air gaps under bolus on the dose distribution of the whole breast. The commercial Super-Flex bolus and 3D-printed polylactic acid (PLA bolus were applied to investigate the skin dose of the breast with the MOSFET measurement. Two boluses of 3 and 5 mm thicknesses were selected.There was a good agreement between the dose distribution for a virtual bolus generated by the TPS and PLA bolus. The difference in dose distribution between the virtual bolus and Super-Flex bolus was significant within the bolus and breast due to unwanted air gaps. The average differences between calculated and measured doses in a 200 and 300 cc with PLA bolus were not significant, which were -0.7% and -0.6% for 3mm, and -1.1% and -1.1% for 5 mm, respectively. With the Super-Flex bolus, however, significant dose differences were observed (-5.1% and -3.2% for 3mm, and -6.3% and -4.2% for 5 mm.The 3D-printed solid bolus can reduce the uncertainty of the daily setup and help to overcome the dose discrepancy by unwanted air gaps in the breast cancer radiation therapy.

Allele-specific MMP-3 transcription under in vivo conditions

Energy Technology Data Exchange (ETDEWEB)

Chaoyong, Zhu [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Odeberg, Jacob [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Department of Biotechnology, AlbaNova University Center, Royal Institute of Technology, Stockholm (Sweden); Hamsten, Anders [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden); Eriksson, Per [Atherosclerosis Research Unit, King Gustav V Research Institute, Department of Medicine, Karolinska Institute, Stockholm (Sweden)

2006-09-29

A common matrix metalloproteinases-3 (MMP-3) -1612 5A/6A promoter polymorphism is associated with risk for cardiovascular disease, rheumatoid arthritis, and other diseases. Here we used the haplotype chromatin immunoprecipitation method to study allele-specific MMP-3 expression under in vivo conditions in heterozygous THP-1 cells. Pyrosequencing was used to analyse the ratio of 5A-allele to 6A-allele after chromatin immunoprecipitation using an antibody against phosphorylated active RNA polymerase II. There was no allele-specific difference in transcriptional activity during basal conditions, i.e., in unstimulated monocytic THP-1 cells. However, after stimulation of MMP-3 expression by monocyte differentiation or incubation with IL-1{beta}, the haplotype containing the 5A-allele was associated with higher transcriptional activity compared with the 6A-containing haplotype. Electromobility shift assay demonstrated increased binding of nuclear proteins to the 5A-allele after monocyte differentiation. In conclusion, the common MMP-3 5A/6A promoter polymorphism appears to be functional only during specific environmental conditions involving inflammation.

Spontaneous presence of FOXO3-specific T cells in cancer patients

DEFF Research Database (Denmark)

Larsen, Stine Kiaer; Ahmad, Shamaila Munir; Idorn, Manja

2014-01-01

In the present study, we describe forkhead box O3 (FOXO3)-specific, cytotoxic CD8(+) T cells existent among peripheral-blood mononuclear cells (PBMCs) of cancer patients. FOXO3 immunogenicity appears specific, as we did not detect reactivity toward FOXO3 among T cells in healthy individuals. FOXO3...... may naturally serve as a target antigen for tumor-reactive T cells as it is frequently over-expressed in cancer cells. In addition, expression of FOXO3 plays a critical role in immunosuppression mediated by tumor-associated dendritic cells (TADCs). Indeed, FOXO3-specific cytotoxic T lymphocytes (CTLs......) were able to specifically recognize and kill both FOXO3-expressing cancer cells as well as dendritic cells. Thus, FOXO3 was processed and presented by HLA-A2 on the cell surface of both immune cells and cancer cells. As FOXO3 programs TADCs to become tolerogenic, FOXO3 signaling thereby comprises...

Synthesis of (plus or minus) [5-3H] N'-Nitrosoanatabine, a tobacco-specific nitrosamine

International Nuclear Information System (INIS)

Desai, Dhimant; Lin, Guoying; Morimoto, Hiromi; Williams, Philip G.; El-Bayoumy, Karam; Amin, Shantu

2002-01-01

Tobacco-specific N'-nitrosamines (TSNA) are a unique class of systemic organ-specific carcinogens. The TSNA are formed by N-nitrosation of nicotine and of the minor tobacco alkaloids after harvesting of tobacco and during smoking. The N-nitrosation of anatabine leads to N'-nitrosoanatabine (NAT; 1-nitroso-1,2,3,4-tetrahydro-2,3'-bipyridyl) which requires in-depth assays in laboratory animals other than the rat. Furthermore, delineation of its tissue distribution and metabolism is needed for structure:activity comparisons with other TSNA and for the assessment of potential human risk from this TSNA. We have, therefore, synthesized (+)[5-3H]NAT. 5-Bromo-3-pyridine-carboxaldehyde was condensed with ethyl carbamate prior to Diels-Alder reaction with 1,4-butadiene to give the racemic anatabine ring system. Hydrolysis followed by reduction with LiAlT4 and nitrosation, led to (+)[5-3H]NAT (60 percent yield, specific activity 266 mCi/mmol, radiochemical purity of >99 percent)

Standard Technical Specifications General Electric plants, BWR/4:Bases (Sections 3.4-3.10). Volume 3, Revision 1

International Nuclear Information System (INIS)

1995-04-01

This report documents the results of the combined effort of the NRC and the industry to produce improved Standard Technical Specifications (STS), Revision 1 for General Electric BWR/4 Plants. The changes reflected in Revision 1 resulted from the experience gained from license amendment applications to convert to these improved STS or to adopt partial improvements to existing technical specifications. This NUREG is the result of extensive public technical meetings and discussions between the Nuclear Regulatory Commission (NRC) staff and various nuclear power plant licensees, Nuclear Steam Supply System (NSSS) Owners Groups, NSSS vendors, and the Nuclear Energy Institute (NEI). The improved STS were developed based on the criteria in the Final Commission Policy Statement on Technical Specifications Improvements for Nuclear Power Reactors, dated July 22, 1993. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume 1 contains the specifications for all chapters and sections of the improved STS. Volume 2 contains he Bases for Chapters 2.0 and 3.0, and Sections 3.1-3.3 of the improved STS. This document, Volume 3, contains the Bases for Sections 3.4-3.10 of the improved STS

Creating a normative database of age-specific 3D geometrical data, bone density, and bone thickness of the developing skull: a pilot study.

Science.gov (United States)

Delye, Hans; Clijmans, Tim; Mommaerts, Maurice Yves; Sloten, Jos Vnder; Goffin, Jan

2015-12-01

Finite element models (FEMs) of the head are used to study the biomechanics of traumatic brain injury and depend heavily on the use of accurate material properties and head geometry. Any FEM aimed at investigating traumatic head injury in children should therefore use age-specific dimensions of the head, as well as age-specific material properties of the different tissues. In this study, the authors built a database of age-corrected skull geometry, skull thickness, and bone density of the developing skull to aid in the development of an age-specific FEM of a child's head. Such a database, containing age-corrected normative skull geometry data, can also be used for preoperative surgical planning and postoperative long-term follow-up of craniosynostosis surgery results. Computed tomography data were processed for 187 patients (age range 0-20 years old). A 3D surface model was calculated from segmented skull surfaces. Skull models, reference points, and sutures were processed into a MATLAB-supported database. This process included automatic calculation of 2D measurements as well as 3D measurements: length of the coronal suture, length of the lambdoid suture, and the 3D anterior-posterior length, defined as the sum of the metopic and sagittal suture. Skull thickness and skull bone density calculations were included. Cephalic length, cephalic width, intercoronal distance, lateral orbital distance, intertemporal distance, and 3D measurements were obtained, confirming the well-established general growth pattern of the skull. Skull thickness increases rapidly in the first year of life, slowing down during the second year of life, while skull density increases with a fast but steady pace during the first 3 years of life. Both skull thickness and density continue to increase up to adulthood. This is the first report of normative data on 2D and 3D measurements, skull bone thickness, and skull bone density for children aged 0-20 years. This database can help build an age-specific

Generation of a C3c specific monoclonal antibody and assessment of C3c as a putative inflammatory marker derived from complement factor C3

DEFF Research Database (Denmark)

Palarasah, Yaseelan; Skjodt, Karsten; Brandt, Jette

2010-01-01

complex (C5b-C9) and quantification of complement split products by precipitation-in-gel techniques (e.g. C3d). We have developed a mouse monoclonal antibody (mAb) that is able to detect fluid phase C3c without interference from other products generated from the complement component C3. The C3c specific m....... The C3c mAb was confirmed to be C3c specific, as it showed no cross-reactivity with native (un-cleaved) C3, with C3b, iC3b, or with C3d. Also, no significant reaction was observed with C3 fragments in factor I deficient sera or plasma. This antibody forms the basis for the generation of a robust ELISA...... that allows for a quick and reliable evaluation of complement activation and consumption as a marker for inflammatory processes. We established the C3c plasma range in 100 healthy Danish blood donors with a mean of 3.47 μg/ml and a range of 2.12-4.92 μg/ml. We believe that such an antibody might...

Use of 3D printers to create a patient‐specific 3D bolus for external beam therapy

Science.gov (United States)

Baker, Jamie; Hsia, An Ting; Xu, Zhigang

2015-01-01

The purpose of this paper is to demonstrate that an inexpensive 3D printer can be used to manufacture patient‐specific bolus for external beam therapy, and to show we can accurately model this printed bolus in our treatment planning system for accurate treatment delivery. Percent depth‐dose measurements and tissue maximum ratios were used to determine the characteristics of the printing materials, acrylonitrile butadiene styrene and polylactic acid, as bolus material with physical density of 1.04 and 1.2 g/cm3, and electron density of 3.38×1023electrons/cm3 and 3.80×1023 electrons/cm3, respectively. Dose plane comparisons using Gafchromic EBT2 film and the RANDO phantom were used to verify accurate treatment planning. We accurately modeled a printing material in Eclipse treatment planning system, assigning it a Hounsfield unit of 260. We were also able to verify accurate treatment planning using gamma analysis for dose plane comparisons. With gamma criteria of 5% dose difference and 2 mm DTA, we were able to have 86.5% points passing, and with gamma criteria of 5% dose difference and 3 mm DTA, we were able to have 95% points passing. We were able to create a patient‐specific bolus using an inexpensive 3D printer and model it in our treatment planning system for accurate treatment delivery. PACS numbers: 87.53.Jw, 87.53.Kn, 87.56.ng PMID:26103485

Establishment of human sperm-specific voltage-dependent anion channel 3 recombinant vector for the production of a male contraceptive vaccine

Directory of Open Access Journals (Sweden)

Asmarinah Asmarinah

2012-05-01

Full Text Available Background: The aim of this study was to construct a recombinant vector of human sperm specific VDAC3 gene for production of VDAC3 antibody, which is potential as male contraception vaccine.Methods: Target fragment sequence of VDAC3 gene was obtained through amplification of human sperm VDAC3 cDNA with primers covering exon 5 to exon 8. Its PCR product in size of 435 bp was cloned to the pET101/D-TOPO expression vector (5753 bp. E. coli bacteria were transformed with this vector. Cloning of VDAC3 fragment gene to the vector was confirmed by the using of XbaI restriction enzyme and PCR colony method with primers covering exons 5-8 of the human VDAC3 gene.Results: Alignment analysis of amplified fragment covering exon 5 to exon 8 of VDAC3 gene showed 94% homology to human VDAC3 gene from databank. After cloning to the expression vector and transformation to E. coli competent cells, twelve colonies could grow in culture media. Gel electrophoresis of sliced VDAC3 recombinant vector showed a single band in the size of 6181 bp in 8 colonies. After application of PCR colony and amplicon sequencing, the result showed a single band in the size of 435 bp and fragment sequence with 94% identity to human VDAC3 gene.Conclusion: The construction of human sperm specific VDAC3 gene recombinant vector was established in this study. In the future, this recombinant vector will be used to produce VDAC3 antibody for the development of a male contraception vaccine. (Med J Indones. 2012;21:61-5Keywords: Contraception, recombinant vector, sperm, VDAC3

Male germ cell-specific expression of a novel Patched-domain containing gene Ptchd3

International Nuclear Information System (INIS)

Fan Jun; Akabane, Hiroto; Zheng Xuehai; Zhou Xuan; Zhang Li; Liu Qiang; Zhang Yonglian; Yang Jing; Zhu Guozhang

2007-01-01

The Hedgehog (Hh) signaling pathway plays an important role in various biological processes, including pattern formation, cell fate determination, proliferation, and differentiation. Hh function is mediated through its membrane receptor Patched. Herein, we have characterized a novel Patched-domain containing gene Ptchd3 in mouse. Messenger RNA of Ptchd3 was exclusively detected in the testis, and existed in two isoforms Ptchd3a and Ptchd3b. The expression of these two mRNA isoforms was shown to be developmentally regulated in testes, and specifically found in male germ cells. Further analysis revealed that the Ptchd3 protein was located on the midpiece of mouse, rat and human sperm. Collectively, these results indicate that Ptchd3 is a novel male germ cell-specific gene and may be involved in the Hh signaling to regulate sperm development and/or sperm function

Poly(3-hexylthiophene): TIPS-pentacene blends aiming transistor applications

Energy Technology Data Exchange (ETDEWEB)

Silva Ozório, Maiza da, E-mail: ozoriounesp@gmail.com; Nogueira, Gabriel Leonardo; Morais, Rogério Miranda; Silva Martin, Cibely da; Constantino, Carlos José Leopoldo; Alves, Neri

2016-06-01

Poly(3-hexylthiophene):6,13-bis(triisopropylsilylethynyl)-pentacene (P3HT:TP) blends with a ratio of 1:1 (wt/wt) were deposited via spin coating on anodized oxide (Al{sub 2}O{sub 3}). A phase separation of the compounds was observed, resulting in the formation of crystalline aggregates of TP molecules that segregate vertically on the surface. The form of segregation depends on the oxide surface treatment used. Spectroscopy analysis shows a higher molecular order of P3HT in the blend than for neat film and that TP molecules are also distributed in the polymeric matrix. Regarding the OFET characteristics, charge carrier mobilities of 1.2 × 10{sup −3} cm{sup 2} V{sup −1} s{sup −1} and 2.0 × 10{sup −3} cm{sup 2} V{sup −1} s{sup −1} were obtained from devices for untreated and (hexamethyldisilazane) HMDS-treated Al{sub 2}O{sub 3} gate dielectric, respectively. These results confirm that P3HT:TP blends have good potential as an active layer in organic field effect transistors (OFETs). - Highlights: • Phase separation occurs in the P3HT:TP blend. • The P3HT:TP blends form aggregates that segregate vertically to the surface. • The molecular order of the P3HT is higher for the blend than for the neat film. • Treatment of surface with HMDS influence in the formation of the aggregate • The P3HT:TP blends have great viability of using for application in transistors.

Database on Aims and Visions in the COINCO Corridor

DEFF Research Database (Denmark)

2005-01-01

This database contains aims and visions regarding overall regional development as well as more specific aims and visions related to transport and infrastructure in the Corridor Oslo-Göteborg-Copenhagen-Berlin. The sources used for this database are the most essential planning documents from Denmark...

Is Fitts' law continuous in discrete aiming?

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Rita Sleimen-Malkoun

Full Text Available The lawful continuous linear relation between movement time and task difficulty (i.e., index of difficulty; ID in a goal-directed rapid aiming task (Fitts' law has been recently challenged in reciprocal performance. Specifically, a discontinuity was observed at critical ID and was attributed to a transition between two distinct dynamic regimes that occurs with increasing difficulty. In the present paper, we show that such a discontinuity is also present in discrete aiming when ID is manipulated via target width (experiment 1 but not via target distance (experiment 2. Fitts' law's discontinuity appears, therefore, to be a suitable indicator of the underlying functional adaptations of the neuro-muscular-skeletal system to task properties/requirements, independently of reciprocal or discrete nature of the task. These findings open new perspectives to the study of dynamic regimes involved in discrete aiming and sensori-motor mechanisms underlying the speed-accuracy trade-off.

[Specific humoral immunity after single immunization with mumps vaccine: data of a 3-year follow-up].

Science.gov (United States)

Otrashevskaia, A V; Bukin, E K; Krasil'nikov, I V; Ignat'ev, G M

2011-01-01

The level and spectrum of humoral specific immunity were studied in 60 volunteers immunized with Russian mumps vaccine. Specific IgG levels were measured by enzyme immunoassay (EIA) and neutralization test using the Leningrad-3 (L-3) mumps virus (MV) vaccine strain and 5 heterologous MV strains of various genotypes (A, B, C, D, and H). The maximum functional activity of antibodies was recorded at an average of 18 months postvaccination. Within 3 years after vaccination, starting at 6 months, specific IgG neutralized all 6 MV strains having varying activity in relation to the genotype. Neutralizing titers (NT) against the L-3 strain were 1.3-1.7-fold higher than those against heterologous MV strains throughout the follow-up. Despite a tendency towards lower specific IgG levels, within 3 years postvaccination, EIA IgG titers remained to be 2.5 -log, L-3 strain HT were -log, or more, and the titers against 5 heterologous MV strains were 2 -log2 or more in all the volunteers.

Interventions aimed at increasing research use in nursing: a systematic review

Directory of Open Access Journals (Sweden)

Moore Katherine

2007-05-01

nursing, and the evidence to support or refute specific interventions is inconclusive. To advance the field, we recommend that investigators: (1 use theoretically informed interventions to increase research use, (2 measure research use longitudinally using theoretically informed and psychometrically sound measures of research use, as well as, measuring patient outcomes relevant to the intervention, and (3 use more robust and methodologically sound study designs to evaluate interventions. If investigators aim to establish a link between using research and improved patient outcomes they must first identify those interventions that are effective at increasing research use.

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism

Directory of Open Access Journals (Sweden)

Meera Shah

2016-08-01

Full Text Available The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.

Aim For a Healthy Weight

Science.gov (United States)

... out of your control, you can make positive lifestyle changes to lose weight and to maintain a healthy weight. These include a healthy eating plan and being more physically active. Take the Challenge When it comes to aiming for a healthy ...

Analysis specifications for the CC3 biosphere model BIOTRAC

International Nuclear Information System (INIS)

Szekely, J.G.; Wojciechowski, L.C.; Stephens, M.E.; Halliday, H.A.

1994-12-01

AECL Research is assessing a concept for disposing of Canada's nuclear fuel waste in a vault deep in plutonic rock of the Canadian Shield. A computer program called the Systems Variability Analysis Code (SYVAC) has been developed as an analytical tool for the postclosure (long-term) assessment of the concept. SYVAC3, the third generation of the code, is an executive program that directs repeated simulation of the disposal system to take into account parameter variation. For the postclosure assessment, the system model, CC3 (Canadian Concept, generation 3), was developed to describe a hypothetical disposal system that includes a disposal vault, the local geosphere and the biosphere in the vicinity of any discharge zones. BIOTRAC (BIOsphere TRansport And Consequences) is the biosphere model in the CC3 system model. The specifications for BIOTRAC, which were developed over a period of seven years, were subjected to numerous walkthrough examinations by the Biosphere Model Working Group to ensure that the intent of the model developers would be correctly specified for transformation into FORTRAN code. The FORTRAN version of BIOTRAC was written from interim versions of these specifications. Improvements to the code are based on revised versions of these specifications. The specifications consist of a data dictionary; sets of synopses, data flow diagrams and mini specs for the component models of BIOTRAC (surface water, soil, atmosphere, and food chain and dose); and supporting calculations (interface to the geosphere, consequences, and mass balance). (author). 20 refs., tabs., figs

Specific requirements of GS-R3 related to process implementation

International Nuclear Information System (INIS)

Florescu, N.

2009-01-01

The PowerPoint presentation gives: an overview of IAEA management system requirements or topics; - the requirements specific to processes and process implementation; - the key practical challenge of using the process approach specified in IAEA SG GS-G3.1 and GS-G3.5. The following items are thoroughly discussed: - Requirements related to specific process implementation and developing processes; - Process management; Generic management; - System processes: - Control of documents; Control of products; Control of records; - Purchasing; - Communication; - Managing organizational change; - Other requirements concerning the process management system; - General management system; - Grading; - Documentation; - Fulfilling the requirements of interested parties; - Management responsibility; - Planning responsibility and authority for the management system monitoring and measurement; - Independent assessment; - Management system review; - Non-conformances, corrective and preventive actions; - Improvement key practical challenge of using the process approach specified in IAEA SG GS-G3.1 and GS-G3.5; - Key challenge: - Process common to all stages; - Phases of process development proposed by IAEA. The following conclusions complete the presentation: GS-R-3 sets basic requirements for process-based integrated management system; - Some key generic processes required, no specific process model favoured namely, no reference to management, core and support processes; - Up to organization to determine appropriate process model; - Easily applicable to a wide range of facilities and activities, including those of a regulatory body; - Specific requirements are found in specific Safety Guide. (author)

Specific-heat measurements on dilute 3He-4He mixtures

International Nuclear Information System (INIS)

Zeeuw, H.C.M. van der.

1985-01-01

The author measured the specific heat of dilute 3 He- 4 He mixtures in the concentration range from X = 1 x 10 -3 to X = 3 x 10 -3 and in the temperature range from 100 mK to 600 mK. This has been done by means of a thermal relaxation method. This method provides some interesting features and is applied, to our knowledge, for the first time to dilute 3 He- 4 He mixtures. To reach the required temperature range for our experiments a 4 He circulating 3 He- 4 He dilution refrigerator has been constructed. The results confirm the deviation of the 3 He contribution to the specific heat from the ideal Fermi gas behaviour. (Auth.)

Refractive aim and visual outcome after phacoemulsification: A 2 ...

African Journals Online (AJOL)

2016-03-24

Mar 24, 2016 ... was met, 21 eyes (14.3%) did not meet their refractive aim, 20 eyes (12.7%) were ... countries, where blindness is associated with considerable ... and better, the total range of refractive errors postoperatively ... required intraocular lenses (IOL), medical record efficiency, ..... problem that can be alleviated.

A 3D Monte Carlo Method for Estimation of Patient-specific Internal Organs Absorbed Dose for 99mTc-hynic-Tyr3-octreotide Imaging

International Nuclear Information System (INIS)

Momennezhad, Mehdi; Nasseri, Shahrokh; Zakavi, Seyed Rasoul; Parach, Ali Asghar; Ghorbani, Mahdi; Asl, Ruhollah Ghahraman

2016-01-01

Single-photon emission computed tomography (SPECT)-based tracers are easily available and more widely used than positron emission tomography (PET)-based tracers, and SPECT imaging still remains the most prevalent nuclear medicine imaging modality worldwide. The aim of this study is to implement an image-based Monte Carlo method for patient-specific three-dimensional (3D) absorbed dose calculation in patients after injection of 99m Tc-hydrazinonicotinamide (hynic)-Tyr 3 -octreotide as a SPECT radiotracer. 99m Tc patient-speci@@@@@@c S values and the absorbed doses were calculated with GATE code for each source-target organ pair in four patients who were imaged for suspected neuroendocrine tumors. Each patient underwent multiple whole-body planar scans as well as SPECT imaging over a period of 1-24 h after intravenous injection of 99m hynic-Tyr 3 -octreotide. The patient-specific S values calculated by GATE Monte Carlo code and the corresponding S values obtained by MIRDOSE program differed within 4.3% on an average for self-irradiation, and differed within 69.6% on an average for cross-irradiation. However, the agreement between total organ doses calculated by GATE code and MIRDOSE program for all patients was reasonably well (percentage difference was about 4.6% on an average). Normal and tumor absorbed doses calculated with GATE were slightly higher than those calculated with MIRDOSE program. The average ratio of GATE absorbed doses to MIRDOSE was 1.07 ± 0.11 (ranging from 0.94 to 1.36). According to the results, it is proposed that when cross-organ irradiation is dominant, a comprehensive approach such as GATE Monte Carlo dosimetry be used since it provides more reliable dosimetric results

Alginate Immobilization of Metabolic Enzymes (AIME) for High ...

Science.gov (United States)

Alginate Immobilization of Metabolic Enzymes (AIME) for High-Throughput Screening Assays DE DeGroot, RS Thomas, and SO SimmonsNational Center for Computational Toxicology, US EPA, Research Triangle Park, NC USAThe EPA’s ToxCast program utilizes a wide variety of high-throughput screening (HTS) assays to assess chemical perturbations of molecular and cellular endpoints. A key criticism of using HTS assays for toxicity assessment is the lack of xenobiotic metabolism (XM) which precludes both metabolic detoxification as well as bioactivation of chemicals tested in vitro thereby mischaracterizing the potential risk posed by these chemicals. To address this deficiency, we have developed an extracellular platform to retrofit existing HTS assays with XM activity. This platform utilizes the S9 fraction of liver homogenate encapsulated in an alginate gel network which reduces the cytotoxicity caused by direct addition of S9 to cells in culture. Alginate microspheres containing encapsulated human liver S9 were cross-linked to solid supports extending from a 96-well plate lid and were assayed using a pro-luciferin substrate specific for CYP3A4 (IPA). We demonstrate that S9 was successfully encapsulated and remained enzymatically active post-encapsulation with 5-10X the CYP3A4 activity as compared to 1 µg solubilized human liver S9. Ketoconazole, a known inhibitor of human CYP3A4, inhibited CYP3A4 activity in a concentration-dependent manner (IC50: 0.27 µM) and inhibiti

A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.

Science.gov (United States)

Shah, Meera; Su, Dan; Scheliga, Judith S; Pluskal, Tomáš; Boronat, Susanna; Motamedchaboki, Khatereh; Campos, Alexandre Rosa; Qi, Feng; Hidalgo, Elena; Yanagida, Mitsuhiro; Wolf, Dieter A

2016-08-16

The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8+ T Cell-Lineage-Specific Function

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Brendan E. Russ

2017-12-01

Full Text Available Infection triggers large-scale changes in the phenotype and function of T cells that are critical for immune clearance, yet the gene regulatory mechanisms that control these changes are largely unknown. Using ChIP-seq for specific histone post-translational modifications (PTMs, we mapped the dynamics of ∼25,000 putative CD8+ T cell transcriptional enhancers (TEs differentially utilized during virus-specific T cell differentiation. Interestingly, we identified a subset of dynamically regulated TEs that exhibited acquisition of a non-canonical (H3K4me3+ chromatin signature upon differentiation. This unique TE subset exhibited characteristics of poised enhancers in the naive CD8+ T cell subset and demonstrated enrichment for transcription factor binding motifs known to be important for virus-specific CD8+ T cell differentiation. These data provide insights into the establishment and maintenance of the gene transcription profiles that define each stage of virus-specific T cell differentiation.

In vivo fluorescence imaging of hepatocellular carcinoma using a novel GPC3-specific aptamer probe

Science.gov (United States)

Zhao, Menglong; Dong, Lili; Liu, Zhuang; Yang, Shuohui

2018-01-01

Background Glypican-3 (GPC3) is highly expressed in most of the hepatocellular carcinomas (HCCs), even in small HCCs. It may be used as a potential biomarker for early detection of HCC. The aptamer is a promising targeting agent with unique advantages over antibody. This study was to introduce a novel GPC3 specific aptamer (AP613-1), to verify its specific binding property in vitro, and to evaluate its targeting efficiency in vivo by performing near-infrared (NIR) fluorescence imaging on an HCC xenograft model. Methods AP613-1 was generated from the systematic evolution of ligands by exponential enrichment. Flow cytometry and aptamer-based immunofluorescence imaging were performed to verify the binding affinity of AP613-1 to GPC3 in vitro. NIR Fluorescence images of nude mice with unilateral (n=12) and bilateral (n=4) subcutaneous xenograft tumors were obtained. Correlation between the tumor fluorescence intensities in vivo and ex vivo was analyzed. Results AP613-1 could specifically bind to GPC3 in vitro. In vivo and ex vivo tumors, fluorescence intensities were in excellent correlation (Pfluorescence intensity is significantly higher in tumors given Alexa Fluor 750 (AF750) labeled AP613-1 than in those given AF750 labeled initial ssDNA library both in vivo (Pfluorescence intensities than A549 tumors both in vivo (P=0.016) and ex vivo (P=0.004). Conclusions AP613-1 displays a specific binding affinity to GPC3 positive HCC. Fluorescently labeled AP613-1 could be used as an imaging probe to subcutaneous HCC in xenograft models. PMID:29675356

Liquid lipases for enzymatic concentration of n-3 polyunsaturated fatty acids in monoacylglycerols via ethanolysis: Catalytic specificity and parameterization.

Science.gov (United States)

He, Yongjin; Li, Jingbo; Kodali, Sitharam; Balle, Thomas; Chen, Bilian; Guo, Zheng

2017-01-01

This work examined catalytic specificity and fatty acid selectivity of five liquid lipases C. antarctica lipase A and B (CAL-A/B), and lipase TL (T. lanuginosus), Eversa Transfrom and NS in ethanolysis of fish oil with the aim to concentrate n-3 PUFAs into monoacylglycerols (MAGs) products. Lipase TL, Eversa Transform & NS entail a much faster reaction and produce higher MAGs yield (>30%); whereas CAL-A obtains the highest concentration of n-3 PUFAs/DHA/EPA into MAGs products (88.30%); followed by lipase NS (81.02%). 13 C NMR analysis indicates that CAL-B and lipase TL are sn-1,3 specific; but CAL-A and lipase Eversa Transform are non-regiospecific or weak sn-2 specific; which plausibly explains high enrichment effect of the latter two lipases. All liquid lipases are observed reusable for a certain times (lipase Eversa Transform up to 12 times), demonstrating their competitive advantage over immobilized form for industrial application because of their higher activity and cheaper operation cost. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis specifications for the CC3 geosphere model GEONET

International Nuclear Information System (INIS)

Melnyk, T.W.

1995-04-01

AECL is assessing a concept for disposing of Canada's nuclear fuel waste in a sealed vault deep in plutonic rock of the Canadian Shield. A computer program has been developed as an analytical tool for the postclosure assessment case study, a system model, CC3 (Canadian Concept, generation 3), has been developed to describe a hypothetical disposal system. This system model includes separate models for the engineered barriers within the disposal vault, the geosphere in which the vault is emplaced, and the biosphere in the vicinity of any discharge zones. The system model is embedded within a computer code SYVAC3, (SYstems Variability Analysis Code, generation 3), which takes parameter uncertainty into account by repeated simulation of the system. GEONET (GEOsphere NETwork) is the geosphere model component of this system model. It simulates contaminant transport from the vault to the biosphere along a transport network composed of one-dimensional transport segments that are connected together in three-dimensional space. This document is a set of specifications for GEONET that were developed over a number of years. Improvements to the code will be based on revisions to these specifications. The specifications consist of a model synopsis, describing all the relevant equations and assumptions used in the model, a set of formal data flow diagrams and minispecifications, and a data dictionary. (author). 26 refs., 20 figs

Patient specific 3D printed phantom for IMRT quality assurance

International Nuclear Information System (INIS)

Ehler, Eric D; Higgins, Patrick D; Dusenbery, Kathryn E; Barney, Brett M

2014-01-01

The purpose of this study was to test the feasibility of a patient specific phantom for patient specific dosimetric verification. Using the head and neck region of an anthropomorphic phantom as a substitute for an actual patient, a soft-tissue equivalent model was constructed with the use of a 3D printer. Calculated and measured dose in the anthropomorphic phantom and the 3D printed phantom was compared for a parallel-opposed head and neck field geometry to establish tissue equivalence. A nine-field IMRT plan was constructed and dose verification measurements were performed for the 3D printed phantom as well as traditional standard phantoms. The maximum difference in calculated dose was 1.8% for the parallel-opposed configuration. Passing rates of various dosimetric parameters were compared for the IMRT plan measurements; the 3D printed phantom results showed greater disagreement at superficial depths than other methods. A custom phantom was created using a 3D printer. It was determined that the use of patient specific phantoms to perform dosimetric verification and estimate the dose in the patient is feasible. In addition, end-to-end testing on a per-patient basis was possible with the 3D printed phantom. Further refinement of the phantom construction process is needed for routine use. (paper)

The Accuracy of 3D Optical Reconstruction and Additive Manufacturing Processes in Reproducing Detailed Subject-Specific Anatomy

Directory of Open Access Journals (Sweden)

Paolo Ferraiuoli

2017-10-01

Full Text Available 3D reconstruction and 3D printing of subject-specific anatomy is a promising technology for supporting clinicians in the visualisation of disease progression and planning for surgical intervention. In this context, the 3D model is typically obtained from segmentation of magnetic resonance imaging (MRI, computed tomography (CT or echocardiography images. Although these modalities allow imaging of the tissues in vivo, assessment of quality of the reconstruction is limited by the lack of a reference geometry as the subject-specific anatomy is unknown prior to image acquisition. In this work, an optical method based on 3D digital image correlation (3D-DIC techniques is used to reconstruct the shape of the surface of an ex vivo porcine heart. This technique requires two digital charge-coupled device (CCD cameras to provide full-field shape measurements and to generate a standard tessellation language (STL file of the sample surface. The aim of this work was to quantify the error of 3D-DIC shape measurements using the additive manufacturing process. The limitations of 3D printed object resolution, the discrepancy in reconstruction of the surface of cardiac soft tissue and a 3D printed model of the same surface were evaluated. The results obtained demonstrated the ability of the 3D-DIC technique to reconstruct localised and detailed features on the cardiac surface with sub-millimeter accuracy.

N-tritioacetoxyphthalimide: A new high specific activity tritioacetylating reagent

International Nuclear Information System (INIS)

Saljoughian, M.; Morimoto, Hiromi; Than, Chit

1996-01-01

The authors' aim was to develop a nonvolatile, stable, and facile tritioacetylating reagent and to demonstrate its use on simple peptides. Accordingly, the authors made the synthesis of high specific activity N-(tritioacetoxy) derivatives of succinimide, phthalimide, and naphthalimide a major focus. As the preferred approach, N-(tritioacetoxy)phthalimide was prepared by radical dehalogenation of N-(iodoacetoxy)phthalimide using high specific activity tributyltin tritide. This tritiated acetylation reagent was characterized by 3 H and 1 H NMR spectroscopy and by radio-HPLC. Efficacy of the reagent was investigated by tritioacetylation of several peptides at their N-terminal amino group. 26 refs., 1 fig

Effect of long-term propranolol administration on specific binding of 3H-WB-4101 with rat mesenteric vascular membranes

International Nuclear Information System (INIS)

Ismailov, S.I.; Rozhanets, V.V.; Val'dman, A.V.

1985-01-01

The aim of this investigation was, first, to study the affinity of certain beta-adrenoblockers for specific binding sites of 3 H-WB-4101 (identifiable as alpha-adrenoreceptors) of brain membranes and, second, to study the characteristics of these same receptors in membranes of mesenteric vessels of rats during long-term administration of propranolol. Isotherms of specific binding, because of the limited quantity of vascular membranes, were determined by the use of three concentrations of 3 H-WB-4101: 0.1, 0.5, and 1.0 nM. It is shown that some beta-adrenoblockers have weak affinity for alpha-adrenoreceptors of brain synaptic membranes exhibited only when these compounds are present in relatively high concentrations. It is also shown that administration of propranolol for 15 days led to a significant decrease in affinity of the alpha-adrenorecptors for their specific antagonist WB-4101

Multiple Avirulence Loci and Allele-Specific Effector Recognition Control the Pm3 Race-Specific Resistance of Wheat to Powdery Mildew[OPEN

Science.gov (United States)

Roffler, Stefan; Stirnweis, Daniel; Treier, Georges; Herren, Gerhard; Korol, Abraham B.; Wicker, Thomas

2015-01-01

In cereals, several mildew resistance genes occur as large allelic series; for example, in wheat (Triticum aestivum and Triticum turgidum), 17 functional Pm3 alleles confer agronomically important race-specific resistance to powdery mildew (Blumeria graminis). The molecular basis of race specificity has been characterized in wheat, but little is known about the corresponding avirulence genes in powdery mildew. Here, we dissected the genetics of avirulence for six Pm3 alleles and found that three major Avr loci affect avirulence, with a common locus_1 involved in all AvrPm3-Pm3 interactions. We cloned the effector gene AvrPm3a2/f2 from locus_2, which is recognized by the Pm3a and Pm3f alleles. Induction of a Pm3 allele-dependent hypersensitive response in transient assays in Nicotiana benthamiana and in wheat demonstrated specificity. Gene expression analysis of Bcg1 (encoded by locus_1) and AvrPm3 a2/f2 revealed significant differences between isolates, indicating that in addition to protein polymorphisms, expression levels play a role in avirulence. We propose a model for race specificity involving three components: an allele-specific avirulence effector, a resistance gene allele, and a pathogen-encoded suppressor of avirulence. Thus, whereas a genetically simple allelic series controls specificity in the plant host, recognition on the pathogen side is more complex, allowing flexible evolutionary responses and adaptation to resistance genes. PMID:26452600

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

OpenAIRE

Chen, Mee-Yew; Kirkwood, Carl D.; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J.; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

2017-01-01

Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time o...

The Collaborative Lithium Trials (CoLT: specific aims, methods, and implementation

Directory of Open Access Journals (Sweden)

Hooper Stephen R

2008-08-01

Full Text Available Abstract Background Lithium is a benchmark treatment for bipolar illness in adults. However, there has been relatively little methodologically stringent research regarding the use of lithium in youth suffering from bipolarity. Methods Under the auspices of the Best Pharmaceuticals for Children Act (BPCA, a Written Request (WR pertaining to the study of lithium in pediatric mania was issued by the United States Food and Drug Administration (FDA to the National Institute of Child Health and Human Development (NICHD in 2004. Accordingly, the NICHD issued a Request for Proposals (RFP soliciting submissions to pursue this research. Subsequently, the NICHD awarded a contract to a group of investigators in order to conduct these studies. Results The Collaborative Lithium Trials (CoLT investigators, the BPCA-Coordinating Center, and the NICHD developed protocols to provide data that will: (1 establish evidence-based dosing strategies for lithium; (2 characterize the pharmacokinetics and biodisposition of lithium; (3 examine the acute efficacy of lithium in pediatric bipolarity; (4 investigate the long-term effectiveness of lithium treatment; and (5 characterize the short- and long-term safety of lithium. By undertaking two multi-phase trials rather than multiple single-phase studies (as was described in the WR, the feasibility of the research to be undertaken was enhanced while ensuring all the data outlined in the WR would be obtained. The first study consists of: (1 an 8-week open-label, randomized, escalating dose Pharmacokinetic Phase; (2 a 16-week Long-Term Effectiveness Phase; (3 a 28-week double-blind Discontinuation Phase; and (4 an 8-week open-label Restabilization Phase. The second study consists of: (1 an 8-week, double-blind, parallel-group, placebo-controlled Efficacy Phase; (2 an open-label Long-Term Effectiveness lasting either 16 or 24 weeks (depending upon blinded treatment assignment during the Efficacy Phase; (3 a 28-week double

Synthesis of (plus or minus) [5-{sup 3}H] N'-Nitrosoanatabine, a tobacco-specific nitrosamine

Energy Technology Data Exchange (ETDEWEB)

Desai, Dhimant; Lin, Guoying; Morimoto, Hiromi; Williams, Philip G.; El-Bayoumy, Karam; Amin, Shantu

2002-06-14

Tobacco-specific N'-nitrosamines (TSNA) are a unique class of systemic organ-specific carcinogens. The TSNA are formed by N-nitrosation of nicotine and of the minor tobacco alkaloids after harvesting of tobacco and during smoking. The N-nitrosation of anatabine leads to N'-nitrosoanatabine (NAT; 1-nitroso-1,2,3,4-tetrahydro-2,3'-bipyridyl) which requires in-depth assays in laboratory animals other than the rat. Furthermore, delineation of its tissue distribution and metabolism is needed for structure:activity comparisons with other TSNA and for the assessment of potential human risk from this TSNA. We have, therefore, synthesized (+)[5-3H]NAT. 5-Bromo-3-pyridine-carboxaldehyde was condensed with ethyl carbamate prior to Diels-Alder reaction with 1,4-butadiene to give the racemic anatabine ring system. Hydrolysis followed by reduction with LiAlT4 and nitrosation, led to (+)[5-3H]NAT (60 percent yield, specific activity 266 mCi/mmol, radiochemical purity of >99 percent).

TUMOR-SPECIFIC EXPRESSION AND ALTERNATIVE SPLICING OF THE COL6A3 GENE IN PANCREATIC CANCER

Science.gov (United States)

Arafat, Hwyda; Lazar, Melissa; Salem, Khalifa; Chipitsyna, Galina; Gong, Qiaoke; Pan, Te-Cheng; Zhang, Rui-Zhu; Yeo, Charles J.; Chu, Mon-Li

2011-01-01

Introduction Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease in which a prominent desmoplastic reaction is a defining characteristic. Fibrillar collagens, such as collagen I and to a lesser extent, collagen III and V comprise the majority of this stromal fibrosis. Type VI collagen (COL6) forms a microfibrillar network associated with type I collagen fibrils. The expression of COL6 has been linked to inflammation and survival. Importantly, tumor-specific alternative splicing in COL6A3 has been identified in several cancers by genome exon arrays. We evaluated the expression and localization of COL6A3 in PDA and premalignant lesions and explored the presence of alternative splicing events. Methods We analyzed paired PDA-normal (n=18), IPMN (n=5), pancreatic cystadenoma (n=5), and eight PDA cell lines with RT-PCR, using unique primers that identify total COL6A3 gene and alternative splicing sites in several of its exons. Western blot analysis and immunohistochemistry were used to analyze the expression levels and localization of COL6A3 protein in the different lesions, and in two animal models of PDA. Results COL6A3 protein levels were significantly upregulated in 77% of the paired PDA-adjacent tissue examined. COL6A3 was mainly present in the desmoplastic stroma of PDA, with high deposition around the malignant ducts and in between the sites of stromal fatty infiltration. Analysis of the COL6A3 splice variants showed tumor-specific consistent inclusion of exons 3 and 6 in 17 of the 18 (94%) paired PDA-adjacent tissues. Inclusion of exon 4 was exclusively tumor-specific, with barely detectable expression in the adjacent tissues. IPMN and pancreatic cystadenomas showed no expression of any of the examined exons. Total COL6A3 mRNA and exon 6 were identified in six PDA cell lines, but only two cell lines (MIA PACA-2 and ASPC-1) expressed exons 3 and 4. In both the xenograft and transgenic models of PDA, COL6A3 immunoreactivity was present in the stroma

Deliverable 3.3.2 Specification of tests and test groups

DEFF Research Database (Denmark)

Peterson, Carrie Beth; Mitseva, Anelia; Harpur, Jill

2009-01-01

Deliverable 3.3.2: Specification of tests and test groups One of the main goals of the ISISEMD project is to offer innovative ICT services to improve the quality of life of elderly persons with cognitive problems or mild dementia and their informal and formal caregivers who provide every day care...... for them. This will be done via integrating intelligent scalable ICT services which will be tested for a period of 12 months under realistic conditions. Offering the services could not be complete without evaluating quality of life improvement, user acceptance and user satisfaction with a representative...... group of the target user groups. This document is devoted to describing important aspects of services evaluation such as: who the test participants will be, inclusion and exclusion criterion, selection standards, how the test participants will be recruited, ethical considerations, etc. Test methodology...

Specific phosphorylation of histone demethylase KDM3A determines target gene expression in response to heat shock.

Directory of Open Access Journals (Sweden)

Mo-bin Cheng

2014-12-01

Full Text Available Histone lysine (K residues, which are modified by methyl- and acetyl-transferases, diversely regulate RNA synthesis. Unlike the ubiquitously activating effect of histone K acetylation, the effects of histone K methylation vary with the number of methyl groups added and with the position of these groups in the histone tails. Histone K demethylases (KDMs counteract the activity of methyl-transferases and remove methyl group(s from specific K residues in histones. KDM3A (also known as JHDM2A or JMJD1A is an H3K9me2/1 demethylase. KDM3A performs diverse functions via the regulation of its associated genes, which are involved in spermatogenesis, metabolism, and cell differentiation. However, the mechanism by which the activity of KDM3A is regulated is largely unknown. Here, we demonstrated that mitogen- and stress-activated protein kinase 1 (MSK1 specifically phosphorylates KDM3A at Ser264 (p-KDM3A, which is enriched in the regulatory regions of gene loci in the human genome. p-KDM3A directly interacts with and is recruited by the transcription factor Stat1 to activate p-KDM3A target genes under heat shock conditions. The demethylation of H3K9me2 at the Stat1 binding site specifically depends on the co-expression of p-KDM3A in the heat-shocked cells. In contrast to heat shock, IFN-γ treatment does not phosphorylate KDM3A via MSK1, thereby abrogating its downstream effects. To our knowledge, this is the first evidence that a KDM can be modified via phosphorylation to determine its specific binding to target genes in response to thermal stress.

Vitamin C induces specific demethylation of H3K9me2 in mouse embryonic stem cells via Kdm3a/b.

Science.gov (United States)

Ebata, Kevin T; Mesh, Kathryn; Liu, Shichong; Bilenky, Misha; Fekete, Alexander; Acker, Michael G; Hirst, Martin; Garcia, Benjamin A; Ramalho-Santos, Miguel

2017-01-01

Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in naïve ES cells. Vitamin C treatment reduces global levels of H3K9me2, but not other histone methylation marks analyzed, as measured by western blot, immunofluorescence and mass spectrometry. Vitamin C leads to widespread loss of H3K9me2 at large chromosomal domains as well as gene promoters and repeat elements. Vitamin C-induced loss of H3K9me2 occurs rapidly within 24 h and is reversible. Importantly, we found that the histone demethylases Kdm3a and Kdm3b are required for vitamin C-induced demethylation of H3K9me2. Moreover, we show that vitamin C-induced Kdm3a/b-mediated H3K9me2 demethylation and Tet-mediated DNA demethylation are independent processes at specific loci. Lastly, we document Kdm3a/b are partially required for the upregulation of germline genes by vitamin C. These results reveal a specific role for vitamin C in histone demethylation in ES cells and document that DNA methylation and H3K9me2 cooperate to silence germline genes in pluripotent cells.

X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner

NARCIS (Netherlands)

Welstead, G.G.; Creyghton, M.P.; Bilodeau, S.; Cheng, A.W.; Markoulaki, S.; Young, R.A.; Jaenisch, R.

2012-01-01

Embryogenesis requires the timely and coordinated activation of developmental regulators. It has been suggested that the recently discovered class of histone demethylases (UTX and JMJD3) that specifically target the repressive H3K27me3 modification play an important role in the activation of

[A workplace intervention aimed at increasing awareness in nursing personnel performing manual handling activities].

Science.gov (United States)

Scorpiniti, A; Lorusso, A; L'Abbate, N

2007-01-01

Here we describe a workplace intervention aimed at reducing the risk of low back pain in nursing personnel. The intervention we carried out included a specific ergonomic training and an exercise program according to the Feldenkrais Method. After the intervention, we evaluated its effect on the execution of manual handling activities in nurses. We found an increased rate of correct manual handling in the post-intervention period.

Establishment of Infrastructure for Domestic-Specific Level 3 PSA based on MACCS2

Energy Technology Data Exchange (ETDEWEB)

Jang, Seung-Cheol; Han, Seok-Jung; Choi, Sun-Yeong; Lee, Seung-Jun [KAERI, Daejeon (Korea, Republic of); Kim, Wan-Seob [Korea Reliability Technology and System, Daejeon (Korea, Republic of)

2015-05-15

Research activities related to the Level 3 PSA have naturally disappeared since the use of risk surrogates. Recently, Level 3 PSA was only performed to the extent of the purpose of operating license for the plant under construction. Since the Fukushima accident, concern about a comprehensive site-specific Level 3 PSA has been raised for some compelling reasons, especially the evaluation of the domestic multi-unit site risk effect including other site radiological sources (e.g., spent fuel pool, multi-units). Unfortunately, there are no domestic-specific consequence analysis code and input database required to perform a site-specific Level 3 PSA. The paper focuses on the development of the input data management system for domestic-specific Level 3 PSA based MACCS2 (MELCOR Accident Consequence Code System). The authors call it KOSCA-MACCS2 (Korea Off-Site Consequence Analysis based in MACCS2). It serves as an integrated platform for a domestic-specific Level 3 PSA. Also, it provides the pre-processing modules to automatically generate MACCS2 input from diverse types of the domestic-specific data including numerical map data, e.g., meteorological data, numerical population map, digital land use map, economic statistics and so on. Note that some functions should be still developed and added on it, e.g., post-processing module to convert MACCS2 outputs to graphic report forms, and so on. Henceforth, it is necessary to develop a Korean-specific Level 3 PSA code as a substitution for the foreign software, MACCS2.

Dielectric properties of 3D-printed materials for anatomy specific 3D-printed MRI coils

Science.gov (United States)

Behzadnezhad, Bahareh; Collick, Bruce D.; Behdad, Nader; McMillan, Alan B.

2018-04-01

Additive manufacturing provides a low-cost and rapid means to translate 3D designs into the construction of a prototype. For MRI, this type of manufacturing can be used to construct various components including the structure of RF coils. In this paper, we characterize the material properties (dielectric constant and loss tangent) of several common 3D-printed polymers in the MRI frequency range of 63-300 MHz (for MRI magnetic field strengths of 1.5-7 T), and utilize these material properties in full-wave electromagnetic simulations to design and construct a very low-cost subject/anatomy-specific 3D-printed receive-only RF coil that fits close to the body. We show that the anatomy-specific coil exhibits higher signal-to-noise ratio compared to a conventional flat surface coil.

Radiation hybrids from human chromosome 3: A basis for the construction of region and specific sublibraries

International Nuclear Information System (INIS)

Atchison, L.; Cosmis, R.L.; Atchison, M.L.

1990-01-01

The authors are interested in identifying genes on human chromosome involved in disease processes. To date at least 20 different loci on this chromosome are implicated with various disease states. DNA libraries containing clones derived from a small chromosomal subregion implicated in a particular disease would greatly assist these studies. They have utilized the radiation hybrid (RH) technique to generate a series of somatic cell hybrids that contain small segments of human chromosome 3 as the only human genetic material. A Chinese hamster-human cell hybrid (Q314-2) containing only human chromosome 3 was used to prepare radiation hybrids. Cells were lethally X-irradiated with 6,000 rads and fused to Urd(??) Chinese hamster cells by PEG 1000 treatment. The majority of hybrids (>72%) analyzed retained portions of chromosome 3. The amount of chromosome 3 in each hybrid ranged from nearly all of the chromosome to very little. Currently these hybrids are being further characterized with single copy probes of known map location in order to isolate regions of chromosome 3 that contain specific disease locus. These reduced hybrids can then be used for the construction of region specific libraries and for the generation of new DNA probes from the specific region of interest

Characterization of antigen-specific, Ia-restricted, L3T4+ cytolytic T lymphocytes and assessment of thymic influence on their self specificity

International Nuclear Information System (INIS)

Golding, H.; Munitz, T.I.; Singer, A.

1985-01-01

The goals of the present study were: (a) to generate antigen-specific L3T4+ cytolytic T lymphocytes (CTL), (b) to determine their major histocompatibility complex (MHC) restriction specificity, and (c) to assess the influence of thymic MHC determinants on their self specificity. The authors found that L3T4+ CTL specific for either trinitrophenyl (TNP)-modified self determinants or minor histocompatibility antigens could be generated from Lyt-2- responder T cells provided that the response cultures were supplemented with supernatants rich in helper factors. Such antigen-specific L3T4+ CTL were Ia-restricted by the criteria that they lysed only Ia+ target cells and that their lysis of Ia+ target cells was specifically inhibited by anti-Ia monoclonal antibodies. The relative frequency of L3T4+ pCTL was found to be only 5-10% of the total anti-TNP pCTL present in the spleens of normal mice. Finally, the authors utilized radiation bone marrow chimeras to assess the influence of the thymic haplotype on the self-Ia specificity of L3T4+ CTL. Both bulk culture and limiting dilution experiments revealed that the self-Ia specificity of L3T4+ anti-TNP CTL from F1----parent and A----B allogeneic chimeras was not markedly skewed toward the haplotype of the chimeric thymus. These results contrast with those obtained previously for L3T4+ anti-TNP Th cells and demonstrate that in the radiation bone marrow chimera model of T cell differentiation, the self specificity of Th cells but not pCTL is markedly influenced by the haplotype of the chimeric thymus

Isoform-specific proteasomal degradation of Rbfox3 during chicken embryonic development

Energy Technology Data Exchange (ETDEWEB)

Kim, Kee K.; Adelstein, Robert S.; Kawamoto, Sachiyo, E-mail: kawamots@mail.nih.gov

2014-08-08

Highlights: • Protein stability of Rbfox3 splice isoforms is differentially regulated. • Rbfox3-d31, an Rbfox3 isoform lacking the RRM, is highly susceptible to degradation. • The protein stability of Rbfox3-d31 is regulated by the ubiquitin–proteasome pathway. • Rbfox3-d31 inhibits the nuclear localization of Rbfox2. • Rbfox3-d31 inhibits the splicing activity of Rbfox2. - Abstract: Rbfox3, a neuron-specific RNA-binding protein, plays an important role in neuronal differentiation during development. An isoform Rbfox3-d31, which excludes the 93-nucleotide cassette exon within the RNA recognition motif of chicken Rbfox3, has been previously identified. However, the cellular functions of Rbfox3-d31 remain largely unknown. Here we find that Rbfox3-d31 mRNA is highly expressed during the early developmental stages of the chicken embryo, while Rbfox3-d31 protein is barely detected during the same stage due to its rapid degradation mediated by the ubiquitin–proteasome pathway. Importantly, this degradation is specific to the Rbfox3-d31 isoform and it does not occur with full-length Rbfox3. Furthermore, suppression of Rbfox3-d31 protein degradation with the proteasome inhibitor MG132 attenuates the splicing activity of another Rbfox family member Rbfox2 by altering the subcellular localization of Rbfox2. These results suggest that Rbfox3-d31 functions as a repressor for the splicing activity of the Rbfox family and its protein level is regulated in an isoform-specific manner in vivo.

Standard Technical Specifications General Electric plants, BWR/4: Bases (Sections 2.0-3.3). Volume 2, Revision 1

International Nuclear Information System (INIS)

1995-04-01

This report documents the results of the combined effort of the NRC and the industry produce improved Standard Technical Specifications (STS), Revision 1 for General Electric BWR/4 Plants. The changes reflected in Revision 1 resulted from the experience gained from license amendment applications to convert to these improved ST or to adopt partial improvements to existing technical specifications. This NUREG is the result of extensive public technical meetings and discussions between the Nuclear Regulatory Commission (NRC) staff and various nuclear power plant licensees, Nuclear Steam Supply System (NSSS) Owners Groups, NSSS vendors, and the Nuclear Energy Institute (NEI). The improved STS were developed based on the criteria in the Final Commission Policy Statement on Technical Specifications Improvements for Nuclear Power Reactors, dated July 22, 1993. The improved STS will be used as the basis for individual nuclear power plant licensees to develop improved plant-specific technical specifications. This report contains three volumes. Volume I contains the Specifications for all chapters and sections of the improved STS. This document, Volume 2, contains the Bases for Chapters 2.0 and 3.0, and Sections 3.1-3.3 of the improved STS. Volume 3 contains the Bases for Sections 3.4-3.10 of the improved STS

KIF3A and IL-4 are disease-specific biomarkers for psoriatic arthritis susceptibility

Science.gov (United States)

Ragazzo, Michele; Manzo, Laura; Costanza, Gaetana; Bowes, John; Hüffmeier, Ulrike; Potenza, Saverio; Sangiuolo, Federica; Reis, André; Barton, Anne; Novelli, Giuseppe; Orlandi, Augusto; Giardina, Emiliano

2017-01-01

To date, the genes associated with Psoriatic Arthritis (PsA) are principally involved in inflammation, immune response and epidermal differentiation, without any information about the relationship between disease and bone metabolism genes. Our work was focused on 5q31 locus, which contains several genetic variants significantly associated with PsA. The study involved 1526 subjects (500 PsA, 426 PsV, 600 controls). The region was evaluated by selecting and genotyping the SNPs of interest by Real Time PCR and direct sequencing. The results were subjected to biostatistic and bioinformatic analysis. The case-control study highlighted a significant association between KIF3A/IL-4 and PsA, but not with PsV (Psoriasis Vulgaris) patients. In addition, the haplotype analysis revealed two haplotypes significantly associated with PsA susceptibility. The Linkage Disequilibrium (LD) study showed the presence of a specific block in high LD within 132,692,628-132,737,638 bp of 5q31, giving additional evidence of specific association of the 5q31 region in PsA patients. Moreover, KIF3A expression was assessed by immunohistochemistry assays which showed a marked and significant difference of KIF3A expression between pathological and normal tissues. Our analysis described KIF3A and IL-4 as novel susceptibility genes for PsA, suggesting a clear implication of bone metabolism genes in the disease etiopathogenesis. PMID:29221136

African-American Men with Gleason Score 3+3=6 Prostate Cancer Produce Less Prostate Specific Antigen than Caucasian Men: A Potential Impact on Active Surveillance.

Science.gov (United States)

Kryvenko, Oleksandr N; Balise, Raymond; Soodana Prakash, Nachiketh; Epstein, Jonathan I

2016-02-01

We assess the difference in prostate specific antigen production between African-American and Caucasian men with Gleason score 3+3=6 prostate cancer. We measured tumor volume in 414 consecutive radical prostatectomies from men with National Comprehensive Cancer Network(®) low risk prostate cancer (348 Caucasian, 66 African-American) who had Gleason score 3+3=6 disease at radical prostatectomy. We then compared clinical presentation, pathological findings, prostate specific antigen, prostate specific antigen density and prostate specific antigen mass (an absolute amount of prostate specific antigen in patient's circulation) between African-American and Caucasian men. The t-test and Wilcoxon rank sum were used for comparison of means. African-American and Caucasian men had similar clinical findings based on age, body mass index and prostate specific antigen. There were no statistically significant differences between the dominant tumor nodule volume and total tumor volume (mean 0.712 vs 0.665 cm(3), p=0.695) between African-American and Caucasian men. Prostates were heavier in African-American men (mean 55.4 vs 46.3 gm, p prostate tissue contributing to prostate specific antigen in African-American men, prostate specific antigen mass was not different from that of Caucasian men (mean 0.55 vs 0.558 μg, p=0.95). Prostate specific antigen density was significantly less in African-American men due to larger prostates (mean 0.09 vs 0.105, p prostate cancer produce less prostate specific antigen than Caucasian men. African-American and Caucasian men had equal serum prostate specific antigen and prostate specific antigen mass despite significantly larger prostates in African-American men with all other parameters, particularly total tumor volume, being the same. This finding has practical implications in T1c cases diagnosed with prostate cancer due to prostate specific antigen screening. Lowering the prostate specific antigen density threshold in African-American men may

A feasibility study for using ABS plastic and a low-cost 3D printer for patient-specific brachytherapy mould design.

Science.gov (United States)

Harris, Benjamin D; Nilsson, Sanna; Poole, Christopher M

2015-09-01

This feasibility study aims to determine if a low-cost 3D printer (BitsFromBytes 3D Touch) with ABS plastic can print custom mould structures and catheter channels defined in a brachytherapy treatment planning system (Nucletron Oncentra) for patient-specific treatment. Printer accuracy was evaluated through physical measurement, and print quality was investigated by adjusting print parameters (print speed, layer thickness, percentage infill). Catheter positioning and reproducibility were measured over repeated insertions. ABS plastic water equivalency was investigated by comparing Ir-192 HDR source dose distributions, measured with radiochromic film, in ABS plastic and in water. Structures and catheter channels were printed accurately to within 0.5 mm laterally and 1 mm in the vertical print direction. Adjusting print parameters could reduce print time, albeit with reduced print quality. 3.5 mm channel diameters allowed for easy catheter insertion. Catheter positioning was reproducible to within 0.5 mm but, because of catheter flex within the channel, was on average 1 mm offset from defined TPS positions. This offset could be accounted for by repeating the treatment planning CT scan with the printed mould positioned on the patient. Dose attenuation in ABS plastic and in water was equivalent to within the measurement limitations. While clinical uses for this particular low-cost printer and ABS plastic are limited by print size restrictions and non-certification for biocompatibility, it has been demonstrated that a low-cost 3D printer set-up can accurately create custom moulds and catheter channels potentially acceptable for clinical use.

Bunch mode specific rate corrections for PILATUS3 detectors

Energy Technology Data Exchange (ETDEWEB)

Trueb, P., E-mail: peter.trueb@dectris.com [DECTRIS Ltd, 5400 Baden (Switzerland); Dejoie, C. [ETH Zurich, 8093 Zurich (Switzerland); Kobas, M. [DECTRIS Ltd, 5400 Baden (Switzerland); Pattison, P. [EPF Lausanne, 1015 Lausanne (Switzerland); Peake, D. J. [School of Physics, The University of Melbourne, Victoria 3010 (Australia); Radicci, V. [DECTRIS Ltd, 5400 Baden (Switzerland); Sobott, B. A. [School of Physics, The University of Melbourne, Victoria 3010 (Australia); Walko, D. A. [Argonne National Laboratory, Argonne, IL 60439 (United States); Broennimann, C. [DECTRIS Ltd, 5400 Baden (Switzerland)

2015-04-09

The count rate behaviour of PILATUS3 detectors has been characterized for seven bunch modes at four different synchrotrons. The instant retrigger technology of the PILATUS3 application-specific integrated circuit is found to reduce the dependency of the required rate correction on the synchrotron bunch mode. The improvement of using bunch mode specific rate corrections based on a Monte Carlo simulation is quantified. PILATUS X-ray detectors are in operation at many synchrotron beamlines around the world. This article reports on the characterization of the new PILATUS3 detector generation at high count rates. As for all counting detectors, the measured intensities have to be corrected for the dead-time of the counting mechanism at high photon fluxes. The large number of different bunch modes at these synchrotrons as well as the wide range of detector settings presents a challenge for providing accurate corrections. To avoid the intricate measurement of the count rate behaviour for every bunch mode, a Monte Carlo simulation of the counting mechanism has been implemented, which is able to predict the corrections for arbitrary bunch modes and a wide range of detector settings. This article compares the simulated results with experimental data acquired at different synchrotrons. It is found that the usage of bunch mode specific corrections based on this simulation improves the accuracy of the measured intensities by up to 40% for high photon rates and highly structured bunch modes. For less structured bunch modes, the instant retrigger technology of PILATUS3 detectors substantially reduces the dependency of the rate correction on the bunch mode. The acquired data also demonstrate that the instant retrigger technology allows for data acquisition up to 15 million photons per second per pixel.

Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and Anaphylaxis: A Pilot Study.

Science.gov (United States)

Yanagida, Noriyuki; Sato, Sakura; Maruyama, Nobuyuki; Takahashi, Kyohei; Nagakura, Ken-Ichi; Ogura, Kiyotake; Asaumi, Tomoyuki; Ebisawa, Motohiro

2018-01-01

Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3-specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in predicting OFC results and anaphylaxis. We conducted a retrospective review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP® assay system and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC using 3,072 mg of BW protein between July 2006 and March 2014 at Sagamihara National Hospital, Kanagawa, Japan. We analyzed 60 patients aged 1.9-13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC. The patients without symptoms had significantly lower Fag e 3-sIgE than those with non-anaphylactic (p tested factor that significantly predicted positive OFC results (odds ratio 8.93, 95% confidence interval 3.10-25.73, p < 0.001) and OFC-induced anaphylaxis (2.67, 1.12-6.35, p = 0.027). We suggest that a threshold Fag e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction to BW. Fag e 3-sIgE predicted OFC results and OFC-induced anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC-induced anaphylaxis. © 2018 The Author(s) Published by S. Karger AG, Basel.

Saccharomyces cerevisiae Ngl3p is an active 3′–5′ exonuclease with a specificity towards poly-A RNA reminiscent of cellular deadenylases

DEFF Research Database (Denmark)

Feddersen, Ane; Dedic, Emil; Poulsen, Esben Guldahl

2012-01-01

RNAs that yeast Ngl3p is a functional 3′–5′ exonuclease most active at slightly acidic conditions. We further show that the enzyme depends on divalent metal ions for activity and possesses specificity towards poly-A RNA similar to what has been observed for cellular deadenylases. The results suggest that Ngl3p...

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand

Science.gov (United States)

Chen, Mee-Yew; Kirkwood, Carl D.; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J.; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

2017-01-01

ABSTRACT Background: Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Methods: Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0–5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Results: Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). Conclusions: The level of IgA in colostrum or breast milk and level of placental Ig

Rotavirus specific maternal antibodies and immune response to RV3-BB neonatal rotavirus vaccine in New Zealand.

Science.gov (United States)

Chen, Mee-Yew; Kirkwood, Carl D; Bines, Julie; Cowley, Daniel; Pavlic, Daniel; Lee, Katherine J; Orsini, Francesca; Watts, Emma; Barnes, Graeme; Danchin, Margaret

2017-05-04

Maternal antibodies, acquired passively via placenta and/or breast milk, may contribute to the reduced efficacy of oral rotavirus vaccines observed in children in developing countries. This study aimed to investigate the effect of rotavirus specific maternal antibodies on the serum IgA response or stool excretion of vaccine virus after any dose of an oral rotavirus vaccine, RV3-BB, in parallel to a Phase IIa clinical trial conducted at Dunedin Hospital, New Zealand. At the time of the study rotavirus vaccines had not been introduced in New Zealand and the burden of rotavirus disease was evident. Rotavirus specific IgG and serum neutralizing antibody (SNA) levels in cord blood and IgA levels in colostrum and breast milk samples collected ∼4 weeks, ∼20 weeks and ∼28 weeks after birth were measured. Infants were randomized to receive the first dose of vaccine at 0-5 d (neonatal schedule) or 8 weeks (infant schedule). Breast feeding was with-held for 30 minutes before and after vaccine administration. The relationship between rotavirus specific IgG and SNA levels in cord blood and IgA in colostrum and breast milk at the time of first active dose of RV3-BB vaccine and level of IgA response and stool excretion after 3 doses of vaccine was assessed using linear and logistic regression. Forty infants received 3 doses of RV3-BB rotavirus vaccine and were included in the analysis of the neonatal and infant groups. Rotavirus specific IgA in colostrum (neonatal schedule group) and breast milk at 4 weeks (infant schedule group) was identified in 14/21 (67%) and 14/17 (82%) of infants respectively. There was little evidence of an association between IgA in colostrum or breast milk IgA at 4 weeks, or between cord IgG or SNA level, and IgA response or stool excretion after 3 doses of RV3-BB, or after one dose (neonatal schedule) (all p>0.05). The level of IgA in colostrum or breast milk and level of placental IgG and SNA did not impact on the serum IgA response or

14-3-3 checkpoint regulatory proteins interact specifically with DNA repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif

DEFF Research Database (Denmark)

Andersen, Sofie Dabros; Keijzers, Guido; Rampakakis, Emmanouil

2012-01-01

Human exonuclease 1 (hEXO1) acts directly in diverse DNA processing events, including replication, mismatch repair (MMR), and double strand break repair (DSBR), and it was also recently described to function as damage sensor and apoptosis inducer following DNA damage. In contrast, 14-3-3 proteins...... are specifically induced by replication inhibition leading to protein ubiquitination and degradation. We demonstrate direct and robust interaction between hEXO1 and six of the seven 14-3-3 isoforms in vitro, suggestive of a novel protein interaction network between DNA repair and cell cycle control. Binding...... and most likely a second unidentified binding motif. 14-3-3 associations do not appear to directly influence hEXO1 in vitro nuclease activity or in vitro DNA replication initiation. Moreover, specific phosphorylation variants, including hEXO1 S746A, are efficiently imported to the nucleus; to associate...

Functional characterization of Foxp3-specific spontaneous immune responses

DEFF Research Database (Denmark)

Larsen, Susanne Købke; Munir, S; Andersen, Anders Woetmann

2013-01-01

Tumor-infiltrating CD4+CD25+ regulatory T cells (Tregs) are associated with an impaired prognosis in several cancers. The transcription factor forkhead box P3 (Foxp3) is generally expressed in Tregs. Here, we identify and characterize spontaneous cytotoxic immune responses to Foxp3-expressing cel....... Consequently, induction of Foxp3-specific cytotoxic T-cell responses appears as an attractive tool to boost spontaneous or therapeutically provoked immune responses, for example, for the therapy of cancer....

Use of the FLUKA Monte Carlo code for 3D patient-specific dosimetry on PET-CT and SPECT-CT images*

Science.gov (United States)

Botta, F; Mairani, A; Hobbs, R F; Vergara Gil, A; Pacilio, M; Parodi, K; Cremonesi, M; Coca Pérez, M A; Di Dia, A; Ferrari, M; Guerriero, F; Battistoni, G; Pedroli, G; Paganelli, G; Torres Aroche, L A; Sgouros, G

2014-01-01

Patient-specific absorbed dose calculation for nuclear medicine therapy is a topic of increasing interest. 3D dosimetry at the voxel level is one of the major improvements for the development of more accurate calculation techniques, as compared to the standard dosimetry at the organ level. This study aims to use the FLUKA Monte Carlo code to perform patient-specific 3D dosimetry through direct Monte Carlo simulation on PET-CT and SPECT-CT images. To this aim, dedicated routines were developed in the FLUKA environment. Two sets of simulations were performed on model and phantom images. Firstly, the correct handling of PET and SPECT images was tested under the assumption of homogeneous water medium by comparing FLUKA results with those obtained with the voxel kernel convolution method and with other Monte Carlo-based tools developed to the same purpose (the EGS-based 3D-RD software and the MCNP5-based MCID). Afterwards, the correct integration of the PET/SPECT and CT information was tested, performing direct simulations on PET/CT images for both homogeneous (water) and non-homogeneous (water with air, lung and bone inserts) phantoms. Comparison was performed with the other Monte Carlo tools performing direct simulation as well. The absorbed dose maps were compared at the voxel level. In the case of homogeneous water, by simulating 108 primary particles a 2% average difference with respect to the kernel convolution method was achieved; such difference was lower than the statistical uncertainty affecting the FLUKA results. The agreement with the other tools was within 3–4%, partially ascribable to the differences among the simulation algorithms. Including the CT-based density map, the average difference was always within 4% irrespective of the medium (water, air, bone), except for a maximum 6% value when comparing FLUKA and 3D-RD in air. The results confirmed that the routines were properly developed, opening the way for the use of FLUKA for patient-specific, image

Aims and first assessments of the French hydrogen pathways project HyFrance3

Energy Technology Data Exchange (ETDEWEB)

Le Duigou, Alain [CEA/DEN/DANS/I-Tese, Gif-sur-Yvette (France); Quemere, Marie-Marguerite [EDF R et D, Moret sur Loing (France). Dept. EPI; Marion, Pierre [IFP, Rueil Malmaison (FR)] (and others)

2010-07-01

The HyFrance Group was originally formed in France to support the European project HyWays, by providing (former projects HyFrance1 and HyFrance2) the French data and possible hydrogen pathways according to national specificities. HyFrance3 is a new project that focuses on the economic competitiveness of different steps of the hydrogen chain, from the production to end usage, at the time horizon of 2030 in France. The project is coordinated by CEA with the other partners being: ADEME (co-funding), AFH2, CNRS, IFP, Air Liquide, EdF, GdF Suez, TOTAL, ALPHEA. The project is divided into 4 sub-projects, that address present and future French hydrogen industrial markets for chemical and refinery uses, the analysis of the interplay between wind energy production and storage of hydrogen for different automotive requirements (refuelling stations, BtL plants, H2/NG mix), massive hydrogen storage to balance various offer and demand characteristics, and the supply network (pipeline option competitiveness vs. trucked in supply) to distribute hydrogen in a French region for automotive applications. Technical and economical issues, as well as GHG emissions, are addressed. (orig.)

Evaluation and cultural adaptation of a German version of the AIMS2-SF questionnaire (German AIMS2-SF).

NARCIS (Netherlands)

Rosemann, T.J.; Korner, T.; Wensing, M.J.P.; Schneider, A.; Szecsenyi, J.

2005-01-01

OBJECTIVES: The aim of the study was to examine the validity of a translated and culturally adapted version of the Arthritis Impact Measurement Scales 2, Short Form (AIMS2-SF) in patients suffering from osteoarthritis (OA) in primary care. METHODS: A structured procedure was used for the translation

The preparation and properties of a highly specific antiserum elicited with 3-dehydrocholylglycine 3-succinyl-bovine serum albumin conjugate

International Nuclear Information System (INIS)

Orban, E.C.; Pal, Z.

1986-01-01

This report describes the synthesis of a new cholylglycine derivative-bovine serum albumin conjugate. The hapten is linked to the carrier protein at the C-3 position, through a hemisuccinate bridge. Antiserum elicited by this antigen is highly specific to cholylglycine. Cross-reactions with free cholic acid (less than 0.1%) or cholyltaurine (0.5%) are minimal. (author)

Developing a dashboard to help measure and achieve the triple aim: a population-based cohort study.

Science.gov (United States)

Seow, Hsien-Yeang; Sibley, Lyn M

2014-08-30

Health system planners aim to pursue the three goals of Triple Aim: 1) reduce health care costs; 2) improve population health; and 3) improve the care experience. Moreover, they also need measures that can reliably predict future health care needs in order to manage effectively the health system performance. Yet few measures exist to assess Triple Aim and predict future needs at a health system level. The purpose of this study is to explore the novel application of a case-mix adjustment method in order to measure and help improve the Triple Aim of health system performance. We applied a case-mix adjustment method to a population-based analysis to assess its usefulness as a measure of health system performance and Triple Aim. The study design was a retrospective, cohort study of adults from Ontario, Canada using administrative databases: individuals were assigned a predicted illness burden score using a case-mix adjustment system from diagnoses and health utilization data in 2008, and then followed forward to assess the actual health care utilization and costs in the following year (2009). We applied the Johns Hopkins Adjusted Clinical Group (ACG) Case-Mix System to categorize individuals into 60 levels of healthcare need, called ACGs. The outcomes were: 1) Number of individuals per ACG; 2) Total system costs per ACG; and 3) Mean cost per person per ACG, which together formed a health system "dashboard". We identified 11.4 million adults. 16.1% were aged 65 or older, 3.2 million (28%) did not use health care services that year, and 45,000 (0.4%) were in the highest acuity ACG category using 12 times more than an average adult. The sickest 1%, 5% and 15% of the population use about 10%, 30% and 50% of total health system costs respectively. The dashboard measures 2 dimensions of Triple Aim: 1) reduced costs: when total system costs per ACG or when average costs per person is reduced; and 2) improved population health: when more people move into healthier rather than

Construction and Biological Evaluation of a Novel Integrin ανβ3-Specific Carrier for Targeted siRNA Delivery In Vitro

Directory of Open Access Journals (Sweden)

Xueqi Chen

2017-02-01

Full Text Available (1 Background: The great potential of RNA interference (RNAi-based gene therapy is premised on the effective delivery of small interfering RNAs (siRNAs to target tissues and cells. Hence, we aimed at developing and examining a novel integrin αvβ3-specific delivery carrier for targeted transfection of siRNA to malignant tumor cells; (2 Methods: Arginine-glycine-aspartate motif (RGD was adopted as a tissue target for specific recognition of integrin αvβ3. To enable siRNA binding, a chimeric peptide was synthesized by adding nonamer arginine residues (9R at the carboxy terminus of cyclic-RGD dimer, designated as c(RGD2-9R. The efficiency of 9R peptide transferring siRNA was biologically evaluated in vitro by flow cytometry, confocal microscopy, and Western blot; (3 Results: An optimal 10:1 molar ratio of c(RGD2-9R to siRNA was confirmed by the electrophoresis on agarose gels. Both the flow cytometry and confocal microscopy results testified that transfection of c(RGD2-9R as an siRNA delivery carrier was obviously higher than the naked-siRNA group. The results of Western blot demonstrated that these 9R peptides were able to transduce siRNA to HepG2 cells in vitro, resulting in efficient gene silencing; and (4 Conclusion: The chimeric peptide of c(RGD2-9R can be developed as an effective siRNA delivery carrier and shows potential as a new strategy for RNAi-based gene therapy.

Reconstituted AIM2 inflammasome in cell-free system.

Science.gov (United States)

Kaneko, Naoe; Ito, Yuki; Iwasaki, Tomoyuki; Takeda, Hiroyuki; Sawasaki, Tatsuya; Migita, Kiyoshi; Agematsu, Kazunaga; Kawakami, Atsushi; Morikawa, Shinnosuke; Mokuda, Sho; Kurata, Mie; Masumoto, Junya

2015-11-01

Absent in melanoma 2 (AIM2) is an intracellular pattern-recognition receptor, which is a member of the PYHIN protein family, consisting of a PYD domain and an IFN-inducible nuclear localization (HIN) domain. AIM2 is reported to oligomerize with adaptor protein ASC upon sensing bacterial and viral cytosolic DNA in order to form the AIM2 inflammasome, which activates caspase-1 leading to IL-1β secretion. Dysregulation of AIM2 inflammasome is supposed to result in autoinflammatory and autoimmune diseases. Thus, the development of new targeted drugs against AIM2 inflammasome would be important for the treatment of these diseases. However, since AIM2 inflammasome is an intracellular receptor, enforced internalization of both ligands and candidate molecules is necessary for the screening of AIM2-inflammasome-targeted molecules. We developed a reconstituted AIM2 inflammasome in a cell-free system with amplified luminescent proximity homogeneous assay (Alpha). Strong Alpha signal was detected upon incubation with poly-deoxyadenylic-deoxythymidylic acid, poly(dA:dT), whereas no Alpha signal was detected upon incubation with muramyl dipeptide, one of the NLR ligands of Nod2 ligand. The interaction between AIM2 and ASC was disrupted by an anti-human ASC monoclonal antibody, CRID3, a class of diarylsulfonylurea-containing compounds, and glycyrrhizin, a substance found in liquorice root. Thus, the reconstituted AIM2 inflammasome in a cell-free system is useful for screening AIM2-inflammasome-targeted therapeutic molecules. Copyright © 2015 Elsevier B.V. All rights reserved.

B700, a murine melanoma-specific antigen, binds Vitamin D3; conservation of binding among albuminoid molecules

International Nuclear Information System (INIS)

Farzaneh, N.K.; Walden, T.L. Jr.; Hearing, V.J.; Gersten, D.M.

1990-01-01

B700, a murine melanoma-specific antigen, is a member of the serum albumin protein family. Other members of this family include serum albumin (SMA), a-fetoprotein (AFP), vitamin D binding protein (DBP), and C700. The primary structure and biochemical functions of B700, as well as its in vivo metabolic fate are largely unknown. The authors examined the functional characteristics of MSA, AFP, and DBP, and for their ability to specifically bind [ 3 H]-1,25-dihydroxy-vitamin D 3 . Scatchard analysis revealed a single binding site for B700 with a Kd of 51,000 M and a Bmax of 4.51 x 10 -7 . There is no significant difference between the Kd and Bmax values among the albuminoid proteins. However, differences in the binding sites could be distinguished by competition of the 1,25-dihydroxy vitamin D 3 with other steroids. 2nM of vitamin D 3 , vitamin D 2 , or estrogen competed for the specific binding of 1,25-dihydroxy vitamin D 3 by B700 but not by DBP. The MSA binding site for 1,25 dihydroxy vitamin D 3 more closely resembles that of DBP than B700. These data indicate that the binding function of the albuminoid proteins has been conserved in the B700 melanoma antigen

Applications of patient-specific 3D printing in medicine.

Science.gov (United States)

Heller, Martin; Bauer, Heide-Katharina; Goetze, Elisabeth; Gielisch, Matthias; Roth, Klaus E; Drees, Philipp; Maier, Gerrit S; Dorweiler, Bernhard; Ghazy, Ahmed; Neufurth, Meik; Müller, Werner E G; Schröder, Heinz C; Wang, Xiaohong; Vahl, Christian-Friedrich; Al-Nawas, Bilal

Already three decades ago, the potential of medical 3D printing (3DP) or rapid prototyping for improved patient treatment began to be recognized. Since then, more and more medical indications in different surgical disciplines have been improved by using this new technique. Numerous examples have demonstrated the enormous benefit of 3DP in the medical care of patients by, for example, planning complex surgical interventions preoperatively, reducing implantation steps and anesthesia times, and helping with intraoperative orientation. At the beginning of every individual 3D model, patient-specific data on the basis of computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound data is generated, which is then digitalized and processed using computer-aided design/computer-aided manufacturing (CAD/CAM) software. Finally, the resulting data sets are used to generate 3D-printed models or even implants. There are a variety of different application areas in the various medical fields, eg, drill or positioning templates, or surgical guides in maxillofacial surgery, or patient-specific implants in orthopedics. Furthermore, in vascular surgery it is possible to visualize pathologies such as aortic aneurysms so as to improve the planning of surgical treatment. Although rapid prototyping of individual models and implants is already applied very successfully in regenerative medicine, most of the materials used for 3DP are not yet suitable for implantation in the body. Therefore, it will be necessary in future to develop novel therapy approaches and design new materials in order to completely reconstruct natural tissue.

Downregulation of an Aim-1 Kinase Couples with Megakaryocytic Polyploidization of Human Hematopoietic Cells

Science.gov (United States)

Kawasaki, Akira; Matsumura, Itaru; Miyagawa, Jun-ichiro; Ezoe, Sachiko; Tanaka, Hirokazu; Terada, Yasuhiko; Tatsuka, Masaaki; Machii, Takashi; Miyazaki, Hiroshi; Furukawa, Yusuke; Kanakura, Yuzuru

2001-01-01

During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ipl)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3–dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-rasG12V), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-1(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes. PMID:11266445

Pursuing the Triple Aim: The First 7 Years.

Science.gov (United States)

Whittington, John W; Nolan, Kevin; Lewis, Ninon; Torres, Trissa

2015-06-01

POLICY POINTS: In 2008, researchers at the Institute for Healthcare Improvement (IHI) proposed the Triple Aim, strategic organizing principles for health care organizations and geographic communities that seek, simultaneously, to improve the individual experience of care and the health of populations and to reduce the per capita costs of care for populations. In 2010, the Triple Aim became part of the US national strategy for tackling health care issues, especially in the implementation of the Patient Protection and Affordable Care Act (ACA) of 2010. Since that time, IHI and others have worked together to determine how the implementation of the Triple Aim has progressed. Drawing on our 7 years of experience, we describe 3 major principles that guided the organizations and communities working on this endeavor: creating the right foundation for population management, managing services at scale for the population, and establishing a learning system to drive and sustain the work over time. In 2008, researchers at the Institute for Healthcare Improvement (IHI) described the Triple Aim as simultaneously "improving the individual experience of care; improving the health of populations; and reducing the per capita costs of care for populations." IHI and its close colleagues had determined that both individual and societal changes were needed. In 2007, IHI began recruiting organizations from around the world to participate in a collaborative to implement what became known as the Triple Aim. The 141 participating organizations included health care systems, hospitals, health care insurance companies, and others closely tied to health care. In addition, key groups outside the health care system were represented, such as public health agencies, social services groups, and community coalitions. This collaborative provided a structure for observational research. By noting the contrasts between the contexts and structures of those sites in the collaborative that progressed and

Prostate-specific antigen (PSA/hK3): a further player in the field of breast cancer diagnostics?

OpenAIRE

Mannello, Ferdinando; Gazzanelli, Giancarlo

2001-01-01

Since its identification, much information has been obtained about prostate-specific antigen (PSA, or human glandular kallikrein 3 [hK3]), a kallikrein-like serine protease that is the most valuable tumour marker for the screening, diagnosis and management of human prostate carcinoma. Recently, it has become widely accepted that PSA is also present in many nonprostatic sources, casting doubts about the specificity of its tissue expression. Here we summarize the findings on the biomolecular ex...

The new OGC Catalogue Services 3.0 specification - status of work

Science.gov (United States)

Bigagli, Lorenzo; Voges, Uwe

2013-04-01

We report on the work of the Open Geospatial Consortium Catalogue Services 3.0 Standards Working Group (OGC Cat 3.0 SWG for short), started in March 2008, with the purpose to process change requests on the Catalogue Services 2.0.2 Implementation Specification (OGC 07-006r1) and produce a revised version thereof, comprising the related XML schemas and abstract test suite. The work was initially intended as a minor revision (version 2.1), but later retargeted as a major update of the standard and rescheduled (the anticipated roadmap ended in 2008). The target audience of Catalogue Services 3.0 includes: • Implementors of catalogue services solutions. • Designers and developers of catalogue services profiles. • Providers/users of catalogue services. The two main general areas of enhancement included: restructuring the specification document according to the OGC standard for modular specifications (OGC 08-131r3, also known as Core and Extension model); incorporating the current mass-market technologies for discovery on the Web, namely OpenSearch. The document was initially split into four parts: the general model and the three protocol bindings HTTP, Z39.50, and CORBA. The CORBA binding, which was very rarely implemented, and the Z39.50 binding have later been dropped. Parts of the Z39.50 binding, namely Search/Retrieve via URL (SRU; same semantics as Z39.50, but stateless), have been provided as a discussion paper (OGC 12-082) for possibly developing a future SRU profile. The Catalogue Services 3.0 specification is structured as follows: • Part 1: General Model (Core) • Part 2: HTTP Protocol Binding (CSW) In CSW, the GET/KVP encoding is mandatory. The POST/XML encoding is optional. SOAP is supported as a special case of the POST/XML encoding. OpenSearch must always be supported, regardless of the implemented profiles, along with the OpenSearch Geospatial and Temporal Extensions (OGC 10-032r2). The latter specifies spatial (e.g. point-plus-radius, bounding

Lack of specific (3H) prazosin binding sites in dog and rabbit cerebral arteries

International Nuclear Information System (INIS)

Ferron, P.M.; Banner, W. Jr.; Duckles, S.P.

1984-01-01

In order to explore the characteristics of alpha adrenergic receptors on cerebrovascular smooth muscle, specific binding sites for the alpha 1 adrenergic ligand, ( 3 H) prazosin, were studied in blood vessel homogenates. No specific ( 3 H) prazosin binding was found in either rabbit or dog cerebral arteries, but specific binding was demonstrated in the rabbit saphenous and ear arteries. In the ear artery 3 H-prazosin binding was saturable with a K/sub d/ of 0.51 +/- 0.20 nM and a Bmax of 89 +/- 29 fmoles/mg protein. To confirm the adequacy of our membrane preparation, homogenates of both dog and rabbit cerebral arteries showed saturable specific binding with two different ligands: one for muscarinic receptors, [ 3 H](-) quinuclidinyl benzilate (QNB) and one for alpha 2 adrenergic receptors, ( 3 H) yohimbine. The results of these studies demonstrate a lack of alpha 1 adrenergic receptors on cerebral blood vessels, confirming functional studies showing only a weak contractile response to norepinephrine. 29 references, 3 figures, 2 tables

A Generalised Approach to Petri Nets and Algebraic Specifications

International Nuclear Information System (INIS)

Sivertsen, Terje

1998-02-01

The present report represents a continuation of the work on Petri nets and algebraic specifications. The reported research has focused on generalising the approach introduced in HWR-454, with the aim of facilitating the translation of a wider class of Petri nets into algebraic specification. This includes autonomous Petri nets with increased descriptive power, as well as non-autonomous Petri nets allowing the modelling of systems (1) involving extensive data processing; (2) with transitions synchronized on external events; (3) whose evolutions are time dependent. The generalised approach has the important property of being modular in the sense that the translated specifications can be gradually extended to include data processing, synchronization, and timing. The report also discusses the relative merits of state-based and transition-based specifications, and includes a non-trivial case study involving automated proofs of a large number of interrelated theorems. The examples in the report illustrate the use of the new HRP Prover. Of particular importance in this context is the automatic transformation between state-based and transitionbased specifications. It is expected that the approach introduced in HWR-454 and generalised in the present report will prove useful in future work on combination of wide variety of specification techniques

Automated Instrumentation, Monitoring and Visualization of PVM Programs Using AIMS

Science.gov (United States)

Mehra, Pankaj; VanVoorst, Brian; Yan, Jerry; Lum, Henry, Jr. (Technical Monitor)

1994-01-01

We present views and analysis of the execution of several PVM (Parallel Virtual Machine) codes for Computational Fluid Dynamics on a networks of Sparcstations, including: (1) NAS Parallel Benchmarks CG and MG; (2) a multi-partitioning algorithm for NAS Parallel Benchmark SP; and (3) an overset grid flowsolver. These views and analysis were obtained using our Automated Instrumentation and Monitoring System (AIMS) version 3.0, a toolkit for debugging the performance of PVM programs. We will describe the architecture, operation and application of AIMS. The AIMS toolkit contains: (1) Xinstrument, which can automatically instrument various computational and communication constructs in message-passing parallel programs; (2) Monitor, a library of runtime trace-collection routines; (3) VK (Visual Kernel), an execution-animation tool with source-code clickback; and (4) Tally, a tool for statistical analysis of execution profiles. Currently, Xinstrument can handle C and Fortran 77 programs using PVM 3.2.x; Monitor has been implemented and tested on Sun 4 systems running SunOS 4.1.2; and VK uses XIIR5 and Motif 1.2. Data and views obtained using AIMS clearly illustrate several characteristic features of executing parallel programs on networked workstations: (1) the impact of long message latencies; (2) the impact of multiprogramming overheads and associated load imbalance; (3) cache and virtual-memory effects; and (4) significant skews between workstation clocks. Interestingly, AIMS can compensate for constant skew (zero drift) by calibrating the skew between a parent and its spawned children. In addition, AIMS' skew-compensation algorithm can adjust timestamps in a way that eliminates physically impossible communications (e.g., messages going backwards in time). Our current efforts are directed toward creating new views to explain the observed performance of PVM programs. Some of the features planned for the near future include: (1) ConfigView, showing the physical topology

The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters

DEFF Research Database (Denmark)

Nielsen, Mette J; Nedergaard, Anders F; Sun, Shu

2013-01-01

AIM: The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3). METHODS: The monoclonal antibody...... was raised against the N-protease mediated cleavage site of the N-terminal propeptide of type III collagen and a competitive ELISA was developed using the selected antibody. The assay was evaluated in relation to neo-epitope specificity, technical performance, and as a marker for liver fibrosis and muscle...... mass using the rat carbon tetrachloride (CCl4) model and a study of immobilization induced muscle loss in humans, respectively. RESULTS: The ELISA was neo-epitope specific, technically stable and can be assessed in serum and plasma samples. In the CCl4 liver fibrosis model it was observed that serum...

Expression of Rac1 alternative 3' UTRs is a cell specific mechanism with a function in dendrite outgrowth in cortical neurons.

Science.gov (United States)

Braz, Sandra Oliveira; Cruz, Andrea; Lobo, Andrea; Bravo, Joana; Moreira-Ribeiro, Joana; Pereira-Castro, Isabel; Freitas, Jaime; Relvas, Joao B; Summavielle, Teresa; Moreira, Alexandra

2017-06-01

The differential expression of mRNAs containing tandem alternative 3' UTRs, achieved by mechanisms of alternative polyadenylation and post-transcriptional regulation, has been correlated with a variety of cellular states. In differentiated cells and brain tissues there is a general use of distal polyadenylation signals, originating mRNAs with longer 3' UTRs, in contrast with proliferating cells and other tissues such as testis, where most mRNAs contain shorter 3' UTRs. Although cell type and state are relevant in many biological processes, how these mechanisms occur in specific brain cell types is still poorly understood. Rac1 is a member of the Rho family of small GTPases with essential roles in multiple cellular processes, including cell differentiation and axonal growth. Here we used different brain cell types and tissues, including oligodendrocytes, microglia, astrocytes, cortical and hippocampal neurons, and optical nerve, to show that classical Rho GTPases express mRNAs with alternative 3' UTRs differently, by gene- and cell- specific mechanisms. In particular, we show that Rac1 originate mRNA isoforms with longer 3' UTRs specifically during neurite growth of cortical, but not hippocampal neurons. Furthermore, we demonstrate that the longest Rac1 3' UTR is necessary for driving the mRNA to the neurites, and also for neurite outgrowth in cortical neurons. Our results indicate that the expression of Rac1 longer 3' UTR is a gene and cell-type specific mechanism in the brain, with a new physiological function in cortical neuron differentiation. Copyright © 2017 Elsevier B.V. All rights reserved.

DMPD: Fifty years of interferon research: aiming at a moving target. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available mmunity. 2006 Sep;25(3):343-8. (.png) (.svg) (.html) (.csml) Show Fifty years of interferon research: aiming at a moving target. Pubm...edID 16979566 Title Fifty years of interferon research: aiming at a moving target.

A key role for poly(ADP-ribose polymerase 3 in ectodermal specification and neural crest development.

Directory of Open Access Journals (Sweden)

Michèle Rouleau

2011-01-01

Full Text Available The PARP family member poly(ADP-ribose polymerase 3 (PARP3 is structurally related to the well characterized PARP1 that orchestrates cellular responses to DNA strand breaks and cell death by the synthesis of poly(ADP-ribose. In contrast to PARP1 and PARP2, the functions of PARP3 are undefined. Here, we reveal critical functions for PARP3 during vertebrate development.We have used several in vitro and in vivo approaches to examine the possible functions of PARP3 as a transcriptional regulator, a function suggested from its previously reported association with several Polycomb group (PcG proteins. We demonstrate that PARP3 gene occupancy in the human neuroblastoma cell line SK-N-SH occurs preferentially with developmental genes regulating cell fate specification, tissue patterning, craniofacial development and neurogenesis. Addressing the significance of this association during zebrafish development, we show that morpholino oligonucleotide-directed inhibition of parp3 expression in zebrafish impairs the expression of the neural crest cell specifier sox9a and of dlx3b/dlx4b, the formation of cranial sensory placodes, inner ears and pectoral fins. It delays pigmentation and severely impedes the development of the median fin fold and tail bud.Our findings demonstrate that Parp3 is crucial in the early stages of zebrafish development, possibly by exerting its transcriptional regulatory functions as early as during the specification of the neural plate border.

Development and application of the RE-AIM QuEST mixed methods framework for program evaluation.

Science.gov (United States)

Forman, Jane; Heisler, Michele; Damschroder, Laura J; Kaselitz, Elizabeth; Kerr, Eve A

2017-06-01

To increase the likelihood of successful implementation of interventions and promote dissemination across real-world settings, it is essential to evaluate outcomes related to dimensions other than Effectiveness alone. Glasgow and colleagues' RE-AIM framework specifies four additional types of outcomes that are important to decision-makers: Reach, Adoption, Implementation (including cost), and Maintenance. To further strengthen RE-AIM, we propose integrating qualitative assessments in an expanded framework: RE-AIM Qualitative Evaluation for Systematic Translation (RE-AIM QuEST), a mixed methods framework. RE-AIM QuEST guides formative evaluation to identify real-time implementation barriers and explain how implementation context may influence translation to additional settings. RE-AIM QuEST was used to evaluate a pharmacist-led hypertension management intervention at 3 VA facilities in 2008-2009. We systematically reviewed each of the five RE-AIM dimensions and created open-ended companion questions to quantitative measures and identified qualitative and quantitative data sources, measures, and analyses. To illustrate use of the RE-AIM QuEST framework, we provide examples of real-time, coordinated use of quantitative process measures and qualitative methods to identify site-specific issues, and retrospective use of these data sources and analyses to understand variation across sites and explain outcomes. For example, in the Reach dimension, we conducted real-time measurement of enrollment across sites and used qualitative data to better understand and address barriers at a low-enrollment site. The RE-AIM QuEST framework may be a useful tool for improving interventions in real-time, for understanding retrospectively why an intervention did or did not work, and for enhancing its sustainability and translation to other settings.

The feasibility of producing patient-specific acrylic cranioplasty implants with a low-cost 3D printer.

Science.gov (United States)

Tan, Eddie T W; Ling, Ji Min; Dinesh, Shree Kumar

2016-05-01

OBJECT Commercially available, preformed patient-specific cranioplasty implants are anatomically accurate but costly. Acrylic bone cement is a commonly used alternative. However, the manual shaping of the bone cement is difficult and may not lead to a satisfactory implant in some cases. The object of this study was to determine the feasibility of fabricating molds using a commercial low-cost 3D printer for the purpose of producing patient-specific acrylic cranioplasty implants. METHODS Using data from a high-resolution brain CT scan of a patient with a calvarial defect posthemicraniectomy, a skull phantom and a mold were generated with computer software and fabricated with the 3D printer using the fused deposition modeling method. The mold was used as a template to shape the acrylic implant, which was formed via a polymerization reaction. The resulting implant was fitted to the skull phantom and the cranial index of symmetry was determined. RESULTS The skull phantom and mold were successfully fabricated with the 3D printer. The application of acrylic bone cement to the mold was simple and straightforward. The resulting implant did not require further adjustment or drilling prior to being fitted to the skull phantom. The cranial index of symmetry was 96.2% (the cranial index of symmetry is 100% for a perfectly symmetrical skull). CONCLUSIONS This study showed that it is feasible to produce patient-specific acrylic cranioplasty implants with a low-cost 3D printer. Further studies are required to determine applicability in the clinical setting. This promising technique has the potential to bring personalized medicine to more patients around the world.

TCR Gene Transfer: MAGE-C2/HLA-A2 and MAGE-A3/HLA-DP4 Epitopes as Melanoma-Specific Immune Targets

Directory of Open Access Journals (Sweden)

Trudy Straetemans

2012-01-01

Full Text Available Adoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients. Further development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent “on-target” reactivity towards healthy tissues and at the same time direct a clinically effective response towards tumor tissues. Candidate epitopes that meet these criteria are MAGE-C2336-344/HLA-A2 (MC2/A2 and MAGE-A3243-258/HLA-DP4 (MA3/DP4. We molecularly characterized TCRαβ genes of an MC2/A2-specific CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma patients who responded clinically to MAGE vaccination. We identified MC2/A2 and MA3/DP4-specific TCR-Vα3/Vβ28 and TCR-Vα38/Vβ2 chains and validated these TCRs in vitro upon gene transfer into primary human T cells. The MC2 and MA3 TCR were surface-expressed and mediated CD8 T-cell functions towards melanoma cell lines and CD4 T-cell functions towards dendritic cells, respectively. We intend to start testing these MAGE-specific TCRs in phase I clinical trial.

MO-H-19A-03: Patient Specific Bolus with 3D Printing Technology for Electron Radiotherapy

International Nuclear Information System (INIS)

Zou, W; Swann, B; Siderits, R; McKenna, M; Khan, A; Yue, N; Zhang, M; Fisher, T

2014-01-01

Purpose: Bolus is widely used in electron radiotherapy to achieve desired dose distribution. 3D printing technologies provide clinicians with easy access to fabricate patient specific bolus accommodating patient body surface irregularities and tissue inhomogeneity. This study presents the design and the clinical workflow of 3D printed bolus for patient electron therapy in our clinic. Methods: Patient simulation CT images free of bolus were exported from treatment planning system (TPS) to an in-house developed software package. Bolus with known material properties was designed in the software package and then exported back to the TPS as a structure. Dose calculation was carried out to examine the coverage of the target. After satisfying dose distribution was achieved, the bolus structure was transferred in Standard Tessellation Language (STL) file format for the 3D printer to generate the machine codes for printing. Upon receiving printed bolus, a quick quality assurance was performed with patient resimulated with bolus in place to verify the bolus dosimetric property before treatment started. Results: A patient specific bolus for electron radiotherapy was designed and fabricated in Form 1 3D printer with methacrylate photopolymer resin. Satisfying dose distribution was achieved in patient with bolus setup. Treatment was successfully finished for one patient with the 3D printed bolus. Conclusion: The electron bolus fabrication with 3D printing technology was successfully implemented in clinic practice

MO-H-19A-03: Patient Specific Bolus with 3D Printing Technology for Electron Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Zou, W; Swann, B; Siderits, R; McKenna, M; Khan, A; Yue, N; Zhang, M [Rutgers University, New Brunswick, NJ (United States); Fisher, T [Memorial Medical Center, Modesto, CA (United States)

2014-06-15

Purpose: Bolus is widely used in electron radiotherapy to achieve desired dose distribution. 3D printing technologies provide clinicians with easy access to fabricate patient specific bolus accommodating patient body surface irregularities and tissue inhomogeneity. This study presents the design and the clinical workflow of 3D printed bolus for patient electron therapy in our clinic. Methods: Patient simulation CT images free of bolus were exported from treatment planning system (TPS) to an in-house developed software package. Bolus with known material properties was designed in the software package and then exported back to the TPS as a structure. Dose calculation was carried out to examine the coverage of the target. After satisfying dose distribution was achieved, the bolus structure was transferred in Standard Tessellation Language (STL) file format for the 3D printer to generate the machine codes for printing. Upon receiving printed bolus, a quick quality assurance was performed with patient resimulated with bolus in place to verify the bolus dosimetric property before treatment started. Results: A patient specific bolus for electron radiotherapy was designed and fabricated in Form 1 3D printer with methacrylate photopolymer resin. Satisfying dose distribution was achieved in patient with bolus setup. Treatment was successfully finished for one patient with the 3D printed bolus. Conclusion: The electron bolus fabrication with 3D printing technology was successfully implemented in clinic practice.

Cell-Specific Actions of a Human LHX3 Gene Enhancer During Pituitary and Spinal Cord Development

Science.gov (United States)

Park, Soyoung; Mullen, Rachel D.

2013-01-01

The LIM class of homeodomain protein 3 (LHX3) transcription factor is essential for pituitary gland and nervous system development in mammals. In humans, mutations in the LHX3 gene underlie complex pediatric syndromes featuring deficits in anterior pituitary hormones and defects in the nervous system. The mechanisms that control temporal and spatial expression of the LHX3 gene are poorly understood. The proximal promoters of the human LHX3 gene are insufficient to guide expression in vivo and downstream elements including a conserved enhancer region appear to play a role in tissue-specific expression in the pituitary and nervous system. Here we characterized the activity of this downstream enhancer region in regulating gene expression at the cellular level during development. Human LHX3 enhancer-driven Cre reporter transgenic mice were generated to facilitate studies of enhancer actions. The downstream LHX3 enhancer primarily guides gene transcription in α-glycoprotein subunit -expressing cells secreting the TSHβ, LHβ, or FSHβ hormones and expressing the GATA2 and steroidogenic factor 1 transcription factors. In the developing nervous system, the enhancer serves as a targeting module active in V2a interneurons. These results demonstrate that the downstream LHX3 enhancer is important in specific endocrine and neural cell types but also indicate that additional regulatory elements are likely involved in LHX3 gene expression. Furthermore, these studies revealed significant gonadotrope cell heterogeneity during pituitary development, providing insights into the cellular physiology of this key reproductive regulatory cell. The human LHX3 enhancer-driven Cre reporter transgenic mice also provide a valuable tool for further developmental studies of cell determination and differentiation in the pituitary and nervous system. PMID:24100213

SU-E-T-316: The Design of a Risk Index Method for 3D Patient Specific QA

Energy Technology Data Exchange (ETDEWEB)

Cho, W; Wu, H [Seoul National University Hospital, Seoul (Korea, Republic of); Xing, L [Stanford University, Stanford, CA (United States); Suh, T [Catholic UniversityMedical College, Seoul (Korea, Republic of)

2014-06-01

Purpose: To suggest a new guidance for the evaluation of 3D patient specific QA, a structure-specific risk-index (RI) method was designed and implemented. Methods: A new algorithm was designed to assign the score of Pass, Fail or Pass with Risk to all 3D voxels in each structure by improving a conventional Gamma Index (GI) algorithm, which implied the degree of the risk of under-dose to the treatment target or over-dose to the organ at risks (OAR). Structure-specific distance to agreement (DTOA), dose difference and minimum checkable dose were applied to the GI algorithm, and additional parameters such as dose gradient factor and dose limit of structures were used to the RI method. Maximum passing rate (PR) and minimum PR were designed and calculated for each structure with the RI method. 3D doses were acquired from a spine SBRT plan by simulating the shift of beam iso-center, and tested to show the feasibility of the suggested method. Results: When the iso-center was shifted by 1 mm, 2 mm, and 3 mm, the PR of conventional GI method between shifted and non-shifted 3D doses were 99.9%, 97.4%, and 89.7% for PTV, 99.8%, 84.8%, and 63.2% for spinal cord, and 100%, 99.5%, 91.7% for right lung. The minimum PRs from the RI method were 98.9%, 96.9%, and 89.5% for PTV, and 96.1%, 79.3%, 57.5% for spinal cord, and 92.5%, 92.0%, 84.4% for right lung, respectively. The maximum PRs from the RI method were equal or less than the PRs from the conventional GI evaluation. Conclusion: Designed 3D RI method showed more strict acceptance level than the conventional GI method, especially for OARs. The RI method is expected to give the degrees of risks in the delivered doses, as well as the degrees of agreements between calculated 3D doses and measured (or simulated) 3D doses.

SU-E-T-316: The Design of a Risk Index Method for 3D Patient Specific QA

International Nuclear Information System (INIS)

Cho, W; Wu, H; Xing, L; Suh, T

2014-01-01

Purpose: To suggest a new guidance for the evaluation of 3D patient specific QA, a structure-specific risk-index (RI) method was designed and implemented. Methods: A new algorithm was designed to assign the score of Pass, Fail or Pass with Risk to all 3D voxels in each structure by improving a conventional Gamma Index (GI) algorithm, which implied the degree of the risk of under-dose to the treatment target or over-dose to the organ at risks (OAR). Structure-specific distance to agreement (DTOA), dose difference and minimum checkable dose were applied to the GI algorithm, and additional parameters such as dose gradient factor and dose limit of structures were used to the RI method. Maximum passing rate (PR) and minimum PR were designed and calculated for each structure with the RI method. 3D doses were acquired from a spine SBRT plan by simulating the shift of beam iso-center, and tested to show the feasibility of the suggested method. Results: When the iso-center was shifted by 1 mm, 2 mm, and 3 mm, the PR of conventional GI method between shifted and non-shifted 3D doses were 99.9%, 97.4%, and 89.7% for PTV, 99.8%, 84.8%, and 63.2% for spinal cord, and 100%, 99.5%, 91.7% for right lung. The minimum PRs from the RI method were 98.9%, 96.9%, and 89.5% for PTV, and 96.1%, 79.3%, 57.5% for spinal cord, and 92.5%, 92.0%, 84.4% for right lung, respectively. The maximum PRs from the RI method were equal or less than the PRs from the conventional GI evaluation. Conclusion: Designed 3D RI method showed more strict acceptance level than the conventional GI method, especially for OARs. The RI method is expected to give the degrees of risks in the delivered doses, as well as the degrees of agreements between calculated 3D doses and measured (or simulated) 3D doses

WE-D-BRA-05: Pseudo In Vivo Patient Dosimetry Using a 3D-Printed Patient-Specific Phantom

International Nuclear Information System (INIS)

Ger, R; Craft, DF; Burgett, EA; Price, RR; Kry, SF; Howell, RM

2015-01-01

Purpose: To test the feasibility of using 3D-printed patient-specific phantoms for intensity-modulated radiation therapy (IMRT) quality assurance (QA). Methods: We created a patient-specific whole-head phantom using a 3D printer. The printer data file was created from high-resolution DICOM computed tomography (CT) images of 3-year old child treated at our institution for medulloblastoma. A custom-modified extruder system was used to create tissue-equivalent materials. For the printing process, the Hounsfield Units from the CT images were converted to proportional volumetric densities. A 5-field IMRT plan was created from the patient CT and delivered to the 3D- phantom. Dose was measured by an ion chamber placed through the eye. The ion chamber was placed at the posterior edge of the planning target volume in a high dose gradient region. CT scans of the patient and 3D-phantom were fused by using commercial treatment planning software (TPS). The patient’s plan was calculated on the phantom CT images. The ion chamber’s active volume was delineated in the TPS; dose per field and total dose were obtained. Measured and calculated doses were compared. Results: The 3D-phantom dimensions and tissue densities were in good agreement with the patient. However, because of a printing error, there was a large discrepancy in the density in the frontal cortex. The calculated and measured treatment plan doses were 1.74 Gy and 1.72 Gy, respectively. For individual fields, the absolute dose difference between measured and calculated values was on average 3.50%. Conclusion: This study demonstrated the feasibility of using 3D-printed patient-specific phantoms for IMRT QA. Such phantoms would be particularly advantageous for complex IMRT treatment plans featuring high dose gradients and/or for anatomical sites with high variation in tissue densities. Our preliminary findings are promising. We anticipate that, once the printing process is further refined, the agreement between

WE-D-BRA-05: Pseudo In Vivo Patient Dosimetry Using a 3D-Printed Patient-Specific Phantom

Energy Technology Data Exchange (ETDEWEB)

Ger, R; Craft, DF [The University of Texas Graduate School of Biomedical Sciences (United States); Burgett, EA [Idaho State University, Pocatello, idaho (United States); Price, RR [RANDJ Consulting, Frederick, MD (United States); Kry, SF; Howell, RM [The University of Texas Graduate School of Biomedical Sciences (United States); The University of Texas MD Anderson Cancer Ctr., Houston, TX (United States)

2015-06-15

Purpose: To test the feasibility of using 3D-printed patient-specific phantoms for intensity-modulated radiation therapy (IMRT) quality assurance (QA). Methods: We created a patient-specific whole-head phantom using a 3D printer. The printer data file was created from high-resolution DICOM computed tomography (CT) images of 3-year old child treated at our institution for medulloblastoma. A custom-modified extruder system was used to create tissue-equivalent materials. For the printing process, the Hounsfield Units from the CT images were converted to proportional volumetric densities. A 5-field IMRT plan was created from the patient CT and delivered to the 3D- phantom. Dose was measured by an ion chamber placed through the eye. The ion chamber was placed at the posterior edge of the planning target volume in a high dose gradient region. CT scans of the patient and 3D-phantom were fused by using commercial treatment planning software (TPS). The patient’s plan was calculated on the phantom CT images. The ion chamber’s active volume was delineated in the TPS; dose per field and total dose were obtained. Measured and calculated doses were compared. Results: The 3D-phantom dimensions and tissue densities were in good agreement with the patient. However, because of a printing error, there was a large discrepancy in the density in the frontal cortex. The calculated and measured treatment plan doses were 1.74 Gy and 1.72 Gy, respectively. For individual fields, the absolute dose difference between measured and calculated values was on average 3.50%. Conclusion: This study demonstrated the feasibility of using 3D-printed patient-specific phantoms for IMRT QA. Such phantoms would be particularly advantageous for complex IMRT treatment plans featuring high dose gradients and/or for anatomical sites with high variation in tissue densities. Our preliminary findings are promising. We anticipate that, once the printing process is further refined, the agreement between

SLC2A3 single-nucleotide polymorphism and duplication influence cognitive processing and population-specific risk for attention-deficit/hyperactivity disorder.

Science.gov (United States)

Merker, Sören; Reif, Andreas; Ziegler, Georg C; Weber, Heike; Mayer, Ute; Ehlis, Ann-Christine; Conzelmann, Annette; Johansson, Stefan; Müller-Reible, Clemens; Nanda, Indrajit; Haaf, Thomas; Ullmann, Reinhard; Romanos, Marcel; Fallgatter, Andreas J; Pauli, Paul; Strekalova, Tatyana; Jansch, Charline; Vasquez, Alejandro Arias; Haavik, Jan; Ribasés, Marta; Ramos-Quiroga, Josep Antoni; Buitelaar, Jan K; Franke, Barbara; Lesch, Klaus-Peter

2017-07-01

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurodevelopmental disorder with profound cognitive, behavioral, and psychosocial impairments with persistence across the life cycle. Our initial genome-wide screening approach for copy number variants (CNVs) in ADHD implicated a duplication of SLC2A3, encoding glucose transporter-3 (GLUT3). GLUT3 plays a critical role in cerebral glucose metabolism, providing energy for the activity of neurons, which, in turn, moderates the excitatory-inhibitory balance impacting both brain development and activity-dependent neural plasticity. We therefore aimed to provide additional genetic and functional evidence for GLUT3 dysfunction in ADHD. Case-control association analyses of SLC2A3 single-nucleotide polymorphisms (SNPs) and CNVs were conducted in several European cohorts of patients with childhood and adult ADHD (SNP, n = 1,886 vs. 1,988; CNV, n = 1,692 vs. 1,721). These studies were complemented by SLC2A3 expression analyses in peripheral cells, functional EEG recordings during neurocognitive tasks, and ratings of food energy content. Meta-analysis of all cohorts detected an association of SNP rs12842 with ADHD. While CNV analysis detected a population-specific enrichment of SLC2A3 duplications only in German ADHD patients, the CNV + rs12842 haplotype influenced ADHD risk in both the German and Spanish cohorts. Duplication carriers displayed elevated SLC2A3 mRNA expression in peripheral blood cells and altered event-related potentials reflecting deficits in working memory and cognitive response control, both endophenotypic traits of ADHD, and an underestimation of energy units of high-caloric food. Taken together, our results indicate that both common and rare SLC2A3 variation impacting regulation of neuronal glucose utilization and energy homeostasis may result in neurocognitive deficits known to contribute to ADHD risk. © 2017 Association for Child and Adolescent Mental Health.

AIMES Final Technical Report

Energy Technology Data Exchange (ETDEWEB)

Katz, Daniel S [Univ. of Illinois, Urbana-Champaign, IL (United States). National Center for Supercomputing Applications (NCSA); Jha, Shantenu [Rutgers Univ., New Brunswick, NJ (United States); Weissman, Jon [Univ. of Minnesota, Minneapolis, MN (United States); Turilli, Matteo [Rutgers Univ., New Brunswick, NJ (United States)

2017-01-31

This is the final technical report for the AIMES project. Many important advances in science and engineering are due to large-scale distributed computing. Notwithstanding this reliance, we are still learning how to design and deploy large-scale production Distributed Computing Infrastructures (DCI). This is evidenced by missing design principles for DCI, and an absence of generally acceptable and usable distributed computing abstractions. The AIMES project was conceived against this backdrop, following on the heels of a comprehensive survey of scientific distributed applications. AIMES laid the foundations to address the tripartite challenge of dynamic resource management, integrating information, and portable and interoperable distributed applications. Four abstractions were defined and implemented: skeleton, resource bundle, pilot, and execution strategy. The four abstractions were implemented into software modules and then aggregated into the AIMES middleware. This middleware successfully integrates information across the application layer (skeletons) and resource layer (Bundles), derives a suitable execution strategy for the given skeleton and enacts its execution by means of pilots on one or more resources, depending on the application requirements, and resource availabilities and capabilities.

Affect and person specificity in mood regulation

OpenAIRE

Corby, Emma Kate

2007-01-01

489 university students in three countries completed questionnaires in a study investigating affect and person specificity in the use of mood regulation strategies. The major aims of the study were to (1) describe the relationship between specific affective states and the strategies utilised, (2) explore the role that individual differences variables played in the tendency to use particular strategies, and (3) measure the impact that the use of different strategies had upon subjective well-b...

Strategically Assessing International Business Course-Specific Learning Aims

Science.gov (United States)

Kashlak, Roger; Lorenzi, Peter; Cummings, Jeffrey

2007-01-01

During the past 30 years, there have been calls for universities and business schools to internationalize curriculum, students and faculty. As most U.S. business schools have added international components to their respective programs, the assessment of these programs was subsequently recommended from accreditation and competitive perspectives. To…

The Nanos3-3'UTR is required for germ cell specific NANOS3 expression in mouse embryos.

Directory of Open Access Journals (Sweden)

Hitomi Suzuki

Full Text Available BACKGROUND: The regulation of gene expression via a 3' untranslated region (UTR plays essential roles in the discrimination of the germ cell lineage from somatic cells during embryogenesis. This is fundamental to the continuation of a species. Mouse NANOS3 is an essential protein required for the germ cell maintenance and is specifically expressed in these cells. However, the regulatory mechanisms that restrict the expression of this gene in the germ cells is largely unknown at present. METHODOLOGY/PRINCIPAL FINDINGS: In our current study, we show that differences in the stability of Nanos3 mRNA between germ cells and somatic cells is brought about in a 3'UTR-dependent manner in mouse embryos. Although Nanos3 is transcribed in both cell lineages, it is efficiently translated only in the germ lineage. We also find that the translational suppression of NANOS3 in somatic cells is caused by a 3'UTR-mediated mRNA destabilizing mechanism. Surprisingly, even when under the control of the CAG promoter which induces strong ubiquitous transcription in both germ cells and somatic cells, the addition of the Nanos3-3'UTR sequence to the coding region of exogenous gene was effective in restricting protein expression in germ cells. CONCLUSIONS/SIGNIFICANCE: Our current study thus suggests that Nanos3-3'UTR has an essential role in translational control in the mouse embryo.

Tissue-specific and cation/anion-specific DNA methylation variations occurred in C. virgata in response to salinity stress.

Directory of Open Access Journals (Sweden)

Xiang Gao

Full Text Available Salinity is a widespread environmental problem limiting productivity and growth of plants. Halophytes which can adapt and resist certain salt stress have various mechanisms to defend the higher salinity and alkalinity, and epigenetic mechanisms especially DNA methylation may play important roles in plant adaptability and plasticity. In this study, we aimed to investigate the different influences of various single salts (NaCl, Na2SO4, NaHCO3, Na2CO3 and their mixed salts on halophyte Chloris. virgata from the DNA methylation prospective, and discover the underlying relationships between specific DNA methylation variations and specific cations/anions through the methylation-sensitive amplification polymorphism analysis. The results showed that the effects on DNA methylation variations of single salts were ranked as follows: Na2CO3> NaHCO3> Na2SO4> NaCl, and their mixed salts exerted tissue-specific effects on C. virgata seedlings. Eight types of DNA methylation variations were detected and defined in C. virgata according to the specific cations/anions existed in stressful solutions; in addition, mix-specific and higher pH-specific bands were the main type in leaves and roots independently. These findings suggested that mixed salts were not the simple combination of single salts. Furthermore, not only single salts but also mixed salts showed tissue-specific and cations/anions-specific DNA methylation variations.

Tissue-specific and cation/anion-specific DNA methylation variations occurred in C. virgata in response to salinity stress.

Science.gov (United States)

Gao, Xiang; Cao, Donghui; Liu, Jie; Wang, Xiaoping; Geng, Shujuan; Liu, Bao; Shi, Decheng

2013-01-01

Salinity is a widespread environmental problem limiting productivity and growth of plants. Halophytes which can adapt and resist certain salt stress have various mechanisms to defend the higher salinity and alkalinity, and epigenetic mechanisms especially DNA methylation may play important roles in plant adaptability and plasticity. In this study, we aimed to investigate the different influences of various single salts (NaCl, Na2SO4, NaHCO3, Na2CO3) and their mixed salts on halophyte Chloris. virgata from the DNA methylation prospective, and discover the underlying relationships between specific DNA methylation variations and specific cations/anions through the methylation-sensitive amplification polymorphism analysis. The results showed that the effects on DNA methylation variations of single salts were ranked as follows: Na2CO3> NaHCO3> Na2SO4> NaCl, and their mixed salts exerted tissue-specific effects on C. virgata seedlings. Eight types of DNA methylation variations were detected and defined in C. virgata according to the specific cations/anions existed in stressful solutions; in addition, mix-specific and higher pH-specific bands were the main type in leaves and roots independently. These findings suggested that mixed salts were not the simple combination of single salts. Furthermore, not only single salts but also mixed salts showed tissue-specific and cations/anions-specific DNA methylation variations.

Tlx3 promotes glutamatergic neuronal subtype specification through direct interactions with the chromatin modifier CBP.

Directory of Open Access Journals (Sweden)

Atsushi Shimomura

Full Text Available Nervous system development relies on the generation of precise numbers of excitatory and inhibitory neurons. The homeodomain transcription factor, T-cell leukemia 3 (Tlx3, functions as the master neuronal fate regulator by instructively promoting the specification of glutamatergic excitatory neurons and suppressing the specification of gamma-aminobutyric acid (GABAergic neurons. However, how Tlx3 promotes glutamatergic neuronal subtype specification is poorly understood. In this study, we found that Tlx3 directly interacts with the epigenetic co-activator cyclic adenosine monophosphate (cAMP-response element-binding protein (CREB-binding protein (CBP and that the Tlx3 homeodomain is essential for this interaction. The interaction between Tlx3 and CBP was enhanced by the three amino acid loop extension (TALE-class homeodomain transcription factor, pre-B-cell leukemia transcription factor 3 (Pbx3. Using mouse embryonic stem (ES cells stably expressing Tlx3, we found that the interaction between Tlx3 and CBP became detectable only after these Tlx3-expressing ES cells were committed to a neural lineage, which coincided with increased Pbx3 expression during neural differentiation from ES cells. Forced expression of mutated Tlx3 lacking the homeodomain in ES cells undergoing neural differentiation resulted in significantly reduced expression of glutamatergic neuronal subtype markers, but had little effect on the expression on pan neural markers. Collectively, our results strongly suggest that functional interplay between Tlx3 and CBP plays a critical role in neuronal subtype specification, providing novel insights into the epigenetic regulatory mechanism that modulates the transcriptional efficacy of a selective set of neuronal subtype-specific genes during differentiation.

Analysis specifications for the CC3 biosphere model biotrac

Energy Technology Data Exchange (ETDEWEB)

Szekely, J G; Wojciechowski, L C; Stephens, M E; Halliday, H A

1994-12-01

The CC3 (Canadian Concept, generation 3) model BIOTRAC (Biosphere Transport and Consequences) describes the movement in the biosphere of releases from an underground disposal vault, and the consequent radiological dose to a reference individual. Concentrations of toxic substances in different parts of the biosphere are also calculated. BIOTRAC was created specifically for the postclosure analyses of the Environmental Impact Statement that AECL is preparing on the concept for disposal of Canada`s nuclear fuel waste. The model relies on certain assumptions and constraints on the system, which are described by Davis et al. Accordingly, great care must be exercised if BIOTRAC is used for any other purpose.

Nanomedicinal products: a survey on specific toxicity and side effects

Directory of Open Access Journals (Sweden)

Brand W

2017-08-01

Full Text Available Walter Brand,1,* Cornelle W Noorlander,1,* Christina Giannakou,2,3 Wim H De Jong,2 Myrna W Kooi,1 Margriet VDZ Park,2 Rob J Vandebriel,2 Irene EM Bosselaers,4 Joep HG Scholl,5 Robert E Geertsma2 1Centre for Safety of Substances and Products, 2Centre for Health Protection, National Institute for Public Health and the Environment (RIVM, Bilthoven, 3Department of Toxicogenomics, Maastricht University, Maastricht, 4Section Pharmacology, Toxicology and Pharmacokinetics, Medicines Evaluation Board (CBG-MEB, Utrecht, 5Research & Analysis Department, Netherlands Pharmacovigilance Centre Lareb, ‘s-Hertogenbosch, the Netherlands *These authors contributed equally to this work Abstract: Due to their specific properties and pharmacokinetics, nanomedicinal products (NMPs may present different toxicity and side effects compared to non-nanoformulated, conventional medicines. To facilitate the safety assessment of NMPs, we aimed to gain insight into toxic effects specific for NMPs by systematically analyzing the available toxicity data on approved NMPs in the European Union. In addition, by comparing five sets of products with the same active pharmaceutical ingredient (API in a conventional formulation versus a nanoformulation, we aimed to identify any side effects specific for the nano aspect of NMPs. The objective was to investigate whether specific toxicity could be related to certain structural types of NMPs and whether a nanoformulation of an API altered the nature of side effects of the product in humans compared to a conventional formulation. The survey of toxicity data did not reveal nanospecific toxicity that could be related to certain types of structures of NMPs, other than those reported previously in relation to accumulation of iron nanoparticles (NPs. However, given the limited data for some of the product groups or toxicological end points in the analysis, conclusions with regard to (a lack of potential nanomedicine-specific effects need to be

Bio-AIMS Collection of Chemoinformatics Web Tools based on Molecular Graph Information and Artificial Intelligence Models.

Science.gov (United States)

Munteanu, Cristian R; Gonzalez-Diaz, Humberto; Garcia, Rafael; Loza, Mabel; Pazos, Alejandro

2015-01-01

The molecular information encoding into molecular descriptors is the first step into in silico Chemoinformatics methods in Drug Design. The Machine Learning methods are a complex solution to find prediction models for specific biological properties of molecules. These models connect the molecular structure information such as atom connectivity (molecular graphs) or physical-chemical properties of an atom/group of atoms to the molecular activity (Quantitative Structure - Activity Relationship, QSAR). Due to the complexity of the proteins, the prediction of their activity is a complicated task and the interpretation of the models is more difficult. The current review presents a series of 11 prediction models for proteins, implemented as free Web tools on an Artificial Intelligence Model Server in Biosciences, Bio-AIMS (http://bio-aims.udc.es/TargetPred.php). Six tools predict protein activity, two models evaluate drug - protein target interactions and the other three calculate protein - protein interactions. The input information is based on the protein 3D structure for nine models, 1D peptide amino acid sequence for three tools and drug SMILES formulas for two servers. The molecular graph descriptor-based Machine Learning models could be useful tools for in silico screening of new peptides/proteins as future drug targets for specific treatments.

Cell type-specific roles of Jak3 in IL-2-induced proliferative signal transduction

International Nuclear Information System (INIS)

Fujii, Hodaka

2007-01-01

Binding of interleukin-2 (IL-2) to its specific receptor induces activation of two members of Jak family protein tyrosine kinases, Jak1 and Jak3. An IL-2 receptor (IL-2R)-reconstituted NIH 3T3 fibroblast cell line proliferates in response to IL-2 only when hematopoietic lineage-specific Jak3 is ectopically expressed. However, the mechanism of Jak3-dependent proliferation in the fibroblast cell line is not known. Here, I showed that Jak3 expression is dispensable for IL-2-induced activation of Jak1 and Stat proteins and expression of nuclear proto-oncogenes in the IL-2R-reconstituted fibroblast cell line. Jak3 expression markedly enhanced these IL-2-induced signaling events. In contrast, Jak3 expression was essential for induction of cyclin genes involved in the G1-S transition. These data suggest a critical role of Jak3 in IL-2 signaling in the fibroblast cell line and may provide further insight into the cell type-specific mechanism of cytokine signaling

Cell type-specific roles of Jak3 in IL-2-induced proliferative signal transduction

Science.gov (United States)

Fujii, Hodaka

2007-01-01

Binding of IL-2 to its specific receptor induces activation of two members of Jak family protein tyrosine kinases, Jak1 and Jak3. An IL-2R-reconstituted NIH 3T3 fibroblast cell line proliferates in response to IL-2 only when hematopoietic lineage-specific Jak3 is ectopically expressed. However, the mechanism of Jak3-dependent proliferation in the fibroblast cell line is not known. Here, I showed that Jak3 expression is dispensable for IL-2-induced activation of Jak1 and Stat proteins and expression of nuclear proto-oncogenes in the IL-2R-reconstituted fibroblast cell line. However, Jak3 expression markedly enhanced these IL-2-induced signaling events. In contrast, Jak3 expression was essential for induction of cyclin genes involved in the G1-S transition. These data suggest a critical role of Jak3 in IL-2 signaling in the fibroblast cell line and may provide further insight into the cell type-specific mechanism of cytokine signaling. PMID:17266928

Patient specific 3D visualisation of human brain | Baichoo ...

African Journals Online (AJOL)

University of Mauritius Research Journal. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 15, No 1 (2009) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. Patient specific 3D visualisation of human brain.

Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System

Directory of Open Access Journals (Sweden)

Raul Vizcardo

2018-03-01

Full Text Available Summary: Induced pluripotent stem cell (iPSC-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4+CD8+ double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ+ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs. iTEs exhibit phenotypic and functional similarities to naive T cells both in vitro and in vivo, including the capacity for expansion, memory formation, and tumor suppression. These data illustrate the limitations of current methods and provide a tool to develop the next generation of iPSC-based antigen-specific immunotherapies. : A barrier for clinical application of iPSC-derived CD8 T cells using OP9/DLL1 is their abnormal biology. Vizcardo et al. show that a 3D thymic culture system enables the generation of a homogeneous antigen-specific T cell subset, named iTEs, which closely mimics naive T cells and exhibits potent anti-tumor activity. Keywords: thymopoiesis, T cell differentiation, iPSC differentiation, adoptive cell transfer, naïve T cell, recent rhymic emigrants, fetal thymus organ culture, immunotherapy, 3D culture, tumor antigen specific T cell

The technique for 3D printing patient-specific models for auricular reconstruction.

Science.gov (United States)

Flores, Roberto L; Liss, Hannah; Raffaelli, Samuel; Humayun, Aiza; Khouri, Kimberly S; Coelho, Paulo G; Witek, Lukasz

2017-06-01

Currently, surgeons approach autogenous microtia repair by creating a two-dimensional (2D) tracing of the unaffected ear to approximate a three-dimensional (3D) construct, a difficult process. To address these shortcomings, this study introduces the fabrication of patient-specific, sterilizable 3D printed auricular model for autogenous auricular reconstruction. A high-resolution 3D digital photograph was captured of the patient's unaffected ear and surrounding anatomic structures. The photographs were exported and uploaded into Amira, for transformation into a digital (.stl) model, which was imported into Blender, an open source software platform for digital modification of data. The unaffected auricle as digitally isolated and inverted to render a model for the contralateral side. The depths of the scapha, triangular fossa, and cymba were deepened to accentuate their contours. Extra relief was added to the helical root to further distinguish this structure. The ear was then digitally deconstructed and separated into its individual auricular components for reconstruction. The completed ear and its individual components were 3D printed using polylactic acid filament and sterilized following manufacturer specifications. The sterilized models were brought to the operating room to be utilized by the surgeon. The models allowed for more accurate anatomic measurements compared to 2D tracings, which reduced the degree of estimation required by surgeons. Approximately 20 g of the PLA filament were utilized for the construction of these models, yielding a total material cost of approximately $1. Using the methodology detailed in this report, as well as departmentally available resources (3D digital photography and 3D printing), a sterilizable, patient-specific, and inexpensive 3D auricular model was fabricated to be used intraoperatively. This technique of printing customized-to-patient models for surgeons to use as 'guides' shows great promise. Copyright © 2017 European

Outcome and safety analysis of 3D printed patient specific pedicle screw jigs for complex spinal deformities: A comparative study.

Science.gov (United States)

Garg, Bhavuk; Gupta, Manish; Singh, Menaka; Kalyanasundaram, Dinesh

2018-05-03

Spinal deformities are very challenging to treat and have a great risk of neurological complications due to hardware placement during corrective surgery. Various techniques have been introduced to ensure safe and accurate placement of pedicle screws. Patient-specific screw guides with pre-drawn and pre-validated trajectory seems to be an attractive option. We have focused on developing 3D printing technique for complex spinal deformities in India. This study also aimed to compare the placement of pedicle screw with 3D printing and free hand technique. This is a retrospective comparative clinical study at an academic institutional setting. A total of 20 patients were enrolled during the study, 10 were operated with the help of 3D printing (group 1) and 10 were operated with freehand technique (group 2). Group 1 included 6 congenital, 3 adolescent idiopathic scoliosis (AIS), one post tubercular kyphosis and Group 2 included 5 congenital, 4 AIS and one post tubercular kyphosis patient. Primary outcomes were measured in terms of screw violation and secondary outcome were measured in terms of Surgical time, Blood loss, Radiation exposure (no. of shoots required) and complications. MIMICS v18.0 Software was used for 3D reconstruction from CT scan images of all the patients. 3-Matic software was used to create drill guide. 3-D printer from Stratasys Mojo ABS P 430 model material cartilage (a thermoplastic material) was used for printing of vertebrae model and jigs. Two sample test of proportion was used to compare correctly and wrongly pedicle screw placement with 3D printing and freehand technique. T-test with equal variance was used for operating surgical time and blood loss. This work was carried out by collaboration of Orthopaedics Department, All India Institute of Medical Sciences (AIIMS), New Delhi and Biomedical Engineering Department, Indian Institute of Technology (IIT) Delhi. This project received the grant of USD 60000 from Department of Biotechnology (DBT

Coach development programmes to improve interpersonal coach behaviours: a systematic review using the re-aim framework.

Science.gov (United States)

Evans, M Blair; McGuckin, Matthew; Gainforth, Heather L; Bruner, Mark W; Côté, Jean

2015-07-01

Although evidence supports the effectiveness of interpersonal Coach Development Programmes (CDPs), which are designed to foster coach-athlete relationships, an intervention's impact is shaped by numerous factors over and above effectiveness. The purpose of this systematic review was to examine the extent that published articles describing interpersonal CDP trials reported on indicators of internal and external validity, as conceptualised in the RE-AIM framework (ie, Reach, Effectiveness, Adoption, Implementation and Maintenance). The search strategy was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, involving a database search and supplemental manual search of key articles and journals. After initial screening, the full-text search strategy involved identifying articles describing CDP trials and then selecting a specific subgroup of articles involving interpersonal CDP trials and excluding ineligible articles. Resulting trials were coded using a 47-item sport coaching adaptation of the RE-AIM coding sheet. 17 published articles met eligibility criteria, representing 10 distinct CDP trials. After attaining coder agreement, global ratings of RE-AIM indicators within interpersonal CDP trials ranged from the low to moderate quality. Whereas indicators of effectiveness and implementation were reported to some extent across all studies, maintenance within sport organisations and a number of specific indicators from across dimensions were rarely reported. These findings inform the future design and evaluation of CDPs that have the potential to be adopted in numerous settings and reach athletes and coaches who can most benefit. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Preparation and characterization of a novel nanobody against T-cell immunoglobulin and mucin-3 (TIM-3).

Science.gov (United States)

Homayouni, Vida; Ganjalikhani-Hakemi, Mazdak; Rezaei, Abbas; Khanahmad, Hossein; Behdani, Mahdi; Lomedasht, Fatemeh Kazemi

2016-11-01

As T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune regulatory molecule; its blocking or stimulating could alter the pattern of immune response towards a desired condition. Based on the unique features of nanobodies, we aimed to construct an anti-TIM-3 nanobody as an appropriate tool for manipulating immune responses for future therapeutic purposes. We immunized a camel with TIM-3 antigen and then, synthesized a VHH phage: mid library from its B cell's transcriptome using nested PCR. Library selection against TIM-3antigen was performed in three rounds of panning. Using phage-ELISA, the most reactive colonies were selected for sub-cloning in soluble protein expression vectors. The Nanobody was purified and confirmed with a nickel-nitrilotriacetic acid (Ni-NTA) column, SDS-PAGE and Western blotting. A flowcytometric analysis was performed to analyze the binding and biologic activities of theTIM-3 specific nanobody with TIM-3 expressing HL-60 and HEK cell lines. Specific 15kD band representing for nanobody was observed on the gel and confirmed with Western blotting. The nanobody showed significant specific immune-reactivity against TIM-3 with a relatively high binding affinity. The nanobody significantly suppressed the proliferation of TIM-3 expressing HL-60 cell line. Finally, we successfully prepared a functional anti-humanTIM-3 specific nanobody with a high affinity and an anti-proliferative activity on an AML cell line in vitro.

Preparation and characterization of a novel nanobody against T-cell immunoglobulin and mucin-3 (TIM-3

Directory of Open Access Journals (Sweden)

Vida Homayouni

2016-11-01

Full Text Available Objective(s: As T-cell immunoglobulin and mucin domain 3 (TIM-3 is an immune regulatory molecule; its blocking or stimulating could alter the pattern of immune response towards a desired condition. Based on the unique features of nanobodies, we aimed to construct an anti-TIM-3 nanobody as an appropriate tool for manipulating immune responses for future therapeutic purposes. Materials and Methods:We immunized a camel with TIM-3 antigen and then, synthesized a VHH phagemid library from its B cell’s transcriptome using nested PCR. Library selection against TIM-3antigen was performed in three rounds of panning. Using phage-ELISA, the most reactive colonies were selected for sub-cloning in soluble protein expression vectors. The Nanobody was purified and confirmed with a nickel-nitrilotriacetic acid (Ni-NTA column, SDS-PAGE and Western blotting. A flowcytometric analysis was performed to analyze the binding and biologic activities of theTIM-3 specific nanobody with TIM-3 expressing HL-60 and HEK cell lines. Results:Specific 15kD band representing for nanobody was observed on the gel and confirmed with Western blotting. The nanobody showed significant specific immune-reactivity against TIM-3 with a relatively high binding affinity. The nanobody significantly suppressed the proliferation of TIM-3 expressing HL-60 cell line. Conclusion: Finally, we successfully prepared a functional anti-humanTIM-3 specific nanobody with a high affinity and an anti-proliferative activity on an AML cell line in vitro.

3D printed abdominal aortic aneurysm phantom for image guided surgical planning with a patient specific fenestrated endovascular graft system

Science.gov (United States)

Meess, Karen M.; Izzo, Richard L.; Dryjski, Maciej L.; Curl, Richard E.; Harris, Linda M.; Springer, Michael; Siddiqui, Adnan H.; Rudin, Stephen; Ionita, Ciprian N.

2017-03-01

Following new trends in precision medicine, Juxatarenal Abdominal Aortic Aneurysm (JAAA) treatment has been enabled by using patient-specific fenestrated endovascular grafts. The X-ray guided procedure requires precise orientation of multiple modular endografts within the arteries confirmed via radiopaque markers. Patient-specific 3D printed phantoms could familiarize physicians with complex procedures and new devices in a risk-free simulation environment to avoid periprocedural complications and improve training. Using the Vascular Modeling Toolkit (VMTK), 3D Data from a CTA imaging of a patient scheduled for Fenestrated EndoVascular Aortic Repair (FEVAR) was segmented to isolate the aortic lumen, thrombus, and calcifications. A stereolithographic mesh (STL) was generated and then modified in Autodesk MeshMixer for fabrication via a Stratasys Eden 260 printer in a flexible photopolymer to simulate arterial compliance. Fluoroscopic guided simulation of the patient-specific FEVAR procedure was performed by interventionists using all demonstration endografts and accessory devices. Analysis compared treatment strategy between the planned procedure, the simulation procedure, and the patient procedure using a derived scoring scheme. Results: With training on the patient-specific 3D printed AAA phantom, the clinical team optimized their procedural strategy. Anatomical landmarks and all devices were visible under x-ray during the simulation mimicking the clinical environment. The actual patient procedure went without complications. Conclusions: With advances in 3D printing, fabrication of patient specific AAA phantoms is possible. Simulation with 3D printed phantoms shows potential to inform clinical interventional procedures in addition to CTA diagnostic imaging.

Many Routes to an Antibody Heavy-Chain CDR3: Necessary, Yet Insufficient, for Specific Binding

Science.gov (United States)

D’Angelo, Sara; Ferrara, Fortunato; Naranjo, Leslie; Erasmus, M. Frank; Hraber, Peter; Bradbury, Andrew R. M.

2018-01-01

Because of its great potential for diversity, the immunoglobulin heavy-chain complementarity-determining region 3 (HCDR3) is taken as an antibody molecule’s most important component in conferring binding activity and specificity. For this reason, HCDR3s have been used as unique identifiers to investigate adaptive immune responses in vivo and to characterize in vitro selection outputs where display systems were employed. Here, we show that many different HCDR3s can be identified within a target-specific antibody population after in vitro selection. For each identified HCDR3, a number of different antibodies bearing differences elsewhere can be found. In such selected populations, all antibodies with the same HCDR3 recognize the target, albeit at different affinities. In contrast, within unselected populations, the majority of antibodies with the same HCDR3 sequence do not bind the target. In one HCDR3 examined in depth, all target-specific antibodies were derived from the same VDJ rearrangement, while non-binding antibodies with the same HCDR3 were derived from many different V and D gene rearrangements. Careful examination of previously published in vivo datasets reveals that HCDR3s shared between, and within, different individuals can also originate from rearrangements of different V and D genes, with up to 26 different rearrangements yielding the same identical HCDR3 sequence. On the basis of these observations, we conclude that the same HCDR3 can be generated by many different rearrangements, but that specific target binding is an outcome of unique rearrangements and VL pairing: the HCDR3 is necessary, albeit insufficient, for specific antibody binding. PMID:29568296

Creating a normative database of age-specific 3D geometrical data, bone density, and bone thickness of the developing skull: a pilot study

NARCIS (Netherlands)

Delye, H.H.; Clijmans, T.; Mommaerts, M.Y.; Sloten, J.V.; Goffin, J.

2015-01-01

OBJECT Finite element models (FEMs) of the head are used to study the biomechanics of traumatic brain injury and depend heavily on the use of accurate material properties and head geometry. Any FEM aimed at investigating traumatic head injury in children should therefore use age-specific dimensions

The 3rd International Joint Conference ICIEOM-ADINGOR-IISE-AIM-ASEM (IJC2017) PROCEEDINGS - “New Global Perspectives on Industrial Engineering and Management”

OpenAIRE

Poler Escoto, Raúl; Mula Bru, Josefa; Díaz-Madroñero Boluda, Francisco Manuel; Sanchis Gisbert, Raquel

2017-01-01

The IJC2017 Proceedings contains the contributions presented in the 3rd International Joint Conference ICIEOM – ADINGOR – IISE – AIM - ASEM : “XXIII International Conference on Industrial Engineering and Operations Management”, “International ADINGOR Conference 2017”, “International IISE Conference 2017”, “International AIM Conference 2017” and “International ASEM Conference 2017”. This International Joint Conference is a result of an agreement among ADINGOR (Asociación para el Desarrollo ...

Analysis of different alternatives for a reactor aimed to produce Co60. Neutronic part

International Nuclear Information System (INIS)

Relloso, J.M.

1990-01-01

Different alternatives are presented for a reactor aimed to produce radioisotopes with a low enrichment fuel element geometrically equal to those of low enrichment. Different alternatives are presented which essentially differ in the core's configuration, fuel management and 'meat' fuel material: U3O8, U3Si or U3Si2 in aluminium matrix. Fluxes at different irradiation positions and power full peak factors are described for each case. The main aspects to be taken into account for cobalt irradiation and the method to be followed to measure the reactor as a function of a required production are presented. (Author) [es

Testis-Specific Histone Variant H3t Gene Is Essential for Entry into Spermatogenesis

Directory of Open Access Journals (Sweden)

Jun Ueda

2017-01-01

Full Text Available Cellular differentiation is associated with dynamic chromatin remodeling in establishing a cell-type-specific epigenomic landscape. Here, we find that mouse testis-specific and replication-dependent histone H3 variant H3t is essential for very early stages of spermatogenesis. H3t gene deficiency leads to azoospermia because of the loss of haploid germ cells. When differentiating spermatogonia emerge in normal spermatogenesis, H3t appears and replaces the canonical H3 proteins. Structural and biochemical analyses reveal that H3t-containing nucleosomes are more flexible than the canonical nucleosomes. Thus, by incorporating H3t into the genome during spermatogonial differentiation, male germ cells are able to enter meiosis and beyond.

Mutations in TET2 and DNMT3A genes are associated with changes in global and gene-specific methylation in acute myeloid leukemia.

Science.gov (United States)

Ponciano-Gómez, Alberto; Martínez-Tovar, Adolfo; Vela-Ojeda, Jorge; Olarte-Carrillo, Irma; Centeno-Cruz, Federico; Garrido, Efraín

2017-10-01

Acute myeloid leukemia is characterized by its high biological and clinical heterogeneity, which represents an important barrier for a precise disease classification and accurate therapy. While epigenetic aberrations play a pivotal role in acute myeloid leukemia pathophysiology, molecular signatures such as change in the DNA methylation patterns and genetic mutations in enzymes needed to the methylation process can also be helpful for classifying acute myeloid leukemia. Our study aims to unveil the relevance of DNMT3A and TET2 genes in global and specific methylation patterns in acute myeloid leukemia. Peripheral blood samples from 110 untreated patients with acute myeloid leukemia and 15 healthy control individuals were collected. Global 5-methylcytosine and 5-hydroxymethylcytosine in genomic DNA from peripheral blood leukocytes were measured by using the MethylFlashTM Quantification kits. DNMT3A and TET2 expression levels were evaluated by real-time quantitative polymerase chain reaction. The R882A hotspot of DNMT3A and exons 6-10 of TET2 were amplified by polymerase chain reaction and sequenced using the Sanger method. Methylation patterns of 16 gene promoters were evaluated by pyrosequencing after treating DNA with sodium bisulfite, and their transcriptional products were measured by real-time quantitative polymerase chain reaction.Here, we demonstrate altered levels of 5-methylcytosine and 5-hydroxymethylcytosine and highly variable transcript levels of DNMT3A and TET2 in peripheral blood leukocytes from acute myeloid leukemia patients. We found a mutation prevalence of 2.7% for DNMT3A and 11.8% for TET2 in the Mexican population with this disease. The average overall survival of acute myeloid leukemia patients with DNMT3A mutations was only 4 months. In addition, we showed that mutations in DNMT3A and TET2 may cause irregular DNA methylation patterns and transcriptional expression levels in 16 genes known to be involved in acute myeloid leukemia pathogenesis

Structural Basis of Histone Demethylase KDM6B Histone 3 Lysine 27 Specificity

DEFF Research Database (Denmark)

Jones, Sarah E; Olsen, Lars; Gajhede, Michael

2018-01-01

KDM subfamily 6 enzymes KDM6A and KDM6B specifically catalyze demethylation of di- and trimethylated lysine on histone 3 lysine 27 (H3K27me3/2) and play an important role in repression of developmental genes. Despite identical amino acid sequence in the immediate surroundings of H3K9me3/2 (ARKS...

SU-F-J-176: Development of a Patient-Specific 3D Couplant Pad for Ultrasound IGRT

Energy Technology Data Exchange (ETDEWEB)

Kim, H; Chang, A [Soonchunhyang University Hospital, Seoul (Korea, Republic of); Ye, S [Seoul National University, Seoul (Korea, Republic of)

2016-06-15

Purpose: to overcome the several issues of ultrasound image-guided radiation therapy (US IGRT) such as probe pressure and optical tracking disability by using a patient-specific three-dimensional couplant pad (CP) fabricated by a patient’s skin mold using a 3D printing technique. Methods: A CP was then fabricated by pouring gelatin solution into a fixed-shape container accommodating the patient skin mold fabricated by a 3D printer. A breast phantom was fabricated with the compound of gelatin and agarose and a phantom study was carried out. From four patients who underwent US IGRT, total 486 ultrasound images with and without a CP were acquired before treatment. Effectiveness of the use of the CP was evaluated. Results: The positioning accuracies in the phantom study were 0.9 ± 0.3 mm and 1.3 ± 0.4 mm with and without the CP in 3D vector amplitude, respectively. In the patient study, the use of CP reduced the mean target shift from 4.7 mm to 3.7 mm in 3D vector amplitude and the one standard deviation from 2.2 mm to 1.7 mm. It also improved the image contrast around the treatment target by 10 %. The centroid offset of the target volume affected from the US scanning coverage and the target deformation due to the excessive probe pressure was decreased from 4.4 mm to 2.9 mm due to the use of CP. Its difference among three different users was statistically significant (p=0.020) without the use of CP but not significantly different (p=0.133) with the use of CP. Conclusion: Our patient-specific 3D CP using a mold by 3D printing technique is a promising strategy for improving tracking accuracy, image quality, and inter-observer variation for ultrasound-based image guided radiotherapy. In addition to its conventional advantage of non-invasiveness, US can be more facilitated in radiotherapy by the developed CP.

SU-F-J-176: Development of a Patient-Specific 3D Couplant Pad for Ultrasound IGRT

International Nuclear Information System (INIS)

Kim, H; Chang, A; Ye, S

2016-01-01

Purpose: to overcome the several issues of ultrasound image-guided radiation therapy (US IGRT) such as probe pressure and optical tracking disability by using a patient-specific three-dimensional couplant pad (CP) fabricated by a patient’s skin mold using a 3D printing technique. Methods: A CP was then fabricated by pouring gelatin solution into a fixed-shape container accommodating the patient skin mold fabricated by a 3D printer. A breast phantom was fabricated with the compound of gelatin and agarose and a phantom study was carried out. From four patients who underwent US IGRT, total 486 ultrasound images with and without a CP were acquired before treatment. Effectiveness of the use of the CP was evaluated. Results: The positioning accuracies in the phantom study were 0.9 ± 0.3 mm and 1.3 ± 0.4 mm with and without the CP in 3D vector amplitude, respectively. In the patient study, the use of CP reduced the mean target shift from 4.7 mm to 3.7 mm in 3D vector amplitude and the one standard deviation from 2.2 mm to 1.7 mm. It also improved the image contrast around the treatment target by 10 %. The centroid offset of the target volume affected from the US scanning coverage and the target deformation due to the excessive probe pressure was decreased from 4.4 mm to 2.9 mm due to the use of CP. Its difference among three different users was statistically significant (p=0.020) without the use of CP but not significantly different (p=0.133) with the use of CP. Conclusion: Our patient-specific 3D CP using a mold by 3D printing technique is a promising strategy for improving tracking accuracy, image quality, and inter-observer variation for ultrasound-based image guided radiotherapy. In addition to its conventional advantage of non-invasiveness, US can be more facilitated in radiotherapy by the developed CP.

Apoptosis inhibitor of macrophage (AIM) diminishes lipid droplet-coating proteins leading to lipolysis in adipocytes

International Nuclear Information System (INIS)

Iwamura, Yoshihiro; Mori, Mayumi; Nakashima, Katsuhiko; Mikami, Toshiyuki; Murayama, Katsuhisa; Arai, Satoko; Miyazaki, Toru

2012-01-01

Highlights: ► AIM induces lipolysis in a distinct manner from that of hormone-dependent lipolysis. ► AIM ablates activity of peroxisome proliferator-activated receptor in adipocytes. ► AIM reduces mRNA levels of lipid-droplet coating proteins leading to lipolysis. -- Abstract: Under fasting conditions, triacylglycerol in adipose tissue undergoes lipolysis to supply fatty acids as energy substrates. Such lipolysis is regulated by hormones, which activate lipases via stimulation of specific signalling cascades. We previously showed that macrophage-derived soluble protein, AIM induces obesity-associated lipolysis, triggering chronic inflammation in fat tissue which causes insulin resistance. However, the mechanism of how AIM mediates lipolysis remains unknown. Here we show that AIM induces lipolysis in a manner distinct from that of hormone-dependent lipolysis, without activation or augmentation of lipases. In vivo and in vitro, AIM did not enhance phosphorylation of hormone-sensitive lipase (HSL) in adipocytes, a hallmark of hormone-dependent lipolysis activation. Similarly, adipose tissue from obese AIM-deficient and wild-type mice showed comparable HSL phosphorylation. Consistent with the suppressive effect of AIM on fatty acid synthase activity, the amount of saturated and unsaturated fatty acids was reduced in adipocytes treated with AIM. This response ablated transcriptional activity of peroxisome proliferator-activated receptor (PPARγ), leading to diminished gene expression of lipid-droplet coating proteins including fat-specific protein 27 (FSP27) and Perilipin, which are indispensable for triacylglycerol storage in adipocytes. Accordingly, the lipolytic effect of AIM was overcome by a PPARγ-agonist or forced expression of FSP27, while it was synergized by a PPARγ-antagonist. Overall, distinct modes of lipolysis appear to take place in different physiological situations; one is a supportive response against nutritional deprivation achieved by

Chapter A6. Section 6.3. Specific Electrical Conductance

Science.gov (United States)

Radtke, Dean B.; Davis, Jerri V.; Wilde, Franceska D.

2005-01-01

Electrical conductance is a measure of the capacity of a substance to conduct an electrical current. The specific electrical conductance (conductivity) of water is a function of the types and quantities of dissolved substances it contains, normalized to a unit length and unit cross section at a specified temperature. This section of the National Field Manual (NFM) describes U.S. Geological Survey (USGS) guidance and protocols for measurement of conductivity in ground and surface waters.

The nucleolar SUMO-specific protease SMT3IP1/SENP3 attenuates Mdm2-mediated p53 ubiquitination and degradation

Energy Technology Data Exchange (ETDEWEB)

Nishida, Tamotsu, E-mail: nishida@gene.mie-u.ac.jp [Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu 514-8507 (Japan); Yamada, Yoshiji [Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu 514-8507 (Japan)

2011-03-11

Research highlights: {yields} SMT3IP1 interacts with p53 and Mdm2, and desumoylates both proteins. {yields} SMT3IP1 competes with p53 for binding to the central acidic domain of Mdm2. {yields} SMT3IP1 binding to Mdm2 inhibits Mdm2-mediated p53 ubiquitination and degradation. {yields} We postulate that SMT3IP1 acts as a new regulator of the p53-Mdm2 pathway. -- Abstract: SUMO (small ubiquitin-like modifier) modification plays multiple roles in several cellular processes. Sumoylation is reversibly regulated by SUMO-specific proteases. SUMO-specific proteases have recently been implicated in cell proliferation and early embryogenesis, but the underlying mechanisms remain unknown. Here, we show that a nucleolar SUMO-specific protease, SMT3IP1/SENP3, controls the p53-Mdm2 pathway. We found that SMT3IP1 interacts with p53 and Mdm2, and desumoylates both proteins. Overexpression of SMT3IP1 in cells resulted in the accumulation of Mdm2 in the nucleolus and increased stability of the p53 protein. In addition, SMT3IP1 bound to the acidic domain of Mdm2, which also mediates the p53 interaction, and competed with p53 for binding. Increasing expression of SMT3IP1 suppressed Mdm2-mediated p53 ubiquitination and subsequent proteasomal degradation. Interestingly, the desumoylation activity of SMT3IP1 was not necessary for p53 stabilization. These results suggest that SMT3IP1 is a new regulator of the p53-Mdm2 pathway.

The nucleolar SUMO-specific protease SMT3IP1/SENP3 attenuates Mdm2-mediated p53 ubiquitination and degradation

International Nuclear Information System (INIS)

Nishida, Tamotsu; Yamada, Yoshiji

2011-01-01

Research highlights: → SMT3IP1 interacts with p53 and Mdm2, and desumoylates both proteins. → SMT3IP1 competes with p53 for binding to the central acidic domain of Mdm2. → SMT3IP1 binding to Mdm2 inhibits Mdm2-mediated p53 ubiquitination and degradation. → We postulate that SMT3IP1 acts as a new regulator of the p53-Mdm2 pathway. -- Abstract: SUMO (small ubiquitin-like modifier) modification plays multiple roles in several cellular processes. Sumoylation is reversibly regulated by SUMO-specific proteases. SUMO-specific proteases have recently been implicated in cell proliferation and early embryogenesis, but the underlying mechanisms remain unknown. Here, we show that a nucleolar SUMO-specific protease, SMT3IP1/SENP3, controls the p53-Mdm2 pathway. We found that SMT3IP1 interacts with p53 and Mdm2, and desumoylates both proteins. Overexpression of SMT3IP1 in cells resulted in the accumulation of Mdm2 in the nucleolus and increased stability of the p53 protein. In addition, SMT3IP1 bound to the acidic domain of Mdm2, which also mediates the p53 interaction, and competed with p53 for binding. Increasing expression of SMT3IP1 suppressed Mdm2-mediated p53 ubiquitination and subsequent proteasomal degradation. Interestingly, the desumoylation activity of SMT3IP1 was not necessary for p53 stabilization. These results suggest that SMT3IP1 is a new regulator of the p53-Mdm2 pathway.

The Nd-Mn exchange interaction, low temperature specific heat and magnetism of Nd{sub 2/3}Ca{sub 1/3}MnO{sub 3}

Energy Technology Data Exchange (ETDEWEB)

Beznosov, Anatoly [B. Verkin Institute for Low Temperature Physics and Engineering NASU, 47 Lenin Avenue, Kharkov 61103 (Ukraine); Fertman, Elena, E-mail: fertman@ilt.kharkov.ua [B. Verkin Institute for Low Temperature Physics and Engineering NASU, 47 Lenin Avenue, Kharkov 61103 (Ukraine); Desnenko, Vladimir [B. Verkin Institute for Low Temperature Physics and Engineering NASU, 47 Lenin Avenue, Kharkov 61103 (Ukraine); Kajnakova, Marcela; Feher, Alexander [Centre of Low Temperature Physics of the Faculty of Science UPJS and IEP SAS, Park Angelinum 9, 04154 Kosice (Slovakia)

2011-10-15

The low temperature specific heat and magnetic characteristics of Nd{sub 2/3}Ca{sub 1/3}MnO{sub 3} perovskite are studied in a wide range of magnetic fields (up to 9 T). Temperature dependent specific heat data show a broadened Schottky-like anomaly below 20 K caused by splitting of the Nd{sup 3+} ions ground-state doublet in the effective molecular field H{sub ex}, determined by exchange interaction between Nd and Mn spin systems supplemented by an applied external magnetic field. Existence of the splitting at zero magnetic field and expressed field dependence is the evidence of a strong exchange coupling between Nd and Mn magnetic subsystems. The Nd-ions magnetic ordering leads to an additional contribution to the magnetic moment of the system below 30 K, producing anomalies of the magnetic loss and field-cooled and zero-field-cooled magnetizations. The observed broadened Schottky-like anomalies are fitted for each applied magnetic field by the sum of three Schottky functions. Applied magnetic field extends the anomaly region and shifts it to higher temperatures. Splitting of the higher crystal field Kramers doublets gives an additional contribution to the heat capacity in magnetic fields. The ground state doublet g-factors g{sub ||} and g{sub perpendicular} were estimated to be 3.4 and 2.2, respectively, and H{sub ex} was estimated to be 9 T. The Nd{sup 3+} ions magnetic moment estimated from the magnetization data agrees with the value obtained from the specific heat data. - Highlights: > Low temperature specific heat of Nd{sub 2/3}Ca{sub 1/3}MnO{sub 3} has been measured in magnetic fields up to 9 T. > Schottky-like anomalies are fitted for each magnetic field by a sum of three Schottky functions. > An effective magnetic field of the Mn spin system on Nd ion has been estimated as H{sub ex}=9 T. > Nd{sup 3+} ground-state g-factors have been estimated as g{sub ||}=3.4 and g{sub perpendicular} =2.2. > Magnetic ordering of the Nd subsystem has been revealed below

CEACAM3-mediated phagocytosis of human-specific bacterial pathogens involves the adaptor molecule Nck

OpenAIRE

Peterson, Lisa

2010-01-01

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) are exploited by human-specific pathogens to anchor themselves to or invade host cells. Interestingly, human granulocytes express a specific isoform, CEACAM3, that can direct efficient, opsonin-independent phagocytosis of CEACAM-binding Neisseria, Moraxella and Haemophilus species. As opsonin-independent phagocytosis of CEACAM-binding Neisseria depends on Src-family protein tyrosine kinase (PTK) phosphorylation of the CEACAM3 ...

Cardiac-Specific SOCS3 Deletion Prevents In Vivo Myocardial Ischemia Reperfusion Injury through Sustained Activation of Cardioprotective Signaling Molecules.

Directory of Open Access Journals (Sweden)

Takanobu Nagata

Full Text Available Myocardial ischemia reperfusion injury (IRI adversely affects cardiac performance and the prognosis of patients with acute myocardial infarction. Although myocardial signal transducer and activator of transcription (STAT 3 is potently cardioprotective during IRI, the inhibitory mechanism responsible for its activation is largely unknown. The present study aimed to investigate the role of the myocardial suppressor of cytokine signaling (SOCS-3, an intrinsic negative feedback regulator of the Janus kinase (JAK-STAT signaling pathway, in the development of myocardial IRI. Myocardial IRI was induced in mice by ligating the left anterior descending coronary artery for 1 h, followed by different reperfusion times. One hour after reperfusion, the rapid expression of JAK-STAT-activating cytokines was observed. We precisely evaluated the phosphorylation of cardioprotective signaling molecules and the expression of SOCS3 during IRI and then induced myocardial IRI in wild-type and cardiac-specific SOCS3 knockout mice (SOCS3-CKO. The activation of STAT3, AKT, and ERK1/2 rapidly peaked and promptly decreased during IRI. This decrease correlated with the induction of SOCS3 expression up to 24 h after IRI in wild-type mice. The infarct size 24 h after reperfusion was significantly reduced in SOCS3-CKO compared with wild-type mice. In SOCS3-CKO mice, STAT3, AKT, and ERK1/2 phosphorylation was sustained, myocardial apoptosis was prevented, and the expression of anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1 was augmented. Cardiac-specific SOCS3 deletion led to the sustained activation of cardioprotective signaling molecules including and prevented myocardial apoptosis and injury during IRI. Our findings suggest that SOCS3 may represent a key factor that exacerbates the development of myocardial IRI.

Evidence for a helical and a chiral phase transition in the Gd(hfac)3NITiPr magnetic specific heat

International Nuclear Information System (INIS)

Cinti, F.; Rettori, A.; Barucci, M.; Olivieri, E.; Risegari, L.; Ventura, G.; Caneschi, A.; Gatteschi, D.; Rovai, D.; Pini, M.G.; Affronte, M.; Mariani, M.; Lascialfari, A.

2007-01-01

New specific heat data taken at very low temperatures (0.03 3 NITiPr show a clear λ anomaly at T N =0.039K signaling the onset of the 3D helimagnetic phase. They match fairly well with previously reported data which showed the onset of the chiral phase transition at T 0 =2.08K. Also new magnetic susceptibility data taken in the neighborhood at T 0 are repeated

Structure of matrix metalloproteinase-3 with a platinum-based inhibitor.

Science.gov (United States)

Belviso, Benny Danilo; Caliandro, Rocco; Siliqi, Dritan; Calderone, Vito; Arnesano, Fabio; Natile, Giovanni

2013-06-18

An X-ray investigation has been performed with the aim of characterizing the binding sites of a platinum-based inhibitor (K[PtCl3(DMSO)]) of matrix metalloproteinase-3 (stromelysin-1). The platinum complex targets His224 in the S1' specificity loop, representing the first step in the selective inhibition process (PDB ID code 4JA1).

Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression

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Liangping Su

2018-03-01

Full Text Available Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3 in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11, attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases.

Specificity of elevated intercostal space ECG recording for the type 1 Brugada ECG pattern

DEFF Research Database (Denmark)

Holst, Anders G; Tangø, Mogens; Batchvarov, Velislav

2012-01-01

Right precordial (V1-3) elevated electrode placement ECG (EEP-ECG) is often used in the diagnosis of Brugada syndrome (BrS). However, the specificity of this has only been studied in smaller studies in Asian populations. We aimed to study this in a larger European population.......Right precordial (V1-3) elevated electrode placement ECG (EEP-ECG) is often used in the diagnosis of Brugada syndrome (BrS). However, the specificity of this has only been studied in smaller studies in Asian populations. We aimed to study this in a larger European population....

Ethics and aims in psychotherapy: a contribution from Kant.

Science.gov (United States)

Callender, J S

1998-08-01

Psychotherapy is an activity which takes many forms and which has many aims. The present paper argues that it can be viewed as a form of moral suasion. Kant's concepts of free will and ethics are described and these are then applied to the processes and outcome of psychotherapy. It is argued that his ideas, by linking rationality, free will and ethics into a single philosophical system, offer a valuable theoretical framework for thinking about aims and ethical issues in psychotherapy.

3USS: a web server for detecting alternative 3'UTRs from RNA-seq experiments.

KAUST Repository

Le Pera, Loredana; Mazzapioda, Mariagiovanna; Tramontano, Anna

2015-01-01

Protein-coding genes with multiple alternative polyadenylation sites can generate mRNA 3'UTR sequences of different lengths, thereby causing the loss or gain of regulatory elements, which can affect stability, localization and translation efficiency. 3USS is a web-server developed with the aim of giving experimentalists the possibility to automatically identify alternative 3 ': UTRs (shorter or longer with respect to a reference transcriptome), an option that is not available in standard RNA-seq data analysis procedures. The tool reports as putative novel the 3 ': UTRs not annotated in available databases. Furthermore, if data from two related samples are uploaded, common and specific alternative 3 ': UTRs are identified and reported by the server.3USS is freely available at http://www.biocomputing.it/3uss_server.

3USS: a web server for detecting alternative 3'UTRs from RNA-seq experiments.

KAUST Repository

Le Pera, Loredana

2015-01-22

Protein-coding genes with multiple alternative polyadenylation sites can generate mRNA 3\\'UTR sequences of different lengths, thereby causing the loss or gain of regulatory elements, which can affect stability, localization and translation efficiency. 3USS is a web-server developed with the aim of giving experimentalists the possibility to automatically identify alternative 3 \\': UTRs (shorter or longer with respect to a reference transcriptome), an option that is not available in standard RNA-seq data analysis procedures. The tool reports as putative novel the 3 \\': UTRs not annotated in available databases. Furthermore, if data from two related samples are uploaded, common and specific alternative 3 \\': UTRs are identified and reported by the server.3USS is freely available at http://www.biocomputing.it/3uss_server.

Preparation and high-performance liquid chromatography of 3'-phosphoadenosine-5'-phospho[35S]sulfate with a predetermined specific activity

International Nuclear Information System (INIS)

Delfert, D.M.; Conrad, H.E.

1985-01-01

3'-Phosphoadenosine-5'-phospho[35S]sulfate (PAP 35 S) was prepared by incubating ATP and carrier-free H 2 ( 35 )SO 4 with a 100,000g supernatant fraction prepared from chick embryo chondrocytes. The product was partially purified by paper electrophoresis and mixed with unlabeled PAPS to give a solution of PAP 35 S with a specific activity and a concentration approximating those required for the desired metabolic studies. The product was analyzed by high-performance liquid chromatography on an anion-exchange column to determine the proportion of the 35 SO 4 cpm and A260 material found in the PAPS and other contaminating nucleotides. The PAP 35 S was purified further by preparative high-performance liquid chromatography. The exact specific activity of the PAP 35 S was then determined by using this PAP 35 S preparation as the SO 4 donor in a sulfotransferase reaction using a microsomal preparation from the chick embryo chondrocytes as the enzyme and an 3 H-labeled oligosaccharide as the SO 4 acceptor. The sulfated oligosaccharide was then isolated and the number of 3 H and 35 SO 4 counts per minute in this product were used to calculate the specific activity of the donor. The features of this generally useful approach for preparing PAP 35 S of any desired specific activity and concentration are discussed

NKT sublineage specification and survival requires the ubiquitin-modifying enzyme TNFAIP3/A20.

Science.gov (United States)

Drennan, Michael B; Govindarajan, Srinath; Verheugen, Eveline; Coquet, Jonathan M; Staal, Jens; McGuire, Conor; Taghon, Tom; Leclercq, Georges; Beyaert, Rudi; van Loo, Geert; Lambrecht, Bart N; Elewaut, Dirk

2016-09-19

Natural killer T (NKT) cells are innate lymphocytes that differentiate into NKT1, NKT2, and NKT17 sublineages during development. However, the signaling events that control NKT sublineage specification and differentiation remain poorly understood. Here, we demonstrate that the ubiquitin-modifying enzyme TNFAIP3/A20, an upstream regulator of T cell receptor (TCR) signaling in T cells, is an essential cell-intrinsic regulator of NKT differentiation. A20 is differentially expressed during NKT cell development, regulates NKT cell maturation, and specifically controls the differentiation and survival of NKT1 and NKT2, but not NKT17, sublineages. Remaining A20-deficient NKT1 and NKT2 thymocytes are hyperactivated in vivo and secrete elevated levels of Th1 and Th2 cytokines after TCR ligation in vitro. Defective NKT development was restored by compound deficiency of MALT1, a key downstream component of TCR signaling in T cells. These findings therefore show that negative regulation of TCR signaling during NKT development controls the differentiation and survival of NKT1 and NKT2 cells. © 2016 Drennan et al.

3D site specific sample preparation and analysis of 3D devices (FinFETs) by atom probe tomography.

Science.gov (United States)

Kambham, Ajay Kumar; Kumar, Arul; Gilbert, Matthieu; Vandervorst, Wilfried

2013-09-01

With the transition from planar to three-dimensional device architectures such as Fin field-effect-transistors (FinFETs), new metrology approaches are required to meet the needs of semiconductor technology. It is important to characterize the 3D-dopant distributions precisely as their extent, positioning relative to gate edges and absolute concentration determine the device performance in great detail. At present the atom probe has shown its ability to analyze dopant distributions in semiconductor and thin insulating materials with sub-nm 3D-resolution and good dopant sensitivity. However, so far most reports have dealt with planar devices or restricted the measurements to 2D test structures which represent only limited challenges in terms of localization and site specific sample preparation. In this paper we will discuss the methodology to extract the dopant distribution from real 3D-devices such as a 3D-FinFET device, requiring the sample preparation to be carried out at a site specific location with a positioning accuracy ∼50 nm. Copyright © 2013 Elsevier B.V. All rights reserved.

SU-G-BRB-01: A Novel 3D Printed Patient-Specific Phantom for Spine SBRT Quality Assurance: Comparison of 3D Printing Techniques

Energy Technology Data Exchange (ETDEWEB)

Lee, S; Kim, M; Lee, M; Suh, T [Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of); Department of Biomedical Engineering, The Catholic University of Korea, Seoul (Korea, Republic of)

2016-06-15

Purpose: The novel 3 dimensional (3D)-printed spine quality assurance (QA) phantoms generated by two different 3D-printing technologies, digital light processing (DLP) and Polyjet, were developed and evaluated for spine stereotactic body radiation treatment (SBRT). Methods: The developed 3D-printed spine QA phantom consisted of an acrylic body and a 3D-printed spine phantom. DLP and Polyjet 3D printers using the high-density acrylic polymer were employed to produce spine-shaped phantoms based on CT images. To verify dosimetric effects, the novel phantom was made it enable to insert films between each slabs of acrylic body phantom. Also, for measuring internal dose of spine, 3D-printed spine phantom was designed as divided laterally exactly in half. Image fusion was performed to evaluate the reproducibility of our phantom, and the Hounsfield unit (HU) was measured based on each CT image. Intensity-modulated radiotherapy plans to deliver a fraction of a 16 Gy dose to a planning target volume (PTV) based on the two 3D-printing techniques were compared for target coverage and normal organ-sparing. Results: Image fusion demonstrated good reproducibility of the fabricated spine QA phantom. The HU values of the DLP- and Polyjet-printed spine vertebrae differed by 54.3 on average. The PTV Dmax dose for the DLP-generated phantom was about 1.488 Gy higher than for the Polyjet-generated phantom. The organs at risk received a lower dose when the DLP technique was used than when the Polyjet technique was used. Conclusion: This study confirmed that a novel 3D-printed phantom mimicking a high-density organ can be created based on CT images, and that a developed 3D-printed spine phantom could be utilized in patient-specific QA for SBRT. Despite using the same main material, DLP and Polyjet yielded different HU values. Therefore, the printing technique and materials must be carefully chosen in order to accurately produce a patient-specific QA phantom.

SU-G-BRB-01: A Novel 3D Printed Patient-Specific Phantom for Spine SBRT Quality Assurance: Comparison of 3D Printing Techniques

International Nuclear Information System (INIS)

Lee, S; Kim, M; Lee, M; Suh, T

2016-01-01

Purpose: The novel 3 dimensional (3D)-printed spine quality assurance (QA) phantoms generated by two different 3D-printing technologies, digital light processing (DLP) and Polyjet, were developed and evaluated for spine stereotactic body radiation treatment (SBRT). Methods: The developed 3D-printed spine QA phantom consisted of an acrylic body and a 3D-printed spine phantom. DLP and Polyjet 3D printers using the high-density acrylic polymer were employed to produce spine-shaped phantoms based on CT images. To verify dosimetric effects, the novel phantom was made it enable to insert films between each slabs of acrylic body phantom. Also, for measuring internal dose of spine, 3D-printed spine phantom was designed as divided laterally exactly in half. Image fusion was performed to evaluate the reproducibility of our phantom, and the Hounsfield unit (HU) was measured based on each CT image. Intensity-modulated radiotherapy plans to deliver a fraction of a 16 Gy dose to a planning target volume (PTV) based on the two 3D-printing techniques were compared for target coverage and normal organ-sparing. Results: Image fusion demonstrated good reproducibility of the fabricated spine QA phantom. The HU values of the DLP- and Polyjet-printed spine vertebrae differed by 54.3 on average. The PTV Dmax dose for the DLP-generated phantom was about 1.488 Gy higher than for the Polyjet-generated phantom. The organs at risk received a lower dose when the DLP technique was used than when the Polyjet technique was used. Conclusion: This study confirmed that a novel 3D-printed phantom mimicking a high-density organ can be created based on CT images, and that a developed 3D-printed spine phantom could be utilized in patient-specific QA for SBRT. Despite using the same main material, DLP and Polyjet yielded different HU values. Therefore, the printing technique and materials must be carefully chosen in order to accurately produce a patient-specific QA phantom.

Species-specific nested PCR as a diagnostic tool for Brucella ovis infection in rams

Directory of Open Access Journals (Sweden)

L.F. Costa

2013-02-01

Full Text Available The aim of the present study was to evaluate a species-specific nested PCR based on a previously described species-specific PCR for detection of B. ovis in semen and urine samples of experimentally infected rams. The performance of the species-specific nested PCR was compared with the results of a genus-specific PCR. Fourteen rams were experimentally infected with the Brucella ovis REO 198 strain and samples of semen and urine were collected every week up to 180 days post infection. Out of 83 semen samples collected, 42 (50.6% were positive for the species-specific nested PCR, and 23 (27.7% were positive for the genus-specific PCR. Out of 75 urine samples, 49 (65.3% were positive for the species-specific nested PCR, whereas 11 (14.6% were genus-specific PCR positive. Species-specific nested PCR was significantly more sensitive (P<0.001 than the genus-specific PCR in semen and urine from experimentally infected rams. In conclusion, the species-specific nested PCR developed in this study may be used as a diagnostic tool for the detection of B. ovis in semen and urine samples from suspected rams.

Specific heat of V3GaH/sub x/

International Nuclear Information System (INIS)

Cort, B.; Stewart, G.R.; Huang, S.Z.; Meng, R.L.; Chu, C.W.

1981-01-01

Specific-heat measurements have been made on V 3 GaH/sub x/ for x = 0, 0.2, 1.4, and 1.9 in the temperature range 1.2--20 K. In addition to increased lattice parameter and depressed transition temperature with increased hydrogen concentrations, the Debye temperature increases and the electronic density of states drops, both dramatically. Decreased electron-phonon coupling is also indicated with hydrogenation

Identification of STAT1 and STAT3 specific inhibitors using comparative virtual screening and docking validation.

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Malgorzata Szelag

Full Text Available Signal transducers and activators of transcription (STATs facilitate action of cytokines, growth factors and pathogens. STAT activation is mediated by a highly conserved SH2 domain, which interacts with phosphotyrosine motifs for specific STAT-receptor contacts and STAT dimerization. The active dimers induce gene transcription in the nucleus by binding to a specific DNA-response element in the promoter of target genes. Abnormal activation of STAT signaling pathways is implicated in many human diseases, like cancer, inflammation and auto-immunity. Searches for STAT-targeting compounds, exploring the phosphotyrosine (pTyr-SH2 interaction site, yielded many small molecules for STAT3 but sparsely for other STATs. However, many of these inhibitors seem not STAT3-specific, thereby questioning the present modeling and selection strategies of SH2 domain-based STAT inhibitors. We generated new 3D structure models for all human (hSTATs and developed a comparative in silico docking strategy to obtain further insight into STAT-SH2 cross-binding specificity of a selection of previously identified STAT3 inhibitors. Indeed, by primarily targeting the highly conserved pTyr-SH2 binding pocket the majority of these compounds exhibited similar binding affinity and tendency scores for all STATs. By comparative screening of a natural product library we provided initial proof for the possibility to identify STAT1 as well as STAT3-specific inhibitors, introducing the 'STAT-comparative binding affinity value' and 'ligand binding pose variation' as selection criteria. In silico screening of a multi-million clean leads (CL compound library for binding of all STATs, likewise identified potential specific inhibitors for STAT1 and STAT3 after docking validation. Based on comparative virtual screening and docking validation, we developed a novel STAT inhibitor screening tool that allows identification of specific STAT1 and STAT3 inhibitory compounds. This could increase our

Synthesis of high specific activity [1-3H]-D-glucose

International Nuclear Information System (INIS)

Saljoughian, M.; Morimoto, Hiromi; Williams, P.G.; Lee, Hakno

1991-01-01

Specifically labeled [1- 3 H]-D-glucose has been used for metabolic and mechanistic studies in erythrocytes. In vitro metabolism of the a and b anomers of the tritiated glucose was readily traced by 3 H NMR spectroscopy. Initial studies used labeled glucose obtained by catalytic exchange labeling (at 4.5-9 Ci/mmole, or 15-30% tritiated at the C-1 position), and this necessitated sample glucose concentrations of 2-4 times physiological. The availability of glucose at maximum specific activity (28.7 Ci/mmole, 100% at the C-1 position) would allow the authors to observe metabolic behavior using 1 mM levels of glucose. Accordingly, they have devised a new route for the synthesis of C-1 tritiated glucose, involving the synthesis of 4,6-O-benzylidene-D-gluconolactone followed by reduction with supertritide. Preliminary work with commercial superdeuteride is complete, and chromatographic and NMR analyses are promising. The analogous tritium reactions are currently underway, and experimental results are presented for all stages of investigation. This strategy should be generally applicable to the labeling of many reducing sugars, with the substrates 2-deoxyglucose and maltotriose being of particular interest to their research

Specific heat of Nb{sub 3}Sn: The case for a single gap

Energy Technology Data Exchange (ETDEWEB)

Jo, Y. J., E-mail: jophy@knu.ac.kr [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Zhou, Jian; Sung, Zu Hawn; Lee, Peter J.; Larbalestier, D. C. [National High Magnetic Field Laboratory, Florida State University, Tallahassee, Florida 32310 (United States)

2014-10-01

The important influence of multiple gaps in the superconductivity of MgB{sub 2} and Fe-based compounds, especially because of the possibility that manipulation of a second gap can significantly raise the upper critical field H{sub c2}, has refocused attention on Nb{sub 3}Sn because anomalies in both specific heat and point-contact tunneling studies have led to the proposal that Nb{sub 3}Sn is also a two-gap superconductor. Here, we search for evidence of the second gap in a careful study of the influence of the homogenization temperature on the sample uniformity. We show that it is very difficult to fabricate samples that are both homogeneous and stoichiometric. We find so-called “second-gap” anomalies disappear only after high temperature and long-term annealing. Such a well-annealed sample shows only a strong, electron-phonon-coupled, single-gap behavior. In contrast, samples reacted and annealed at lower temperatures, as in the earlier two-gap studies, show small chemical composition variations of the A15 phase. We propose that the second gap sightings are actually due to variation of T{sub c} within very difficult-to-fully homogenize samples. A curiosity of the A15 Nb{sub 3}Sn phase is that almost any mixture of Nb and Sn tries to form a stoichiometric A15 composition, but the residue of course contains off-stoichiometric A15, Nb, and other phases when the Nb:Sn ratio departs from the true 3:1 stoichiometry.

Specific heat and magnetic susceptibility vs long range order in V3Ga

International Nuclear Information System (INIS)

Junod, A.; Fluekiger, R.; Treyvaud, A.; Muller, J.

1976-01-01

A new technique of studying the magnetic susceptibility together with the specific heat and the superconducting transition of typical A15-type compounds in different ordering states enables us to consistently isolate the spin paramagnetism. Satisfactory results are obtained for V 3 Ga and these are compared with data on V 3 Au and Nb 3 (Au-Pt). (author)

Overexpression of Cardiac-Specific Kinase TNNI3K Promotes Mouse Embryonic Stem Cells Differentiation into Cardiomyocytes.

Science.gov (United States)

Wang, Yin; Wang, Shi-Qiang; Wang, Li-Peng; Yao, Yu-Hong; Ma, Chun-Yan; Ding, Jin-Feng; Ye, Jue; Meng, Xian-Min; Li, Jian-Jun; Xu, Rui-Xia

2017-01-01

Backgroud/Aims: The biological function of cardiac troponin I-interacting kinase (TNNI3K), a cardiac-specific functional kinase, is largely unknown. We investigated the effect of human TNNI3K (hTNNI3K) on the differentiation of mouse embryonic stem cells (mESCs) into cardiomyocytes. First, the time-space expression of endogenous Tnni3k was detected by real-time polymerase chain reaction (PCR) and western blotting at 16 different time-points over a period of 28 days. Further, action potentials and calcium current with/without 5 µM nifedipine were measured by patch clamp for mESC-derived cardiomyocytes. HTNNI3K and mouse-derived siRNA were transfected into mESC using lentivirus vector to induce hTNNI3K overexpression and knock-down, respectively. The number of troponin-T (cTnT) positive cells was greater in the group with TNNI3K overexpression as compared to that in control group, while less such cells were detected in the mTnni3k knock-down group as evaluated on flow cytometry (FCM) and ImageXpress Micro system. After upregulation of connexin43, cardiac troponin-I (Ctni), Ctni, Gata4 were detected in mESCs with TNNI3K overexpression; however, overexpression of α-Actinin and Mlc2v was not detected. Interestingly, Ctnt, connexin40 and connexin45, the markers of ventricular, atrial, and pacemaker cells, respectively, were detected in by real-time PCR in TNNI3K overexpression group. our study indicated that TNNI3K overexpression promoted mESC differentiating into beating cardiomyocytes and induced up-regulating expression of cTnT by PKCε signal pathway, which suggested a modulation of TNNI3K activity as a potential therapeutic approach for ischemic cardiac disease. © 2017 The Author(s) Published by S. Karger AG, Basel.

Student Teachers’ Attitude towards Twitter for Educational Aims

Directory of Open Access Journals (Sweden)

Victoria I. Marín

2014-07-01

Full Text Available This paper presents an educational experience with 100 student teachers from different courses of the University of the Balearic Islands (Spain in which Twitter is used for various different activities. The aim of this experiment was to explore student teachers’ perceptions in order to value their attitude towards Twitter for educational aims. Afterwards, students were asked to write down their reflections on an eportfolio. Data was collected from their eportfolio evidence, which was analysed to review their attitude towards the use of Twitter for educational purposes and for their future teaching and professional development. The conclusions indicate the need to conduct different educational activities in which Twitter is used in various ways. In addition, conclusions reflect on the real impact of Twitter on students’ learning enhancement, in order to improve student teachers’ attitudes towards social media in education. Therefore, this article contributes to the body of existing research on the use of technology in education, specifically to the possibilities of the use of social media and microblogging in Teacher Education.

Numerical capacities as domain-specific predictors beyond early mathematics learning: a longitudinal study.

Science.gov (United States)

Reigosa-Crespo, Vivian; González-Alemañy, Eduardo; León, Teresa; Torres, Rosario; Mosquera, Raysil; Valdés-Sosa, Mitchell

2013-01-01

The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3(rd) and 4(th) grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively "start-up" tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school.

Evaluation of Waterford Steam Electric Station Unit 3 technical specifications

International Nuclear Information System (INIS)

Baxter, D.E.; Bruske, S.J.

1985-09-01

This document was prepared for the Nuclear Regulatory Commission (NRC) to assist them in determining whether the Waterford Steam Electric Station Unit 3 Technical Specifications (T/S), which govern plant systems configurations and operations, are in conformance with the requirements of the Final Safety Analysis Report (FSAR) as amended, and the requirements of the Safety Evaluation Report (SER) as supplemented. A comparative audit of the FSAR as amended, and the SER as supplemented was performed with the Waterford T/S. Several discrepancies were identified and subsequently resolved by the cognizant NRC reviewer. Pending completion of the resolutions noted in Part 3 of this report, the Waterford Steam Electric Station Unit 3 T/S, to the extent reviewed, are in conformance with the FSAR and SER

Epidermal growth factor-induced mobilization of a ganglioside-specific sialidase (NEU3) to membrane ruffles

International Nuclear Information System (INIS)

Yamaguchi, Kazunori; Hata, Keiko; Wada, Tadashi; Moriya, Setsuko; Miyagi, Taeko

2006-01-01

Human ganglioside-specific sialidase, NEU3, localized at cell membranes is thought to regulate various biological processes at cell surfaces. We here explored functional subcellular localization of the sialidase by immunofluorescence and found accumulation at leading edges of cell membranes in the presence of serum in culture. In response to EGF, the sialidase redistributed rapidly to ruffling cell membranes of squamous carcinoma A431 cells and co-localized with Rac-1. NEU3 overexpression enhanced Rac-1 activation and cell migration as compared with controls in HeLa cells as well as in A431 cells. Consistent with co-localization with Rac-1 by immunofluorescence, NEU3 was found to co-precipitate with activated Rac bound to GST-PAK-1 fusion protein. NEU3 silencing by siRNA, in contrast, resulted in inhibition of Rac-1 activation. These results indicate that NEU3 is able to mobilize to membrane ruffles in response to growth stimuli and activate the Rac-1 signaling by co-localization with Rac-1, leading to increased cell motility

Evaluating the benefits of government funded R & D aimed at the private sector

Science.gov (United States)

Greenberg, J. S.

1977-01-01

Federal funding of technological research and development is discussed with regard to the procedures for an economic analysis with the goals of (1) determining when the public sector should invest in a research and development program, (2) evaluating the likelihood of private sector participation in terms of public sector participation, and (3) considering the major factors in the formulation of a research and development program in terms of defining initiatives. Public sector investments are evaluated, noting procedures for determining whether benefits exceed costs. The role of the public sector research and development planning is described, considering the procedure for private sector implementation decisions and a methodology for evaluating the possibility of private sector commercialization. The economic value of the public sector research and development program is presented with attention given to a specific case of NASA-sponsored research and development aimed toward the commercialization of new public communications services.

Aims and methods of education: A recapitulation

Directory of Open Access Journals (Sweden)

Pantić Nataša

2007-01-01

Full Text Available This paper gives an overview of principal distinction between the aims of the so-called "traditional" and "progressive" education and respective pedagogies associated with each. The term "traditional" education is used to denote the kind of education that prepares people for their role in society as it is, while the term "progressive" is used for education that aspires to equip mankind with capacity to shape the change of society. The paper raises some critical questions about the role of pedagogy in achieving the aims of the progressive model, arguing that the employment of "progressive" methods does not necessarily guarantee the achievement of the commonly professed purposes of progressive education. This is illustrated in the paper by the results of a study in English schools showing how despite the claim of progressive methods, teachers tend to retain traditional attitudes and on the other hand, how even traditional teaching methods can serve the progressive purpose. This is not to advocate for the traditional pedagogy, but to suggest that it might be something other than pedagogy that makes a critical difference in educating liberal-minded citizens of the future. In this sense the paper explores the role of other factors that make a difference towards progressive education, such as democratization of human relations in school ethos and respect for children's freedom.

3D material cytometry (3DMaC): a very high-replicate, high-throughput analytical method using microfabricated, shape-specific, cell-material niches.

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Parratt, Kirsten; Jeong, Jenny; Qiu, Peng; Roy, Krishnendu

2017-08-08

Studying cell behavior within 3D material niches is key to understanding cell biology in health and diseases, and developing biomaterials for regenerative medicine applications. Current approaches to studying these cell-material niches have low throughput and can only analyze a few replicates per experiment resulting in reduced measurement assurance and analytical power. Here, we report 3D material cytometry (3DMaC), a novel high-throughput method based on microfabricated, shape-specific 3D cell-material niches and imaging cytometry. 3DMaC achieves rapid and highly multiplexed analyses of very high replicate numbers ("n" of 10 4 -10 6 ) of 3D biomaterial constructs. 3DMaC overcomes current limitations of low "n", low-throughput, and "noisy" assays, to provide rapid and simultaneous analyses of potentially hundreds of parameters in 3D biomaterial cultures. The method is demonstrated here for a set of 85 000 events containing twelve distinct cell-biomaterial micro-niches along with robust, customized computational methods for high-throughput analytics with potentially unprecedented statistical power.

Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression.

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Su, Liangping; Li, Hongyuan; Huang, Cheng; Zhao, Tingting; Zhang, Yongjun; Ba, Xueqing; Li, Zhongwei; Zhang, Yu; Huang, Baiqu; Lu, Jun; Zhao, Yanmei; Li, Xiaoxue

2018-03-06

Mounting evidence shows that histone methylation, a typical epigenetic mark, is crucial for gene expression regulation during aging. Decreased trimethylation of Lys 36 on histone H3 (H3K36me3) in worms and yeast is reported to shorten lifespan. The function of H3K36me2 in aging remains unclear. In this study, we identified Caenorhabditis elegans SET-18 as a histone H3K36 dimethyltransferase. SET-18 deletion extended lifespan and increased oxidative stress resistance, dependent on daf-16 activity in the insulin/IGF pathway. In set-18 mutants, transcription of daf-16 isoform a (daf-16a) was specifically upregulated. Accordingly, a decrease in H3K36me2 on daf-16a promoter was observed. Muscle-specific expression of SET-18 increased in aged worms (day 7 and day 11), attributable to elevation of global H3K36me2 and inhibition of daf-16a expression. Consequently, longevity was shortened. These findings suggested that chromatic repression mediated by tissue-specific H3K36 dimethyltransferase might be detrimental to lifespan and may have implications in human age-related diseases. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Genetic and biochemical characterization of an acquired subgroup B3 metallo-β-lactamase gene, blaAIM-1, and its unique genetic context in Pseudomonas aeruginosa from Australia.

Science.gov (United States)

Yong, Dongeun; Toleman, Mark A; Bell, Jan; Ritchie, Brett; Pratt, Rachael; Ryley, Henry; Walsh, Timothy R

2012-12-01

Three clinical Pseudomonas aeruginosa isolates (WCH2677, WCH2813, and WCH2837) isolated from the Women's and Children's Hospital, Adelaide, Australia, produced a metallo-β-lactamase (MBL)-positive Etest result. All isolates were PCR negative for known MBL genes. A gene bank was created, and an MBL gene, designated bla(AIM-1), was cloned and fully characterized. The encoded enzyme, AIM-1, is a group B3 MBL that has the highest level of identity to THIN-B and L1. It is chromosomal and flanked by two copies (one intact and one truncated) of an ISCR element, ISCR15. Southern hybridization studies indicated the movement of both ISCR15 and bla(AIM-1) within the three different clinical isolates. AIM-1 hydrolyzes most β-lactams, with the exception of aztreonam and, to a lesser extent, ceftazidime; however, it possesses significantly higher k(cat) values for cefepime and carbapenems than most other MBLs. AIM-1 was the first mobile group B3 enzyme detected and signals further problems for already beleaguered antimicrobial regimes to treat serious P. aeruginosa and other Gram-negative infections.

Neutron diffraction, specific heat and magnetic susceptibility of Ni3(PO4)2

International Nuclear Information System (INIS)

Escobal, J.; Pizarro, J.L.; Mesa, J.L.; Rojo, J.M.; Bazan, B.; Arriortua, M.I.; Rojo, T.

2005-01-01

The Ni 3 (PO 4 ) 2 phosphate was synthesized by the ceramic method in air atmosphere. The crystal structure consists of a three-dimensional skeleton constructed from Ni 3 O 14 edge-sharing octahedra, which are interconnected by (PO 4 ) 3- oxoanions with tetrahedral geometry. The magnetic behavior was studied on powdered sample by using susceptibility, specific heat and neutron diffraction data. The nickel(II) orthophosphate exhibits a three-dimensional magnetic ordering at approximately 17.1 K. However, its complex crystal structure hampers any parametrization of the J-exchange parameter. The specific heat measurements of Ni 3 (PO 4 ) 2 exhibit a three-dimensional magnetic ordering (λ-type) peak at 17.1 K. Measurements above T N suggest the presence of a small short-range order in this phase. The total magnetic entropy was found to be 28.1 KJ/mol at 50 K. The magnetic structure of the nickel(II) phosphate exhibits ferromagnetic interactions inside the Ni 3 O 14 trimers which are antiferromagnetically coupled between them, giving rise to a purely antiferromagnetic structure

Mod-5A wind turbine generator program design report. Volume 4: Drawings and specifications, book 3

Science.gov (United States)

1984-01-01

The design, development and analysis of the 7.3 MW MOD-5A wind turbine generator is documented. This volume contains the drawings and specifications developed for the final design. This volume is divided into 5 books of which this is the third, containing drawings 47A380074 through 47A380126. A full breakdown parts listing is provided as well as a where used list.

Apoptosis inhibitor of macrophage (AIM) diminishes lipid droplet-coating proteins leading to lipolysis in adipocytes

Energy Technology Data Exchange (ETDEWEB)

Iwamura, Yoshihiro; Mori, Mayumi; Nakashima, Katsuhiko [Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Mikami, Toshiyuki; Murayama, Katsuhisa [Genomic Science Laboratories, Dainippon Sumitomo Pharma Co. Ltd., 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-0022 (Japan); Arai, Satoko [Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Miyazaki, Toru, E-mail: tm@m.u-tokyo.ac.jp [Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

2012-06-08

Highlights: Black-Right-Pointing-Pointer AIM induces lipolysis in a distinct manner from that of hormone-dependent lipolysis. Black-Right-Pointing-Pointer AIM ablates activity of peroxisome proliferator-activated receptor in adipocytes. Black-Right-Pointing-Pointer AIM reduces mRNA levels of lipid-droplet coating proteins leading to lipolysis. -- Abstract: Under fasting conditions, triacylglycerol in adipose tissue undergoes lipolysis to supply fatty acids as energy substrates. Such lipolysis is regulated by hormones, which activate lipases via stimulation of specific signalling cascades. We previously showed that macrophage-derived soluble protein, AIM induces obesity-associated lipolysis, triggering chronic inflammation in fat tissue which causes insulin resistance. However, the mechanism of how AIM mediates lipolysis remains unknown. Here we show that AIM induces lipolysis in a manner distinct from that of hormone-dependent lipolysis, without activation or augmentation of lipases. In vivo and in vitro, AIM did not enhance phosphorylation of hormone-sensitive lipase (HSL) in adipocytes, a hallmark of hormone-dependent lipolysis activation. Similarly, adipose tissue from obese AIM-deficient and wild-type mice showed comparable HSL phosphorylation. Consistent with the suppressive effect of AIM on fatty acid synthase activity, the amount of saturated and unsaturated fatty acids was reduced in adipocytes treated with AIM. This response ablated transcriptional activity of peroxisome proliferator-activated receptor (PPAR{gamma}), leading to diminished gene expression of lipid-droplet coating proteins including fat-specific protein 27 (FSP27) and Perilipin, which are indispensable for triacylglycerol storage in adipocytes. Accordingly, the lipolytic effect of AIM was overcome by a PPAR{gamma}-agonist or forced expression of FSP27, while it was synergized by a PPAR{gamma}-antagonist. Overall, distinct modes of lipolysis appear to take place in different physiological

Ocean Science Video Challenge Aims to Improve Science Communication

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Showstack, Randy

2013-10-01

Given today's enormous management and protection challenges related to the world's oceans, a new competition calls on ocean scientists to effectively communicate their research in videos that last up to 3 minutes. The Ocean 180 Video Challenge, named for the number of seconds in 3 minutes, aims to improve ocean science communication while providing high school and middle school teachers and students with new and interesting educational materials about current science topics.

Anti-adipogenic effects of KD025 (SLx-2119), a ROCK2-specific inhibitor, in 3T3-L1 cells.

Science.gov (United States)

Diep, Duy Trong Vien; Hong, Kyungki; Khun, Triyeng; Zheng, Mei; Ul-Haq, Asad; Jun, Hee-Sook; Kim, Young-Bum; Chun, Kwang-Hoon

2018-02-06

Adipose tissue is a specialized organ that synthesizes and stores fat. During adipogenesis, Rho and Rho-associated kinase (ROCK) 2 are inactivated, which enhances the expression of pro-adipogenic genes and induces the loss of actin stress fibers. Furthermore, pan ROCK inhibitors enhance adipogenesis in 3T3-L1 cells. Here, we show that KD025 (formerly known as SLx-2119), a ROCK2-specific inhibitor, suppresses adipogenesis in 3T3-L1 cells partially through a ROCK2-independent mechanism. KD025 downregulated the expression of key adipogenic transcription factors PPARγ and C/EBPα during adipogenesis in addition to lipogenic factors FABP4 and Glut4. Interestingly, adipogenesis was blocked by KD025 during days 1~3 of differentiation; after differentiation terminated, lipid accumulation was unaffected. Clonal expansion occurred normally in KD025-treated cells. These results suggest that KD025 could function during the intermediate stage after clonal expansion. Data from depletion of ROCKs showed that KD025 suppressed cell differentiation partially independent of ROCK's activity. Furthermore, no further loss of actin stress fibers emerged in KD025-treated cells during and after differentiation compared to control cells. These results indicate that in contrast to the pro-adipogenic effect of pan-inhibitors, KD025 suppresses adipogenesis in 3T3-L1 cells by regulating key pro-adipogenic factors. This outcome further implies that KD025 could be a potential anti-adipogenic/obesity agent.

Analysis of Individuals from a Dengue-Endemic Region Helps Define the Footprint and Repertoire of Antibodies Targeting Dengue Virus 3 Type-Specific Epitopes.

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Andrade, Daniela V; Katzelnick, Leah C; Widman, Doug G; Balmaseda, Angel; de Silva, Aravinda M; Baric, Ralph S; Harris, Eva

2017-09-19

The four dengue virus serotypes (DENV1 to 4) cause dengue, a major public health problem worldwide. Individuals exposed to primary DENV infections develop serotype-specific neutralizing antibodies, including strongly neutralizing antibodies targeting quaternary epitopes. To date, no studies have measured the levels and kinetics of serum antibodies directed to such epitopes among populations in regions where dengue is endemic. Here, we use a recombinant DENV4 (rDENV4/3-M14) displaying a major DENV3 type-specific quaternary epitope recognized by human monoclonal antibody 5J7 to measure the proportion, magnitude, and kinetics of DENV3 type-specific neutralizing antibody responses targeting this epitope. Primary DENV3 sera from 30 individuals in a dengue hospital-based study in Nicaragua were studied 3, 6, 12, and 18 months post-infection, alongside samples collected annually 1 to 4 years post-primary DENV3 infection from 10 individuals in a cohort study in Nicaragua. We found substantial individual variation in the proportion of DENV3 type-specific neutralizing antibody titers attributed to the 5J7 epitope (range, 0 to 100%), with the mean significantly increasing from 22.6% to 41.4% from 3 to 18 months. We extended the transplanted DENV3 5J7 epitope on the virion (rDENV4/3-M16), resulting in increased recognition in several individuals, helping define the footprint of the epitope. However, 37% and 13% of the subjects still showed little to no recognition of the 5J7 epitope at 3 and 18 months, respectively, indicating that one or more additional DENV3 type-specific epitopes exist. Overall, this study demonstrates how DENV-immune plasma from populations from areas of endemicity, when coupled with structurally guided recombinant viruses, can help characterize the epitope-specific neutralizing antibody response in natural DENV infections, with direct implications for design and evaluation of dengue vaccines. IMPORTANCE The four serotypes of dengue virus cause dengue

Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control.

Science.gov (United States)

Hashimoto, H; Toide, K; Kitamura, R; Fujita, M; Tagawa, S; Itoh, S; Kamataki, T

1993-12-01

CYP3 A4 is the adult-specific form of cytochrome P450 in human livers [Komori, M., Nishio, K., Kitada, M., Shiramatsu, K., Muroya, K., Soma, M., Nagashima, K. & Kamataki, T. (1990) Biochemistry 29, 4430-4433]. The sequences of three genomic clones for CYP3A4 were analyzed for all exons, exon-intron junctions and the 5'-flanking region from the major transcription site to nucleotide position -1105, and compared with those of the CYP3A7 gene, a fetal-specific form of cytochrome P450 in humans. The results showed that the identity of 5'-flanking sequences between CYP3A4 and CYP3A7 genes was 91%, and that each 5'-flanking region had characteristic sequences termed as NFSE (P450NF-specific element) and HFLaSE (P450HFLa specific element), respectively. A basic transcription element (BTE) also lay in the 5'-flanking region of the CYP3A4 gene as seen in many CYP genes [Yanagida, A., Sogawa, K., Yasumoto, K. & Fujii-Kuriyama, Y. (1990) Mol. Cell. Biol. 10, 1470-1475]. The BTE binding factor (BTEB) was present in both adult and fetal human livers. To examine the transcriptional activity of the CYP3A4 gene, DNA fragments in the 5'-flanking region of the gene were inserted in front of the simian virus 40 promoter and the chloramphenicol acetyltransferase structural gene, and the constructs were transfected in HepG2 cells. The analysis of the chloramphenicol acetyltransferase activity indicated that (a) specific element(s) which could bind with a factor(s) in livers was present in the 5'-flanking region of the CYP3A4 gene to show the transcriptional activity.

Patient-specific dosimetry of 99mTc-HYNIC-Tyr3-Octreotide in patients with neuroendocrine tumors

International Nuclear Information System (INIS)

Chalkia, M.T.; Stefanoyiannis, A.P.; Prentakis, A.; Chatziioannou, S.N.; Armeniakos, I.; Geronikola-Trapali, X.; Liotsou, T.; Efstathopoulos, E.P.

2015-01-01

Full text of publication follows. Aim: a high concentration of somatostatin receptors is expressed in Neuroendocrine Tumors (NETs). The relatively new radiopharmaceutical 99m Tc-HYNIC-TOC ( 99m Tc-hydrazino-nicotinamide-Tyr3-Octreotide) is a somatostatin analogue which binds to somatostatin receptors with high affinity (particularly subtype 2 and, to a lesser extent, subtypes 3 and 5). Consequently, its use in clinical practice for the diagnosis of NETs is gradually gaining acceptance. The aim of this study is to present a 2-dimensional image-based dosimetric protocol for the commercially available 99m Tc-HYNIC-TOC. Application of this protocol results in the estimation of absorbed dose values for several organs and tumors, shedding light to the eligibility of patients for potential subsequent Peptide Receptor Radionuclide Therapy (PRRT). Materials and methods: 4 patients (3 females, 1 male) with metastatic NETs were administered with 725-920 MBq of 99m Tc-HYNIC-TOC. Anterior and posterior whole-body scans were acquired at 0, 2, 4, 5, 24 and 27 h p.i. using a single-head gamma camera. A SPECT scan was additionally obtained at 4 h p.i. for tumor localization. Quantitative analysis of planar images was based on the conjugate view method. Raw data were corrected for attenuation, self- attenuation, scatter and background activity. Absorbed doses were estimated using the MIRD schema. Volumes of organs and tumors were also obtained from planar images. Preliminary phantom-based validation of activity and volume estimated values was carried out. The % deviation of nominal and estimated activity and volume values was subsequently introduced in the dosimetric protocol, in the form of corresponding correction factors, which further enhance the precision of patients' dosimetric results. Results: the ranges of absorbed doses per unit of administered activity estimated for organs and tumors are: -) Kidneys: 0.010 - 0.026 mGy/MBq; -) Spleen: 0.041 - 0.065 mGy/MBq; -) Liver

Crystal structure of APOBEC3A bound to single-stranded DNA reveals structural basis for cytidine deamination and specificity.

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Kouno, Takahide; Silvas, Tania V; Hilbert, Brendan J; Shandilya, Shivender M D; Bohn, Markus F; Kelch, Brian A; Royer, William E; Somasundaran, Mohan; Kurt Yilmaz, Nese; Matsuo, Hiroshi; Schiffer, Celia A

2017-04-28

Nucleic acid editing enzymes are essential components of the immune system that lethally mutate viral pathogens and somatically mutate immunoglobulins, and contribute to the diversification and lethality of cancers. Among these enzymes are the seven human APOBEC3 deoxycytidine deaminases, each with unique target sequence specificity and subcellular localization. While the enzymology and biological consequences have been extensively studied, the mechanism by which APOBEC3s recognize and edit DNA remains elusive. Here we present the crystal structure of a complex of a cytidine deaminase with ssDNA bound in the active site at 2.2 Å. This structure not only visualizes the active site poised for catalysis of APOBEC3A, but pinpoints the residues that confer specificity towards CC/TC motifs. The APOBEC3A-ssDNA complex defines the 5'-3' directionality and subtle conformational changes that clench the ssDNA within the binding groove, revealing the architecture and mechanism of ssDNA recognition that is likely conserved among all polynucleotide deaminases, thereby opening the door for the design of mechanistic-based therapeutics.

Use of 14-3-3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease

Science.gov (United States)

Green, A; Thompson, E; Stewart, G; Zeidler, M; McKenzie, J; MacLeod, M; Ironside, J; Will, R; Knight, R

2001-01-01

OBJECTIVES—The detection of the protein 14-3-3 in the CSF has been shown to be a reliable and sensitive marker for sporadic Creutzfeldt-Jakob disease (CJD). Other brain-specific proteins such as neuron specific enolase (NSE), S-100b, and tau protein have also been reported to be increased in the CSF of patients with sporadic CJD. In 1996a variant of CJD (vCJD) was described which is likely to be causally linked to the bovine spongiform encephalopathy agent. This study reports and compares the findings of CSF brain specific protein analysis in 45 patients with vCJD and in 34 control patients.
METHODS—The CSF from 45 patients with vCJD and 34 controls were investigated for the presence of 14-3-3 by SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting with chemiluminescent detection. Tau protein, S-100b, and NSE concentrations in CSF were measured using enzyme immunoassays.
RESULTS—Protein 14-3-3 was detected in the CSF of 22/45 patients with vCJD and in 3/34 controls. The mean concentrations of NSE, S-100b, and tau protein in CSF were significantly raised in patients with vCJD compared with controls. The positive predictive value of CSF 14-3-3 was 86% and the negative predictive value was 63%. These values are lower than those reported for sporadic CJD. An increased CSF tau had a positive predictive value of 93% and a negative predictive value of 81%. The combination of CSF 14-3-3 and/or increased CSF tau had a positive predictive value of 91% and a negative predictive value of 84%.
CONCLUSIONS—CSF protein 14-3-3 is not as useful a marker for vCJD as it is for sporadic CJD. Increased concentration of CSF tau was found to be a sensitive marker of vCJD but as concentrations may be increased in many forms of non-CJD dementia, this may limit its usefulness as a diagnostic test.

 PMID:11385008

GRP1 PH Domain, Like AKT1 PH Domain, Possesses a Sentry Glutamate Residue Essential for Specific Targeting to Plasma Membrane PI(3,4,5)P3

Science.gov (United States)

Pilling, Carissa; Landgraf, Kyle E.; Falke, Joseph J.

2011-01-01

During the appearance of the signaling lipid PI(3,4,5)P3, an important subset of pleckstrin homology (PH) domains target signaling proteins to the plasma membrane. To ensure proper pathway regulation, such PI(3,4,5)P3-specific PH domains must exclude the more prevalant, constitutive plasma membrane lipid PI(4,5)P2 and bind the rare PI(3,4,5)P3 target lipid with sufficiently high affinity. Our previous study of the E17K mutant of protein kinase B (AKT1) PH domain, together with evidence from Carpten et al (1), revealed that the native AKT1 E17 residue serves as a sentry glutamate that excludes PI(4,5)P2, thereby playing an essential role in specific PI(3,4,5)P3 targeting (2). The sentry glutamate hypothesis proposes that an analogous sentry glutamate residue is a widespread feature of PI(3,4,5)P3-specific PH domains, and that charge reversal mutation at the sentry glutamate position will yield both increased PI(4,5)P2 affinity and constitutive plasma membrane targeting. To test this hypothesis the present study investigates the E345 residue, a putative sentry glutamate, of General Receptor for Phosphoinositides 1 (GRP1) PH domain. The results show that incorporation of the E345K charge reversal mutation into GRP1 PH domain enhances PI(4,5)P2 affinity 8-fold and yields constitutive plasma membrane targeting in cells, reminiscent of the effects of the E17K mutation in AKT1 PH domain. Hydrolysis of plasma membrane PI(4,5)P2 releases E345K GRP1 PH domain into the cytoplasm and the efficiency of this release increases when target Arf6 binding is disrupted. Overall, the findings provide strong support for the sentry glutamate hypothesis and suggest that the GRP1 E345K mutation will be linked to changes in cell physiology and human pathologies, as demonstrated for AKT1 E17K (1, 3). Analysis of available PH domain structures suggests that a lone glutamate residue (or, in some cases an aspartate) is a common, perhaps ubiquitous, feature of PI(3,4,5)P3-specific binding

Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells

Science.gov (United States)

Hepworth, Matthew R.; Fung, Thomas C.; Masur, Samuel H.; Kelsen, Judith R.; McConnell, Fiona M.; Dubrot, Juan; Withers, David R.; Hugues, Stephanie; Farrar, Michael A.; Reith, Walter; Eberl, Gerard; Baldassano, Robert N.; Laufer, Terri M.; Elson, Charles O.; Sonnenberg, Gregory F.

2015-01-01

Inflammatory CD4+ T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. While selection of self-specific T cells in the thymus limits responses to tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells, and that MHCII+ ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on human colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4+ T cells in the intestine, and suggest that this process is dysregulated in human IBD. PMID:25908663

Demonstration of specific binding sites for 3H-RRR-alpha-tocopherol on human erythrocytes

International Nuclear Information System (INIS)

Kitabchi, A.E.; Wimalasena, J.

1982-01-01

Previous work from our laboratory demonstrated specific binding sites for 3 H-RRR-alpha-tocopherol ( 3 H-d alpha T) in membranes of rat adrenal cells. As tocopherol deficiency is associated with increased susceptibility of red blood cells to hemolysis, we investigated tocopherol binding sites in human RBCs. Erythrocytes were found to have specific binding sites for 3 H-d alpha T that exhibited saturability and time and cell-concentration dependence as well as reversibility of binding. Kinetic studies of binding demonstrated two binding sites--one with high affinity (Ka of 2.6 x 10(7) M-1), low capacity (7,600 sites per cell) and the other with low affinity (1.2 x 10(6) M-1), high capacity (150,000 sites per cell). In order to localize the binding sites further, RBCs were fractionated and greater than 90% of the tocopherol binding was located in the membranes. Similar to the findings in intact RBCs, the membranes exhibited two binding sites with a respective Ka of 3.3 x 10(7) M-1 and 1.5 x 10(6) M-1. Specificity data for binding demonstrated 10% binding for RRR-gamma-tocopherol, but not other tocopherol analog exhibited competition for 3 H-d alpha T binding sites. Instability data suggested a protein nature for these binding sites. Preliminary studies on Triton X-100 solubilized fractions resolved the binding sites to a major component with an Mr of 65,000 and a minor component with an Mr of 125,000. We conclude that human erythrocyte membranes contain specific binding sites for RRR-alpha-tocopherol. These sites may be of physiologic significance in the function of tocopherol on the red blood cell membrane

Preferred SH3 domain partners of ADAM metalloproteases include shared and ADAM-specific SH3 interactions.

Directory of Open Access Journals (Sweden)

Iivari Kleino

Full Text Available 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.

Motivations, aims and communication around advance directives: a mixed-methods study into the perspective of their owners and the influence of a current illness.

Science.gov (United States)

van Wijmen, Matthijs P S; Pasman, H Roeline W; Widdershoven, Guy A M; Onwuteaka-Philipsen, Bregje D

2014-06-01

What are motivations of owners of an advance directive (AD) to draft an AD, what do they aim for with their AD and do they communicate about their AD? Written questionnaires were sent to a cohort of people owning different types of ADs (n=5768). A purposive sample of people suffering from an illness was selected from the cohort for an in-depth interview (n=29). About half of our population had no direct motivation to draft their AD. Most mentioned motivation for the other half was an illness of a family member or friend. Many different and specific aims for drafting an AD were mentioned. An often mentioned more general aim in people with different ADs was to prevent unnecessary lengthening of life or treatment (14-16%). Most respondents communicated about having an AD with close-ones (63-88%) and with their GP (65-79%). In the interviews people gave vivid examples of experiences of what they hoped to prevent at the end of life. Some mentioned difficulties foreseeing the future and gave examples of response shift. ADs can give directions to caregivers about what people want at the end of life. ADs have to be discussed in detail by their owners and caregivers, since owners often have specific aims with their AD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Numerical Capacities as Domain-Specific Predictors beyond Early Mathematics Learning: A Longitudinal Study

Science.gov (United States)

Reigosa-Crespo, Vivian; González-Alemañy, Eduardo; León, Teresa; Torres, Rosario; Mosquera, Raysil; Valdés-Sosa, Mitchell

2013-01-01

The first aim of the present study was to investigate whether numerical effects (Numerical Distance Effect, Counting Effect and Subitizing Effect) are domain-specific predictors of mathematics development at the end of elementary school by exploring whether they explain additional variance of later mathematics fluency after controlling for the effects of general cognitive skills, focused on nonnumerical aspects. The second aim was to address the same issues but applied to achievement in mathematics curriculum that requires solutions to fluency in calculation. These analyses assess whether the relationship found for fluency are generalized to mathematics content beyond fluency in calculation. As a third aim, the domain specificity of the numerical effects was examined by analyzing whether they contribute to the development of reading skills, such as decoding fluency and reading comprehension, after controlling for general cognitive skills and phonological processing. Basic numerical capacities were evaluated in children of 3rd and 4th grades (n=49). Mathematics and reading achievements were assessed in these children one year later. Results showed that the size of the Subitizing Effect was a significant domain-specific predictor of fluency in calculation and also in curricular mathematics achievement, but not in reading skills, assessed at the end of elementary school. Furthermore, the size of the Counting Effect also predicted fluency in calculation, although this association only approached significance. These findings contrast with proposals that the core numerical competencies measured by enumeration will bear little relationship to mathematics achievement. We conclude that basic numerical capacities constitute domain-specific predictors and that they are not exclusively “start-up” tools for the acquisition of Mathematics; but they continue modulating this learning at the end of elementary school. PMID:24255710

Modelling 3D spatial objects in a geo-DBMS using a 3D primitive

Science.gov (United States)

Arens, Călin; Stoter, Jantien; van Oosterom, Peter

2005-03-01

There is a growing interest in modelling the world in three dimensions, both in applications and in science. At the same time, geographical information systems are changing into integrated architecture in which administrative and spatial data are maintained in one environment. It is for this reason that mainstream Data Base Management Systems (DBMSs) have implemented spatial data types according to the 'Simple Feature Specifications for SQL', described by the OpenGeospatial Consortium. However, these specifications are 2D, as indeed are the implementations in DBMSs. At the Section GIS Technology of TU Delft, research has been carried out in which a 3D primitive was implemented in a DBMS (Oracle Spatial). To explore the possibilities and complications, a fairly simple 3D primitive was chosen to start with: a polyhedron. In the future the study will be extended with more complex primitives, the ultimate aim being to build 3D models with features closer to the real world. Besides the data structure, a validation function was developed to check the geometric accuracy of the data. Rules for validation were established and translated into prototype implementations with the aid of literature. In order to manipulate the data, a list of useful 3D functions was specified. Most of these were translated into algorithms, which were implemented in the DBMS. The algorithms for these functions were obtained from the relevant literature. The research also comprised a comparative performance test on spatial indexing in 2D and 3D, using an R-tree. Finally, existing software was used to visualize 3D objects structured with the implemented 3D primitive. This research is a first attempt to implement a true 3D primitive in a DBMS. Future research will focus on extending and improving the implementations and on optimizing maintenance and query of 3D objects in DBMSs.

Implantation of 3D-Printed Patient-Specific Aneurysm Models into Cadaveric Specimens: A New Training Paradigm to Allow for Improvements in Cerebrovascular Surgery and Research

Directory of Open Access Journals (Sweden)

Arnau Benet

2015-01-01

Full Text Available Aim. To evaluate the feasibility of implanting 3D-printed brain aneurysm model in human cadavers and to assess their utility in neurosurgical research, complex case management/planning, and operative training. Methods. Two 3D-printed aneurysm models, basilar apex and middle cerebral artery, were generated and implanted in four cadaveric specimens. The aneurysms were implanted at the same anatomical region as the modeled patient. Pterional and orbitozygomatic approaches were done on each specimen. The aneurysm implant, manipulation capabilities, and surgical clipping were evaluated. Results. The 3D aneurysm models were successfully implanted to the cadaveric specimens’ arterial circulation in all cases. The features of the neck in terms of flexibility and its relationship with other arterial branches allowed for the practice of surgical maneuvering characteristic to aneurysm clipping. Furthermore, the relationship of the aneurysm dome with the surrounding structures allowed for better understanding of the aneurysmal local mass effect. Noticeably, all of these observations were done in a realistic environment provided by our customized embalming model for neurosurgical simulation. Conclusion. 3D aneurysms models implanted in cadaveric specimens may represent an untapped training method for replicating clip technique; for practicing certain approaches to aneurysms specific to a particular patient; and for improving neurosurgical research.

A Novel Complementation Assay for Quick and Specific Screen of Genes Encoding Glycerol-3-Phosphate Acyltransferases

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Jie Lei

2018-03-01

Full Text Available The initial step in glycerolipid biosynthesis, especially in diverse allopolyploid crop species, is poorly understood, mainly due to the lack of an effective and convenient method for functional characterization of genes encoding glycerol-3-phosphate acyltransferases (GPATs catalyzing this reaction. Here we present a novel complementation assay for quick and specific characterization of GPAT-encoding genes. Its key design involves rational construction of yeast conditional lethal gat1Δgat2Δ double mutant bearing the heterologous Arabidopsis AtGPAT1 gene whose leaky expression under repressed conditions does not support any non-specific growth, thereby circumventing the false positive problem encountered with the system based on the gat1Δgat2Δ mutant harboring the native episomal GAT1 gene whose leaky expression appears to be sufficient for generating enough GPAT activities for the non-specific restoration of the mutant growth. A complementation assay developed based on this novel mutant enables quick phenotypic screen of GPAT sequences. A high degree of specificity of our assay was exemplified by its ability to differentiate effectively GPAT-encoding genes from those of other fatty acyltransferases and lipid-related sequences. Using this assay, we show that Arabidopsis AtGPAT1, AtGPAT5, and AtGPAT7 can complement the phosphatidate biosynthetic defect in the double mutants. Collectively, our assay provides a powerful tool for rapid screening, validation and optimization of GPAT sequences, aiding future engineering of the initial step of the triacylglycerol biosynthesis in oilseeds.

How 3D patient-specific instruments improve accuracy of pelvic bone tumour resection in a cadaveric study.

Science.gov (United States)

Sallent, A; Vicente, M; Reverté, M M; Lopez, A; Rodríguez-Baeza, A; Pérez-Domínguez, M; Velez, R

2017-10-01

To assess the accuracy of patient-specific instruments (PSIs) versus standard manual technique and the precision of computer-assisted planning and PSI-guided osteotomies in pelvic tumour resection. CT scans were obtained from five female cadaveric pelvises. Five osteotomies were designed using Mimics software: sacroiliac, biplanar supra-acetabular, two parallel iliopubic and ischial. For cases of the left hemipelvis, PSIs were designed to guide standard oscillating saw osteotomies and later manufactured using 3D printing. Osteotomies were performed using the standard manual technique in cases of the right hemipelvis. Post-resection CT scans were quantitatively analysed. Student's t -test and Mann-Whitney U test were used. Compared with the manual technique, PSI-guided osteotomies improved accuracy by a mean 9.6 mm (p 5 mm and 27% (n = 8) were > 10 mm. In the PSI cases, deviations were 10% (n = 3) and 0 % (n = 0), respectively. For angular deviation from pre-operative plans, we observed a mean improvement of 7.06° (p Cite this article : A. Sallent, M. Vicente, M. M. Reverté, A. Lopez, A. Rodríguez-Baeza, M. Pérez-Domínguez, R. Velez. How 3D patient-specific instruments improve accuracy of pelvic bone tumour resection in a cadaveric study. Bone Joint Res 2017;6:577-583. DOI: 10.1302/2046-3758.610.BJR-2017-0094.R1. © 2017 Sallent et al.

Towards a unified theory of task-specific motivation

NARCIS (Netherlands)

De Brabander, Cornelis; Martens, Rob

2014-01-01

This study aims to integrate the current proliferation of motivation theories in a Unified Model of Task-specific Motivation (UMTM). According to this model readiness for action results from an interaction between four relatively independent types of valences that can be classified as affective or

Specific heat studies of pure Nb3Sn single crystals at low temperature

International Nuclear Information System (INIS)

Escudero, R; Morales, F; Bernes, S

2009-01-01

Specific heat measurements performed on high purity vapor-grown Nb 3 Sn crystals show clear features related to both the martensitic and superconducting transitions. Our measurements indicate that the martensitic anomaly does not display hysteresis, meaning that the martensitic transition could be a weak first-order or a second-order thermodynamic transition. Careful measurements of the two transition temperatures display an inverse correlation between them. At low temperature, specific heat measurements show the existence of a single superconducting energy gap feature.

Dual-specificity phosphatase 3 deficiency or inhibition limits platelet activation and arterial thrombosis.

Science.gov (United States)

Musumeci, Lucia; Kuijpers, Marijke J; Gilio, Karen; Hego, Alexandre; Théâtre, Emilie; Maurissen, Lisbeth; Vandereyken, Maud; Diogo, Catia V; Lecut, Christelle; Guilmain, William; Bobkova, Ekaterina V; Eble, Johannes A; Dahl, Russell; Drion, Pierre; Rascon, Justin; Mostofi, Yalda; Yuan, Hongbin; Sergienko, Eduard; Chung, Thomas D Y; Thiry, Marc; Senis, Yotis; Moutschen, Michel; Mustelin, Tomas; Lancellotti, Patrizio; Heemskerk, Johan W M; Tautz, Lutz; Oury, Cécile; Rahmouni, Souad

2015-02-17

A limitation of current antiplatelet therapies is their inability to separate thrombotic events from bleeding occurrences. A better understanding of the molecular mechanisms leading to platelet activation is important for the development of improved therapies. Recently, protein tyrosine phosphatases have emerged as critical regulators of platelet function. This is the first report implicating the dual-specificity phosphatase 3 (DUSP3) in platelet signaling and thrombosis. This phosphatase is highly expressed in human and mouse platelets. Platelets from DUSP3-deficient mice displayed a selective impairment of aggregation and granule secretion mediated by the collagen receptor glycoprotein VI and the C-type lectin-like receptor 2. DUSP3-deficient mice were more resistant to collagen- and epinephrine-induced thromboembolism compared with wild-type mice and showed severely impaired thrombus formation on ferric chloride-induced carotid artery injury. Intriguingly, bleeding times were not altered in DUSP3-deficient mice. At the molecular level, DUSP3 deficiency impaired Syk tyrosine phosphorylation, subsequently reducing phosphorylation of phospholipase Cγ2 and calcium fluxes. To investigate DUSP3 function in human platelets, a novel small-molecule inhibitor of DUSP3 was developed. This compound specifically inhibited collagen- and C-type lectin-like receptor 2-induced human platelet aggregation, thereby phenocopying the effect of DUSP3 deficiency in murine cells. DUSP3 plays a selective and essential role in collagen- and C-type lectin-like receptor 2-mediated platelet activation and thrombus formation in vivo. Inhibition of DUSP3 may prove therapeutic for arterial thrombosis. This is the first time a protein tyrosine phosphatase, implicated in platelet signaling, has been targeted with a small-molecule drug. © 2014 American Heart Association, Inc.

The diverse aims of science.

Science.gov (United States)

Potochnik, Angela

2015-10-01

There is increasing attention to the centrality of idealization in science. One common view is that models and other idealized representations are important to science, but that they fall short in one or more ways. On this view, there must be an intermediary step between idealized representation and the traditional aims of science, including truth, explanation, and prediction. Here I develop an alternative interpretation of the relationship between idealized representation and the aims of science. I suggest that continuing, widespread idealization calls into question the idea that science aims for truth. If instead science aims to produce understanding, this would enable idealizations to directly contribute to science's epistemic success. I also use the fact of widespread idealization to motivate the idea that science's wide variety aims, epistemic and non-epistemic, are best served by different kinds of scientific products. Finally, I show how these diverse aims—most rather distant from truth—result in the expanded influence of social values on science. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neural Correlates of Expert Behavior During a Domain-Specific Attentional Cueing Task in Badminton Players.

Science.gov (United States)

Wang, Chun-Hao; Tu, Kuo-Cheng

2017-06-01

The present study aimed to investigate the neural correlates associated with sports expertise during a domain-specific task in badminton players. We compared event-related potentials activity from collegiate male badminton players and a set of matched athletic controls when they performed a badminton-specific attentional cueing task in which the uncertainty and validity were manipulated. The data showed that, regardless of cue type, the badminton players had faster responses along with greater P3 amplitudes than the athletic controls on the task. Specifically, the contingent negative variation amplitude was smaller for the players than for the controls in the condition involving higher uncertainty. Such an effect, however, was absent in the condition with lower uncertainty. We conclude that expertise in sports is associated with proficient modulation of brain activity during cognitive and motor preparation, as well as response execution, when performing a task related to an individual's specific sport domain.

Identification of a functional element in the promoter of the silkworm (Bombyx mori) fat body-specific gene Bmlp3.

Science.gov (United States)

Xu, Hanfu; Deng, Dangjun; Yuan, Lin; Wang, Yuancheng; Wang, Feng; Xia, Qingyou

2014-08-01

30K proteins are a group of structurally related proteins that play important roles in the life cycle of the silkworm Bombyx mori and are largely synthesized and regulated in a time-dependent manner in the fat body. Little is known about the upstream regulatory elements associated with the genes encoding these proteins. In the present study, the promoter of Bmlp3, a fat body-specific gene encoding a 30K protein family member, was characterized by joining sequences containing the Bmlp3 promoter with various amounts of 5' upstream sequences to a luciferase reporter gene. The results indicated that the sequences from -150 to -250bp and -597 to -675bp upstream of the Bmlp3 transcription start site were necessary for high levels of luciferase activity. Further analysis showed that a 21-bp sequence located between -230 and -250 was specifically recognized by nuclear factors from silkworm fat bodies and BmE cells, and could enhance luciferase reporter-gene expression 2.8-fold in BmE cells. This study provides new insights into the Bmlp3 promoter and contributes to the further clarification of the function and developmental regulation of Bmlp3. Copyright © 2014. Published by Elsevier B.V.

Communication: Mode specific quantum dynamics of the F + CHD{sub 3} → HF + CD{sub 3} reaction

Energy Technology Data Exchange (ETDEWEB)

Qi, Ji; Song, Hongwei; Yang, Minghui, E-mail: yangmh@wipm.ac.cn, E-mail: juliana@unq.edu.ar, E-mail: uwe.manthe@uni-bielefeld.de [Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Palma, Juliana, E-mail: yangmh@wipm.ac.cn, E-mail: juliana@unq.edu.ar, E-mail: uwe.manthe@uni-bielefeld.de [Departamento de Ciencia y Tecnología, Universidad Nacional de Quilmes, CONICET, Sáenz Peña 352, Bernal B1876BXD (Argentina); Manthe, Uwe, E-mail: yangmh@wipm.ac.cn, E-mail: juliana@unq.edu.ar, E-mail: uwe.manthe@uni-bielefeld.de [Theoretische Chemie, Fakultät für Chemie, Universität Bielefeld, Universitätsstr. 25, D-33615 Bielefeld (Germany); Guo, Hua [Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131 (United States)

2016-05-07

The mode specific reactivity of the F + CHD{sub 3} → HF + CD{sub 3} reaction is investigated using an eight-dimensional quantum dynamical model on a recently developed ab initio based full-dimensional potential energy surface. Our results indicate prominent resonance structures at low collision energies and absence of an energy threshold in reaction probabilities. It was also found that excitation of the C–D stretching or CD{sub 3} umbrella mode has a relatively small impact on reactivity. On the other hand, the excitation of the C–H vibration (v{sub 1}) in CHD{sub 3} is shown to significantly increase the reactivity, which, like several recent quasi-classical trajectory studies, is at odds with the available experimental data. Possible sources of the disagreement are discussed.

Specific heat measurements of CePt{sub 3}Si and Ce{sub 1+x}Pt{sub 3+y}Si{sub 1+z}

Energy Technology Data Exchange (ETDEWEB)

Motoyama, G. [Graduate School of Material Science, University of Hyogo, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan)]. E-mail: motoyama@sci.u-hyogo.ac.jp; Watanabe, M. [Graduate School of Material Science, University of Hyogo, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan); Maeda, K. [Graduate School of Material Science, University of Hyogo, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan); Oda, Y. [Graduate School of Material Science, University of Hyogo, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan); Ueda, K. [Graduate School of Material Science, University of Hyogo, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan); Kohara, T. [Graduate School of Material Science, University of Hyogo, Kamigori-cho, Ako-gun, Hyogo 678-1297 (Japan)

2007-03-15

We have measured the specific heat of a series of polycrystalline CePt{sub 3}Si and Ce{sub 1+x}Pt{sub 3+y}Si{sub 1+z} samples whose compositions vary slightly from the stoichiometric composition. We observed two peaks derived from magnetic anomalies on the specific heat measurements of the Ce{sub 1+x}Pt{sub 3+y}Si{sub 1+z} samples. One of the peaks relates to the antiferromagnetic phase transition at T{sub N}=2.2K. The other is a large peak at 2.7K observed for the sample that showed a ferromagnetic anomaly at 3.0K on the temperature dependence of the magnetization. Heat treatment had different effects between these anomalies.

Low-temperature specific heat measurements on the NdCoxFe1-xO3 system

International Nuclear Information System (INIS)

Bartolome, F.; Kuz'min, M.D.; Bartolome, J.; Blasco, J.; Garcia, J.

1995-01-01

Low-temperature specific heat measurements have been carried out on the NdCo x Fe 1-x O 3 perovskite system (x=0, 0.25, 0.5, 0.9, 1). Magnetic ordering of Nd 3+ ions have been observed in NdCoO 3 (at 1.20 K) and NdFeO 3 (at 1.05 K). The studied dilutions, unlike the pure Fe or Co compounds, do not show a magnetic order of the Nd ions due to the stronger molecular field caused by decompensation of the internal field upon the introduction of the (Co 3+ ) magnetic vacancies in the antiferromagnetically ordered Fe subsystem. The specific heat curve of the system at x=0.9 resembles spin-glass behaviour. ((orig.))

The peripheral binding of 14-3-3γ to membranes involves isoform-specific histidine residues.

Directory of Open Access Journals (Sweden)

Helene J Bustad

Full Text Available Mammalian 14-3-3 protein scaffolds include seven conserved isoforms that bind numerous phosphorylated protein partners and regulate many cellular processes. Some 14-3-3-isoforms, notably γ, have elevated affinity for membranes, which might contribute to modulate the subcellular localization of the partners and substantiate the importance of investigating molecular mechanisms of membrane interaction. By applying surface plasmon resonance we here show that the binding to phospholipid bilayers is stimulated when 14-3-3γ is complexed with its partner, a peptide corresponding to the Ser19-phosphorylated N-terminal region of tyrosine hydroxylase. Moreover, membrane interaction is dependent on salts of kosmotropic ions, which also stabilize 14-3-3γ. Electrostatic analysis of available crystal structures of γ and of the non-membrane-binding ζ-isoform, complemented with molecular dynamics simulations, indicate that the electrostatic potential distribution of phosphopeptide-bound 14-3-3γ is optimal for interaction with the membrane through amphipathic helices at the N-terminal dimerization region. In addition, His158, and especially His195, both specific to 14-3-3γ and located at the convex lateral side, appeared to be pivotal for the ligand induced membrane interaction, as corroborated by site-directed mutagenesis. The participation of these histidine residues might be associated to their increased protonation upon membrane binding. Overall, these results reveal membrane-targeting motifs and give insights on mechanisms that furnish the 14-3-3γ scaffold with the capacity for tuned shuffling from soluble to membrane-bound states.

An HTS-compatible 3D colony formation assay to identify tumor-specific chemotherapeutics.

Science.gov (United States)

Horman, Shane R; To, Jeremy; Orth, Anthony P

2013-12-01

There has been increasing interest in the development of cellular behavior models that take advantage of three-dimensional (3D) cell culture. To enable assessment of differential perturbagen impacts on cell growth in 2D and 3D, we have miniaturized and adapted for high-throughput screening (HTS) the soft agar colony formation assay, employing a laser-scanning cytometer to image and quantify multiple cell types simultaneously. The assay is HTS compatible, providing high-quality, image-based, replicable data for multiple, co-cultured cell types. As proof of concept, we subjected colorectal carcinoma colonies in 3D soft agar to a mini screen of 1528 natural product compounds. Hit compounds from the primary screen were rescreened in an HTS 3D co-culture matrix containing colon stromal cells and cancer cells. By combining tumor cells and normal, nontransformed colon epithelial cells in one primary screening assay, we were able to obtain differential IC50 data, thereby distinguishing tumor-specific compounds from general cytotoxic compounds. Moreover, we were able to identify compounds that antagonized tumor colony formation in 3D only, highlighting the importance of this assay in identifying agents that interfere with 3D tumor structural growth. This screening platform provides a fast, simple, and robust method for identification of tumor-specific agents in a biologically relevant microenvironment.

"Anomalous" excitation in hydrogen-bonded molecular crystals - a Raman scattering study of specifically deuterated acetanilide (C 6D 5-CONH-CD 3)

Science.gov (United States)

Sauvajol, J. L.; De Nunzio, G.; Almairac, R.; Moret, J.; Barthés, M.; Bataillon, Place E.

1991-01-01

The focus of experimental and theoretical works about crystalline Acetanilide has been the "anomalous" temperature-dependent ir absorption and Raman peaks at about 1650 cm -1 and the multiband structure in the N-H stretch region. A lively discussion about the assignment of these "anomalous" bands has arisen and is still in progress. The present Raman experiments should be placed in this context as an attempt to identify the molecular degrees of freedom which originate the "anomalous" bands. In this aim Raman experiments have been performed on specifically deuterated Acetanilide [C 6D 5-CONH-CD 3] single crystal in the low-frequency (phonon) and C=O stretching regions. On cooling a distinct band at about 1495 cm -1 increases in intensity. We assign this peak to the equivalent of the 1650 cm -1 band in Acetanilide. The temperature dependence of this Raman line was studied. The results are discussed in the light of the models proposed to explain the anomalous behaviour of the 1650 cm -1 Raman line in Acetanilide.

Synthesis of [14α, 15α-3H]-17α-cyanomethyl-17β-hydroxyestra-4.9-diene-3-one - a specifically tritium labelled gestagen

International Nuclear Information System (INIS)

Roemer, J.; Wagner, H.

1978-05-01

Synthesis of [14α, 15α- 3 H 2 ]-17α-cyanomethyl-17β-hydroxyestra-4.9-diene-3-one from quantitativly tritiated [14α, 15α- 3 H 2 ]-3-methoxyestra-1,3,5(10),8-tetraene-17β-ol is described. The determination of the radiochemical purity and chemical yield was carried out by thin-layer chromatography. Preparative thin-layer chromatography was used for purifying the final product. By-products formed in the course of synthesis could be detected by determining and comparing specific activities of the intermediate products. Radiolytic investigations revealed the instability of the tritium labelled dienone system. (author)

Diversity of PR3-ANCA epitope specificity in Wegener's granulomatosis. Analysis using the biosensor technology

NARCIS (Netherlands)

Rarok, Agnieszka; van der Geld, Y.M.; Stegeman, Coen; Limburg, Piet; Kallenberg, Cees

Wegener's granulomatosis is a systemic disease characterized by the presence of antineutrophil cytoplasm autoantibodies specific for proteinase 3 (PR3-ANCA). The functional characteristics of PR3-ANCA differ between quiescent and active disease, suggesting changes in the properties of the

How specific is specific self-efficacy?

DEFF Research Database (Denmark)

Nielsen, Tine; Makransky, Guido; Vang, Maria Louison

2017-01-01

academic learning self-efficacy (SAL-SE) and specific academic exam self-efficacy (SAE-SE), each scale being measurement invariant relative to age, Gender, admission method and specific course targeted. Furthermore, significant and relevant differences between the SAL-SE and SAE-SE scores dependent......Self-efficacy is an important and much used construct in psychology and social science studies. The validity of the measurements used is not always sufficiently evaluated. The aim was to evaluate the psychometric properties of the Danish translation of the self-efficacy subscale of The Motivated...... Strategies for Learning Questionnaire (MSLQ-SE) within a higher education context. Rasch measurement models were employed focusing on measurement invariance and dimensionality. Results with one students sample showed the MSLQ-SE to be not one, but two separate unidimensional subscales, measuring specific...

Tissue-specific and pathogen-induced regulation of a Nicotiana plumbaginifolia beta-1,3-glucanase gene.

Science.gov (United States)

Castresana, C; de Carvalho, F; Gheysen, G; Habets, M; Inzé, D; Van Montagu, M

1990-01-01

The Nicotiana plumbaginifolia gn1 gene encoding a beta-1,3-glucanase isoform has been characterized. The gn1 product represents an isoform distinct from the previously identified tobacco beta-1,3-glucanases. By expressing gn1 in Escherichia coli, we have determined directly that the encoded protein does, indeed, correspond to a beta-1,3-glucanase. In N. plumbaginifolia, gn1 was found to be expressed in roots and older leaves. Transgenic tobacco plants containing the 5'-noncoding region of gn1 fused to the beta-glucuronidase (GUS) reporter gene also showed maximum levels of GUS activity in roots and older leaves. No detectable activity was present in the upper part of the transgenic plants with the exception of stem cells at the bases of emerging shoots. The expression conferred by the gn1 promoter was differentially induced in response to specific plant stress treatments. Studies of three plant-bacteria interactions showed high levels of GUS activity when infection resulted in a hypersensitive reaction. Increased gene expression was confined to cells surrounding the necrotic lesions. The observed expression pattern suggests that the characterized beta-1,3-glucanase plays a role both in plant development and in the defense response against pathogen infection. PMID:2152158

In vitro characterization of 3D printed scaffolds aimed at bone tissue regeneration.

Science.gov (United States)

Boga, João C; Miguel, Sónia P; de Melo-Diogo, Duarte; Mendonça, António G; Louro, Ricardo O; Correia, Ilídio J

2018-05-01

The incidence of fractures and bone-related diseases like osteoporosis has been increasing due to aging of the world's population. Up to now, grafts and titanium implants have been the principal therapeutic approaches used for bone repair/regeneration. However, these types of treatment have several shortcomings, like limited availability, risk of donor-to-recipient infection and tissue morbidity. To overcome these handicaps, new 3D templates, capable of replicating the features of the native tissue, are currently being developed by researchers from the area of tissue engineering. These 3D constructs are able to provide a temporary matrix on which host cells can adhere, proliferate and differentiate. Herein, 3D cylindrical scaffolds were designed to mimic the natural architecture of hollow bones, and to allow nutrient exchange and bone neovascularization. 3D scaffolds were produced with tricalcium phosphate (TCP)/alginic acid (AA) using a Fab@home 3D printer. Furthermore, graphene oxide (GO) was incorporated into the structure of some scaffolds to further enhance their mechanical properties. The results revealed that the scaffolds incorporating GO displayed greater porosity, without impairing their mechanical properties. These scaffolds also presented a controlled swelling profile, enhanced biomineralization capacity and were able to increase the Alkaline Phosphatase (ALP) activity. Such characteristics make TCP/AA scaffolds functionalized with GO promising 3D constructs for bone tissue engineering applications. Copyright © 2018 Elsevier B.V. All rights reserved.

An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

Science.gov (United States)

Kutys, Matthew L; Yamada, Kenneth M

2014-09-01

Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

Specific phosphopeptide binding regulates a conformational change in the PI 3-kinase SH2 domain associated with enzyme activation.

Science.gov (United States)

Shoelson, S E; Sivaraja, M; Williams, K P; Hu, P; Schlessinger, J; Weiss, M A

1993-01-01

SH2 (src-homology 2) domains define a newly recognized binding motif that mediates the physical association of target phosphotyrosyl proteins with downstream effector enzymes. An example of such phosphoprotein-effector coupling is provided by the association of phosphatidylinositol 3-kinase (PI 3-kinase) with specific phosphorylation sites within the PDGF receptor, the c-Src/polyoma virus middle T antigen complex and the insulin receptor substrate IRS-1. Notably, phosphoprotein association with the SH2 domains of p85 also stimulates an increase in catalytic activity of the PI 3-kinase p110 subunit, which can be mimicked by phosphopeptides corresponding to targeted phosphoprotein phosphorylation sites. To investigate how phosphoprotein binding to the p85 SH2 domain stimulates p110 catalytic activation, we have examined the differential effects of phosphotyrosine and PDGF receptor-, IRS-1- and c-Src-derived phosphopeptides on the conformation of an isolated SH2 domain of PI 3-kinase. Although phosphotyrosine and both activating and non-activating phosphopeptides bind to the SH2 domain, activating phosphopeptides bind with higher affinity and induce a qualitatively distinct conformational change as monitored by CD and NMR spectroscopy. Amide proton exchange and protease protection assays further show that high affinity, specific phosphopeptide binding induces non-local dynamic SH2 domain stabilization. Based on these findings we propose that specific phosphoprotein binding to the p85 subunit induces a change in SH2 domain structure which is transmitted to the p110 subunit and regulates enzymatic activity by an allosteric mechanism. Images PMID:8382612

Action Information Management System (AIMS): a User's View

Science.gov (United States)

Wiskerchen, M.

1984-01-01

The initial approach used in establishing a user-defined information system to fulfill the needs of users at NASA Headquarters was unsuccessful in bringing this pilot endeaveor to full project status. The persistence of several users and the full involvement of the Ames Research Center were the ingredients needed to make the AIMS project a success. The lesson learned from this effort is that NASA should always work from its organizational strengths as a Headquarters-Center partnership.

AIM cryocooler developments for HOT detectors

Science.gov (United States)

Rühlich, I.; Mai, M.; Withopf, A.; Rosenhagen, C.

2014-06-01

Significantly increased FPA temperatures for both Mid Wave and Long Wave IR detectors, i.e. HOT detectors, which have been developed in recent years are now leaving the development phase and are entering real application. HOT detectors allowing to push size weight and power (SWaP) of Integrated Detectors Cooler Assemblies (IDCA's) to a new level. Key component mainly driving achievable weight, volume and power consumption is the cryocooler. AIM cryocooler developments are focused on compact, lightweight linear cryocoolers driven by compact and high efficient digital cooler drive electronics (DCE) to also achieve highest MTTF targets. This technology is using moving magnet driving mechanisms and dual or single piston compressors. Whereas SX030 which was presented at SPIE in 2012 consuming less 3 WDC to operate a typical IDCA at 140K, next smaller cooler SX020 is designed to provide sufficient cooling power at detector temperature above 160K. The cooler weight of less than 200g and a total compressor length of 60mm makes it an ideal solution for all applications with limited weight and power budget, like in handheld applications. For operating a typical 640x512, 15μm MW IR detector the power consumption will be less than 1.5WDC. MTTF for the cooler will be in excess of 30,000h and thus achieving low maintenance cost also in 24/7 applications. The SX020 compressor is based on a single piston design with integrated passive balancer in a new design achieves very low exported vibration in the order of 100mN in the compressor axis. AIM is using a modular approach, allowing the chose between 5 different compressor types for one common Stirling expander. The 6mm expander with a total length of 74mm is now available in a new design that fits into standard dewar bores originally designed for rotary coolers. Also available is a 9mm coldfinger in both versions. In development is an ultra-short expander with around 35mm total length to achieve highest compactness. Technical

Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3.

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Shoba Subramanian

Full Text Available The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 degrade host hemoglobin to provide free amino acids for parasite protein synthesis. Hemoglobin hydrolysis has been described as an ordered process initiated by aspartic proteases, but cysteine protease inhibitors completely block the process, suggesting that cysteine proteases can also initiate hemoglobin hydrolysis. To characterize the specific roles of falcipains, we used three approaches. First, using random P(1 - P(4 amino acid substrate libraries, falcipain-2 and falcipain-3 demonstrated strong preference for cleavage sites with Leu at the P(2 position. Second, with overlapping peptides spanning alpha and beta globin and proteolysis-dependent (18O labeling, hydrolysis was seen at many cleavage sites. Third, with intact hemoglobin, numerous cleavage products were identified. Our results suggest that hemoglobin hydrolysis by malaria parasites is not a highly ordered process, but rather proceeds with rapid cleavage by falcipains at multiple sites. However, falcipain-2 and falcipain-3 show strong specificity for P(2 Leu in small peptide substrates, in agreement with the specificity in optimized small molecule inhibitors that was identified previously. These results are consistent with a principal role of falcipain-2 and falcipain-3 in the hydrolysis of hemoglobin by P. falciparum and with the possibility of developing small molecule inhibitors with optimized specificity as antimalarial agents.

Synthesis of high specific activity [ethyl-1,2-3H]-labeled chlorpyrifos oxon and diazoxon

International Nuclear Information System (INIS)

Zhang, Nanjing; Morimoto, Hiromi; Williams, Philip G.; Casida, John E

2000-01-01

[Ethyl-1,2-3H] Chlorpyrifos oxon and [ethyl-1,2-3H] diazoxon were synthesized at a specific activity of 79 and 58 Ci/mmol, respectively, by catalytic tritiation of the corresponding monovinyl analogs over Pd/C. Direct evidence is provided that the high specific activity results from isotope exchange of the terminal vinylic protons prior to saturation of the double bond. This radiosynthesis procedure is applicable to the toxicologically-important oxon metabolites of many commercial O-O-diethyl phosphorothioate pesticides

Anticancer efficacy of the metabolic blocker 3-bromopyruvate: specific molecular targeting.

Science.gov (United States)

Ganapathy-Kanniappan, Shanmugasundaram; Kunjithapatham, Rani; Geschwind, Jean-Francois

2013-01-01

The anticancer efficacy of the pyruvate analog 3-bromopyruvate has been demonstrated in multiple tumor models. The chief principle underlying the antitumor effects of 3-bromopyruvate is its ability to effectively target the energy metabolism of cancer cells. Biochemically, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as the primary target of 3-bromopyruvate. Its inhibition results in the depletion of intracellular ATP, causing cell death. Several reports have also demonstrated that in addition to GAPDH inhibition, the induction of cellular stress also contributes to 3-bromopyruvate treatment-dependent apoptosis. Furthermore, recent evidence shows that 3-bromopyruvate is taken up selectively by tumor cells via the monocarboxylate transporters (MCTs) that are frequently overexpressed in cancer cells (for the export of lactate produced during aerobic glycolysis). The preferential uptake of 3-bromopyruvate via MCTs facilitates selective targeting of tumor cells while leaving healthy and non-malignant tissue untouched. Taken together, the specificity of molecular (GAPDH) targeting and selective uptake by tumor cells, underscore the potential of 3-bromopyruvate as a potent and promising anticancer agent. In this review, we highlight the mechanistic characteristics of 3-bromopyruvate and discuss its potential for translation into the clinic.

Antitumor and cytotoxic properties of a humanized antibody specific for the GM3(Neu5Gc) ganglioside.

Science.gov (United States)

Dorvignit, Denise; García-Martínez, Liliana; Rossin, Aurélie; Sosa, Katya; Viera, Justo; Hernández, Tays; Mateo, Cristina; Hueber, Anne-Odile; Mesa, Circe; López-Requena, Alejandro

2015-12-01

Gangliosides are sialic acid-bearing glycosphingolipids expressed on all mammalian cell membranes, and participate in several cellular processes. During malignant transformation their expression changes, both at the quantitative and qualitative levels. Of particular interest is the overexpression by tumor cells of Neu5Gc-gangliosides, which are absent, or detected in trace amounts, in human normal cells. The GM3(Neu5Gc) ganglioside in particular has been detected in many human tumors, and it is considered one of the few tumor specific antigen. We previously demonstrated that a humanized antibody specific for this molecule, named 14F7hT, retained the binding and cytotoxic properties of the mouse antibody. In this work, we confirm that 14F7hT exerts a non-apoptotic cell death mechanism in vitro and shows its potent in vivo antitumor activity on a solid mouse myeloma model. Also, we demonstrate, in contrast to the murine counterpart, the capacity of this antibody to induce antibody-dependent cell-mediated cytotoxicity using human effector cells, which increases its potential for the treatment of GM3(Neu5Gc)-expressing human tumors. Copyright © 2015 Elsevier GmbH. All rights reserved.

Evidence for a helical and a chiral phase transition in the Gd(hfac){sub 3}NITiPr magnetic specific heat

Energy Technology Data Exchange (ETDEWEB)

Cinti, F. [INFM and Department of Physics, University of Florence, 50019 Sesto Fiorentino (Italy)]. E-mail: fabio.cinti@fi.infn.it; Rettori, A. [INFM and Department of Physics, University of Florence, 50019 Sesto Fiorentino (Italy); Barucci, M. [INFM and Department of Physics, University of Florence, 50019 Sesto Fiorentino (Italy); Olivieri, E. [INFM and Department of Physics, University of Florence, 50019 Sesto Fiorentino (Italy); Risegari, L. [INFM and Department of Physics, University of Florence, 50019 Sesto Fiorentino (Italy); Ventura, G. [INFM and Department of Physics, University of Florence, 50019 Sesto Fiorentino (Italy); Caneschi, A. [Department of Inorganic Chemistry, University of Florence, 50019 Sesto Fiorentino (Italy); Gatteschi, D. [Department of Inorganic Chemistry, University of Florence, 50019 Sesto Fiorentino (Italy); Rovai, D. [Department of Inorganic Chemistry, University of Florence, 50019 Sesto Fiorentino (Italy); Pini, M.G. [ISC-CNR, 50019 Sesto Fiorentino (Italy); Affronte, M. [INFM-S3 and Department of Physics, University of Modena, 41100 Modena (Italy); Mariani, M. [INFM and Department of Physics, University of Pavia, 27100 Pavia (Italy); Lascialfari, A. [Istituto di Fisiologia e Chimica Biologica, University of Milano, Milano (Italy); INFM and Department of Physics, University of Pavia, 27100 Pavia (Italy)

2007-03-15

New specific heat data taken at very low temperatures (0.033}NITiPr show a clear {lambda} anomaly at T{sub N}=0.039K signaling the onset of the 3D helimagnetic phase. They match fairly well with previously reported data which showed the onset of the chiral phase transition at T{sub 0}=2.08K. Also new magnetic susceptibility data taken in the neighborhood at T{sub 0} are repeated.

Inhibiting HIF-1α Decreases Expression of TNF-α and Caspase-3 in Specific Brain Regions Exposed Kainic Acid-Induced Status Epilepticus

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Jixue Yang

2016-01-01

Full Text Available Background/Aims: A recent study demonstrates that pro-inflammatory cytokines (PICs, i.e., IL-1β, IL-6 and TNF-α in specific brain regions of rats play a role in regulating kainic acid (KA-induced status epilepticus (SE via a GABAergic mechanism. The purposes of this report were to examine contributions of hypoxia inducible factor subtype 1α (HIF-1α to expression of PICs in these specific brain regions in epileptic rats. Particularly, we investigated the parietal cortex, hippocampus and amygdala. In addition, we further examined expression of Caspase-3 indicating cell apoptosis in those brain regions of epileptic rats after infusing 2-methoxyestradiol (2-MET, inhibitor of HIF-1α and etanercept (TNF-α receptor antagonist. Methods: ELISA was used to determine the levels of HIF-1α and PICs and western blot analysis was used to examine Caspase-3 expression. Results: Our data show that HIF-1α was significantly increased in the parietal cortex, hippocampus and amygdala 1, 3 and 7 days after induction of SE (Pvs. control rats. Our results also show that inhibiting HIF-1α by central infusion of 2-MET significantly decreased the amplified TNF-α expression in these brain regions evoked by SE (Pvs. vehicle control, but did not modify IL-1β and IL-6. Our results demonstrate that 2-MET and etanercept attenuated an increase in Caspase-3 evoked by SE. Conclusion: Overall, we suggest that HIF-1α activated by SE is likely to contribute to epileptic activity via a TNF-α pathway, which has pharmacological implications to target specific HIF-1α and TNF-α pathways for neuronal dysfunction and vulnerability related to epilepsy.

Standard technical specifications, Westinghouse Plants: Bases (Sections 3.4--3.9). Volume 3, Revision 1

International Nuclear Information System (INIS)

1995-04-01

This NUREG contains the improved Standard Technical Specifications (STS) for Westinghouse plants. Revision 1 incorporates the cumulative changes to Revision 0, which was published in September 1992. The changes reflected in Revision 1 resulted from the experience gained from license amendment applications to convert to these improved STS or to adopt partial improvements to existing technical specifications. This NUREG is the result of extensive public technical meetings and discussions between the Nuclear Regulatory Commission (NRC) staff and various nuclear power plant licensees, Nuclear Steam Supply System (NSSS) Owners Groups, specifically the Westinghouse Owners Group (WOG), NSSS vendors, and the Nuclear Energy Institute (NEI). The improved STS were developed based on the criteria in the Final Commission Policy Statement on Technical Specifications Improvements for Nuclear Power Reactors, dated July 22, 1993 (58 FR 39132). Licensees are encouraged to upgrade their technical specifications consistent with those criteria and conforming, to the extent practical and consistent with the licensing basis for the facility, to Revision 1 to the improved STS. The Commission continues to place the highest priority on requests for complete conversions to the improved STS. Licensees adopting portions of the improved STS to existing technical specifications should adopt all related requirements, as applicable, to achieve a high degree of standardization and consistency

Specific heat of 4He and 3He--4He mixtures at their lambda transition

International Nuclear Information System (INIS)

Gasparini, F.M.; Moldover, M.R.

1975-01-01

We have measured the specific heat near the lambda transition of pure 4 He and of five 3 He-- 4 He mixtures up to a mole fraction of 0.39 3 He in 4 He. Our data for 4 He confirm the results of Ahlers revealing an asymmetry in the exponents above and below T/sub lambda/ when the specific heat is represented by a simple-power-law temperature dependence. Our results for these exponents (α = 0.012 plus-or-minus 0.002 and α' = -0.012 plus-or-minus 0.004) differ somewhat from Ahlers's. Our results can be reconciled with the requirement of scaling (α = α') only by supposing substantial contributions to C/sub p/ are made by singular correction terms to a simple power law. The measured specific heat of the mixtures richest in 3 He appears to be finite, continuous, and cusped at the lambda line. These qualitative features have been termed ''renormalization'' by Fisher. An analysis of our mixture data with a power-law temperature dependence does not yield a fully renormalized exponent, but rather an effective exponent. Derivatives at the lambda line were used to calculate the specific heat along paths of constant pressure and constant relative chemical potential.This specific heat behaves very much like C/sub p/ of pure 4 He, this behavior supporting the idea of universality for the specific-heat exponents. It is also true that the same asymmetry in the branches above and below T/sub lambda/ which is []bserved in pure 4 He is retained in the mixtures. The persistence of the asymmetry of C/subp//sub phi/ as one moves along the lambda line towards increasing 3 He concentration (at the saturated vapor pressure of the mixtures) is analogous to the persistence of the asymmetry of C/subp/ as one moves along the lambda line towards increasing pressure in pure 4 He

XML specifications DanRIS

DEFF Research Database (Denmark)

2009-01-01

XML specifications for DanRIS (Danish Registration- og InformationsSystem), where the the aim is: Improved exchange of data Improved data processing Ensuring future access to all gathered data from the year 1999 until now......XML specifications for DanRIS (Danish Registration- og InformationsSystem), where the the aim is: Improved exchange of data Improved data processing Ensuring future access to all gathered data from the year 1999 until now...

In silico design, synthesis, and assays of specific substrates for proteinase 3: influence of fluorogenic and charged groups.

Science.gov (United States)

Narawane, Shailesh; Budnjo, Adnan; Grauffel, Cédric; Haug, Bengt Erik; Reuter, Nathalie

2014-02-13

Neutrophil serine proteases are specific regulators of the immune response, and proteinase 3 is a major target antigen in antineutrophil cytoplasmic antibody-associated vasculitis. FRET peptides containing 2-aminobenzoic acid (Abz) and N-(2,4-dinitrophenyl)ethylenediamine (EDDnp) as fluorophore and quencher groups, respectively, have been widely used to probe proteases specificity. Using in silico design followed by enzymatic assays, we show that Abz and EDDnp significantly contribute to substrate hydrolysis by PR3. We also propose a new substrate specific for PR3.

50 CFR 32.3 - What are the procedures for publication of refuge-specific hunting regulations?

Science.gov (United States)

2010-10-01

... and publication of the opening of a wildlife refuge area to migratory game bird, upland game or big game hunting. (b) Refuge-specific hunting regulations may contain the following items: (1) Wildlife... FISHING General Provisions § 32.3 What are the procedures for publication of refuge-specific hunting...

Genre-Specific Semantic Video Indexing

NARCIS (Netherlands)

Wu, J.; Worring, M.

2010-01-01

In many applications, we find large video collections from different genres where the user is often only interested in one or two specific video genres. So, when users are querying the system with a specific semantic concept, they are likely aiming a genre specific instantiation of this concept.

Patient-specific 3D FLAIR for enhanced visualization of brain white matter lesions in multiple sclerosis.

Science.gov (United States)

Gabr, Refaat E; Pednekar, Amol S; Govindarajan, Koushik A; Sun, Xiaojun; Riascos, Roy F; Ramírez, María G; Hasan, Khader M; Lincoln, John A; Nelson, Flavia; Wolinsky, Jerry S; Narayana, Ponnada A

2017-08-01

To improve the conspicuity of white matter lesions (WMLs) in multiple sclerosis (MS) using patient-specific optimization of single-slab 3D fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Sixteen MS patients were enrolled in a prospective 3.0T MRI study. FLAIR inversion time and echo time were automatically optimized for each patient during the same scan session based on measurements of the relative proton density and relaxation times of the brain tissues. The optimization criterion was to maximize the contrast between gray matter (GM) and white matter (WM), while suppressing cerebrospinal fluid. This criterion also helps increase the contrast between WMLs and WM. The performance of the patient-specific 3D FLAIR protocol relative to the fixed-parameter protocol was assessed both qualitatively and quantitatively. Patient-specific optimization achieved a statistically significant 41% increase in the GM-WM contrast ratio (P < 0.05) and 32% increase in the WML-WM contrast ratio (P < 0.01) compared with fixed-parameter FLAIR. The increase in WML-WM contrast ratio correlated strongly with echo time (P < 10 -11 ). Two experienced neuroradiologists indicated substantially higher lesion conspicuity on the patient-specific FLAIR images over conventional FLAIR in 3-4 cases (intrarater correlation coefficient ICC = 0.72). In no case was the image quality of patient-specific FLAIR considered inferior to conventional FLAIR by any of the raters (ICC = 0.32). Changes in proton density and relaxation times render fixed-parameter FLAIR suboptimal in terms of lesion contrast. Patient-specific optimization of 3D FLAIR increases lesion conspicuity without scan time penalty, and has potential to enhance the detection of subtle and small lesions in MS. 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:557-564. © 2016 International Society for Magnetic Resonance in Medicine.

O'nyong nyong virus molecular determinants of unique vector specificity reside in non-structural protein 3.

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Kali D Saxton-Shaw

Full Text Available O'nyong nyong virus (ONNV and Chikungunya virus (CHIKV are two closely related alphaviruses with very different infection patterns in the mosquito, Anopheles gambiae. ONNV is the only alphavirus transmitted by anopheline mosquitoes, but specific molecular determinants of infection of this unique vector specificity remain unidentified. Fifteen distinct chimeric viruses were constructed to evaluate both structural and non-structural regions of the genome and infection patterns were determined through artificial infectious feeds in An. gambiae with each of these chimeras. Only one region, non-structural protein 3 (nsP3, was sufficient to up-regulate infection to rates similar to those seen with parental ONNV. When ONNV non-structural protein 3 (nsP3 replaced nsP3 from CHIKV virus in one of the chimeric viruses, infection rates in An. gambiae went from 0% to 63.5%. No other single gene or viral region addition was able to restore infection rates. Thus, we have shown that a non-structural genome element involved in viral replication is a major element involved in ONNV's unique vector specificity.

Evolution of specific 3'-5'-linkages in RNA in pre-biotic soup: a new hypothesis.

Science.gov (United States)

Kumar, Vaijayanti A

2016-11-02

This article reviews the different possibilities towards progression of the formation of DNA/RNA in the chemical world, before life, in enzyme-free conditions. The advent of deoxyribo- and ribopentose-sugars, nucleosides, nucleotides and oligonucleotides in the prebiotic soup is briefly discussed. Further, the formation of early single stranded oligomers, base-pairing possibilities and information transfer based on the stability parameters of the derived duplexes is reviewed. Each theory has its own merits and demerits which we have elaborated upon. Lastly, using clues from this literature, a possible explanation for the specific 3'-5'-linkages in RNA is proposed.

3D-printed upper limb prostheses: a review.

Science.gov (United States)

Ten Kate, Jelle; Smit, Gerwin; Breedveld, Paul

2017-04-01

This paper aims to provide an overview with quantitative information of existing 3D-printed upper limb prostheses. We will identify the benefits and drawbacks of 3D-printed devices to enable improvement of current devices based on the demands of prostheses users. A review was performed using Scopus, Web of Science and websites related to 3D-printing. Quantitative information on the mechanical and kinematic specifications and 3D-printing technology used was extracted from the papers and websites. The overview (58 devices) provides the general specifications, the mechanical and kinematic specifications of the devices and information regarding the 3D-printing technology used for hands. The overview shows prostheses for all different upper limb amputation levels with different types of control and a maximum material cost of $500. A large range of various prostheses have been 3D-printed, of which the majority are used by children. Evidence with respect to the user acceptance, functionality and durability of the 3D-printed hands is lacking. Contrary to what is often claimed, 3D-printing is not necessarily cheap, e.g., injection moulding can be cheaper. Conversely, 3D-printing provides a promising possibility for individualization, e.g., personalized socket, colour, shape and size, without the need for adjusting the production machine. Implications for rehabilitation Upper limb deficiency is a condition in which a part of the upper limb is missing as a result of a congenital limb deficiency of as a result of an amputation. A prosthetic hand can restore some of the functions of a missing limb and help the user in performing activities of daily living. Using 3D-printing technology is one of the solutions to manufacture hand prostheses. This overview provides information about the general, mechanical and kinematic specifications of all the devices and it provides the information about the 3D-printing technology used to print the hands.

Critical evaluation of a badminton-specific endurance test.

Science.gov (United States)

Fuchs, Michael; Faude, Oliver; Wegmann, Melissa; Meyer, Tim

2014-03-01

To overcome the limitations of traditional 1-dimensional fitness tests in analyzing physiological properties of badminton players, a badminton-specific endurance test (BST) was created. This study aimed at analyzing the influence of various fitness dimensions on BST performance. 18 internationally competing male German badminton players (22.4 ± 3.2 y, 79.2 ± 7.7 kg, 1.84 ± 0.06 m, world-ranking position [WRP] 21-501) completed a straight-sprint test, a change-of-direction speed test, various jump tests (countermovement jump, drop jump, standing long jump), a multistage running test (MST), and the BST. During this on-court field test players have to respond to a computerized sign indicating direction and speed of badminton-specific movements by moving into the corresponding corners. Significant correlations were found between performance in MST and BST (individual anaerobic threshold [IAT], r = .63, P = .005; maximum velocity [Vmax], r = .60, P = .009). A negative correlation (r = -.59, P = .014) was observed between IAT in BST and drop-jump contact time. No further associations between performance indices could be detected. Apart from a small portion explained by MST results (IAT, R2 = .40; Vmax, R2 = .36), the majority of BST performance cannot be explained by the determined physiological correlates. Moreover, it was impossible to predict the WRP of a player on the basis of BST results (r = -.15, P = .55). Neither discipline-specific performance nor basic physiological properties were appropriately reflected by a BST in elite badminton players. This does not substantiate its validity for regular use as a testing tool. However, it may be useful for monitoring on-court training sessions.

A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets.

Science.gov (United States)

Okwuosa, Tochukwu C; Stefaniak, Dominika; Arafat, Basel; Isreb, Abdullah; Wan, Ka-Wai; Alhnan, Mohamed A

2016-11-01

The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus. Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.

[Validity of a standard questionnaire to assess physical activity for specific medical checkups and health guidance].

Science.gov (United States)

Kawakami, Ryoko; Miyachi, Motohiko

2010-10-01

This study aimed to determine the validity of a standard questionnaire to assess amount of physical activity (PA) and cardiorespiratory fitness (VO2peak). A total of 483 men and women, aged 20 to 69 years, participated. The standard questionnaire included 3 items about exercise, PA, and walking speed. All questions were designed to require an answer of Yes or No. Subjects were classified into one of four groups regarding the number of Yes answers to the three questions, giving activity levels of 0 to 3. The amount of PA was measured objectively with a tn-axial accelerometer which could also calculate daily step counts, and the amounts of PA under 3 metabolic equivalents (METs) and at 3 METs or more. VO2peak. was measured by incremental cycle exercise tests with indirect calorimetry. The daily step counts, the amount of PA at 3 METs or more, and the VO2peak. were significantly higher in subjects who answered Yes to each question than in those who answered No. Sensitivity and specificity of each question were 62-73% and 45-71% for the amount of PA established with the "Exercise and Physical Activity Reference for Health Promotion 2006 (EPAR2006)". The sum of sensitivity and specificity was the highest when the cutoff value was activity level 2 (sensitivity 73%, specificity 68%). Sensitivity and specificity for VO2max established by EPAR2006 were lower than those for the amount of PA. These results suggest that only answering simple questions with a standard questionnaire is sufficient for estimation of PA levels for specific medical checkups and health guidance, even though the accuracy is somewhat limited.

Effectiveness of cultural adaptations of interventions aimed at smoking cessation, diet, and/or physical activity in ethnic minorities. a systematic review.

Directory of Open Access Journals (Sweden)

Vera Nierkens

Full Text Available BACKGROUND: The importance of cultural adaptations in behavioral interventions targeting ethnic minorities in high-income societies is widely recognized. Little is known, however, about the effectiveness of specific cultural adaptations in such interventions. AIM: To systematically review the effectiveness of specific cultural adaptations in interventions that target smoking cessation, diet, and/or physical activity and to explore features of such adaptations that may account for their effectiveness. METHODS: Systematic review using MEDLINE, PsycINFO, Embase, and the Cochrane Central Register of Controlled Trials registers (1997-2009. INCLUSION CRITERIA: a effectiveness study of a lifestyle intervention targeted to ethnic minority populations living in a high income society; b interventions included cultural adaptations and a control group that was exposed to the intervention without the cultural adaptation under study; c primary outcome measures included smoking cessation, diet, or physical activity. RESULTS: Out of 44904 hits, we identified 17 studies, all conducted in the United States. In five studies, specific cultural adaptations had a statistically significant effect on primary outcomes. The remaining studies showed no significant effects on primary outcomes, but some presented trends favorable for cultural adaptations. We observed that interventions incorporating a package of cultural adaptations, cultural adaptations that implied higher intensity and those incorporating family values were more likely to report statistically significant effects. Adaptations in smoking cessation interventions seem to be more effective than adaptations in interventions aimed at diet and physical activity. CONCLUSION: This review indicates that culturally targeted behavioral interventions may be more effective if cultural adaptations are implemented as a package of adaptations, the adaptation includes family level, and where the adaptation results in a

Modeling a Predictive Energy Equation Specific for Maintenance Hemodialysis.

Science.gov (United States)

Byham-Gray, Laura D; Parrott, J Scott; Peters, Emily N; Fogerite, Susan Gould; Hand, Rosa K; Ahrens, Sean; Marcus, Andrea Fleisch; Fiutem, Justin J

2017-03-01

Hypermetabolism is theorized in patients diagnosed with chronic kidney disease who are receiving maintenance hemodialysis (MHD). We aimed to distinguish key disease-specific determinants of resting energy expenditure to create a predictive energy equation that more precisely establishes energy needs with the intent of preventing protein-energy wasting. For this 3-year multisite cross-sectional study (N = 116), eligible participants were diagnosed with chronic kidney disease and were receiving MHD for at least 3 months. Predictors for the model included weight, sex, age, C-reactive protein (CRP), glycosylated hemoglobin, and serum creatinine. The outcome variable was measured resting energy expenditure (mREE). Regression modeling was used to generate predictive formulas and Bland-Altman analyses to evaluate accuracy. The majority were male (60.3%), black (81.0%), and non-Hispanic (76.7%), and 23% were ≥65 years old. After screening for multicollinearity, the best predictive model of mREE ( R 2 = 0.67) included weight, age, sex, and CRP. Two alternative models with acceptable predictability ( R 2 = 0.66) were derived with glycosylated hemoglobin or serum creatinine. Based on Bland-Altman analyses, the maintenance hemodialysis equation that included CRP had the best precision, with the highest proportion of participants' predicted energy expenditure classified as accurate (61.2%) and with the lowest number of individuals with underestimation or overestimation. This study confirms disease-specific factors as key determinants of mREE in patients on MHD and provides a preliminary predictive energy equation. Further prospective research is necessary to test the reliability and validity of this equation across diverse populations of patients who are receiving MHD.

Investigation of change in specifications during a product's lifecycle

DEFF Research Database (Denmark)

Sudin, Mohd Nizam Bin; Ahmed, Saeema

2009-01-01

design attributes likely be changed; the initiation of change and how change in specifications are described. For this purpose, document analysis for a complex product has been carried out. In total, 271 reports of change request of an aero-engine that were associated to change in specifications were......Engineering changes (ECs) constitutes a normal part of a product’s lifecycle. This paper aims to understand why changes are made to a product’s specification during a product’s lifecycle including understanding: the distribution of changes; the drivers for changes; how changes are discovered; which...... the request was initiated. The study showed that experience plays a vital role in discovering the need to change a complex product...

Discovery and Characterization of PRCAT47: A Novel Prostate Lineage and Cancer-Specific Long Noncoding RNA

Science.gov (United States)

2017-07-01

including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and...localized and metastatic prostate cancer, and displayed strong transcriptional induction by AR. Preliminary data suggested that PRCAT47 has...diagnostic biomarker. Specific Aim 3: Interrogating the therapeutic potential of PRCAT47 using clinical grade antisense oligos (ASOs). Summary of Results

Student Aims Performance in a Predominately Hispanic District

Science.gov (United States)

Chebultz, Lance

2012-01-01

School districts in the United States have undergone large changes over the last decade to accommodate No Child Left Behind (NCLB). Arizona accommodated NCLB through Arizona's Instrument to Measure Standards (AIMS). Expectations were established for all students, varying by group of students based on grade, special education status, free/reduced…

Can there be a T3 ln T kind of behaviour of the low temperature specific heat of liquid 3He without the paramagnons?

International Nuclear Information System (INIS)

Tripathy, D.N.; Mishra, S.

1996-01-01

It is shown that even without invoking the concepts like paramagnons, the temperature dependence of the interparticle correlations in a system of liquid 3 He can give rise a T 3 ln T kind of behaviour of its low temperature fermionic specific heat. It is found to be coming from the self-energy corrections to the bare single particle energy involving the particle-hole propagator. Looking at the similar kind of behaviour observed by us recently for an electron liquid, one may conclude that the T 3 ln T behaviour is perhaps universal for all fermi systems, although for liquid 3 He the very dependence also follows from the paramagnon effects. It is interesting to see that unlike earlier theories, an extremely good fit is obtained with the experimental data over the entire range of low temperatures. (orig.)

Fabrication and Characterization of Surrogate Glasses Aimed to Validate Nuclear Forensic Techniques

Science.gov (United States)

2017-12-01

the glass formed during a nuclear event, trinitite [14]. The SiO2 composition is generally greater than 50% for trinitite and can vary appreciably...CHARACTERIZATION OF SURROGATE GLASSES AIMED TO VALIDATE NUCLEAR FORENSIC TECHNIQUES by Ken G. Foos December 2017 Thesis Advisor: Claudia...December 2017 3. REPORT TYPE AND DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE FABRICATION AND CHARACTERIZATION OF SURROGATE GLASSES AIMED TO

Exploiting stock data: a survey of state of the art computational techniques aimed at producing beliefs regarding investment portfolios

Directory of Open Access Journals (Sweden)

Mario Linares Vásquez

2008-01-01

Full Text Available Selecting an investment portfolio has inspired several models aimed at optimising the set of securities which an in-vesttor may select according to a number of specific decision criteria such as risk, expected return and planning hori-zon. The classical approach has been developed for supporting the two stages of portfolio selection and is supported by disciplines such as econometrics, technical analysis and corporative finance. However, with the emerging field of computational finance, new and interesting techniques have arisen in line with the need for the automatic processing of vast volumes of information. This paper surveys such new techniques which belong to the body of knowledge con-cerning computing and systems engineering, focusing on techniques particularly aimed at producing beliefs regar-ding investment portfolios.

Older adults' perceptions of technologies aimed at falls prevention, detection or monitoring: a systematic review.

Science.gov (United States)

Hawley-Hague, Helen; Boulton, Elisabeth; Hall, Alex; Pfeiffer, Klaus; Todd, Chris

2014-06-01

Over recent years a number of Information and Communication Technologies (ICTs) have emerged aiming at falls prevention, falls detection and alarms for use in case of fall. There are also a range of ICT interventions, which have been created or adapted to be pro-active in preventing falls, such as those which provide strength and balance training to older adults in the prevention of falls. However, there are issues related to the adoption and continued use of these technologies by older adults. This review provides an overview of older adults' perceptions of falls technologies. We undertook systematic searches of MEDLINE, EMBASE, CINAHL and PsychINFO, COMPENDEX and the Cochrane database. Key search terms included 'older adults', 'seniors', 'preference', 'attitudes' and a wide range of technologies, they also included the key word 'fall*'. We considered all studies that included older adults aged 50 and above. Studies had to include technologies related specifically to falls prevention, detection or monitoring. The Joanna Briggs Institute (JBI) tool and the Quality Assessment Tool for Quantitative Studies by the Effective Public Health Practice Project (EPHPP) were used. We identified 76 potentially relevant papers. Some 21 studies were considered for quality review. Twelve qualitative studies, three quantitative studies and 6 mixed methods studies were included. The literature related to technologies aimed at predicting, monitoring and preventing falls suggest that intrinsic factors related to older adults' attitudes around control, independence and perceived need/requirements for safety are important for their motivation to use and continue using technologies. Extrinsic factors such as usability, feedback gained and costs are important elements which support these attitudes and perceptions. Positive messages about the benefits of falls technologies for promoting healthy active ageing and independence are critical, as is ensuring that the technologies are simple

Novel polymorphisms within the Dlk1-Dio3 imprinted locus in rat: a putative genetic basis for strain-specific allelic gene expression

Directory of Open Access Journals (Sweden)

Laura J Sittig

2012-12-01

Full Text Available The imprinted iodothyronine deiodinase-III (Dio3 thyroid hormone metabolizing gene exhibits paternal expression in most fetal tissues, yet exhibits aberrant, maternal expression in the hippocampus in F1 offspring of Sprague Dawley (SD x Brown Norway (BN rats. The maternal hippocampal expression is associated with lower Dio3 mRNA levels specifically in the hippocampus. Here, we tested the hypothesis that genetic polymorphisms between the SD and BN parent strains cause this aberrant allelic Dio3 expression and contribute to behavioral sequelae of higher thyroid hormone levels locally in the hippocampus, including anxiety-related behavior. We mapped and sequenced the Dio3 gene and several previously unmapped regions in the Dlk1-Dio3 locus that could regulate imprinting of the Dio3 gene. In the Dio3 promoter we identified four novel polymorphisms between the BN and SD strains. Next we took advantage of the fact that the Long Evans (LE strain exhibits identical polymorphisms as the SD strain in the region 5’ and including the Dio3 gene. By reciprocally crossing LE and BN strains we tested the relationship among Dio3 promoter region polymorphisms and Dio3 mRNA expression in the hippocampus. Aberrant strain-specific hippocampal Dio3 allelic expression replicated in the LE-BN reciprocal crosses, suggesting that hippocampal-specific imprinting of the Dio3 gene is not the result of a unique genetic or epigenetic characteristic of the SD rat strain, or a unique epistatic interaction between SD and BN. To our knowledge no other studies have reported a genetic x epigenetic interaction of genetic origin in the brain.

Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders

Science.gov (United States)

Paterson, Clare; Wang, Yanhong; Hyde, Thomas M.; Weinberger, Daniel R.; Kleinman, Joel E.; Law, Amanda J.

2018-01-01

Objective Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I–IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. Method NRG3 isoform classes I–IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. Results NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Conclusions

Validation of a serum neutralization test for detection of antibodies specific to cyprinid herpesvirus 3 in infected common and koi carp (Cyprinus carpio).

Science.gov (United States)

Cabon, J; Louboutin, L; Castric, J; Bergmann, S; Bovo, G; Matras, M; Haenen, O; Olesen, N J; Morin, T

2017-05-01

Cyprinid herpesvirus 3 (CyHV-3) is the aetiological agent of a serious infective, notifiable disease affecting common carp and varieties. In survivors, infection is generally characterized by a subclinical latency phase with restricted viral replication. The CyHV-3 genome is difficult to detect in such carrier fish that represent a potential source of dissemination if viral reactivation occurs. In this study, the analytical and diagnostic performance of an alternative serum neutralization (SN) method based on the detection of CyHV-3-specific antibodies was assessed using 151 serum or plasma samples from healthy and naturally or experimentally CyHV-3-infected carp. French CyHV-3 isolate 07/108b was neutralized efficiently by sera from carp infected with European, American and Taiwanese CyHV-3 isolates, but no neutralization was observed using sera specific to other aquatic herpesviruses. Diagnostic sensitivity, diagnostic specificity and repeatability of 95.9%, 99.0% and 99.3%, respectively, were obtained, as well as a compliance rate of 89.9% in reproducibility testing. Neutralizing antibodies were steadily detected in infected carp subjected to restrictive or permissive temperature variations over more than 25 months post-infection. The results suggest that this non-lethal diagnostic test could be used in the future to improve the epidemiological surveillance and control of CyHV-3 disease. © 2016 John Wiley & Sons Ltd.

Antigen-specific cytotoxic T cell and antigen-specific proliferating T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3

NARCIS (Netherlands)

Spits, H.; Yssel, H.; Leeuwenberg, J.; de Vries, J. E.

1985-01-01

T3 is a human differentiation antigen expressed exclusively on mature T cells. In this study it is shown that anti-T3 monoclonal antibodies, in addition to their capacity to induce T cells to proliferate, are able to induce antigen-specific cytotoxic T lymphocyte clones to mediate antigen

Measurement of specific [3H]-ouabain binding to different types of human leucocytes

DEFF Research Database (Denmark)

Boon, Arnold; Oh, V M; Taylor, John E.

1984-01-01

We have studied the specific binding of [3H]-ouabain to intact mononuclear leucocytes (82% lymphocytes) and polymorphonuclear leucocytes. In both types of cells [3H]-ouabain binding was saturable, confined to a single site of high affinity, slow to reach equilibrium, slow to reverse, temperature...... were expressed per square micron of cell surface area the difference between the two cell types was proportionately greater (83 and 186 sites per micron 2 respectively). We conclude that the [3H]-ouabain binding sites on mononuclear and polymorphonuclear leucocytes are similar in nature, but different...

Genome-wide methylation profiling identifies an essential role of reactive oxygen species in pediatric glioblastoma multiforme and validates a methylome specific for H3 histone family 3A with absence of G-CIMP/isocitrate dehydrogenase 1 mutation.

Science.gov (United States)

Jha, Prerana; Pia Patric, Irene Rosita; Shukla, Sudhanshu; Pathak, Pankaj; Pal, Jagriti; Sharma, Vikas; Thinagararanjan, Sivaarumugam; Santosh, Vani; Suri, Vaishali; Sharma, Mehar Chand; Arivazhagan, Arimappamagan; Suri, Ashish; Gupta, Deepak; Somasundaram, Kumaravel; Sarkar, Chitra

2014-12-01

Pediatric glioblastoma multiforme (GBM) is rare, and there is a single study, a seminal discovery showing association of histone H3.3 and isocitrate dehydrogenase (IDH)1 mutation with a DNA methylation signature. The present study aims to validate these findings in an independent cohort of pediatric GBM, compare it with adult GBM, and evaluate the involvement of important functionally altered pathways. Genome-wide methylation profiling of 21 pediatric GBM cases was done and compared with adult GBM data (GSE22867). We performed gene mutation analysis of IDH1 and H3 histone family 3A (H3F3A), status evaluation of glioma cytosine-phosphate-guanine island methylator phenotype (G-CIMP), and Gene Ontology analysis. Experimental evaluation of reactive oxygen species (ROS) association was also done. Distinct differences were noted between methylomes of pediatric and adult GBM. Pediatric GBM was characterized by 94 hypermethylated and 1206 hypomethylated cytosine-phosphate-guanine (CpG) islands, with 3 distinct clusters, having a trend to prognostic correlation. Interestingly, none of the pediatric GBM cases showed G-CIMP/IDH1 mutation. Gene Ontology analysis identified ROS association in pediatric GBM, which was experimentally validated. H3F3A mutants (36.4%; all K27M) harbored distinct methylomes and showed enrichment of processes related to neuronal development, differentiation, and cell-fate commitment. Our study confirms that pediatric GBM has a distinct methylome compared with that of adults. Presence of distinct clusters and an H3F3A mutation-specific methylome indicate existence of epigenetic subgroups within pediatric GBM. Absence of IDH1/G-CIMP status further indicates that findings in adult GBM cannot be simply extrapolated to pediatric GBM and that there is a strong need for identification of separate prognostic markers. A possible role of ROS in pediatric GBM pathogenesis is demonstrated for the first time and needs further evaluation. © The Author(s) 2014

Program for accident and incident management support, AIMS

International Nuclear Information System (INIS)

Putra, M.A.

1993-12-01

A prototype of an advisory computer program is presented which could be used in monitoring and analyzing an ongoing incident in a nuclear power plant. The advisory computer program, called the Accident and Incident Management Support (AIMS), focuses on processing a set of data that is to be transmitted from a nuclear power plant to a national or regional emergency center during an incident. The AIMS program will assess the reactor conditions by processing the measured plant parameters. The applied model of the power plant contains a level of complexity that is comparable with the simplified plant model that the power plant operator uses. A standardized decay heat function and a steam water property library is used in the integral balance equations for mass and energy. A simulation of the station blackout accident of the Borssele plant is used to test the program. The program predicts successively: (1) the time of dryout of the steam generators, (2) the time of saturation of the primary system, and (3) the onset of core uncovery. The coolant system with the actual water levels will be displayed on the screen. (orig./HP)

Synthesis of [1,2-3H] testosterone of high specific radioactivity

International Nuclear Information System (INIS)

Sun Jiaxiu; Sun Zhiwei; Shen Decun

1987-01-01

[1,2- 3 H] testosterone of specific activity as high as 51 Ci/mmol, and radiochemical purity more than 99% has been prepared. The experimental conditions, such as reaction time, ratio of raw material to catalyst and separation method have been studied. The product was separated by silica-paper TLC (thin-laryer chromatography) at first, then purified by high performance liquid chromatography. The product has good stability with a purity of 95% after one year storage

Sensitivity and specificity of the 3-item memory test in the assessment of post traumatic amnesia.

Science.gov (United States)

Andriessen, Teuntje M J C; de Jong, Ben; Jacobs, Bram; van der Werf, Sieberen P; Vos, Pieter E

2009-04-01

To investigate how the type of stimulus (pictures or words) and the method of reproduction (free recall or recognition after a short or a long delay) affect the sensitivity and specificity of a 3-item memory test in the assessment of post traumatic amnesia (PTA). Daily testing was performed in 64 consecutively admitted traumatic brain injured patients, 22 orthopedically injured patients and 26 healthy controls until criteria for resolution of PTA were reached. Subjects were randomly assigned to a test with visual or verbal stimuli. Short delay reproduction was tested after an interval of 3-5 minutes, long delay reproduction was tested after 24 hours. Sensitivity and specificity were calculated over the first 4 test days. The 3-word test showed higher sensitivity than the 3-picture test, while specificity of the two tests was equally high. Free recall was a more effortful task than recognition for both patients and controls. In patients, a longer delay between registration and recall resulted in a significant decrease in the number of items reproduced. Presence of PTA is best assessed with a memory test that incorporates the free recall of words after a long delay.

Phase Startup Initiative Phases 3 and 4 Test Plan and Test Specification ( OCRWM)

Energy Technology Data Exchange (ETDEWEB)

PAJUNEN, A.L.; LANGEVIN, M.J.

2000-08-07

Construction for the Spent Nuclear Fuel (SNF) Project facilities is continuing per the Level III Baseline Schedule, and installation of the Fuel Retrieval System (FRS) and Integrated Water Treatment System (IWTS) in K West Basin is now complete. In order to accelerate the project, a phased start up strategy to initiate testing of the FRS and IWTS early in the overall project schedule was proposed (Williams 1999). Wilkinson (1999) expands the definition of the original proposal into four functional testing phases of the Phased Startup Initiative (PSI). Phases 1 and 2 are based on performing functional tests using dummy fuel. This test plan provides overall guidance for Phase 3 and 4 tests, which are performed using actual irradiated N fuel assemblies. The overall objective of the Phase 3 and 4 testing is to verify how the FRS and IWTS respond while processing actual fuel. Conducting these tests early in the project schedule will allow identification and resolution of equipment and process problems before they become activities on the start-up critical path. The specific objectives of this test plan are to: Define the Phase 3 and 4 test scope for the FRS and IWTS; Provide detailed test requirements that can be used to write the specific test procedures; Define data required and measurements to be taken. Where existing methods to obtain these do not exist, enough detail will be provided to define required additional equipment; and Define specific test objectives and acceptance criteria.

Phase Startup Initiative Phases 3 and 4 Test Plan and Test Specification (OCRWM)

International Nuclear Information System (INIS)

PAJUNEN, A.L.; LANGEVIN, M.J.

2000-01-01

Construction for the Spent Nuclear Fuel (SNF) Project facilities is continuing per the Level III Baseline Schedule, and installation of the Fuel Retrieval System (FRS) and Integrated Water Treatment System (IWTS) in K West Basin is now complete. In order to accelerate the project, a phased start up strategy to initiate testing of the FRS and IWTS early in the overall project schedule was proposed (Williams 1999). Wilkinson (1999) expands the definition of the original proposal into four functional testing phases of the Phased Startup Initiative (PSI). Phases 1 and 2 are based on performing functional tests using dummy fuel. This test plan provides overall guidance for Phase 3 and 4 tests, which are performed using actual irradiated N fuel assemblies. The overall objective of the Phase 3 and 4 testing is to verify how the FRS and IWTS respond while processing actual fuel. Conducting these tests early in the project schedule will allow identification and resolution of equipment and process problems before they become activities on the start-up critical path. The specific objectives of this test plan are to: Define the Phase 3 and 4 test scope for the FRS and IWTS; Provide detailed test requirements that can be used to write the specific test procedures; Define data required and measurements to be taken. Where existing methods to obtain these do not exist, enough detail will be provided to define required additional equipment; and Define specific test objectives and acceptance criteria

An intervention aimed at reducing plagiarism in undergraduate nursing students.

Science.gov (United States)

Smedley, Alison; Crawford, Tonia; Cloete, Linda

2015-05-01

Plagiarism is a current and developing problem in the tertiary education sector where students access information and reproduce it as their own. It is identified as occurring in many tertiary level degrees including nursing and allied health profession degrees. Nursing specifically, is a profession where standards and ethics are required and honesty is paramount. The aim of this study was to evaluate the change in nursing student's knowledge and understanding of plagiarism before and after an educational intervention in their first semester of the Bachelor of nursing degree at a private college of higher education in Sydney, Australia. This study concluded that an educational intervention can increase knowledge and awareness of plagiarism among nursing students. Copyright © 2014 Elsevier Ltd. All rights reserved.

3D Rapid Prototyping for Otolaryngology-Head and Neck Surgery: Applications in Image-Guidance, Surgical Simulation and Patient-Specific Modeling.

Science.gov (United States)

Chan, Harley H L; Siewerdsen, Jeffrey H; Vescan, Allan; Daly, Michael J; Prisman, Eitan; Irish, Jonathan C

2015-01-01

The aim of this study was to demonstrate the role of advanced fabrication technology across a broad spectrum of head and neck surgical procedures, including applications in endoscopic sinus surgery, skull base surgery, and maxillofacial reconstruction. The initial case studies demonstrated three applications of rapid prototyping technology are in head and neck surgery: i) a mono-material paranasal sinus phantom for endoscopy training ii) a multi-material skull base simulator and iii) 3D patient-specific mandible templates. Digital processing of these phantoms is based on real patient or cadaveric 3D images such as CT or MRI data. Three endoscopic sinus surgeons examined the realism of the endoscopist training phantom. One experienced endoscopic skull base surgeon conducted advanced sinus procedures on the high-fidelity multi-material skull base simulator. Ten patients participated in a prospective clinical study examining patient-specific modeling for mandibular reconstructive surgery. Qualitative feedback to assess the realism of the endoscopy training phantom and high-fidelity multi-material phantom was acquired. Conformance comparisons using assessments from the blinded reconstructive surgeons measured the geometric performance between intra-operative and pre-operative reconstruction mandible plates. Both the endoscopy training phantom and the high-fidelity multi-material phantom received positive feedback on the realistic structure of the phantom models. Results suggested further improvement on the soft tissue structure of the phantom models is necessary. In the patient-specific mandible template study, the pre-operative plates were judged by two blinded surgeons as providing optimal conformance in 7 out of 10 cases. No statistical differences were found in plate fabrication time and conformance, with pre-operative plating providing the advantage of reducing time spent in the operation room. The applicability of common model design and fabrication techniques

Adequate procedures for specific exams

International Nuclear Information System (INIS)

Staevie, G.L.G.; Gattringer, D.K.; Dal Mas, C.R.; Tessman, M.

1996-01-01

Some ideal procedures for specific radiographic exams are briefly presented. The aim is to improve the quality standard, establishing a specific method for each exam in order to decrease films waste and reduce the patient dose exposure

The GRP1 PH domain, like the AKT1 PH domain, possesses a sentry glutamate residue essential for specific targeting to plasma membrane PI(3,4,5)P(3).

Science.gov (United States)

Pilling, Carissa; Landgraf, Kyle E; Falke, Joseph J

2011-11-15

During the appearance of the signaling lipid PI(3,4,5)P(3), an important subset of pleckstrin homology (PH) domains target signaling proteins to the plasma membrane. To ensure proper pathway regulation, such PI(3,4,5)P(3)-specific PH domains must exclude the more prevalant, constitutive plasma membrane lipid PI(4,5)P(2) and bind the rare PI(3,4,5)P(3) target lipid with sufficiently high affinity. Our previous study of the E17K mutant of the protein kinase B (AKT1) PH domain, together with evidence from Carpten et al. [Carpten, J. D., et al. (2007) Nature 448, 439-444], revealed that the native AKT1 E17 residue serves as a sentry glutamate that excludes PI(4,5)P(2), thereby playing an essential role in specific PI(3,4,5)P(3) targeting [Landgraf, K. E., et al. (2008) Biochemistry 47, 12260-12269]. The sentry glutamate hypothesis proposes that an analogous sentry glutamate residue is a widespread feature of PI(3,4,5)P(3)-specific PH domains, and that charge reversal mutation at the sentry glutamate position will yield both increased PI(4,5)P(2) affinity and constitutive plasma membrane targeting. To test this hypothesis, we investigated the E345 residue, a putative sentry glutamate, of the general receptor for phosphoinositides 1 (GRP1) PH domain. The results show that incorporation of the E345K charge reversal mutation into the GRP1 PH domain enhances PI(4,5)P(2) affinity 8-fold and yields constitutive plasma membrane targeting in cells, reminiscent of the effects of the E17K mutation in the AKT1 PH domain. Hydrolysis of plasma membrane PI(4,5)P(2) releases the E345K GRP1 PH domain into the cytoplasm, and the efficiency of this release increases when Arf6 binding is disrupted. Overall, the findings provide strong support for the sentry glutamate hypothesis and suggest that the GRP1 E345K mutation will be linked to changes in cell physiology and human pathologies, as demonstrated for AKT1 E17K [Carpten, J. D., et al. (2007) Nature 448, 439-444; Lindhurst, M. J., et al

3D printing of patient-specific anatomy: A tool to improve patient consent and enhance imaging interpretation by trainees.

Science.gov (United States)

Liew, Yaoren; Beveridge, Erin; Demetriades, Andreas K; Hughes, Mark A

2015-01-01

We report the use of three-dimensional or 3D printed, patient-specific anatomy as a tool to improve informed patient consent and patient understanding in a case of posterior lumbar fixation. Next, we discuss its utility as an educational tool to enhance imaging interpretation by neurosurgery trainees.

A 3-plex methylation assay combined with the FGFR3 mutation assay sensitively detects recurrent bladder cancer in voided urine

DEFF Research Database (Denmark)

Kandimalla, Raju; Masius, Roy; Beukers, Willemien

2013-01-01

is to determine the sensitivity and specificity of a urine assay for the diagnosis of recurrences in patients with a previous primary NMIBC G1/G2 by using cystoscopy as the reference standard. Experimental Design: We selected eight CpG islands (CGI) methylated in bladder cancer from our earlier genome-wide study......Purpose: DNA methylation is associated with bladder cancer and these modifications could serve as useful biomarkers. FGFR3 mutations are present in 60% to 70% of non–muscle invasive bladder cancer (NMIBC). Low-grade bladder cancer recurs in more than 50% of patients. The aim of this study......, and nonmalignant urines (n = 130). Results: The 3-plex assay identified recurrent bladder cancer in voided urine with a sensitivity of 74% in the validation set. In combination with the FGFR3 mutation assay, a sensitivity of 79% was reached (specificity of 77%). Sensitivity of FGFR3 and cytology was 52% and 57...

Petal-specific subfunctionalization of an APETALA3 paralog in the Ranunculales and its implications for petal evolution.

Science.gov (United States)

Sharma, Bharti; Guo, Chunce; Kong, Hongzhi; Kramer, Elena M

2011-08-01

• The petals of the lower eudicot family Ranunculaceae are thought to have been derived many times independently from stamens. However, investigation of the genetic basis of their identity has suggested an alternative hypothesis: that they share a commonly inherited petal identity program. This theory is based on the fact that an ancient paralogous lineage of APETALA3 (AP3) in the Ranunculaceae appears to have a conserved, petal-specific expression pattern. • Here, we have used a combination of approaches, including RNAi, comparative gene expression and molecular evolutionary studies, to understand the function of this petal-specific AP3 lineage. • Functional analysis of the Aquilegia locus AqAP3-3 has demonstrated that the paralog is required for petal identity with little contribution to the identity of the other floral organs. Expanded expression studies and analyses of molecular evolutionary patterns provide further evidence that orthologs of AqAP3-3 are primarily expressed in petals and are under higher purifying selection across the family than the other AP3 paralogs. • Taken together, these findings suggest that the AqAP3-3 lineage underwent progressive subfunctionalization within the order Ranunculales, ultimately yielding a specific role in petal identity that has probably been conserved, in stark contrast with the multiple independent origins predicted by botanical theories. © 2011 The Authors. New Phytologist © 2011 New Phytologist Trust.

SU-E-T-472: A Multi-Dimensional Measurements Comparison to Analyze a 3D Patient Specific QA Tool

International Nuclear Information System (INIS)

Ashmeg, S; Jackson, J; Zhang, Y; Oldham, M; Yin, F; Ren, L

2014-01-01

Purpose: To quantitatively evaluate a 3D patient specific QA tool using 2D film and 3D Presage dosimetry. Methods: A brain IMRT case was delivered to Delta4, EBT2 film and Presage plastic dosimeter. The film was inserted in the solid water slabs at 7.5cm depth for measurement. The Presage dosimeter was inserted into a head phantom for 3D dose measurement. Delta4's Anatomy software was used to calculate the corresponding dose to the film in solid water slabs and to Presage in the head phantom. The results from Anatomy were compared to both calculated results from Eclipse and measured dose from film and Presage to evaluate its accuracy. Using RIT software, we compared the “Anatomy” dose to the EBT2 film measurement and the film measurement to ECLIPSE calculation. For 3D analysis, DICOM file of “Anatomy” was extracted and imported to CERR software, which was used to compare the Presage dose to both “Anatomy” calculation and ECLIPSE calculation. Gamma criteria of 3% - 3mm and 5% - 5mm was used for comparison. Results: Gamma passing rates of film vs “Anatomy”, “Anatomy” vs ECLIPSE and film vs ECLIPSE were 82.8%, 70.9% and 87.6% respectively when 3% - 3mm criteria is used. When the criteria is changed to 5% - 5mm, the passing rates became 87.8%, 76.3% and 90.8% respectively. For 3D analysis, Anatomy vs ECLIPSE showed gamma passing rate of 86.4% and 93.3% for 3% - 3mm and 5% - 5mm respectively. The rate is 77.0% for Presage vs ECLIPSE analysis. The Anatomy vs ECLIPSE were absolute dose comparison. However, film and Presage analysis were relative comparison Conclusion: The results show higher passing rate in 3D than 2D in “Anatomy” software. This could be due to the higher degrees of freedom in 3D than in 2D for gamma analysis

A genetic variant of the sperm-specific SLO3 K+ channel has altered pH and Ca2+ sensitivities.

Science.gov (United States)

Geng, Yanyan; Ferreira, Juan J; Dzikunu, Victor; Butler, Alice; Lybaert, Pascale; Yuan, Peng; Magleby, Karl L; Salkoff, Lawrence; Santi, Celia M

2017-05-26

To fertilize an oocyte, sperm must first undergo capacitation in which the sperm plasma membrane becomes hyperpolarized via activation of potassium (K + ) channels and resultant K + efflux. Sperm-specific SLO3 K + channels are responsible for these membrane potential changes critical for fertilization in mouse sperm, and they are only sensitive to pH i However, in human sperm, the major K + conductance is both Ca 2+ - and pH i -sensitive. It has been debated whether Ca 2+ -sensitive SLO1 channels substitute for human SLO3 (hSLO3) in human sperm or whether human SLO3 channels have acquired Ca 2+ sensitivity. Here we show that hSLO3 is rapidly evolving and reveal a natural structural variant with enhanced apparent Ca 2+ and pH sensitivities. This variant allele (C382R) alters an amino acid side chain at a principal interface between the intramembrane-gated pore and the cytoplasmic gating ring of the channel. Because the gating ring contains sensors to intracellular factors such as pH and Ca 2+ , the effectiveness of transduction between the gating ring and the pore domain appears to be enhanced. Our results suggest that sperm-specific genes can evolve rapidly and that natural genetic variation may have led to a SLO3 variant that differs from wild type in both pH and intracellular Ca 2+ sensitivities. Whether this physiological variation confers differences in fertility among males remains to be established. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Numerical Simulation of 3D Solid-Liquid Turbulent Flow in a Low Specific Speed Centrifugal Pump: Flow Field Analysis

Directory of Open Access Journals (Sweden)

Baocheng Shi

2014-06-01

Full Text Available For numerically simulating 3D solid-liquid turbulent flow in low specific speed centrifugal pumps, the iteration convergence problem caused by complex internal structure and high rotational speed of pump is always a problem for numeral simulation researchers. To solve this problem, the combination of three measures of dynamic underrelaxation factor adjustment, step method, and rotational velocity control means according to residual curves trends of operating parameters was used to improve the numerical convergence. Numeral simulation of 3D turbulent flow in a low specific speed solid-liquid centrifugal pump was performed, and the results showed that the improved solution strategy is greatly helpful to the numerical convergence. Moreover, the 3D turbulent flow fields in pumps have been simulated for the bottom ash-particles with the volume fraction of 10%, 20%, and 30% at the same particle diameter of 0.1 mm. The two-phase calculation results are compared with those of single-phase clean water flow. The calculated results gave the main region of the abrasion of the impeller and volute casing and improve the hydraulic design of the impeller in order to decrease the abrasion and increase the service life of the pump.

DMPD: CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multipleligand specificities and functions. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available ) (.html) (.csml) Show CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multipleligand specificities and function...d NK cell membrane receptor with multipleligand specificities and functions. Authors Ross GD, Vetvicka V. Pu...igand specificities and functions. Ross GD, Vetvicka V. Clin Exp Immunol. 1993 May;92(2):181-4. (.png) (.svg...8485905 CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multiplel

Quantitative measurement of pathogen specific human memory T cell repertoire diversity using a CDR3β-specific microarray

Directory of Open Access Journals (Sweden)

Gorski Jack

2007-09-01

Full Text Available Abstract Background Providing quantitative microarray data that is sensitive to very small differences in target sequence would be a useful tool in any number of venues where a sample can consist of a multiple related sequences present in various abundances. Examples of such applications would include measurement of pseudo species in viral infections and the measurement of species of antibodies or T cell receptors that constitute immune repertoires. Difficulties that must be overcome in such a method would be to account for cross-hybridization and for differences in hybridization efficiencies between the arrayed probes and their corresponding targets. We have used the memory T cell repertoire to an influenza-derived peptide as a test case for developing such a method. Results The arrayed probes were corresponded to a 17 nucleotide TCR-specific region that distinguished sequences differing by as little as a single nucleotide. Hybridization efficiency between highly related Cy5-labeled subject sequences was normalized by including an equimolar mixture of Cy3-labeled synthetic targets representing all 108 arrayed probes. The same synthetic targets were used to measure the degree of cross hybridization between probes. Reconstitution studies found the system sensitive to input ratios as low as 0.5% and accurate in measuring known input percentages (R2 = 0.81, R = 0.90, p 0.05. Conclusion This novel strategy appears to be robust and can be adapted to any situation where complex mixtures of highly similar sequences need to be quantitatively resolved.

ALLERGEN-SPECIFIC IMMUNOTHERAPY IN CHILDREN WITH POLLINOSIS

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R. M. Torshkhoeva

2014-01-01

Full Text Available Aim: to compare clinical efficacy and safety of sublingual and parenteral allergen-specific immunotherapy in children with pollinosis. Patients and methods: 143 patients with pollinosis aged from 5 to 16 years old were included into the study. They were divided into 4 groups and received allergen-specific immunotherapy. Patients of the groups I and III were administered water-salt mixtures of extracts of tree pollen allergens. Patients from the II group received standardized adjuvant mixture of extracts of tree pollen allergens. Patients from the IV group were administered standardized extract of birch pollen allergens. Prophylaxis with water-salt solutions was performed before seasons of increased allergy risk during 3 years in autumns and winters. Prophylaxis with standardized extracts of allergens was performed uninterruptedly for 3 years. Results: allergen-specific immunotherapy prevents increase of sensitization and enlargement of allergen spectrum of elevated organism perceptibility, as well as prevents aggravation of disease course and conversion to more severe forms. It also decreases requirements of anti-allergic drugs and therefore elongates the duration of remission. Conclusions: allergen-specific immunotherapy with the use of standardized allergens is the most effective method of treatment of pollen sensitization in children. In order to increase its efficacy not less than 3 courses of immunotherapy are needed.

Teachers' Acceptance of Absenteeism: Towards Developing a Specific Scale

Science.gov (United States)

Shapira-Lishchinsky, Orly; Ishan, Gamal

2013-01-01

Purpose: This study aims to develop and validate a measure of a specific attitude toward teachers' absenteeism that predicts this behavior more accurately than other general measures of job attitudes. Design/methodology/approach: Participants were 443 teachers from 21 secondary schools in Israel. In the first phase, the teachers answered anonymous…

The specificity of Several Kinds Lipases on n-3 Polyunsaturated Fatty Acids

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Jenny Elisabeth, T Yuliani, P M Tambunan, J M Purba

2001-04-01

Full Text Available Several lipases from microbial and plant, i.e Rhizomucor miehei, Pseudomonas sp., Candida antartica, rice bran, and Carica papaya latex (CPL were examined for synthesis of omega-3 (n-3 PUFA-rich glyceride by hydrolysis and acidolysis reaction. Tuna oil was used in hydrolysis reaction, whereas tuna and palm oils were used as source of triglyceride (TAG molecules and n-3 PUFA concentrate from tuna oil as source of EPA and DHA in acidolysis reaction.For hydrolysis reaction, the rice bran and CPL lipases showed the lowest hydrolytic activity of the tuna oil, whereas the R. miehei lipase showed the highest hydrolytic activity but was unable to hydrolyze EPA and DHA. On the contrary, the C. antartica and Pseudomonas sp. lipases acted stronger on hydrolysis of DHA ester bond than EPA.For acidolysis reaction, all the lipases showed ability to incorporate n-3 PUFA into tuna and palm oils. C. antartica lipase had the maximum DHA incorporation into tuna and palm oils, rice bran lipase had relatively similar ability with R. miehei lipase, and the CPL lipase had the lowest ability. This study proved that rice bran and CPL lipases also had transesterification activity and showed the feasibility of the rice bran lipase to be a biocatalyst for n-3 PUFA-rich glyceride production. Increasing the substrate ratio, of n-3 PUFA concentrate and tuna or palm oil, could increase the EPA and DHA incorporation. The R. miehei, rice bran, and CPL lipases unabled to incorporate DHA into DHA-containing glyceride molecule, whereas C. antartica lipase had the capability in high ratio of n-3 PUFA concentrate to oil. Therefore, the lipases were easier to incorporate n-3 PUFA into palm oil than tuna oil, since the TAG molecules of palm oil was not as complex as tuna oil. It could be suggested that the lipases did not only have acyl chain and positional specificity, but also the whole glyceride structure specificity.

fMRI Evidence of Acupoints Specificity in Two Adjacent Acupoints

Directory of Open Access Journals (Sweden)

Hua Liu

2013-01-01

Full Text Available Objectives. Acupoint specificity is the foundation of acupuncture treatment. The aim of this study is to investigate whether the acupoint specificity exists in two adjacent acupoints. Design and Setting. Two adjacent real acupoints, LR3 (Taichong and ST44 (Neiting, and a nearby nonacupoint were selected. Thirty-three health volunteers were divided into three groups in random order, and each group only received acupuncture at one of the three points. While they received acupuncture, fMRI scan was performed. Results. The common cerebral activated areas responding to LR3 and ST44 included the contralateral primary somatosensory area (SI and ipsilateral cerebellum. Acupuncture at LR3 specifically activated contralateral middle occipital gyrus, ipsilateral medial frontal gyrus, superior parietal lobe, middle temporal gyrus, rostral anterior cingulate cortex (rACC, lentiform nucleus, insula, and contralateral thalamus. Stimulation at ST44 selectively activated ipsilateral secondary somatosensory area (SII, contralateral middle frontal gyrus, inferior frontal gyrus, lingual gyrus, lentiform nucleus, and bilateral posterior cingulate cortex (PCC. Conclusions. Acupuncture at adjacent acupoints elicits distinct cerebral activation patterns, and those specific patterns might be involved in the mechanism of the specific therapeutic effects of different acupoints.

[Aiming for zero blindness].

Science.gov (United States)

Nakazawa, Toru

2015-03-01

chose CHOP as our primary target for drug development. Currently, we are in the process of screening a library of 1274 drugs, all of which are already used in human subjects, for CHOP inhibitors. The last topic of our discussion is future possibilities for glaucoma management. First, we discuss the development of next generation in vivo imaging modalities that allow detailed description of pathomechanisms of this multifactorial disease, glaucoma. The purpose of this research was to improve the efficacy of glaucoma diagnosis and to visualize its pathology at a cellular/molecular level and develop molecule-specific therapies. Currently available visual field tests are subjective, since they rely on a determination of the threshold of light perception, and are affected by poor reproducibility. The current dependence on visual field tests to ascertain the progression of glaucoma is thus a serious limitation on an important task of ophthalmologists. We, therefore, turned our focus to the establishment of an in vivo imaging method to detect dying retinal ganglion cells, which would highlight the pathologic state of glaucoma with high sensitivity. To this end, we used confocal scanning ophthalmoscopy to assess the usefulness of SYTOX Orange as a cell death probe. Our results showed that this probe could reveal dying retinal ganglion cells clearly, quickly and with high sensitivity. We, therefore, believe that the clinical application of probes that can sensitively detect dying retinal ganglion cells is a highly promising approach. This also applies to the use of molecular tools that can provide information on the molecular pathology of glaucoma. Finally, we would like to introduce our national collaborative work on the analysis of "big-data". The project aims to collect as wide a range of data as possible at an unprecedented scale. The data to be registered ranges from basic glaucoma data, such as IOP and visual field test results, to data from the most sophisticated

Determination of Urine 3-HPMA, a Stable Acrolein Metabolite in a Rat Model of Spinal Cord Injury

OpenAIRE

Zheng, Lingxing; Park, Jonghyuck; Walls, Michael; Tully, Melissa; Jannasch, Amber; Cooper, Bruce; Shi, Riyi

2013-01-01

Acrolein has been suggested to be involved in a variety of pathological conditions. The monitoring of acrolein is of significant importance in delineating the pathogenesis of various diseases. Aimed at overcoming the reactivity and volatility of acrolein, we describe a specific and stable metabolite of acrolein in urine, N-acetyl-S-3-hydroxypropylcysteine (3-HPMA), as a potential surrogate marker for acrolein quantification. Using the LC/MS/MS method, we demonstrated that 3-HPMA was significa...

Specific immunotherapy in renal cancer: a systematic review.

Science.gov (United States)

Hirbod-Mobarakeh, Armin; Gordan, Hesam Addin; Zahiri, Zahra; Mirshahvalad, Mohammad; Hosseinverdi, Sima; Rini, Brian I; Rezaei, Nima

2017-02-01

Renal cell cancer (RCC) is the tenth most common malignancy in adults. In recent years, several approaches of active and passive immunotherapy have been studied extensively in clinical trials of patients with RCC. The aim of this systematic review was to assess the clinical efficacy of various approaches of specific immunotherapy in patients with RCC. We searched Medline, Scopus, CENTRAL, TRIP, DART, OpenGrey and ProQuest without any language filter through to 9 October 2015. One author reviewed search results for irrelevant and duplicate studies and two other authors independently extracted data from the studies. We collated study findings and calculated a weighted treatment effect across studies using Review Manager (version 5.3. Copenhagen: The Nordic Cochrane Centre, the Cochrane Collaboration). We identified 14 controlled studies with 4013 RCC patients after excluding irrelevant and duplicate studies from 11,319 references retrieved from a literature search. Overall, five autologous tumor cell vaccines, one peptide-based vaccine, one virus-based vaccine and one dendritic cell (DC)-based vaccine were studied in nine controlled studies of active specific immunotherapies. A total of three passive immunotherapies including autologous cytokine-induced killer (CIK) cells, auto lymphocyte therapy (ALT) and autologous lymphokine-activated killer (LAK) cells were studied in four controlled studies. The clinical efficacy of tumor lysate-pulsed DCs, with CIK cells was studied in one controlled trial concurrently. The overall quality of studies was fair. Meta-analysis of seven studies showed that patients undergoing specific immunotherapy had significantly higher overall survival (OS) than those in the control group [hazard ratio (HR) = 0.72; 95% confidence interval (CI) = 0.58-0.89, p = 0.003]. In addition, a meta-analysis of four studies showed that there was a significant difference in progression-free survival (PFS) between patients undergoing specific immunotherapy

Roles of s3 site residues of nattokinase on its activity and substrate specificity.

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Wu, Shuming; Feng, Chi; Zhong, Jin; Huan, Liandong

2007-09-01

Nattokinase (Subtilisin NAT, NK) is a bacterial serine protease with high fibrinolytic activity. To probe their roles on protease activity and substrate specificity, three residues of S3 site (Gly(100), Ser(101) and Leu(126)) were mutated by site-directed mutagenesis. Kinetics parameters of 20 mutants were measured using tetrapeptides as substrates, and their fibrinolytic activities were determined by fibrin plate method. Results of mutation analysis showed that Gly(100) and Ser(101) had reverse steric and electrostatic effects. Residues with bulky or positively charged side chains at position 100 decreased the substrate binding and catalytic activity drastically, while residues with the same characters at position 101 could obviously enhance protease and fibrinolytic activity of NK. Mutation of Leu(126) might impair the structure of the active cleft and drastically decreased the activity of NK. Kinetics studies of the mutants showed that S3 residues were crucial to keep protease activity while they moderately affected substrate specificity of NK. The present study provided some original insight into the P3-S3 interaction in NK and other subtilisins, as well as showed successful protein engineering cases to improve NK as a potential therapeutic agent.

Circulating gluten-specific FOXP3+CD39+ regulatory T cells have impaired suppressive function in patients with celiac disease.

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Cook, Laura; Munier, C Mee Ling; Seddiki, Nabila; van Bockel, David; Ontiveros, Noé; Hardy, Melinda Y; Gillies, Jana K; Levings, Megan K; Reid, Hugh H; Petersen, Jan; Rossjohn, Jamie; Anderson, Robert P; Zaunders, John J; Tye-Din, Jason A; Kelleher, Anthony D

2017-12-01

Celiac disease is a chronic immune-mediated inflammatory disorder of the gut triggered by dietary gluten. Although the effector T-cell response in patients with celiac disease has been well characterized, the role of regulatory T (Treg) cells in the loss of tolerance to gluten remains poorly understood. We sought to define whether patients with celiac disease have a dysfunction or lack of gluten-specific forkhead box protein 3 (FOXP3) + Treg cells. Treated patients with celiac disease underwent oral wheat challenge to stimulate recirculation of gluten-specific T cells. Peripheral blood was collected before and after challenge. To comprehensively measure the gluten-specific CD4 + T-cell response, we paired traditional IFN-γ ELISpot with an assay to detect antigen-specific CD4 + T cells that does not rely on tetramers, antigen-stimulated cytokine production, or proliferation but rather on antigen-induced coexpression of CD25 and OX40 (CD134). Numbers of circulating gluten-specific Treg cells and effector T cells both increased significantly after oral wheat challenge, peaking at day 6. Surprisingly, we found that approximately 80% of the ex vivo circulating gluten-specific CD4 + T cells were FOXP3 + CD39 + Treg cells, which reside within the pool of memory CD4 + CD25 + CD127 low CD45RO + Treg cells. Although we observed normal suppressive function in peripheral polyclonal Treg cells from patients with celiac disease, after a short in vitro expansion, the gluten-specific FOXP3 + CD39 + Treg cells exhibited significantly reduced suppressive function compared with polyclonal Treg cells. This study provides the first estimation of FOXP3 + CD39 + Treg cell frequency within circulating gluten-specific CD4 + T cells after oral gluten challenge of patients with celiac disease. FOXP3 + CD39 + Treg cells comprised a major proportion of all circulating gluten-specific CD4 + T cells but had impaired suppressive function, indicating that Treg cell dysfunction might be a key

Phased Startup Initiative Phases 3 and 4 Test Plan and Test Specification (OCRWM)

International Nuclear Information System (INIS)

PITNER, A.L.

2000-01-01

Construction for the Spent Nuclear Fuel (SNF) Project facilities is continuing per the Level III Baseline Schedule, and installation of the Fuel Retrieval System (FRS) and Integrated Water Treatment System (IWTS) in K West Basin is now complete. In order to accelerate the project, a phased start up strategy to initiate testing of the FRS and IWTS early in the overall project schedule was proposed (Williams 1999). Wilkinson (1999) expands the definition of the original proposal into four functional testing phases of the Phased Startup Initiative (PSI). Phases 1 and 2 are based on performing functional tests using dummy fuel. These tests are described in separate planning documents. This test plan provides overall guidance for Phase 3 and 4 tests, which are performed using actual irradiated N fuel assemblies. The overall objective of the Phase 3 and 4 testing is to verify how the FRS and IWTS respond while processing actual fuel. Conducting these tests early in the project schedule will allow identification and resolution of equipment and process problems before they become activities on the start-up critical path. The specific objectives of this test plan are to: (1) Define the test scope for the FRS and IWTS; (2) Provide detailed test requirements that can be used to write the specific test procedures; (3) Define data required and measurements to be taken. Where existing methods to obtain these do not exist, enough detail will be provided to define required additional equipment; and (4) Define specific test objectives and acceptance criteria

The effect of interventions aiming to optimise the prescription of antibiotics in dental care-A systematic review.

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Löffler, Christin; Böhmer, Femke

2017-01-01

Abundant evidence in dentistry suggests that antibiotics are prescribed despite the existence of guidelines aiming to reduce the development of antibiotic resistance. This review investigated (1) which type of interventions aiming to optimise prescription of antibiotics exist in dentistry, (2) the effect of these interventions and (3) the specific strengths and limitations of the studies reporting on these interventions. Literature search was based on Medline, Embase, Global Health, Cochrane CENTRAL, ClinicalTrials.gov and Current Controlled Trials. Studies with one of the two primary outcomes were included: (1) The number of antibiotics prescribed and/or (2) the accuracy of the prescription, commonly measured as a percentage of adherence to local clinical guidelines. Nine studies met these inclusion criteria. Five studies reported on the prescription of antibiotics in primary dental care and four studies focused on outpatient dental care. Interventions used in primary dental care included a combination of audit, feedback, education, local consensus, dissemination of guidelines and/or academic detailing. Trials in the outpatient setting made use of expert panel discussions, educational feedback on previous acts of prescribing, the dissemination of guidelines and the establishment of internal guidelines. All studies successfully reduced the number of antibiotics prescribed and/or increased the accuracy of the prescription. However, most studies were confounded by a high risk of selection bias, selective outcome reporting and high variance across study groups. In particular, information relating to study design and methodology was insufficient. Only three studies related the prescriptions to the number of patients treated with antibiotics. This systematic review was able to offer conclusions which took the limitations of the investigated studies into account. Unfortunately, few studies could be included and many of these studies were confounded by a low quality of

The effect of interventions aiming to optimise the prescription of antibiotics in dental care-A systematic review.

Directory of Open Access Journals (Sweden)

Christin Löffler

Full Text Available Abundant evidence in dentistry suggests that antibiotics are prescribed despite the existence of guidelines aiming to reduce the development of antibiotic resistance. This review investigated (1 which type of interventions aiming to optimise prescription of antibiotics exist in dentistry, (2 the effect of these interventions and (3 the specific strengths and limitations of the studies reporting on these interventions.Literature search was based on Medline, Embase, Global Health, Cochrane CENTRAL, ClinicalTrials.gov and Current Controlled Trials. Studies with one of the two primary outcomes were included: (1 The number of antibiotics prescribed and/or (2 the accuracy of the prescription, commonly measured as a percentage of adherence to local clinical guidelines.Nine studies met these inclusion criteria. Five studies reported on the prescription of antibiotics in primary dental care and four studies focused on outpatient dental care. Interventions used in primary dental care included a combination of audit, feedback, education, local consensus, dissemination of guidelines and/or academic detailing. Trials in the outpatient setting made use of expert panel discussions, educational feedback on previous acts of prescribing, the dissemination of guidelines and the establishment of internal guidelines. All studies successfully reduced the number of antibiotics prescribed and/or increased the accuracy of the prescription. However, most studies were confounded by a high risk of selection bias, selective outcome reporting and high variance across study groups. In particular, information relating to study design and methodology was insufficient. Only three studies related the prescriptions to the number of patients treated with antibiotics.This systematic review was able to offer conclusions which took the limitations of the investigated studies into account. Unfortunately, few studies could be included and many of these studies were confounded by a low

WE-DE-207B-11: Implementation of Size-Specific 3D Beam Modulation Filters On a Dedicated Breast CT Platform Using Breast Immobilization

Energy Technology Data Exchange (ETDEWEB)

Hernandez, A [Department of Radiology, Biomedical Engineering Graduate Group, University of California Davis, Sacramento, CA (United States); Boone, J [Departments of Radiology and Biomedical Engineering, University of California Davis, Sacramento, CA (United States)

2016-06-15

Purpose: To implement a 3D beam modulation filter (3D-BMF) in dedicated breast CT (bCT) and develop a method for conforming the patient’s breast to a pre-defined shape, optimizing the effects of the filter. This work expands on previous work reporting the methodology for designing a 3D-BMF that can spare unnecessary dose and improve signal equalization at the detector by preferentially filtering the beam in the thinner anterior and peripheral breast regions. Methods: Effective diameter profiles were measured for 219 segmented bCT images, grouped into volume quintiles, and averaged within each group to represent the range of breast sizes found clinically. These profiles were then used to generate five size-specific computational phantoms and fabricate five size-specific UHMW phantoms. Each computational phantom was utilized for designing a size-specific 3D-BMF using previously reported methods. Glandular dose values and projection images were simulated in MCNP6 with and without the 3DBMF using the system specifications of our prototype bCT scanner “Doheny”. Lastly, thermoplastic was molded around each of the five phantom sizes and used to produce a series of breast immobilizers for use in conforming the patient’s breast during bCT acquisition. Results: After incorporating the 3D-BMF, MC simulations estimated an 80% average reduction in the detector dynamic range requirements across all phantom sizes. The glandular dose was reduced on average 57% after normalizing by the number of quanta reaching the detector under the thickest region of the breast. Conclusion: A series of bCT-derived breast phantoms were used to design size-specific 3D-BMFs and breast immobilizers that can be used on the bCT platform to conform the patient’s breast and therefore optimally exploit the benefits of the 3D-BMF. Current efforts are focused on fabricating several prototype 3D-BMFs and performing phantom scans on Doheny for MC simulation validation and image quality analysis

WE-DE-207B-11: Implementation of Size-Specific 3D Beam Modulation Filters On a Dedicated Breast CT Platform Using Breast Immobilization

International Nuclear Information System (INIS)

Hernandez, A; Boone, J

2016-01-01

Purpose: To implement a 3D beam modulation filter (3D-BMF) in dedicated breast CT (bCT) and develop a method for conforming the patient’s breast to a pre-defined shape, optimizing the effects of the filter. This work expands on previous work reporting the methodology for designing a 3D-BMF that can spare unnecessary dose and improve signal equalization at the detector by preferentially filtering the beam in the thinner anterior and peripheral breast regions. Methods: Effective diameter profiles were measured for 219 segmented bCT images, grouped into volume quintiles, and averaged within each group to represent the range of breast sizes found clinically. These profiles were then used to generate five size-specific computational phantoms and fabricate five size-specific UHMW phantoms. Each computational phantom was utilized for designing a size-specific 3D-BMF using previously reported methods. Glandular dose values and projection images were simulated in MCNP6 with and without the 3DBMF using the system specifications of our prototype bCT scanner “Doheny”. Lastly, thermoplastic was molded around each of the five phantom sizes and used to produce a series of breast immobilizers for use in conforming the patient’s breast during bCT acquisition. Results: After incorporating the 3D-BMF, MC simulations estimated an 80% average reduction in the detector dynamic range requirements across all phantom sizes. The glandular dose was reduced on average 57% after normalizing by the number of quanta reaching the detector under the thickest region of the breast. Conclusion: A series of bCT-derived breast phantoms were used to design size-specific 3D-BMFs and breast immobilizers that can be used on the bCT platform to conform the patient’s breast and therefore optimally exploit the benefits of the 3D-BMF. Current efforts are focused on fabricating several prototype 3D-BMFs and performing phantom scans on Doheny for MC simulation validation and image quality analysis

Efficient and Specific Analysis of Red Blood Cell Glycerophospholipid Fatty Acid Composition

OpenAIRE

Klem, Sabrina; Klingler, Mario; Demmelmair, Hans; Koletzko, Berthold

2012-01-01

BACKGROUND: Red blood cell (RBC) n-3 fatty acid status is related to various health outcomes. Accepted biological markers for the fatty acid status determination are RBC phospholipids, phosphatidylcholine, and phosphatidyletholamine. The analysis of these lipid fractions is demanding and time consuming and total phospholipid n-3 fatty acid levels might be affected by changes of sphingomyelin contents in the RBC membrane during n-3 supplementation. AIM: We developed a method for the specific a...

3D reconstruction of a patient-specific surface model of the proximal femur from calibrated x-ray radiographs: A validation study

International Nuclear Information System (INIS)

Zheng Guoyan; Schumann, Steffen

2009-01-01

Twenty-three femurs (one plastic bone and twenty-two cadaver bones) with both nonpathologic and pathologic cases were considered to validate a statistical shape model based technique for three-dimensional (3D) reconstruction of a patient-specific surface model from calibrated x-ray radiographs. The 3D reconstruction technique is based on an iterative nonrigid registration of the features extracted from a statistically instantiated 3D surface model to those interactively identified from the radiographs. The surface models reconstructed from the radiographs were compared to the associated ground truths derived either from a 3D CT-scan reconstruction method or from a 3D laser-scan reconstruction method and an average error distance of 0.95 mm were found. Compared to the existing works, our approach has the advantage of seamlessly handling both nonpathologic and pathologic cases even when the statistical shape model that we used was constructed from surface models of nonpathologic bones.

How Does Attention Relate to the Ability-Specific and Position-Specific Components of Reasoning Measured by APM?

Science.gov (United States)

Ren, Xuezhu; Goldhammer, Frank; Moosbrugger, Helfried; Schweizer, Karl

2012-01-01

The aim of the present study was to clarify the nature of the ability-specific and position-specific components of Raven's Advanced Progressive Matrices (APM) by relating them to a number of types of attention. The ability-specific component represents the constant part of cognitive performance whereas the position-specific component reflects the…

MKP1 phosphatase mediates G1-specific dephosphorylation of H3Serine10P in response to DNA damage

Energy Technology Data Exchange (ETDEWEB)

Sharma, Ajit K.; Khan, Shafqat A.; Sharda, Asmita; Reddy, Divya V; Gupta, Sanjay, E-mail: sgupta@actrec.gov.in

2015-08-15

Highlights: • Reversible reduction of H3S10 phosphorylation after DNA damage is G1 phase specific. • Dynamic balance between MAP kinases, MKP1 and MSK1 regulate H3S10P during DDR. • MKP1 associates with chromatin bearing γH2AX in response to DNA damage. • Inhibition of MKP1 activity with specific inhibitor promotes radiation-induced cell death. - Abstract: Histone mark, H3S10 phosphorylation plays a dual role in a cell by maintaining relaxed chromatin for active transcription in interphase and condensed chromatin state in mitosis. The level of H3S10P has also been shown to alter on DNA damage; however, its cell cycle specific behavior and regulation during DNA damage response is largely unexplored. In the present study, we demonstrate G1 cell cycle phase specific reversible loss of H3S10P in response to IR-induced DNA damage is mediated by opposing activities of phosphatase, MKP1 and kinase, MSK1 of the MAP kinase pathway. We also show that the MKP1 recruits to the chromatin in response to DNA damage and correlates with the decrease of H3S10P, whereas MKP1 is released from chromatin during recovery phase of DDR. Furthermore, blocking of H3S10 dephosphorylation by MKP1 inhibition impairs DNA repair process and results in poor survival of WRL68 cells. Collectively, our data proposes a pathway regulating G1 cell cycle phase specific reversible reduction of H3S10P on IR induced DNA damage and also raises the possibility of combinatorial modulation of H3S10P with specific inhibitors to target the cancer cells in G1-phase of cell cycle.

Clinical accuracy of a patient-specific femoral osteotomy guide in minimally-invasive posterior hip arthroplasty.

Science.gov (United States)

Schneider, Adrian K; Pierrepont, Jim W; Hawdon, Gabrielle; McMahon, Stephen

2018-04-01

Patient specific guides can be a valuable tool in improving the precision of planned femoral neck osteotomies, especially in minimally invasive hip surgery, where bony landmarks are often inaccessible. The aim of our study was to validate the accuracy of a novel patient specific femoral osteotomy guide for THR through a minimally invasive posterior approach, the direct superior approach (DSA). As part of our routine preoperative planning 30 patients underwent low dose CT scans of their arthritic hip. 3D printed patient specific femoral neck osteotomy guides were then produced. Intraoperatively, having cleared all soft tissue from the postero-lateral neck of the enlocated hip, the guide was placed and pinned onto the posterolateral femoral neck. The osteotomy was performed using an oscillating saw and the uncemented hip components were implanted as per routine. Postoperatively, the achieved level of the osteotomy at the medial calcar was compared with the planned level of resection using a 3D/2D matching analysis (Mimics X-ray module, Materialise, Belgium). A total of 30 patients undergoing uncemented Trinity™ acetabular and TriFit TS™ femoral component arthroplasty (Corin, UK) were included in our analysis. All but one of our analysed osteotomies were found to be within 3 mm from the planned height of osteotomy. In one patient the level of osteotomy deviated 5 mm below the planned level of resection. Preoperative planning and the use of patient specific osteotomy guides provides an accurate method of performing femoral neck osteotomies in minimally invasive hip arthroplasty using the direct superior approach. IV (Case series).

Ultimate Educational Aims, Overridingness, and Personal Well-Being

Science.gov (United States)

Haji, Ishtiyaque; Cuypers, Stefaan E.

2011-01-01

Discussion regarding education's aims, especially its ultimate aims, is a key topic in the philosophy of education. These aims or values play a pivotal role in regulating and structuring moral and other types of normative education. We outline two plausible strategies to identify and justify education's ultimate aims. The first associates these…

Natural teeth-retained splint based on a patient-specific 3D-printed mandible used for implant surgery and vestibuloplasty: A case report.

Science.gov (United States)

Xing, Helin; Wu, Jinshuang; Zhou, Lei; Yang, Sefei

2017-12-01

With respect to improving the quality of oral rehabilitation, the management of keratinized mucosa is as important as bone condition for implant success. To enhance this management, a natural teeth-retained splint based on a patient-specific 3-dimensional (3D) printed mandible was used in vestibuloplasty to provide sufficient keratinized mucosa around dental implants to support long-term implant maintenance. A 28-year-old male patient had a fracture of the anterior andible 1 year ago, and the fracture was treated with titanium. The patient had lost mandibular incisors on both the sides and had a shallow vestibule and little keratinized mucosa. In the first-stage implant surgery, 2 implants were inserted and the titanium fracture fixation plates and screws were removed at the same time. During second-stage implant surgery, vestibuloplasty was performed, and the natural teeth-retained splint was applied. The splint was made based upon a patient-specific 3D-printed mandible. At 30-day follow-up, the splint was modified and reset. The modified splint was removed after an additional 60 days, and the patient received prosthetic treatment. After prosthetic treatment, successful oral rehabilitation was achieved. Within 1 year and 3 years after implant prosthesis finished, the patient exhibited a good quantity of keratinized gingiva. The proposed splint is a simple and time-effective technique for correcting soft tissue defects in implant dentistry that ensures a good quantity of keratinized mucosa.

Marine omega-3 polyunsaturated fatty acids induce sex-specific changes in reinforcer-controlled behaviour and neurotransmitter metabolism in a spontaneously hypertensive rat model of ADHD

Directory of Open Access Journals (Sweden)

Dervola Kine S

2012-12-01

Full Text Available Abstract Background Previous reports suggest that omega-3 (n-3 polyunsaturated fatty acids (PUFA supplements may reduce ADHD-like behaviour. Our aim was to investigate potential effects of n-3 PUFA supplementation in an animal model of ADHD. Methods We used spontaneously hypertensive rats (SHR. SHR dams were given n-3 PUFA (EPA and DHA-enriched feed (n-6/n-3 of 1:2.7 during pregnancy, with their offspring continuing on this diet until sacrificed. The SHR controls and Wistar Kyoto (WKY control rats were given control-feed (n-6/n-3 of 7:1. During postnatal days (PND 25–50, offspring were tested for reinforcement-dependent attention, impulsivity and hyperactivity as well as spontaneous locomotion. The animals were then sacrificed at PND 55–60 and their neostriata were analysed for monoamine and amino acid neurotransmitters with high performance liquid chromatography. Results n-3 PUFA supplementation significantly enhanced reinforcement-controlled attention and reduced lever-directed hyperactivity and impulsiveness in SHR males whereas the opposite or no effects were observed in females. Analysis of neostriata from the same animals showed significantly enhanced dopamine and serotonin turnover ratios in the male SHRs, whereas female SHRs showed no change, except for an intermediate increase in serotonin catabolism. In contrast, both male and female SHRs showed n-3 PUFA-induced reduction in non-reinforced spontaneous locomotion, and sex-independent changes in glycine levels and glutamate turnover. Conclusions Feeding n-3 PUFAs to the ADHD model rats induced sex-specific changes in reinforcement-motivated behaviour and a sex-independent change in non-reinforcement-associated behaviour, which correlated with changes in presynaptic striatal monoamine and amino acid signalling, respectively. Thus, dietary n-3 PUFAs may partly ameliorate ADHD-like behaviour by reinforcement-induced mechanisms in males and partly via reinforcement-insensitive mechanisms

ACA and the Triple Aim: Musings of a Health Care Actuary.

Science.gov (United States)

McCarthy, Mac

2015-01-01

In 2008, the Institute for Healthcare Improvement (IHI) promulgated the Triple Aim, which advocates simultaneous improvements in patient experiences, improved population health and lower cost per capita. In 2010, the Patient Protection and Affordable Care Act (ACA) promised quality, affordable health care for all Americans. It's fair to assume that the framers of ACA were aware of the Triple Aim, and it is likely that much of ACA was heavily influenced by IHI's positions. So it is reasonable, from time to time, to assess ACA's impact on health care against the Triple Aim principles.

S3QL: A distributed domain specific language for controlled semantic integration of life sciences data

Directory of Open Access Journals (Sweden)

de Lencastre Hermínia

2011-07-01

Full Text Available Abstract Background The value and usefulness of data increases when it is explicitly interlinked with related data. This is the core principle of Linked Data. For life sciences researchers, harnessing the power of Linked Data to improve biological discovery is still challenged by a need to keep pace with rapidly evolving domains and requirements for collaboration and control as well as with the reference semantic web ontologies and standards. Knowledge organization systems (KOSs can provide an abstraction for publishing biological discoveries as Linked Data without complicating transactions with contextual minutia such as provenance and access control. We have previously described the Simple Sloppy Semantic Database (S3DB as an efficient model for creating knowledge organization systems using Linked Data best practices with explicit distinction between domain and instantiation and support for a permission control mechanism that automatically migrates between the two. In this report we present a domain specific language, the S3DB query language (S3QL, to operate on its underlying core model and facilitate management of Linked Data. Results Reflecting the data driven nature of our approach, S3QL has been implemented as an application programming interface for S3DB systems hosting biomedical data, and its syntax was subsequently generalized beyond the S3DB core model. This achievement is illustrated with the assembly of an S3QL query to manage entities from the Simple Knowledge Organization System. The illustrative use cases include gastrointestinal clinical trials, genomic characterization of cancer by The Cancer Genome Atlas (TCGA and molecular epidemiology of infectious diseases. Conclusions S3QL was found to provide a convenient mechanism to represent context for interoperation between public and private datasets hosted at biomedical research institutions and linked data formalisms.

Enzyme-Linked Immunosorbent Assay Specific for (1→6) Branched, (1→3)-β-d-Glucan Detection in Environmental Samples

OpenAIRE

Milton, Donald K.; Alwis, K. Udeni; Fisette, Leslie; Muilenberg, Michael

2001-01-01

(1→3)-β-d-Glucans have been recognized as a potential causative agent responsible for bioaerosol-induced respiratory symptoms observed in both indoor and occupational environments. A specific enzyme immunoassay was developed to quantify (1→6) branched, (1→3)-β-d-glucans in environmental samples. The assay was based on the use of a high-affinity receptor (galactosyl ceramide) specific for (1→3)-β-d-glucans as a capture reagent and a monoclonal antibody specific for fungal cell wall β-d-glucans...

Sensitivity and specificity of dried blood spots for HIV-1 viral load quantification: A laboratory assessment of 3 commercial assays.

Science.gov (United States)

Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien

2016-11-01

The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS.Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined.A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was 25% of the specimens differed by >0.5 log cps/mL.All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1).The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens.

A method of teaching critical care skills to undergraduate student midwives using the Maternal-Acute Illness Management (M-AIM) training day.

Science.gov (United States)

McCarthy, Rose; Nuttall, Janet; Smith, Joyce; Hollins Martin, Caroline J

2014-11-01

The most recent Confidential Enquiry into Maternal Deaths (CMACE, 2011) identified human errors, specifically those of midwives and obstetricians/doctors as a fundamental component in contributing to maternal death in the U.K. This paper discusses these findings and outlines a project to provide training in Maternal-Acute Illness Management (M-AIM) to final year student midwives. Contents of the program are designed to educate and simulate AIM skills and increase confidence and clinical ability in early recognition, management and referral of the acutely ill woman. An outline of the Maternal-AIM program delivered at the University of Salford (Greater Manchester, UK) is presented to illustrate how this particular institution has responded to a perceived need voiced by local midwifery leaders. It is proposed that developing this area of expertise in the education system will better prepare student midwives for contemporary midwifery practice. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Poly(A-Specific Ribonuclease Mediates 3′-End Trimming of Argonaute2-Cleaved Precursor MicroRNAs

Directory of Open Access Journals (Sweden)

Mayuko Yoda

2013-11-01

Full Text Available MicroRNAs (miRNAs are typically generated as ∼22-nucleotide double-stranded RNAs via the processing of precursor hairpins by the ribonuclease III enzyme Dicer, after which they are loaded into Argonaute (Ago proteins to form an RNA-induced silencing complex (RISC. However, the biogenesis of miR-451, an erythropoietic miRNA conserved in vertebrates, occurs independently of Dicer and instead requires cleavage of the 3′ arm of the pre-miR-451 precursor hairpin by Ago2. The 3′ end of the Ago2-cleaved pre-miR-451 intermediate is then trimmed to the mature length by an unknown nuclease. Here, using a classical chromatographic approach, we identified poly(A-specific ribonuclease (PARN as the enzyme responsible for the 3′–5′ exonucleolytic trimming of Ago2-cleaved pre-miR-451. Surprisingly, our data show that trimming of Ago2-cleaved precursor miRNAs is not essential for target silencing, indicating that RISC is functional with miRNAs longer than the mature length. Our findings define the maturation step in the miRNA biogenesis pathway that depends on Ago2-mediated cleavage.

Specific heat of rare earth cobaltates RCoO{sub 3} (R = La, Pr and Nd)

Energy Technology Data Exchange (ETDEWEB)

Thakur, Rasna, E-mail: rasnathakur@yahoo.com [Department of Physics, Barkatullah University, Bhopal 462026 (India); Srivastava, Archana [Department of Physics, Sri Sathya Sai College for Women, Bhopal 462024 (India); Thakur, Rajesh K.; Gaur, N.K. [Department of Physics, Barkatullah University, Bhopal 462026 (India)

2012-03-05

Highlights: Black-Right-Pointing-Pointer We have reported the temperature dependence (5 K {<=} T {<=} 1000 K) of the lattice contribution to the specific heat of rhombohedral LaCoO{sub 3} and orthocobaltates RCoO{sub 3} (R = Pr and Nd). Black-Right-Pointing-Pointer The strong electron phonon interactions are present in these compounds and lattice distortions can affect them substantially. Black-Right-Pointing-Pointer Thus Rigid Ion Model (RIM) is used for the first time to study the cohesive and thermal properties of the cobaltates RCoO{sub 3} with rare earth cation (R = La, Pr and Nd). Black-Right-Pointing-Pointer The values of specific heat calculated by us have shown remarkably good agreement with corresponding experimental data. Black-Right-Pointing-Pointer In addition, the results on the temperature dependence of cohesive energy ({phi}), molecular force constant (f), Reststrahlen frequency ({upsilon}), Debye temperature ({theta}{sub D}) and Gruneisen parameter ({gamma}) are also reported. - Abstract: We have reported the temperature dependence (5 K {<=} T {<=} 1000 K) of the lattice contribution to the specific heat of rhombohedral LaCoO{sub 3} and orthocobaltates RCoO{sub 3} (R = Pr and Nd). The strong electron phonon interactions are present in these compounds and lattice distortions can affect them substantially. Thus Rigid Ion Model (RIM) is used for the first time to study the cohesive and thermal properties of the cobaltates RCoO{sub 3} with rare earth cation (R = La, Pr and Nd). The values of specific heat calculated by us have shown remarkably good agreement with corresponding experimental data. In addition, the results on the temperature dependence of cohesive energy ({phi}), molecular force constant (f), Reststrahlen frequency ({upsilon}), Debye temperature ({theta}{sub D}) and Gruneisen parameter ({gamma}) are also reported.

Patient-specific pediatric silicone heart valve models based on 3D ultrasound

Science.gov (United States)

Ilina, Anna; Lasso, Andras; Jolley, Matthew A.; Wohler, Brittany; Nguyen, Alex; Scanlan, Adam; Baum, Zachary; McGowan, Frank; Fichtinger, Gabor

2017-03-01

PURPOSE: Patient-specific heart and valve models have shown promise as training and planning tools for heart surgery, but physically realistic valve models remain elusive. Available proprietary, simulation-focused heart valve models are generic adult mitral valves and do not allow for patient-specific modeling as may be needed for rare diseases such as congenitally abnormal valves. We propose creating silicone valve models from a 3D-printed plastic mold as a solution that can be adapted to any individual patient and heart valve at a fraction of the cost of direct 3D-printing using soft materials. METHODS: Leaflets of a pediatric mitral valve, a tricuspid valve in a patient with hypoplastic left heart syndrome, and a complete atrioventricular canal valve were segmented from ultrasound images. A custom software was developed to automatically generate molds for each valve based on the segmentation. These molds were 3D-printed and used to make silicone valve models. The models were designed with cylindrical rims of different sizes surrounding the leaflets, to show the outline of the valve and add rigidity. Pediatric cardiac surgeons practiced suturing on the models and evaluated them for use as surgical planning and training tools. RESULTS: Five out of six surgeons reported that the valve models would be very useful as training tools for cardiac surgery. In this first iteration of valve models, leaflets were felt to be unrealistically thick or stiff compared to real pediatric leaflets. A thin tube rim was preferred for valve flexibility. CONCLUSION: The valve models were well received and considered to be valuable and accessible tools for heart valve surgery training. Further improvements will be made based on surgeons' feedback.

European Commission action aimed at constructing a European regulatory framework

International Nuclear Information System (INIS)

Ristori, D.

2010-01-01

The challenge of a low-carbon economy provides a new incentive for the development of renewable energies as well as of nuclear energy. The latter calls for a high level of safety and security. The EU has a role in providing a legal framework for this purpose as well as ensuring that these standards are respected internationally. For over 50 years the EURATOM Treaty has offered the legal basis for a wide range of initiatives supporting this policy. The EU has competences under chapter 3, 'Health and Safety', for the establishment of basic safety standards for the protection against ionizing radiation. These have extended beyond the scope of nuclear energy and now include medical exposures as well as natural radiation sources. The latest revision of the BSS-Directive, to be proposed in 2011, was an opportunity for the consolidation of all Community legislation. A ruling of the Court of Justice in 1999 paved the way for the establishment of standards on the safety of nuclear installations. A common vision on this matter was achieved through the creation of a body of European Safety Regulators (ENSREG) and the adoption of a specific Safety Directive in 2009. This new Directive translates internationally agreed safety standards into legally binding EU legislation and strengthens the position of national Regulators. (author)

Direct ex vivo detection of HLA-DR3-restricted cytomegalovirus- and Mycobacterium tuberculosis-specific CD4+ T cells.

Science.gov (United States)

Bronke, Corine; Palmer, Nanette M; Westerlaken, Geertje H A; Toebes, Mireille; van Schijndel, Gijs M W; Purwaha, Veenu; van Meijgaarden, Krista E; Schumacher, Ton N M; van Baarle, Debbie; Tesselaar, Kiki; Geluk, Annemieke

2005-09-01

In order to detect epitope-specific CD4+ T cells in mycobacterial or viral infections in the context of human class II major histocompatibility complex protein human leukocyte antigen (HLA)-DR3, two HLA-DR3 tetrameric molecules were successfully produced. One contained an immunodominant HLA-DR3-restricted T-cell epitope derived from the 65-kDa heat-shock protein of Mycobacterium tuberculosis, peptide 1-13. For the other tetramer, we used an HLA-DR3-restricted T-cell epitope derived from cytomegalovirus (CMV) pp65 lower matrix protein, peptide 510-522, which induced high levels of interferon (IFN)-gamma-producing CD4+ T cells in three of four HLA-DR3-positive CMV-seropositive individuals up to 0.84% of CD4+ T cells by intracellular cytokine staining. In peripheral blood mononuclear cells from M. tuberculosis-exposed, Mycobacterium bovis bacille Calmette-Guérin (BCG)-vaccinated, or CMV-seropositive individuals, we were able to directly detect with both tetramers epitope-specific T cells up to 0.62% and 0.45% of the CD4+ T-cell population reactive to M. tuberculosis and CMV, respectively. After a 6-day culture with peptide p510-522, the frequency of CMV-specific tetramer-binding T cells was expanded up to 9.90% tetramer+ CFSElow (5,6-carboxyfluorescein diacetate succinimidyl ester) cells within the CD4+ T-cell population, further confirming the specificity of the tetrameric molecules. Thus, HLA-DR3/peptide tetrameric molecules can be used to investigate HLA-DR3-restricted antigen-specific CD4+ T cells in clinical disease or after vaccination.

Advanced 3D Mesh Manipulation in Stereolithographic Files and Post-Print Processing for the Manufacturing of Patient-Specific Vascular Flow Phantoms.

Science.gov (United States)

O'Hara, Ryan P; Chand, Arpita; Vidiyala, Sowmya; Arechavala, Stacie M; Mitsouras, Dimitrios; Rudin, Stephen; Ionita, Ciprian N

2016-02-27

Complex vascular anatomies can cause the failure of image-guided endovascular procedures. 3D printed patient-specific vascular phantoms provide clinicians and medical device companies the ability to preemptively plan surgical treatments, test the likelihood of device success, and determine potential operative setbacks. This research aims to present advanced mesh manipulation techniques of stereolithographic (STL) files segmented from medical imaging and post-print surface optimization to match physiological vascular flow resistance. For phantom design, we developed three mesh manipulation techniques. The first method allows outlet 3D mesh manipulations to merge superfluous vessels into a single junction, decreasing the number of flow outlets and making it feasible to include smaller vessels. Next we introduced Boolean operations to eliminate the need to manually merge mesh layers and eliminate errors of mesh self-intersections that previously occurred. Finally we optimize support addition to preserve the patient anatomical geometry. For post-print surface optimization, we investigated various solutions and methods to remove support material and smooth the inner vessel surface. Solutions of chloroform, alcohol and sodium hydroxide were used to process various phantoms and hydraulic resistance was measured and compared with values reported in literature. The newly mesh manipulation methods decrease the phantom design time by 30 - 80% and allow for rapid development of accurate vascular models. We have created 3D printed vascular models with vessel diameters less than 0.5 mm. The methods presented in this work could lead to shorter design time for patient specific phantoms and better physiological simulations.

Effects of Economic Policies Aimed at Encouraging a Healthier Grain Consumption

OpenAIRE

Nordstrom, Jonas; Thunstrom, Linda

2007-01-01

In this paper, we evaluate the effects of policy reforms aimed at achieving two policy objectives for grain consumption; (a) to double the intake of bread and breakfast cereals and (b) to ensure that half of the bread and breakfast cereals consumed are whole grain products. The overall aim of these policy objectives are to increase the dietary fibre intake from grain consumption so as to significantly contribute to the general recommended (minimum) increase of the fibre intake. Based on param...