Atomic layer epitaxy of Ruddlesden-Popper SrO(SrTiO{sub 3}){sub n} films by means of metalorganic aerosol deposition

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

Jungbauer, M.; Hühn, S.; Moshnyaga, V.

2014-12-22

We report an atomic layer epitaxial growth of Ruddlesden-Popper (RP) thin films of SrO(SrTiO{sub 3}){sub n} (n = ∞, 2, 3, 4) by means of metalorganic aerosol deposition (MAD). The films are grown on SrTiO{sub 3}(001) substrates by means of a sequential deposition of Sr-O/Ti-O{sub 2} atomic monolayers, monitored in-situ by optical ellipsometry. X-ray diffraction and transmission electron microscopy (TEM) reveal the RP structure with n = 2–4 in accordance with the growth recipe. RP defects, observed by TEM in a good correlation with the in-situ ellipsometry, mainly result from the excess of SrO. Being maximal at the film/substrate interface, the SrO excess rapidlymore » decreases and saturates after 5–6 repetitions of the SrO(SrTiO{sub 3}){sub 4} block at the level of 2.4%. This identifies the SrTiO{sub 3} substrate surface as a source of RP defects under oxidizing conditions within MAD. Advantages and limitations of MAD as a solution-based and vacuum-free chemical deposition route were discussed in comparison with molecular beam epitaxy.« less

MADNESS: A Multiresolution, Adaptive Numerical Environment for Scientific Simulation

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

Harrison, Robert J.; Beylkin, Gregory; Bischoff, Florian A.

2016-01-01

MADNESS (multiresolution adaptive numerical environment for scientific simulation) is a high-level software environment for solving integral and differential equations in many dimensions that uses adaptive and fast harmonic analysis methods with guaranteed precision based on multiresolution analysis and separated representations. Underpinning the numerical capabilities is a powerful petascale parallel programming environment that aims to increase both programmer productivity and code scalability. This paper describes the features and capabilities of MADNESS and briefly discusses some current applications in chemistry and several areas of physics.

Structure of an intermediate conformer of the spindle checkpoint protein Mad2

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

Hara, Mayuko; Özkan, Engin; Sun, Hongbin

2015-08-24

The spindle checkpoint senses unattached kinetochores during prometaphase and inhibits the anaphase-promoting complex or cyclosome (APC/C), thus ensuring accurate chromosome segregation. The checkpoint protein mitotic arrest deficient 2 (Mad2) is an unusual protein with multiple folded states. Mad2 adopts the closed conformation (C-Mad2) in a Mad1–Mad2 core complex. In mitosis, kinetochore-bound Mad1–C-Mad2 recruits latent, open Mad2 (O-Mad2) from the cytosol and converts it to an intermediate conformer (I-Mad2), which can then bind and inhibit the APC/C activator cell division cycle 20 (Cdc20) as C-Mad2. In this paper, we report the crystal structure and NMR analysis of I-Mad2 bound to C-Mad2.more » Although I-Mad2 retains the O-Mad2 fold in crystal and in solution, its core structural elements undergo discernible rigid-body movements and more closely resemble C-Mad2. Residues exhibiting methyl chemical shift changes in I-Mad2 form a contiguous, interior network that connects its C-Mad2–binding site to the conformationally malleable C-terminal region. Mutations of residues at the I-Mad2–C-Mad2 interface hinder I-Mad2 formation and impede the structural transition of Mad2. Finally, our study provides insight into the conformational activation of Mad2 and establishes the basis of allosteric communication between two distal sites in Mad2.« less

FINDING A METHOD FOR THE MADNESS: A COMPARATIVE ANALYSIS OF STRATEGIC DESIGN METHODOLOGIES

DTIC Science & Technology

2017-06-01

FINDING A METHOD FOR THE MADNESS: A COMPARATIVE ANALYSIS OF STRATEGIC DESIGN METHODOLOGIES BY AMANDA DONNELLY A THESIS...work develops a comparative model for strategic design methodologies, focusing on the primary elements of vision, time, process, communication and...collaboration, and risk assessment. My analysis dissects and compares three potential design methodologies including, net assessment, scenarios and

Resolution of the Band Gap Prediction Problem for Materials Design

DOE PAGES

Crowley, Jason M.; Tahir-Kheli, Jamil; Goddard, William A.

2016-03-04

An important property with any new material is the band gap. Standard density functional theory methods grossly underestimate band gaps. This is known as the band gap problem. Here in this paper, we show that the hybrid B3PW91 density functional returns band gaps with a mean absolute deviation (MAD) from experiment of 0.22 eV over 64 insulators with gaps spanning a factor of 500 from 0.014 to 7 eV. The MAD is 0.28 eV over 70 compounds with gaps up to 14.2 eV, with a mean error of -0.03 eV. To benchmark the quality of the hybrid method, we comparedmore » the hybrid method to the rigorous GW many-body perturbation theory method. Surprisingly, the MAD for B3PW91 is about 1.5 times smaller than the MAD for GW. Furthermore, B3PW91 is 3-4 orders of magnitude faster computationally. Hence, B3PW91 is a practical tool for predicting band gaps of materials before they are synthesized and represents a solution to the band gap prediction problem.« less

Purification, crystallization and preliminary crystallographic study of an IDS-epimerase from Agrobacterium tumefaciens BY6

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

Bäuerle, Bettina; Sandalova, Tatyana; Schneider, Gunter

2006-08-01

This is the first report of the crystallization of an IDS-epimerase from A. tumefaciens BY6 and its l-selenomethionine derivative. The initial degradation of all stereoisomers of the complexing agent iminodisuccinate (IDS) is enabled by an epimerase in the bacterial strain Agrobacterium tumefaciens BY6. This protein was produced in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion method. Crystals of IDS-epimerase were obtained under several conditions. The best diffracting crystals were grown in 22% PEG 3350, 0.2 M (NH{sub 4}){sub 2}SO{sub 4} and 0.1 M bis-Tris propane pH 7.2 at 293 K. These crystals belong to the monoclinic space groupmore » P2{sub 1}, with unit-cell parameters a = 55.4, b = 104.2, c = 78.6 Å, β = 103.3°, and diffracted to 1.7 Å resolution. They contain two protein molecules per asymmetric unit. In order to solve the structure using the MAD phasing method, crystals of the l-selenomethionine-substituted epimerase were grown in the presence of 20% PEG 3350, 0.2 M Na{sub 2}SO{sub 4} and 0.1 M bis-Tris propane pH 8.5.« less

MADNESS: A Multiresolution, Adaptive Numerical Environment for Scientific Simulation

DOE PAGES

Harrison, Robert J.; Beylkin, Gregory; Bischoff, Florian A.; ...

2016-01-01

We present MADNESS (multiresolution adaptive numerical environment for scientific simulation) that is a high-level software environment for solving integral and differential equations in many dimensions that uses adaptive and fast harmonic analysis methods with guaranteed precision that are based on multiresolution analysis and separated representations. Underpinning the numerical capabilities is a powerful petascale parallel programming environment that aims to increase both programmer productivity and code scalability. This paper describes the features and capabilities of MADNESS and briefly discusses some current applications in chemistry and several areas of physics.

Crystallization and preliminary X-ray crystallographic analysis of the cysteine protease inhibitor clitocypin

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

Galeša, Katja; Brzin, Jože; Sabotič, Jerica

2006-01-01

Clitocypin is a cysteine protease inhibitor from the mushroom Clitocybe nebularis. The protein has been purified from natural sources and crystallized in a variety of non-isomorphous forms belonging to monoclinic and triclinic space groups. Clitocypin is a cysteine protease inhibitor from the mushroom Clitocybe nebularis. The protein has been purified from natural sources and crystallized in a variety of non-isomorphous forms belonging to monoclinic and triclinic space groups. A diffraction data set to 1.55 Å resolution was obtained from a crystal belonging to space group P2, with unit-cell parameters a = 38.326, b = 33.597, c = 55.568 Å, βmore » = 104°. An inability to achieve isomorphism forced the use of MAD and SAD phasing methods. Phasing is in progress.« less

Rice MADS6 Interacts with the Floral Homeotic Genes SUPERWOMAN1, MADS3, MADS58, MADS13, and DROOPING LEAF in Specifying Floral Organ Identities and Meristem Fate[C][W][OA

PubMed Central

Li, Haifeng; Liang, Wanqi; Hu, Yun; Zhu, Lu; Yin, Changsong; Xu, Jie; Dreni, Ludovico; Kater, Martin M.; Zhang, Dabing

2011-01-01

AGAMOUS-LIKE6 (AGL6) genes play essential roles in flower development, but whether and how they work with floral organ identity genes remain less understood. Here, we describe interactions of the rice (Oryza sativa) AGL6 gene MADS6 with other rice floral homeotic genes in flower development. Genetic analyses revealed that MADS6 specifies the identity of the three inner whorls and floral meristem determinacy redundantly with SUPERWOMAN1/MADS16 (B-gene) or MADS3 (C-gene). MADS6 was shown to define carpel/ovule development and floral determinacy by interacting with MADS13 (D-gene) and control the palea and floral meristem identities together with the YABBY gene DROOPING LEAF. Expression analyses revealed that the transcript levels of six B-, C-, and E-class genes were reduced in mads6-1 at the early flower developmental stage, suggesting that MADS6 is a key regulator of early flower development. Moreover, MADS6 can directly bind to a putative regulatory motif on MADS58 (C-gene), and mads6-1 mads58 displayed phenotypes similar to that of mads6-1. These results suggest that MADS6 is a key player in specifying flower development via interacting with other floral homeotic genes in rice, thus providing new insights into the mechanism by which flower development is controlled. PMID:21784949

Parallelization of a spatial random field characterization process using the Method of Anchored Distributions and the HTCondor high throughput computing system

NASA Astrophysics Data System (ADS)

Osorio-Murillo, C. A.; Over, M. W.; Frystacky, H.; Ames, D. P.; Rubin, Y.

2013-12-01

A new software application called MAD# has been coupled with the HTCondor high throughput computing system to aid scientists and educators with the characterization of spatial random fields and enable understanding the spatial distribution of parameters used in hydrogeologic and related modeling. MAD# is an open source desktop software application used to characterize spatial random fields using direct and indirect information through Bayesian inverse modeling technique called the Method of Anchored Distributions (MAD). MAD relates indirect information with a target spatial random field via a forward simulation model. MAD# executes inverse process running the forward model multiple times to transfer information from indirect information to the target variable. MAD# uses two parallelization profiles according to computational resources available: one computer with multiple cores and multiple computers - multiple cores through HTCondor. HTCondor is a system that manages a cluster of desktop computers for submits serial or parallel jobs using scheduling policies, resources monitoring, job queuing mechanism. This poster will show how MAD# reduces the time execution of the characterization of random fields using these two parallel approaches in different case studies. A test of the approach was conducted using 1D problem with 400 cells to characterize saturated conductivity, residual water content, and shape parameters of the Mualem-van Genuchten model in four materials via the HYDRUS model. The number of simulations evaluated in the inversion was 10 million. Using the one computer approach (eight cores) were evaluated 100,000 simulations in 12 hours (10 million - 1200 hours approximately). In the evaluation on HTCondor, 32 desktop computers (132 cores) were used, with a processing time of 60 hours non-continuous in five days. HTCondor reduced the processing time for uncertainty characterization by a factor of 20 (1200 hours reduced to 60 hours.)

Contribution of microwave accelerated distillation in the extraction of the essential oil of Zygophyllum album L.

PubMed

Tigrine-Kordjani, Nacéra; Meklati, Brahim Youcef; Chemat, Farid

2011-01-01

The aerial parts of Zygophyllum album L. are used in folk medicine as an antidiabetic agent and as a drug active against several pathologies. In this work we present the chemical composition of Algerian essential oils obtained by microwave accelerated distillation (MAD) extraction, a solventless method assisted by microwave. Under the same analytical conditions and using GC-FID and GC-MS, the chemical composition of the essential oil of Zygophyllum album L. extracted by MAD was compared with that achieved using hydrodistillation (HD). The extracted compounds were hydrosoluble, and they were removed from the aqueous solution by a liquid extraction with an organic solvent. Employing MAD (100°C, 30  min), the essential oil contained mainly oxygenated monoterpenes with major constituents: carvone and α-terpineol. However, most of the compounds present in the hydrodistilled volatile fraction were not terpene species, with β-damascenone as a major constituent. The MAD method appears to be more efficient than HD: after 30  min extraction time, the obtained yields (i.e. 0.002%) were comparable to those provided by HD after 3  h extraction. MAD seems to be more convenient since the volatile fraction is richer in oxygenated monoterpenes, species that are recognised for their olfactory value and their contribution to the fragrance of the essential oil. Copyright © 2010 John Wiley & Sons, Ltd.

Validation of Cut-Points for Evaluating the Intensity of Physical Activity with Accelerometry-Based Mean Amplitude Deviation (MAD).

PubMed

Vähä-Ypyä, Henri; Vasankari, Tommi; Husu, Pauliina; Mänttäri, Ari; Vuorimaa, Timo; Suni, Jaana; Sievänen, Harri

2015-01-01

Our recent study of three accelerometer brands in various ambulatory activities showed that the mean amplitude deviation (MAD) of the resultant acceleration signal performed best in separating different intensity levels and provided excellent agreement between the three devices. The objective of this study was to derive a regression model that estimates oxygen consumption (VO2) from MAD values and validate the MAD-based cut-points for light, moderate and vigorous locomotion against VO2 within a wide range of speeds. 29 participants performed a pace-conducted non-stop test on a 200 m long indoor track. The initial speed was 0.6 m/s and it was increased by 0.4 m/s every 2.5 minutes until volitional exhaustion. The participants could freely decide whether they preferred to walk or run. During the test they carried a hip-mounted tri-axial accelerometer and mobile metabolic analyzer. The MAD was calculated from the raw acceleration data and compared to directly measured incident VO2. Cut-point between light and moderate activity was set to 3.0 metabolic equivalent (MET, 1 MET = 3.5 ml · kg-1 · min-1) and between moderate and vigorous activity to 6.0 MET as per standard use. The MAD and VO2 showed a very strong association. Within individuals, the range of r values was from 0.927 to 0.991 providing the mean r = 0.969. The optimal MAD cut-point for 3.0 MET was 91 mg (milligravity) and 414 mg for 6.0 MET. The present study showed that the MAD is a valid method in terms of the VO2 within a wide range of ambulatory activities from slow walking to fast running. Being a device-independent trait, the MAD facilitates directly comparable, accurate results on the intensity of physical activity with all accelerometers providing tri-axial raw data.

Expression of mucosal addressin cell adhesion molecule 1 on vessel endothelium of gastric mucosa in patients with nodular gastritis

PubMed Central

Ohara, Hiroshi; Isomoto, Hajime; Wen, Chun-Yang; Ejima, Chieko; Murata, Masahiro; Miyazaki, Masanobu; Takeshima, Fuminao; Mizuta, Yohei; Murata, Ikuo; Koji, Takehiko; Nagura, Hiroshi; Kohno, Shigeru

2003-01-01

AIM: The interaction of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) with integrin α4β7 mediates lymphocyte recruitment into mucosa-associated lymphoid tissue (MALT). Nodular gastritis is characterized by a unique military pattern on endoscopy representing increased numbers of lymphoid follicles with germinal center, strongly associated with H pylori infection. The purpose of this study was to address the implication of the MAdCAM-1/integrin β7 pathway in NG. METHODS: We studied 17 patients with NG and H pylori infection and 19 H pylori-positive and 14 H pylori-negative controls. A biopsy sample was taken from the antrum and snap-frozen for immunohistochemical analysis of MAdCAM-1 and integrin β7. In simultaneous viewing of serial sections, the percentage of MAdCAM-1-positive to von Willebrand factor-positive vessels was calculated. We also performed immunostaining with anti-CD20, CD4, CD8 and CD68 antibodies to determine the lymphocyte subsets co-expressing integrin β7. RESULTS: Vascular endothelial MAdCAM-1 expression was more enhanced in gastric mucosa with than without H pylori infection. Of note, the percentages of MAdCAM-1-positive vessels were significantly higher in the lamina propria of NG patients than in H pylori-positive controls. Strong expression of MAdCAM-1 was identified adjacent to lymphoid follicles and dense lymphoid aggregates. Integrin β7-expressing mononuclear cells, mainly composed of CD20 and CD4 lymphocytes, were associated with vessels lined with MAdCAM-1-expressing endothelium. CONCLUSION: Our results suggest that the MAdCAM-1/ integrin α4β7 homing system may participate in gastric inflammation in response to H pylori-infection and contributes to MALT formation, typically leading to the development of NG. PMID:14669317

Adapting rice anther culture to gene transformation and RNA interference.

PubMed

Chen, Caiyan; Xiao, Han; Zhang, Wenli; Wang, Aiju; Xia, Zhihui; Li, Xiaobing; Zhai, Wenxue; Cheng, Zhukuan; Zhu, Lihuang

2006-10-01

Anther culture offers a rapid method of generating homozygous lines for breeding program and genetic analysis. To produce homozygous transgenic lines of rice (Oryza sativa L.) in one step, we developed an efficient protocol of anther-callus-based transformation mediated by Agrobacterium after optimizing several factors influencing efficient transformation, including callus induction and Agrobacterium density for co-cultivation. Using this protocol, we obtained 145 independent green transformants from five cultivars of japonica rice by transformation with a binary vector pCXK1301 bearing the rice gene, Xa21 for resistance to bacterial blight, of which 140 were further confirmed by PCR and Southern hybridization analysis, including haploids (32.1%), diploids (62.1%) and mixoploids (7.5%). Fifteen diploids were found to be doubled haploids, which accounted for 10.7% of the total positive lines. Finally, by including 28 from colchicine induced or spontaneous diploidization of haploids later after transformation, a total of 43 doubled haploids (30.7%) of Xa21 transgenic lines were obtained. We also generated two RNAi transgenic haploids of the rice OsMADS2 gene, a putative redundant gene of OsMADS4 based on their sequence similarity, to investigate its possible roles in rice flower development by this method. Flowers from the two OsMADS2 RNAi transgenic haploids displayed obvious homeotic alternations, in which lodicules were transformed into palea/lemma-like tissues, whereas identities of other floral organs were maintained. The phenotypic alternations were proved to result from specific transcriptional suppression of OsMADS2 gene by the introduced RNAi transgene. The results confirmed that OsMADS2 is involved in lodicule development of rice flower and functionally redundant with OsMADS4 gene. Our results demonstrated that rice anther culture could be adapted to gene transformation and RNAi analysis in rice.

The regulation of MADS-box gene expression during ripening of banana and their regulatory interaction with ethylene

PubMed Central

Elitzur, Tomer; Vrebalov, Julia; Giovannoni, James J.; Goldschmidt, Eliezer E.; Friedman, Haya

2010-01-01

Six MaMADS-box genes have been cloned from the banana fruit cultivar Grand Nain. The similarity of these genes to tomato LeRIN is low and neither MaMADS2 nor MaMADS1 complement the tomato rin mutation. Nevertheless, the expression patterns, specifically in fruit and the induction during ripening and in response to ethylene and 1-MCP, suggest that some of these genes may participate in ripening. MaMADS1, 2, and 3, are highly expressed in fruit only, while the others are expressed in fruit as well as in other organs. Moreover, the suites of MaMADS-box genes and their temporal expression differ in peel and pulp during ripening. In the pulp, the increase in MaMADS2, 3, 4, and 5 expression preceded an increase in ethylene production, but coincides with the CO2 peak. However, MaMADS1 expression in pulp coincided with ethylene production, but a massive increase in its expression occurred late during ripening, together with a second wave in the expression of MaMADS2, 3, and 4. In the peel, on the other hand, an increase in expression of MaMADS1, 3, and to a lesser degree also of MaMADS4 and 2 coincided with an increase in ethylene production. Except MaMADS3, which was induced by ethylene in pulp and peel, only MaMADS4, and 5 in pulp and MaMADS1 in peel were induced by ethylene. 1-MCP applied at the onset of the increase in ethylene production, increased the levels of MaMADS4 and MaMADS1 in pulp, while it decreased MaMADS1, 3, 4, and 5 in peel, suggesting that MaMADS4 and MaMADS1 are negatively controlled by ethylene at the onset of ethylene production only in pulp. Only MaMADS2 is neither induced by ethylene nor by 1-MCP, and it is expressed mainly in pulp. Our results suggest that two independent ripening programs are employed in pulp and peel which involve the activation of mainly MaMADS2, 4, and 5 and later on also MaMADS1 in pulp, and mainly MaMADS1, and 3 in peel. Hence, our results are consistent with MaMADS2, a SEP3 homologue, acting in the pulp upstream of the increase in ethylene production similarly to LeMADS-RIN. PMID:20200120

The regulation of MADS-box gene expression during ripening of banana and their regulatory interaction with ethylene.

PubMed

Elitzur, Tomer; Vrebalov, Julia; Giovannoni, James J; Goldschmidt, Eliezer E; Friedman, Haya

2010-03-01

Six MaMADS-box genes have been cloned from the banana fruit cultivar Grand Nain. The similarity of these genes to tomato LeRIN is low and neither MaMADS2 nor MaMADS1 complement the tomato rin mutation. Nevertheless, the expression patterns, specifically in fruit and the induction during ripening and in response to ethylene and 1-MCP, suggest that some of these genes may participate in ripening. MaMADS1, 2, and 3, are highly expressed in fruit only, while the others are expressed in fruit as well as in other organs. Moreover, the suites of MaMADS-box genes and their temporal expression differ in peel and pulp during ripening. In the pulp, the increase in MaMADS2, 3, 4, and 5 expression preceded an increase in ethylene production, but coincides with the CO(2) peak. However, MaMADS1 expression in pulp coincided with ethylene production, but a massive increase in its expression occurred late during ripening, together with a second wave in the expression of MaMADS2, 3, and 4. In the peel, on the other hand, an increase in expression of MaMADS1, 3, and to a lesser degree also of MaMADS4 and 2 coincided with an increase in ethylene production. Except MaMADS3, which was induced by ethylene in pulp and peel, only MaMADS4, and 5 in pulp and MaMADS1 in peel were induced by ethylene. 1-MCP applied at the onset of the increase in ethylene production, increased the levels of MaMADS4 and MaMADS1 in pulp, while it decreased MaMADS1, 3, 4, and 5 in peel, suggesting that MaMADS4 and MaMADS1 are negatively controlled by ethylene at the onset of ethylene production only in pulp. Only MaMADS2 is neither induced by ethylene nor by 1-MCP, and it is expressed mainly in pulp. Our results suggest that two independent ripening programs are employed in pulp and peel which involve the activation of mainly MaMADS2, 4, and 5 and later on also MaMADS1 in pulp, and mainly MaMADS1, and 3 in peel. Hence, our results are consistent with MaMADS2, a SEP3 homologue, acting in the pulp upstream of the increase in ethylene production similarly to LeMADS-RIN.

DIF Analysis with Multilevel Data: A Simulation Study Using the Latent Variable Approach

ERIC Educational Resources Information Center

Jin, Ying; Eason, Hershel

2016-01-01

The effects of mean ability difference (MAD) and short tests on the performance of various DIF methods have been studied extensively in previous simulation studies. Their effects, however, have not been studied under multilevel data structure. MAD was frequently observed in large-scale cross-country comparison studies where the primary sampling…

Monopolar spindle 1 (MPS1) kinase promotes production of closed MAD2 (C-MAD2) conformer and assembly of the mitotic checkpoint complex.

PubMed

Tipton, Aaron R; Ji, Wenbin; Sturt-Gillespie, Brianne; Bekier, Michael E; Wang, Kexi; Taylor, William R; Liu, Song-Tao

2013-12-06

MPS1 kinase is an essential component of the spindle assembly checkpoint (SAC), but its functioning mechanisms are not fully understood. We have shown recently that direct interaction between BUBR1 and MAD2 is critical for assembly and function of the human mitotic checkpoint complex (MCC), the SAC effector. Here we report that inhibition of MPS1 kinase activity by reversine disrupts BUBR1-MAD2 as well as CDC20-MAD2 interactions, causing premature activation of the anaphase-promoting complex/cyclosome. The effect of MPS1 inhibition is likely due to reduction of closed MAD2 (C-MAD2), as expressing a MAD2 mutant (MAD2(L13A)) that is locked in the C conformation rescued the checkpoint defects. In the presence of reversine, exogenous C-MAD2 does not localize to unattached kinetochores but is still incorporated into the MCC. Contrary to a previous report, we found that sustained MPS1 activity is required for maintaining both the MAD1·C-MAD2 complex and open MAD2 (O-MAD2) at unattached kinetochores to facilitate C-MAD2 production. Additionally, mitotic phosphorylation of BUBR1 is also affected by MPS1 inhibition but seems dispensable for MCC assembly. Our results support the notion that MPS1 kinase promotes C-MAD2 production and subsequent MCC assembly to activate the SAC.

Loss of LOFSEP Transcription Factor Function Converts Spikelet to Leaf-Like Structures in Rice1[OPEN

PubMed Central

Zhu, Wanwan

2018-01-01

SEPALLATA (SEP)-like genes, which encode a subfamily of MADS-box transcription factors, are essential for specifying floral organ and meristem identity in angiosperms. Rice (Oryza sativa) has five SEP-like genes with partial redundancy and overlapping expression domains, yet their functions and evolutionary conservation are only partially known. Here, we describe the biological role of one of the SEP genes of rice, OsMADS5, in redundantly controlling spikelet morphogenesis. OsMADS5 belongs to the conserved LOFSEP subgroup along with OsMADS1 and OsMADS34. OsMADS5 was expressed strongly across a broad range of reproductive stages and tissues. No obvious phenotype was observed in the osmads5 single mutants when compared with the wild type, which was largely due to the functional redundancy among the three LOFSEP genes. Genetic and molecular analyses demonstrated that OsMADS1, OsMADS5, and OsMADS34 together regulate floral meristem determinacy and specify the identities of spikelet organs by positively regulating the other MADS-box floral homeotic genes. Experiments conducted in yeast also suggested that OsMADS1, OsMADS5, and OsMADS34 form protein-protein interactions with other MADS-box floral homeotic members, which seems to be a typical, conserved feature of plant SEP proteins. PMID:29217592

Comparison between mono-bloc and bi-bloc mandibular advancement devices for obstructive sleep apnea.

PubMed

Lee, Woo Hyun; Wee, Jee Hye; Lee, Chul Hee; Kim, Min-Su; Rhee, Chae-Seo; Yun, Pil-Young; Yoon, In-Young; Kim, Jeong-Whun

2013-11-01

Although mandibular advancement device (MAD) is widely used, there are a few papers comparing the efficacy and compliance at the same time according to the type of MAD. The aim of this study is to compare the efficacy and compliance between mono-bloc and bi-bloc MAD in the treatment of obstructive sleep apnea (OSA). Ninety-three patients who treated with mono-bloc MAD and 60 patients with bi-bloc MAD from January 2007 through September 2011 were retrospectively enrolled. All the patients underwent full-night polysomnography(PSG) before and 3 months after MAD was applied. The response rate was significantly higher in the patients using mono-bloc than those using bi-bloc MAD (77.4 vs. 58.3 %; P = 0.012). In contrast, the compliance rate of MAD use was significantly higher in the patients using bi-bloc than those using mono-bloc MAD (68.8 vs. 83.3 %; P = 0.044) at 1 year. According to the severity of OSA, the response rate was significantly higher in severe OSA than in mild to moderate OSA (P = 0.033 for mono-bloc MAD and P = 0.048 for bi-bloc MAD). However, there was no difference in the compliance between mild to moderate OSA and severe OSA. Our study showed that mono-bloc MAD was superior to bi-bloc MAD in efficacy while bi-bloc MAD is superior to mono-bloc MAD in compliance. We propose that both the efficacy and compliance should be considered in using MAD for treatment of OSA.

The pineapple AcMADS1 promoter confers high level expression in tomato and arabidopsis flowering and fruiting tissues, but AcMADS1 does not complement the tomato LeMADS-RIN (rin) mutant

USDA-ARS?s Scientific Manuscript database

A previous EST study identified a MADS box transcription factor coding sequence, AcMADS1, that is strongly induced during non-climacteric pineapple fruit ripening. Phylogenetic analyses place the AcMADS1 protein in the same superclade as LeMADS-RIN, a master regulator of fruit ripening upstream of e...

Mad Cow Disease

MedlinePlus

... Safe Videos for Educators Search English Español Mad Cow Disease KidsHealth / For Teens / Mad Cow Disease What's ... are people to get it? What Is Mad Cow Disease? Mad cow disease is an incurable, fatal ...

Mad Cow Disease (For Parents)

MedlinePlus

... Safe Videos for Educators Search English Español Mad Cow Disease KidsHealth / For Parents / Mad Cow Disease What's ... Is Being Done About It Print About Mad Cow Disease Mad cow disease has been in the ...

MadSciNet: The 24-hour exploding laboratory.

Science.gov Websites

Page New! Help Improve The Madsci Network Help Support MadSci MAD Head MAD egg Welcome to the laboratory that never sleeps! MadSci Network represents a collective cranium of scientists providing answers Sunday May 27, 2018. Lynn MadSci Network is a non-profit organization operating in partnership with Third

MADS goes genomic in conifers: towards determining the ancestral set of MADS-box genes in seed plants.

PubMed

Gramzow, Lydia; Weilandt, Lisa; Theißen, Günter

2014-11-01

MADS-box genes comprise a gene family coding for transcription factors. This gene family expanded greatly during land plant evolution such that the number of MADS-box genes ranges from one or two in green algae to around 100 in angiosperms. Given the crucial functions of MADS-box genes for nearly all aspects of plant development, the expansion of this gene family probably contributed to the increasing complexity of plants. However, the expansion of MADS-box genes during one important step of land plant evolution, namely the origin of seed plants, remains poorly understood due to the previous lack of whole-genome data for gymnosperms. The newly available genome sequences of Picea abies, Picea glauca and Pinus taeda were used to identify the complete set of MADS-box genes in these conifers. In addition, MADS-box genes were identified in the growing number of transcriptomes available for gymnosperms. With these datasets, phylogenies were constructed to determine the ancestral set of MADS-box genes of seed plants and to infer the ancestral functions of these genes. Type I MADS-box genes are under-represented in gymnosperms and only a minimum of two Type I MADS-box genes have been present in the most recent common ancestor (MRCA) of seed plants. In contrast, a large number of Type II MADS-box genes were found in gymnosperms. The MRCA of extant seed plants probably possessed at least 11-14 Type II MADS-box genes. In gymnosperms two duplications of Type II MADS-box genes were found, such that the MRCA of extant gymnosperms had at least 14-16 Type II MADS-box genes. The implied ancestral set of MADS-box genes for seed plants shows simplicity for Type I MADS-box genes and remarkable complexity for Type II MADS-box genes in terms of phylogeny and putative functions. The analysis of transcriptome data reveals that gymnosperm MADS-box genes are expressed in a great variety of tissues, indicating diverse roles of MADS-box genes for the development of gymnosperms. This study is the first that provides a comprehensive overview of MADS-box genes in conifers and thus will provide a framework for future work on MADS-box genes in seed plants. © The Author 2014. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessing mixed anxiety-depressive disorder. A national primary care survey.

PubMed

Balestrieri, Matteo; Isola, Miriam; Quartaroli, Mauro; Roncolato, Maurizio; Bellantuono, Cesario

2010-04-30

Prevalence and risk factors associated with mixed anxiety-depressive disorder (MAD) have yet to be established. Using MINI 5.0.1 and HADS, a two-week survey involving 21,644 primary care patients was carried out. We found 1.8% of subjects with MAD and 20% of subjects with a co-morbid anxiety and depression (CAD) disorder. MAD patients without a past history of anxiety/affective episodes were defined as "pure MAD" (pMAD: 0.9% of the sample). While MAD patients showed a number of differences vs. the other groups of patients in the socio-demographic statistics, pMAD patients were not different, apart from a higher proportion of males vs. CAD patients. Nearly in all the comparisons, MAD and pMAD patients showed lower association with life events and with a familial predisposition than the other patients. On HADS assessment, MAD showed a higher risk of anxiety and depressive symptoms than anxiety diagnoses, a lower risk of depressive symptoms than depressive diagnoses and a lower risk of both anxiety and depressive symptoms than CAD. Since more than a half of MAD patients were classified as pMAD, the hypothesis that MAD should be viewed as a partial remission of a major depression is not entirely confirmed in our study. Copyright (c) 2008 Elsevier Ltd. All rights reserved.

Interactions of OsMADS1 with Floral Homeotic Genes in Rice Flower Development.

PubMed

Hu, Yun; Liang, Wanqi; Yin, Changsong; Yang, Xuelian; Ping, Baozhe; Li, Anxue; Jia, Ru; Chen, Mingjiao; Luo, Zhijing; Cai, Qiang; Zhao, Xiangxiang; Zhang, Dabing; Yuan, Zheng

2015-09-01

During reproductive development, rice plants develop unique flower organs which determine the final grain yield. OsMADS1, one of SEPALLATA-like MADS-box genes, has been unraveled to play critical roles in rice floral organ identity specification and floral meristem determinacy. However, the molecular mechanisms underlying interactions of OsMADS1 with other floral homeotic genes in regulating flower development remains largely elusive. In this work, we studied the genetic interactions of OsMADS1 with B-, C-, and D-class genes along with physical interactions among their proteins. We show that the physical and genetic interactions between OsMADS1 and OsMADS3 are essential for floral meristem activity maintenance and organ identity specification; while OsMADS1 physically and genetically interacts with OsMADS58 in regulating floral meristem determinacy and suppressing spikelet meristem reversion. We provided important genetic evidence to support the neofunctionalization of two rice C-class genes (OsMADS3 and OsMADS58) during flower development. Gene expression profiling and quantitative RT-PCR analyses further revealed that OsMADS1 affects the expression of many genes involved in floral identity and hormone signaling, and chromatin immunoprecipitation (ChIP)-PCR assay further demonstrated that OsMADS17 is a direct target gene of OsMADS1. Taken together, these results reveal that OsMADS1 has diversified regulatory functions in specifying rice floral organ and meristem identity, probably through its genetic and physical interactions with different floral homeotic regulators. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Validate Mitotic Checkpoint and Kinetochore Motor Proteins in Breast Cancer Cells as Targets for the Development of Novel Anti-Mitotic Drugs

DTIC Science & Technology

2004-07-01

checkpoint pathway remains to MAD1 MAD1 xMADI be clarified, it is dear that all of them MAD2 MAD2 xMAD2 are essential for cells to arrest in mitosis MPS1 ...TrK in response to unattached kineto- chores. Given that MPS1 , BUB1 and (G) Structural Proteins/Unknown Functions the Mad3-related BUBR1 are all pro...BUB3, MADI, MAD2, MAD3, and MPS1 have been shown to be essential for establishing the checkpoint response in all eukaryotes examined to date (Abrieu et

[Madness in Foucault: art and madness, madness and unreason].

PubMed

Providello, Guilherme Gonzaga Duarte; Yasui, Silvio

2013-10-01

After presenting the ideas on madness and its interface with art as expressed in the writings of Michel Foucault, Peter Pál Pelbart, and Gilles Deleuze, the article explores how these authors question the relationship between art and madness. It begins with the notion that madness does not tell the truth about art, and vice versa, but that there are links between both that must be delved into if we are to engage in deeper reflection on the topic. The text problematizes the statement that madness is the absence of an oeuvre and examines how this impacts the possibility of achieving an artistic oeuvre. It further problematizes the idea of madness as excluded language, that is, the idea that madness implies not only the exclusion of the body but also the disqualification of discourse.

Involvement of a banana MADS-box transcription factor gene in ethylene-induced fruit ripening.

PubMed

Liu, Juhua; Xu, Biyu; Hu, Lifang; Li, Meiying; Su, Wei; Wu, Jing; Yang, Jinghao; Jin, Zhiqiang

2009-01-01

To investigate the regulation of MADS-box genes in banana (Musa acuminata L. AAA group cv. Brazilian) fruit development and postharvest ripening, we isolated from banana fruit a MADS-box gene designated MuMADS1. Amino acid alignment indicated MuMADS1 belongs to the AGAMOUS subfamily, and phylogenetic analysis indicates that this gene is most similar to class D MADS-box genes. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that MuMADS1 is expressed in the stamen and pistil of male and female flowers and in the rhizome, the vegetative reproductive organ of the banana plant. In preharvest banana fruit, MuMADS1 is likely expressed throughout banana fruit development. In postharvest banana ripening, MuMADS1 is associated with ethylene biosynthesis. Expression patterns of MuMADS1 during postharvest ripening as determined by real-time RT-PCR suggest that differential expression of MuMADS1 may not only be induced by ethylene biosynthesis associated with postharvest banana ripening, but also may be induced by exogenous ethylene.

Performance of quantum Monte Carlo for calculating molecular bond lengths

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

Cleland, Deidre M., E-mail: deidre.cleland@csiro.au; Per, Manolo C., E-mail: manolo.per@csiro.au

2016-03-28

This work investigates the accuracy of real-space quantum Monte Carlo (QMC) methods for calculating molecular geometries. We present the equilibrium bond lengths of a test set of 30 diatomic molecules calculated using variational Monte Carlo (VMC) and diffusion Monte Carlo (DMC) methods. The effect of different trial wavefunctions is investigated using single determinants constructed from Hartree-Fock (HF) and Density Functional Theory (DFT) orbitals with LDA, PBE, and B3LYP functionals, as well as small multi-configurational self-consistent field (MCSCF) multi-determinant expansions. When compared to experimental geometries, all DMC methods exhibit smaller mean-absolute deviations (MADs) than those given by HF, DFT, and MCSCF.more » The most accurate MAD of 3 ± 2 × 10{sup −3} Å is achieved using DMC with a small multi-determinant expansion. However, the more computationally efficient multi-determinant VMC method has a similar MAD of only 4.0 ± 0.9 × 10{sup −3} Å, suggesting that QMC forces calculated from the relatively simple VMC algorithm may often be sufficient for accurate molecular geometries.« less

Madness Decolonized?: Madness as Transnational Identity in Gail Hornstein's Agnes's Jacket.

PubMed

Miller, Gavin

2017-02-13

The US psychologist Gail Hornstein's monograph, Agnes's Jacket: A Psychologist's Search for the Meanings of Madness (2009), is an important intervention in the identity politics of the mad movement. Hornstein offers a resignified vision of mad identity that embroiders the central trope of an "anti-colonial" struggle to reclaim the experiential world "colonized" by psychiatry. A series of literal and figurative appeals makes recourse to the inner world and (corresponding) cultural world of the mad as well as to the ethno-symbolic cultural materials of dormant nationhood. This rhetoric is augmented by a model in which the mad comprise a diaspora without an origin, coalescing into a single transnational community. The mad are also depicted as persons displaced from their metaphorical homeland, the "inner" world "colonized" by the psychiatric regime. There are a number of difficulties with Hornstein's rhetoric, however. Her "ethnicity-and-rights" response to the oppression of the mad is symptomatic of Western parochialism, while her proposed transmutation of putative psychopathology from limit upon identity to parameter of successful identity is open to contestation. Moreover, unless one accepts Hornstein's porous vision of mad identity, her self-ascribed insider status in relation to the mad community may present a problematic "re-colonization" of mad experience.

Role for the banana AGAMOUS-like gene MaMADS7 in regulation of fruit ripening and quality.

PubMed

Liu, Juhua; Liu, Lin; Li, Yujia; Jia, Caihong; Zhang, Jianbin; Miao, Hongxia; Hu, Wei; Wang, Zhuo; Xu, Biyu; Jin, Zhiqiang

2015-11-01

MADS-box transcription factors play important roles in organ development. In plants, most studies on MADS-box genes have mainly focused on flower development and only a few concerned fruit development and ripening. A new MADS-box gene named MaMADS7 was isolated from banana fruit by rapid amplification of cDNA ends (RACE) based on a MADS-box fragment obtained from a banana suppression subtractive hybridization (SSH) cDNA library. MaMADS7 is an AGAMOUS-like MADS-box gene that is preferentially expressed in the ovaries and fruits and in tobacco its protein product localizes to the nucleus. This study found that MaMADS7 expression can be induced by exogenous ethylene. Ectopic expression of MaMADS7 in tomato resulted in broad ripening phenotypes. The expression levels of seven ripening and quality-related genes, ACO1, ACS2, E4, E8, PG, CNR and PSY1 in MaMADS7 transgenic tomato fruits were greatly increased while the expression of the AG-like MADS-box gene TAGL1 was suppressed. Compared with the control, the contents of β-carotene, lycopene, ascorbic acid and organic acid in transformed tomato fruits were increased, while the contents of glucose and fructose were slightly decreased. MaMADS7 interacted with banana 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase gene 1 (MaACO1) and tomato phytoene synthase gene (LePSY1) promoters. Our results indicated that MaMADS7 plays an important role in initiating endogenous ethylene biosynthesis and fruit ripening. © 2015 Scandinavian Plant Physiology Society.

Molecular cloning and function analysis of two SQUAMOSA-Like MADS-box genes from Gossypium hirsutum L.

PubMed

Zhang, Wenxiang; Fan, Shuli; Pang, Chaoyou; Wei, Hengling; Ma, Jianhui; Song, Meizhen; Yu, Shuxun

2013-07-01

The MADS-box genes encode a large family of transcription factors having diverse roles in plant development. The SQUAMOSA (SQUA)/APETALA1 (AP1)/FRUITFULL (FUL) subfamily genes are essential regulators of floral transition and floral organ identity. Here we cloned two MADS-box genes, GhMADS22 and GhMADS23, belonging to the SQUA/AP1/FUL subgroup from Gossypium hirsutum L. Phylogenetic analysis and sequence alignment showed that GhMADS22 and GhMADS23 belonged to the euFUL and euAP1 subclades, respectively. The two genes both had eight exons and seven introns from the start codon to the stop codon according to the alignment between the obtained cDNA sequence and the Gossypium raimondii L. genome sequence. Expression profile analysis showed that GhMADS22 and GhMADS23 were highly expressed in developing shoot apices, bracts, and sepals. Gibberellic acid promoted GhMADS22 and GhMADS23 expression in the shoot apex. Transgenic Arabidopsis lines overexpressing 35S::GhMADS22 had abnormal flowers and bolted earlier than wild type under long-day conditions (16 h light/8 h dark). Moreover, GhMADS22 overexpression delayed floral organ senescence and abscission and it could also respond to abscisic acid. In summary, GhMADS22 may have functions in promoting flowering, improving resistance and delaying senescence for cotton and thus it may be a candidate target for promoting early-maturation in cotton breeding. © 2013 Institute of Botany, Chinese Academy of Sciences.

Bone morphogenetic protein 9 (BMP9) induces effective bone formation from reversibly immortalized multipotent adipose-derived (iMAD) mesenchymal stem cells.

PubMed

Lu, Shun; Wang, Jing; Ye, Jixing; Zou, Yulong; Zhu, Yunxiao; Wei, Qiang; Wang, Xin; Tang, Shengli; Liu, Hao; Fan, Jiaming; Zhang, Fugui; Farina, Evan M; Mohammed, Maryam M; Song, Dongzhe; Liao, Junyi; Huang, Jiayi; Guo, Dan; Lu, Minpeng; Liu, Feng; Liu, Jianxiang; Li, Li; Ma, Chao; Hu, Xue; Lee, Michael J; Reid, Russell R; Ameer, Guillermo A; Zhou, Dongsheng; He, Tongchuan

2016-01-01

Regenerative medicine and bone tissue engineering using mesenchymal stem cells (MSCs) hold great promise as an effective approach to bone and skeletal reconstruction. While adipose tissue harbors MSC-like progenitors, or multipotent adipose-derived cells (MADs), it is important to identify and characterize potential biological factors that can effectively induce osteogenic differentiation of MADs. To overcome the time-consuming and technically challenging process of isolating and culturing primary MADs, here we establish and characterize the reversibly immortalized mouse multipotent adipose-derived cells (iMADs). The isolated mouse primary inguinal MAD cells are reversibly immortalized via the retrovirus-mediated expression of SV40 T antigen flanked with FRT sites. The iMADs are shown to express most common MSC markers. FLP-mediated removal of SV40 T antigen effectively reduces the proliferative activity and cell survival of iMADs, indicating the immortalization is reversible. Using the highly osteogenic BMP9, we find that the iMADs are highly responsive to BMP9 stimulation, express multiple lineage regulators, and undergo osteogenic differentiation in vitro upon BMP9 stimulation. Furthermore, we demonstrate that BMP9-stimulated iMADs form robust ectopic bone with a thermoresponsive biodegradable scaffold material. Collectively, our results demonstrate that the reversibly immortalized iMADs exhibit the characteristics of multipotent MSCs and are highly responsive to BMP9-induced osteogenic differentiation. Thus, the iMADs should provide a valuable resource for the study of MAD biology, which would ultimately enable us to develop novel and efficacious strategies for MAD-based bone tissue engineering.

HbMADS4, a MADS-box Transcription Factor from Hevea brasiliensis, Negatively Regulates HbSRPP.

PubMed

Li, Hui-Liang; Wei, Li-Ran; Guo, Dong; Wang, Ying; Zhu, Jia-Hong; Chen, Xiong-Ting; Peng, Shi-Qing

2016-01-01

In plants MADS-box transcription factors (TFs) play important roles in growth and development. However, no plant MADS-box gene has been identified to have a function related to secondary metabolites regulation. Here, a MADS-box TF gene, designated as HbMADS4 , was isolated from Hevea brasiliensis by the yeast one-hybrid experiment to screen the latex cDNA library using the promoter of the gene encoding H. brasiliensis small rubber particle protein (HbSRPP) as bait. HbMADS4 was 984-bp containing 633-bp open reading frame encoding a deduced protein of 230 amino acid residues with a typical conserved MADS-box motif at the N terminus. HbMADS4 was preferentially expressed in the latex, but little expression was detected in the leaves, flowers, and roots. Its expression was inducible by methyl jasmonate and ethylene. Furthermore, transient over-expression and over-expression of HbMADS4 in transgenic tobacco plants significantly suppressed the activity of the HbSRP promoter. Altogether, it is proposed that HbMADS4 is a negative regulator of HbSRPP which participates in the biosynthesis of natural rubber.

MAD2-p31comet axis deficiency reduces cell proliferation, migration and sensitivity of microtubule-interfering agents in glioma.

PubMed

Wu, Dang; Wang, Lepeng; Yang, Yanhong; Huang, Jin; Hu, Yuhua; Shu, Yongwei; Zhang, Jingyu; Zheng, Jing

2018-03-25

Mitotic arrest deficient-like-1 (MAD2, also known as MAD2L1) is thought to be an important spindle assembly checkpoint protein, which ensures accurate chromosome segregation and is closely associated with poor prognosis in many cancer. As a MAD2 binding protein, p31 comet counteracts the function of MAD2 and leads to mitotic checkpoint silence. In this study, we explore the function of MAD2-p31 comet axis in malignant glioma cells. Our results showed that disruption of MAD2-p31 comet axis by MAD2 knockdown or p31 comet overexpression suppressed cell proliferation, survival and migration of glioma, indicating that MAD2-p31 comet axis is required for maintaining glioma cells malignancy. It is noted that MAD2 depletion or p31 comet overexpression reduced the sensitivity of glioma cells to microtubule-interfering agents paclitaxel and vinblastine, providing clinical guidance for application of such drugs. Taken together, our findings suggest that MAD2-p31 comet axis may serve as a potential therapeutic target for glioma. Copyright © 2018. Published by Elsevier Inc.

Overexpression of a MADS-Box Gene from Birch (Betula platyphylla) Promotes Flowering and Enhances Chloroplast Development in Transgenic Tobacco

PubMed Central

Qu, Guan-Zheng; Zheng, Tangchun; Liu, Guifeng; Wang, Wenjie; Zang, Lina; Liu, Huanzhen; Yang, Chuanping

2013-01-01

In this study, a MADS-box gene (BpMADS), which is an ortholog of AP1 from Arabidopsis, was isolated from birch (Betula platyphylla). Transgenic Arabidopsis containing a BpMADS promoter::GUS construct was produced, which exhibited strong GUS staining in sepal tissues. Ectopic expression of BpMADS significantly enhanced the flowering of tobacco (35S::BpMADS). In addition, the chloroplasts of transgenic tobacco exhibited much higher growth and division rates, as well rates of photosynthesis, than wild-type. A grafting experiment demonstrated that the flowering time of the scion was not affected by stock that overexpressed BpMADS. In addition, the overexpression of BpMADS resulted in the upregulation of some flowering-related genes in tobacco. PMID:23691043

Overexpression of a MADS-box gene from birch (Betula platyphylla) promotes flowering and enhances chloroplast development in transgenic tobacco.

PubMed

Qu, Guan-Zheng; Zheng, Tangchun; Liu, Guifeng; Wang, Wenjie; Zang, Lina; Liu, Huanzhen; Yang, Chuanping

2013-01-01

In this study, a MADS-box gene (BpMADS), which is an ortholog of AP1 from Arabidopsis, was isolated from birch (Betula platyphylla). Transgenic Arabidopsis containing a BpMADS promoter::GUS construct was produced, which exhibited strong GUS staining in sepal tissues. Ectopic expression of BpMADS significantly enhanced the flowering of tobacco (35S::BpMADS). In addition, the chloroplasts of transgenic tobacco exhibited much higher growth and division rates, as well rates of photosynthesis, than wild-type. A grafting experiment demonstrated that the flowering time of the scion was not affected by stock that overexpressed BpMADS. In addition, the overexpression of BpMADS resulted in the upregulation of some flowering-related genes in tobacco.

Abject Magic: Reasoning Madness in Justine Larbalestier's "Magic or Madness" Trilogy

ERIC Educational Resources Information Center

Potter, Troy

2013-01-01

This paper explores the representation of magic and madness in Justine Larbalestier's "Magic or Madness" trilogy (2005-2007). Throughout the series, magic is constructed as an abject and disabling force that threatens to disable magic-wielders, either through madness or death. Despite being represented as a ubiquitous force, the…

Genome-wide identification and analysis of the MADS-box gene family in apple.

PubMed

Tian, Yi; Dong, Qinglong; Ji, Zhirui; Chi, Fumei; Cong, Peihua; Zhou, Zongshan

2015-01-25

The MADS-box gene family is one of the most widely studied families in plants and has diverse developmental roles in flower pattern formation, gametophyte cell division and fruit differentiation. Although the genome-wide analysis of this family has been performed in some species, little is known regarding MADS-box genes in apple (Malus domestica). In this study, 146 MADS-box genes were identified in the apple genome and were phylogenetically clustered into six subgroups (MIKC(c), MIKC*, Mα, Mβ, Mγ and Mδ) with the MADS-box genes from Arabidopsis and rice. The predicted apple MADS-box genes were distributed across all 17 chromosomes at different densities. Additionally, the MADS-box domain, exon length, gene structure and motif compositions of the apple MADS-box genes were analysed. Moreover, the expression of all of the apple MADS-box genes was analysed in the root, stem, leaf, flower tissues and five stages of fruit development. All of the apple MADS-box genes, with the exception of some genes in each group, were expressed in at least one of the tissues tested, which indicates that the MADS-box genes are involved in various aspects of the physiological and developmental processes of the apple. To the best of our knowledge, this report describes the first genome-wide analysis of the apple MADS-box gene family, and the results should provide valuable information for understanding the classification, cloning and putative functions of this family. Copyright © 2014 Elsevier B.V. All rights reserved.

Socio-Economic Status: A Barrier to Access to Mandibular Advancement Device Therapy for Patients with Obstructive Sleep Apnea Syndrome in France

PubMed Central

Fleury, Marion; Le Vaillant, Marc; Pelletier-Fleury, Nathalie

2015-01-01

Background Obstructive sleep apnea syndrome (OSAS) is a major public health problem which affects between 5 to 10% of the general population. OSAS is known to be associated with high rates of morbidity and mortality mainly due to cardiovascular diseases and traffic accidents. The burden of illness is high for the individual and society. There are 2 treatment options for OSAS, Continuous Positive Airway Pressure (CPAP) and Mandibular Advancement Device therapy (MAD). CPAP is known to be an effective but very constraining treatment. Patients are usually poorly adherent. MAD is a more recent treatment easier to use and consequently better tolerated, but MAD can only be prescribed to patients with satisfactory oral hygiene. Oral health constitutes a real issue particularly among underprivileged groups in France. Through this link, the question of whether low socio-economic status constitutes a barrier to access to care for patients with OSAS is raised. Methods and Principal Findings In a multicenter prospective cohort of 2822 consecutive OSAS patients in whom MAD has been proposed as an alternative to CPAP between May 15, 2007 and December 1st, 2014, we identified the factors that lead to a patient diagnosed with OSAS to be treated by MAD instead of CPAP. A logistic regression was performed using a stepwise forward procedure. The main outcome of the study was that treatment by MAD was significantly associated with both educational attainment, as determined by the age at which the patient left full-time education, ≥18 years compared with <18 (adjusted odds ratio (aOR): 1.64, 95% CI 1.23 to 2.20), and the patient's occupational category. Executives and higher intellectual professions, intermediate professions, technicians, foremen and employees were significantly more likely to be treated by MAD than workers (aOR: 2.21, 95% CI 1.88 to 2.58; aOR: 1.74, 95% CI 1.15 to 2.63; aOR: 1.96, 95% CI 1.11 to 3.47, respectively). Conclusions Overall, these results suggest that low socio-economic status constitutes a barrier to access to MAD for patients with OSAS in France. MAD use in patients with OSAS highlights inequalities in health care access. PMID:26402443

A Randomized Crossover Trial Evaluating Continuous Positive Airway Pressure Versus Mandibular Advancement Device on Health Outcomes in Veterans With Posttraumatic Stress Disorder

PubMed Central

El-Solh, Ali A.; Homish, Gregory G.; Ditursi, Guy; Lazarus, John; Rao, Nithin; Adamo, David; Kufel, Thomas

2017-01-01

Study Objectives: Despite the overall improvement in posttraumatic stress disorder (PTSD) symptomatology with continuous positive airway pressure (CPAP) therapy, adherence to CPAP is far worse in veterans with PTSD compared to the general population with obstructive sleep apnea (OSA). The aim of this study was to compare the efficacy, adherence, and preference of CPAP versus mandibular advancement device (MAD) and the effect of these treatments on health outcomes in veterans with PTSD. Methods: Forty-two subjects with PTSD and newly diagnosed OSA by polysomnography were treated in a randomized, crossover trial of 12 weeks with CPAP alternating with MAD separated by a 2-week washout period. The primary outcome was the difference in titration residual apnea-hypopnea index (AHI) between CPAP and MAD. Secondary outcome measures included PTSD Checklist and health-related quality of life (Medical Outcomes Study 36-Item Short Form and Pittsburgh Sleep Quality Index). Results: Analyses were limited to the 35 subjects (mean age 52.7 ± 11.6 years) who completed the trial, regardless of compliance with their assigned treatment. CPAP was more efficacious in reducing AHI and improving nocturnal oxygenation than MAD (P < .001 and P = .04, respectively). Both treatments reduced PTSD severity and ameliorated scores of the Medical Outcomes Study Short Form 36 and Pittsburgh Sleep Quality Index, although no differences were detected between the CPAP and MAD arms. The reported adherence to MAD was significantly higher than CPAP (P < .001), with 58% preferring MAD to CPAP. Conclusions: Although CPAP is more efficacious than MAD at improving sleep apnea, both treatment modalities imparted comparable benefits for veterans with PTSD in relation to PTSD severity and health-related quality of life. MAD offers a viable alternative for veterans with OSA and PTSD who are nonadherent to CPAP. Clinical Trial Registration: Title: A Randomized Cross Over Trial of Two Treatments for Sleep Apnea in Veterans With Post-Traumatic Stress Disorder; URL: https://www.clinicaltrials.gov/ct/show/NCT01569022; Identifier: NCT01569022 Citation: El-Solh AA, Homish GG, Ditursi G, Lazarus J, Rao N, Adamo D, Kufel T. A randomized crossover trial evaluating continuous positive airway pressure versus mandibular advancement device on health outcomes in veterans with posttraumatic stress disorder. J Clin Sleep Med. 2017;13(11):1327–1335 PMID:29065960

The regulation of MADS-box gene expression during ripening of banana and their regulatory interation with ethylene

USDA-ARS?s Scientific Manuscript database

MADS-box genes (MaMADS1-6), potential components of the developmental control of ripening have been cloned from Grand Nain banana cultivar. Similarity of these genes to tomato LeRIN is very low and neither MaMADS2 nor MaMADS1 complement the tomato rin mutation. Nevertheless, the expression patterns...

A balance of Mad and Myc expression dictates larval cell apoptosis and adult stem cell development during Xenopus intestinal metamorphosis.

PubMed

Okada, Morihiro; Miller, Thomas C; Wen, Luan; Shi, Yun-Bo

2017-05-11

The Myc/Mad/Max network has long been shown to be an important factor in regulating cell proliferation, death and differentiation in diverse cell types. In general, Myc-Max heterodimers activate target gene expression to promote cell proliferation, although excess of c-Myc can also induce apoptosis. In contrast, Mad competes against Myc to form Mad-Max heterodimers that bind to the same target genes to repress their expression and promote differentiation. The role of the Myc/Mad/Max network during vertebrate development, especially, the so-called postembryonic development, a period around birth in mammals, is unclear. Using thyroid hormone (T3)-dependent Xenopus metamorphosis as a model, we show here that Mad1 is induced by T3 in the intestine during metamorphosis when larval epithelial cell death and adult epithelial stem cell development take place. More importantly, we demonstrate that Mad1 is expressed in the larval cells undergoing apoptosis, whereas c-Myc is expressed in the proliferating adult stem cells during intestinal metamorphosis, suggesting that Mad1 may have a role in cell death during development. By using transcription activator-like effector nuclease-mediated gene-editing technology, we have generated Mad1 knockout Xenopus animals. This has revealed that Mad1 is not essential for embryogenesis or metamorphosis. On the other hand, consistent with its spatiotemporal expression profile, Mad1 knockout leads to reduced larval epithelial apoptosis but surprisingly also results in increased adult stem cell proliferation. These findings not only reveal a novel role of Mad1 in regulating developmental cell death but also suggest that a balance of Mad and Myc controls cell fate determination during adult organ development.

Sequential Bayesian Geostatistical Inversion and Evaluation of Combined Data Worth for Aquifer Characterization at the Hanford 300 Area

NASA Astrophysics Data System (ADS)

Murakami, H.; Chen, X.; Hahn, M. S.; Over, M. W.; Rockhold, M. L.; Vermeul, V.; Hammond, G. E.; Zachara, J. M.; Rubin, Y.

2010-12-01

Subsurface characterization for predicting groundwater flow and contaminant transport requires us to integrate large and diverse datasets in a consistent manner, and quantify the associated uncertainty. In this study, we sequentially assimilated multiple types of datasets for characterizing a three-dimensional heterogeneous hydraulic conductivity field at the Hanford 300 Area. The datasets included constant-rate injection tests, electromagnetic borehole flowmeter tests, lithology profile and tracer tests. We used the method of anchored distributions (MAD), which is a modular-structured Bayesian geostatistical inversion method. MAD has two major advantages over the other inversion methods. First, it can directly infer a joint distribution of parameters, which can be used as an input in stochastic simulations for prediction. In MAD, in addition to typical geostatistical structural parameters, the parameter vector includes multiple point values of the heterogeneous field, called anchors, which capture local trends and reduce uncertainty in the prediction. Second, MAD allows us to integrate the datasets sequentially in a Bayesian framework such that it updates the posterior distribution, as a new dataset is included. The sequential assimilation can decrease computational burden significantly. We applied MAD to assimilate different combinations of the datasets, and then compared the inversion results. For the injection and tracer test assimilation, we calculated temporal moments of pressure build-up and breakthrough curves, respectively, to reduce the data dimension. A massive parallel flow and transport code PFLOTRAN is used for simulating the tracer test. For comparison, we used different metrics based on the breakthrough curves not used in the inversion, such as mean arrival time, peak concentration and early arrival time. This comparison intends to yield the combined data worth, i.e. which combination of the datasets is the most effective for a certain metric, which will be useful for guiding the further characterization effort at the site and also the future characterization projects at the other sites.

Intensity Thresholds on Raw Acceleration Data: Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD) Approaches

PubMed Central

Bakrania, Kishan; Yates, Thomas; Rowlands, Alex V.; Esliger, Dale W.; Bunnewell, Sarah; Sanders, James; Davies, Melanie; Khunti, Kamlesh; Edwardson, Charlotte L.

2016-01-01

Objectives (1) To develop and internally-validate Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD) thresholds for separating sedentary behaviours from common light-intensity physical activities using raw acceleration data collected from both hip- and wrist-worn tri-axial accelerometers; and (2) to compare and evaluate the performances between the ENMO and MAD metrics. Methods Thirty-three adults [mean age (standard deviation (SD)) = 27.4 (5.9) years; mean BMI (SD) = 23.9 (3.7) kg/m2; 20 females (60.6%)] wore four accelerometers; an ActiGraph GT3X+ and a GENEActiv on the right hip; and an ActiGraph GT3X+ and a GENEActiv on the non-dominant wrist. Under laboratory-conditions, participants performed 16 different activities (11 sedentary behaviours and 5 light-intensity physical activities) for 5 minutes each. ENMO and MAD were computed from the raw acceleration data, and logistic regression and receiver-operating-characteristic (ROC) analyses were implemented to derive thresholds for activity discrimination. Areas under ROC curves (AUROC) were calculated to summarise performances and thresholds were assessed via executing leave-one-out-cross-validations. Results For both hip and wrist monitor placements, in comparison to the ActiGraph GT3X+ monitors, the ENMO and MAD values derived from the GENEActiv devices were observed to be slightly higher, particularly for the lower-intensity activities. Monitor-specific hip and wrist ENMO and MAD thresholds showed excellent ability for separating sedentary behaviours from motion-based light-intensity physical activities (in general, AUROCs >0.95), with validation indicating robustness. However, poor classification was experienced when attempting to isolate standing still from sedentary behaviours (in general, AUROCs <0.65). The ENMO and MAD metrics tended to perform similarly across activities and accelerometer brands. Conclusions Researchers can utilise these robust monitor-specific hip and wrist ENMO and MAD thresholds, in order to accurately separate sedentary behaviours from common motion-based light-intensity physical activities. However, caution should be taken if isolating sedentary behaviours from standing is of particular interest. PMID:27706241

Functional characterization of GhSOC1 and GhMADS42 homologs from upland cotton (Gossypium hirsutum L.).

PubMed

Zhang, Xiaohong; Wei, Jianghui; Fan, Shuli; Song, Meizhen; Pang, Chaoyou; Wei, Hengling; Wang, Chengshe; Yu, Shuxun

2016-01-01

In Arabidopsis flowering pathway, MADS-box genes encode transcription factors, with their structures and functions highly conserved in many species. In our study, two MADS-box genes GhSOC1 and GhMADS42 (Gossypium hirsutum L.) were cloned from upland cotton CCRI36 and transformed into Arabidopsis. GhSOC1 was additionally transformed into upland cotton. Comparative analysis demonstrated sequence conservation between GhSOC1 and GhMADS42 and genes of other plant species. Tissue-specific expression analysis of GhSOC1 and GhMADS42 revealed spatiotemporal expression patterns involving high transcript levels in leaves, shoot apical buds, and flowers. In addition, overexpression of both GhSOC1 and GhMADS42 in Arabidopsis accelerated flowering, with GhMADS42 transgenic plants showing abnormal floral organ phenotypes. Overexpression of GhSOC1 in upland cotton also produced variations in floral organs. Furthermore, chromatin immunoprecipitation assay demonstrated that GhSOC1 could regulate GhMADS41 and GhMADS42, but not FLOWERING LOCUS T, by directly binding to the genes promoter. Finally, yeast two-hybrid and bimolecular fluorescence complementation approaches were undertaken to better understand the interaction of GhSOC1 and other MADS-box factors. These experiments showed that GhSOC1 can interact with APETALA1/FRUITFULL-like proteins in cotton. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Three-Dimensional Bayesian Geostatistical Aquifer Characterization at the Hanford 300 Area using Tracer Test Data

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

Chen, Xingyuan; Murakami, Haruko; Hahn, Melanie S.

2012-06-01

Tracer testing under natural or forced gradient flow holds the potential to provide useful information for characterizing subsurface properties, through monitoring, modeling and interpretation of the tracer plume migration in an aquifer. Non-reactive tracer experiments were conducted at the Hanford 300 Area, along with constant-rate injection tests and electromagnetic borehole flowmeter (EBF) profiling. A Bayesian data assimilation technique, the method of anchored distributions (MAD) [Rubin et al., 2010], was applied to assimilate the experimental tracer test data with the other types of data and to infer the three-dimensional heterogeneous structure of the hydraulic conductivity in the saturated zone of themore » Hanford formation. In this study, the Bayesian prior information on the underlying random hydraulic conductivity field was obtained from previous field characterization efforts using the constant-rate injection tests and the EBF data. The posterior distribution of the conductivity field was obtained by further conditioning the field on the temporal moments of tracer breakthrough curves at various observation wells. MAD was implemented with the massively-parallel three-dimensional flow and transport code PFLOTRAN to cope with the highly transient flow boundary conditions at the site and to meet the computational demands of MAD. A synthetic study proved that the proposed method could effectively invert tracer test data to capture the essential spatial heterogeneity of the three-dimensional hydraulic conductivity field. Application of MAD to actual field data shows that the hydrogeological model, when conditioned on the tracer test data, can reproduce the tracer transport behavior better than the field characterized without the tracer test data. This study successfully demonstrates that MAD can sequentially assimilate multi-scale multi-type field data through a consistent Bayesian framework.« less

Genome-wide identification of the MADS-box transcription factor family in pear (Pyrus bretschneideri) reveals evolution and functional divergence.

PubMed

Wang, Runze; Ming, Meiling; Li, Jiaming; Shi, Dongqing; Qiao, Xin; Li, Leiting; Zhang, Shaoling; Wu, Jun

2017-01-01

MADS-box transcription factors play significant roles in plant developmental processes such as floral organ conformation, flowering time, and fruit development. Pear ( Pyrus ), as the third-most crucial temperate fruit crop, has been fully sequenced. However, there is limited information about the MADS family and its functional divergence in pear. In this study, a total of 95 MADS-box genes were identified in the pear genome, and classified into two types by phylogenetic analysis. Type I MADS-box genes were divided into three subfamilies and type II genes into 14 subfamilies. Synteny analysis suggested that whole-genome duplications have played key roles in the expansion of the MADS family, followed by rearrangement events. Purifying selection was the primary force driving MADS-box gene evolution in pear, and one gene pairs presented three codon sites under positive selection. Full-scale expression information for PbrMADS genes in vegetative and reproductive organs was provided and proved by transcriptional and reverse transcription PCR analysis. Furthermore, the PbrMADS11(12) gene, together with partners PbMYB10 and PbbHLH3 was confirmed to activate the promoters of the structural genes in anthocyanin pathway of red pear through dual luciferase assay. In addition, the PbrMADS11 and PbrMADS12 were deduced involving in the regulation of anthocyanin synthesis response to light and temperature changes. These results provide a solid foundation for future functional analysis of PbrMADS genes in different biological processes, especially of pigmentation in pear.

Genome-wide identification of the MADS-box transcription factor family in pear (Pyrus bretschneideri) reveals evolution and functional divergence

PubMed Central

Li, Jiaming; Shi, Dongqing; Qiao, Xin; Li, Leiting; Zhang, Shaoling

2017-01-01

MADS-box transcription factors play significant roles in plant developmental processes such as floral organ conformation, flowering time, and fruit development. Pear (Pyrus), as the third-most crucial temperate fruit crop, has been fully sequenced. However, there is limited information about the MADS family and its functional divergence in pear. In this study, a total of 95 MADS-box genes were identified in the pear genome, and classified into two types by phylogenetic analysis. Type I MADS-box genes were divided into three subfamilies and type II genes into 14 subfamilies. Synteny analysis suggested that whole-genome duplications have played key roles in the expansion of the MADS family, followed by rearrangement events. Purifying selection was the primary force driving MADS-box gene evolution in pear, and one gene pairs presented three codon sites under positive selection. Full-scale expression information for PbrMADS genes in vegetative and reproductive organs was provided and proved by transcriptional and reverse transcription PCR analysis. Furthermore, the PbrMADS11(12) gene, together with partners PbMYB10 and PbbHLH3 was confirmed to activate the promoters of the structural genes in anthocyanin pathway of red pear through dual luciferase assay. In addition, the PbrMADS11 and PbrMADS12 were deduced involving in the regulation of anthocyanin synthesis response to light and temperature changes. These results provide a solid foundation for future functional analysis of PbrMADS genes in different biological processes, especially of pigmentation in pear. PMID:28924499

Characterization of two rice MADS box genes that control flowering time.

PubMed

Kang, H G; Jang, S; Chung, J E; Cho, Y G; An, G

1997-08-31

Plants contain a variety of the MADS box genes that encode regulatory proteins and play important roles in both the formation of flower meristem and the determination of floral organ identity. We have characterized two flower-specific cDNAs from rice, designated OsMADS7 and OsMADS8. The cDNAs displayed the structure of a typical plant MADS box gene, which consists of the MADS domain, I region, K domain, and C-terminal region. These genes were classified as members of the AGL2 gene family based on sequence homology. The OsMADS7 and 8 proteins were most homologous to OM1 and FBP2, respectively. The OsMADS7 and 8 transcripts were detectable primarily in carpels and also weakly in anthers. During flower development, the OsMADS genes started to express at the young flower stage and the expression continued to the late stage of flower development. The OsMADS7 and 8 genes were mapped on the long arms of the chromosome 8 and 9, respectively. To study the functions of the genes, the cDNA clones were expressed ectopically using the CaMV 35S promoter in a heterologous tobacco plant system. Transgenic plants expressing the OsMADS genes exhibited the phenotype of early flowering and dwarfism. The strength of the phenotypes was proportional to the levels of transgene expression and the phenotypes were co-inherited with the kanamycin resistant gene to the next generation. These results indicate that OsMADS7 and 8 are structurally related to the AGL2 family and are involved in controlling flowering time.

MadDM: Computation of dark matter relic abundance

NASA Astrophysics Data System (ADS)

Backović, Mihailo; Kong, Kyoungchul; McCaskey, Mathew

2017-12-01

MadDM computes dark matter relic abundance and dark matter nucleus scattering rates in a generic model. The code is based on the existing MadGraph 5 architecture and as such is easily integrable into any MadGraph collider study. A simple Python interface offers a level of user-friendliness characteristic of MadGraph 5 without sacrificing functionality. MadDM is able to calculate the dark matter relic abundance in models which include a multi-component dark sector, resonance annihilation channels and co-annihilations. The direct detection module of MadDM calculates spin independent / spin dependent dark matter-nucleon cross sections and differential recoil rates as a function of recoil energy, angle and time. The code provides a simplified simulation of detector effects for a wide range of target materials and volumes.

Protection of neurons from high glucose-induced injury by deletion of MAD2B

PubMed Central

Meng, Xianfang; Wang, Xiaolan; Tian, Xiujuan; Yang, Zhihua; Li, Man; Zhang, Chun

2014-01-01

Diabetic encephalopathy may lead to cognitive deficits in diabetic patients and diminish quality of life. It has been shown that protracted hyperglycaemia is directly associated with neuronal apoptosis, which is involved in diabetic encephalopathy. The anaphase-promoting complex (APC) is essential for the survival of post-mitotic neurons. In our previous study, we found that the mitotic arrest deficient protein MAD2B, one of APC inhibitors, was expressed in neurons in central nervous system. However, whether MAD2B is involved in hyperglycaemia-induced apoptosis and thus takes part in diabetic encephalopathy is still unknown. To address this issue, we first explored the expression of MAD2B and cyclin B1 detected by immunofluorescence and Western blot. It was found that hyperglycaemia remarkably increased the expression of MAD2B and accumulation of cyclin B1 in cortices of diabetes mellitus rat model and in cultured primary neurons. To further explore the role of MAD2B in hyperglycaemia-induced neuronal injury, we depleted MAD2B expression by a specifically targeted shRNA against MAD2B. We observed that MAD2B deficiency alleviated cyclin B1 expression and apoptotic neuronal death. These results demonstrate that MAD2B expression is the main culprit for accumulation of cyclin B1 and apoptosis in neurons under high glucose. Moreover, inhibition of the expression of MAD2B prevented neurons from entering an aberrant S phase that led differentiated neurons into apoptotic cell death. These results suggest that hyperglycaemia induced neuronal apoptosis through inducing expression of MAD2B, which represents a novel mechanism of diabetic encephalopathy. PMID:24444371

A balance of Mad and Myc expression dictates larval cell apoptosis and adult stem cell development during Xenopus intestinal metamorphosis

PubMed Central

Okada, Morihiro; Miller, Thomas C; Wen, Luan; Shi, Yun-Bo

2017-01-01

The Myc/Mad/Max network has long been shown to be an important factor in regulating cell proliferation, death and differentiation in diverse cell types. In general, Myc–Max heterodimers activate target gene expression to promote cell proliferation, although excess of c-Myc can also induce apoptosis. In contrast, Mad competes against Myc to form Mad–Max heterodimers that bind to the same target genes to repress their expression and promote differentiation. The role of the Myc/Mad/Max network during vertebrate development, especially, the so-called postembryonic development, a period around birth in mammals, is unclear. Using thyroid hormone (T3)-dependent Xenopus metamorphosis as a model, we show here that Mad1 is induced by T3 in the intestine during metamorphosis when larval epithelial cell death and adult epithelial stem cell development take place. More importantly, we demonstrate that Mad1 is expressed in the larval cells undergoing apoptosis, whereas c-Myc is expressed in the proliferating adult stem cells during intestinal metamorphosis, suggesting that Mad1 may have a role in cell death during development. By using transcription activator-like effector nuclease-mediated gene-editing technology, we have generated Mad1 knockout Xenopus animals. This has revealed that Mad1 is not essential for embryogenesis or metamorphosis. On the other hand, consistent with its spatiotemporal expression profile, Mad1 knockout leads to reduced larval epithelial apoptosis but surprisingly also results in increased adult stem cell proliferation. These findings not only reveal a novel role of Mad1 in regulating developmental cell death but also suggest that a balance of Mad and Myc controls cell fate determination during adult organ development. PMID:28492553

Retention of mandibular advancement devices in the treatment of obstructive sleep apnea: an in vitro pilot study.

PubMed

Vanderveken, Olivier M; Van de Heyning, Paul; Braem, Marc J

2014-05-01

In order for a mandibular advancement device (MAD) to be efficacious, it must remain seated on the teeth during sleep. Quantitative data on the retentive characteristics of MADs are currently unavailable. The present pilot study is the first to describe an in vitro setup testing the retentive characteristics of different monobloc MADs. A hydraulic cyclic test machine was used with MADs seated on dental casts to measure retention forces upon removal of the MADs. A custom-made monobloc (CM-mono), a thermoplastic monobloc (TP-mono), and a thermoplastic duobloc (TP-duo) configured as a monobloc were tested. Two protrusions were investigated, representing 25 and 65% of the maximal protrusion. The effects of the type of MAD, duration of the test, and amount of protrusion on removal forces were measured. The measured removal forces of all three MADs tested differed significantly, with the TP-duo showing the highest values (P < 0.0001). The effects of wear due to the repetitive cyclic loading became obvious by the production of wear particles in all MADs tested. However, only the TP-duo showed a significant reduction in time in removal forces for both protrusion positions (P < 0.0001; P = 0.0011). The effect of the amount of protrusion on the removal forces differed significantly between all three MADs tested (P = 0.0074). This in vitro pilot study reveals significant differences in retention forces for the MADs tested. The findings are consistent with clinical effects of nightly loss of MADs as reported in the literature and are within the range of reported physiological mouth-opening forces. Future research is needed to determine the key design features of MADs that explain these differences.

Cloning, expression, crystallization and preliminary X-ray data analysis of norcoclaurine synthase from Thalictrum flavum

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

Pasquo, Alessandra; Bonamore, Alessandra; Franceschini, Stefano

The cloning, expression, crystallization and preliminary X-ray data analysis of norcoclaurine synthase from T. flavum, a protein which catalyzes the first committed step in the biosynthesis of benzylisoquinoline alkaloids, are reported. Norcoclaurine synthase (NCS) catalyzes the condensation of 3,4-dihydroxyphenylethylamine (dopamine) and 4-hydroxyphenylacetaldehyde (4-HPAA) as the first committed step in the biosynthesis of benzylisoquinoline alkaloids in plants. The protein was cloned, expressed and purified. Crystals were obtained at 294 K by the hanging-drop vapour-diffusion method using ammonium sulfate and sodium chloride as precipitant agents and diffract to better than 3.0 Å resolution using a synchrotron-radiation source. The crystals belong to themore » trigonal space group P3{sub 1}21, with unit-cell parameters a = b = 86.31, c = 118.36 Å. A selenomethionine derivative was overexpressed, purified and crystallized in the same space group. A complete MAD data set was collected at 2.7 Å resolution. The model is under construction.« less

Genetic Interaction of OsMADS3, DROOPING LEAF, and OsMADS13 in Specifying Rice Floral Organ Identities and Meristem Determinacy1[W][OA

PubMed Central

Li, Haifeng; Liang, Wanqi; Yin, Changsong; Zhu, Lu; Zhang, Dabing

2011-01-01

Grass plants develop unique floral patterns that determine grain production. However, the molecular mechanism underlying the specification of floral organ identities and meristem determinacy, including the interaction among floral homeotic genes, remains largely unknown in grasses. Here, we report the interactions of rice (Oryza sativa) floral homeotic genes, OsMADS3 (a C-class gene), OsMADS13 (a D-class gene), and DROOPING LEAF (DL), in specifying floral organ identities and floral meristem determinacy. The interaction among these genes was revealed through the analysis of double mutants. osmads13-3 osmads3-4 displayed a loss of floral meristem determinacy and generated abundant carpelloid structures containing severe defective ovules in the flower center, which were not detectable in the single mutant. In addition, in situ hybridization and yeast two-hybrid analyses revealed that OsMADS13 and OsMADS3 did not regulate each other’s transcription or interact at the protein level. This indicates that OsMADS3 plays a synergistic role with OsMADS13 in both ovule development and floral meristem termination. Strikingly, osmads3-4 dl-sup6 displayed a severe loss of floral meristem determinacy and produced supernumerary whorls of lodicule-like organs at the forth whorl, suggesting that OsMADS3 and DL synergistically terminate the floral meristem. Furthermore, the defects of osmads13-3 dl-sup6 flowers appeared identical to those of dl-sup6, and the OsMADS13 expression was undetectable in dl-sup6 flowers. These observations suggest that DL and OsMADS13 may function in the same pathway specifying the identity of carpel/ovule and floral meristem. Collectively, we propose a model to illustrate the role of OsMADS3, DL, and OsMADS13 in the specification of flower organ identity and meristem determinacy in rice. PMID:21444646

Ectopic expression of pMADS3 in transgenic petunia phenocopies the petunia blind mutant.

PubMed Central

Tsuchimoto, S; van der Krol, A R; Chua, N H

1993-01-01

We cloned a MADS-box gene, pMADS3, from Petunia hybrida, which shows high sequence homology to the Arabidopsis AGAMOUS and Antirrhinum PLENA. pMADS3 is expressed exclusively in stamens and carpels of wild-type petunia plants. In the petunia mutant blind, which shows homeotic conversions of corolla limbs into antheroid structures with pollen grains and small parts of sepals into carpelloid tissue, pMADS3 is expressed in all floral organs as well as in leaves. Ectopic expression of pMADS3 in transgenic petunia leads to phenocopies of the blind mutant, i.e., the formation of antheroid structures on limbs and carpelloid tissue on sepals. Transgenic tobacco plants that overexpress pMADS3 exhibit an even more severe phenotype, with the sepals forming a carpel-like structure encasing the interior floral organs. Our results identify BLIND as a negative regulator of pMADS3, which specifies stamens and carpels during petunia flower development. PMID:8104573

Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex.

PubMed

Hewitt, Laura; Tighe, Anthony; Santaguida, Stefano; White, Anne M; Jones, Clifford D; Musacchio, Andrea; Green, Stephen; Taylor, Stephen S

2010-07-12

Mps1 is an essential component of the spindle assembly checkpoint. In this study, we describe a novel Mps1 inhibitor, AZ3146, and use it to probe the role of Mps1's catalytic activity during mitosis. When Mps1 is inhibited before mitotic entry, subsequent recruitment of Mad1 and Mad2 to kinetochores is abolished. However, if Mps1 is inhibited after mitotic entry, the Mad1-C-Mad2 core complex remains kinetochore bound, but O-Mad2 is not recruited to the core. Although inhibiting Mps1 also interferes with chromosome alignment, we see no obvious effect on aurora B activity. In contrast, kinetochore recruitment of centromere protein E (CENP-E), a kinesin-related motor protein, is severely impaired. Strikingly, inhibition of Mps1 significantly increases its own abundance at kinetochores. Furthermore, we show that Mps1 can dimerize and transphosphorylate in cells. We propose a model whereby Mps1 transphosphorylation results in its release from kinetochores, thus facilitating recruitment of O-Mad2 and CENP-E and thereby simultaneously promoting checkpoint signaling and chromosome congression.

Comparative phylogenetic analysis and transcriptional profiling of MADS-box gene family identified DAM and FLC-like genes in apple (Malusx domestica)

PubMed Central

Kumar, Gulshan; Arya, Preeti; Gupta, Khushboo; Randhawa, Vinay; Acharya, Vishal; Singh, Anil Kumar

2016-01-01

The MADS-box transcription factors play essential roles in various processes of plant growth and development. In the present study, phylogenetic analysis of 142 apple MADS-box proteins with that of other dicotyledonous species identified six putative Dormancy-Associated MADS-box (DAM) and four putative Flowering Locus C-like (FLC-like) proteins. In order to study the expression of apple MADS-box genes, RNA-seq analysis of 3 apical and 5 spur bud stages during dormancy, 6 flower stages and 7 fruit development stages was performed. The dramatic reduction in expression of two MdDAMs, MdMADS063 and MdMADS125 and two MdFLC-like genes, MdMADS135 and MdMADS136 during dormancy release suggests their role as flowering-repressors in apple. Apple orthologs of Arabidopsis genes, FLOWERING LOCUS T, FRIGIDA, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 and LEAFY exhibit similar expression patterns as reported in Arabidopsis, suggesting functional conservation in floral signal integration and meristem determination pathways. Gene ontology enrichment analysis of predicted targets of DAM revealed their involvement in regulation of reproductive processes and meristematic activities, indicating functional conservation of SVP orthologs (DAM) in apple. This study provides valuable insights into the functions of MADS-box proteins during apple phenology, which may help in devising strategies to improve important traits in apple. PMID:26856238

Meta-analysis of randomised controlled trials of oral mandibular advancement devices and continuous positive airway pressure for obstructive sleep apnoea-hypopnoea

PubMed Central

Sharples, Linda D.; Clutterbuck-James, Abigail L.; Glover, Matthew J.; Bennett, Maxine S.; Chadwick, Rebecca; Pittman, Marcus A.; Quinnell, Timothy G.

2017-01-01

Summary Obstructive sleep apnoea-hypopnoea (OSAH) causes excessive daytime sleepiness, impairs quality-of-life, and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment and mandibular advancement devices (MAD) have been shown to be effective in individual trials but their effectiveness particularly relative to disease severity is unclear. A MEDLINE, Embase and Science Citation Index search updating two systematic reviews to August 2013 identified 77 RCTs in adult OSAH patients comparing: MAD with conservative management (CM); MAD with CPAP; or CPAP with CM. Overall MAD and CPAP significantly improved apnoea-hypopnoea index (AHI) (MAD −9.3/hr (p < 0.001), CPAP −25.4 (p < 0.001)). In direct comparisons mean AHI and Epworth sleepiness scale score were lower (7.0/hr (p < 0.001) and 0.67 (p = 0.093) respectively) for CPAP. There were no CPAP vs. MAD trials in mild OSAH but in comparisons with CM, MAD and CPAP reduced ESS similarly (MAD 2.01 (p < 0.001); CPAP 1.23 (p = 0.012). Both MAD and CPAP are clinically effective in the treatment of OSAH. Although CPAP has a greater treatment effect, MAD is an appropriate treatment for patients who are intolerant of CPAP and may be comparable to CPAP in mild disease. PMID:26163056

Comparative phylogenetic analysis and transcriptional profiling of MADS-box gene family identified DAM and FLC-like genes in apple (Malusx domestica).

PubMed

Kumar, Gulshan; Arya, Preeti; Gupta, Khushboo; Randhawa, Vinay; Acharya, Vishal; Singh, Anil Kumar

2016-02-09

The MADS-box transcription factors play essential roles in various processes of plant growth and development. In the present study, phylogenetic analysis of 142 apple MADS-box proteins with that of other dicotyledonous species identified six putative Dormancy-Associated MADS-box (DAM) and four putative Flowering Locus C-like (FLC-like) proteins. In order to study the expression of apple MADS-box genes, RNA-seq analysis of 3 apical and 5 spur bud stages during dormancy, 6 flower stages and 7 fruit development stages was performed. The dramatic reduction in expression of two MdDAMs, MdMADS063 and MdMADS125 and two MdFLC-like genes, MdMADS135 and MdMADS136 during dormancy release suggests their role as flowering-repressors in apple. Apple orthologs of Arabidopsis genes, FLOWERING LOCUS T, FRIGIDA, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 and LEAFY exhibit similar expression patterns as reported in Arabidopsis, suggesting functional conservation in floral signal integration and meristem determination pathways. Gene ontology enrichment analysis of predicted targets of DAM revealed their involvement in regulation of reproductive processes and meristematic activities, indicating functional conservation of SVP orthologs (DAM) in apple. This study provides valuable insights into the functions of MADS-box proteins during apple phenology, which may help in devising strategies to improve important traits in apple.

Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea.

PubMed

Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

2016-11-01

Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP.This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA.Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively.The MAD treatment resulted in a significant reduction in apnea-hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA.These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP.

Wg Signaling via Zw3 and Mad Restricts Self-Renewal of Sensory Organ Precursor Cells in Drosophila

PubMed Central

Quijano, Janine C.; Stinchfield, Michael J.; Newfeld, Stuart J.

2011-01-01

It is well known that the Dpp signal transducer Mad is activated by phosphorylation at its carboxy-terminus. The role of phosphorylation on other regions of Mad is not as well understood. Here we report that the phosphorylation of Mad in the linker region by the Wg antagonist Zw3 (homolog of vertebrate Gsk3-β) regulates the development of sensory organs in the anterior–dorsal quadrant of the wing. Proneural expression of Mad-RNA interference (RNAi) or a Mad transgene with its Zw3/Gsk3-β phosphorylation sites mutated (MGM) generated wings with ectopic sensilla and chemosensory bristle duplications. Studies with pMad-Gsk (an antibody specific to Zw3/Gsk3-β-phosphorylated Mad) in larval wing disks revealed that this phosphorylation event is Wg dependent (via an unconventional mechanism), is restricted to anterior–dorsal sensory organ precursors (SOP) expressing Senseless (Sens), and is always co-expressed with the mitotic marker phospho-histone3. Quantitative analysis in both Mad-RNAi and MGM larval wing disks revealed a significant increase in the number of Sens SOP. We conclude that the phosphorylation of Mad by Zw3 functions to prevent the self-renewal of Sens SOP, perhaps facilitating their differentiation via asymmetric division. The conservation of Zw3/Gsk3-β phosphorylation sites in vertebrate homologs of Mad (Smads) suggests that this pathway, the first transforming growth factor β-independent role for any Smad protein, may be widely utilized for regulating mitosis during development. PMID:21868604

Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea

PubMed Central

Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

2016-01-01

Abstract Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP. This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA. Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively. The MAD treatment resulted in a significant reduction in apnea–hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA. These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP. PMID:27861349

Miscarriages of transmission: body, text, and method.

PubMed

Goodrich, P

An introductory and exploratory attempt to examine the possibility of viewing the famous writings of Judge Daniel Paul Schreber as the intimations of translawyering. Volubly convinced he was becoming a woman, Judge Schreber announced that he would nail his flag to the feminine and was incarcerated as mad for his pains and his pleasures. It is time to release him and to read his work not as madness but as a unique conjunction of desire and law. Copyright © 2016. Published by Elsevier Ltd.

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

Lovelace, III, Henry H.

In accelerator physics, models of a given machine are used to predict the behaviors of the beam, magnets, and radiofrequency cavities. The use of the computational model has become wide spread to ease the development period of the accelerator lattice. There are various programs that are used to create lattices and run simulations of both transverse and longitudinal beam dynamics. The programs include Methodical Accelerator Design(MAD) MAD8, MADX, Zgoubi, Polymorphic Tracking Code (PTC), and many others. In this discussion the BMAD (Baby Methodical Accelerator Design) is presented as an additional tool in creating and simulating accelerator lattices for the studymore » of beam dynamics in the Relativistic Heavy Ion Collider (RHIC).« less

[Mandibular advancement devices in the treatment of obstructive sleep apnea].

PubMed

Korczyński, Piotr; Górska, Katarzyna; Wilk, Krzysztof; Bielicki, Piotr; Byśkiniewicz, Krzysztof; Baczkowski, Tadeusz

2004-12-01

Obstructive sleep apnea (OSA) affects approximately 450,000 people in Poland. Use of nasal continuous positive airway pressure (nCPAP) devices and laryngeal surgery are widely accepted OSA treatment methods. In 1995 ASDA approved oral devices for treatment of OSA patients. The aim of the study was to determine efficiency of mandibular advancement devices (MAD) in OSA therapy. The study group included 20 patients with OSA, all of whom did not tolerate nCPAP and did not have indications or did not agree for surgical treatment. Control polysomnography was carried out in 11 patients using MAD. In 64% of patients AHI was lower then 10. No correlation between MAD use and AHI values was found. 45% of patients declared improvement of sleep quality and life comfort. Use of mandibular advancement devices is an important alternative therapy of OSA.

Clinical effectiveness and cost-effectiveness results from the randomised controlled Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and long-term economic analysis of oral devices and continuous positive airway pressure.

PubMed

Sharples, Linda; Glover, Matthew; Clutterbuck-James, Abigail; Bennett, Maxine; Jordan, Jake; Chadwick, Rebecca; Pittman, Marcus; East, Clare; Cameron, Malcolm; Davies, Mike; Oscroft, Nick; Smith, Ian; Morrell, Mary; Fox-Rushby, Julia; Quinnell, Timothy

2014-10-01

Obstructive sleep apnoea-hypopnoea (OSAH) causes excessive daytime sleepiness (EDS), impairs quality of life (QoL) and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment is clinically effective but undermined by intolerance, and its cost-effectiveness is borderline in milder cases. Mandibular advancement devices (MADs) are another option, but evidence is lacking regarding their clinical effectiveness and cost-effectiveness in milder disease. (1) Conduct a randomised controlled trial (RCT) examining the clinical effectiveness and cost-effectiveness of MADs against no treatment in mild to moderate OSAH. (2) Update systematic reviews and an existing health economic decision model with data from the Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and newly published results to better inform long-term clinical effectiveness and cost-effectiveness of MADs and CPAP in mild to moderate OSAH. A crossover RCT comparing clinical effectiveness and cost-effectiveness of three MADs: self-moulded [SleepPro 1™ (SP1); Meditas Ltd, Winchester, UK]; semibespoke [SleepPro 2™ (SP2); Meditas Ltd, Winchester, UK]; and fully bespoke [bespoke MAD (bMAD); NHS Oral-Maxillofacial Laboratory, Addenbrooke's Hospital, Cambridge, UK] against no treatment, in 90 adults with mild to moderate OSAH. All devices improved primary outcome [apnoea-hypopnoea index (AHI)] compared with no treatment: relative risk 0.74 [95% confidence interval (CI) 0.62 to 0.89] for SP1; relative risk 0.67 (95% CI 0.59 to 0.76) for SP2; and relative risk 0.64 (95% CI 0.55 to 0.76) for bMAD (p < 0.001). Differences between MADs were not significant. Sleepiness [as measured by the Epworth Sleepiness Scale (ESS)] was scored 1.51 [95% CI 0.73 to 2.29 (SP1)] to 2.37 [95% CI 1.53 to 3.22 (bMAD)] lower than no treatment (p < 0.001), with SP2 and bMAD significantly better than SP1. All MADs improved disease-specific QoL. Compliance was lower for SP1, which was unpopular at trial exit. At 4 weeks, all devices were cost-effective at £20,000/quality-adjusted life-year (QALY), with SP2 the best value below £39,800/QALY. A MEDLINE, EMBASE and Science Citation Index search updating two existing systematic reviews (one from November 2006 and the other from June 2008) to August 2013 identified 77 RCTs in adult OSAH patients comparing MAD with conservative management (CM), MADs with CPAP or CPAP with CM. MADs and CPAP significantly improved AHI [MAD -9.3/hour (p < 0.001); CPAP -25.4/hour (p < 0.001)]. Effect difference between CPAP and MADs was 7.0/hour (p < 0.001), favouring CPAP. No trials compared CPAP with MADs in mild OSAH. MAD and CPAP reduced the ESS score similarly [MAD 1.6 (p < 0.001); CPAP 1.6 (p < 0.001)]. An existing model assessed lifetime cost-utility of MAD and CPAP in mild to moderate OSAH, using the revised meta-analysis to update input values. The TOMADO provided utility estimates, mapping ESS score to European Quality of Life-5 Dimensions three-level version for device cost-utility. Using SP2 as the standard device, MADs produced higher mean costs and mean QALYs than CM [incremental cost-effectiveness ratio (ICER) £6687/QALY]. From a willingness to pay (WTP) of £15,367/QALY, CPAP is cost-effective, although the likelihood of MADs (p = 0.48) and CPAP (p = 0.49) being cost-effective is very similar. Both were better than CM, but there was much uncertainty in the choice between CPAP and MAD (at a WTP £20,000/QALY, the probability of being the most cost-effective was 47% for MAD and 52% for CPAP). When SP2 lifespan increased to 18 months, the ICER for CPAP compared with MAD became £44,066. The ICER for SP1 compared with CM was £1552, and for bMAD compared with CM the ICER was £13,836. The ICER for CPAP compared with SP1 was £89,182, but CPAP produced lower mean costs and higher mean QALYs than bMAD. Differential compliance rates for CPAP reduces cost-effectiveness so MADs become less costly and more clinically effective with CPAP compliance 90% of SP2. Mandibular advancement devices are clinically effective and cost-effective in mild to moderate OSAH. A semi-bespoke MAD is the appropriate first choice in most patients in the short term. Future work should explore whether or not adjustable MADs give additional clinical and cost benefits. Further data on longer-term cardiovascular risk and its risk factors would reduce uncertainty in the health economic model and improve precision of effectiveness estimates. This trial is registered as ISRCTN02309506. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 67. See the NIHR Journals Library website for further project information.

Clinical effectiveness and cost-effectiveness results from the randomised controlled Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and long-term economic analysis of oral devices and continuous positive airway pressure.

PubMed Central

Sharples, Linda; Glover, Matthew; Clutterbuck-James, Abigail; Bennett, Maxine; Jordan, Jake; Chadwick, Rebecca; Pittman, Marcus; East, Clare; Cameron, Malcolm; Davies, Mike; Oscroft, Nick; Smith, Ian; Morrell, Mary; Fox-Rushby, Julia; Quinnell, Timothy

2014-01-01

BACKGROUND Obstructive sleep apnoea-hypopnoea (OSAH) causes excessive daytime sleepiness (EDS), impairs quality of life (QoL) and increases cardiovascular disease and road traffic accident risks. Continuous positive airway pressure (CPAP) treatment is clinically effective but undermined by intolerance, and its cost-effectiveness is borderline in milder cases. Mandibular advancement devices (MADs) are another option, but evidence is lacking regarding their clinical effectiveness and cost-effectiveness in milder disease. OBJECTIVES (1) Conduct a randomised controlled trial (RCT) examining the clinical effectiveness and cost-effectiveness of MADs against no treatment in mild to moderate OSAH. (2) Update systematic reviews and an existing health economic decision model with data from the Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and newly published results to better inform long-term clinical effectiveness and cost-effectiveness of MADs and CPAP in mild to moderate OSAH. TOMADO A crossover RCT comparing clinical effectiveness and cost-effectiveness of three MADs: self-moulded [SleepPro 1™ (SP1); Meditas Ltd, Winchester, UK]; semibespoke [SleepPro 2™ (SP2); Meditas Ltd, Winchester, UK]; and fully bespoke [bespoke MAD (bMAD); NHS Oral-Maxillofacial Laboratory, Addenbrooke's Hospital, Cambridge, UK] against no treatment, in 90 adults with mild to moderate OSAH. All devices improved primary outcome [apnoea-hypopnoea index (AHI)] compared with no treatment: relative risk 0.74 [95% confidence interval (CI) 0.62 to 0.89] for SP1; relative risk 0.67 (95% CI 0.59 to 0.76) for SP2; and relative risk 0.64 (95% CI 0.55 to 0.76) for bMAD (p < 0.001). Differences between MADs were not significant. Sleepiness [as measured by the Epworth Sleepiness Scale (ESS)] was scored 1.51 [95% CI 0.73 to 2.29 (SP1)] to 2.37 [95% CI 1.53 to 3.22 (bMAD)] lower than no treatment (p < 0.001), with SP2 and bMAD significantly better than SP1. All MADs improved disease-specific QoL. Compliance was lower for SP1, which was unpopular at trial exit. At 4 weeks, all devices were cost-effective at £20,000/quality-adjusted life-year (QALY), with SP2 the best value below £39,800/QALY. META-ANALYSIS A MEDLINE, EMBASE and Science Citation Index search updating two existing systematic reviews (one from November 2006 and the other from June 2008) to August 2013 identified 77 RCTs in adult OSAH patients comparing MAD with conservative management (CM), MADs with CPAP or CPAP with CM. MADs and CPAP significantly improved AHI [MAD -9.3/hour (p < 0.001); CPAP -25.4/hour (p < 0.001)]. Effect difference between CPAP and MADs was 7.0/hour (p < 0.001), favouring CPAP. No trials compared CPAP with MADs in mild OSAH. MAD and CPAP reduced the ESS score similarly [MAD 1.6 (p < 0.001); CPAP 1.6 (p < 0.001)]. LONG-TERM COST-EFFECTIVENESS An existing model assessed lifetime cost-utility of MAD and CPAP in mild to moderate OSAH, using the revised meta-analysis to update input values. The TOMADO provided utility estimates, mapping ESS score to European Quality of Life-5 Dimensions three-level version for device cost-utility. Using SP2 as the standard device, MADs produced higher mean costs and mean QALYs than CM [incremental cost-effectiveness ratio (ICER) £6687/QALY]. From a willingness to pay (WTP) of £15,367/QALY, CPAP is cost-effective, although the likelihood of MADs (p = 0.48) and CPAP (p = 0.49) being cost-effective is very similar. Both were better than CM, but there was much uncertainty in the choice between CPAP and MAD (at a WTP £20,000/QALY, the probability of being the most cost-effective was 47% for MAD and 52% for CPAP). When SP2 lifespan increased to 18 months, the ICER for CPAP compared with MAD became £44,066. The ICER for SP1 compared with CM was £1552, and for bMAD compared with CM the ICER was £13,836. The ICER for CPAP compared with SP1 was £89,182, but CPAP produced lower mean costs and higher mean QALYs than bMAD. Differential compliance rates for CPAP reduces cost-effectiveness so MADs become less costly and more clinically effective with CPAP compliance 90% of SP2. CONCLUSIONS Mandibular advancement devices are clinically effective and cost-effective in mild to moderate OSAH. A semi-bespoke MAD is the appropriate first choice in most patients in the short term. Future work should explore whether or not adjustable MADs give additional clinical and cost benefits. Further data on longer-term cardiovascular risk and its risk factors would reduce uncertainty in the health economic model and improve precision of effectiveness estimates. TRIAL REGISTRATION This trial is registered as ISRCTN02309506. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 67. See the NIHR Journals Library website for further project information. PMID:25359435

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

33 CFR 147.839 - Mad Dog Truss Spar Platform safety zone.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Mad Dog Truss Spar Platform... SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES SAFETY ZONES § 147.839 Mad Dog Truss Spar Platform safety zone. (a) Description. Mad Dog Truss Spar Platform, Green Canyon 782 (GC 782), located at position...

RED, a Spindle Pole-associated Protein, Is Required for Kinetochore Localization of MAD1, Mitotic Progression, and Activation of the Spindle Assembly Checkpoint*

PubMed Central

Yeh, Pei-Chi; Yeh, Chang-Ching; Chen, Yi-Cheng; Juang, Yue-Li

2012-01-01

The spindle assembly checkpoint (SAC) is essential for ensuring the proper attachment of kinetochores to the spindle and, thus, the precise separation of paired sister chromatids during mitosis. The SAC proteins are recruited to the unattached kinetochores for activation of the SAC in prometaphase. However, it has been less studied whether activation of the SAC also requires the proteins that do not localize to the kinetochores. Here, we show that the nuclear protein RED, also called IK, a down-regulator of human leukocyte antigen (HLA) II, interacts with the human SAC protein MAD1. Two RED-interacting regions identified in MAD1 are from amino acid residues 301–340 and 439–480, designated as MAD1(301–340) and MAD1(439–480), respectively. Our observations reveal that RED is a spindle pole-associated protein that colocalizes with MAD1 at the spindle poles in metaphase and anaphase. Depletion of RED can cause a shorter mitotic timing, a failure in the kinetochore localization of MAD1 in prometaphase, and a defect in the SAC. Furthermore, the RED-interacting peptides MAD1(301–340) and MAD1(439–480), fused to enhanced green fluorescence protein, can colocalize with RED at the spindle poles in prometaphase, and their expression can abrogate the SAC. Taken together, we conclude that RED is required for kinetochore localization of MAD1, mitotic progression, and activation of the SAC. PMID:22351768

Virus-induced gene silencing unravels multiple transcription factors involved in floral growth and development in Phalaenopsis orchids.

PubMed

Hsieh, Ming-Hsien; Pan, Zhao-Jun; Lai, Pei-Han; Lu, Hsiang-Chia; Yeh, Hsin-Hung; Hsu, Chia-Chi; Wu, Wan-Lin; Chung, Mei-Chu; Wang, Shyh-Shyan; Chen, Wen-Huei; Chen, Hong-Hwa

2013-09-01

Orchidaceae, one of the largest angiosperm families, has significant commercial value. Isolation of genes involved in orchid floral development and morphogenesis, scent production, and colouration will advance knowledge of orchid flower formation and facilitate breeding new varieties to increase the commercial value. With high-throughput virus-induced gene silencing (VIGS), this study identified five transcription factors involved in various aspects of flower morphogenesis in the orchid Phalaenopsis equestris. These genes are PeMADS1, PeMADS7, PeHB, PebHLH, and PeZIP. Silencing PeMADS1 and PebHLH resulted in reduced flower size together with a pelaloid column containing petal-like epidermal cells and alterations of epidermal cell arrangement in lip lateral lobes, respectively. Silencing PeMADS7, PeHB, and PeZIP alone resulted in abortion of the first three fully developed flower buds of an inflorescence, which indicates the roles of the genes in late flower development. Furthermore, double silencing PeMADS1 and PeMADS6, C- and B-class MADS-box genes, respectively, produced a combinatorial phenotype with two genes cloned in separate vectors. Both PeMADS1 and PeMADS6 are required to ensure the normal development of the lip and column as well as the cuticle formation on the floral epidermal cell surface. Thus, VIGS allows for unravelling the interaction between two classes of MADS transcription factors for dictating orchid floral morphogenesis.

Virus-induced gene silencing unravels multiple transcription factors involved in floral growth and development in Phalaenopsis orchids

PubMed Central

Hsieh, Ming-Hsien; Pan, Zhao-Jun; Lai, Pei-Han; Lu, Hsiang-Chia; Yeh, Hsin-Hung; Hsu, Chia-Chi; Wu, Wan-Lin; Chung, Mei-Chu; Wang, Shyh-Shyan; Chen, Wen-Huei; Chen, Hong-Hwa

2013-01-01

Orchidaceae, one of the largest angiosperm families, has significant commercial value. Isolation of genes involved in orchid floral development and morphogenesis, scent production, and colouration will advance knowledge of orchid flower formation and facilitate breeding new varieties to increase the commercial value. With high-throughput virus-induced gene silencing (VIGS), this study identified five transcription factors involved in various aspects of flower morphogenesis in the orchid Phalaenopsis equestris. These genes are PeMADS1, PeMADS7, PeHB, PebHLH, and PeZIP. Silencing PeMADS1 and PebHLH resulted in reduced flower size together with a pelaloid column containing petal-like epidermal cells and alterations of epidermal cell arrangement in lip lateral lobes, respectively. Silencing PeMADS7, PeHB, and PeZIP alone resulted in abortion of the first three fully developed flower buds of an inflorescence, which indicates the roles of the genes in late flower development. Furthermore, double silencing PeMADS1 and PeMADS6, C- and B-class MADS-box genes, respectively, produced a combinatorial phenotype with two genes cloned in separate vectors. Both PeMADS1 and PeMADS6 are required to ensure the normal development of the lip and column as well as the cuticle formation on the floral epidermal cell surface. Thus, VIGS allows for unravelling the interaction between two classes of MADS transcription factors for dictating orchid floral morphogenesis. PMID:23956416

Characterization of an AGAMOUS-like MADS Box Protein, a Probable Constituent of Flowering and Fruit Ripening Regulatory System in Banana

PubMed Central

Roy Choudhury, Swarup; Roy, Sujit; Nag, Anish; Singh, Sanjay Kumar; Sengupta, Dibyendu N.

2012-01-01

The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ∼95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development. PMID:22984496

Characterization of an AGAMOUS-like MADS box protein, a probable constituent of flowering and fruit ripening regulatory system in banana.

PubMed

Roy Choudhury, Swarup; Roy, Sujit; Nag, Anish; Singh, Sanjay Kumar; Sengupta, Dibyendu N

2012-01-01

The MADS-box family of genes has been shown to play a significant role in the development of reproductive organs, including dry and fleshy fruits. In this study, the molecular properties of an AGAMOUS like MADS box transcription factor in banana cultivar Giant governor (Musa sp, AAA group, subgroup Cavendish) has been elucidated. We have detected a CArG-box sequence binding AGAMOUS MADS-box protein in banana flower and fruit nuclear extracts in DNA-protein interaction assays. The protein fraction in the DNA-protein complex was analyzed by mass spectrometry and using this information we have obtained the full length cDNA of the corresponding protein. The deduced protein sequence showed ~95% amino acid sequence homology with MA-MADS5, a MADS-box protein described previously from banana. We have characterized the domains of the identified AGAMOUS MADS-box protein involved in DNA binding and homodimer formation in vitro using full-length and truncated versions of affinity purified recombinant proteins. Furthermore, in order to gain insight about how DNA bending is achieved by this MADS-box factor, we performed circular permutation and phasing analysis using the wild type recombinant protein. The AGAMOUS MADS-box protein identified in this study has been found to predominantly accumulate in the climacteric fruit pulp and also in female flower ovary. In vivo and in vitro assays have revealed specific binding of the identified AGAMOUS MADS-box protein to CArG-box sequence in the promoters of major ripening genes in banana fruit. Overall, the expression patterns of this MADS-box protein in banana female flower ovary and during various phases of fruit ripening along with the interaction of the protein to the CArG-box sequence in the promoters of major ripening genes lead to interesting assumption about the possible involvement of this AGAMOUS MADS-box factor in banana fruit ripening and floral reproductive organ development.

DNA methylation and small interference RNAs participate in the regulation of MADS-box genes involved in dormancy in sweet cherry (Prunus avium L.).

PubMed

Rothkegel, Karin; Sánchez, Evelyn; Montes, Christian; Greve, Macarena; Tapia, Sebastián; Bravo, Soraya; Prieto, Humberto; Almeida, Andréa Miyasaka

2017-12-01

Epigenetic modifications can yield information about connections between genotype, phenotype variation and environmental conditions. Bud dormancy release in temperate perennial fruit trees depends on internal and environmental signals such as cold accumulation and photoperiod. Previous investigations have noted the participation of epigenetic mechanisms in the control of this physiological process. We examined whether epigenetic modifications were modulated in MADS-box genes, potential candidates for the regulation of bud dormancy and flowering in sweet cherry (Prunus avium L.). We identified and cloned two MADS-box genes homologous to the already-characterized dormancy regulators DORMANCY-ASSOCIATED MADS-box (DAM3 and DAM5) from Prunus persica (L.) Batsch. Bisulfite sequencing of the identified genes (PavMADS1 and PavMADS2), Methylated DNA Immunoprecipitation and small RNA deep sequencing were performed to analyze the presence of DNA methylations that could be guided by non-coding RNAs in the floral buds exposed to differential chilling hours. The results obtained reveal an increase in the level of DNA methylation and abundance of matching small interference RNAs (siRNAs) in the promoter of PavMADS1 when the chilling requirement is complete. For the first intron and 5' UTR of PavMADS1, de novo DNA methylation could be associated with the increase in the abundance of 24-nt siRNA matching the promoter area. Also, in the second large intron of PavMADS1, maintenance DNA methylation in all cytosine contexts is associated with the presence of homologous siRNAs in that zone. For PavMADS2, only maintenance methylation was present in the CG context, and no matching siRNAs were detected. Silencing of PavMADS1 and PavMADS2 coincided with an increase in Flowering Locus T expression during dormancy. In conclusion, DNA methylations and siRNAs appear to be involved in the silencing of PavMADS1 during cold accumulation and dormancy release in sweet cherry. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Radiographic measurement reliability of lumbar lordosis in ankylosing spondylitis.

PubMed

Lee, Jung Sub; Goh, Tae Sik; Park, Shi Hwan; Lee, Hong Seok; Suh, Kuen Tak

2013-04-01

Intraobserver and interobserver reliabilities of the several different methods to measure lumbar lordosis have been reported. However, it has not been studied sofar in patients with ankylosing spondylitis (AS). We evaluated the inter and intraobserver reliabilities of six specific measures of global lumbar lordosis in patients with AS. Ninety-one consecutive patients with AS who met the most recently modified New York criteria were enrolled and underwent anteroposterior and lateral radiographs of whole spine. The radiographs were divided into non-ankylosis (no bony bridge in the lumbar spine), incomplete ankylosis (lumbar spines were partially connected by bony bridge) and complete ankylosis groups to evaluate the reliability of the Cobb L1-S1, Cobb L1-L5, centroid, posterior tangent L1-S1, posterior tangent L1-L5, and TRALL methods. The radiographs were composed of 39 non-ankylosis, 27 incomplete ankylosis and 25 complete ankylosis. Intra- and inter-class correlation coefficients (ICCs) of all six methods were generally high. The ICCs were all ≥0.77 (excellent) for the six radiographic methods in the combined group. However, a comparison of the ICCs, 95 % confidence intervals and mean absolute difference (MAD) between groups with varying degrees of ankylosis showed that the reliability of the lordosis measurements decreased in proportion to the severity of ankylosis. The Cobb L1-S1, Cobb L1-L5 and posterior tangent L1-S1 method demonstrated higher ICCs for both inter and intraobserver comparisons and the other methods showed lower ICCs in all groups. The intraobserver MAD was similar in the Cobb L1-S1 and Cobb L1-L5 (2.7°-4.3°), but the other methods showed higher intraobserver MAD. Interobserver MAD of Cobb L1-L5 only showed low in all group. These results are the first to provide a reliability analysis of different global lumbar lordosis measurement methods in AS. The findings in this study demonstrated that the Cobb L1-L5 method is reliable for measuring the global lumbar lordosis in AS.

A soybean MADS-box protein modulates floral organ numbers, petal identity and sterility

PubMed Central

2014-01-01

Background The MADS-box transcription factors play fundamental roles in reproductive developmental control. Although the roles of many plant MADS-box proteins have been extensively studied, there are almost no functional studies of them in soybean, an important protein and oil crop in the world. In addition, the MADS-box protein orthologs may have species-specific functions. Controlling male fertility is an important goal in plant hybrid breeding but is difficult in some crops like soybean. The morphological structure of soybean flowers prevents the cross-pollination. Understanding the molecular mechanisms for floral development will aid in engineering new sterile materials that could be applied in hybrid breeding programs in soybean. Result Through microarray analysis, a flower-enriched gene in soybean was selected and designated as GmMADS28. GmMADS28 belongs to AGL9/SEP subfamily of MADS-box proteins, localized in nucleus and showed specific expression patterns in floral meristems as well as stamen and petal primordia. Expression of GmMADS28 in the stamens and petals of a soybean mutant NJS-10Hfs whose stamens are converted into petals was higher than in those of wild-type plants. Constitutive expression of GmMADS28 in tobacco promoted early flowering and converted stamens and sepals to petals. Interestingly, transgenic plants increased the numbers of sepal, petal and stamen from five to six and exhibited male sterility due to the shortened and curly filaments and the failure of pollen release from the anthers. The ectopic expression of GmMADS28 was found to be sufficient to activate expression of tobacco homologs of SOC1, LEAFY, AGL8/FUL, and DEF. In addition, we observed the interactions of GmMADS28 with soybean homologs of SOC1, AP1, and AGL8/FUL proteins. Conclusion In this study, we observed the roles of GmMADS28 in the regulation of floral organ number and petal identity. Compared to other plant AGL9/SEP proteins, GmMADS28 specifically regulates floral organ number, filament length and pollen release. The sterility caused by the ectopic expression of GmMADS28 offers a promising way to genetically produce new sterile material that could potentially be applied in the hybrid breeding of crops like soybean. PMID:24693922

A soybean MADS-box protein modulates floral organ numbers, petal identity and sterility.

PubMed

Huang, Fang; Xu, Guangli; Chi, Yingjun; Liu, Haicui; Xue, Qian; Zhao, Tuanjie; Gai, Junyi; Yu, Deyue

2014-04-02

The MADS-box transcription factors play fundamental roles in reproductive developmental control. Although the roles of many plant MADS-box proteins have been extensively studied, there are almost no functional studies of them in soybean, an important protein and oil crop in the world. In addition, the MADS-box protein orthologs may have species-specific functions. Controlling male fertility is an important goal in plant hybrid breeding but is difficult in some crops like soybean. The morphological structure of soybean flowers prevents the cross-pollination. Understanding the molecular mechanisms for floral development will aid in engineering new sterile materials that could be applied in hybrid breeding programs in soybean. Through microarray analysis, a flower-enriched gene in soybean was selected and designated as GmMADS28. GmMADS28 belongs to AGL9/SEP subfamily of MADS-box proteins, localized in nucleus and showed specific expression patterns in floral meristems as well as stamen and petal primordia. Expression of GmMADS28 in the stamens and petals of a soybean mutant NJS-10Hfs whose stamens are converted into petals was higher than in those of wild-type plants. Constitutive expression of GmMADS28 in tobacco promoted early flowering and converted stamens and sepals to petals. Interestingly, transgenic plants increased the numbers of sepal, petal and stamen from five to six and exhibited male sterility due to the shortened and curly filaments and the failure of pollen release from the anthers. The ectopic expression of GmMADS28 was found to be sufficient to activate expression of tobacco homologs of SOC1, LEAFY, AGL8/FUL, and DEF. In addition, we observed the interactions of GmMADS28 with soybean homologs of SOC1, AP1, and AGL8/FUL proteins. In this study, we observed the roles of GmMADS28 in the regulation of floral organ number and petal identity. Compared to other plant AGL9/SEP proteins, GmMADS28 specifically regulates floral organ number, filament length and pollen release. The sterility caused by the ectopic expression of GmMADS28 offers a promising way to genetically produce new sterile material that could potentially be applied in the hybrid breeding of crops like soybean.

Genome-wide identification and analysis of the MADS-box gene family in bread wheat (Triticum aestivum L.)

PubMed Central

Yang, Congcong; Ding, Puyang; Liu, Yaxi; Qiao, Linyi; Chang, Zhijian; Geng, Hongwei; Wang, Penghao; Jiang, Qiantao; Wang, Jirui; Chen, Guoyue; Wei, Yuming; Zheng, Youliang; Lan, Xiujin

2017-01-01

The MADS-box genes encode transcription factors with key roles in plant growth and development. A comprehensive analysis of the MADS-box gene family in bread wheat (Triticum aestivum) has not yet been conducted, and our understanding of their roles in stress is rather limited. Here, we report the identification and characterization of the MADS-box gene family in wheat. A total of 180 MADS-box genes classified as 32 Mα, 5 Mγ, 5 Mδ, and 138 MIKC types were identified. Evolutionary analysis of the orthologs among T. urartu, Aegilops tauschii and wheat as well as homeologous sequences analysis among the three sub-genomes in wheat revealed that gene loss and chromosomal rearrangements occurred during and/or after the origin of bread wheat. Forty wheat MADS-box genes that were expressed throughout the investigated tissues and development stages were identified. The genes that were regulated in response to both abiotic stresses (i.e., phosphorus deficiency, drought, heat, and combined drought and heat) and biotic stresses (i.e., Fusarium graminearum, Septoria tritici, stripe rust and powdery mildew) were detected as well. A few notable MADS-box genes were specifically expressed in a single tissue and those showed relatively higher expression differences between the stress and control treatment. The expression patterns of considerable MADS-box genes differed from those of their orthologs in Brachypodium, rice, and Arabidopsis. Collectively, the present study provides new insights into the possible roles of MADS-box genes in response to stresses and will be valuable for further functional studies of important candidate MADS-box genes. PMID:28742823

Genome-wide identification and analysis of the MADS-box gene family in bread wheat (Triticum aestivum L.).

PubMed

Ma, Jian; Yang, Yujie; Luo, Wei; Yang, Congcong; Ding, Puyang; Liu, Yaxi; Qiao, Linyi; Chang, Zhijian; Geng, Hongwei; Wang, Penghao; Jiang, Qiantao; Wang, Jirui; Chen, Guoyue; Wei, Yuming; Zheng, Youliang; Lan, Xiujin

2017-01-01

The MADS-box genes encode transcription factors with key roles in plant growth and development. A comprehensive analysis of the MADS-box gene family in bread wheat (Triticum aestivum) has not yet been conducted, and our understanding of their roles in stress is rather limited. Here, we report the identification and characterization of the MADS-box gene family in wheat. A total of 180 MADS-box genes classified as 32 Mα, 5 Mγ, 5 Mδ, and 138 MIKC types were identified. Evolutionary analysis of the orthologs among T. urartu, Aegilops tauschii and wheat as well as homeologous sequences analysis among the three sub-genomes in wheat revealed that gene loss and chromosomal rearrangements occurred during and/or after the origin of bread wheat. Forty wheat MADS-box genes that were expressed throughout the investigated tissues and development stages were identified. The genes that were regulated in response to both abiotic stresses (i.e., phosphorus deficiency, drought, heat, and combined drought and heat) and biotic stresses (i.e., Fusarium graminearum, Septoria tritici, stripe rust and powdery mildew) were detected as well. A few notable MADS-box genes were specifically expressed in a single tissue and those showed relatively higher expression differences between the stress and control treatment. The expression patterns of considerable MADS-box genes differed from those of their orthologs in Brachypodium, rice, and Arabidopsis. Collectively, the present study provides new insights into the possible roles of MADS-box genes in response to stresses and will be valuable for further functional studies of important candidate MADS-box genes.

OsMADS26 Negatively Regulates Resistance to Pathogens and Drought Tolerance in Rice1[OPEN

PubMed Central

Khong, Giang Ngan; Richaud, Frédérique; Parizot, Boris; Mai, Chung Duc; Bès, Martine; Bourrié, Isabelle; Meynard, Donaldo; Beeckman, Tom; Selvaraj, Michael Gomez; Manabu, Ishitani; Brugidou, Christophe; Nang Do, Vinh; Guiderdoni, Emmanuel; Morel, Jean-Benoit; Gantet, Pascal

2015-01-01

Functional analyses of MADS-box transcription factors in plants have unraveled their role in major developmental programs (e.g. flowering and floral organ identity) as well as stress-related developmental processes, such as abscission, fruit ripening, and senescence. Overexpression of the rice (Oryza sativa) MADS26 gene in rice has revealed a possible function related to stress response. Here, we show that OsMADS26-down-regulated plants exhibit enhanced resistance against two major rice pathogens: Magnaporthe oryzae and Xanthomonas oryzae. Despite this enhanced resistance to biotic stresses, OsMADS26-down-regulated plants also displayed enhanced tolerance to water deficit. These phenotypes were observed in both controlled and field conditions. Interestingly, alteration of OsMADS26 expression does not have a strong impact on plant development. Gene expression profiling revealed that a majority of genes misregulated in overexpresser and down-regulated OsMADS26 lines compared with control plants are associated to biotic or abiotic stress response. Altogether, our data indicate that OsMADS26 acts as an upstream regulator of stress-associated genes and thereby, a hub to modulate the response to various stresses in the rice plant. PMID:26424158

Mad-X a worthy successor for MAD8?

NASA Astrophysics Data System (ADS)

Schmidt, F.

2006-03-01

MAD-X is the successor at CERN to MAD8, a program for accelerator design and simulation with a long history. We had to give up on MAD8 since the code had evolved in such a way that the maintenance and upgrades had become increasingly difficult. In particular, the memory management with the Zebra banks seemed outdated. MAD-X was first released in June, 2002. It offers most of the MAD8 functionality, with some additions, corrections, and extensions. The most important of these extensions is the interface to PTC, the Polymorphic Tracking Code by E. Forest. The most relevant new features of MAD-X are: languages: C, Fortran77, and Fortran90; dynamic memory allocation: in the core program written in C; strictly modular organization, modified and extended input language; symplectic and arbitrary exact description of all elements via PTC; Taylor Maps and Normal Form techniques using PTC. It is also important to note that we have adopted a new style for program development and maintenance that relies heavily on active maintenance of modules by the users themselves. Proposals for collaboration as with KEK, Japan and GSI, Germany are therefore very welcome.

Fluence-field modulated x-ray CT using multiple aperture devices

NASA Astrophysics Data System (ADS)

Stayman, J. Webster; Mathews, Aswin; Zbijewski, Wojciech; Gang, Grace; Siewerdsen, Jeffrey; Kawamoto, Satomi; Blevis, Ira; Levinson, Reuven

2016-03-01

We introduce a novel strategy for fluence field modulation (FFM) in x-ray CT using multiple aperture devices (MADs). MAD filters permit FFM by blocking or transmitting the x-ray beam on a fine (0.1-1 mm) scale. The filters have a number of potential advantages over other beam modulation strategies including the potential for a highly compact design, modest actuation speed and acceleration requirements, and spectrally neutral filtration due to their essentially binary action. In this work, we present the underlying MAD filtration concept including a design process to achieve a specific class of FFM patterns. A set of MAD filters is fabricated using a tungsten laser sintering process and integrated into an x-ray CT test bench. A characterization of the MAD filters is conducted and compared to traditional attenuating bowtie filters and the ability to flatten the fluence profile for a 32 cm acrylic phantom is demonstrated. MAD-filtered tomographic data was acquired on the CT test bench and reconstructed without artifacts associated with the MAD filter. These initial studies suggest that MAD-based FFM is appropriate for integration in clinical CT system to create patient-specific fluence field profile and reduce radiation exposures.

Interpreting MAD within multiple accretion regimes

NASA Astrophysics Data System (ADS)

Mocz, Philip; Guo, Xinyi

2015-02-01

General relativistic magnetohydrodynamic (GRMHD) simulations of accreting black holes in the radiatively inefficient regime show that systems with sufficient magnetic poloidal flux become magnetically arrested disc (MAD) systems, with a well-defined relationship between the magnetic flux and the mass accretion rate. Recently, Zamaninasab et al. report that the jet magnetic flux and accretion disc luminosity are tightly correlated over 7 orders of magnitude for a sample of 76 radio-loud active galaxies, concluding that the data are explained by the MAD mode of accretion. Their analysis assumes radiatively efficient accretion, and their sample consists primarily of radiatively efficient sources, while GRMHD simulations of MAD thus far have been carried out in the radiatively inefficient regime. We propose a model to interpret MAD systems in the context of multiple accretion regimes, and apply it to the sample in Zamaninasab et al., along with additional radiatively inefficient sources from archival data. We show that most of the radiatively inefficient radio-loud galaxies are consistent with being MAD systems. Assuming the MAD relationship found in radiatively inefficient simulations holds at other accretion regimes, a significant fraction of our sample can be candidates for MAD systems. Future GRMHD simulations have yet to verify the validity of this assumption.

Superoxide reductase from the syphilis spirochete Treponema pallidum: crystallization and structure determination using soft X-rays

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

Santos-Silva, Teresa; Trincão, José; Carvalho, Ana L.

2005-11-01

Superoxide reductase is a non-haem iron-containing protein involved in resistance to oxidative stress. The oxidized form of the protein has been crystallized and its three-dimensional structure solved. A highly redundant X-ray diffraction data set was collected on a rotating-anode generator using Cu Kα X-ray radiation. Four Fe atoms were located in the asymmetric unit corresponding to four protein molecules arranged as a dimer of homodimers. Superoxide reductase is a 14 kDa metalloprotein containing a catalytic non-haem iron centre [Fe(His){sub 4}Cys]. It is involved in defence mechanisms against oxygen toxicity, scavenging superoxide radicals from the cell. The oxidized form of Treponemamore » pallidum superoxide reductase was crystallized in the presence of polyethylene glycol and magnesium chloride. Two crystal forms were obtained depending on the oxidizing agents used after purification: crystals grown in the presence of K{sub 3}Fe(CN){sub 6} belonged to space group P2{sub 1} (unit-cell parameters a = 60.3, b = 59.9, c = 64.8 Å, β = 106.9°) and diffracted beyond 1.60 Å resolution, while crystals grown in the presence of Na{sub 2}IrCl{sub 6} belonged to space group C2 (a = 119.4, b = 60.1, c = 65.6 Å, β = 104.9°) and diffracted beyond 1.55 Å. A highly redundant X-ray diffraction data set from the C2 crystal form collected on a copper rotating-anode generator (λ = 1.542 Å) clearly defined the positions of the four Fe atoms present in the asymmetric unit by SAD methods. A MAD experiment at the iron absorption edge confirmed the positions of the previously determined iron sites and provided better phases for model building and refinement. Molecular replacement using the P2{sub 1} data set was successful using a preliminary trace as a search model. A similar arrangement of the four protein molecules could be observed.« less

Design of dual multiple aperture devices for dynamical fluence field modulated CT.

PubMed

Mathews, Aswin John; Tilley, Steven; Gang, Grace; Kawamoto, Satomi; Zbijewski, Wojciech; Siewerdsen, Jeffrey H; Levinson, Reuven; Webster Stayman, J

2016-07-01

A Multiple Aperture Device (MAD) is a novel x-ray beam modulator that uses binary filtration on a fine scale to spatially modulate an x-ray beam. Using two MADs in series enables a large variety of fluence profiles by shifting the MADS relative to each other. This work details the design and control of dual MADs for a specific class of desired fluence patterns. Specifically, models of MAD operation are integrated into a best fit objective followed by CMA-ES optimization. To illustrate this framework we demonstrate the design process for an abdominal phantom with the goal of uniform detected signal. Achievable fluence profiles show good agreement with target fluence profiles, and the ability to flatten projections when a phantom is scanned is demonstrated. Simulated data reconstruction using traditional tube current modulation (TCM) and MAD filtering with TCM are investigated with the dual MAD system demonstrating more uniformity in noise and illustrating the potential for dose reduction under a maximum noise level constraint.

78 FR 35930 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

... Peachtree Street NE., Atlanta, Georgia 30309: 1. Charles P. Stephens, Atlanta, Georgia, individually and as trustee of MAD Trust for S.D. Stephens, SDT U/A 12-23-92 trust, MAD GST for CA Stephens trust, and MAD GST for SR Stephens trust; Sandra D. Stephens, Atlanta, Georgia, individually and as trustee of MAD Trust...

Functional characterization of AGAMOUS-subfamily members from cotton during reproductive development and in response to plant hormones.

PubMed

de Moura, Stéfanie Menezes; Artico, Sinara; Lima, Cássio; Nardeli, Sarah Muniz; Berbel, Ana; Oliveira-Neto, Osmundo Brilhante; Grossi-de-Sá, Maria Fátima; Ferrándiz, Cristina; Madueño, Francisco; Alves-Ferreira, Márcio

2017-03-01

Expression analysis of the AG -subfamily members from G. hirsutum during flower and fruit development. Reproductive development in cotton, including the fruit and fiber formation, is a complex process; it involves the coordinated action of gene expression regulators, and it is highly influenced by plant hormones. Several studies have reported the identification and expression of the transcription factor family MADS-box members in cotton ovules and fibers; however, their roles are still elusive during the reproductive development in cotton. In this study, we evaluated the expression profiles of five MADS-box genes (GhMADS3, GhMADS4, GhMADS5, GhMADS6 and GhMADS7) belonging to the AGAMOUS-subfamily in Gossypium hirsutum. Phylogenetic and protein sequence analyses were performed using diploid (G. arboreum, G. raimondii) and tetraploid (G. barbadense, G. hirsutum) cotton genomes, as well as the AG-subfamily members from Arabidopsis thaliana, Petunia hybrida and Antirrhinum majus. qPCR analysis showed that the AG-subfamily genes had high expression during flower and fruit development in G. hirsutum. In situ hybridization analysis also substantiates the involvement of AG-subfamily members on reproductive tissues of G. hirsutum, including ovule and ovary. The effect of plant hormones on AG-subfamily genes expression was verified in cotton fruits treated with gibberellin, auxin and brassinosteroid. All the genes were significantly regulated in response to auxin, whereas only GhMADS3, GhMADS4 and GhMADS7 genes were also regulated by brassinosteroid treatment. In addition, we have investigated the GhMADS3 and GhMADS4 overexpression effects in Arabidopsis plants. Interestingly, the transgenic plants from both cotton AG-like genes in Arabidopsis significantly altered the fruit size compared to the control plants. This alteration suggests that cotton AG-like genes might act regulating fruit formation. Our results demonstrate that members of the AG-subfamily in G. hirsutum present a conserved expression profile during flower development, but also demonstrate their expression during fruit development and in response to phytohormones.

Identification and Characterization of the MADS-Box Genes and Their Contribution to Flower Organ in Carnation (Dianthus caryophyllus L.)

PubMed Central

Zhang, Xiaoni; Wang, Qijian; Yang, Shaozong; Lin, Shengnan; Bao, Manzhu; Wu, Quanshu; Wang, Caiyun; Fu, Xiaopeng

2018-01-01

Dianthus is a large genus containing many species with high ornamental economic value. Extensive breeding strategies permitted an exploration of an improvement in the quality of cultivated carnation, particularly in flowers. However, little is known on the molecular mechanisms of flower development in carnation. Here, we report the identification and description of MADS-box genes in carnation (DcaMADS) with a focus on those involved in flower development and organ identity determination. In this study, 39 MADS-box genes were identified from the carnation genome and transcriptome by the phylogenetic analysis. These genes were categorized into four subgroups (30 MIKCc, two MIKC*, two Mα, and five Mγ). The MADS-box domain, gene structure, and conserved motif compositions of the carnation MADS genes were analysed. Meanwhile, the expression of DcaMADS genes were significantly different in stems, leaves, and flower buds. Further studies were carried out for exploring the expression of DcaMADS genes in individual flower organs, and some crucial DcaMADS genes correlated with their putative function were validated. Finally, a new expression pattern of DcaMADS genes in flower organs of carnation was provided: sepal (three class E genes and two class A genes), petal (two class B genes, two class E genes, and one SHORT VEGETATIVE PHASE (SVP)), stamen (two class B genes, two class E genes, and two class C), styles (two class E genes and two class C), and ovary (two class E genes, two class C, one AGAMOUS-LIKE 6 (AGL6), one SEEDSTICK (STK), one B sister, one SVP, and one Mα). This result proposes a model in floral organ identity of carnation and it may be helpful to further explore the molecular mechanism of flower organ identity in carnation. PMID:29617274

Identification and Characterization of the MADS-Box Genes and Their Contribution to Flower Organ in Carnation (Dianthus caryophyllus L.).

PubMed

Zhang, Xiaoni; Wang, Qijian; Yang, Shaozong; Lin, Shengnan; Bao, Manzhu; Bendahmane, Mohammed; Wu, Quanshu; Wang, Caiyun; Fu, Xiaopeng

2018-04-04

Dianthus is a large genus containing many species with high ornamental economic value. Extensive breeding strategies permitted an exploration of an improvement in the quality of cultivated carnation, particularly in flowers. However, little is known on the molecular mechanisms of flower development in carnation. Here, we report the identification and description of MADS-box genes in carnation ( DcaMADS ) with a focus on those involved in flower development and organ identity determination. In this study, 39 MADS-box genes were identified from the carnation genome and transcriptome by the phylogenetic analysis. These genes were categorized into four subgroups (30 MIKC c , two MIKC*, two Mα, and five Mγ). The MADS-box domain, gene structure, and conserved motif compositions of the carnation MADS genes were analysed. Meanwhile, the expression of DcaMADS genes were significantly different in stems, leaves, and flower buds. Further studies were carried out for exploring the expression of DcaMADS genes in individual flower organs, and some crucial DcaMADS genes correlated with their putative function were validated. Finally, a new expression pattern of DcaMADS genes in flower organs of carnation was provided: sepal (three class E genes and two class A genes), petal (two class B genes, two class E genes, and one SHORT VEGETATIVE PHASE ( SVP )), stamen (two class B genes, two class E genes, and two class C), styles (two class E genes and two class C), and ovary (two class E genes, two class C, one AGAMOUS-LIKE 6 ( AGL6 ), one SEEDSTICK ( STK ), one B sister , one SVP , and one Mα ). This result proposes a model in floral organ identity of carnation and it may be helpful to further explore the molecular mechanism of flower organ identity in carnation.

Mads.jl

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

Vesselinov, Velimir; O'Malley, Daniel; Lin, Youzuo

2016-07-01

Mads.jl (Model analysis and decision support in Julia) is a code that streamlines the process of using data and models for analysis and decision support. It is based on another open-source code developed at LANL and written in C/C++ (MADS; http://mads.lanl.gov; LA-CC-11- 035). Mads.jl can work with external models of arbitrary complexity as well as built-in models of flow and transport in porous media. It enables a number of data- and model-based analyses including model calibration, sensitivity analysis, uncertainty quantification, and decision analysis. The code also can use a series of alternative adaptive computational techniques for Bayesian sampling, Monte Carlo,more » and Bayesian Information-Gap Decision Theory. The code is implemented in the Julia programming language, and has high-performance (parallel) and memory management capabilities. The code uses a series of third party modules developed by others. The code development will also include contributions to the existing third party modules written in Julia; this contributions will be important for the efficient implementation of the algorithm used by Mads.jl. The code also uses a series of LANL developed modules that are developed by Dan O'Malley; these modules will be also a part of the Mads.jl release. Mads.jl will be released under GPL V3 license. The code will be distributed as a Git repo at gitlab.com and github.com. Mads.jl manual and documentation will be posted at madsjulia.lanl.gov.« less

Structure of the catalytic domain of Plasmodium falciparum ARF GTPase-activating protein (ARFGAP)

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

Cook, William J.; Senkovich, Olga; Chattopadhyay, Debasish

2012-03-26

The crystal structure of the catalytic domain of the ADP ribosylation factor GTPase-activating protein (ARFGAP) from Plasmodium falciparum has been determined and refined to 2.4 {angstrom} resolution. Multiwavelength anomalous diffraction (MAD) data were collected utilizing the Zn{sup 2+} ion bound at the zinc-finger domain and were used to solve the structure. The overall structure of the domain is similar to those of mammalian ARFGAPs. However, several amino-acid residues in the area where GAP interacts with ARF1 differ in P. falciparum ARFGAP. Moreover, a number of residues that form the dimer interface in the crystal structure are unique in P. falciparummore » ARFGAP.« less

Cloning of a MADS box gene (GhMADS3) from cotton and analysis of its homeotic role in transgenic tobacco.

PubMed

Guo, Yulong; Zhu, Qinlong; Zheng, Shangyong; Li, Mingyang

2007-06-01

A MADS box gene (GhMADS3) was cloned from cotton (Gossypium hirsutum L.) based on EST sequences. The predicted protein sequence of GhMADS3 showed 85%, 73%, and 62% identity with Theobroma cacao TcAG, Antirrhinum majus FAR, and Arabidopsis thaliana AG, respectively, and was grouped with AG homologues when the full length sequences excluding N-extensions were compared. GhMADS3 expressed in the wild type cotton flower primarily in stamens and carpels, which was comparable to AG in Arabidopsis. However, it was not expressed in floral buds of a homeotic cotton variant chv1. Ectopic expression of GhMADS3 in tobacco (Nicotiana tabacum L.) resulted in flowers with sepal-to-carpel and petal-to-stamen transformation. The carpelloid first whorl organs, with stigmatic tissue on their upper edges, had a white appearance when compared with the dark green color of the wild type sepals. At times, long filaments were observed at the fusion site of the first carpelloid oranges. The second whorl organs in staminoid were usually smaller than the wild type and the color was changed from pink to white. These results suggest that GhMADS3 has a homeotic role in flower development.

The AGL6-like gene OsMADS6 regulates floral organ and meristem identities in rice.

PubMed

Li, Haifeng; Liang, Wanqi; Jia, Ruidong; Yin, Changsong; Zong, Jie; Kong, Hongzhi; Zhang, Dabing

2010-03-01

Although AGAMOUS-LIKE6 (AGL6) MADS-box genes are ancient with wide distributions in gymnosperms and angiosperms, their functions remain poorly understood. Here, we show the biological role of the AGL6-like gene, OsMADS6, in specifying floral organ and meristem identities in rice (Oryza sativa L.). OsMADS6 was strongly expressed in the floral meristem at early stages. Subsequently, OsMADS6 transcripts were mainly detectable in paleas, lodicules, carpels and the integument of ovule, as well as in the receptacle. Compared to wild type plants, osmads6 mutants displayed altered palea identity, extra glume-like or mosaic organs, abnormal carpel development and loss of floral meristem determinacy. Strikingly, mutation of a SEPALLATA (SEP)-like gene, OsMADS1 (LHS1), enhanced the defect of osmads6 flowers, and no inner floral organs or glume-like structures were observed in whorls 2 and 3 of osmads1-z osmads6-1 flowers. Furthermore, the osmads1-z osmads6-1 double mutants developed severely indeterminate floral meristems. Our finding, therefore, suggests that the ancient OsMADS6 gene is able to specify "floral state" by determining floral organ and meristem identities in monocot crop rice together with OsMADS1.

Isolation and characterization of a SEPALLATA-like gene, ZjMADS1, from marine angiosperm Zostera japonica.

PubMed

Kakinuma, Makoto; Inoue, Miho; Morita, Teruwo; Tominaga, Hiroshi; Maegawa, Miyuki; Coury, Daniel A; Amano, Hideomi

2012-05-01

In flowering plants, floral homeotic MADS-box genes, which constitute a large multigene family, play important roles in the specification of floral organs as defined by the ABCDE model. In this study, a MADS-box gene, ZjMADS1, was isolated and characterized from the marine angiosperm Zostera japonica. The predicted length of the ZjMADS1 protein was 246 amino acids (AA), and the AA sequence was most similar to those of the SEPALLATA (SEP) subfamily, corresponding to E-function genes. Southern blot analysis suggested the presence of two SEP3-like genes in the Z. japonica genome. ZjMADS1 mRNA levels were extremely high in the spadices, regardless of the developmental stage, compared to other organs from the reproductive and vegetative shoots. These results suggest that the ZjMADS1 gene may be involved in spadix development in Z. japonica and act as an E-function gene in floral organ development in marine angiosperms. Copyright © 2011 Elsevier Ltd. All rights reserved.

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling.

PubMed

Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

2017-01-10

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1-Bub3 and BubR1-Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1-Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/C Cdc20 ) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1-Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment.

Three-dimensional Bayesian geostatistical aquifer characterization at the Hanford 300 Area using tracer test data

NASA Astrophysics Data System (ADS)

Chen, Xingyuan; Murakami, Haruko; Hahn, Melanie S.; Hammond, Glenn E.; Rockhold, Mark L.; Zachara, John M.; Rubin, Yoram

2012-06-01

Tracer tests performed under natural or forced gradient flow conditions can provide useful information for characterizing subsurface properties, through monitoring, modeling, and interpretation of the tracer plume migration in an aquifer. Nonreactive tracer experiments were conducted at the Hanford 300 Area, along with constant-rate injection tests and electromagnetic borehole flowmeter tests. A Bayesian data assimilation technique, the method of anchored distributions (MAD) (Rubin et al., 2010), was applied to assimilate the experimental tracer test data with the other types of data and to infer the three-dimensional heterogeneous structure of the hydraulic conductivity in the saturated zone of the Hanford formation.In this study, the Bayesian prior information on the underlying random hydraulic conductivity field was obtained from previous field characterization efforts using constant-rate injection and borehole flowmeter test data. The posterior distribution of the conductivity field was obtained by further conditioning the field on the temporal moments of tracer breakthrough curves at various observation wells. MAD was implemented with the massively parallel three-dimensional flow and transport code PFLOTRAN to cope with the highly transient flow boundary conditions at the site and to meet the computational demands of MAD. A synthetic study proved that the proposed method could effectively invert tracer test data to capture the essential spatial heterogeneity of the three-dimensional hydraulic conductivity field. Application of MAD to actual field tracer data at the Hanford 300 Area demonstrates that inverting for spatial heterogeneity of hydraulic conductivity under transient flow conditions is challenging and more work is needed.

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

O'Malley, Daniel; Vesselinov, Velimir V.

MADSpython (Model analysis and decision support tools in Python) is a code in Python that streamlines the process of using data and models for analysis and decision support using the code MADS. MADS is open-source code developed at LANL and written in C/C++ (MADS; http://mads.lanl.gov; LA-CC-11-035). MADS can work with external models of arbitrary complexity as well as built-in models of flow and transport in porous media. The Python scripts in MADSpython facilitate the generation of input and output file needed by MADS as wells as the external simulators which include FEHM and PFLOTRAN. MADSpython enables a number of data-more » and model-based analyses including model calibration, sensitivity analysis, uncertainty quantification, and decision analysis. MADSpython will be released under GPL V3 license. MADSpython will be distributed as a Git repo at gitlab.com and github.com. MADSpython manual and documentation will be posted at http://madspy.lanl.gov.« less

Is anyone really M.A.D.?: the occurrence and course of mixed anxiety-depressive disorder in a sample of primary care patients.

PubMed

Weisberg, Risa B; Maki, Kristin M; Culpepper, Larry; Keller, Martin B

2005-04-01

We examined the occurrence and 1-year course of mixed anxiety-depressive disorder (MAD) in a sample of primary care patients. Participants are part of the Primary Care Anxiety Project, a naturalistic, longitudinal study of anxiety disorders in primary care. Participants completed a questionnaire screening for anxiety symptoms. Those screening positive were invited for an interview to diagnose MAD and DSM-IV Axis I disorders. Participants were then interviewed at 6 and 12 months postintake. Of 1634 participants completing an intake interview, four participants (0.2%) met complete DSM-IV MAD criteria. The adjusted probability of remitting from MAD in 1 year was 80%. Although this was not a prevalence study, results indicate a very low occurrence of MAD across 15 primary care settings. Further, they indicate that this diagnosis may not be stable across time and raise doubts about its utility.

The study of two barley Type I-like MADS-box genes as potential targets of epigenetic regulation during seed development

PubMed Central

2012-01-01

Background MADS-box genes constitute a large family of transcription factors functioning as key regulators of many processes during plant vegetative and reproductive development. Type II MADS-box genes have been intensively investigated and are mostly involved in vegetative and flowering development. A growing number of studies of Type I MADS-box genes in Arabidopsis, have assigned crucial roles for these genes in gamete and seed development and have demonstrated that a number of Type I MADS-box genes are epigenetically regulated by DNA methylation and histone modifications. However, reports on agronomically important cereals such as barley and wheat are scarce. Results Here we report the identification and characterization of two Type I-like MADS-box genes, from barley (Hordeum vulgare), a monocot cereal crop of high agronomic importance. Protein sequence and phylogenetic analysis showed that the putative proteins are related to Type I MADS-box proteins, and classified them in a distinct cereal clade. Significant differences in gene expression among seed developmental stages and between barley cultivars with varying seed size were revealed for both genes. One of these genes was shown to be induced by the seed development- and stress-related hormones ABA and JA whereas in situ hybridizations localized the other gene to specific endosperm sub-compartments. The genomic organization of the latter has high conservation with the cereal Type I-like MADS-box homologues and the chromosomal position of both genes is close to markers associated with seed quality traits. DNA methylation differences are present in the upstream and downstream regulatory regions of the barley Type I-like MADS-box genes in two different developmental stages and in response to ABA treatment which may be associated with gene expression differences. Conclusions Two barley MADS-box genes were studied that are related to Type I MADS-box genes. Differential expression in different seed developmental stages as well as in barley cultivars with different seed size was evidenced for both genes. The two barley Type I MADS-box genes were found to be induced by ABA and JA. DNA methylation differences in different seed developmental stages and after exogenous application of ABA is suggestive of epigenetic regulation of gene expression. The study of barley Type I-like MADS-box genes extends our investigations of gene regulation during endosperm and seed development in a monocot crop like barley. PMID:22985436

Immediate intraoral adaptation of mandibular advancing appliances of thermoplastic material for the treatment of obstructive sleep apnea.

PubMed

Schönhofer, B; Hochban, W; Vieregge, H J; Brünig, H; Köhler, D

2000-01-01

In the treatment of obstructive sleep apnea (OSA), mandibular advancing devices (MAD) are usually individually fabricated on plaster casts of both jaws from polymethyl-methacrylate. The potential disadvantages of these devices are (1) the costs and (2) the time required to construct the device. In this study, the efficacy and feasibility of a cheap MAD consisting of thermoplastic material (SnorBan((R))), which can be directly moulded intraorally, were evaluated. In a prospective study, the effect of an MAD consisting of thermoplastic material was investigated in 22 consecutive patients with OSA [respiratory disturbance index (RDI) 32.6 +/- 18.4/h]. Polysomnographic sleep was recorded prior to treatment and after 3 months of treatment with the MAD. Three of the 22 patients who did not tolerate the MAD were excluded from the analysis, whereas 11 patients were classified as responders. In the responder group, the mean RDI decreased from 27.6 +/-7.3 to 7.3 +/- 2.9 (p < 0. 01), correspondingly the sleep quality and the Epworth Sleepiness Scale improved (p < 0.05). Eight patients proved to be non-responders without relevant changes for the measured parameters. In 50% (11 of 22) of the patients, the MAD improved the OSA to a clinically relevant degree. In contrast to the majority of established MAD, the MAD investigated is cheap and immediately adaptable and thus a feasible strategy to 'screen' the efficacy of this therapeutic principle. Thus the construction of unnecessary MAD is avoided. Copyright 2000 S. Karger AG, Basel

Changes in ethylene signaling and MADS box gene expression are associated with banana finger drop.

PubMed

Hubert, O; Piral, G; Galas, C; Baurens, F-C; Mbéguié-A-Mbéguié, D

2014-06-01

Banana finger drop was examined in ripening banana harvested at immature (iMG), early (eMG) and late mature green (lMG) stages, with contrasting ripening rates and ethylene sensitivities. Concomitantly, 11 ethylene signal transduction components (ESTC) and 6 MADS box gene expressions were comparatively studied in median (control zone, CZ) and pedicel rupture (drop zone DZ) areas in peel tissue. iMG fruit did not ripen or develop finger drop while eMG and lMG fruits displayed a similar finger drop pattern. Several ESTC and MADS box gene mRNAs were differentially induced in DZ and CZ and sequentially in eMG and lMG fruits. MaESR2, 3 and MaEIL1, MaMADS2 and MaMADS5 had a higher mRNA level in eMG and acted earlier, whereas MaERS1, MaCTR1, MaEIL3/AB266319, MaEIL4/AB266320 and MaEIL5/AB266321, MaMADS4 and to a lesser extent MaMADS2 and 5 acted later in lMG. In this fruit, MaERS1 and 3, MaCTR1, MaEIL3, 4 and MaEIL5/AB266321, and MaMADS4 were enhanced by finger drop, suggesting their specific involvement in this process. MaEIL1, MaMADS1 and 3, induced at comparable levels in DZ and CZ, are probably related to the overall fruit ripening process. These findings led us to consider that developmental cues are the predominant finger drop regulation factor. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Microwave-assisted Derivatization of Fatty Acids for Its Measurement in Milk Using High-Performance Liquid Chromatography.

PubMed

Shrestha, Rojeet; Miura, Yusuke; Hirano, Ken-Ichi; Chen, Zhen; Okabe, Hiroaki; Chiba, Hitoshi; Hui, Shu-Ping

2018-01-01

Fatty acid (FA) profiling of milk has important applications in human health and nutrition. Conventional methods for the saponification and derivatization of FA are time-consuming and laborious. We aimed to develop a simple, rapid, and economical method for the determination of FA in milk. We applied a beneficial approach of microwave-assisted saponification (MAS) of milk fats and microwave-assisted derivatization (MAD) of FA to its hydrazides, integrated with HPLC-based analysis. The optimal conditions for MAS and MAD were determined. Microwave irradiation significantly reduced the sample preparation time from 80 min in the conventional method to less than 3 min. We used three internal standards for the measurement of short-, medium- and long-chain FA. The proposed method showed satisfactory analytical sensitivity, recovery and reproducibility. There was a significant correlation in the milk FA concentrations between the proposed and conventional methods. Being quick, economic, and convenient, the proposed method for the milk FA measurement can be substitute for the convention method.

Crystallization and preliminary X-ray crystallographic analysis of MacA from Actinobacillus actinomycetemcomitans

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

Piao, Shunfu; Xu, Yongbin; Ha, Nam-Chul, E-mail: hnc@pusan.ac.kr

2008-05-01

A periplasmic membrane-fusion protein MacA from Actinobacillus actinomycetemcomitans, an essential component of the multidrug efflux pump in Gram-negative bacteria, was crystallized. Periplasmic membrane-fusion proteins (MFPs) are an essential component of the multidrug efflux pump in Gram-negative bacteria. They play a crucial role in bridging the outer membrane porin TolC and two distinct types of inner membrane transporters. The MFP MacA bridges the inner membrane ABC-type multidrug transporter MacB and the outer membrane porin TolC. MacA from the pathogenic bacterium Actinobacillus actinomycetemcomitans was expressed in Escherichia coli B834 (DE3) and the recombinant protein was purified using Ni–NTA affinity, Q anion-exchange andmore » gel-filtration chromatography. The purified MacA protein was crystallized using the vapour-diffusion method. A MAD diffraction data set was collected to a resolution of 3.0 Å at 100 K. The crystal belongs to space group P622, with unit-cell parameters a = b = 109.2, c = 255.4 Å, α = β = 90, γ = 120°, and contains one molecule in the asymmetric unit.« less

A sequential multi-target Mps1 phosphorylation cascade promotes spindle checkpoint signaling

PubMed Central

Ji, Zhejian; Gao, Haishan; Jia, Luying; Li, Bing; Yu, Hongtao

2017-01-01

The master spindle checkpoint kinase Mps1 senses kinetochore-microtubule attachment and promotes checkpoint signaling to ensure accurate chromosome segregation. The kinetochore scaffold Knl1, when phosphorylated by Mps1, recruits checkpoint complexes Bub1–Bub3 and BubR1–Bub3 to unattached kinetochores. Active checkpoint signaling ultimately enhances the assembly of the mitotic checkpoint complex (MCC) consisting of BubR1–Bub3, Mad2, and Cdc20, which inhibits the anaphase-promoting complex or cyclosome bound to Cdc20 (APC/CCdc20) to delay anaphase onset. Using in vitro reconstitution, we show that Mps1 promotes APC/C inhibition by MCC components through phosphorylating Bub1 and Mad1. Phosphorylated Bub1 binds to Mad1–Mad2. Phosphorylated Mad1 directly interacts with Cdc20. Mutations of Mps1 phosphorylation sites in Bub1 or Mad1 abrogate the spindle checkpoint in human cells. Therefore, Mps1 promotes checkpoint activation through sequentially phosphorylating Knl1, Bub1, and Mad1. This sequential multi-target phosphorylation cascade makes the checkpoint highly responsive to Mps1 and to kinetochore-microtubule attachment. DOI: http://dx.doi.org/10.7554/eLife.22513.001 PMID:28072388

Multiple interactions amongst floral homeotic MADS box proteins.

PubMed Central

Davies, B; Egea-Cortines, M; de Andrade Silva, E; Saedler, H; Sommer, H

1996-01-01

Most known floral homeotic genes belong to the MADS box family and their products act in combination to specify floral organ identity by an unknown mechanism. We have used a yeast two-hybrid system to investigate the network of interactions between the Antirrhinum organ identity gene products. Selective heterodimerization is observed between MADS box factors. Exclusive interactions are detected between two factors, DEFICIENS (DEF) and GLOBOSA (GLO), previously known to heterodimerize and control development of petals and stamens. In contrast, a third factor, PLENA (PLE), which is required for reproductive organ development, can interact with the products of MADS box genes expressed at early, intermediate and late stages. We also demonstrate that heterodimerization of DEF and GLO requires the K box, a domain not found in non-plant MADS box factors, indicating that the plant MADS box factors may have different criteria for interaction. The association of PLENA and the temporally intermediate MADS box factors suggests that part of their function in mediating between the meristem and organ identity genes is accomplished through direct interaction. These data reveal an unexpectedly complex network of interactions between the factors controlling flower development and have implications for the determination of organ identity. Images PMID:8861961

Identifying Outliers of Non-Gaussian Groundwater State Data Based on Ensemble Estimation for Long-Term Trends

NASA Astrophysics Data System (ADS)

Park, E.; Jeong, J.; Choi, J.; Han, W. S.; Yun, S. T.

2016-12-01

Three modified outlier identification methods: the three sigma rule (3s), inter quantile range (IQR) and median absolute deviation (MAD), which take advantage of the ensemble regression method are proposed. For validation purposes, the performance of the methods is compared using simulated and actual groundwater data with a few hypothetical conditions. In the validations using simulated data, all of the proposed methods reasonably identify outliers at a 5% outlier level; whereas, only the IQR method performs well for identifying outliers at a 30% outlier level. When applying the methods to real groundwater data, the outlier identification performance of the IQR method is found to be superior to the other two methods. However, the IQR method is found to have a limitation in the false identification of excessive outliers, which may be supplemented by joint applications with the other methods (i.e., the 3s rule and MAD methods). The proposed methods can be also applied as a potential tool for future anomaly detection by model training based on currently available data.

Kinetochore localized Mad2 and Cdc20 is itself insufficient for triggering the mitotic checkpoint when Mps1 is low in Drosophila melanogaster neuroblasts.

PubMed

Herriott, Ashleigh; Sweeney, Michele; Whitaker, Michael; Taggart, Michael; Huang, Jun-Yong

2012-12-15

The relationships between the kinetochore and checkpoint control remain unresolved. Here, we report the characterization of the in vivo behavior of Cdc20 and Mad2 and the relevant spindle assembly checkpoint (SAC) functions in the neuroblasts of a Drosophila Mps1 weak allele (ald (B4-2) ). ald (B4-2) third instar larvae brain samples contain only around 16% endogenous Mps1 protein, and the SAC function is abolished. However, this does not lead to rapid anaphase onset and mitotic exit, in contrast to the loss of Mad2 alone in a mad2 (EY) mutant. The level of GFP-Cdc20 recruitment to the kinetochore is unaffected in ald (B4-2) neuroblasts, while the level of GFP-Mad2 is reduced to just about 20%. Cdc20 and Mad2 display only monophasic exponential kinetics at the kinetochores. The ald (B4-2) heterozygotes expressed approximately 65% of normal Mps1 protein levels, and this is enough to restore the SAC function. The kinetochore recruitment of GFP-Mad2 in response to SAC activation increases by around 80% in heterozygotes, compared with just about 20% in ald (B4-2) mutant. This suggests a correlation between Mps1 levels and Mad2 kinetochore localization and perhaps the existence of a threshold level at which Mps1 is fully functional. The failure to arrest the mitotic progression in ald (B4-2) neuroblasts in response to colchicine treatment suggests that when Mps1 levels are low, approximately 20% of normal GFP-Mad2, alongside normal levels of GFP-Cdc20 kinetochore recruitments, is insufficient for triggering SAC signal propagation.

Information for People Treated with Human Growth Hormone (Summary)

MedlinePlus

... from pituitary hGH treatment have been found. “Mad Cow” Disease “Mad cow” disease in cattle is the same kind of disease as CJD ... who ate beef from animals infected with mad cow disease got a form of CJD called variant ...

Overexpression of a novel MADS-box gene SlFYFL delays senescence, fruit ripening and abscission in tomato

PubMed Central

Xie, Qiaoli; Hu, Zongli; Zhu, Zhiguo; Dong, Tingting; Zhao, Zhiping; Cui, Baolu; Chen, Guoping

2014-01-01

MADS-domain proteins are important transcription factors involved in many biological processes of plants. In our study, a tomato MADS-box gene, SlFYFL, was isolated. SlFYFL is expressed in all tissues of tomato and significantly higher in mature leave, fruit of different stages, AZ (abscission zone) and sepal. Delayed leaf senescence and fruit ripening, increased storability and longer sepals were observed in 35S:FYFL tomato. The accumulation of carotenoid was reduced, and ethylene content, ethylene biosynthetic and responsive genes were down-regulated in 35S:FYFL fruits. Abscission zone (AZ) did not form normally and abscission zone development related genes were declined in AZs of 35S:FYFL plants. Yeast two-hybrid assay revealed that SlFYFL protein could interact with SlMADS-RIN, SlMADS1 and SlJOINTLESS, respectively. These results suggest that overexpression of SlFYFL regulate fruit ripening and development of AZ via interactions with the ripening and abscission zone-related MADS box proteins. PMID:24621662

Sensitive determination of cholesterol and its metabolic steroid hormones by UHPLC-MS/MS via derivatization coupled with dual ultrasonic-assisted dispersive liquid-liquid microextraction.

PubMed

Zhao, Xian-En; Yan, Ping; Wang, Renjun; Zhu, Shuyun; You, Jinmao; Bai, Yu; Liu, Huwei

2016-08-01

Quantitative analysis of cholesterol and its metabolic steroid hormones plays a vital role in diagnosing endocrine disorders and understanding disease progression, as well as in clinical medicine studies. Because of their extremely low abundance in body fluids, it remains a challenging task to develop a sensitive detection method. A hyphenated technique of dual ultrasonic-assisted dispersive liquid-liquid microextraction (dual-UADLLME) coupled with microwave-assisted derivatization (MAD) was proposed for cleansing, enrichment and sensitivity enhancement. 4'-Carboxy-substituted rosamine (CSR) was synthesized and used as derivatization reagent. An ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was developed for determination of cholesterol and its metabolic steroid hormones in the multiple reaction monitoring mode. Parameters of dual-UADLLME, MAD and UHPLC-MS/MS were all optimized. Satisfactory linearity, recovery, repeatability, accuracy and precision, absence of matrix effect and extremely low limits of detection (LODs, 0.08-0.15 pg mL(-1) ) were achieved. Through the combination of dual-UADLLME and MAD, a determination method for cholesterol and its metabolic steroid hormones in human plasma, serum and urine samples was developed and validated with high sensitivity, selectivity, accuracy and perfect matrix effect results. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Six independent fucose-binding sites in the crystal structure of Aspergillus oryzae lectin

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

Makyio, Hisayoshi; Shimabukuro, Junpei; Suzuki, Tatsuya

The crystal structure of AOL (a fucose-specific lectin of Aspergillus oryzae) has been solved by SAD (single-wavelength anomalous diffraction) and MAD (multi-wavelength anomalous diffraction) phasing of seleno-fucosides. The overall structure is a six-bladed β-propeller similar to that of other fucose-specific lectins. The fucose moieties of the seleno-fucosides are located in six fucose-binding sites. Although the Arg and Glu/Gln residues bound to the fucose moiety are common to all fucose-binding sites, the amino-acid residues involved in fucose binding at each site are not identical. The varying peak heights of the seleniums in the electron density map suggest that each fucose-binding sitemore » has a different carbohydrate binding affinity. - Highlights: • The six-bladed β-propeller structure of AOL was solved by seleno-sugar phasing. • The mode of fucose binding is essentially conserved at all six binding sites. • The seleno-fucosides exhibit slightly different interactions and electron densities. • These findings suggest that the affinity for fucose is not identical at each site.« less

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

Chang, J; Gu, X; Lu, W

Purpose: A novel distance-dose weighting method for label fusion was developed to increase segmentation accuracy in dosimetrically important regions for prostate radiation therapy. Methods: Label fusion as implemented in the original SIMPLE (OS) for multi-atlas segmentation relies iteratively on the majority vote to generate an estimated ground truth and DICE similarity measure to screen candidates. The proposed distance-dose weighting puts more values on dosimetrically important regions when calculating similarity measure. Specifically, we introduced distance-to-dose error (DDE), which converts distance to dosimetric importance, in performance evaluation. The DDE calculates an estimated DE error derived from surface distance differences between the candidatemore » and estimated ground truth label by multiplying a regression coefficient. To determine the coefficient at each simulation point on the rectum, we fitted DE error with respect to simulated voxel shift. The DEs were calculated by the multi-OAR geometry-dosimetry training model previously developed in our research group. Results: For both the OS and the distance-dose weighted SIMPLE (WS) results, the evaluation metrics for twenty patients were calculated using the ground truth segmentation. The mean difference of DICE, Hausdorff distance, and mean absolute distance (MAD) between OS and WS have shown 0, 0.10, and 0.11, respectively. In partial MAD of WS which calculates MAD within a certain PTV expansion voxel distance, the lower MADs were observed at the closer distances from 1 to 8 than those of OS. The DE results showed that the segmentation from WS produced more accurate results than OS. The mean DE error of V75, V70, V65, and V60 were decreased by 1.16%, 1.17%, 1.14%, and 1.12%, respectively. Conclusion: We have demonstrated that the method can increase the segmentation accuracy in rectum regions adjacent to PTV. As a result, segmentation using WS have shown improved dosimetric accuracy than OS. The WS will provide dosimetrically important label selection strategy in multi-atlas segmentation. CPRIT grant RP150485.« less

MADS-box genes in maize: Frequent targets of selection during domestication

USDA-ARS?s Scientific Manuscript database

MADS-box genes encode transcription factors that are key regulators of plant inflorescence and flower development. We examined DNA sequence variation in 32 maize MADS-box genes and 32 random loci from the maize genome and investigated their involvement in maize domestication and improvement. Using n...

Archiving Derrida

ERIC Educational Resources Information Center

Morris, Marla

2003-01-01

Derrida's archive, broadly speaking, is brilliantly mad, for he digs exegetically into the most difficult textual material and combines the most unlikely texts--from Socrates to Freud, from postcards to encyclopedias, from madness(es) to the archive, from primal scenes to death. In this paper, the author would like to do a brief study of the…

Interdisciplinary Critical Inquiry: Teaching about the Social Construction of Madness

ERIC Educational Resources Information Center

Connor-Greene, Patricia A.

2006-01-01

Theories and treatments of mental illness reflect the social, philosophical, and historical context in which they developed. This article describes ways to invite students to grapple with complex questions about "madness" from an interdisciplinary perspective. Looking at the construct of madness through multiple lenses (e.g., literature,…

Casein kinase II is required for the spindle assembly checkpoint by regulating Mad2p in fission yeast

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

Shimada, Midori; Yamamoto, Ayumu; Murakami-Tonami, Yuko

2009-10-23

The spindle checkpoint is a surveillance mechanism that ensures the fidelity of chromosome segregation in mitosis. Here we show that fission yeast casein kinase II (CK2) is required for this checkpoint function. In the CK2 mutants mitosis occurs in the presence of a spindle defect, and the spindle checkpoint protein Mad2p fails to localize to unattached kinetochores. The CK2 mutants are sensitive to the microtubule depolymerising drug thiabendazole, which is counteracted by ectopic expression of mad2{sup +}. The level of Mad2p is low in the CK2 mutants. These results suggest that CK2 has a role in the spindle checkpoint bymore » regulating Mad2p.« less

Comparison of success criteria based on long-term symptoms and new-onset hypertension in mandibular advancement device treatment for obstructive sleep apnoea: observational cohort study.

PubMed

Wee, Jee Hye; Lim, Jae Hyun; Gelera, January E; Rhee, Chae-Seo; Kim, Jeong-Whun

2018-05-08

To identify adequate criteria to determine the success or failure of mandibular advancement device (MAD) treatment for obstructive sleep apnoea (OSA) based on long-term symptoms and new-onset hypertension. Observational cohort study. A tertiary care hospital setting in South Korea. Patients (age >18 years) who were diagnosed with OSA by a polysomnography (PSG) or Watch peripheral arterial tonometry (PAT), and who had been treated with MAD between January 2007 and December 2014 were enrolled. Patients underwent PSG or Watch PAT twice; before and 3 months after the application of MAD. The patients were categorised into success and failure groups using seven different criteria. MAD compliance, witnessed apnoea and snoring, Epworth Sleepiness Scale score and occurrence of new-onset hypertension were surveyed via telephonic interview to determine the criteria that could identify success and failure of MAD. A total of 97 patients were included. The mean follow-up duration was 60.5 months, and the mean apnoea-hypopnoea index (AHI) was 35.5/hour. Two of the seven criteria could significantly differentiate the success and failure groups based on long-term symptoms, including (1) AHI<10/hour with MAD and (2) AHI<10/hour and AHI reduction of >50% with MAD. Kaplan-Meier survival analysis showed that one criterion of AHI<15/hour with MAD could differentiate the success and failure groups based on new-onset hypertension (p=0.035). The receiver operating characteristic curve analysis indicated that the cut-off AHI for new-onset hypertension was 16.8/hour (71.4% sensitivity and 75.0% specificity). Our long-term follow-up survey for symptoms and new-onset hypertension suggested that some of the polysomnographic success criteria, that is, AHI<10/hour with MAD, AHI<10/hour and AHI reduction of >50% with MAD and AHI<15/hour with MAD may be useful in distinguishing the success group from failure one. Further prospective longitudinal studies are warranted to validate these criteria. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Socrates and the Madness of Method

ERIC Educational Resources Information Center

Schneider, Jack

2012-01-01

What do we know about Socrates and the teaching method that, having taken his name, has become widely used from kindergarten through postgraduate seminars? The practitioners employing so-called Socratic methods include vastly different styles, the author says, noting that "we may be mistaking common phrasing for common practice." The differences…

Treatment of obstructive sleep apnoea-hypopnea syndrome by mandible advanced device reduced neuron apoptosis in frontal cortex of rabbits.

PubMed

Lu, Hai-Yan; Wang, Wen; Zhou, Zheng; Liu, Chun-Yan; Liu, Ye; Xiao, Wei; Dong, Fu-Sheng; Wang, Jie

2018-05-25

To investigate effects of mandible advanced device (MAD) therapy for obstructive sleep apnoea-hypopnea syndrome (OSAHS) on the neuron apoptosis and acetylcholine esterase activity in frontal cortex. Thirty male New Zealand white rabbits were randomly divided into three groups (n = 10 in each group): group OSAHS, group MAD, and control group. Hydrophilic polyacrylamide gel was injected into soft palate of the animals to induce OSAHS in group OSAHS and group MAD. The group MAD animals wore MAD to relief the obstructiveness. The control group was not given any treatment. Computed tomography (CT) examination of the upper airway and polysomnography (PSG) recordings were performed in supine position. All rabbits were induced to sleep in a supine position for 4 to 6 hours every day and were observed for consecutive 8 weeks. The frontal cortices of three groups were dissected and the neuron apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry. Acetylcholine esterase (AchE) activity in the frontal cortex was measured by spectrophotometry. The group OSAHS exhibited high neuron apoptosis rate and low AchE activity than those of group MAD and control group. The blood oxygen saturation was negatively correlated with neuronal apoptosis rate and positively correlated with AchE activity. Applying MAD in OSAHS animals significantly improve the neuronal damage and function deficits by apnoea-hypoxia caused by narrowed upper airway. This study provided evidence that MAD therapy for OSAHS can significantly decrease neuronal apoptosis and increase AchE activity in the frontal cortex.

MAD ointment ameliorates Imiquimod-induced psoriasiform dermatitis by inhibiting the IL-23/IL-17 axis in mice.

PubMed

OuYang, Qiong; Pan, YaQian; Luo, HanQiong; Xuan, ChunXiao; Liu, JinE; Liu, Jun

2016-10-01

Psoriasis is a chronic auto-immune inflammation disease with skin lesions and abnormal keratinocyte proliferation. The IL-23/IL-17 axis plays an important role in the pathogenesis of psoriasis. Madecassoside (MAD) was the most important constituents isolated from Centella asiatica, which has long been used in dermatology, and it is supposed that MAD may have effects on psoriasis. In the present study, the BALB/c mice ear and back skin received IMQ for 6 consecutive days to induce psoriasis-like dermatitis. MAD ointment was applied 6h later after IMQ treatment, and the IL-23/IL-17 pathway was investigated. The HE staining, BrdU and Psoriasis Area and Severity Index (PASI) were used to score the severity of keratinocyte proliferation and inflammation of the skin. Real-time PCR and Western Blot were used to detect the IL-23/IL-17 related cytokines. Flow Cytometry were applied to observe the numbers of Th17 cells. Daily application of IMQ for 6days on mouse ear skin and back skin induced psoriasis-like dermatitis. Real-time PCR showed that mRNA level of IL-23, IL-22, IL-17A were significantly decreased by MAD ointment treatment in ear skin. HE staining and BrdU incorporation implied that MAD ointment reduced keratinocyte proliferation. Flow Cytometry results showed MAD ointment decreased the numbers of Th17 cells. Thus, MAD ointment ameliorates Imiquimod-induced skin inflammation and abnormal keratinocyte through regulate the IL-23/IL-17 axis. Copyright © 2016 Elsevier B.V. All rights reserved.

Genome-wide identification, characterisation and expression analysis of the MADS-box gene family in Prunus mume.

PubMed

Xu, Zongda; Zhang, Qixiang; Sun, Lidan; Du, Dongliang; Cheng, Tangren; Pan, Huitang; Yang, Weiru; Wang, Jia

2014-10-01

MADS-box genes encode transcription factors that play crucial roles in plant development, especially in flower and fruit development. To gain insight into this gene family in Prunus mume, an important ornamental and fruit plant in East Asia, and to elucidate their roles in flower organ determination and fruit development, we performed a genome-wide identification, characterisation and expression analysis of MADS-box genes in this Rosaceae tree. In this study, 80 MADS-box genes were identified in P. mume and categorised into MIKC, Mα, Mβ, Mγ and Mδ groups based on gene structures and phylogenetic relationships. The MIKC group could be further classified into 12 subfamilies. The FLC subfamily was absent in P. mume and the six tandemly arranged DAM genes might experience a species-specific evolution process in P. mume. The MADS-box gene family might experience an evolution process from MIKC genes to Mδ genes to Mα, Mβ and Mγ genes. The expression analysis suggests that P. mume MADS-box genes have diverse functions in P. mume development and the functions of duplicated genes diverged after the duplication events. In addition to its involvement in the development of female gametophytes, type I genes also play roles in male gametophytes development. In conclusion, this study adds to our understanding of the roles that the MADS-box genes played in flower and fruit development and lays a foundation for selecting candidate genes for functional studies in P. mume and other species. Furthermore, this study also provides a basis to study the evolution of the MADS-box family.

Banana MaMADS Transcription Factors Are Necessary for Fruit Ripening and Molecular Tools to Promote Shelf-Life and Food Security1[OPEN

PubMed Central

Elitzur, Tomer; Yakir, Esther; Quansah, Lydia; Zhangjun, Fei; Vrebalov, Julia; Khayat, Eli; Giovannoni, James J.

2016-01-01

Genetic solutions to postharvest crop loss can reduce cost and energy inputs while increasing food security, especially for banana (Musa acuminata), which is a significant component of worldwide food commerce. We have functionally characterized two banana E class (SEPALLATA3 [SEP3]) MADS box genes, MaMADS1 and MaMADS2, homologous to the tomato (Solanum lycopersicum) RIN-MADS ripening gene. Transgenic banana plants repressing either gene (via antisense or RNA interference [RNAi]) were created and exhibited specific ripening delay and extended shelf-life phenotypes, including delayed color development and softening. The delay in fruit ripening is associated with a delay in climacteric respiration and reduced synthesis of the ripening hormone ethylene; in the most severe repressed lines, no ethylene was produced and ripening was most delayed. Unlike tomato rin mutants, banana fruits of all transgenic repression lines responded to exogenous ethylene by ripening normally, likely due to incomplete transgene repression and/or compensation by other MADS box genes. Our results show that, although MADS box ripening gene necessity is conserved across diverse taxa (monocots to dicots), unlike tomato, banana ripening requires at least two necessary members of the SEPALLATA MADS box gene group, and either can serve as a target for ripening control. The utility of such genes as tools for ripening control is especially relevant in important parthenocarpic crops such as the vegetatively propagated and widely consumed Cavendish banana, where breeding options for trait improvement are severely limited. PMID:26956665

Banana MaMADS Transcription Factors Are Necessary for Fruit Ripening and Molecular Tools to Promote Shelf-Life and Food Security.

PubMed

Elitzur, Tomer; Yakir, Esther; Quansah, Lydia; Zhangjun, Fei; Vrebalov, Julia; Khayat, Eli; Giovannoni, James J; Friedman, Haya

2016-05-01

Genetic solutions to postharvest crop loss can reduce cost and energy inputs while increasing food security, especially for banana (Musa acuminata), which is a significant component of worldwide food commerce. We have functionally characterized two banana E class (SEPALLATA3 [SEP3]) MADS box genes, MaMADS1 and MaMADS2, homologous to the tomato (Solanum lycopersicum) RIN-MADS ripening gene. Transgenic banana plants repressing either gene (via antisense or RNA interference [RNAi]) were created and exhibited specific ripening delay and extended shelf-life phenotypes, including delayed color development and softening. The delay in fruit ripening is associated with a delay in climacteric respiration and reduced synthesis of the ripening hormone ethylene; in the most severe repressed lines, no ethylene was produced and ripening was most delayed. Unlike tomato rin mutants, banana fruits of all transgenic repression lines responded to exogenous ethylene by ripening normally, likely due to incomplete transgene repression and/or compensation by other MADS box genes. Our results show that, although MADS box ripening gene necessity is conserved across diverse taxa (monocots to dicots), unlike tomato, banana ripening requires at least two necessary members of the SEPALLATA MADS box gene group, and either can serve as a target for ripening control. The utility of such genes as tools for ripening control is especially relevant in important parthenocarpic crops such as the vegetatively propagated and widely consumed Cavendish banana, where breeding options for trait improvement are severely limited. © 2016 American Society of Plant Biologists. All Rights Reserved.

Cloning, Characterization, Regulation, and Function of Dormancy-Associated MADS-Box Genes from Leafy Spurge

USDA-ARS?s Scientific Manuscript database

DORMANCY-ASSOCIATED MADS-BOX (DAM) genes are SHORT VEGETATIVE PHASE–Like MADS box transcription factors linked to endodormancy induction. We have cloned and characterized several cDNA and genomic clones of DAM genes from the model perennial weed leafy spurge (Euphorbia esula). We present evidence fo...

Phylogenomics of MADS-Box Genes in Plants - Two Opposing Life Styles in One Gene Family.

PubMed

Gramzow, Lydia; Theißen, Günter

2013-09-12

The development of multicellular eukaryotes, according to their body plan, is often directed by members of multigene families that encode transcription factors. MADS (for MINICHROMOSOME MAINTENANCE1, AGAMOUS, DEFICIENS and SERUM RESPONSE FACTOR)-box genes form one of those families controlling nearly all major aspects of plant development. Knowing the complete complement of MADS-box genes in sequenced plant genomes will allow a better understanding of the evolutionary patterns of these genes and the association of their evolution with the evolution of plant morphologies. Here, we have applied a combination of automatic and manual annotations to identify the complete set of MADS-box genes in 17 plant genomes. Furthermore, three plant genomes were reanalyzed and published datasets were used for four genomes such that more than 2,600 genes from 24 species were classified into the two types of MADS-box genes, Type I and Type II. Our results extend previous studies, highlighting the remarkably different evolutionary patterns of Type I and Type II genes and provide a basis for further studies on the evolution and function of MADS-box genes.

MAD2 expression in oral squamous cell carcinoma and its relationship to tumor grade and proliferation.

PubMed

Rizzardi, Clara; Torelli, Lucio; Schneider, Manuela; Giudici, Fabiola; Zandona, Lorenzo; Biasotto, Matteo; Di Lenarda, Roberto; Melato, Mauro

2014-12-01

Defects in the cell-cycle surveillance mechanism, called the spindle checkpoint, might contribute to the chromosomal instability observed in human cancers, including oral squamous cell carcinoma. MAD2 and BUBR1 are key components of the spindle checkpoint, whose role in oral carcinogenesis and clinical relevance still need to be elucidated. We analyzed the expression of MAD2 in 49 cases of oral squamous cell carcinoma by immunohistochemistry and compared the findings with clinicopathological parameters, proliferative activity, BUBR1 expression and DNA ploidy. MAD2 was over-expressed in 18 (36.7%) cases. Tumors with over-expression of MAD2 were associated with the progression of histological grade from well to poor differentiation (p<0.001), the extent of lymph nodes involvement (PN) (p=0.0339) and Ki-67 labeling index (p<0.001). MAD2 may be involved in oral carcinogenesis and may represent an important prognostic factor associated with a more malignant phenotype of oral squamous cell carcinoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

The Influence of Media Communication on Risk Perception and Behavior Related to Mad Cow Disease in South Korea

PubMed Central

Park, Jee-Eun; Sohn, Aeree

2013-01-01

Objectives The purpose of this study was to ascertain the influence of media communication on risk behavior related to mad cow disease (MCD). Methods Mothers of elementary school students in Seoul were recruited as the survey participants of this study. Results Media reports affected risk behavior related to MCD. Also, knowledge and attitude toward MCD affects risk behavior. Conclusion Risk-related information provided by the media should maintain consistency and objectivity. For effective risk communication, there should be an open communication between the government and public, experts, and related industries, who should all collaborate. PMID:24159557

A pavement Moisture Accelerated Distress (MAD) identification system, volume 2

NASA Astrophysics Data System (ADS)

Carpenter, S. H.; Darter, M. I.; Dempsey, B. J.

1981-09-01

A users manual is designed which provides the engineer with a rational method of examining a pavement and determining rehabilitation needs that are related to the causes of the existing distress, particularly moisture related distress. The key elements in this procedure are the MAD Index developed in Volume 1, the Pavement Condition Index (PCI) and the Moisture Distress Index (MDI). Step by step procedures are presented for calculating each parameter. Complete distress identification manuals are included for asphalt surfaced highways and jointed reinforced concrete highways with pictures and descriptions of all major distress types. Descriptions of the role moisture plays in the development of each distress type are included.

Ancestral and more recently acquired syntenic relationships of MADS-box genes uncovered by the Physcomitrella patens pseudochromosomal genome assembly.

PubMed

Barker, Elizabeth I; Ashton, Neil W

2016-03-01

The Physcomitrella pseudochromosomal genome assembly revealed previously invisible synteny enabling realisation of the full potential of shared synteny as a tool for probing evolution of this plant's MADS-box gene family. Assembly of the sequenced genome of Physcomitrella patens into 27 mega-scaffolds (pseudochromosomes) has confirmed the major predictions of our earlier model of expansion of the MADS-box gene family in the Physcomitrella lineage. Additionally, microsynteny has been conserved in the immediate vicinity of some recent duplicates of MADS-box genes. However, comparison of non-syntenic MIKC MADS-box genes and neighbouring genes indicates that chromosomal rearrangements and/or sequence degeneration have destroyed shared synteny over longer distances (macrosynteny) around MADS-box genes despite subsets comprising two or three MIKC genes having remained syntenic. In contrast, half of the type I MADS-box genes have been transposed creating new syntenic relations with MIKC genes. This implies that conservation of ancient ancestral synteny of MIKC genes and of more recently acquired synteny of type I and MIKC genes may be selectively advantageous. Our revised model predicts the birth rate of MIKC genes in Physcomitrella is higher than that of type I genes. However, this difference is attributable to an early tandem duplication and an early segmental duplication of MIKC genes prior to the two polyploidisations that account for most of the expansion of the MADS-box gene family in Physcomitrella. Furthermore, this early segmental duplication spawned two chromosomal lineages: one with a MIKC (C) gene, belonging to the PPM2 clade, in close proximity to one or a pair of MIKC* genes and another with a MIKC (C) gene, belonging to the PpMADS-S clade, characterised by greater separation from syntenic MIKC* genes. Our model has evolutionary implications for the Physcomitrella karyotype.

Gaius Caligula's mental illness.

PubMed

Sidwell, Barbara

2010-01-01

The strange behavior of emperor Gaius has been the subject of debate for many historians. Some charge him with madness and attribute it to his illness in A.D. 37, whereas others believe it occurred later, or else had nothing to do with his sickness.We have no real evidence to reconstruct his mental state. Therefore speculations about madness are fruitless, as they can't be proven. Also, his madness belongs to a discourse which originates mainly from the senatorial narrative that sought to discredit him through any means possible. Thus, his acts should be seen from other angles, and the search for "mad Caligula" abandoned.

Heterologous overexpression of the birch FRUITFULL-like MADS-box gene BpMADS4 prevents normal senescence and winter dormancy in Populus tremula L.

PubMed

Hoenicka, Hans; Nowitzki, Olaf; Hanelt, Dieter; Fladung, Matthias

2008-04-01

MADS-box genes have been shown to be important to flower and vegetative tissue development, senescence and winter dormancy in many plant species. Heterologous overexpression of known MADS-box genes has also been used for unravelling gene regulation mechanisms in forest tree species. The constitutive expression of the BpMADS4 gene from birch in poplar, known to induce early flowering in birch and apple, induced broad changes in senescence and winter dormancy but no early flowering. Other analyses revealed that 35S::BpMADS4 poplars maintained photosynthetic activity, chlorophyll and proteins in leaves under winter conditions. BpMADS4 may be influencing transcription factors regulating the senescence and dormancy process due to homology with poplar proteins related to both traits. Little is known of the regulatory genes that co-ordinate senescence, dormancy, chlorophyll/protein degradation, and photosynthesis at the molecular level. Dissecting the molecular characteristics of senescence regulation will probably involve the understanding of multiple and novel regulatory pathways. The results presented here open new horizons for the identification of regulatory mechanisms related to dormancy and senescence in poplar and other temperate tree species. They confirm recent reports of common signalling intermediates between flowering time and growth cessation in trees (Böhlenius et al. in Science 312:1040-1043, 2006) and additionally indicate similar connections between flowering time signals and senescence.

Suppression of OsMADS7 in rice endosperm stabilizes amylose content under high temperature stress.

PubMed

Zhang, Hua; Xu, Heng; Feng, Mengjie; Zhu, Ying

2018-01-01

High temperature significantly alters the amylose content of rice, resulting in mature grains with poor eating quality. However, only few genes and/or quantitative trait loci involved in this process have been isolated and the molecular mechanisms of this effect remain unclear. Here, we describe a floral organ identity gene, OsMADS7, involved in stabilizing rice amylose content at high temperature. OsMADS7 is greatly induced by high temperature at the early filling stage. Constitutive suppression of OsMADS7 stabilizes amylose content under high temperature stress but results in low spikelet fertility. However, rice plants with both stable amylose content at high temperature and normal spikelet fertility can be obtained by specifically suppressing OsMADS7 in endosperm. GBSSI is the major enzyme responsible for amylose biosynthesis. A low filling rate and high expression of GBSSI were detected in OsMADS7 RNAi plants at high temperature, which may be correlated with stabilized amylose content in these transgenic seeds under high temperature. Thus, specific suppression of OsMADS7 in endosperm could improve the stability of rice amylose content at high temperature, and such transgenic materials may be a valuable genetic resource for breeding rice with elite thermal resilience. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

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

Takahashi, Akinori; Kikuguchi, Chisato; Morita, Masahiro

Highlights: Black-Right-Pointing-Pointer CNOT3 depletion increases the mitotic index. Black-Right-Pointing-Pointer CNOT3 inhibits the expression of MAD1. Black-Right-Pointing-Pointer CNOT3 destabilizes the MAD1 mRNA. Black-Right-Pointing-Pointer MAD1 knockdown attenuates the CNOT3 depletion-induced mitotic arrest. -- Abstract: The stability of mRNA influences the dynamics of gene expression. The CCR4-NOT complex, the major deadenylase in mammalian cells, shortens the mRNA poly(A) tail and contributes to the destabilization of mRNAs. The CCR4-NOT complex plays pivotal roles in various physiological functions, including cell proliferation, apoptosis, and metabolism. Here, we show that CNOT3, a subunit of the CCR4-NOT complex, is involved in the regulation of the spindle assembly checkpoint,more » suggesting that the CCR4-NOT complex also plays a part in the regulation of mitosis. CNOT3 depletion increases the population of mitotic-arrested cells and specifically increases the expression of MAD1 mRNA and its protein product that plays a part in the spindle assembly checkpoint. We showed that CNOT3 depletion stabilizes the MAD1 mRNA, and that MAD1 knockdown attenuates the CNOT3 depletion-induced increase of the mitotic index. Basing on these observations, we propose that CNOT3 is involved in the regulation of the spindle assembly checkpoint through its ability to regulate the stability of MAD1 mRNA.« less

Accelerated Learning: Madness with a Method.

ERIC Educational Resources Information Center

Zemke, Ron

1995-01-01

Accelerated learning methods have evolved into a variety of holistic techniques that involve participants in the learning process and overcome negative attitudes about learning. These components are part of the mix: the brain, learning environment, music, imaginative activities, suggestion, positive mental state, the arts, multiple intelligences,…

Studies in Language Learning and Spanish Linguistics. Festschrift in Honor of Tracy D. Terrell.

ERIC Educational Resources Information Center

Hashemipour, Peggy, Ed.; Maldonado, Ricardo, Ed.; van Naerssen, Margaret, Ed.

Essays on Spanish linguistics and related topics are dedicated to linguist Tracy D. Terrell. An introductory section gives a brief biography and a list of his publications. Essays include: "The Natural Approach to Language Teaching: An Update" (Tracy D. Terrell); "Two Mad, Mad, Mad Worlds: Notes on Natural Approach and the Writing…

[Women and madness in the Eneid].

PubMed

Totola, Giorgia

2012-01-01

The article presents female cases of madness in Latin Vergilian Literature, comparing the Greek Dyonisian divine possession of the Maenads and Bacchae with the madness of Dido and Amata. Transcultural psychiatry is here proposed as a useful tool for reading the descriptions of the Aeneid - to try to understand every kind of world where barriers disappear between visible and invisible.

MADS Users' Guide

NASA Technical Reports Server (NTRS)

Moerder, Daniel D.

2014-01-01

MADS (Minimization Assistant for Dynamical Systems) is a trajectory optimization code in which a user-specified performance measure is directly minimized, subject to constraints placed on a low-order discretization of user-supplied plant ordinary differential equations. This document describes the mathematical formulation of the set of trajectory optimization problems for which MADS is suitable, and describes the user interface. Usage examples are provided.

Identifying outliers of non-Gaussian groundwater state data based on ensemble estimation for long-term trends

NASA Astrophysics Data System (ADS)

Jeong, Jina; Park, Eungyu; Han, Weon Shik; Kim, Kueyoung; Choung, Sungwook; Chung, Il Moon

2017-05-01

A hydrogeological dataset often includes substantial deviations that need to be inspected. In the present study, three outlier identification methods - the three sigma rule (3σ), inter quantile range (IQR), and median absolute deviation (MAD) - that take advantage of the ensemble regression method are proposed by considering non-Gaussian characteristics of groundwater data. For validation purposes, the performance of the methods is compared using simulated and actual groundwater data with a few hypothetical conditions. In the validations using simulated data, all of the proposed methods reasonably identify outliers at a 5% outlier level; whereas, only the IQR method performs well for identifying outliers at a 30% outlier level. When applying the methods to real groundwater data, the outlier identification performance of the IQR method is found to be superior to the other two methods. However, the IQR method shows limitation by identifying excessive false outliers, which may be overcome by its joint application with other methods (for example, the 3σ rule and MAD methods). The proposed methods can be also applied as potential tools for the detection of future anomalies by model training based on currently available data.

MuMADS1 and MaOFP1 regulate fruit quality in a tomato ovate mutant.

PubMed

Liu, Juhua; Zhang, Jing; Wang, Jingyi; Zhang, Jianbin; Miao, Hongxia; Jia, Caihong; Wang, Zhuo; Xu, Biyu; Jin, Zhiqiang

2018-05-01

Fruit ripening and quality are common botanical phenomena that are closely linked and strictly regulated by transcription factors. It was previously discovered that a banana MADS-box protein named MuMADS1 interacted with an ovate family protein named MaOFP1 to regulate banana fruit ripening. To further investigate the role of MuMADS1 and MaOFP1 in the regulation of fruit quality, a combination of genetic transformation and transcriptional characterization was used. The results indicated that the co-expression of MuMADS1 and MaOFP1 in the ovate mutant could compensate for fruit shape and inferior qualities relating to fruit firmness, soluble solids and sugar content. The number of differentially expressed genes (DEGs) was 1395 in WT vs. ovate, with 883 up-regulated and 512 down-regulated genes, while the numbers of DEGs gradually decreased with the transformation of MuMADS1 and MaOFP1 into ovate. 'Starch and sucrose metabolism' constituted the primary metabolic pathway, and the gene numbers in this pathway were obviously different when MuMADS1 and MaOFP1 were integrated into ovate. A series of metabolic genes involved in cell wall biosynthesis were up-regulated in the WT vs. ovate, which probably resulted in the firmer texture and lower sugar contents in the ovate fruit. These results demonstrate that MuMADS1 and MaOFP1 are coregulators of fruit quality, facilitating the dissection of the molecular mechanisms underlying fruit quality formation. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

The pragmatics of "madness": performance analysis of a Bangladeshi woman's "aberrant" lament.

PubMed

Wilce, J M

1998-03-01

A fine-grained analysis of the transcript of a Bangladeshi woman's lament is used to argue for an anthropology of "madness" that attends closely to performance and performativity. The emergent, interactive production of wept speech, together with the conflicting use to which it is put by the performer and her relatives, is linked problematically to performance genres and to ethnopsychiatric indexes of madness. Tuneful weeping is taken by relatives to be performative of madness, in a sense something like Austin's. Yet, exploration of the divergent linguistic ideologies which are brought to bear on the lament not only enables more nuanced ethnographic treatment but also has reflexive ramifications for medical and psychological anthropology. This leads to a critique of the referentialism in our own treatment of language. The role played by transparent reference is overshadowed by indexicality and by dialogical processes of proposing and resisting labels for speech genres attributed to the "mad."

Emotional and deliberative reactions to a public crisis: Mad Cow disease in France.

PubMed

Sinaceur, Marwan; Heath, Chip; Cole, Steve

2005-03-01

Although most theories of choice are cognitive, recent research has emphasized the role of emotions. We used a novel context--the Mad Cow crisis in France--to investigate how emotions alter choice even when consequences are held constant. A field study showed that individuals reduced beef consumption in months after many newspaper articles featured the emotional label "Mad Cow," but beef consumption was unaffected after articles featured scientific labels for the same disease. The reverse pattern held for the disease-related actions of a government bureaucracy. A lab study showed that the Mad Cow label induces people to make choices based solely on emotional reactions, whereas scientific labels induce people to consider their own probability judgments. Although the Mad Cow label produces less rational behavior than scientific labels, it is two to four times more common in the environment.

On Method and Madness: Teaching Writers to Write.

ERIC Educational Resources Information Center

Mills, Pat

1994-01-01

Maintains that, in teaching and in teaching writing, methods matter if they are organic methods that grow out of real-life experiences. Notes that in another sense, all that matters is getting both teacher and student to wake up to their own lives and to what they know, absolutely, within themselves. (SR)

Science with ESO's Multi-conjugate Adaptive-optics Demonstrator - MAD

NASA Astrophysics Data System (ADS)

Melnick, Jorge; Marchetti, Enrico; Amico, Paola

2012-07-01

ESO's Multi-conjugate Adaptive-optics Demonstrator (MAD) was a prototype designed and built to demonstrate wide-field adaptive optics science on large telescopes. The outstanding results obtained during commissioning and guaranteed time observations (GTO) prompted ESO to issue and open call to the community for 23 science demonstration (SD) observing nights distributed in three runs (in order to provide access to the summer an winter skies). Thus, in total MAD was used for science for 33 nights including the 10 nights of GTO time. date, 19 articles in refereed journals (including one in Nature) have been published based fully or partially o MAD data. To the best of our knowledge, these are not only the first, but also the only scientific publication from MCAO instruments world-wide to date (at least in Astronomy). The scientific impact of these publication, as measured by the h-index, is comparable to that of other AO instruments on the VLT, although over the years these instruments have been allocated many more nights than MAD. In this contribution we present an overview of the scientific results from MAD and a more detailed discussion of the most cited papers.

The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding

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

Ye, Qiaozhen; Kim, Dong Hyun; Dereli, Ihsan

Proteins of the conserved HORMA domain family, including the spindle assembly checkpoint protein MAD2 and the meiotic HORMADs, assemble into signaling complexes by binding short peptides termed “closure motifs”. The AAA+ ATPase TRIP13 regulates both MAD2 and meiotic HORMADs by disassembling these HORMA domain–closure motif complexes, but its mechanisms of substrate recognition and remodeling are unknown. Here, we combine X-ray crystallography and crosslinking mass spectrometry to outline how TRIP13 recognizes MAD2 with the help of the adapter protein p31comet. We show that p31comet binding to the TRIP13 N-terminal domain positions the disordered MAD2 N-terminus for engagement by the TRIP13 “poremore » loops”, which then unfold MAD2 in the presence of ATP. N-terminal truncation of MAD2 renders it refractory to TRIP13 action in vitro, and in cells causes spindle assembly checkpoint defects consistent with loss of TRIP13 function. Similar truncation of HORMAD1 in mouse spermatocytes compromises its TRIP13-mediated removal from meiotic chromosomes, highlighting a conserved mechanism for recognition and disassembly of HORMA domain–closure motif complexes by TRIP13.« less

SVP-like MADS-box protein from Carya cathayensis forms higher-order complexes.

PubMed

Wang, Jingjing; Hou, Chuanming; Huang, Jianqin; Wang, Zhengjia; Xu, Yingwu

2015-03-01

To properly regulate plant flowering time and construct floral pattern, MADS-domain containing transcription factors must form multimers including homo- and hetero-dimers. They are also active in forming hetero-higher-order complexes with three to five different molecules. However, it is not well known if a MADS-box protein can also form homo-higher-order complex. In this study a biochemical approach is utilized to provide insight into the complex formation for an SVP-like MADS-box protein cloned from hickory. The results indicated that the protein is a heterogeneous higher-order complex with the peak population containing over 20 monomers. Y2H verified the protein to form homo-complex in yeast cells. Western blot of the hickory floral bud sample revealed that the protein exists in higher-order polymers in native. Deletion assays indicated that the flexible C-terminal residues are mainly responsible for the higher-order polymer formation and the heterogeneity. Current results provide direct biochemical evidences for an active MADS-box protein to be a high order complex, much higher than a quartermeric polymer. Analysis suggests that a MADS-box subset may be able to self-assemble into large complexes, and thereby differentiate one subfamily from the other in a higher-order structural manner. Present result is a valuable supplement to the action of mechanism for MADS-box proteins in plant development. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Treatment success with titratable thermoplastic mandibular advancement devices for obstructive sleep apnea: A comparison of patient characteristics.

PubMed

Wang, Tang-Chuan; Tsou, Yung-An; Wu, Yi-Fan; Huang, Chia-Chang; Lin, Wesley Wen-Yang; Li, Yu-Fen; Chen, Michael Yuan-Chien; Tai, Chih-Jaan; Tsai, Ming-Hsui

2017-03-01

A titratable thermoplastic mandibular advancement device (MAD) is clearly an effective treatment option in some patients with obstructive sleep apnea (OSA). Determining which patients may be more likely to respond to treatment with thermoplastic MADs and to adhere to treatment would be of obvious clinical relevance. This was an experimental descriptive study (N = 60). Patients with OSA were instructed to wear a titratable thermoplastic MAD for 3 months. Treatment success was defined as a ≥50% reduction from baseline in the apnea-hypopnea index (AHI) or AHI <10 when wearing MAD. Adherence was defined as MAD use ≥5 nights/week. Treatment was successful in 66.7% of patients and 60.0% were adherent. All polysomnographic parameters and visual analogue scale scores (sleep quality, snoring, waking refreshed) were significantly improved after treatment. The patients in whom treatment failed had significantly higher neck circumferences (39.3 cm vs. 37.5 cm, p = 0.014), higher baseline AHI values (26.6 vs. 18.0, p = 0.016), and smaller AHI reduction (-31.8 vs -53.1, p < 0.001) than those in the group in whom treatment succeeded. There were no significant differences in polysomnographic, cephalometric, or visual analogue scale measures between patients for whom treatment was and was not successful, regardless of baseline values or the change rates after the MAD was placed. Titratable thermoplastic MADs can improve indicators of sleep quality, even in patients in whom treatment is considered to have failed.

MADS-Box gene diversity in seed plants 300 million years ago.

PubMed

Becker, A; Winter, K U; Meyer, B; Saedler, H; Theissen, G

2000-10-01

MADS-box genes encode a family of transcription factors which control diverse developmental processes in flowering plants ranging from root development to flower and fruit development. Through phylogeny reconstructions, most of these genes can be subdivided into defined monophyletic gene clades whose members share similar expression patterns and functions. Therefore, the establishment of the diversity of gene clades was probably an important event in land plant evolution. In order to determine when these clades originated, we isolated cDNAs of 19 different MADS-box genes from Gnetum gnemon, a gymnosperm model species and thus a representative of the sister group of the angiosperms. Phylogeny reconstructions involving all published MADS-box genes were then used to identify gene clades containing putative orthologs from both angiosperm and gymnosperm lineages. Thus, the minimal number of MADS-box genes that were already present in the last common ancestor of extant gymnosperms and angiosperms was determined. Comparative expression studies involving pairs of putatively orthologous genes revealed a diversity of patterns that has been largely conserved since the time when the angiosperm and gymnosperm lineages separated. Taken together, our data suggest that there were already at least seven different MADS-box genes present at the base of extant seed plants about 300 MYA. These genes were probably already quite diverse in terms of both sequence and function. In addition, our data demonstrate that the MADS-box gene families of extant gymnosperms and angiosperms are of similar complexities.

Comparative efficacy of CPAP, MADs, exercise-training, and dietary weight loss for sleep apnea: a network meta-analysis.

PubMed

Iftikhar, Imran H; Bittencourt, Lia; Youngstedt, Shawn D; Ayas, Najib; Cistulli, Peter; Schwab, Richard; Durkin, Martin W; Magalang, Ulysses J

2017-02-01

To synthesize evidence from available studies on the relative efficacies of continuous positive airway pressure (CPAP), mandibular advancement device (MAD), supervised aerobic exercise training, and dietary weight loss in patients with obstructive sleep apnea (OSA). Network meta-analysis of 80 randomized controlled trials (RCTs) short-listed from PubMed, SCOPUS, Web of science, and Cochrane register (inception - September 8, 2015). Individuals with OSA. CPAP, MADs, exercise training, and dietary weight loss. CPAP decreased apnea-hypopnea index (AHI) the most [by 25.27 events/hour (22.03-28.52)] followed by exercise training, MADs, and dietary weight loss. While the difference between exercise training and CPAP was non-significant [-8.04 (-17.00 to 0.92), a significant difference was found between CPAP and MADs on AHI and oxygen desaturation index (ODI) [-10.06 (-14.21 to -5.91) and -7.82 (-13.04 to -2.59), respectively]. Exercise training significantly improved Epworth sleepiness scores (ESS) [by 3.08 (0.68-5.48)], albeit with a non-significant difference compared to MADs and CPAP. CPAP is the most efficacious in complete resolution of sleep apnea and in improving the indices of saturation during sleep. While MADs offer a reasonable alternative to CPAP, exercise training which significantly improved daytime sleepiness (ESS) could be used as adjunctive to the former two. Copyright © 2016 Elsevier B.V. All rights reserved.

Gene silencing pathway RNA-dependent RNA polymerase of Neurospora crassa: yeast expression and crystallization of selenomethionated QDE-1 protein.

PubMed

Laurila, Minni R L; Salgado, Paula S; Makeyev, Eugene V; Nettelship, Joanne; Stuart, David I; Grimes, Jonathan M; Bamford, Dennis H

2005-01-01

The RNA-dependent RNA polymerase, QDE-1, is a component of the RNA silencing pathway in Neurospora crassa. The enzymatically active carboxy-terminal fragment QDE-1 DeltaN has been expressed in Saccharomyces cerevisiae in the presence and absence of selenomethionine (SeMet). The level of SeMet incorporation was estimated by mass spectrometry to be approximately 98%. Both native and SeMet proteins were crystallized in space group P2(1) with unit cell parameters a=101.2, b=122.5, c=114.4A, beta=108.9 degrees , and 2 molecules per asymmetric unit. The native and SeMet crystals diffract to 2.3 and 3.2A, respectively, the latter are suitable for MAD structure determination.

Impact of social inequalities at birth on the longevity of children born 1914–1916: A cohort study

PubMed Central

Le Fur, Sophie; Bougnères, Pierre; Valleron, Alain-Jacques

2017-01-01

Background Testing whether familial socioeconomic status (SES) in childhood is a predictor of mortality has rarely been done on historical cohorts. Methods The birth certificates of 4,805 individuals born 1914–1916 in 16 districts of the Paris region were retrieved. The handwritten information provided the occupation of parents, the legitimacy status, life events (e.g. marriage, divorce), and the precise date of death when after 1945 (i.e. age 31 years (y) in the cohort). We used the median age at death (MAD) as a global measure of mortality, then studied separately survival to and after 31 y. Multivariate Imputation by Chained Equations (MICE), Generalized Additive Models (GAMs) and mixed effect Cox models were used. Results MAD showed large variations according to paternal occupation. The lowest MAD in both sexes was that of workers’ children: it was 56.3 y (95% CI: [48.6–62.7]) in men and 67.4 y (95% CI: [60.8–72.7]) in women, respectively (95% CI: 13.4 y [5.7–21.3]) and 12.3 y (95% CI: [4.0–19.2]) below the highest MAD attained. MAD experienced by illegitimate children was 18.9 y (95% CI: [13.3–32.3]) shorter than of legitimate children. The multivariate analysis revealed that in both sexes survival to age 31 y was predicted independently by legitimacy and paternal occupation. Paternal occupation was found significantly associated with mortality after age 31 y in females only: accordingly difference in life expectancy at age 31 y was 4.4 y (95% CI: [1.2–7.6]) between upper class and workers’ daughters. Conclusions Paternal occupation and legitimacy status were strong predictors of offspring longevity in this one-century historical cohort born during World War One. PMID:29036185

Anti-MAdCAM Antibody Increases ß7+ T Cells and CCR9 Gene Expression in the Peripheral Blood of Patients With Crohn’s Disease

PubMed Central

Hassan-Zahraee, Mina; Banerjee, Anindita; Cheng, John B; Zhang, Weidong; Ahmad, Alaa; Page, Karen; von Schack, David; Zhang, Baohong; Martin, Steven W; Nayak, Satyaprakash; Reddy, Padma; Xi, Li; Neubert, Hendrik; Fernandez Ocana, Mireia; Gorelick, Ken; Clare, Robert; Vincent, Michael; Cataldi, Fabio; Hung, Kenneth

2018-01-01

Abstract Objective To define pharmacodynamic biomarkers in the peripheral blood of patients with Crohn’s disease [CD] after treatment with PF-00547659, an anti-human mucosal addressin cell adhesion molecule-1 [MAdCAM-1] monoclonal antibody. Methods In this Phase 2, randomised, double-blind, controlled study [OPERA], blood samples were analysed from patients with moderate to severe active CD who received placebo or 22.5 mg, 75 mg, or 225 mg of PF-00547659 subcutaneously at baseline and at Weeks 4 and 8, with follow-up at Week 12. Soluble MAdCAM [sMAdCAM] was measured by mass spectrometry, β7-expressing T cells by flow cytometry, and gene transcriptome by RNA sequencing. Results A slight increase in sMAdCAM was measured in the placebo group from baseline to Week 12 [6%], compared with significant decreases in all PF-00547659 groups [–87% to –98%]. A slight increase from baseline to Week 12 was observed in frequency and molecules of equivalent soluble fluorochrome for β7+ central memory T cells in the placebo group [4%], versus statistically significant increases in the active treatment groups [48% to 81%]. Similar trends were seen for β7+ effector memory T cells [placebo, 8%; PF-00547659, 84–138%] and β7+ naïve T cells [8%; 13–50%]. CCR9 gene expression had statistically significant up-regulation [p = 1.09e-06; false discovery rate < 0.1] with PF-00547659 treatment, and was associated with an increase in β7+ T cells. Conclusions Results of the OPERA study demonstrate positive pharmacology and dose-dependent changes in pharmacodynamic biomarker measurements in blood, including changes in cellular composition of lymphocytes and corresponding CCR9 gene expression changes. PMID:28961803

Socio-Economic Status: A Barrier to Access to Mandibular Advancement Device Therapy for Patients with Obstructive Sleep Apnea Syndrome in France.

PubMed

Fleury, Marion; Le Vaillant, Marc; Pelletier-Fleury, Nathalie

2015-01-01

Obstructive sleep apnea syndrome (OSAS) is a major public health problem which affects between 5 to 10% of the general population. OSAS is known to be associated with high rates of morbidity and mortality mainly due to cardiovascular diseases and traffic accidents. The burden of illness is high for the individual and society. There are 2 treatment options for OSAS, Continuous Positive Airway Pressure (CPAP) and Mandibular Advancement Device therapy (MAD). CPAP is known to be an effective but very constraining treatment. Patients are usually poorly adherent. MAD is a more recent treatment easier to use and consequently better tolerated, but MAD can only be prescribed to patients with satisfactory oral hygiene. Oral health constitutes a real issue particularly among underprivileged groups in France. Through this link, the question of whether low socio-economic status constitutes a barrier to access to care for patients with OSAS is raised. In a multicenter prospective cohort of 2822 consecutive OSAS patients in whom MAD has been proposed as an alternative to CPAP between May 15, 2007 and December 1st, 2014, we identified the factors that lead to a patient diagnosed with OSAS to be treated by MAD instead of CPAP. A logistic regression was performed using a stepwise forward procedure. The main outcome of the study was that treatment by MAD was significantly associated with both educational attainment, as determined by the age at which the patient left full-time education, ≥18 years compared with <18 (adjusted odds ratio (aOR): 1.64, 95% CI 1.23 to 2.20), and the patient's occupational category. Executives and higher intellectual professions, intermediate professions, technicians, foremen and employees were significantly more likely to be treated by MAD than workers (aOR: 2.21, 95% CI 1.88 to 2.58; aOR: 1.74, 95% CI 1.15 to 2.63; aOR: 1.96, 95% CI 1.11 to 3.47, respectively). Overall, these results suggest that low socio-economic status constitutes a barrier to access to MAD for patients with OSAS in France. MAD use in patients with OSAS highlights inequalities in health care access.

A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO).

PubMed

Quinnell, Timothy G; Bennett, Maxine; Jordan, Jake; Clutterbuck-James, Abigail L; Davies, Michael G; Smith, Ian E; Oscroft, Nicholas; Pittman, Marcus A; Cameron, Malcolm; Chadwick, Rebecca; Morrell, Mary J; Glover, Matthew J; Fox-Rushby, Julia A; Sharples, Linda D

2014-10-01

Mandibular advancement devices (MADs) are used to treat obstructive sleep apnoea-hypopnoea syndrome (OSAHS) but evidence is lacking regarding their clinical and cost-effectiveness in less severe disease. To compare clinical- and cost-effectiveness of a range of MADs against no treatment in mild to moderate OSAHS. This open-label, randomised, controlled, crossover trial was undertaken at a UK sleep centre. Adults with Apnoea-Hypopnoea Index (AHI) 5-<30/h and Epworth Sleepiness Scale (ESS) score ≥9 underwent 6 weeks of treatment with three non-adjustable MADs: self-moulded (SleepPro 1; SP1); semi-bespoke (SleepPro 2; SP2); fully-bespoke MAD (bMAD); and 4 weeks no treatment. Primary outcome was AHI scored by a polysomnographer blinded to treatment. Secondary outcomes included ESS, quality of life, resource use and cost. 90 patients were randomised and 83 were analysed. All devices reduced AHI compared with no treatment by 26% (95% CI 11% to 38%, p=0.001) for SP1, 33% (95% CI 24% to 41%) for SP2 and 36% (95% CI 24% to 45%, p<0.001) for bMAD. ESS was 1.51 (95% CI 0.73 to 2.29, p<0.001, SP1) to 2.37 (95% CI 1.53 to 3.22, p<0.001, bMAD) lower than no treatment (p<0.001 for all). Compliance was lower for SP1, which was the least preferred treatment at trial exit. All devices were cost-effective compared with no treatment at a £20,000/quality-adjusted life year (QALY) threshold. SP2 was the most cost-effective up to £39,800/QALY. Non-adjustable MADs achieve clinically important improvements in mild to moderate OSAHS and are cost-effective. Of those trialled, the semi-bespoke MAD is an appropriate first choice. ISRCTN02309506. 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.

Fast Geostatistical Inversion using Randomized Matrix Decompositions and Sketchings for Heterogeneous Aquifer Characterization

NASA Astrophysics Data System (ADS)

O'Malley, D.; Le, E. B.; Vesselinov, V. V.

2015-12-01

We present a fast, scalable, and highly-implementable stochastic inverse method for characterization of aquifer heterogeneity. The method utilizes recent advances in randomized matrix algebra and exploits the structure of the Quasi-Linear Geostatistical Approach (QLGA), without requiring a structured grid like Fast-Fourier Transform (FFT) methods. The QLGA framework is a more stable version of Gauss-Newton iterates for a large number of unknown model parameters, but provides unbiased estimates. The methods are matrix-free and do not require derivatives or adjoints, and are thus ideal for complex models and black-box implementation. We also incorporate randomized least-square solvers and data-reduction methods, which speed up computation and simulate missing data points. The new inverse methodology is coded in Julia and implemented in the MADS computational framework (http://mads.lanl.gov). Julia is an advanced high-level scientific programing language that allows for efficient memory management and utilization of high-performance computational resources. Inversion results based on series of synthetic problems with steady-state and transient calibration data are presented.

A universal, accurate intensity-based classification of different physical activities using raw data of accelerometer.

PubMed

Vähä-Ypyä, Henri; Vasankari, Tommi; Husu, Pauliina; Suni, Jaana; Sievänen, Harri

2015-01-01

Accelerometers are increasingly used for objective assessment of physical activity. However, because of lack of the proprietary analysis algorithms, direct comparisons between accelerometer brands are difficult. In this study, we propose and evaluate open source methods for commensurate assessment of raw accelerometer data irrespective of the brand. Twenty-one participants carried simultaneously three different tri-axial accelerometers on their waist during five different sedentary activities and five different intensity levels of bipedal movement from slow walking to running. Several time and frequency domain traits were calculated from the measured raw data, and their performance in classifying the activities was compared. Of the several traits, the mean amplitude deviation (MAD) provided consistently the best performance in separating the sedentary activities and different speeds of bipedal movement from each other. Most importantly, the universal cut-off limits based on MAD classified sedentary activities and different intensity levels of walking and running equally well for all three accelerometer brands and reached at least 97% sensitivity and specificity in each case. Irrespective of the accelerometer brand, a simply calculable MAD with universal cut-off limits provides a universal method to evaluate physical activity and sedentary behaviour using raw accelerometer data. A broader application of the present approach is expected to render different accelerometer studies directly comparable with each other. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

Molecular mechanisms of floral organ specification by MADS domain proteins.

PubMed

Yan, Wenhao; Chen, Dijun; Kaufmann, Kerstin

2016-02-01

Flower development is a model system to understand organ specification in plants. The identities of different types of floral organs are specified by homeotic MADS transcription factors that interact in a combinatorial fashion. Systematic identification of DNA-binding sites and target genes of these key regulators show that they have shared and unique sets of target genes. DNA binding by MADS proteins is not based on 'simple' recognition of a specific DNA sequence, but depends on DNA structure and combinatorial interactions. Homeotic MADS proteins regulate gene expression via alternative mechanisms, one of which may be to modulate chromatin structure and accessibility in their target gene promoters. Copyright © 2015 Elsevier Ltd. All rights reserved.

Atrioventricular Block Induced by Mad-Honey Intoxication

PubMed Central

Cagli, Kumral Ergun; Tufekcioglu, Omac; Sen, Nihat; Aras, Dursun; Topaloglu, Serkan; Basar, Nur; Pehlivan, Sevil

2009-01-01

An unusual type of food poisoning, mad-honey intoxication, can be observed in the Black Sea region of Turkey and various other parts of the world. It can occur after ingestion of grayanotoxin-contaminated honey produced from the nectar of Rhododendron ponticum and other plant species, chiefly of the Ericaceae and Sapindaceae families. Mad-honey intoxication can result in severe cardiac complications, such as complete atrioventricular block. The diagnosis is generally reached on the basis of the patient's history of honey intake. In this report, we describe the case of a patient who had mad-honey–related complete atrioventricular block; in this instance, the diagnosis was confirmed by a pollen analysis of the suspect honey. PMID:19693312

Historical Notes. A Madness in the Methods. Cubic and Quartic Equations: Are the General Solving Techniques Still Important?

ERIC Educational Resources Information Center

Francis, Richard L.

1991-01-01

Described is an outline for a school mathematics project dealing with the theory of equations, specifically solutions to polynomials of the third and of the fourth degree. Cardano's method for solution of cubic equations and Ferrari's method for solution of quartic equations are included with examples. (JJK)

Editors' Introduction to the Thematic Issue: Mad about Methods? Teaching Research Methods in Political Science

ERIC Educational Resources Information Center

Adriaensen, Johan; Kerremans, Bart; Slootmaeckers, Koen

2015-01-01

The contributors to this special issue all seek to address the challenge of teaching research methods to political science students. This introduction aims to provide a concise framework for the various innovations presented throughout this issue, situating them in the wider literature. Particular emphasis is placed on the factors that distinguish…

Structure of Lmaj006129AAA, a hypothetical protein from Leishmania major

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

Arakaki, Tracy; Le Trong, Isolde; Structural Genomics of Pathogenic Protozoa

2006-03-01

The crystal structure of a conserved hypothetical protein from L. major, Pfam sequence family PF04543, structural genomics target ID Lmaj006129AAA, has been determined at a resolution of 1.6 Å. The gene product of structural genomics target Lmaj006129 from Leishmania major codes for a 164-residue protein of unknown function. When SeMet expression of the full-length gene product failed, several truncation variants were created with the aid of Ginzu, a domain-prediction method. 11 truncations were selected for expression, purification and crystallization based upon secondary-structure elements and disorder. The structure of one of these variants, Lmaj006129AAH, was solved by multiple-wavelength anomalous diffraction (MAD)more » using ELVES, an automatic protein crystal structure-determination system. This model was then successfully used as a molecular-replacement probe for the parent full-length target, Lmaj006129AAA. The final structure of Lmaj006129AAA was refined to an R value of 0.185 (R{sub free} = 0.229) at 1.60 Å resolution. Structure and sequence comparisons based on Lmaj006129AAA suggest that proteins belonging to Pfam sequence families PF04543 and PF01878 may share a common ligand-binding motif.« less

Historical epistemology of the body-mind interaction in psychiatry

PubMed Central

Berrios, German E.

2018-01-01

This paper deals with the history of the relationship between the mind-body dualism and the epistemology of madness. Earlier versions of such dualism posed little problem in regard to the manner of their communication. The Cartesian view that mind and body did, in fact, name different substances introduced a problem of incommunicability that is yet to be resolved. Earlier views that madness may be related to changes in the brain began gaining empirical support during the 17th century. Writers on madness chose to resolve the mind-body problem differently Some stated that such communication was not needed; others, that mind was a redundant concept, as madness could be fully explained by structural changes in the brain; and yet others described psychological spaces for madness to inhabit as a symbolic conflict. The epistemology of the neurosciences bypasses the conundrum, as it processes all together the variables representing the brain, subjectivity, and behavior and bridges the “philosophical” gap by means of correlational structures. PMID:29946206

Mad1 kinetochore recruitment by Mps1-mediated phosphorylation of Bub1 signals the spindle checkpoint.

PubMed

London, Nitobe; Biggins, Sue

2014-01-15

The spindle checkpoint is a conserved signaling pathway that ensures genomic integrity by preventing cell division when chromosomes are not correctly attached to the spindle. Checkpoint activation depends on the hierarchical recruitment of checkpoint proteins to generate a catalytic platform at the kinetochore. Although Mad1 kinetochore localization is the key regulatory downstream event in this cascade, its receptor and mechanism of recruitment have not been conclusively identified. Here, we demonstrate that Mad1 kinetochore association in budding yeast is mediated by phosphorylation of a region within the Bub1 checkpoint protein by the conserved protein kinase Mps1. Tethering this region of Bub1 to kinetochores bypasses the checkpoint requirement for Mps1-mediated kinetochore recruitment of upstream checkpoint proteins. The Mad1 interaction with Bub1 and kinetochores can be reconstituted in the presence of Mps1 and Mad2. Together, this work reveals a critical mechanism that determines kinetochore activation of the spindle checkpoint.

Physcomitrella MADS-box genes regulate water supply and sperm movement for fertilization.

PubMed

Koshimizu, Shizuka; Kofuji, Rumiko; Sasaki-Sekimoto, Yuko; Kikkawa, Masahide; Shimojima, Mie; Ohta, Hiroyuki; Shigenobu, Shuji; Kabeya, Yukiko; Hiwatashi, Yuji; Tamada, Yosuke; Murata, Takashi; Hasebe, Mitsuyasu

2018-01-01

MIKC classic (MIKC C )-type MADS-box genes encode transcription factors that function in various developmental processes, including angiosperm floral organ identity. Phylogenetic analyses of the MIKC C -type MADS-box family, including genes from non-flowering plants, suggest that the increased numbers of these genes in flowering plants is related to their functional divergence; however, their precise functions in non-flowering plants and their evolution throughout land plant diversification are unknown. Here, we show that MIKC C -type MADS-box genes in the moss Physcomitrella patens function in two ways to enable fertilization. Analyses of protein localization, deletion mutants and overexpression lines of all six genes indicate that three MIKC C -type MADS-box genes redundantly regulate cell division and growth in the stems for appropriate external water conduction, as well as the formation of sperm with motile flagella. The former function appears to be maintained in the flowering plant lineage, while the latter was lost in accordance with the loss of sperm.

[Surrealism and madness].

PubMed

Flora, Κ

2017-01-01

This article attempts an approach of madness by surrealism, as reflected in the pathway of the surrealist movement. In the light of enlargement of the concept of mental illness and the experience of madness, an approach is being attempted regarding the early surrealist views as they precursory appear e.g. from the case of Hieronymus Bosch to the meeting of the dominant psychiatry and the surrealist movement in the 19th and 20th century. Then, the paper attempts to present the main positions of representatives of the movement, such as Breton, Dali and Kalas. These three surrealists were chosen among others, for this brief report, as the representatives of three remarkable moments in the surrealistic route. Breton introduces the element of fiction and hyper-reality while he questions the distinction between normal and abnormal element. Dali with his paranoid critical method reconciles actual representations with mythical and symbolic elements, breaking through the limits between objectivity and subjectivity. Kalas puts forward the social origin of insanity along with the fundamental surrealist notions of individual freedom and will. For a more complete understanding of this attempt, it was considered useful to include elements of the main views on madness from the standpoint of a critical approach in psychiatry and psychology. The surrealistic view seems to be close to this critical approach which is likely to have been affected by it on the level in which the movements and scientific fields meet and interact. The relationship between surrealism, the notion and expression of madness and the absurd seems to be inherent to the very development of the movement through its core and individual pursuits. In conclusion, the relationship between surrealism and the notion and expression of the madness and the absurd seems to be inherent to the very birth of the movement through its main positions and pursuits. The question of so-called reality, its overshoot and the vision of a hyperreality that will incorporates the challenges and contradictions of this reality, are points loudly expressed through artistic activities and scientific researches and practices. A common ground to all these aspects is the liberation of desire, the questioning of rationality, the integration and acceptance of the absurd, as well as, the dispute of it as such, and finally the social change-driven by the individual psychological development.

There's Method in Our Madness: Interpersonal Attraction as a Multidimensional Construct

ERIC Educational Resources Information Center

Latta, R. Michael

1976-01-01

Examines the similarity-attraction relationship using rating scale and bogus pipeline (a pseudophysiological monitoring device) techniques within the context of individual differences in social desirability biases and variations in experimental demands. (Author/RK)

Sequestration of CDH1 by MAD2L2 prevents premature APC/C activation prior to anaphase onset

PubMed Central

Listovsky, Tamar

2013-01-01

The switch from activation of the anaphase-promoting complex/cyclosome (APC/C) by CDC20 to CDH1 during anaphase is crucial for accurate mitosis. APC/CCDC20 ubiquitinates a limited set of substrates for subsequent degradation, including Cyclin B1 and Securin, whereas APC/CCDH1 has a broader specificity. This switch depends on dephosphorylation of CDH1 and the APC/C, and on the degradation of CDC20. Here we show, in human cells, that the APC/C inhibitor MAD2L2 also contributes to ensuring the sequential activation of the APC/C by CDC20 and CDH1. In prometaphase, MAD2L2 sequestered free CDH1 away from the APC/C. At the onset of anaphase, MAD2L2 was rapidly degraded by APC/CCDC20, releasing CDH1 to activate the dephosphorylated APC/C. Loss of MAD2L2 led to premature association of CDH1 with the APC/C, early destruction of APC/CCDH1 substrates, and accelerated mitosis with frequent mitotic aberrations. Thus, MAD2L2 helps to ensure a robustly bistable switch between APC/CCDC20 and APC/CCDH1 during the metaphase-to-anaphase transition, thereby contributing to mitotic fidelity. PMID:24100295

Metastable Atom-Activated Dissociation Mass Spectrometry of Phosphorylated and Sulfonated Peptides in Negative Ion Mode

NASA Astrophysics Data System (ADS)

Cook, Shannon L.; Jackson, Glen P.

2011-06-01

The dissociation behavior of phosphorylated and sulfonated peptide anions was explored using metastable atom-activated dissociation mass spectrometry (MAD-MS) and collision-induced dissociation (CID). A beam of high kinetic energy helium (He) metastable atoms was exposed to isolated phosphorylated and sulfonated peptides in the 3- and 2- charge states. Unlike CID, where phosphate losses are dominant, the major dissociation channels observed using MAD were Cα - C peptide backbone cleavages and neutral losses of CO2, H2O, and [CO2 + H2O] from the charge reduced (oxidized) product ion, consistent with an electron detachment dissociation (EDD) mechanism such as Penning ionization. Regardless of charge state or modification, MAD provides ample backbone cleavages with little modification loss, which allows for unambiguous PTM site determination. The relative abundance of certain fragment ions in MAD is also demonstrated to be somewhat sensitive to the number and location of deprotonation sites, with backbone cleavage somewhat favored adjacent to deprotonated sites like aspartic acid residues. MAD provides a complementary dissociation technique to CID, ECD, ETD, and EDD for peptide sequencing and modification identification. MAD offers the unique ability to analyze highly acidic peptides that contain few to no basic amino acids in either negative or positive ion mode.

MADS-box genes and floral development: the dark side.

PubMed

Heijmans, Klaas; Morel, Patrice; Vandenbussche, Michiel

2012-09-01

The origin of the flower during evolution has been a crucial step in further facilitating plants to colonize a wide range of different niches on our planet. The >250 000 species of flowering plants existing today display an astonishing diversity in floral architecture. For this reason, the flower is a very attractive subject for evolutionary developmental (evo-devo) genetics studies. Research during the last two decades has provided compelling evidence that the origin and functional diversification of MIKC(c) MADS-box transcription factors has played a critical role during evolution of flowering plants. As master regulators of floral organ identity, MADS-box proteins are at the heart of the classic ABC model for floral development. Despite the enormous progress made in the field of floral development, there still remain aspects that are less well understood. Here we highlight some of the dark corners within our current knowledge on MADS-box genes and flower development, which would be worthwhile investigating in more detail in future research. These include the general question of to what extent MADS-box gene functions are conserved between species, the function of TM8-clade MADS-box genes which so far have remained uncharacterized, the divergence within the A-function, and post-transcriptional regulation of the ABC-genes.

Phycomyces MADB interacts with MADA to form the primary photoreceptor complex for fungal phototropism.

PubMed

Sanz, Catalina; Rodríguez-Romero, Julio; Idnurm, Alexander; Christie, John M; Heitman, Joseph; Corrochano, Luis M; Eslava, Arturo P

2009-04-28

The fungus Phycomyces blakesleeanus reacts to environmental signals, including light, gravity, touch, and the presence of nearby objects, by changing the speed and direction of growth of its fruiting body (sporangiophore). Phototropism, growth toward light, shares many features in fungi and plants but the molecular mechanisms remain to be fully elucidated. Phycomyces mutants with altered phototropism were isolated approximately 40 years ago and found to have mutations in the mad genes. All of the responses to light in Phycomyces require the products of the madA and madB genes. We showed that madA encodes a protein similar to the Neurospora blue-light photoreceptor, zinc-finger protein WC-1. We show here that madB encodes a protein similar to the Neurospora zinc-finger protein WC-2. MADA and MADB interact to form a complex in yeast 2-hybrid assays and when coexpressed in E. coli, providing evidence that phototropism and other responses to light are mediated by a photoresponsive transcription factor complex. The Phycomyces genome contains 3 genes similar to wc-1, and 4 genes similar to wc-2, many of which are regulated by light in a madA or madB dependent manner. We did not detect any interactions between additional WC proteins in yeast 2-hybrid assays, which suggest that MADA and MADB form the major photoreceptor complex in Phycomyces. However, the presence of multiple wc genes in Phycomyces may enable perception across a broad range of light intensities, and may provide specialized photoreceptors for distinct photoresponses.

Effect of mandibular advancement device on sleep bruxism score and sleep quality.

PubMed

Solanki, Nehal; Singh, Balendra Pratap; Chand, Pooran; Siddharth, Ramashankar; Arya, Deeksha; Kumar, Lakshya; Tripathi, Suryakant; Jivanani, Hemant; Dubey, Abhishek

2017-01-01

The use of mandibular advancement devices (MADs) in the treatment of sleep bruxism is gaining widespread importance. However, the effects of MADs on sleep bruxism scores, sleep quality, and occlusal force are not clear. The purpose of this clinical study was to analyze the effect of MADs on sleep bruxism scores, sleep quality, and occlusal force. This uncontrolled before and after study enrolled 30 participants with sleep bruxism. Outcomes assessed were sleep quality, sleep bruxism scores (sleep bruxism bursts and sleep bruxism episodes/hour), and occlusal force before and after 15 and 30 days of using a MAD. Sleep bruxism scores were assessed by ambulatory polysomnography and sleep quality by using the Pittsburgh sleep quality index (PSQI). Occlusal force was recorded by using a digital gnathodynamometer in the first molar region on both sides. Statistical analysis was done by 1-factor repeated measures ANOVA (α=.05). Statistically significant reductions in sleep bruxism bursts/h, sleep bruxism episodes/h, and PSQI scores were found after 15 and 30 days of using a MAD (P<.001). Statistically significant reduction in occlusal force on both sides was found only after 15 days (P<.001) but not after 30 days of using a MAD (P=.292 on left side, and P=.575 on the right side). The study showed a short-term improvement in sleep bruxism scores, sleep quality, and reduction in occlusal force in sleep bruxism participants after using MADs. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Phycomyces MADB interacts with MADA to form the primary photoreceptor complex for fungal phototropism

PubMed Central

Sanz, Catalina; Rodríguez-Romero, Julio; Idnurm, Alexander; Christie, John M.; Heitman, Joseph; Corrochano, Luis M.; Eslava, Arturo P.

2009-01-01

The fungus Phycomyces blakesleeanus reacts to environmental signals, including light, gravity, touch, and the presence of nearby objects, by changing the speed and direction of growth of its fruiting body (sporangiophore). Phototropism, growth toward light, shares many features in fungi and plants but the molecular mechanisms remain to be fully elucidated. Phycomyces mutants with altered phototropism were isolated ≈40 years ago and found to have mutations in the mad genes. All of the responses to light in Phycomyces require the products of the madA and madB genes. We showed that madA encodes a protein similar to the Neurospora blue-light photoreceptor, zinc-finger protein WC-1. We show here that madB encodes a protein similar to the Neurospora zinc-finger protein WC-2. MADA and MADB interact to form a complex in yeast 2-hybrid assays and when coexpressed in E. coli, providing evidence that phototropism and other responses to light are mediated by a photoresponsive transcription factor complex. The Phycomyces genome contains 3 genes similar to wc-1, and 4 genes similar to wc-2, many of which are regulated by light in a madA or madB dependent manner. We did not detect any interactions between additional WC proteins in yeast 2-hybrid assays, which suggest that MADA and MADB form the major photoreceptor complex in Phycomyces. However, the presence of multiple wc genes in Phycomyces may enable perception across a broad range of light intensities, and may provide specialized photoreceptors for distinct photoresponses. PMID:19380729

The Fe-S cluster-containing NEET proteins mitoNEET and NAF-1 as chemotherapeutic targets in breast cancer.

PubMed

Bai, Fang; Morcos, Faruck; Sohn, Yang-Sung; Darash-Yahana, Merav; Rezende, Celso O; Lipper, Colin H; Paddock, Mark L; Song, Luhua; Luo, Yuting; Holt, Sarah H; Tamir, Sagi; Theodorakis, Emmanuel A; Jennings, Patricia A; Onuchic, José N; Mittler, Ron; Nechushtai, Rachel

2015-03-24

Identification of novel drug targets and chemotherapeutic agents is a high priority in the fight against cancer. Here, we report that MAD-28, a designed cluvenone (CLV) derivative, binds to and destabilizes two members of a unique class of mitochondrial and endoplasmic reticulum (ER) 2Fe-2S proteins, mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1), recently implicated in cancer cell proliferation. Docking analysis of MAD-28 to mNT/NAF-1 revealed that in contrast to CLV, which formed a hydrogen bond network that stabilized the 2Fe-2S clusters of these proteins, MAD-28 broke the coordinative bond between the His ligand and the cluster's Fe of mNT/NAF-1. Analysis of MAD-28 performed with control (Michigan Cancer Foundation; MCF-10A) and malignant (M.D. Anderson-metastatic breast; MDA-MB-231 or MCF-7) human epithelial breast cells revealed that MAD-28 had a high specificity in the selective killing of cancer cells, without any apparent effects on normal breast cells. MAD-28 was found to target the mitochondria of cancer cells and displayed a surprising similarity in its effects to the effects of mNT/NAF-1 shRNA suppression in cancer cells, causing a decrease in respiration and mitochondrial membrane potential, as well as an increase in mitochondrial iron content and glycolysis. As expected, if the NEET proteins are targets of MAD-28, cancer cells with suppressed levels of NAF-1 or mNT were less susceptible to the drug. Taken together, our results suggest that NEET proteins are a novel class of drug targets in the chemotherapeutic treatment of breast cancer, and that MAD-28 can now be used as a template for rational drug design for NEET Fe-S cluster-destabilizing anticancer drugs.

Technical note: Data loggers are a valid method for assessing the feeding behavior of dairy cows using the Calan Broadbent Feeding System.

PubMed

Krawczel, P D; Klaiber, L M; Thibeau, S S; Dann, H M

2012-08-01

Assessing feeding behavior is important in understanding the effects of nutrition and management on the well-being of dairy cows. Historically, collection of these data from cows fed with a Calan Broadbent Feeding System (American Calan Inc., Northwood, NH) required the labor-intensive practices of direct observation or video review. The objective of this study was to evaluate the agreement between the output of a HOBO change-of-state data logger (Onset Computer Corp., Bourne, MA), mounted to the door shell and latch plate, and video data summarized with continuous sampling. Data (number of feed bin visits per day and feeding time in minutes per day) were recorded with both methods from 26 lactating cows and 10 nonlactating cows for 3 d per cow (n=108). The agreement of the data logger and video methods was evaluated using the REG procedure of SAS to compare the mean response of the methods against the difference between the methods. The maximum allowable difference (MAD) was set at ±3 for bin visits and ±20 min for feeding time. Ranges for feed bin visits (2 to 140 per d) and feeding time (28 to 267 min/d) were established from video data. Using the complete data set, agreement was partially established between the data logger and video methods for feed bin visits, but not established for feeding time. The complete data set generated by the data logger was screened to remove visits of a duration ≤3 s, reflecting a cow unable to enter a feed bin (representing 7% of all data) and ≥5,400 s, reflecting a failure of the data logger to align properly with its corresponding magnetic field (representing <1% of all data). Using the resulting screened data set, agreement was established for feed bin visits and feeding time. For bin visits, 4% of the data was beyond the MAD. For feeding time, 3% of the data was beyond the MAD and 74% of the data was ±1 min. The insignificant P-value, low coefficient of determination, and concentration of the data within the MAD indicate the agreement of the change-of-state data logger and video data. This suggests the usage of a change-of-state data logger to assess the feeding behavior of cows feeding from a Calan Broadbent Feeding System is appropriate. Use of the screening criteria for data analysis is recommended. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Sexual aggression: mad, bad, and mad.

PubMed

Schopp, Rovert F

2003-06-01

Legal institutions in the Western liberal tradition ordinarily rely primarily on the criminal justice system to address conduct by some individuals that deliberately harms other individuals. The mental health system provides an alternative institutional structure through which societies can address such harmful behavior. Those who deliberately engage in conduct that causes harm to others are traditionally addressed through either the criminal justice or mental health systems on the basis of their being categorized as either "bad or mad." This paper examines some of the relevant reasons for categorizing sexual aggression as bad or mad. It emphasizes the significance of such categorization for the broader set of legal institutions of coercive social control and for the manner in which we respond to persons within those institutions.

The Method behind the Madness: Acquiring Online Journals and a Solution to Provide Access

ERIC Educational Resources Information Center

Skekel, Donna

2005-01-01

Libraries are seeking the best possible solution for integrating online journals into their collections. While exploring the different methods and technology available, many libraries still strive to fulfill the original "library mission" proposed by Charles Cutter in his "Rules for a Dictionary Catalog". Providing comprehensive access to…

A Little More Madness in Our Methods? A Snapshot of How the Educational Leadership, Management and Administration Field Conducts Research

ERIC Educational Resources Information Center

Thomson, Pat

2017-01-01

The field of educational leadership, management and administration (ELMA) uses methods drawn primarily from cognate educational disciplines. But does this matter? This paper explores the methods used in recently published papers through a snapshot of six issues of six ELMA journals. The analysis showed a preponderance of survey, interview and case…

From CBCL to DSM: A Comparison of Two Methods to Screen for DSM-IV Diagnoses Using CBCL Data

ERIC Educational Resources Information Center

Krol, Nicole P. C. M.; De Bruyn, Eric E. J.; Coolen, Jolanda C.; van Aarle, Edward J. M.

2006-01-01

The screening efficiency of 2 methods to convert Child Behavior Checklist (CBCL) assessment data into Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) diagnoses was compared. The Machine-Aided Diagnosis (MAD) method converts CBCL input data directly into DSM-IV symptom criteria. The…

Measures that identify prescription medication misuse, abuse, and related events in clinical trials: ACTTION critique and recommended considerations

PubMed Central

Smith, Shannon M.; Jones, Judith K.; Katz, Nathaniel P.; Roland, Carl L.; Setnik, Beatrice; Trudeau, Jeremiah J.; Wright, Stephen; Burke, Laurie B.; Comer, Sandra D.; Dart, Richard C.; Dionne, Raymond; Haddox, J. David; Jaffe, Jerome H.; Kopecky, Ernest A.; Martell, Bridget A.; Montoya, Ivan D.; Stanton, Marsha; Wasan, Ajay D.; Turk, Dennis C.; Dworkin, Robert H.

2017-01-01

Accurate assessment of inappropriate medication use events (i.e., misuse, abuse, and related events [MAREs]) occurring in clinical trials is an important component in evaluating a medication’s abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions [27]. Only 2 approaches have been reported that are specifically designed to identify and classify MAREs occurring in clinical trials, rather than to measure an individual’s risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion [SR-MAD] instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System [MADDERS]. The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively in order to determine the underlying intent. MADDERS can also be applied retrospectively to completed trial data. SR-MAD can be used prospectively; additional development may be required to standardize its implementation and fully appraise the intent of inappropriate use events. Additional research is needed to further demonstrate the validity and utility of both MADDERS and SR-MAD. PMID:28479207

A Survey of MIKC Type MADS-Box Genes in Non-seed Plants: Algae, Bryophytes, Lycophytes and Ferns

PubMed Central

Thangavel, Gokilavani; Nayar, Saraswati

2018-01-01

MADS box transcription factors have been studied extensively in flowering plants but remain less studied in non-seed plants. MADS box is one such example of a gene which is prevalent across many classes of plants ranging from chlorophyta to embryophyta as well as fungi and animals. MADS box transcription factors are of two types, Type I and Type II. Type II transcription factors (TF) that consist of a MADS domain, I region, K domain, and C terminal domain are discussed in this review. The Type II/ MIKC class is widespread across charophytes and all major lineages of land plants but unknown in green and red algae. These transcription factors have been implicated in floral development in seed plants and thus the question arises, “What is their role in non-seed plants?” From the studies reviewed here it can be gathered that unlike seed plants, MIKCC genes in non-seed plants have roles in both gametophytic and sporophytic generations and contribute to the development of both vegetative and reproductive structures. On the other hand as previously observed in seed plants, MIKC* genes of non-seed plants have a conserved role during gametophyte development. With respect to evolution of MIKC genes in non-seed plants, the number of common ancestors is probably very few at each branch. The expansion of this gene family in seed plants and increased plant complexity seem to be correlated. As gradually the genomes of non-seed plants are becoming available it is worthwhile to gather the existing information about MADS box genes in non-seed plants. This review highlights various MIKC MADS box genes discovered so far in non-seed plants, their possible roles and an insight into their evolution. PMID:29720991

A Survey of MIKC Type MADS-Box Genes in Non-seed Plants: Algae, Bryophytes, Lycophytes and Ferns.

PubMed

Thangavel, Gokilavani; Nayar, Saraswati

2018-01-01

MADS box transcription factors have been studied extensively in flowering plants but remain less studied in non-seed plants. MADS box is one such example of a gene which is prevalent across many classes of plants ranging from chlorophyta to embryophyta as well as fungi and animals. MADS box transcription factors are of two types, Type I and Type II. Type II transcription factors (TF) that consist of a MADS domain, I region, K domain, and C terminal domain are discussed in this review. The Type II/ MIKC class is widespread across charophytes and all major lineages of land plants but unknown in green and red algae. These transcription factors have been implicated in floral development in seed plants and thus the question arises, "What is their role in non-seed plants?" From the studies reviewed here it can be gathered that unlike seed plants, MIKC C genes in non-seed plants have roles in both gametophytic and sporophytic generations and contribute to the development of both vegetative and reproductive structures. On the other hand as previously observed in seed plants, MIKC * genes of non-seed plants have a conserved role during gametophyte development. With respect to evolution of MIKC genes in non-seed plants, the number of common ancestors is probably very few at each branch. The expansion of this gene family in seed plants and increased plant complexity seem to be correlated. As gradually the genomes of non-seed plants are becoming available it is worthwhile to gather the existing information about MADS box genes in non-seed plants. This review highlights various MIKC MADS box genes discovered so far in non-seed plants, their possible roles and an insight into their evolution.

Organization, regulatory sequences, and alternatively spliced transcripts of the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) gene

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

Sampaio, S.O.; Mei, C.; Butcher, E.C.

The mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is expressed selectively at venular sites of lymphocyte extravasation into mucosal lymphoid tissues and lamina propria, where it directs local lymphocyte trafficking. MAdCAM-1 is a multifunctional type I transmembrane adhesion molecule comprising two distal Ig domains involved in {alpha}4{beta}7 integrin binding, a mucin-like region able to display L-selectin-binding carbohydrates, and a membrane-proximal Ig domain homologous to IgA. We show in this work that the MAdCAM-1 gene is located on chromosome 10 and contains five exons. The signal peptide and each one of the three Ig domains are encoded by a distinct exon, whereasmore » the transmembrane, cytoplasmic tail, and 3{prime}-untranslated region of MAdCAM-1 are combined on a single exon. The mucin-like region and the third Ig domain are encoded together on exon 4. An alternatively spliced MAdCAM-1 mRNA is identified that lacks the mucin/IgA-homologous exon 4-encoded sequences. This short variant of MAdCAM-1 may be specialized to support {alpha}4{beta}7-dependent adhesion strengthening, independent of carbohydrate-presenting function. Sequences 5{prime} of the transcription start site include tandem nuclear factor-KB sites; AP-1, AP-2, and signal peptide-1 binding sites; and an estrogen response element. Our findings reinforce the correspondence between the multidomain structure and versatile functions of this vascular addressin, and suggest an additional level of regulation of carbohydrate-presenting capability, and thus of its importance in lectin-mediated vs. {alpha}4{beta}7-dependent adhesive events in lymphocyte trafficking. 46 refs., 6 figs., 1 tab.« less

Metformin Protects Neurons against Oxygen-Glucose Deprivation/Reoxygenation -Induced Injury by Down-Regulating MAD2B.

PubMed

Meng, Xianfang; Chu, Guangpin; Yang, Zhihua; Qiu, Ping; Hu, Yue; Chen, Xiaohe; Peng, Wenpeng; Ye, Chen; He, Fang-Fang; Zhang, Chun

2016-01-01

Metformin, the common medication for type II diabetes, has protective effects on cerebral ischemia. However, the molecular mechanisms are far from clear. Mitotic arrest deficient 2-like protein 2 (MAD2B), an inhibitor of the anaphase-promoting complex (APC), is widely expressed in hippocampal and cortical neurons and plays an important role in mediating high glucose-induced neurotoxicity. The present study investigated whether metformin modifies the expression of MAD2B and to exert its neuroprotective effects in primary cultured cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a widely used in vitro model of ischemia/reperfusion. Primary cortical neurons were cultured, deprived of oxygen-glucose for 1 h, and then recovered with oxygen-glucose for 12 h and 24 h. Cell viability was measured by detecting the levels of lactate dehydrogenase (LDH) in culture medium. The levels of MAD2B, cyclin B and p-histone 3 were measured by Western blot. Cell viability of neurons was reduced under oxygen-glucose deprivation/reoxygenation (OGD/R). The expression of MAD2B was increased under OGD/R. The levels of cyclin B1, which is a substrate of APC, were also increased. Moreover, OGD/R up-regulated the phosphorylation levels of histone 3, which is the induction of aberrant re-entry of post-mitotic neurons. However, pretreatment of neurons with metformin alleviated OGD/R-induced injury. Metformin further decreased the expression of MAD2B, cyclin B1 and phosphorylation levels of histone 3. Metformin exerts its neuroprotective effect through regulating the expression of MAD2B in neurons under OGD/R. © 2016 The Author(s) Published by S. Karger AG, Basel.

Mad Cow Disease and U.S. Beef Trade

DTIC Science & Technology

2006-12-06

1 For additional details and background see CRS Report RS22345, BSE (“Mad Cow Disease:): A Brief Overview, and CRS Report RL32199, Bovine Spongiform ...foreign markets that banned U.S. beef when a cow in Washington state tested positive for bovine spongiform encephalopathy (BSE, or mad cow disease) in...rejection of three shipments of U.S. beef because of the presence of bone fragments. CRS-4 8 See also CRS Report RL32932, Bovine Spongiform

Functional Conservation of MIKC*-Type MADS Box Genes in Arabidopsis and Rice Pollen Maturation[C][W

PubMed Central

Liu, Yuan; Cui, Shaojie; Wu, Feng; Yan, Shuo; Lin, Xuelei; Du, Xiaoqiu; Chong, Kang; Schilling, Susanne; Theißen, Günter; Meng, Zheng

2013-01-01

There are two groups of MADS intervening keratin-like and C-terminal (MIKC)-type MADS box genes, MIKCC type and MIKC* type. In seed plants, the MIKCC type shows considerable diversity, but the MIKC* type has only two subgroups, P- and S-clade, which show conserved expression in the gametophyte. To examine the functional conservation of MIKC*-type genes, we characterized all three rice (Oryza sativa) MIKC*-type genes. All three genes are specifically expressed late in pollen development. The single knockdown or knockout lines, respectively, of the S-clade MADS62 and MADS63 did not show a mutant phenotype, but lines in which both S-clade genes were affected showed severe defects in pollen maturation and germination, as did knockdown lines of MADS68, the only P-clade gene in rice. The rice MIKC*-type proteins form strong heterodimeric complexes solely with partners from the other subclade; these complexes specifically bind to N10-type C-A-rich-G-boxes in vitro and regulate downstream gene expression by binding to N10-type promoter motifs. The rice MIKC* genes have a much lower degree of functional redundancy than the Arabidopsis thaliana MIKC* genes. Nevertheless, our data indicate that the function of heterodimeric MIKC*-type protein complexes in pollen development has been conserved since the divergence of monocots and eudicots, roughly 150 million years ago. PMID:23613199

Identification and validation of mixed anxiety-depression.

PubMed

Hettema, J M; Aggen, S H; Kubarych, T S; Neale, M C; Kendler, K S

2015-10-01

Mixed anxiety-depression (MAD) has been under scrutiny to determine its potential place in psychiatric nosology. The current study sought to investigate its prevalence, clinical characteristics, course and potential validators. Restricted latent-class analyses were fit to 12-month self-reports of depression and anxiety symptom criteria in a large population-based sample of twins. Classes were examined across an array of relevant indicators (demographics, co-morbidity, adverse life events, clinical significance and twin concordance). Longitudinal analyses investigated the stability of, and transitions between, these classes for two time periods approximately 1.5 years apart. In all analyses, a class exhibiting levels of MAD symptomatology distinctly above the unaffected subjects yet having low prevalence of either major depression (MD) or generalized anxiety disorder (GAD) was identified. A restricted four-class model, constraining two classes to have no prior disorder history to distinguish residual or recurrent symptoms from new onsets in the last year, provided an interpretable classification: two groups with no prior history that were unaffected or had MAD and two with prior history having relatively low or high symptom levels. Prevalence of MAD was substantial (9-11%), and subjects with MAD differed quantitatively but not qualitatively from those with lifetime MD or GAD across the clinical validators examined. Our findings suggest that MAD is a commonly occurring, identifiable syndromal subtype that warrants further study and consideration for inclusion in future nosologic systems.

Effects of rapid palatal expansion (RPE) and twin block mandibular advancement device (MAD) on pharyngeal structures in Class II pediatric patients from Cluj-Napoca, Romania.

PubMed

Rădescu, Ovidiu Dănuţ; Colosi, Horațiu Alexandru; Albu, Silviu

2018-05-23

To compare cephalometric changes of pharyngeal structures after rapid palatal expansion (RPE) with those induced by a twin block mandibular advancement device (MAD) with palatal expansion capability. This retrospective study investigated 55 Class II pediatric patients, divided into two groups: 29 patients treated with RPE and 26 patients treated with MAD. Lateral cephalometric measurements were compared before and after treatment. Changes in pharyngeal airway space were statistically significant in both groups (p < 0.001) from a pre-treatment mean distance measured between the lower posterior pharyngeal wall and the hyoid bone (LPF-H) of 25.42 mm in the MAD group and 28.62 mm in the RPE group, to a post-treatment mean LPF-H of 27.96 mm in the MAD group and 31.52 mm in the RPE group. Significant changes in pharyngeal space may be obtained in Class II patients through both rapid palatal expansion and mandibular advancement devices with palatal expansion capability.

Overexpression of the cucumber LEAFY homolog CFL and hormone treatments alter flower development in gloxinia (Sinningia speciosa).

PubMed

Zhang, Ming-Zhe; Ye, Dan; Wang, Li-Lin; Pang, Ji-Liang; Zhang, Yu-Hong; Zheng, Ke; Bian, Hong-Wu; Han, Ning; Pan, Jian-Wei; Wang, Jun-Hui; Zhu, Mu-Yuan

2008-07-01

Leafy (LFY) and LFY-like genes control the initiation of floral meristems and regulate MADS-box genes in higher plants. The Cucumber-FLO-LFY (CFL) gene, a LFY homolog in Cucumis sativus L. is expressed in the primordia, floral primordia, and each whirl of floral organs during the early stage of flower development. In this study, functions of CFL in flower development were investigated by overexpressing the CFL gene in gloxinia (Sinningia speciosa). Our results show that constitutive CFL overexpression significantly promote early flowering without gibberellin (GA(3)) supplement, suggesting that CFL can serve functionally as a LFY homolog in gloxinia. Moreover, GA(3) and abscisic acid (ABA) treatments could modulate the expression of MADS-box genes in opposite directions. GA(3) resembles the overexpression of CFL in the expression of MADS-box genes and the regeneration of floral buds, but ABA inhibits the expression of MADS-box genes and flower development. These results suggest that CFL and downstream MADS-box genes involved in flower development are regulated by GA(3) and ABA.

The effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment.

PubMed

Ng Tang Fui, Mark; Hoermann, Rudolf; Zajac, Jeffrey D; Grossmann, Mathis

2017-10-01

Testosterone treatment in obese dieting men augments the diet-associated loss of fat mass, but protects against loss of lean mass. We assessed whether body composition changes are maintained following withdrawal of testosterone treatment. We conducted a prespecified double-blind randomized placebo-controlled observational follow-up study of a randomized controlled trial (RCT). Participants were men with baseline obesity (body mass index >30 kg/m 2 ) and a repeated total testosterone level <12 nmol/L, previously enrolled in a 56-week testosterone treatment trial combined with a weight loss programme. Main outcome measures were mean adjusted differences (MAD) (95% confidence interval), in body composition between testosterone- and placebo-treated men at the end of the observation period. Of the 100 randomized men, 82 completed the RCT and 64 the subsequent observational study. Median [IQR] observation time after completion of the RCT was 82 weeks [74; 90] in men previously receiving testosterone (cases) and 81 weeks [67;91] in men previously receiving placebo (controls), P=.51. At the end of the RCT, while losing similar amounts of weight, cases had, compared to controls, lost more fat mass, MAD -2.9 kg (-5.7, -0.2), P=.04, but had lost less lean mass MAD 3.4 kg (1.3, 5.5), P=.002. At the end of the observation period, the former between-group differences in fat mass, MAD -0.8 kg (-3.6, 2.0), P=1.0, in lean mass, MAD -1.3 kg (-3.0, 0.5), P=.39, and in appendicular lean mass, MAD -0.1 kg/m 2 (-0.3, 0.1), P=.45, were no longer apparent. During observation, cases lost more lean mass, MAD -3.7 kg (-5.5, -1.9), P=.0005, and appendicular lean mass, MAD -0.5 kg/m 2 (-0.8, -0.3), P<.0001 compared to controls. The favourable effects of testosterone on body composition in men subjected to a concomitant weight loss programme were not maintained at 82 weeks after testosterone treatment cessation. © 2017 John Wiley & Sons Ltd.

Marginal and internal discrepancies of zirconia copings: effects of milling system and finish line design.

PubMed

Ribeiro, Isabella Lima Arrais; Campos, Fernanda; Sousa, Rafael Santiago; Alves, Maria Luiza Lima; Rodrigues, Dalton Matos; Souza, Rodrigo Othavio Assuncão; Bottino, Marco Antonio

2015-01-01

Discrepancies at the abutment/crown interface can affect the longevity of zirconia restorations. The aim was to evaluate the marginal and internal discrepancies (MD and ID) of zirconia copings manufactured by two milling systems with different finish lines. Three aluminum-master-dies (h = 5.5 mm; Ψ =7.5 mm; 6΀), with different finish lines (large chamfer [LC]; tilted chamfer [TC]; rounded shoulder [RS]) were fabricated. Twenty impressions were made from each master die and poured. Sixty zirconia copings were manufactured and divided according to the factors "finish line" and "milling system" (n = 10): CAD LC = Computer-aided design/computer-aided manufacturing (CAD/CAM) + LC; CAD TC = CAD/CAM + TC; CAD RS = CAD/CAM + RS; MAD LC = manually aided design/manually aided manufacturing (MAD/MAM) + LC; MAD TC = MAD/MAM + TC; and MAD RS = MAD/MAM + RS. For MD analysis, each coping was fixed, and the distance between the external edges of the coping and the edge of the cervical preparation was measured (50 points). Using the same copings, the ID of each coping was evaluated, by the replica technique, at 12 points equally distributed among the regions (n = 10): Ray (R), axial (A), and occlusal (Occl). The measurements were performed by optical microscopy (Χ250). The data (μm) were subjected to parametric and non-parametric statistical analyses. For the MAD/MAM system, the "finish line" (P = 0.0001) affected significantly the MD median values (μm): LC = 251.80 a , RS = 68.40 a and TC = 8.10 b (Dunn's test). For the CAD/CAM system, the median MD values (μm) were not affected by the factor "finish line" (P = 0.4037): LC = 0.82 a , RS = 0.52 a , and TC = 0.89 a . For the ID, it was observed interaction between the finish line types and the region (P = 0.0001) and between region and milling system (P = 0.0031) (RM-ANOVA). The CAD/CAM system presented lower MD values, regardless the finish line. However, the MAD/MAM system showed ID values smaller than those of CAD/CAM.

Intensity Thresholds on Raw Acceleration Data: Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD) Approaches.

PubMed

Bakrania, Kishan; Yates, Thomas; Rowlands, Alex V; Esliger, Dale W; Bunnewell, Sarah; Sanders, James; Davies, Melanie; Khunti, Kamlesh; Edwardson, Charlotte L

2016-01-01

(1) To develop and internally-validate Euclidean Norm Minus One (ENMO) and Mean Amplitude Deviation (MAD) thresholds for separating sedentary behaviours from common light-intensity physical activities using raw acceleration data collected from both hip- and wrist-worn tri-axial accelerometers; and (2) to compare and evaluate the performances between the ENMO and MAD metrics. Thirty-three adults [mean age (standard deviation (SD)) = 27.4 (5.9) years; mean BMI (SD) = 23.9 (3.7) kg/m2; 20 females (60.6%)] wore four accelerometers; an ActiGraph GT3X+ and a GENEActiv on the right hip; and an ActiGraph GT3X+ and a GENEActiv on the non-dominant wrist. Under laboratory-conditions, participants performed 16 different activities (11 sedentary behaviours and 5 light-intensity physical activities) for 5 minutes each. ENMO and MAD were computed from the raw acceleration data, and logistic regression and receiver-operating-characteristic (ROC) analyses were implemented to derive thresholds for activity discrimination. Areas under ROC curves (AUROC) were calculated to summarise performances and thresholds were assessed via executing leave-one-out-cross-validations. For both hip and wrist monitor placements, in comparison to the ActiGraph GT3X+ monitors, the ENMO and MAD values derived from the GENEActiv devices were observed to be slightly higher, particularly for the lower-intensity activities. Monitor-specific hip and wrist ENMO and MAD thresholds showed excellent ability for separating sedentary behaviours from motion-based light-intensity physical activities (in general, AUROCs >0.95), with validation indicating robustness. However, poor classification was experienced when attempting to isolate standing still from sedentary behaviours (in general, AUROCs <0.65). The ENMO and MAD metrics tended to perform similarly across activities and accelerometer brands. Researchers can utilise these robust monitor-specific hip and wrist ENMO and MAD thresholds, in order to accurately separate sedentary behaviours from common motion-based light-intensity physical activities. However, caution should be taken if isolating sedentary behaviours from standing is of particular interest.

Metric Madness

ERIC Educational Resources Information Center

Kroon, Cindy D.

2007-01-01

Created for a Metric Day activity, Metric Madness is a board game for two to four players. Students review and practice metric vocabulary, measurement, and calculations by playing the game. Playing time is approximately twenty to thirty minutes.

Agave tequilana MADS genes show novel expression patterns in meristems, developing bulbils and floral organs.

PubMed

Delgado Sandoval, Silvia del Carmen; Abraham Juárez, María Jazmín; Simpson, June

2012-03-01

Agave tequilana is a monocarpic perennial species that flowers after 5-8 years of vegetative growth signaling the end of the plant's life cycle. When fertilization is unsuccessful, vegetative bulbils are induced on the umbels of the inflorescence near the bracteoles from newly formed meristems. Although the regulation of inflorescence and flower development has been described in detail for monocarpic annuals and polycarpic species, little is known at the molecular level for these processes in monocarpic perennials, and few studies have been carried out on bulbils. Histological samples revealed the early induction of umbel meristems soon after the initiation of the vegetative to inflorescence transition in A. tequilana. To identify candidate genes involved in the regulation of floral induction, a search for MADS-box transcription factor ESTs was conducted using an A. tequilana transcriptome database. Seven different MIKC MADS genes classified into 6 different types were identified based on previously characterized A. thaliana and O. sativa MADS genes and sequences from non-grass monocotyledons. Quantitative real-time PCR analysis of the seven candidate MADS genes in vegetative, inflorescence, bulbil and floral tissues uncovered novel patterns of expression for some of the genes in comparison with orthologous genes characterized in other species. In situ hybridization studies using two different genes showed expression in specific tissues of vegetative meristems and floral buds. Distinct MADS gene regulatory patterns in A. tequilana may be related to the specific reproductive strategies employed by this species.

Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome.

PubMed

Vroegop, Anneclaire V M T; Vanderveken, Olivier M; Dieltjens, Marijke; Wouters, Kristien; Saldien, Vera; Braem, Marc J; Van de Heyning, Paul H

2013-06-01

The aim of this study was to assess the value of drug-induced sleep endoscopy (DISE) using a custom-made simulation bite in maximal comfortable protrusion (MCP) of the mandible, in the prediction of treatment outcome for obstructive sleep apnea (OSA) with a mandibular advancement device (MAD). Two hundred patients (74% male; age 46 ± 9 years; apnea-hypopnea index [AHI] 19 ± 13 h(-1) sleep; body mass index [BMI] 27 ± 4 kg m(-2) ) with sleep-disordered breathing underwent DISE with a simulation bite in MCP. One hundred and thirty-five patients with an established diagnosis of OSA commenced MAD treatment. The associations between the findings during DISE with simulation bite and treatment outcome were evaluated. Treatment response was defined as a reduction in AHI following MAD treatment of ≥ 50% compared to baseline. Overall MAD treatment response in the studied population was 69%. The results of this study demonstrated a statistically significant association between a positive effect of the simulation bite on the upper airway patency during DISE and treatment response with MAD (P < 0.01). The results of this study suggest that the use of a simulation bite in maximal comfortable protrusion (MCP) of the mandible, as used during DISE in patients with OSA, tends to be effective in predicting treatment response of MAD treatment. © 2012 European Sleep Research Society.

Novel Mad2-targeting miR-493-3p controls mitotic fidelity and cancer cells' sensitivity to paclitaxel.

PubMed

Tambe, Mahesh; Pruikkonen, Sofia; Mäki-Jouppila, Jenni; Chen, Ping; Elgaaen, Bente Vilming; Straume, Anne Hege; Huhtinen, Kaisa; Cárpen, Olli; Lønning, Per Eystein; Davidson, Ben; Hautaniemi, Sampsa; Kallio, Marko J

2016-03-15

The molecular pathways that contribute to the proliferation and drug response of cancer cells are highly complex and currently insufficiently characterized. We have identified a previously unknown microRNA-based mechanism that provides cancer cells means to stimulate tumorigenesis via increased genomic instability and, at the same time, evade the action of clinically utilized microtubule drugs. We demonstrate miR-493-3p to be a novel negative regulator of mitotic arrest deficient-2 (MAD2), an essential component of the spindle assembly checkpoint that monitors the fidelity of chromosome segregation. The microRNA targets the 3' UTR of Mad2 mRNA thereby preventing translation of the Mad2 protein. In cancer cells, overexpression of miR-493-3p induced a premature mitotic exit that led to increased frequency of aneuploidy and cellular senescence in the progeny cells. Importantly, excess of the miR-493-3p conferred resistance of cancer cells to microtubule drugs. In human neoplasms, miR-493-3p and Mad2 expression alterations correlated with advanced ovarian cancer forms and high miR-493-3p levels were associated with reduced survival of ovarian and breast cancer patients with aggressive tumors, especially in the paclitaxel therapy arm. Our results suggest that intratumoral profiling of miR-493-3p and Mad2 levels can have diagnostic value in predicting the efficacy of taxane chemotherapy.

Assessing the performance of handheld glucose testing for critical care.

PubMed

Kost, Gerald J; Tran, Nam K; Louie, Richard F; Gentile, Nicole L; Abad, Victor J

2008-12-01

We assessed the performance of a point-of-care (POC) glucose meter system (GMS) with multitasking test strip by using the locally-smoothed (LS) median absolute difference (MAD) curve method in conjunction with a modified Bland-Altman difference plot and superimposed International Organization for Standardization (ISO) 15197 tolerance bands. We analyzed performance for tight glycemic control (TGC). A modified glucose oxidase enzyme with a multilayer-gold, multielectrode, four-well test strip (StatStriptrade mark, NOVA Biomedical, Waltham, MA) was used. There was no test strip calibration code. Pragmatic comparison was done of GMS results versus paired plasma glucose measurements from chemistry analyzers in clinical laboratories. Venous samples (n = 1,703) were analyzed at 35 hospitals that used 20 types of chemistry analyzers. Erroneous results were identified using the Bland-Altman plot and ISO 15197 criteria. Discrepant values were analyzed for the TGC interval of 80-110 mg/dL. The GMS met ISO 15197 guidelines; 98.6% (410 of 416) of observations were within tolerance for glucose <75 mg/dL, and for > or =75 mg/dL, 100% were within tolerance. Paired differences (handheld minus reference) averaged -2.2 (SD 9.8) mg/dL; the median was -1 (range, -96 to 45) mg/dL. LS MAD curve analysis revealed satisfactory performance below 186 mg/dL; above 186 mg/dL, the recommended error tolerance limit (5 mg/dL) was not met. No discrepant values appeared. All points fell in Clarke Error Grid zone A. Linear regression showed y = 1.018x - 0.716 mg/dL, and r2 = 0.995. LS MAD curves draw on human ability to discriminate performance visually. LS MAD curve and ISO 15197 performance were acceptable for TGC. POC and reference glucose calibration should be harmonized and standardized.

Robust statistical methods for hit selection in RNA interference high-throughput screening experiments.

PubMed

Zhang, Xiaohua Douglas; Yang, Xiting Cindy; Chung, Namjin; Gates, Adam; Stec, Erica; Kunapuli, Priya; Holder, Dan J; Ferrer, Marc; Espeseth, Amy S

2006-04-01

RNA interference (RNAi) high-throughput screening (HTS) experiments carried out using large (>5000 short interfering [si]RNA) libraries generate a huge amount of data. In order to use these data to identify the most effective siRNAs tested, it is critical to adopt and develop appropriate statistical methods. To address the questions in hit selection of RNAi HTS, we proposed a quartile-based method which is robust to outliers, true hits and nonsymmetrical data. We compared it with the more traditional tests, mean +/- k standard deviation (SD) and median +/- 3 median of absolute deviation (MAD). The results suggested that the quartile-based method selected more hits than mean +/- k SD under the same preset error rate. The number of hits selected by median +/- k MAD was close to that by the quartile-based method. Further analysis suggested that the quartile-based method had the greatest power in detecting true hits, especially weak or moderate true hits. Our investigation also suggested that platewise analysis (determining effective siRNAs on a plate-by-plate basis) can adjust for systematic errors in different plates, while an experimentwise analysis, in which effective siRNAs are identified in an analysis of the entire experiment, cannot. However, experimentwise analysis may detect a cluster of true positive hits placed together in one or several plates, while platewise analysis may not. To display hit selection results, we designed a specific figure called a plate-well series plot. We thus suggest the following strategy for hit selection in RNAi HTS experiments. First, choose the quartile-based method, or median +/- k MAD, for identifying effective siRNAs. Second, perform the chosen method experimentwise on transformed/normalized data, such as percentage inhibition, to check the possibility of hit clusters. If a cluster of selected hits are observed, repeat the analysis based on untransformed data to determine whether the cluster is due to an artifact in the data. If no clusters of hits are observed, select hits by performing platewise analysis on transformed data. Third, adopt the plate-well series plot to visualize both the data and the hit selection results, as well as to check for artifacts.

An update on mandibular advancement devices for the treatment of obstructive sleep apnoea hypopnoea syndrome.

PubMed

Basyuni, Shadi; Barabas, Michal; Quinnell, Tim

2018-01-01

Continuous positive airway pressure (CPAP) remains the gold standard treatment for obstructive sleep apnoea hypopnoea syndrome (OSAHS). However, the high efficacy of CPAP is offset by intolerance and poor compliance, which can undermine effectiveness. This means that alternatives to CPAP are also necessary. In recent years, oral appliances have emerged as the leading alternative to CPAP. There is now a strong body of evidence supporting their use in OSAHS and clinical guidelines now recommend their use in mild OSAHS and in more severe cases when CPAP fails. These devices are by no means a homogenous group as they differ greatly in both design and action. The most commonly used appliances are mandibular advancement devices (MAD) that increase airway diameter with soft tissue displacement achieved by mandibular protrusion. Despite the growing evidence, there are still barriers to MAD provision. Their effectiveness can be difficult to predict and there is debate about the required level of design sophistication. These uncertainties prevent more widespread inclusion of MAD within clinical sleep services. This review will focus on the efficacy, effectiveness, design features, side-effects of and patient selection for MAD therapy. Comparison will also be made between MAD and CPAP therapy.

An update on mandibular advancement devices for the treatment of obstructive sleep apnoea hypopnoea syndrome

PubMed Central

Basyuni, Shadi; Barabas, Michal

2018-01-01

Continuous positive airway pressure (CPAP) remains the gold standard treatment for obstructive sleep apnoea hypopnoea syndrome (OSAHS). However, the high efficacy of CPAP is offset by intolerance and poor compliance, which can undermine effectiveness. This means that alternatives to CPAP are also necessary. In recent years, oral appliances have emerged as the leading alternative to CPAP. There is now a strong body of evidence supporting their use in OSAHS and clinical guidelines now recommend their use in mild OSAHS and in more severe cases when CPAP fails. These devices are by no means a homogenous group as they differ greatly in both design and action. The most commonly used appliances are mandibular advancement devices (MAD) that increase airway diameter with soft tissue displacement achieved by mandibular protrusion. Despite the growing evidence, there are still barriers to MAD provision. Their effectiveness can be difficult to predict and there is debate about the required level of design sophistication. These uncertainties prevent more widespread inclusion of MAD within clinical sleep services. This review will focus on the efficacy, effectiveness, design features, side-effects of and patient selection for MAD therapy. Comparison will also be made between MAD and CPAP therapy. PMID:29445528

Characterization of Tyrosine Nitration and Cysteine Nitrosylation Modifications by Metastable Atom-Activation Dissociation Mass Spectrometry

NASA Astrophysics Data System (ADS)

Cook, Shannon L.; Jackson, Glen P.

2011-02-01

The fragmentation behavior of nitrated and S-nitrosylated peptides were studied using collision induced dissociation (CID) and metastable atom-activated dissociation mass spectrometry (MAD-MS). Various charge states, such as 1+, 2+, 3+, 2-, of modified and unmodified peptides were exposed to a beam of high kinetic energy helium (He) metastable atoms resulting in extensive backbone fragmentation with significant retention of the post-translation modifications (PTMs). Whereas the high electron affinity of the nitrotyrosine moiety quenches radical chemistry and fragmentation in electron capture dissociation (ECD) and electron transfer dissociation (ETD), MAD does produce numerous backbone cleavages in the vicinity of the modification. Fragment ions of nitrosylated cysteine modifications typically exhibit more abundant neutral losses than nitrated tyrosine modifications because of the extremely labile nature of the nitrosylated cysteine residues. However, compared with CID, MAD produced between 66% and 86% more fragment ions, which preserved the labile -NO modification. MAD was also able to differentiate I/L residues in the modified peptides. MAD is able to induce radical ion chemistry even in the presence of strong radical traps and therefore offers unique advantages to ECD, ETD, and CID for determination of PTMs such as nitrated and S-nitrosylated peptides.

DETERMINATION OF ALKYLATED & SULFONATED DIPHENYL OXIDE SULFACTANT BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

EPA Science Inventory

Methods for the determination of the anionic surfactant Dowfax 8390 are described. Dowfax is a complex mixture of various alkylated and sulfonated diphenyl oxides. The primary component of Dowfax is monoalkylated disulfonated diphenyl oxide (MADS). This work uses ion pairing chro...

Globalizing Education, Educating the Local: How Method Made Us Mad

ERIC Educational Resources Information Center

Stronach, Ian

2011-01-01

This book offers a critical and deconstructive account of global discourses on education, arguing that these overblown "hypernarratives" are neither economically, technically nor philosophically defensible. Nor even sane. Their "mythic economic instrumentalism" mimic rather than meet the economic needs of global capitalism in…

Astrophysics: The MAD world of black holes

NASA Astrophysics Data System (ADS)

Gabuzda, Denise

2014-06-01

An analysis of optical and radio observations has revealed how powerful jets are launched from the centres of active galaxies, where supermassive black holes accrete matter through magnetically arrested disks, or MADs. See Letter p.126

SECONDARY GENERAL MOTORS DIESEL ENGINE WITH CONNECTION TO REDUCTION GEAR ...

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

SECONDARY GENERAL MOTORS DIESEL ENGINE WITH CONNECTION TO REDUCTION GEAR BELT DRIVE SYSTEM, LOOKING SOUTH. - Mad River Glen, Single Chair Ski Lift, 62 Mad River Glen Resort Road, Fayston, Washington County, VT

Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease

MedlinePlus

... the CDC Bovine Spongiform Encephalopathy (BSE), or Mad Cow Disease Note: Javascript is disabled or is not ... spongiform encephalopathy) is a progressive neurological disorder of cattle that results from infection by an unusual transmissible ...

Functional diversification of B MADS-box homeotic regulators of flower development: Adaptive evolution in protein-protein interaction domains after major gene duplication events.

PubMed

Hernández-Hernández, Tania; Martínez-Castilla, León Patricio; Alvarez-Buylla, Elena R

2007-02-01

B-class MADS-box genes have been shown to be the key regulators of petal and stamen specification in several eudicot model species such as Arabidopsis thaliana, Antirrhinum majus, and Petunia hybrida. Orthologs of these genes have been found across angiosperms and gymnosperms, and it is thought that the basic regulatory function of B proteins is conserved in seed plant lineages. The evolution of B genes is characterized by numerous duplications that might represent key elements fostering the functional diversification of duplicates with a deep impact on their role in the evolution of the floral developmental program. To evaluate this, we performed a rigorous statistical analysis with B gene sequences. Using maximum likelihood and Bayesian methods, we estimated molecular substitution rates and determined the selective regimes operating at each residue of B proteins. We implemented tests that rely on phylogenetic hypotheses and codon substitution models to detect significant differences in substitution rates (DSRs) and sites under positive adaptive selection (PS) in specific lineages before and after duplication events. With these methods, we identified several protein residues fixed by PS shortly after the origin of PISTILLATA-like and APETALA3-like lineages in angiosperms and shortly after the origin of the euAP3-like lineage in core eudicots, the 2 main B gene duplications. The residues inferred to have been fixed by positive selection lie mostly within the K domain of the protein, which is key to promote heterodimerization. Additionally, we used a likelihood method that accommodates DSRs among lineages to estimate duplication dates for AP3-PI and euAP3-TM6, calibrating with data from the fossil record. The dates obtained are consistent with angiosperm origins and diversification of core eudicots. Our results strongly suggest that novel multimer formation with other MADS proteins could have been crucial for the functional divergence of B MADS-box genes. We thus propose a mechanism of functional diversification and persistence of gene duplicates by the appearance of novel multimerization capabilities after duplications. Multimer formation in different combinations of regulatory proteins can be a mechanistic basis for the origin of novel regulatory functions and a gene regulatory mechanism for the appearance of morphological innovations.

[Epidemiological aspects of human and animal rabies in the urban area of Bamako, Mali].

PubMed

Dao, S; Abdillahi, A M; Bougoudogo, F; Toure, K; Simbe, C

2006-07-01

The district of Bamako is the political and economical capital city of Mali with 1,800,000 inhabitants. The goal of the present retrospective study was to determine the frequency of animal bites, human and animal rabies on the one hand and to determine the frequency and the nature of mad animals on the other hand from January 2000 to December 2003 (4 years). To achieve this goal, we have analysed registers and documents related to rabies in the department of prevention and fight against diseases, the central veterinary laboratory, and also at the lazaret clinic involved in caring for human rabies cases. Human rabies diagnosis has been brought up based upon the following clinical arguments: agitation and lethal hydrophobia within few days following bites by known or unknown animal. Agitation and aggressiveness followed by the animals' death within an observation period of 15 days maximum, allowed to evoke the diagnosis in animals. In Bamako an average of 1470 persons have been bitten each year. In 97.1% of the cases, the mad animal was a dog; cats (1.6%), donkeys, horses, cattle and rats (1.4%) have also been identified on a total of 5870 cases of notified human bites by animals; 10 cases of notified human rabies have been recorded. The dog has been incriminated in 6 cases of human rabies out of 10, in the 4 other cases, it has not been possible to identify the mad animal. Among the 3924 mad animals in observation at the veterinary clinic, 187 have been clinically mad that is 4.8%. The rabies virus has also been researched by direct immunofluorescence in 121 specimens of dead mad animals brain. This research has been positive in 119 cases among which 116 dogs, 2 sheep and 1 cow. Anyway the vaccinal status of people bitten by mad animals has not been clearly established. According to these results, we recommend the implementation of a national specific program to eradicate rabies in Bamako.

Late Pleistocene sediments and fossils near the mouth of Mad River, Humboldt County, California: Facies analysis, sequence development, and possible age correlation

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

Harvey, E.W.

Study of late Pleistocene-age sediments near the mouth of the Mad River revealed a sequence of nearshore marine and shallow bay deposits. This sequence, bounded by unconformities, is informally named the Mouth of Mad unit. The Mouth of mad unit can be divided into four distinct depositional facies at the study site. The lowest facies are the Nearshore Sand and Estuarine Mud, which lie unconformably on a paleosol. The sand facies grades upward into a high-energy, interbedded Nearshore Sand and Gravel facies containing storm and rip-channel deposits. Above the sand and gravel is a Strand-Plain Sand facies. This sand ismore » overlain by a laterally variable sequence of shell-rich Bay facies. The bay deposits can be further divided into five subfacies: (1) a Bioturbated Sand; (2) a Lower Tidal Flat Mud; (3) a Mixed Sand and Mud; (4) an oyster-rich Bay Mud; and (5) an Upper Tidal Flat Mud. The bay sequence is overlain unconformably by younger late Pleistocene-age marine terrace deposits. The depositional environments represented by these facies progress from a shoreline estuary to nearshore deposits, above storm wave base, and slowly back to shoreline and finally shallow bay conditions. The Mouth of Mad unit represents a transgressive-regressive sequence, involving the development of a protective spit. The uppermost mud within the Mouth of Mad unit has been dated, using thermoluminescence age estimation, at 176 [+-] 33 ka, placing it in the late Pleistocene. The Mouth of Mad unit appears to be younger than the fossiliferous deposits at Elk Head, Crannell Junction, Trinidad Head, Moonstone Beach, and the Falor Formation near Maple Creek, and possibly time equivalent with gravel deposits exposed at the western end of School Road in McKinleyville.« less

E-mail management of the modified Atkins Diet for adults with epilepsy is feasible and effective.

PubMed

Cervenka, Mackenzie C; Terao, Natalie N; Bosarge, Jennifer L; Henry, Bobbie J; Klees, Angela A; Morrison, Peter F; Kossoff, Eric H

2012-04-01

The modified Atkins Diet (MAD) is an effective dietary treatment for children with epilepsy. However, adults may have limited access to this therapy because of lack of availability of dietitian or nutrition support or familiarity with the diet by their treating neurologist. This study was designed to investigate the tolerability and efficacy of the MAD administered solely via e-mail to adults with pharmacoresistant epilepsy. A prospective, open-label, proof-of-principle 3-month study design was employed. Adults were enrolled, instructed on how to self-administer a 20 g carbohydrate per day MAD, and followed by the investigators only via e-mail. There were no clinic visits or dietitian contacts during the study period. Twenty-five participants (median age 30 years [range 18-66 years], 68% female) consented and 22 started the MAD. The median prior anticonvulsants was 5 (range 2-10) and seizure frequency was 5 per week (range 1-140). Urinary ketosis was achieved in 21 participants (95%), of which 16 (76%) reported at least 40 mg/dl (moderate). Twenty-one participants (95%) remained on the MAD at 1 month and 14 (64%) at 3 months. After 1 month, 9 (41%) had >50% seizure reduction including one (5%) with >90% seizure reduction using intent-to-treat analysis. After 3 months, 6 (27%) had >50% seizure reduction including 3 (14%) with >90% seizure reduction. The mean ketogenic ratio was 1.1:1 (fat:carbohydrates and protein) for those who provided a MAD food record at follow-up. Over the study period, the median number of e-mails sent by the participants was 6 (range 1-19). The most frequent side effect was weight loss. E-mail administration of the MAD to adults with refractory epilepsy appears to be feasible and effective. Therefore, when dietitian or physician support is limited for adult patients with epilepsy, remote access via telemedicine could provide an alternative. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

[Madness in the German cinema (1913-1933].

PubMed

Aulas, J J

1980-01-01

During these twenty years, from 1913 to 1933, of the history of the German cinema, the cinematographic representation of madness varies according to the fluctuations of the social and economical background. The political and ideological chaos of the immediate post-war years was symbolized in the allegorical imagery of unreason in the expressionist cinema. The same equivalence, the same symbolization can be found in the cinema of the thirties when the crash of Wall-Street foretells a crisis like the former. On the contrary in the course of the so-called "relative stabilization" (1924-1929) the meaning of the representation of madness is totally different from the representation of the previous period. At this period of economical restoration, madness which could henceforth be cured on the psychoanalyst's couch (acc. G. W. Pabst's film: "Geheimnisse einer Seele") became the symbol of the absolute power rediscovered by Germany.

From MAD to SAD: The Italian experience for the low-frequency aperture array of SKA1-LOW

NASA Astrophysics Data System (ADS)

Bolli, P.; Pupillo, G.; Virone, G.; Farooqui, M. Z.; Lingua, A.; Mattana, A.; Monari, J.; Murgia, M.; Naldi, G.; Paonessa, F.; Perini, F.; Pluchino, S.; Rusticelli, S.; Schiaffino, M.; Schillirò, F.; Tartarini, G.; Tibaldi, A.

2016-03-01

This paper describes two small aperture array demonstrators called Medicina and Sardinia Array Demonstrators (MAD and SAD, respectively). The objectives of these instruments are to acquire experience and test new technologies for a possible application to the low-frequency aperture array of the low-frequency telescope of the Square Kilometer Array phase 1 (SKA1-LOW). The MAD experience was concluded in 2014, and it turned out to be an important test bench for implementing calibration techniques based on an artificial source mounted in an aerial vehicle. SAD is based on 128 dual-polarized Vivaldi antennas and is 1 order of magnitude larger than MAD. The architecture and the station size of SAD, which is along the construction phase, are more similar to those under evaluation for SKA1-LOW, and therefore, SAD is expected to provide useful hints for SKA1-LOW.

Modified Atkins diet induces subacute selective ragged-red-fiber lysis in mitochondrial myopathy patients.

PubMed

Ahola, Sofia; Auranen, Mari; Isohanni, Pirjo; Niemisalo, Satu; Urho, Niina; Buzkova, Jana; Velagapudi, Vidya; Lundbom, Nina; Hakkarainen, Antti; Muurinen, Tiina; Piirilä, Päivi; Pietiläinen, Kirsi H; Suomalainen, Anu

2016-11-01

Mitochondrial myopathy (MM) with progressive external ophthalmoplegia (PEO) is a common manifestation of mitochondrial disease in adulthood, for which there is no curative therapy. In mice with MM, ketogenic diet significantly delayed progression of the disease. We asked in this pilot study what effects high-fat, low-carbohydrate "modified Atkins" diet (mAD) had for PEO/MM patients and control subjects and followed up the effects by clinical, morphological, transcriptomic, and metabolomic analyses. All of our five patients, irrespective of genotype, showed a subacute response after 1.5-2 weeks of diet, with progressive muscle pain and leakage of muscle enzymes, leading to premature discontinuation of the diet. Analysis of muscle ultrastructure revealed selective fiber damage, especially in the ragged-red-fibers (RRFs), a MM hallmark. Two years of follow-up showed improvement of muscle strength, suggesting activation of muscle regeneration. Our results indicate that (i) nutrition can modify mitochondrial disease progression, (ii) dietary counseling should be part of MM care, (iii) short mAD is a tool to induce targeted RRF lysis, and (iv) mAD, a common weight-loss method, may induce muscle damage in a population subgroup. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Optimization of monitoring networks based on uncertainty quantification of model predictions of contaminant transport

NASA Astrophysics Data System (ADS)

Vesselinov, V. V.; Harp, D.

2010-12-01

The process of decision making to protect groundwater resources requires a detailed estimation of uncertainties in model predictions. Various uncertainties associated with modeling a natural system, such as: (1) measurement and computational errors; (2) uncertainties in the conceptual model and model-parameter estimates; (3) simplifications in model setup and numerical representation of governing processes, contribute to the uncertainties in the model predictions. Due to this combination of factors, the sources of predictive uncertainties are generally difficult to quantify individually. Decision support related to optimal design of monitoring networks requires (1) detailed analyses of existing uncertainties related to model predictions of groundwater flow and contaminant transport, (2) optimization of the proposed monitoring network locations in terms of their efficiency to detect contaminants and provide early warning. We apply existing and newly-proposed methods to quantify predictive uncertainties and to optimize well locations. An important aspect of the analysis is the application of newly-developed optimization technique based on coupling of Particle Swarm and Levenberg-Marquardt optimization methods which proved to be robust and computationally efficient. These techniques and algorithms are bundled in a software package called MADS. MADS (Model Analyses for Decision Support) is an object-oriented code that is capable of performing various types of model analyses and supporting model-based decision making. The code can be executed under different computational modes, which include (1) sensitivity analyses (global and local), (2) Monte Carlo analysis, (3) model calibration, (4) parameter estimation, (5) uncertainty quantification, and (6) model selection. The code can be externally coupled with any existing model simulator through integrated modules that read/write input and output files using a set of template and instruction files (consistent with the PEST I/O protocol). MADS can also be internally coupled with a series of built-in analytical simulators. MADS provides functionality to work directly with existing control files developed for the code PEST (Doherty 2009). To perform the computational modes mentioned above, the code utilizes (1) advanced Latin-Hypercube sampling techniques (including Improved Distributed Sampling), (2) various gradient-based Levenberg-Marquardt optimization methods, (3) advanced global optimization methods (including Particle Swarm Optimization), and (4) a selection of alternative objective functions. The code has been successfully applied to perform various model analyses related to environmental management of real contamination sites. Examples include source identification problems, quantification of uncertainty, model calibration, and optimization of monitoring networks. The methodology and software codes are demonstrated using synthetic and real case studies where monitoring networks are optimized taking into account the uncertainty in model predictions of contaminant transport.

Crystal structure of a designed, thermostable, heterotrimeric coiled coil.

PubMed Central

Nautiyal, S.; Alber, T.

1999-01-01

Electrostatic interactions are often critical for determining the specificity of protein-protein complexes. To study the role of electrostatic interactions for assembly of helical bundles, we previously designed a thermostable, heterotrimeric coiled coil, ABC, in which charged residues were employed to drive preferential association of three distinct, 34-residue helices. To investigate the basis for heterotrimer specificity, we have used multiwavelength anomalous diffraction (MAD) analysis to determine the 1.8 A resolution crystal structure of ABC. The structure shows that ABC forms a heterotrimeric coiled coil with the intended arrangement of parallel chains. Over half of the ion pairs engineered to restrict helix associations were apparent in the experimental electron density map. As seen in other trimeric coiled coils, ABC displays acute knobs-into-holes packing and a buried anion coordinated by core polar amino acids. These interactions validate the design strategy and illustrate how packing and polar contacts determine structural uniqueness. PMID:10210186

SEPALLATA3: the 'glue' for MADS box transcription factor complex formation

PubMed Central

Immink, Richard GH; Tonaco, Isabella AN; de Folter, Stefan; Shchennikova, Anna; van Dijk, Aalt DJ; Busscher-Lange, Jacqueline; Borst, Jan W; Angenent, Gerco C

2009-01-01

Background Plant MADS box proteins play important roles in a plethora of developmental processes. In order to regulate specific sets of target genes, MADS box proteins dimerize and are thought to assemble into multimeric complexes. In this study a large-scale yeast three-hybrid screen is utilized to provide insight into the higher-order complex formation capacity of the Arabidopsis MADS box family. SEPALLATA3 (SEP3) has been shown to mediate complex formation and, therefore, special attention is paid to this factor in this study. Results In total, 106 multimeric complexes were identified; in more than half of these at least one SEP protein was present. Besides the known complexes involved in determining floral organ identity, various complexes consisting of combinations of proteins known to play a role in floral organ identity specification, and flowering time determination were discovered. The capacity to form this latter type of complex suggests that homeotic factors play essential roles in down-regulation of the MADS box genes involved in floral timing in the flower via negative auto-regulatory loops. Furthermore, various novel complexes were identified that may be important for the direct regulation of the floral transition process. A subsequent detailed analysis of the APETALA3, PISTILLATA, and SEP3 proteins in living plant cells suggests the formation of a multimeric complex in vivo. Conclusions Overall, these results provide strong indications that higher-order complex formation is a general and essential molecular mechanism for plant MADS box protein functioning and attribute a pivotal role to the SEP3 'glue' protein in mediating multimerization. PMID:19243611

Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence.

PubMed

Keller, Brian C; Fredericksen, Brenda L; Samuel, Melanie A; Mock, Richard E; Mason, Peter W; Diamond, Michael S; Gale, Michael

2006-10-01

The emergence of West Nile virus (WNV) in the Western Hemisphere is marked by the spread of pathogenic lineage I strains, which differ from typically avirulent lineage II strains. To begin to understand the virus-host interactions that may influence the phenotypic properties of divergent lineage I and II viruses, we compared the genetic, pathogenic, and alpha/beta interferon (IFN-alpha/beta)-regulatory properties of a lineage II isolate from Madagascar (MAD78) with those of a new lineage I isolate from Texas (TX02). Full genome sequence analysis revealed that MAD78 clustered, albeit distantly, with other lineage II strains, while TX02 clustered with emergent North American isolates, more specifically with other Texas strains. Compared to TX02, MAD78 replicated at low levels in cultured human cells, was highly sensitive to the antiviral actions of IFN in vitro, and demonstrated a completely avirulent phenotype in wild-type mice. In contrast to TX02 and other pathogenic forms of WNV, MAD78 was defective in its ability to disrupt IFN-induced JAK-STAT signaling, including the activation of Tyk2 and downstream phosphorylation and nuclear translocation of STAT1 and STAT2. However, replication of MAD78 was rescued in cells with a nonfunctional IFN-alpha/beta receptor (IFNAR). Consistent with this finding, the virulence of MAD78 was unmasked upon infection of mice lacking IFNAR. Thus, control of the innate host response and IFN actions is a key feature of WNV pathogenesis and replication fitness.

Constitutive expression of the K-domain of a Vaccinium corymbosum SOC1-like (VcSOC1-K) MADS-box gene is sufficient to promote flowering in tobacco.

PubMed

Song, Guo-qing; Walworth, Aaron; Zhao, Dongyan; Hildebrandt, Britton; Leasia, Michael

2013-11-01

The K-domain of a blueberry-derived SOC1 -like gene promotes flowering in tobacco without negatively impacting yield, demonstrating potential for manipulation of flowering time in horticultural crops. The SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) and SOC1-likes, belonging to the MIKC(c) (type II) MADS-box gene subfamily, are major floral activators and integrators of plant flowering. Both MADS-domains and K (Keratin)-domains are highly conserved in MIKC(c)-type MADS proteins. While there are many reports on overexpression of intact MIKC(c)-type MADS-box genes, few studies have been conducted to investigate the effects of the K-domains. In this report, a 474-bp K-domain of Vaccinium SOC1-like (VcSOC1-K) was cloned from the cDNA library of the northern highbush blueberry (Vaccinium corymbosum L.). Functional analysis of the VcSOC1-K was conducted by ectopically expressing of 35S:VcSOC1-K in tobacco. Reverse transcription PCR confirmed expression of the VcSOC1-K in T0 plants. Phenotypically, T1 transgenic plants (10 T1 plants/event) flowered sooner after seeding, and were shorter with fewer leaves at the time of flowering, than nontransgenic plants; but seed pod production of transgenic plants was not significantly affected. These results demonstrate that overexpression of the K-domain of a MIKC(c)-type MADS-box gene alone is sufficient to promote early flowering and more importantly without affecting seed production.

Adaptive evolution in the Arabidopsis MADS-box gene family inferred from its complete resolved phylogeny

PubMed Central

Martínez-Castilla, León Patricio; Alvarez-Buylla, Elena R.

2003-01-01

Gene duplication is a substrate of evolution. However, the relative importance of positive selection versus relaxation of constraints in the functional divergence of gene copies is still under debate. Plant MADS-box genes encode transcriptional regulators key in various aspects of development and have undergone extensive duplications to form a large family. We recovered 104 MADS sequences from the Arabidopsis genome. Bayesian phylogenetic trees recover type II lineage as a monophyletic group and resolve a branching sequence of monophyletic groups within this lineage. The type I lineage is comprised of several divergent groups. However, contrasting gene structure and patterns of chromosomal distribution between type I and II sequences suggest that they had different evolutionary histories and support the placement of the root of the gene family between these two groups. Site-specific and site-branch analyses of positive Darwinian selection (PDS) suggest that different selection regimes could have affected the evolution of these lineages. We found evidence for PDS along the branch leading to flowering time genes that have a direct impact on plant fitness. Sites with high probabilities of having been under PDS were found in the MADS and K domains, suggesting that these played important roles in the acquisition of novel functions during MADS-box diversification. Detected sites are targets for further experimental analyses. We argue that adaptive changes in MADS-domain protein sequences have been important for their functional divergence, suggesting that changes within coding regions of transcriptional regulators have influenced phenotypic evolution of plants. PMID:14597714

Monitoring and Evaluation of Smolt Migration in the Columbia River Basin : Volume VI : Evaluation of the 2000 Predictions of the Run-Timing of Wild Migrant Chinook Salmon and Steelhead Trout, and Hatchery Sockeye Salmon in the Snake River Basin, and Combined Wild Hatchery Salminids Migrating to Rock Island and McNary Dams using Program RealTime.

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

Burgess, Caitlin

1998-07-01

Program RealTime provided tracking and forecasting of the 2000 in season outmigration via the internet for stocks of wild PIT-tagged spring/summer chinook salmon. These stocks were ESUs from nineteen release sites above Lower Granite dam, including Bear Valley Creek, Big Creek, Camas Creek (new), Cape Horn Creek, Catherine Creek, Elk Creek, Herd Creek, Imnaha River, Johnson Creek (new), Lake Creek, Loon Creek, Lostine River, Marsh Creek, Minam River, East Fork Salmon River (new), South Fork Salmon River, Secesh River, Sulfur Creek and Valley Creek. Forecasts were also provided for two stocks of hatchery-reared PIT-tagged summer-run sockeye salmon, from Redfish Lakemore » and Alturas Lake (new); for a subpopulation of the PIT-tagged wild Snake River fall subyearling chinook salmon; for all wild Snake River PIT-tagged spring/summer yearling chinook salmon (new) and steelhead trout (new)detected at Lower Granite Dam during the 2000 outmigration. The 2000 RealTime project began making forecasts for combined wild- and hatchery-reared runs-at-large of subyearling and yearling chinook, coho, and sockeye salmon, and steelhead trout migrating to Rock Island and McNary Dams on the mid-Columbia River and the mainstem Columbia River. Due to the new (in 1999-2000) Snake River basin hatchery protocol of releasing unmarked hatchery-reared fish, the RealTime forecasting project no longer makes run-timing forecasts for wild Snake River runs-at-large using FPC passage indices, as it has done for the previous three years (1997-1999). The season-wide measure of Program RealTime performance, the mean absolute difference (MAD) between in-season predictions and true (observed) passage percentiles, improved relative to previous years for nearly all stocks. The average season-wide MAD of all (nineteen) spring/summer yearling chinook salmon ESUs dropped from 5.7% in 1999 to 4.5% in 2000. The 2000 MAD for the hatchery-reared Redfish Lake sockeye salmon ESU was the lowest recorded, at 6.0%, down from 6.7% in 1999. The MAD for the PIT-tagged ESU of wild Snake River fall sub-yearling chinook salmon, after its second season of run-timing forecasting, was 4.7% in 2000 compared to 5.5% in 1999. The high accuracy of season-wide performance in 2000 was largely due to exceptional Program RealTime performance in the last half of the season. Passage predictions from fifteen of the sixteen spring/summer yearling chinook salmon ESUs available for comparison improved in 2000 compared to 1999. The last-half average MAD over all the yearling chinook salmon ESUs was 4.3% in 2000, compared to 6.5% in 1999. Program RealTime 2000 first-half forecasting performance was slightly worse than that of 1999 (MAD = 4.5%), but still comparable to previous years with a MAD equal to 5.1%. Three yearling chinook ESUs showed moderately large (> 10%) MADs. These stocks had larger-than-average recapture percentages in 2000, producing over-predictions early in the season, in a dynamic reminiscent of migration year 1998 (Burgess et al., 1999). The passage distribution of the new stock of hatchery-reared sockeye salmon from Alturas Lake was well-predicted by Program RealTime, based on only two years of historical data (whole-season MAD = 4.3%). The two new run-of-the-river PIT-tagged stocks of wild yearling chinook salmon and steelhead trout were predicted with very good accuracy (whole-season MADs were 4.8% for steelhead trout and 1.7% for yearling chinook salmon), particularly during the last half of the outmigration. First-half steelhead predictions were among the season's worst (MAD = 10.8%), with over-predictions attributable to the largest passage on record of wild PIT-tagged steelhead trout to Lower Granite Dam. The results of RealTime predictions of passage percentiles of combined wild and hatchery-reared salmonids to Rock Island and McNary were mixed. Some of these passage-indexed runs-at-large were predicted with exceptional accuracy (whole-season MADs for coho salmon outmigrating to Rock Island Dam and McNary Dam were, respectively, 0.58% and 1.24%; for yearling chinook to McNary, 0.59%) while others were not forecast well at all (first-half MADs of sockeye salmon migrating to Rock Island and McNary Dams, respectively, were 19.25% and 12.78%). The worst performances for these mid- and mainstem-Columbia River runs-at-large were probably due to large hatchery release disturbing the smoothly accumulating percentages of normal fish passage. The RealTime project used a stock-specific method of upwardly adjusting PIT-tagged smolt counts at Lower Granite Dam. For chinook and sockeye salmon, the project continued using the 1999 formulation for spill-adjustment. For the new stock of wild PIT-tagged steelhead trout, a formula derived for steelhead trout only was used.« less

Preliminary X-ray crystallographic studies of mouse UPR responsive protein P58(IPK) TPR fragment

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

Tao, Jiahui; Wu, Yunkun; Ron, David

2008-02-01

To investigate the mechanism by which P58(IPK) functions to promote protein folding within the ER, a P58(IPK) TPR fragment without the C-terminal J-domain has been crystallized. Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), which can promote protein folding and misfolded protein degradation and attenuate protein translation and protein translocation into the ER. P58(IPK) has been proposed to function as a molecular chaperone to maintain protein-folding homeostasis in the ER under normal and stressed conditions. P58(IPK) contains nine TPR motifs and a C-terminal J-domain within its primary sequence. To investigate the mechanism by which P58(IPK) functions to promotemore » protein folding within the ER, a P58(IPK) TPR fragment without the C-terminal J-domain was crystallized. The crystals diffract to 2.5 Å resolution using a synchrotron X-ray source. The crystals belong to space group P2{sub 1}, with unit-cell parameters a = 83.53, b = 92.75, c = 84.32 Å, α = 90.00, β = 119.36, γ = 90.00°. There are two P58(IPK) molecules in the asymmetric unit, which corresponds to a solvent content of approximately 60%. Structure determination by MAD methods is under way.« less

Measures That Identify Prescription Medication Misuse, Abuse, and Related Events in Clinical Trials: ACTTION Critique and Recommended Considerations.

PubMed

Smith, Shannon M; Jones, Judith K; Katz, Nathaniel P; Roland, Carl L; Setnik, Beatrice; Trudeau, Jeremiah J; Wright, Stephen; Burke, Laurie B; Comer, Sandra D; Dart, Richard C; Dionne, Raymond; Haddox, J David; Jaffe, Jerome H; Kopecky, Ernest A; Martell, Bridget A; Montoya, Ivan D; Stanton, Marsha; Wasan, Ajay D; Turk, Dennis C; Dworkin, Robert H

2017-11-01

Accurate assessment of inappropriate medication use events (ie, misuse, abuse, and related events) occurring in clinical trials is an important component in evaluating a medication's abuse potential. A meeting was convened to review all instruments measuring such events in clinical trials according to previously published standardized terminology and definitions. Only 2 approaches have been reported that are specifically designed to identify and classify misuse, abuse, and related events occurring in clinical trials, rather than to measure an individual's risk of using a medication inappropriately: the Self-Reported Misuse, Abuse, and Diversion (SR-MAD) instrument and the Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS). The conceptual basis, strengths, and limitations of these methods are discussed. To our knowledge, MADDERS is the only system available to comprehensively evaluate inappropriate medication use events prospectively to determine the underlying intent. MADDERS can also be applied retrospectively to completed trial data. SR-MAD can be used prospectively; additional development may be required to standardize its implementation and fully appraise the intent of inappropriate use events. Additional research is needed to further demonstrate the validity and utility of MADDERS as well as SR-MAD. Identifying a medication's abuse potential requires assessing inappropriate medication use events in clinical trials on the basis of a standardized event classification system. The strengths and limitations of the 2 published methods designed to evaluate inappropriate medication use events are reviewed, with recommended considerations for further development and current implementation. Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Evaluation of sample preparation methods for the detection of total metal content using inductively coupled plasma optical emission spectrometry (ICP-OES) in wastewater and sludge

NASA Astrophysics Data System (ADS)

Dimpe, K. M.; Ngila, J. C.; Mabuba, N.; Nomngongo, P. N.

Heavy metal contamination exists in aqueous wastes and sludge of many industrial discharges and domestic wastewater, among other sources. Determination of metals in the wastewater and sludge requires sample pre-treatment prior to analysis because of certain challenges such as the complexity of the physical state of the sample, which may lead to wrong readings in the measurement. This is particularly the case with low analyte concentration to be detected by the instrument. The purpose of this work was to assess and validate the different sample preparation methods namely, hot plate and microwave-assisted digestion procedures for extraction of metal ions in wastewater and sludge samples prior to their inductively coupled plasma optical emission spectrometric (ICP-OES) determination. For the extraction of As, Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn, three acid mixtures, that is, HNO3/H2O2, HNO3/HClO4/H2O2 and aqua regia + H2O2, were evaluated. Influent wastewater spiked with the SRM (CWW-TM-B) was used for the optimization of acid mixtures affecting the extraction procedure. After sample digestion, the filtration capabilities of cellulose-acetate filter paper and the acrodisc syringe filter with the pore size of 0.45 μm were compared. In terms of performance, acrodisc syringe filter in terms of the improved recoveries obtained, was found to be the best filtration method compared to the filter paper. Based on the analytical results obtained, microwave-assisted digestion (MAD) using aqua regia + H2O2 mixture was found to be the most suitable method for extraction of heavy metals and major elements in all the sample matrices. Therefore, MAD using aqua regia + H2O2 mixture was used for further investigations. The precision of the developed MAD method expressed in terms of relative standard deviations (% RSD) for different metals was found to be <5%. The limits of detection (LOD) and limits of quantification (LOQ) ranged from 0.12% to 2.18 μg L-1 and 0.61% to 3.43 μg L-1, respectively. The accuracy of the developed method (MAD using aqua regia + H2O2) was verified by analyzing two SRMs (CWW-TM-A and CWW-TM-B) and the obtained results were in agreement with certified values with recoveries ranging from 80% to 104% for CWW-TM-A and 84% to 102% for CWW-TM-B. The accuracy of the developed method was verified also by the recovery test in the spiked sludge samples. The accuracy and spike recovery test for different metal ions were in the range 80-104% and 92-106%, respectively. The developed method was applied for extraction of the As, Al, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn in environmental samples, namely wastewater and sludge.

Approximation, Mad Men and the Death of JFK.

PubMed

Bruzzi, Stella

2018-01-01

In this article I take the US television series Mad Men (2007-present) as an exemplary 'approximation', a term I adopt to signal the way in which certain texts construct a changeable, fluid 'truth' resulting from collisions, exchange and dialectical argument. Approximations are layered, their formal layerings mirroring a layered, multifaceted argument. Mad Men integrates and represents real historical events within a fictional setting, and act that suggests that an event or action can never be finished, fixed and not open to reassessment. Specifically, this article examines 'The Grown Ups', Episode 12 of Season 3, which charts the events of 22 November 1963, the day Kennedy was assassinated. Although we might be able to bring to mind the images and conspiracy theories that have been made available since (such Abraham Zapruder's 8 mm home movie footage of the assassination), these images were not available at the time. Mad Men as a series always strives to represent its historical milieu as authentically as possible, so the characters re-enact 22 November 1963 as authentically as possible by watching only what was on television that day (the news bulletin, Walter Kronkite's announcement that Kennedy is dead). The contemporary backdrop to these events, including the resonances of '9/11' through Mad Men , inform and collide with the authenticity on the screen.

High-fat diets and seizure control in myoclonic-astatic epilepsy: a single center's experience.

PubMed

Simard-Tremblay, Elisabeth; Berry, Patricia; Owens, Aaron; Cook, William Byron; Sittner, Haley R; Mazzanti, Marta; Huber, Jennifer; Warner, Molly; Shurtleff, Hillary; Saneto, Russell P

2015-02-01

To determine the efficacy of the Modified Atkins Diet (MAD) and Ketogenic Diet (KD) in seizure control within a population of myoclonic-astatic epilepsy (MAE) patients. This was a retrospective, single center study evaluating the seizure control by high fat diets. Seizure diaries kept by the parents performed seizure counts. All patients met the clinical criteria for MAE. Nine patients met the clinical criteria. We found that both the MAD and KD were efficacious in complete seizure control and allowed other medications to be stopped in seven patients. Two patients had greater than 90% seizure control without medications, one on the KD and the other on the MAD. Seizure freedom has ranged from 13 to 36 months, and during this time four patients have been fully weaned off of diet management. One patient was found to have a mutation in SLC2A1. Our results suggest that strictly defined MAE patients respond to the MAD with prolonged seizure control. Some patients may require the KD for seizure freedom, suggesting a common pathway of increased requirement for fats. Once controlled, those fully responsive to the Diet(s) could be weaned off traditional seizure medications and in many, subsequently off the MAD or KD. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

["I am but mad north-north-west"--Hamlet's portrayed delusion].

PubMed

Schulte Herbrüggen, H

1996-01-01

Whereas science refers to the real world existing independently and conditioned by cause and effect, the world of literature is fictitious, created by the artist in our imagination by means of language, an artefact conditioned by aesthetic laws, a world sui generis. Accordingly, Hamlet is no person, but a literary figure, doing, saying, thinking and feeling only what the poet dictated him word for word. The essential difference between the two worlds is often overlooked. That "blind spot" has a long-standing tradition in European intellectual history and goes back i.a. to the German "Hamlet experience" in the eighteenth, the "Hamlet fever" and the felt spiritual kinship (Seelenverwandtschaft) in the nineteenth century. Teleological literary criticism, centering around Hamlet's "character" and isolating his psychologically evaluated monologues (e.g. Bradley), refrained from Hamlet's fictionality and role-play and led to blurring beyond recognition the boundaries between real person and literary figure (e.g. Freud, Jones) and assisted in reducing a dramatic role to a medical case history. Speaking of Hamlet, one has to start from Shakespeare's text, our subject matter. A dramatic play being a plot turned into dialogue, the poet's vocabulary used (but indirectly also the vocabulary not used) is particularly informative. When referring to Hamlet's "antic disposition", Shakespeare uses a wide range of over 20 different terms, the most frequented being mad/madness (44 times). Evidence of primary importance are the five occasions after the apparition of his father's ghost, when Hamlet speaks of hist "madness" as an assumed role. In Act I "madness occurs first as a mere possibility when Hamlet informs his friends, he might "put an antic disposition on"; in Act II vis-a-vis Rosencrantz and Guildenstern ("I am but mad north-north-west") it is his deliberate action under certain conditions; in Act III it occurs thrice, first in his declaration of intent ("They are coming to the play, I must be idle" (i.e. "mad"), next in answering the king ("I fare of the chamaeleon's dish"), and once again in a particularly explicit distinction for his mother ("I am essentially not in madness, but mad in craft"). The evidence of all other instances of mad/madness represented here corroborates these findings: madness as an adopted role and not as a character trait. - It should also be noted that Shakespeare's main source (Belleforests adaptation of the Amleth-story from Saxo Grammaticus) already knew of the motive of stimulated madness as a cover for revenge. Hamlet assumes the role of a "madman" in order to have full scope for action, first, to test by help of the "play in the play" the truth of his father's apparition as a ghost demanding revenge as well as the actual guilt of Claudius and, when that is established, for preparing and executing his revenge. By acting himself, Hamlet becomes guilty and (Shakespeare having chosen the dramatic genre of tragedy) pays for his success with his life. Considering the constant border-crossings between the spheres of real persons and fictive literary figures in psychological approaches to Hamlet, we stressed the essential difference of a literary work of art from real life. At the same time, the inherent limitations of that difference must be shown as well. Although the world of belles lettres is fictive and non-existent in reality, it does not play in a vacuum. It is fed, in many ways, by the poet's experience of his own days as well as by the work's position within the realm of literary tradition (genre, sources, etc.). It is perhaps easy, to insist on the self-contained nature of literature, making literary criticism an arcane activity of a few elected professionals. The price to pay would be, as Laurence Lerner points out, that great literature will no longer tell us anything about life, and the poet's subtle insights, his wisdom, his understanding of the soul and of the world cease to enrich the general read

40 CFR 51.50 - What definitions apply to this subpart?

Code of Federal Regulations, 2011 CFR

2011-07-01

... organization transmitting the data set, including first name, middle name or initial, and surname. Contact... unit's nameplate by the manufacturer. The data element is reported in megawatts or kilowatts. Method accuracy description (MAD) codes means a set of six codes used to define the accuracy of latitude/longitude...

40 CFR 51.50 - What definitions apply to this subpart?

Code of Federal Regulations, 2014 CFR

2014-07-01

... organization transmitting the data set, including first name, middle name or initial, and surname. Contact... unit's nameplate by the manufacturer. The data element is reported in megawatts or kilowatts. Method accuracy description (MAD) codes means a set of six codes used to define the accuracy of latitude/longitude...

40 CFR 51.50 - What definitions apply to this subpart?

Code of Federal Regulations, 2013 CFR

2013-07-01

... organization transmitting the data set, including first name, middle name or initial, and surname. Contact... unit's nameplate by the manufacturer. The data element is reported in megawatts or kilowatts. Method accuracy description (MAD) codes means a set of six codes used to define the accuracy of latitude/longitude...

40 CFR 51.50 - What definitions apply to this subpart?

Code of Federal Regulations, 2012 CFR

2012-07-01

... organization transmitting the data set, including first name, middle name or initial, and surname. Contact... unit's nameplate by the manufacturer. The data element is reported in megawatts or kilowatts. Method accuracy description (MAD) codes means a set of six codes used to define the accuracy of latitude/longitude...

There's Madness in Your Method: A Philosophical Exploration into the Thought of Paul Feyerabend and Its Implications for Music Education

ERIC Educational Resources Information Center

Louth, Paul

2014-01-01

Drawing on the work of the philosopher of science Paul Feyerabend, this paper argues that the popular yet mistaken notion of scientific method has had a deleterious effect on music education by discouraging us from embracing conflict or pursuing counterinductive ways of thinking about music. Feyerabend argues that knowledge advances not according…

Genome-wide analysis of the MADS-box gene family in polyploid cotton (Gossypium hirsutum) and in its diploid parental species (Gossypium arboreum and Gossypium raimondii).

PubMed

Nardeli, Sarah Muniz; Artico, Sinara; Aoyagi, Gustavo Mitsunori; de Moura, Stéfanie Menezes; da Franca Silva, Tatiane; Grossi-de-Sa, Maria Fatima; Romanel, Elisson; Alves-Ferreira, Marcio

2018-06-01

The MADS-box gene family encodes transcription factors that share a highly conserved domain known to bind to DNA. Members of this family control various processes of development in plants, from root formation to fruit ripening. In this work, a survey of diploid (Gossypium raimondii and Gossypium arboreum) and tetraploid (Gossypium hirsutum) cotton genomes found a total of 147, 133 and 207 MADS-box genes, respectively, distributed in the MIKC, Mα, Mβ, Mγ, and Mδ subclades. A comparative phylogenetic analysis among cotton species, Arabidopsis, poplar and grapevine MADS-box homologous genes allowed us to evaluate the evolution of each MADS-box lineage in cotton plants and identify sequences within well-established subfamilies. Chromosomal localization and phylogenetic analysis revealed that G. raimondii and G. arboreum showed a conserved evolution of the MIKC subclade and a distinct pattern of duplication events in the Mα, Mγ and Mδ subclades. Additionally, G. hirsutum showed a combination of its parental subgenomes followed by a distinct evolutionary history including gene gain and loss in each subclade. qPCR analysis revealed the expression patterns of putative homologs in the AP1, AP3, AGL6, SEP4, AGL15, AG, AGL17, TM8, SVP, SOC and TT16 subfamilies of G. hirsutum. The identification of putative cotton orthologs is discussed in the light of evolution and gene expression data from other plants. This analysis of the MADS-box genes in Gossypium species opens an avenue to understanding the origin and evolution of each gene subfamily within diploid and polyploid species and paves the way for functional studies in cotton species. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Protecting cognition from aging and Alzheimer's disease: a computerized cognitive training combined with reminiscence therapy.

PubMed

Barban, Francesco; Annicchiarico, Roberta; Pantelopoulos, Stelios; Federici, Alessia; Perri, Roberta; Fadda, Lucia; Carlesimo, Giovanni Augusto; Ricci, Claudia; Giuli, Simone; Scalici, Francesco; Turchetta, Chiara Stella; Adriano, Fulvia; Lombardi, Maria Giovanna; Zaccarelli, Chiara; Cirillo, Giulio; Passuti, Simone; Mattarelli, Paolo; Lymperopoulou, Olga; Sakka, Paraskevi; Ntanasi, Eva; Moliner, Reyes; Garcia-Palacios, Azucena; Caltagirone, Carlo

2016-04-01

The aim of this paper was to assess the efficacy of process-based cognitive training (pb-CT) combined with reminiscence therapy (RT) in patients with mild Alzheimer's disease (mAD) and mild cognitive impairment (MCI) and in healthy elderly (HE) subjects. This multicenter, randomized, controlled trial involved 348 participants with mAD, MCI, and HE from four European countries. Participants were randomly assigned to two arms of a crossover design: those in arm A underwent 3 months of computerized pb-CT for memory and executive functions combined with RT and 3 months of rest; those in arm B underwent the reverse. The primary outcome was the effect of the training on memory and executive functions performance. The secondary outcome was the effect of the training on functional abilities in mAD assessed with the instrumental activities of daily living. We found a significant effect of the training for memory in all three groups on delayed recall of the Rey Auditory Verbal Learning Test and for executive functions in HE on the phonological fluency test. MCI and HE participants maintained these effects at follow-up. MCI and mAD participants also showed a significant effect of the training on the Mini-mental state examination scale. Participants with mAD showed more stable instrumental activities of daily living during the training versus the rest period. Our results corroborate the positive effect of pb-CT and its maintenance primarily on memory in HE and MCI participants that did not seem to be potentiated by RT. Moreover, our results are very promising for the mAD participants. Copyright © 2015 John Wiley & Sons, Ltd.

EPA Office of Water (OW): SDWIS - HUC12 Densities for Public Surface Water and Groundwater Sources

EPA Pesticide Factsheets

Public Water System location points, based on information from the Safe Drinking Water Act Information System (SDWIS/Federal) for a 2010 third quarter (SDWIS_2010Q3) baseline period, were applied to relate system latitude and longitude coordinates (LatLongs) to Watershed Boundary Dataset subwatershed polygons (HUC12s). This HUC12 table can be mapped through setting up appropriate table relationships on the attribute HUC_12 with the HUC12 GIS layer that is part of EPA's Reach Address Database (RAD) Version 3. At the present time, the RAD Version 3 contains HUC12 polygons for the conterminous United States (CONUS), Hawaii, Puerto Rico, and the U.S. Virgin Islands (materials for Alaska or for other territories and dependencies are not available as of February, 2010). The records in this table are based on a special QUERY created by the EPA Office of Ground Water and Drinking Water (OGWDW) from the primary SDWIS/FED information to provide a robust point representation for a PWS system. PWS points are selected based on the following prioritization: 1. If the system has a treatment plant with LatLongs and MAD codes; 2. If the system has a treatment plant with LatLongs but without MAD codes; 3. If the system has a well with LatLongs and MAD codes; 4. If the system has a well with LatLongs but without MAD codes; 5. If the system has an intake with LatLongs and MAD codes; 6. If the system has an intake with LatLongs but without MAD codes; 7. If the system has any source

Cognitive Bias by Gender Interaction on N170 Response to Emotional Facial Expressions in Major and Minor Depression.

PubMed

Wu, Xingqu; Chen, Jiu; Jia, Ting; Ma, Wentao; Zhang, Yan; Deng, Zihe; Yang, Laiqi

2016-03-01

States of depression are considered to relate to a cognitive bias reactivity to emotional events. Moreover, gender effect may influence differences in emotional processing. The current study is to investigate whether there is an interaction of cognitive bias by gender on emotional processing in minor depression (MiD) and major depression (MaD). N170 component was obtained during a visual emotional oddball paradigm to manipulate the processing of emotional information in 33 MiD, 36 MaD, and 32 controls (CN). Compared with CN, in male, both MiD and MaD had lower N170 amplitudes for happy faces, but MaD had higher N170 amplitudes for sad faces; in female, both MiD and MaD had lower N170 amplitudes for happy and neutral faces, but higher N170 amplitudes for sad faces. Compared with MaD in male, MiD had higher N170 amplitudes for happy faces, lower N170 amplitudes for sad faces; in female, MiD only had higher N170 amplitudes for sad faces. Interestingly, a negative relationship was observed between N170 amplitude and the HDRS score for identification of happy faces in depressed patients while N170 amplitude was positively correlated with the HDRS score for sad faces identification. These results provide novel evidence for the mood-brightening effect with an interaction of cognitive bias by gender on emotional processing. It further suggests that female depression may be more vulnerable than male during emotional face processing with the unconscious negative cognitive bias and depressive syndromes may exist on a spectrum of severity on emotional face processing.

[Existence, Absence and Power of Madness: A Critical Review of Michel Foucault's Writings on the History and Philosophy of Madness].

PubMed

Brückner, Burkhart; Iwer, Lukas; Thoma, Samuel

2017-03-01

This article discusses Michel Foucault's main writings on "madness and psychiatry" from his early works up to the 1970s. On the one hand, we reconstruct the overall theoretical and methodological development of his positions over the course of the different periods in his oeuvre. On the other hand, we also take a closer look at Foucault's philosophical considerations regarding the subjects of his investigations. After an initial introduction of our conceptual approach, we draw on the most recent research on Foucault to show to what extent the phenomenological description of the topic at hand and the historical-critical perspective that are reflected in his early writings of 1954 (the Introduction to Binswanger's Dream and Existence and Mental Illness and Personality) laid the ground for his later work. Moving on to Foucault's work during the 1960s, we look at the core features and methodological bases of his 1961 classic Folie et déraison (History of Madness). His propositions regarding the "absence of madness" in modernity are conceptualized as an inherently contradictory attempt to liberate the topic under study from the common assumptions at that time. We then situate his 1973/74 lectures on Psychiatric Power in the context of his shift towards analyzing the dynamics of power and highlight the renewed shift of focus in his statements on the "productivity" of madness as an effect of power. Finally, we sum up our critique by taking into account the history of the reception of Foucault's writings and ask about their potential significance for the contemporary philosophy and history of psychiatry.

Mandibuloacral dysplasia: A premature ageing disease with aspects of physiological ageing.

PubMed

Cenni, Vittoria; D'Apice, Maria Rosaria; Garagnani, Paolo; Columbaro, Marta; Novelli, Giuseppe; Franceschi, Claudio; Lattanzi, Giovanna

2018-03-01

Mandibuloacral dysplasia (MAD) is a rare genetic condition characterized by bone abnormalities including localized osteolysis and generalized osteoporosis, skin pigmentation, lipodystrophic signs and mildly accelerated ageing. The molecular defects associated with MAD are mutations in LMNA or ZMPSTE24 (FACE1) gene, causing type A or type B MAD, respectively. Downstream of LMNA or ZMPSTE24 mutations, the lamin A precursor, prelamin A, is accumulated in cells and affects chromatin dynamics and stress response. A new form of mandibuloacral dysplasia has been recently associated with mutations in POLD1 gene, encoding DNA polymerase delta, a major player in DNA replication. Of note, involvement of prelamin A in chromatin dynamics and recruitment of DNA repair factors has been also determined under physiological conditions, at the border between stress response and cellular senescence. Here, we review current knowledge on MAD clinical and pathogenetic aspects and highlight aspects typical of physiological ageing. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Dual personality of Mad1: regulation of nuclear import by a spindle assembly checkpoint protein.

PubMed

Cairo, Lucas V; Ptak, Christopher; Wozniak, Richard W

2013-01-01

Nuclear transport is a dynamic process that can be modulated in response to changes in cellular physiology. We recently reported that the transport activity of yeast nuclear pore complexes (NPCs) is altered in response to kinetochore-microtubule (KT-MT) interaction defects. Specifically, KT detachment from MTs activates a signaling pathway that prevents the nuclear import of cargos by the nuclear transport factor Kap121p. This loss of Kap121p-mediated import is thought to influence the nuclear environment, including the phosphorylation state of nuclear proteins. A key regulator of this process is the spindle assembly checkpoint protein Mad1p. In response to unattached KTs, Mad1p dynamically cycles between NPCs and KTs. This cycling appears to induce NPC molecular rearrangements that prevent the nuclear import of Kap121p-cargo complexes. Here, we discuss the underlying mechanisms and the physiological relevance of Mad1p cycling and the inhibition of Kap121p-mediated nuclear import, focusing on outstanding questions within the pathway.

FlyMAD: rapid thermogenetic control of neuronal activity in freely walking Drosophila.

PubMed

Bath, Daniel E; Stowers, John R; Hörmann, Dorothea; Poehlmann, Andreas; Dickson, Barry J; Straw, Andrew D

2014-07-01

Rapidly and selectively modulating the activity of defined neurons in unrestrained animals is a powerful approach in investigating the circuit mechanisms that shape behavior. In Drosophila melanogaster, temperature-sensitive silencers and activators are widely used to control the activities of genetically defined neuronal cell types. A limitation of these thermogenetic approaches, however, has been their poor temporal resolution. Here we introduce FlyMAD (the fly mind-altering device), which allows thermogenetic silencing or activation within seconds or even fractions of a second. Using computer vision, FlyMAD targets an infrared laser to freely walking flies. As a proof of principle, we demonstrated the rapid silencing and activation of neurons involved in locomotion, vision and courtship. The spatial resolution of the focused beam enabled preferential targeting of neurons in the brain or ventral nerve cord. Moreover, the high temporal resolution of FlyMAD allowed us to discover distinct timing relationships for two neuronal cell types previously linked to courtship song.

Microbial community structure in a thermophilic aerobic digester used as a sludge pretreatment process for the mesophilic anaerobic digestion and the enhancement of methane production.

PubMed

Jang, Hyun Min; Park, Sang Kyu; Ha, Jeong Hyub; Park, Jong Moon

2013-10-01

An effective two-stage sewage sludge digestion process, consisting of thermophilic aerobic digestion (TAD) followed by mesophilic anaerobic digestion (MAD), was developed for efficient sludge reduction and methane production. Using TAD as a biological pretreatment, the total volatile suspended solid reduction (VSSR) and methane production rate (MPR) in the MAD reactor were significantly improved. According to denaturing gradient gel electrophoresis (DGGE) analysis, the results indicated that the dominant bacteria species such as Ureibacillus thermophiles and Bacterium thermus in TAD were major routes for enhancing soluble organic matter. TAD pretreatment using a relatively short SRT of 1 day showed highly increased soluble organic products and positively affected an increment of bacteria populations which performed interrelated microbial metabolisms with methanogenic species in the MAD; consequently, a quantitative real-time PCR indicated greatly increased Methanosarcinales (acetate-utilizing methanogens) in the MAD, resulting in enhanced methane production. Copyright © 2013 Elsevier Ltd. All rights reserved.

Characterization of a Smad motif similar to Drosophila mad in the mouse Msx 1 promoter.

PubMed

Alvarez Martinez, Cristina E; Binato, Renata; Gonzalez, Sayonara; Pereira, Monica; Robert, Benoit; Abdelhay, Eliana

2002-03-01

Mouse Msx 1 gene, orthologous of the Drosophila msh, is involved in several developmental processes. BMP family members are major proteins in the regulation of Msx 1 expression. BMP signaling activates Smad 1/5/8 proteins, which associate to Smad 4 before translocating to the nucleus. Analysis of Msx 1 promoter revealed the presence of three elements similar to the consensus established for Mad, the Smad 1 Drosophila counterpart. Notably, such an element was identified in an enhancer important for Msx 1 regulation. Gel shift analysis demonstrated that proteins from 13.5 dpc embryo associate to this enhancer. Remarkably, supershift assays showed that Smad proteins are present in the complex. Purified Smad 1 and 4 also bind to this fragment. We demonstrate that functional binding sites in this enhancer are confined to the Mad motif and flanking region. Our data suggest that this Mad motif may be functional in response to BMP signaling. ©2002 Elsevier Science (USA).

A MADS box protein interacts with a mating-type protein and is required for fruiting body development in the homothallic ascomycete Sordaria macrospora.

PubMed

Nolting, Nicole; Pöggeler, Stefanie

2006-07-01

MADS box transcription factors control diverse developmental processes in plants, metazoans, and fungi. To analyze the involvement of MADS box proteins in fruiting body development of filamentous ascomycetes, we isolated the mcm1 gene from the homothallic ascomycete Sordaria macrospora, which encodes a putative homologue of the Saccharomyces cerevisiae MADS box protein Mcm1p. Deletion of the S. macrospora mcm1 gene resulted in reduced biomass, increased hyphal branching, and reduced hyphal compartment length during vegetative growth. Furthermore, the S. macrospora Deltamcm1 strain was unable to produce fruiting bodies or ascospores during sexual development. A yeast two-hybrid analysis in conjugation with in vitro analyses demonstrated that the S. macrospora MCM1 protein can interact with the putative transcription factor SMTA-1, encoded by the S. macrospora mating-type locus. These results suggest that the S. macrospora MCM1 protein is involved in the transcriptional regulation of mating-type-specific genes as well as in fruiting body development.

Proteomics and SSH Analyses of ALA-Promoted Fruit Coloration and Evidence for the Involvement of a MADS-Box Gene, MdMADS1

PubMed Central

Feng, Xinxin; An, Yuyan; Zheng, Jie; Sun, Miao; Wang, Liangju

2016-01-01

Skin color is a key quality attribute of fruits and how to improve fruit coloration has long been a major concern. 5-Aminolevulinic acid (ALA), a natural plant growth regulator, can significantly increase anthocyanin accumulation in fruit skin and therefore effectively improve coloration of many fruits, including apple. However, the molecular mechanism how ALA stimulates anthocyanin accumulation in fruit skin remains unknown. Here, we investigated the impact of ALA on apple skin at the protein and mRNA levels. A total of 85 differentially expressed proteins in apple skins between ALA and water treatment (control) were identified by complementary gel-based and gel-free separation techniques. Most of these differentially expressed proteins were up-regulated by ALA. Function analysis suggested that 87.06% of the ALA-responsive proteins were associated with fruit ripening. To further screen ALA-responsive regulators, we constructed a subtracted cDNA library (tester: ALA treatment; driver: control) and obtained 104 differentially expressed unigenes, of which 38 unigenes were indicators for the fruit ripening-related genes. The differentially changed proteins and transcripts did not correspond well at an individual level, but showed similar regulated direction in function at the pathway level. Among the identified fruit ripening-related genes, the expression of MdMADS1, a developmental transcription regulator of fruit ripening, was positively correlated with expression of anthocyanin biosynthetic genes (MdCHS, MdDFR, MdLDOX, and MdUFGT) in apple skin under ALA treatment. Moreover, overexpression of MdMADS1 enhanced anthocyanin content in transformed apple calli, which was further enhanced by ALA. The anthocyanin content in MdMADS1-silenced calli was less than that in the control with ALA treatment, but higher than that without ALA treatment. These results indicated that MdMADS1 is involved in ALA-induced anthocyanin accumulation. In addition, anthocyanin-related verification in apple calli suggested that the regulation of MdMADS1 on anthocyanin biosynthesis was partially independent of fruit ripening process. Taken together, our findings provide insight into the mechanism how ALA regulates anthocyanin accumulation and add new information on transcriptase regulators of fruit coloration. PMID:27872628

Reliability analysis for radiographic measures of lumbar lordosis in adult scoliosis: a case–control study comparing 6 methods

PubMed Central

Hong, Jae Young; Modi, Hitesh N.; Hur, Chang Yong; Song, Hae Ryong; Park, Jong Hoon

2010-01-01

Several methods are used to measure lumbar lordosis. In adult scoliosis patients, the measurement is difficult due to degenerative changes in the vertebral endplate as well as the coronal and sagittal deformity. We did the observational study with three examiners to determine the reliability of six methods for measuring the global lumbar lordosis in adult scoliosis patients. Ninety lateral lumbar radiographs were collected for the study. The radiographs were divided into normal (Cobb < 10°), low-grade (Cobb 10°–19°), high-grade (Cobb  ≥ 20°) group to determine the reliability of Cobb L1–S1, Cobb L1–L5, centroid, posterior tangent L1–S1, posterior tangent L1–L5 and TRALL method in adult scoliosis. The 90 lateral radiographs were measured twice by each of the three examiners using the six measurement methods. The data was analyzed to determine the inter- and intra-observer reliability. In general, for the six radiographic methods, the inter- and intra-class correlation coefficients (ICCs) were all ≥0.82. A comparison of the ICCs and 95% CI for the inter- and intra-observer reliability between the groups with varying degrees of scoliosis showed that, the reliability of the lordosis measurement decreased with increasing severity of scoliosis. In Cobb L1–S1, centroid and posterior tangent L1–S1 methods, the ICCs were relatively lower in the high-grade scoliosis group (≥0.60). And, the mean absolute difference (MAD) in these methods was high in the high-grade scoliosis group (≤7.17°). However, in the Cobb L1–L5 and posterior tangent L1–L5 method, the ICCs were ≥0.86 in all groups. And, in the TRALL method, the ICCs were ≥0.76 in all groups. In addition, in the Cobb L1–L5 and posterior tangent L1–L5 method, the MAD was ≤3.63°. And, in the TRALL method, the MAD was ≤3.84° in all groups. We concluded that the Cobb L1–L5 and the posterior tangent L1–L5 methods are reliable methods for measuring the global lumbar lordosis in adult scoliosis. And the TRALL method is more reliable method than other methods which include the L5–S1 joint in lordosis measurement. PMID:20437183

Nuclear weapons in the 1980s: MAD versus NUTS. Mutual hostage relationship of the superpowers

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

Keeny, S.M. Jr.; Panofsky, W.K.H.

Critics of the strategic relationship of Mutual Assured Destruction (MAD) developed during the 1960s claim it immorally holds entire civilian populations hostage. Some advocate the Nuclear Utilization Target Selection (NUTS) concept, while others argue for a defense-oriented military posture. The interrelationships of these concepts are examined against the background of stockpiled nuclear weapons capable of massive devastation, the technical limits to defense, and the uncertainty that a nuclear war could be controlled. The evidence shows that a MAD world prevails despite NUTS proposals, which may have increased the danger by giving nuclear war the illusion of acceptability. (DCK)

[The representation of madness in William Shakespeare's characters].

PubMed

Stompe, Thomas; Ritter, Kristina; Friedmann, Alexander

2006-08-01

Shakespeare is one of the great creators of human characters of the 16(th) century. Like for many of his contemporaries madness was a central topic of his work. The first part of this paper discusses the sociocultural environment and the semantic field of madness in the Elizabethan age, which forms the background for Shakespeare's characters. In the second part we try to analyze the clinical pictures of the fictive characters of Othello, Hamlet, Lear and Macbeth. While we find melancholy, delusions and hallucinations, other diseases such as schizophrenia are missing entirely. Schizophrenia only appears in the literature more than two hundred years later, in the beginning of modern age.

John Locke on madness: redressing the intellectualist bias.

PubMed

Charland, Louis C

2014-06-01

Locke is famous for defining madness as an intellectual disorder in the realm of ideas. Numerous commentators take this to be his main and only contribution to the history of psychiatry. However, a detailed exegetical review of all the relevant textual evidence suggests that this intellectualist interpretation of Locke's account of madness is both misleading and incomplete. Affective states of various sorts play an important role in that account and are in fact primordial in the determination of human conduct generally. Locke's legacy in this domain must therefore be revised and the intellectualist bias that dominates discussions of his views must be redressed. © The Author(s) 2014.

A free interactive matching program

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

J.-F. Ostiguy

1999-04-16

For physicists and engineers involved in the design and analysis of beamlines (transfer lines or insertions) the lattice function matching problem is central and can be time-consuming because it involves constrained nonlinear optimization. For such problems convergence can be difficult to obtain in general without expert human intervention. Over the years, powerful codes have been developed to assist beamline designers. The canonical example is MAD (Methodical Accelerator Design) developed at CERN by Christophe Iselin. MAD, through a specialized command language, allows one to solve a wide variety of problems, including matching problems. Although in principle, the MAD command interpreter canmore » be run interactively, in practice the solution of a matching problem involves a sequence of independent trial runs. Unfortunately, but perhaps not surprisingly, there still exists relatively few tools exploiting the resources offered by modern environments to assist lattice designer with this routine and repetitive task. In this paper, we describe a fully interactive lattice matching program, written in C++ and assembled using freely available software components. An important feature of the code is that the evolution of the lattice functions during the nonlinear iterative process can be graphically monitored in real time; the user can dynamically interrupt the iterations at will to introduce new variables, freeze existing ones into their current state and/or modify constraints. The program runs under both UNIX and Windows NT.« less

Combined mesophilic anaerobic and thermophilic aerobic digestion process for high-strength food wastewater to increase removal efficiency and reduce sludge discharge.

PubMed

Jang, H M; Park, S K; Ha, J H; Park, J M

2014-01-01

In this study, a process that combines the mesophilic anaerobic digestion (MAD) process with thermophilic aerobic digestion (TAD) for high-strength food wastewater (FWW) treatment was developed to examine the removal of organic matter and methane production. All effluent discharged from the MAD process was separated into solid and liquid portions. The liquid part was discarded and the sludge part was passed to the TAD process for further degradation. Then, the digested sludge from the TAD process was recycled back to the MAD unit to achieve low sludge discharge from the combined process. The reactor combination was operated in two phases: during Phase I, 40 d of total hydraulic retention time (HRT) was applied; during Phase II, 20 d was applied. HRT of the TAD process was fixed at 5 d. For a comparison, a control process (single-stage MAD) was operated with the same HRTs of the combined process. Our results indicated that the combined process showed over 90% total solids, volatile solids and chemical oxygen demand removal efficiencies. In addition, the combined process showed a significantly higher methane production rate than that of the control process. Consequently, the experimental data demonstrated that the combined MAD-TAD process was successfully employed for high-strength FWW treatment with highly efficient organic matter reduction and methane production.

Genetic and epigenetic alteration among three homoeologous genes of a class E MADS box gene in hexaploid wheat.

PubMed

Shitsukawa, Naoki; Tahira, Chikako; Kassai, Ken-Ichiro; Hirabayashi, Chizuru; Shimizu, Tomoaki; Takumi, Shigeo; Mochida, Keiichi; Kawaura, Kanako; Ogihara, Yasunari; Murai, Koji

2007-06-01

Bread wheat (Triticum aestivum) is a hexaploid species with A, B, and D ancestral genomes. Most bread wheat genes are present in the genome as triplicated homoeologous genes (homoeologs) derived from the ancestral species. Here, we report that both genetic and epigenetic alterations have occurred in the homoeologs of a wheat class E MADS box gene. Two class E genes are identified in wheat, wheat SEPALLATA (WSEP) and wheat LEAFY HULL STERILE1 (WLHS1), which are homologs of Os MADS45 and Os MADS1 in rice (Oryza sativa), respectively. The three wheat homoeologs of WSEP showed similar genomic structures and expression profiles. By contrast, the three homoeologs of WLHS1 showed genetic and epigenetic alterations. The A genome WLHS1 homoeolog (WLHS1-A) had a structural alteration that contained a large novel sequence in place of the K domain sequence. A yeast two-hybrid analysis and a transgenic experiment indicated that the WLHS1-A protein had no apparent function. The B and D genome homoeologs, WLHS1-B and WLHS1-D, respectively, had an intact MADS box gene structure, but WLHS1-B was predominantly silenced by cytosine methylation. Consequently, of the three WLHS1 homoeologs, only WLHS1-D functions in hexaploid wheat. This is a situation where three homoeologs are differentially regulated by genetic and epigenetic mechanisms.

On Some Confidence Intervals for Estimating the Mean of a Skewed Population

ERIC Educational Resources Information Center

Shi, W.; Kibria, B. M. Golam

2007-01-01

A number of methods are available in the literature to measure confidence intervals. Here, confidence intervals for estimating the population mean of a skewed distribution are considered. This note proposes two alternative confidence intervals, namely, Median t and Mad t, which are simple adjustments to the Student's t confidence interval. In…

Making and Mining Intellectual Capital: Method or Madness?

ERIC Educational Resources Information Center

Cohen, Stephen L.; Backer, Nena K.

1999-01-01

A process for creating and managing intellectual capital within an organization has the following stages: (1) inquire about causes and effects and infer the implications; (2) invent solutions and inspire others with a cause for change; and (3) install solutions and inspect over the long term to see what is and is not working. (JOW)

Hydrogen Abstraction by Chlorine Atom from Small Organic Molecules Containing Amino Acid Functionalities: An Assessment of Theoretical Procedures

NASA Astrophysics Data System (ADS)

Taylor, Mark S.; Ivanic, Sandra A.; Wood, Geoffrey P. F.; Easton, Christopher J.; Bacskay, George B.; Radom, Leo

2009-07-01

A high-level quantum chemistry investigation has been carried out for the abstraction by chlorine atom of hydrogen from methane and five monosubstituted methanes, chosen to reflect the chemical functionalities contained in amino acids and peptides. A modified W1' procedure is used to calculate benchmark barriers and reaction energies for the six reactions. The reactions demonstrate a broad range of barrier heights and reaction energies, which can be rationalized using curve-crossing and molecular orbital theory models. In addition, the performance of a range of computationally less demanding electronic structure methods is assessed for calculating the energy profiles for the six reactions. It is found that the G3X(MP2)-RAD procedure compares best with the W1' benchmark, demonstrating a mean absolute deviation (MAD) from W1' of 2.1 kJ mol-1. The more economical RMP2/G3XLarge and UB2-PLYP/G3XLarge methods are also shown to perform well, with MADs from W1' of 2.9 and 3.0 kJ mol-1, respectively.

A MAD-Bayes Algorithm for State-Space Inference and Clustering with Application to Querying Large Collections of ChIP-Seq Data Sets.

PubMed

Zuo, Chandler; Chen, Kailei; Keleş, Sündüz

2017-06-01

Current analytic approaches for querying large collections of chromatin immunoprecipitation followed by sequencing (ChIP-seq) data from multiple cell types rely on individual analysis of each data set (i.e., peak calling) independently. This approach discards the fact that functional elements are frequently shared among related cell types and leads to overestimation of the extent of divergence between different ChIP-seq samples. Methods geared toward multisample investigations have limited applicability in settings that aim to integrate 100s to 1000s of ChIP-seq data sets for query loci (e.g., thousands of genomic loci with a specific binding site). Recently, Zuo et al. developed a hierarchical framework for state-space matrix inference and clustering, named MBASIC, to enable joint analysis of user-specified loci across multiple ChIP-seq data sets. Although this versatile framework estimates both the underlying state-space (e.g., bound vs. unbound) and also groups loci with similar patterns together, its Expectation-Maximization-based estimation structure hinders its applicability with large number of loci and samples. We address this limitation by developing MAP-based asymptotic derivations from Bayes (MAD-Bayes) framework for MBASIC. This results in a K-means-like optimization algorithm that converges rapidly and hence enables exploring multiple initialization schemes and flexibility in tuning. Comparison with MBASIC indicates that this speed comes at a relatively insignificant loss in estimation accuracy. Although MAD-Bayes MBASIC is specifically designed for the analysis of user-specified loci, it is able to capture overall patterns of histone marks from multiple ChIP-seq data sets similar to those identified by genome-wide segmentation methods such as ChromHMM and Spectacle.

Mission, MOOCs, and Money

ERIC Educational Resources Information Center

Green, Kenneth C.

2013-01-01

Forget basketball and March Madness. Aside from always pressing financial issues, it is "MOOC madness" that has emerged as the topic "du jour" at a growing number of American colleges and universities. Indeed, in boardrooms all across the country, people are grappling with what the advent of MOOCs--massive open online courses--means to their…

Characterization, Expression and Function of DORMANCY ASSOCIATED MADS-BOX Genes from Leafy Spurge

USDA-ARS?s Scientific Manuscript database

DORMANCY ASSOCIATED MADS-BOX (DAM) genes are related to AGAMOUS-LIKE 24 and SHORT VEGETATIVE PHASE genes of arabidopsis and are differentially regulated coordinately with endodormancy induction and release in buds of several perennial plant species. DAM genes were first shown to directly impact endo...

Cloning, characterization, regulation, and function of dormancy-associated MADS-BOX genes from leafy spurge

USDA-ARS?s Scientific Manuscript database

DORMANCY-ASSOCIATED MADS-BOX (DAM) genes are transcription factors that have been linked to endodormancy induction. The evergrowing mutation in peach, which renders it incapable of entering endodormancy, resulted from a deletion in a series of DAM genes (Bielenberg et al. 2008). Likewise, DAM genes ...

Cloning, Characterization, Regulation, and Function of DORMANCY-ASSOCIATED MADS-BOX Genes from Leafy Spurge

USDA-ARS?s Scientific Manuscript database

DORMANCY-ASSOCIATED MADS-BOX (DAM) genes are transcription factors that have been linked to endodormancy induction. The evergrowing mutation in peach, which renders it incapable of entering endodormancy, resulted from a deletion in a series of DAM genes (Bielenberg et al. 2008). Likewise, DAM genes ...

Microbial Protein-Antigenome Determination (MAD) Technology: A Proteomics-Based Strategy for Rapid Identification of Microbial Targets of Host Humoral Immune Responses

USDA-ARS?s Scientific Manuscript database

Immunogenic, pathogen-specific proteins have excellent potential for development of novel management modalities. Here, we describe an innovative application of proteomics called Microbial protein-Antigenome Determination (MAD) Technology for rapid identification of native microbial proteins that el...

Microbial Protein-Antigenome Determination (MAD) Technology: A Proteomics-Based Strategy for Rapid Identification of Microbial Targets of Host Humoral Immune Responses

USDA-ARS?s Scientific Manuscript database

Immunogenic, pathogen-specific proteins have excellent potential for development of novel management modalities. Here, we describe an innovative application of proteomics called Microbial protein-Antigenome Determination (MAD) Technology for rapid identification of native microbial proteins that eli...

A BRIEF DISCUSSION REGARDING PRION DISEASES AND SARS

EPA Science Inventory

Recent diagnoses of Mad Cow disease in Canadian and American cattle has increased concern for this disease and other TSEs in North America. This presentation provides a quick review of the important features of Mad Cow disease as well as SARS as they might relate to land applicat...

Three-Dimensional Bayesian Geostatistical Aquifer Characterization at the Hanford 300 Area using Tracer Test Data

NASA Astrophysics Data System (ADS)

Chen, X.; Murakami, H.; Hahn, M. S.; Hammond, G. E.; Rockhold, M. L.; Rubin, Y.

2010-12-01

Tracer testing under natural or forced gradient flow provides useful information for characterizing subsurface properties, by monitoring and modeling the tracer plume migration in a heterogeneous aquifer. At the Hanford 300 Area, non-reactive tracer experiments, in addition to constant-rate injection tests and electromagnetic borehole flowmeter (EBF) profiling, were conducted to characterize the heterogeneous hydraulic conductivity field. A Bayesian data assimilation technique, method of anchored distributions (MAD), is applied to assimilate the experimental tracer test data and to infer the three-dimensional heterogeneous structure of the hydraulic conductivity in the saturated zone of the Hanford formation. In this study, the prior information of the underlying random hydraulic conductivity field was obtained from previous field characterization efforts using the constant-rate injection tests and the EBF data. The posterior distribution of the random field is obtained by further conditioning the field on the temporal moments of tracer breakthrough curves at various observation wells. The parallel three-dimensional flow and transport code PFLOTRAN is implemented to cope with the highly transient flow boundary conditions at the site and to meet the computational demand of the proposed method. The validation results show that the field conditioned on the tracer test data better reproduces the tracer transport behavior compared to the field characterized previously without the tracer test data. A synthetic study proves that the proposed method can effectively assimilate tracer test data to capture the essential spatial heterogeneity of the three-dimensional hydraulic conductivity field. These characterization results will improve conceptual models developed for the site, including reactive transport models. The study successfully demonstrates the capability of MAD to assimilate multi-scale multi-type field data within a consistent Bayesian framework. The MAD framework can potentially be applied to combine geophysical data with other types of data in site characterization.

The secular and the supernatural: madness and psychiatry in the short stories of Muriel Spark.

PubMed

Beveridge, A W

2015-01-01

Edinburgh-born Muriel Spark is one of modern Scotland's greatest writers. Examination of her work reveals that the subjects of madness and psychiatry are recurrent themes in her writing. She herself had a mental breakdown when she was a young woman and she took an interest in the world of psychiatry and psychoanalysis. In her short stories, Spark approaches the subject of madness in a variety of ways: she relates it to the supernatural; to writing fiction; and to religion. She frequently juxtaposes secular and supernatural explanations of mental disturbance. Spark adopts a sceptical and, at times, mocking view of psychiatrists and psychiatric treatment. Both psychoanalysis and pills are seen as problematic.

Validation of a hand-held point of care device for lactate in adult and pediatric patients using traditional and locally-smoothed median and maximum absolute difference curves.

PubMed

Colon-Franco, Jessica Marie; Lo, Stanley F; Tarima, Sergey S; Gourlay, David; Drendel, Amy L; Brook Lerner, E

2017-05-01

Lactate is commonly used in septic patients and is a viable biomarker for trauma patients. Its pre-hospital use could assist triaging and managing patients with these conditions. We evaluated the analytical performance of the point-of-care (POC) StatStrip Xpress Lactate Meter (Nova Biomedical) and compared it to the ABL 800 (Radiometer). We measured lactate in 250 adult and 250 pediatric whole blood samples in 2 laboratories. The performance of the POC meter was assessed by traditional linear regression and Bland-Altman plots, and locally-smoothed (LS) median absolute difference and maximum absolute difference (MAD and MaxAD) curves. The StatStrip was linear with acceptable reproducibility at clinically relevant concentrations. Correlation with the ABL800 showed a negative bias for both populations with slope, bias ±SD (% bias) of 0.78, -0.4±0.7 (-14.5%) in children and 0.80-0.3±0.6 (-13.3%) in adults. The proportional bias appeared more significant at concentrations >4mmol/l (36.0mg/dl). The StatStrip misclassified 7.6 and 8.8% pediatric and adult samples, respectively, to lower risk categories defined using guidelines driven cut-offs. The LS MAD curves identified one breakout, concentration where the LS MAD exceeds the total allowable error limit of 0.3mmol/l (2.7mg/dl), at lactate concentrations of 3.8 and 3.2mmol/l (34.2 and 28.8mg/dl) in the pediatric and adult curves, respectively. Breakthroughs, points at which the LS MaxAD curve exceeds the 95th percentile of MaxADs, occur at concentrations above 7.5mmol/l (67.6mg/dl) for both populations where the performance of the POC meter became erratic. We concluded that if serial lactate measurements are performed, the same method should be used for baseline and follow up measurements. The LS MAD and LS MaxAD curves allowed visual and quantitative mapping of the performance of the lactate POC meter over the range of concentrations measured. This approach seems useful for the identification of points at which the performance of a POC meter differs significantly from a comparison method and thresholds of poor analytical performance. Copyright © 2017 Elsevier B.V. All rights reserved.

75 FR 20979 - Six Rivers National Forest, Mad River Ranger District, Ruth, CA, Beaverslide Timber Sale and Fuel...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-22

... DEPARTMENT OF AGRICULTURE Forest Service Six Rivers National Forest, Mad River Ranger District, Ruth, CA, Beaverslide Timber Sale and Fuel Treatment Project AGENCY: Forest Service, USDA. ACTION: Notice of intent to prepare a supplemental environmental impact statement. SUMMARY: The Forest Service is...

Power, Madness and Poverty: [An Article and Responses].

ERIC Educational Resources Information Center

Smith, Carl R., Ed.

1981-01-01

The lead article by H. Drummond examines the cultural context of psychosis and concludes that madness is deeply rooted in social and sexual inequality. The author, a psychiatrist, supports his argument with case studies, reports on the use of drugs with the psychotic, research on efforts to demonstrate that schizophrenia is a biological illness,…

Reviewing the Link between Creativity and Madness: A Postmodern Perspective

ERIC Educational Resources Information Center

Koh, Caroline

2006-01-01

Researchers on creativity and psychology have long been fascinated with the high incidence of psychotic behavior amongst geniuses and individuals of exceptional creativity. The aims of this paper are first, to review the existing findings for a better insight into the socio-contextual factors underpinning the mad genius conundrum, and secondly, to…

Coordinating expression of FLOWERING LOCUS T by DORMANCY ASSOCIATED MADS-BOX-like genes in leafy spurge

USDA-ARS?s Scientific Manuscript database

Leafy spurge is a noxious perennial weed that produces underground adventitious buds, which are crucial for generating new vegetative shoots following periods of freezing temperatures or exposure to various control measures. DORMANCY ASSOCIATED MADS-BOX (DAM) genes have been proposed to play a direc...

The Mad, Mad World of Textbook Adoption

ERIC Educational Resources Information Center

Thomas B Fordham Foundation and Institute, 2004

2004-01-01

Textbook Adoption: The process, in place in twenty-one states, of reviewing textbooks according to state guidelines and then mandating specific books that schools must use, or lists of approved textbooks that schools must choose from. It consistently produces second-rate textbooks that replicate the same flaws and failings over and over again.…

An Act of Methodology: A Document in Madness--Writing Ophelia

ERIC Educational Resources Information Center

Steinnes, Jenny

2012-01-01

This paper is an attempt to stage some questions concerning methodology and education, inspired by Ophelia in Shakespeare's "Hamlet" and by Jacques Derrida's poetic philosophical oeuvres. What are at stake are the long traditions of preferences of sanity over madness, friend over enemy, male over female and of clean, unambiguous univocal language…

A MAD Explanation for the Correlation between Bulk Lorentz Factor and Minimum Variability Timescale

NASA Astrophysics Data System (ADS)

Lloyd-Ronning, Nicole; Lei, Wei-hua; Xie, Wei

2018-04-01

We offer an explanation for the anti-correlation between the minimum variability timescale (MTS) in the prompt emission light curve of gamma-ray bursts (GRBs) and the estimated bulk Lorentz factor of these GRBs, in the context of a magnetically arrested disk (MAD) model. In particular, we show that previously derived limits on the maximum available energy per baryon in a Blandford-Znajek jet leads to a relationship between the characteristic MAD timescale in GRBs and the maximum bulk Lorentz factor: tMAD∝Γ-6, somewhat steeper than (although within the error bars of) the fitted relationship found in the GRB data. Similarly, the MAD model also naturally accounts for the observed anti-correlation between MTS and gamma-ray luminosity L in the GRB data, and we estimate the accretion rates of the GRB disk (given these luminosities) in the context of this model. Both of these correlations (MTS - Γ and MTS - L) are also observed in the AGN data, and we discuss the implications of our results in the context of both GRB and blazar systems.

Impacts of zero valent iron, natural zeolite and Dnase on the fate of antibiotic resistance genes during thermophilic and mesophilic anaerobic digestion of swine manure.

PubMed

Zhang, Junya; Sui, Qianwen; Zhong, Hui; Meng, Xiaoshan; Wang, Ziyue; Wang, Yawei; Wei, Yuansong

2018-06-01

This study investigated the fate of antibiotic resistance genes (ARGs) during mesophilic (mAD) and thermophilic digestion (tAD) of swine manure through zero valent iron (ZVI), natural zeolite and Dnase addition. Changes of microbial community, intI1, heavy metal resistance genes (MRGs) and virulence factors (VFs) were followed to clarify the influencing factors to ARGs reduction. Results showed that AD could realize ARGs reduction with tAD superior to mAD, and ZVI and natural zeolite could further enhance the reduction, especially for natural zeolite addition at mAD. The reduction efficiency of the relative abundance of ARGs was increased by 33.3% and 138.5% after ZVI and natural zeolite addition, respectively, but Dnase deteriorated ARGs reduction at mAD. Most of ARGs could be reduced effectively except sulII and tetM. Network analysis and partial redundancy analysis indicated that co-occurrence of MRGs followed by microbial community contributed the most to the variation of ARGs fate among treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

A MADS Box Protein Interacts with a Mating-Type Protein and Is Required for Fruiting Body Development in the Homothallic Ascomycete Sordaria macrospora

PubMed Central

Nolting, Nicole; Pöggeler, Stefanie

2006-01-01

MADS box transcription factors control diverse developmental processes in plants, metazoans, and fungi. To analyze the involvement of MADS box proteins in fruiting body development of filamentous ascomycetes, we isolated the mcm1 gene from the homothallic ascomycete Sordaria macrospora, which encodes a putative homologue of the Saccharomyces cerevisiae MADS box protein Mcm1p. Deletion of the S. macrospora mcm1 gene resulted in reduced biomass, increased hyphal branching, and reduced hyphal compartment length during vegetative growth. Furthermore, the S. macrospora Δmcm1 strain was unable to produce fruiting bodies or ascospores during sexual development. A yeast two-hybrid analysis in conjugation with in vitro analyses demonstrated that the S. macrospora MCM1 protein can interact with the putative transcription factor SMTA-1, encoded by the S. macrospora mating-type locus. These results suggest that the S. macrospora MCM1 protein is involved in the transcriptional regulation of mating-type-specific genes as well as in fruiting body development. PMID:16835449

Impact of upper airway abnormalities on the success and adherence to mandibular advancement device treatment in patients with Obstructive Sleep Apnea Syndrome.

PubMed

Prescinotto, Renato; Haddad, Fernanda Louise Martinho; Fukuchi, Ilana; Gregório, Luiz Carlos; Cunali, Paulo Afonso; Tufik, Sérgio; Bittencourt, Lia Rita Azeredo

2015-01-01

The mandibular advancement device (MAD) is a option to treat patients with Obstructive Sleep Apnea Syndrome (OSAS). To assess the influence of upper airway abnormalities on the success of and adherence to MAD in patients with OSAS. Prospective study with 30 patients with mild to moderate OSAS and indications for MAD. The protocol included questionnaires addressing sleep and nasal complaints, polysomnography, and upper airway assessment. The analyzed parameters of patients who showed therapeutic success and failure and those who exhibited good and poor treatment adherence were compared. 28 patients completed the protocol; 64.3% responded successfully to treatment with MAD, and 60.7% exhibited good adherence to treatment. Factors associated with greater success rates were younger age (p=0.02), smaller cervical circumference (p=0.05), and lower AHI at baseline (p=0.05). There was a predominance of patients without nasal abnormalities among patients treated successfully compared to those with treatment failure (p=0.04), which was not observed in relation to adherence. Neither pharyngeal nor facial skeletal abnormalities were significantly associated with either therapeutic success or adherence. MAD treatment success was significantly lower among patients with nasal abnormalities; however, treatment adherence was not influenced by the presence of upper airway or facial skeletal abnormalities. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Expressed sequence tags (ESTs) and phylogenetic analysis of floral genes from a paleoherb species, Asarum caudigerum.

PubMed

Zhao, Yinhe; Wang, Guoying; Zhang, Jinpeng; Yang, Junbo; Peng, Shang; Gao, Lianming; Li, Chengyun; Hu, Jinyong; Li, Dezhu; Gao, Lizhi

2006-07-01

Asarum caudigerum (Aristolochiaceae) is an important species of paleoherb in relation to understanding the origin and evolution of angiosperm flowers, due to its basal position in the angiosperms. The aim of this study was to isolate floral-related genes from A. caudigerum, and to infer evolutionary relationships among florally expression-related genes, to further illustrate the origin and diversification of flowers in angiosperms. A subtracted floral cDNA library was constructed from floral buds using suppression subtractive hybridization (SSH). The cDNA of floral buds and leaves at the seedling stage were used as a tester and a driver, respectively. To further identify the function of putative MADS-box transcription factors, phylogenetic trees were reconstructed in order to infer evolutionary relationships within the MADS-box gene family. In the forward-subtracted floral cDNA library, 1920 clones were randomly sequenced, from which 567 unique expressed sequence tags (ESTs) were obtained. Among them, 127 genes failed to show significant similarity to any published sequences in GenBank and thus are putatively novel genes. Phylogenetic analysis indicated that a total of 29 MADS-box transcription factors were members of the APETALA3(AP3) subfamily, while nine others were putative MADS-box transcription factors that formed a cluster with MADS-box genes isolated from Amborella, the basal-most angiosperm, and those from the gymnosperms. This suggests that the origin of A. caudigerum is intermediate between the angiosperms and gymnosperms.

[Perinatal health and medical administrative data: What uses, which stakeholders, what the issues for birth data? - Special REDSIAM].

PubMed

Serfaty, A; Baron, S; Crenn-Hebert, C; Barry, Y; Tala, S

2017-10-01

The uses of medical administrative data (MAD/BDMA) emerged in perinatal health following the work on regionalization of very pre-term birth. They have become more numerous since the late 2000s. The objective of this article is to take stock of the existing work carried out within the REDSIAM-perinatality group, on MAD/BDMA and their uses for the period of "birth". The studied MADs are the Hospital Discharge Data (PMSI) and the French national health database (SNIIRAM). The material includes knowledge shared by the members of the REDSIAM-perinatality group, scientific references and gray literature. Our exploratory study shows that the uses of MAD in perinatal health are diversified at the local, regional and national levels. The works and publications, increasing, take the form of public access of processed data. Collective thinking makes it possible to move from a localized use to an institution, a network or several, to a national use and an inscription in public authorities' responses. In 2015/2016, two institutional sites provide access to data on maternal and child health: Data.Drees and ATIH ScanSanté. MAD/BDMA uses are multiple: epidemiological use (count of births by gestational age, weight in particular; perinatal indicators), quality of care, planning (maternity activities, regionalization of care). There is an increasing interest among stakeholders, producers and/or operators of MAD/BDMA (decision-makers, professionals or researchers). The BDMA, including the PMSI and the SNIIRAM, are used and relevant in Perinatal health with the rise of health networks, the territorialisation of health, in an increased demand for quality of care. Their use will increase the reliability of the data collected and an inscription in the validation studies, more and more numerous in the field of BDMA. The algorithms need to be more finely compiled, validated and enhanced. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Re-evaluation of a novel approach for quantitative myocardial oedema detection by analysing tissue inhomogeneity in acute myocarditis using T2-mapping.

PubMed

Baeßler, Bettina; Schaarschmidt, Frank; Treutlein, Melanie; Stehning, Christian; Schnackenburg, Bernhard; Michels, Guido; Maintz, David; Bunck, Alexander C

2017-12-01

To re-evaluate a recently suggested approach of quantifying myocardial oedema and increased tissue inhomogeneity in myocarditis by T2-mapping. Cardiac magnetic resonance data of 99 patients with myocarditis were retrospectively analysed. Thirthy healthy volunteers served as controls. T2-mapping data were acquired at 1.5 T using a gradient-spin-echo T2-mapping sequence. T2-maps were segmented according to the 16-segments AHA-model. Segmental T2-values, segmental pixel-standard deviation (SD) and the derived parameters maxT2, maxSD and madSD were analysed and compared to the established Lake Louise criteria (LLC). A re-estimation of logistic regression models revealed that all models containing an SD-parameter were superior to any model containing global myocardial T2. Using a combined cut-off of 1.8 ms for madSD + 68 ms for maxT2 resulted in a diagnostic sensitivity of 75% and specificity of 80% and showed a similar diagnostic performance compared to LLC in receiver-operating-curve analyses. Combining madSD, maxT2 and late gadolinium enhancement (LGE) in a model resulted in a superior diagnostic performance compared to LLC (sensitivity 93%, specificity 83%). The results show that the novel T2-mapping-derived parameters exhibit an additional diagnostic value over LGE with the inherent potential to overcome the current limitations of T2-mapping. • A novel quantitative approach to myocardial oedema imaging in myocarditis was re-evaluated. • The T2-mapping-derived parameters maxT2 and madSD were compared to traditional Lake-Louise criteria. • Using maxT2 and madSD with dedicated cut-offs performs similarly to Lake-Louise criteria. • Adding maxT2 and madSD to LGE results in further increased diagnostic performance. • This novel approach has the potential to overcome the limitations of T2-mapping.

Genetic Enhancer Analysis Reveals that FLORAL ORGAN NUMBER2 and OsMADS3 Co-operatively Regulate Maintenance and Determinacy of the Flower Meristem in Rice.

PubMed

Yasui, Yukiko; Tanaka, Wakana; Sakamoto, Tomoaki; Kurata, Tetsuya; Hirano, Hiro-Yuki

2017-05-01

Meristems such as the shoot apical meristem and flower meristem (FM) act as a reservoir of stem cells, which reproduce themselves and supply daughter cells for the differentiation of lateral organs. In Oryza sativa (rice), the FLORAL ORGAN NUMBER2 (FON2) gene, which is similar to Arabidopsis CLAVATA3, is involved in meristem maintenance. In fon2 mutants, the numbers of floral organs are increased due to an enlargement of the FM. To identify new factors regulating meristem maintenance in rice, we performed a genetic screening of mutants that enhanced the fon2 mutation, and found a mutant line (2B-424) in which pistil number was dramatically increased. By using a map-based approach and next-generation sequencing, we found that the line 2B-424 had a complete loss-of-function mutation (a large deletion) in OsMADS3, a class C MADS-box gene that is known to be involved in stamen specification. Disruption of OsMADS3 in the fon2 mutant by CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9) technology caused a flower phenotype similar to that of 2B-424, confirming that the gene responsible for enhancement of fon2 was OsMADS3. Morphological analysis showed that the fon2 and osmads3 mutations synergistically affected pistil development and FM determinacy. We also found that whorl 3 was duplicated in mature flowers and the FM was enlarged at an early developmental stage in severe osmads3 single mutants. These findings suggest that OsMADS3 is involved not only in FM determinacy in late flower development but also in FM activity in early flower development. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast.

PubMed

Chmielewska, Aldona Ewa; Tang, Ngang Heok; Toda, Takashi

2016-01-01

The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80-AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1.

The hairpin region of Ndc80 is important for the kinetochore recruitment of Mph1/MPS1 in fission yeast

PubMed Central

Chmielewska, Aldona Ewa; Tang, Ngang Heok; Toda, Takashi

2016-01-01

ABSTRACT The establishment of proper kinetochore-microtubule attachments facilitates faithful chromosome segregation. Incorrect attachments activate the spindle assembly checkpoint (SAC), which blocks anaphase onset via recruitment of a cohort of SAC components (Mph1/MPS1, Mad1, Mad2, Mad3/BubR1, Bub1 and Bub3) to kinetochores. KNL1, a component of the outer kinetochore KMN network (KNL1/Mis12 complex/Ndc80 complex), acts as a platform for Bub1 and Bub3 localization upon its phosphorylation by Mph1/MPS1. The Ndc80 protein, a major microtubule-binding site, is critical for MPS1 localization to the kinetochores in mammalian cells. Here we characterized the newly isolated mutant ndc80-AK01 in fission yeast, which contains a single point mutation within the hairpin region. This hairpin connects the preceding calponin-homology domain with the coiled-coil region. ndc80-AK01 was hypersensitive to microtubule depolymerizing reagents with no apparent growth defects without drugs. Subsequent analyses indicated that ndc80-AK01 is defective in SAC signaling, as mutant cells proceeded into lethal cell division in the absence of microtubules. Under mitotic arrest conditions, all SAC components (Ark1/Aurora B, Mph1, Bub1, Bub3, Mad3, Mad2 and Mad1) did not localize to the kinetochore. Further genetic analyses indicated that the Ndc80 hairpin region might act as a platform for the kinetochore recruitment of Mph1, which is one of the most upstream SAC components in the hierarchy. Intriguingly, artificial tethering of Mph1 to the kinetochore fully restored checkpoint signaling in ndc80-AK01 cells, further substantiating the notion that Ndc80 is a kinetochore platform for Mph1. The hairpin region of Ndc80, therefore, plays a critical role in kinetochore recruitment of Mph1. PMID:26900649

America's Descent into Madness

ERIC Educational Resources Information Center

Giroux, Henry A.

2014-01-01

This article describes America's descent into madness under the regime of neoliberalism that has emerged in the United States since the late 1970s. In part, this is due to the emergence of a public pedagogy produced by the corporate-owned media that now saturates Americans with a market-driven value system that undermines those formative…

Multi Media Madness--Improving Professional Development for Instructional Technology

ERIC Educational Resources Information Center

Thibeault, Nancy

2004-01-01

Multi Media Madness (3Ms) was a faculty development program where participants were guided by mentors through the development of a multimedia project. Nine faculty participants attended a week long workshop session in June 2003 taught by three mentors. At the end of the workshop series, the participants submitted a project plan that was reviewed,…

Mania and Knowledge. From the Sting of the Gods to Socrates as Educational Gadfly

ERIC Educational Resources Information Center

Erler, Michael

2018-01-01

In Plato's "Phaedrus," Socrates asserts that madness is a good thing if it comes from the gods, and demonstrates this using the example of love. Eroticism becomes thereby philosophy, the lover a philosopher, with Plato's Socrates serving as prototype. The question remains, however, how madness can be reconciled with a philosophical…

Unwinding Madness: What Went Wrong with College Sports--and How to Fix It

ERIC Educational Resources Information Center

Gurney, Gerald; Lopiano, Donna A.; Zimbalist, Andrew

2017-01-01

"Unwinding Madness" is the most comprehensive examination to date of how the NCAA has lost its way in the governance of intercollegiate athletics--and why it is incapable of achieving reform and must be replaced. The NCAA has placed commercial success above its responsibilities to protect the academic primacy, health and well-being of…

Banana MaMADS transcription factors are necessary for fruit ripening and molecular tools to promote shelf-life and food security

USDA-ARS?s Scientific Manuscript database

Genetic solutions to postharvest crop loss can reduce cost and energy inputs while increasing food security, especially for banana (Musa acuminata), which is a significant component of worldwide food commerce. We have functionally characterized two banana E class (SEPALLATA3 [SEP3]) MADS box genes, ...

The Sad, the Mad and the Bad: Co-Existing Discourses of Girlhood

ERIC Educational Resources Information Center

Brown, Marion

2011-01-01

Three significant, prevailing and overlapping narratives of teenage girls have dominated North American popular consciousness since the early 1990s: the sad girl, victimized by male privilege and misogyny of adolescence and beyond; the mad grrrls who rejected this vulnerability through music and media; and the bad girls of much current popular…

Cassandra in the Classroom: Teaching and Moral Madness

ERIC Educational Resources Information Center

Santoro, Doris A.

2017-01-01

Moral madness is a symptom of the moral violence experienced by teachers who are expected to exercise responsibility for their students and their work, but whose moral voice is misrecognized as self-interest and whose moral agency is suppressed. I conduct a feminist ethical analysis of the figure of Cassandra to examine the ways in which teachers…

"Why Will You Say That I Am Mad?" Using Poe's "Tell-Tale Heart" as a Composition Model.

ERIC Educational Resources Information Center

Bates, Laura Raidonis

1998-01-01

Describes an exercise for basic writers which encompasses reading, listening, and writing. Finds that Edgar Allan Poe's "Tell-Tale Heart" has an effective vocabulary, a first-person conversational tone for the "mad" voice, and a second-person direct address that makes it easy to follow. Notes that inexperienced readers can…

DISC BRAKE SYSTEM (CENTER), INCLUDING BELT DRIVE TO SECONDARY GENERAL ...

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

DISC BRAKE SYSTEM (CENTER), INCLUDING BELT DRIVE TO SECONDARY GENERAL MOTORS ENGINE (LEFT)AND FERREL REDUCTION GEAR CONNECTION TO ALLIS-CHALMERS DIESEL ENGINE (RIGHT), LOOKING NORTH. NOTE TORQUE CONVERTER (TOP) AND THROTTLE (BELOW) LINES CONNECTING TO PRIMARY ENGINE. - Mad River Glen, Single Chair Ski Lift, 62 Mad River Glen Resort Road, Fayston, Washington County, VT

76 FR 52263 - Special Local Regulation for Marine Events; Mattaponi Madness Drag Boat Race, Mattaponi River...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-22

...-AA08 Special Local Regulation for Marine Events; Mattaponi Madness Drag Boat Race, Mattaponi River... power boat races to be held on the waters of the Mattaponi River, near Wakema, Virginia. These special.... This action is intended to restrict vessel traffic during the drag boat races on the Mattaponi River...

Music, madness and the body: symptom and cure.

PubMed

MacKinnon, Dolly

2006-03-01

Building on Sander L. Gilman's exemplary work on images of madness and the body, this article examines images of music, madness and the body by discussing the persistent cultural beliefs stemming from Classical Antiquity that underpin music as medicinal. These images reflect the body engaged in therapeutic musical activities, as well as musical sounds forming part of the evidence of the mental diagnostic state of a patient in case records. The historiography of music as medicinal has been overlooked in the history of psychiatry. This article provides a brief background to the cultural beliefs that underlie examples of music as both symptom and cure in 19th- and 20th-century asylum records in Australia, Britain, Europe and North America.

Pharmacology and psychiatry at the origins of Greek medicine: The myth of Melampus and the madness of the Proetides.

PubMed

Olivieri, Matteo F; Marzari, Francesca; Kesel, Andreas J; Bonalume, Laura; Saettini, Francesco

2017-01-01

Melampus is a seer-healer of Greek myth attributed with having healed the young princesses of Argos of madness. Analysis of this legend and its sources sheds light on the early stages of the "medicalizing" shift in the history of ancient Greek medicine. Retrospective psychological diagnosis suggests that the descriptions of the youths' madness rose from actual observation of behavioral and mental disorders. Melampus is credited with having healed them by administering hellebore. Pharmacological analysis of botanical specimens proves that Helleborus niger features actual neurological properties effective in the treatment of mental disorders. The discussion aims at examining the rational aspects of the treatment of mental conditions in Greco-Roman antiquity.

Approximate median regression for complex survey data with skewed response.

PubMed

Fraser, Raphael André; Lipsitz, Stuart R; Sinha, Debajyoti; Fitzmaurice, Garrett M; Pan, Yi

2016-12-01

The ready availability of public-use data from various large national complex surveys has immense potential for the assessment of population characteristics using regression models. Complex surveys can be used to identify risk factors for important diseases such as cancer. Existing statistical methods based on estimating equations and/or utilizing resampling methods are often not valid with survey data due to complex survey design features. That is, stratification, multistage sampling, and weighting. In this article, we accommodate these design features in the analysis of highly skewed response variables arising from large complex surveys. Specifically, we propose a double-transform-both-sides (DTBS)'based estimating equations approach to estimate the median regression parameters of the highly skewed response; the DTBS approach applies the same Box-Cox type transformation twice to both the outcome and regression function. The usual sandwich variance estimate can be used in our approach, whereas a resampling approach would be needed for a pseudo-likelihood based on minimizing absolute deviations (MAD). Furthermore, the approach is relatively robust to the true underlying distribution, and has much smaller mean square error than a MAD approach. The method is motivated by an analysis of laboratory data on urinary iodine (UI) concentration from the National Health and Nutrition Examination Survey. © 2016, The International Biometric Society.

Approximate Median Regression for Complex Survey Data with Skewed Response

PubMed Central

Fraser, Raphael André; Lipsitz, Stuart R.; Sinha, Debajyoti; Fitzmaurice, Garrett M.; Pan, Yi

2016-01-01

Summary The ready availability of public-use data from various large national complex surveys has immense potential for the assessment of population characteristics using regression models. Complex surveys can be used to identify risk factors for important diseases such as cancer. Existing statistical methods based on estimating equations and/or utilizing resampling methods are often not valid with survey data due to complex survey design features. That is, stratification, multistage sampling and weighting. In this paper, we accommodate these design features in the analysis of highly skewed response variables arising from large complex surveys. Specifically, we propose a double-transform-both-sides (DTBS) based estimating equations approach to estimate the median regression parameters of the highly skewed response; the DTBS approach applies the same Box-Cox type transformation twice to both the outcome and regression function. The usual sandwich variance estimate can be used in our approach, whereas a resampling approach would be needed for a pseudo-likelihood based on minimizing absolute deviations (MAD). Furthermore, the approach is relatively robust to the true underlying distribution, and has much smaller mean square error than a MAD approach. The method is motivated by an analysis of laboratory data on urinary iodine (UI) concentration from the National Health and Nutrition Examination Survey. PMID:27062562

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population

PubMed Central

Brain, Keith L.; Kay, Jonathan; Shine, Brian

2009-01-01

Background Despite the rarity of pheochromocytoma, the dangers of uncontrolled severe hypertension and the very effective surgical treatment of this condition mean that diagnosis is important. Urinary or plasma catecholamines or catecholamine-derivatives are commonly used to screen for pheochromocytomas prior to imaging. This study investigates whether derived measures obtained from 24-hour urinary metanephrine results, patient age and sex can better predict tumors in populations with a low pre-test probability. Methods This study takes a pragmatic approach by retrospectively studying the outcomes of an unselected population referred for urinary metanephrine testing (1819 patients) to a tertiary hospital laboratory, and investigates the usefulness of some simple derivative measures for detecting pheochromocytoma. Urinary 24-hour excretion of metanephrine, normetanephrine and 3-methoxytyramine were normalized by dividing by an age- and sex- specific reference range. The ability of products of these normalized measures to predict pheochromocytomas was assessed, compared to a gold standard of biopsy-confirmed tumor. Results The normalized product of urinary metanephrine and normetanephrine excretion (nMAD.nNMT) proved to be a highly sensitive (100%) and specific (99.1%) measure yielding a positive predictive value 82%. Receiver-operator characteristic curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. nMAD.nNMT gave higher sensitivity and specificity than either test alone. Conclusion We suggest that nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pre-test probability. PMID:16990424

Use of multiple correspondence analysis (MCA) to identify interactive meteorological conditions affecting relative throughfall

NASA Astrophysics Data System (ADS)

Van Stan, John T.; Gay, Trent E.; Lewis, Elliott S.

2016-02-01

Forest canopies alter rainfall reaching the surface by redistributing it as throughfall. Throughfall supplies water and nutrients to a variety of ecohydrological components (soil microbial communities, stream water discharge/chemistry, and stormflow pathways) and is controlled by canopy structural interactions with meteorological conditions across temporal scales. This work introduces and applies multiple correspondence analyses (MCAs) to a range of meteorological thresholds (median intensity, median absolute deviation (MAD) of intensity, median wind-driven droplet inclination angle, and MAD of wind speed) for an example throughfall problem: identification of interacting storm conditions corresponding to temporal concentration in relative throughfall beyond the median observation (⩾73% of rain). MCA results from the example show that equalling or exceeding rain intensity thresholds (median and MAD) corresponded with temporal concentration of relative throughfall across all storms. Under these intensity conditions, two wind mechanisms produced significant correspondences: (1) high, steady wind-driven droplet inclination angles increased surface wetting; and (2) sporadic winds shook entrained droplets from surfaces. A discussion is provided showing that these example MCA findings agree well with previous work relying on more historically common methods (e.g., multiple regression and analytical models). Meteorological threshold correspondences to temporal concentration of relative throughfall at our site may be a function of heavy Tillandsia usneoides coverage. Applications of MCA within other forests may provide useful insights to how temporal throughfall dynamics are affected for drainage pathways dependent on different structures (leaves, twigs, branches, etc.).

Large-scale inverse model analyses employing fast randomized data reduction

NASA Astrophysics Data System (ADS)

Lin, Youzuo; Le, Ellen B.; O'Malley, Daniel; Vesselinov, Velimir V.; Bui-Thanh, Tan

2017-08-01

When the number of observations is large, it is computationally challenging to apply classical inverse modeling techniques. We have developed a new computationally efficient technique for solving inverse problems with a large number of observations (e.g., on the order of 107 or greater). Our method, which we call the randomized geostatistical approach (RGA), is built upon the principal component geostatistical approach (PCGA). We employ a data reduction technique combined with the PCGA to improve the computational efficiency and reduce the memory usage. Specifically, we employ a randomized numerical linear algebra technique based on a so-called "sketching" matrix to effectively reduce the dimension of the observations without losing the information content needed for the inverse analysis. In this way, the computational and memory costs for RGA scale with the information content rather than the size of the calibration data. Our algorithm is coded in Julia and implemented in the MADS open-source high-performance computational framework (http://mads.lanl.gov). We apply our new inverse modeling method to invert for a synthetic transmissivity field. Compared to a standard geostatistical approach (GA), our method is more efficient when the number of observations is large. Most importantly, our method is capable of solving larger inverse problems than the standard GA and PCGA approaches. Therefore, our new model inversion method is a powerful tool for solving large-scale inverse problems. The method can be applied in any field and is not limited to hydrogeological applications such as the characterization of aquifer heterogeneity.

Preliminary crystallographic analysis of salicylate 1,2-dioxygenase from Pseudaminobacter salicylatoxidans

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

Matera, I.; Ferraroni, M.; Bürger, S.

2006-06-01

Salicylate 1,2-dioxygenase, a new ring-fission dioxygenase from the naphthalenesulfonate-degrading strain P. salicylatoxidans, which oxidizes salicylate to 2-oxohepta-3,5-dienedioic acid by a novel ring-fission mechanism, has been crystallized. The crystals obtained give diffraction data to 2.9 Å resolution which could assist in the elucidation of the catalytic mechanism of this peculiar dioxygenase. Salicylate 1,2-dioxygenase, a new ring-fission dioxygenase from the naphthalenesulfonate-degrading strain Pseudaminobacter salicylatoxidans which oxidizes salicylate to 2-oxohepta-3,5-dienedioic acid by a novel ring-fission mechanism, has been crystallized. Diffraction-quality crystals of salicylate 1,2-dioxygenase were obtained using the sitting-drop vapour-diffusion method at 277 K from a solution containing 10%(w/v) ethanol, 6%(w/v) PEG 400,more » 0.1 M sodium acetate pH 4.6. Crystals belong to the primitive tetragonal space group P4{sub 3}2{sub 1}2 or P4{sub 1}2{sub 1}2, with unit-cell parameters a = 133.3, c = 191.51 Å. A complete data set at 100 K extending to a maximum resolution of 2.9 Å was collected at a wavelength of 0.8423 Å. Molecular replacement using the coordinates of known extradiol dioxygenases structures as a model has so far failed to provide a solution for salicylate 1,2-dioxygenase. Attempts are currently being made to solve the structure of the enzyme by MAD experiments using the anomalous signal of the catalytic Fe{sup II} ions. The salicylate 1,2-dioxygenase structural model will assist in the elucidation of the catalytic mechanism of this ring-fission dioxygenase from P. salicylatoxidans, which differs markedly from the known gentisate 1,2-dioxygenases or 1-hydroxy-2-naphthoate dioxygenases because of its unique ability to oxidatively cleave salicylate, gentisate and 1-hydroxy-2-naphthoate with high catalytic efficiency.« less

A computationally efficient parallel Levenberg-Marquardt algorithm for highly parameterized inverse model analyses

NASA Astrophysics Data System (ADS)

Lin, Youzuo; O'Malley, Daniel; Vesselinov, Velimir V.

2016-09-01

Inverse modeling seeks model parameters given a set of observations. However, for practical problems because the number of measurements is often large and the model parameters are also numerous, conventional methods for inverse modeling can be computationally expensive. We have developed a new, computationally efficient parallel Levenberg-Marquardt method for solving inverse modeling problems with a highly parameterized model space. Levenberg-Marquardt methods require the solution of a linear system of equations which can be prohibitively expensive to compute for moderate to large-scale problems. Our novel method projects the original linear problem down to a Krylov subspace such that the dimensionality of the problem can be significantly reduced. Furthermore, we store the Krylov subspace computed when using the first damping parameter and recycle the subspace for the subsequent damping parameters. The efficiency of our new inverse modeling algorithm is significantly improved using these computational techniques. We apply this new inverse modeling method to invert for random transmissivity fields in 2-D and a random hydraulic conductivity field in 3-D. Our algorithm is fast enough to solve for the distributed model parameters (transmissivity) in the model domain. The algorithm is coded in Julia and implemented in the MADS computational framework (http://mads.lanl.gov). By comparing with Levenberg-Marquardt methods using standard linear inversion techniques such as QR or SVD methods, our Levenberg-Marquardt method yields a speed-up ratio on the order of ˜101 to ˜102 in a multicore computational environment. Therefore, our new inverse modeling method is a powerful tool for characterizing subsurface heterogeneity for moderate to large-scale problems.

Crystallization and preliminary crystallographic analysis of the transpeptidase domain of penicillin-binding protein 2B from Streptococcus pneumoniae

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

Yamada, Mototsugu, E-mail: mototsugu-yamada@meiji.co.jp; Watanabe, Takashi; Baba, Nobuyoshi

The selenomethionyl-substituted transpeptidase domain of penicillin-binding protein (PBP) 2B from S. pneumoniae was isolated from a limited proteolysis digest of the soluble form of recombinant PBP 2B and then crystallized. MAD data were collected to 2.4 Å resolution. Penicillin-binding protein (PBP) 2B from Streptococcus pneumoniae catalyzes the cross-linking of peptidoglycan precursors that occurs during bacterial cell-wall biosynthesis. A selenomethionyl (SeMet) substituted PBP 2B transpeptidase domain was isolated from a limited proteolysis digest of a soluble form of recombinant PBP 2B and then crystallized. The crystals belonged to space group P4{sub 3}2{sub 1}2, with unit-cell parameters a = b = 86.39,more » c = 143.27 Å. Diffraction data were collected to 2.4 Å resolution using the BL32B2 beamline at SPring-8. The asymmetric unit contains one protein molecule and 63.7% solvent.« less

Spatial pattern analysis of Cu, Zn and Ni and their interpretation in the Campania region (Italy)

NASA Astrophysics Data System (ADS)

Petrik, Attila; Albanese, Stefano; Jordan, Gyozo; Rolandi, Roberto; De Vivo, Benedetto

2017-04-01

The uniquely abundant Campanian topsoil dataset enabled us to perform a spatial pattern analysis on 3 potentially toxic elements of Cu, Zn and Ni. This study is focusing on revealing the spatial texture and distribution of these elements by spatial point pattern and image processing analysis such as lineament density and spatial variability index calculation. The application of these methods on geochemical data provides a new and efficient tool to understand the spatial variation of concentrations and their background/baseline values. The determination and quantification of spatial variability is crucial to understand how fast the change in concentration is in a certain area and what processes might govern the variation. The spatial variability index calculation and image processing analysis including lineament density enables us to delineate homogenous areas and analyse them with respect to lithology and land use. Identification of spatial outliers and their patterns were also investigated by local spatial autocorrelation and image processing analysis including the determination of local minima and maxima points and singularity index analysis. The spatial variability of Cu and Zn reveals the highest zone (Cu: 0.5 MAD, Zn: 0.8-0.9 MAD, Median Deviation Index) along the coast between Campi Flegrei and the Sorrento Peninsula with the vast majority of statistically identified outliers and high-high spatial clustered points. The background/baseline maps of Cu and Zn reveals a moderate to high variability (Cu: 0.3 MAD, Zn: 0.4-0.5 MAD) NW-SE oriented zone including disrupted patches from Bisaccia to Mignano following the alluvial plains of Appenine's rivers. This zone has high abundance of anomaly concentrations identified using singularity analysis and it also has a high density of lineaments. The spatial variability of Ni shows the highest variability zone (0.6-0.7 MAD) around Campi Flegrei where the majority of low outliers are concentrated. The variability of background/baseline map of Ni reveals a shift to the east in case of highest variability zones coinciding with limestone outcrops. The high segmented area between Mignano and Bisaccia partially follows the alluvial plains of Appenine's rivers which seem to be playing a crucial role in the distribution and redistribution pattern of Cu, Zn and Ni in Campania. The high spatial variability zones of the later elements are located in topsoils on volcanoclastic rocks and are mostly related to cultivation and urbanised areas.

A hitchhiker's guide to the MADS world of plants.

PubMed

Gramzow, Lydia; Theissen, Guenter

2010-01-01

Plant life critically depends on the function of MADS-box genes encoding MADS-domain transcription factors, which are present to a limited extent in nearly all major eukaryotic groups, but constitute a large gene family in land plants. There are two types of MADS-box genes, termed type I and type II, and in plants these groups are distinguished by exon-intron and domain structure, rates of evolution, developmental function and degree of functional redundancy. The type I genes are further subdivided into three groups - M alpha, M beta and M gamma - while the type II genes are subdivided into the MIKCC and MIKC* groups. The functional diversification of MIKCC genes is closely linked to the origin of developmental and morphological novelties in the sporophytic (usually diploid) generation of seed plants, most spectacularly the floral organs and fruits of angiosperms. Functional studies suggest different specializations for the different classes of genes; whereas type I genes may preferentially contribute to female gametophyte, embryo and seed development and MIKC*-group genes to male gametophyte development, the MIKCC-group genes became essential for diverse aspects of sporophyte development. Beyond the usual transcriptional regulation, including feedback and feed-forward loops, various specialized mechanisms have evolved to control the expression of MADS-box genes, such as epigenetic control and regulation by small RNAs. In future, more data from genome projects and reverse genetic studies will allow us to understand the birth, functional diversification and death of members of this dynamic and important family of transcription factors in much more detail.

A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex

PubMed Central

Horvath, Anelia; Giatzakis, Christoforos; Tsang, Kitman; Greene, Elizabeth; Osorio, Paulo; Boikos, Sosipatros; Libè, Rossella; Patronas, Yianna; Robinson-White, Audrey; Remmers, Elaine; Bertherat, Jerôme; Nesterova, Maria; Stratakis, Constantine A.

2009-01-01

Bilateral adrenocortical hyperplasia (BAH) is the second most common cause of corticotropin-independent Cushing syndrome (CS). Genetic forms of BAH have been associated with complex syndromes such as Carney Complex and McCune Albright syndrome or may present as isolated micronodular adrenocortical disease (iMAD) usually in children and young adults with CS. A genome-wide association study identified inactivating phosphodiesterase (PDE) 11A (PDE11A) sequencing defects as low-penetrance predisposing factors for iMAD and related abnormalities; we also described a mutation (c.914A>C/H305P) in cAMP-specific PDE8B, in a patient with iMAD. In this study we further characterize this mutation; we also found a novel PDE8B isoform, highly expressed in the adrenal gland. This mutation is shown to significantly affect the ability of the protein to degrade cAMP in vitro. Tumor tissues from patients with iMAD and no mutations in the coding PDE8B sequence or any other related genes (PRKAR1A, PDE11A) showed down-regulated PDE8B expression (compared to normal adrenal cortex). Pde8b is detectable in the adrenal gland of newborn mice and is widely expressed in other mouse tissues. We conclude that PDE8B is another PDE gene linked to iMAD; it is a candidate causative gene for other adrenocortical lesions linked to the cAMP-signaling pathway, and possibly for tumors in other tissues. PMID:18431404

Disruption of Axonal Transport Perturbs Bone Morphogenetic Protein (BMP) - Signaling and Contributes to Synaptic Abnormalities in Two Neurodegenerative Diseases

PubMed Central

Kang, Min Jung; Hansen, Timothy J.; Mickiewicz, Monique; Kaczynski, Tadeusz J.; Fye, Samantha; Gunawardena, Shermali

2014-01-01

Formation of new synapses or maintenance of existing synapses requires the delivery of synaptic components from the soma to the nerve termini via axonal transport. One pathway that is important in synapse formation, maintenance and function of the Drosophila neuromuscular junction (NMJ) is the bone morphogenetic protein (BMP)-signaling pathway. Here we show that perturbations in axonal transport directly disrupt BMP signaling, as measured by its downstream signal, phospho Mad (p-Mad). We found that components of the BMP pathway genetically interact with both kinesin-1 and dynein motor proteins. Thick vein (TKV) vesicle motility was also perturbed by reductions in kinesin-1 or dynein motors. Interestingly, dynein mutations severely disrupted p-Mad signaling while kinesin-1 mutants showed a mild reduction in p-Mad signal intensity. Similar to mutants in components of the BMP pathway, both kinesin-1 and dynein motor protein mutants also showed synaptic morphological defects. Strikingly TKV motility and p-Mad signaling were disrupted in larvae expressing two human disease proteins; expansions of glutamine repeats (polyQ77) and human amyloid precursor protein (APP) with a familial Alzheimer's disease (AD) mutation (APPswe). Consistent with axonal transport defects, larvae expressing these disease proteins showed accumulations of synaptic proteins along axons and synaptic abnormalities. Taken together our results suggest that similar to the NGF-TrkA signaling endosome, a BMP signaling endosome that directly interacts with molecular motors likely exist. Thus problems in axonal transport occurs early, perturbs BMP signaling, and likely contributes to the synaptic abnormalities observed in these two diseases. PMID:25127478

A mathematical model of extremely low frequency ocean induced electromagnetic noise

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

Dautta, Manik, E-mail: manik.dautta@anyeshan.com; Faruque, Rumana Binte, E-mail: rumana.faruque@anyeshan.com; Islam, Rakibul, E-mail: rakibul.islam@anyeshan.com

2016-07-12

Magnetic Anomaly Detection (MAD) system uses the principle that ferromagnetic objects disturb the magnetic lines of force of the earth. These lines of force are able to pass through both water and air in similar manners. A MAD system, usually mounted on an aerial vehicle, is thus often employed to confirm the detection and accomplish localization of large ferromagnetic objects submerged in a sea-water environment. However, the total magnetic signal encountered by a MAD system includes contributions from a myriad of low to Extremely Low Frequency (ELF) sources. The goal of the MAD system is to detect small anomaly signalsmore » in the midst of these low-frequency interfering signals. Both the Range of Detection (R{sub d}) and the Probability of Detection (P{sub d}) are limited by the ratio of anomaly signal strength to the interfering magnetic noise. In this paper, we report a generic mathematical model to estimate the signal-to-noise ratio or SNR. Since time-variant electro-magnetic signals are affected by conduction losses due to sea-water conductivity and the presence of air-water interface, we employ the general formulation of dipole induced electromagnetic field propagation in stratified media [1]. As a first step we employ a volumetric distribution of isolated elementary magnetic dipoles, each having its own dipole strength and orientation, to estimate the magnetic noise observed by a MAD system. Numerical results are presented for a few realizations out of an ensemble of possible realizations of elementary dipole source distributions.« less

Chemical genetic profiling of the microtubule-targeting agent peloruside A in budding yeast Saccharomyces cerevisiae.

PubMed

Wilmes, Anja; Hanna, Reem; Heathcott, Rosemary W; Northcote, Peter T; Atkinson, Paul H; Bellows, David S; Miller, John H

2012-04-15

Peloruside A, a microtubule-stabilising agent from a New Zealand marine sponge, inhibits mammalian cell division by a similar mechanism to that of the anticancer drug paclitaxel. Wild type budding yeast Saccharomyces cerevisiae (haploid strain BY4741) showed growth sensitivity to peloruside A with an IC(50) of 35μM. Sensitivity was increased in a mad2Δ (Mitotic Arrest Deficient 2) deletion mutant (IC(50)=19μM). Mad2 is a component of the spindle-assembly checkpoint complex that delays the onset of anaphase in cells with defects in mitotic spindle assembly. Haploid mad2Δ cells were much less sensitive to paclitaxel than to peloruside A, possibly because the peloruside binding site on yeast tubulin is more similar to mammalian tubulin than the taxoid site where paclitaxel binds. In order to obtain information on the primary and secondary targets of peloruside A in yeast, a microarray analysis of yeast heterozygous and homozygous deletion mutant sets was carried out. Haploinsufficiency profiling (HIP) failed to provide hits that could be validated, but homozygous profiling (HOP) generated twelve validated genes that interact with peloruside A in cells. Five of these were particularly significant: RTS1, SAC1, MAD1, MAD2, and LSM1. In addition to its known target tubulin, based on these microarray 'hits', peloruside A was seen to interact genetically with other cell proteins involved in the cell cycle, mitosis, RNA splicing, and membrane trafficking. Copyright © 2012 Elsevier B.V. All rights reserved.

The Case Survey and Alternative Methods for Research Aggregation

DTIC Science & Technology

1974-06-01

of FolLow-Through programs were found to predollinate Jin one set of pooled data with common statistical characteristics, aod studies of Montessori ...be mad compatible. l"’we" and other mundane d if f icu ties have a t renendous ca ac i tv to ctonsurW ’ i M- and energy. Montessori ), or they could be

[The madness of Herakles in Euripides and Sophocles].

PubMed

Charlier, Philippe

2003-01-01

In the ancient Greek world madness was conceived as a punishment sent by the gods to men found guilty of various sins. Heralkes, who kills his wife Megara and their sons, is the best example of Greek literature offers of the tragic consequences of mental disease. The article conducts a medical observation of Sophocles' and Euripides' descriptions of Herakles' insanity.

Overexpression of the class D MADS-box gene Sl-AGL11 impacts fleshy tissue differentiation and structure in tomato fruits

USDA-ARS?s Scientific Manuscript database

MADS-box transcription factors are key elements of the genetic networks controlling flower and fruit development. Among these, the class D clade are involved in seed, ovule, and funiculus development. The tomato genome comprises two class D genes, Sl-AGL11 and Sl-MBP3, both displaying high expressio...

It's a Mad, Mad Wordle: For a New Take on Text, Try This Fun Word Cloud Generator

ERIC Educational Resources Information Center

Foote, Carolyn

2009-01-01

Nation. New. Common. Generation. These are among the most frequently used words spoken by President Barack Obama in his January 2009 inauguration speech as seen in a fascinating visual display called a Wordle. Educators, too, can harness the power of Wordle to enhance learning. Imagine providing students with a whole new perspective on…

Bearded-Ear Encodes a MADS-box Transcription Factor Critical for Maize Floral Development

USDA-ARS?s Scientific Manuscript database

We cloned bde by positional cloning and found that it encodes zag3, a MADS-box transcription factor in the conserved AGL6 clade. Mutants in the maize homolog of AGAMOUS, zag1, have a subset of bde floral defects. bde; zag1 double mutants have a severe ear phenotype, not observed in either single m...

A Study of Displacement in Jean Rhys' Novel "Wide Sargasso Sea"

ERIC Educational Resources Information Center

Jamal, Inna Malissa bte Che; Singh, Hardev Kaur A/P Jujar; Mani, Manimangai

2014-01-01

"Wide Sargasso Sea," by Jean Rhys, is a novel filled with tragedy; two characters in conflict meet in circumstances not in their best interests but rather for other people. This novel is an illustration of the mad woman in the novel "Jane Eyre," by Charlotte Bronte, as the story of her life before madness is told in the novel…

March Money Madness: The Coaches vs. the Professors

ERIC Educational Resources Information Center

Cottle, Thomas

2009-01-01

College basketball's March Madness has come at a time when one prominent coach's salary has been held up for inspection. Apparently, the fact that the $1.6-million annual income of the University of Connecticut's Jim Calhoun makes him the highest-paid public employee in his state has rankled some people. Or are they more upset that he was caught…

The Phycomyces madA gene encodes a blue-light photoreceptor for phototropism and other light responses.

PubMed

Idnurm, Alexander; Rodríguez-Romero, Julio; Corrochano, Luis M; Sanz, Catalina; Iturriaga, Enrique A; Eslava, Arturo P; Heitman, Joseph

2006-03-21

Phycomyces blakesleeanus is a filamentous zygomycete fungus that produces striking elongated single cells that extend up to 10 cm into the air, with each such sporangiophore supporting a sphere containing the spores for dispersal. This organism has served as a model for the detection of environmental signals as diverse as light, chemicals, touch, wind, gravity, and adjacent objects. In particular, sporangiophore growth is regulated by light, and it exhibits phototropism by bending toward near-UV and blue wavelengths and away from far-UV wavelengths in a manner that is physiologically similar to plant phototropic responses. The Phycomyces madA mutants were first isolated more than 40 years ago, and they exhibit reduced sensitivity to light. Here, we identify two (duplicated) homologs in the White Collar 1 family of blue-light photoreceptors in Phycomyces. We describe that the madA mutant strains contain point mutations in one of these genes and that these mutations cosegregate with a defect in phototropism after genetic crosses. Thus, the phototropic responses of fungi through madA and plants through phototropin rely on diverse proteins; however, these proteins share a conserved flavin-binding domain for photon detection.

The Phycomyces madA gene encodes a blue-light photoreceptor for phototropism and other light responses

PubMed Central

Idnurm, Alexander; Rodríguez-Romero, Julio; Corrochano, Luis M.; Sanz, Catalina; Iturriaga, Enrique A.; Eslava, Arturo P.; Heitman, Joseph

2006-01-01

Phycomyces blakesleeanus is a filamentous zygomycete fungus that produces striking elongated single cells that extend up to 10 cm into the air, with each such sporangiophore supporting a sphere containing the spores for dispersal. This organism has served as a model for the detection of environmental signals as diverse as light, chemicals, touch, wind, gravity, and adjacent objects. In particular, sporangiophore growth is regulated by light, and it exhibits phototropism by bending toward near-UV and blue wavelengths and away from far-UV wavelengths in a manner that is physiologically similar to plant phototropic responses. The Phycomyces madA mutants were first isolated more than 40 years ago, and they exhibit reduced sensitivity to light. Here, we identify two (duplicated) homologs in the White Collar 1 family of blue-light photoreceptors in Phycomyces. We describe that the madA mutant strains contain point mutations in one of these genes and that these mutations cosegregate with a defect in phototropism after genetic crosses. Thus, the phototropic responses of fungi through madA and plants through phototropin rely on diverse proteins; however, these proteins share a conserved flavin-binding domain for photon detection. PMID:16537433

Experimental evaluation of dual multiple aperture devices for fluence field modulated x-ray computed tomography

NASA Astrophysics Data System (ADS)

Mathews, A. J.; Gang, G.; Levinson, R.; Zbijewski, W.; Kawamoto, S.; Siewerdsen, J. H.; Stayman, J. W.

2017-03-01

Acquisition of CT images with comparable diagnostic power can potentially be achieved with lower radiation exposure than the current standard of care through the adoption of hardware-based fluence-field modulation (e.g. dynamic bowtie filters). While modern CT scanners employ elements such as static bowtie filters and tube-current modulation, such solutions are limited in the fluence patterns that they can achieve, and thus are limited in their ability to adapt to broad classes of patient morphology. Fluence-field modulation also enables new applications such as region-of-interest imaging, task specific imaging, reducing measurement noise or improving image quality. The work presented in this paper leverages a novel fluence modulation strategy that uses "Multiple Aperture Devices" (MADs) which are, in essence, binary filters, blocking or passing x-rays on a fine scale. Utilizing two MAD devices in series provides the capability of generating a large number of fluence patterns via small relative motions between the MAD filters. We present the first experimental evaluation of fluence-field modulation using a dual-MAD system, and demonstrate the efficacy of this technique with a characterization of achievable fluence patterns and an investigation of experimental projection data.

On the efficiency of jet production in FR II radio galaxies and quasars

NASA Astrophysics Data System (ADS)

Rusinek, Katarzyna; Sikora, Marek; Kozieł-Wierzbowska, Dorota; Godfrey, Leith

2017-04-01

Jet powers in many radio galaxies with extended radio structures appear to exceed their associated accretion luminosities. In systems with very low accretion rates, this is likely due to the very low accretion luminosities resulting from radiatively inefficient accretion flows. In systems with high accretion rates, the accretion flows are expected to be radiatively efficient, and the production of such powerful jets may require an accretion scenario, which involves magnetically arrested discs (MADs). However, numerical simulations of the MAD scenario indicate that jet production efficiency is large only for geometrically thick accretion flows and scales roughly with (H/R)2, where H is the disc height and R is the distance from the black hole. Using samples of FR II radio galaxies and quasars accreting at moderate accretion rates, we show that their jets are much more powerful than predicted by the MAD scenario. We discuss possible origins of this discrepancy, suggesting that it can be related to approximations adopted in magnetohydrodynamic simulations to treat optically thick accretion flow within the MAD zone, or may indicate that accretion discs are geometrically thicker than the standard theory predicts.

Transient jet formation and state transitions from large-scale magnetic reconnection in black hole accretion discs

NASA Astrophysics Data System (ADS)

Dexter, Jason; McKinney, Jonathan C.; Markoff, Sera; Tchekhovskoy, Alexander

2014-05-01

Magnetically arrested accretion discs (MADs), where the magnetic pressure in the inner disc is dynamically important, provide an alternative mechanism for regulating accretion to what is commonly assumed in black hole systems. We show that a global magnetic field inversion in the MAD state can destroy the jet, significantly increase the accretion rate, and move the effective inner disc edge in to the marginally stable orbit. Reconnection of the MAD field in the inner radii launches a new type of transient outflow containing hot plasma generated by magnetic dissipation. This transient outflow can be as powerful as the steady magnetically dominated Blandford-Znajek jet in the MAD state. The field inversion qualitatively describes many of the observational features associated with the high-luminosity hard-to-soft state transition in black hole X-ray binaries: the jet line, the transient ballistic jet, and the drop in rms variability. These results demonstrate that the magnetic field configuration can influence the accretion state directly, and hence the magnetic field structure is an important second parameter in explaining observations of accreting black holes across the mass and luminosity scales.

Sharpening Up Jupiter

NASA Astrophysics Data System (ADS)

2008-10-01

New image-correction technique delivers sharpest whole-planet ground-based picture ever A record two-hour observation of Jupiter using a superior technique to remove atmospheric blur has produced the sharpest whole-planet picture ever taken from the ground. The series of 265 snapshots obtained with the Multi-Conjugate Adaptive Optics Demonstrator (MAD) prototype instrument mounted on ESO's Very Large Telescope (VLT) reveal changes in Jupiter's smog-like haze, probably in response to a planet-wide upheaval more than a year ago. Sharpening Up Jupiter ESO PR Photo 33/08 Sharpening Up Jupiter Being able to correct wide field images for atmospheric distortions has been the dream of scientists and engineers for decades. The new images of Jupiter prove the value of the advanced technology used by MAD, which uses two or more guide stars instead of one as references to remove the blur caused by atmospheric turbulence over a field of view thirty times larger than existing techniques [1]. "This type of adaptive optics has a big advantage for looking at large objects, such as planets, star clusters or nebulae," says lead researcher Franck Marchis, from UC Berkeley and the SETI Institute in Mountain View, California, USA. "While regular adaptive optics provides excellent correction in a small field of view, MAD provides good correction over a larger area of sky. And in fact, were it not for MAD, we would not have been able to perform these amazing observations." MAD allowed the researchers to observe Jupiter for almost two hours on 16 and 17 August 2008, a record duration, according to the observing team. Conventional adaptive optics systems using a single Jupiter moon as reference cannot monitor Jupiter for so long because the moon moves too far from the planet. The Hubble Space Telescope cannot observe Jupiter continuously for more than about 50 minutes, because its view is regularly blocked by the Earth during Hubble's 96-minute orbit. Using MAD, ESO astronomer Paola Amico, MAD project manager Enrico Marchetti and Sébastien Tordo from the MAD team tracked two of Jupiter's largest moons, Europa and Io - one on each side of the planet - to provide a good correction across the full disc of the planet. "It was the most challenging observation we performed with MAD, because we had to track with high accuracy two moons moving at different speeds, while simultaneously chasing Jupiter," says Marchetti. With this unique series of images, the team found a major alteration in the brightness of the equatorial haze, which lies in a 16 000-kilometre wide belt over Jupiter's equator [2]. More sunlight reflecting off upper atmospheric haze means that the amount of haze has increased, or that it has moved up to higher altitudes. "The brightest portion had shifted south by more than 6000 kilometres," explains team member Mike Wong. This conclusion came after comparison with images taken in 2005 by Wong and colleague Imke de Pater using the Hubble Space Telescope. The Hubble images, taken at infrared wavelengths very close to those used for the VLT study, show more haze in the northern half of the bright Equatorial Zone, while the 2008 VLT images show a clear shift to the south. "The change we see in the haze could be related to big changes in cloud patterns associated with last year's planet-wide upheaval, but we need to look at more data to narrow down precisely when the changes occurred," declares Wong.

Is mad cow disease caused by a bacteria?

PubMed

Broxmeyer, L

2004-01-01

Transmissible spongioform enchephalopathies (TSE's), include bovine spongiform encephalopathy (also called BSE or "mad cow disease"), Creutzfeldt-Jakob disease (CJD) in humans, and scrapie in sheep. They remain a mystery, their cause hotly debated. But between 1994 and 1996, 12 people in England came down with CJD, the human form of mad cow, and all had eaten beef from suspect cows. Current mad cow diagnosis lies solely in the detection of late appearing "prions", an acronym for hypothesized, gene-less, misfolded proteins, somehow claimed to cause the disease. Yet laboratory preparations of prions contain other things, which could include unidentified bacteria or viruses. Furthermore, the rigors of prion purification alone, might, in and of themselves, have killed the causative virus or bacteria. Therefore, even if samples appear to infect animals, it is impossible to prove that prions are causative. Manuelidis found viral-like particles, which even when separated from prions, were responsible for spongiform STE's. Subsequently, Lasmezas's study showed that 55% of mice injected with cattle BSE, and who came down with disease, had no detectable prions. Still, incredibly, prions, are held as existing TSE dogma and Heino Dringer, who did pioneer work on their nature, candidly predicts "it will turn out that the prion concept is wrong." Many animals that die of spongiform TSE's never show evidence of misfolded proteins, and Dr. Frank Bastian, of Tulane, an authority, thinks the disorder is caused by the bacterial DNA he found in this group of diseases. Recently, Roels and Walravens isolated Mycobacterium bovis it from the brain of a cow with the clinical and histopathological signs of mad cow. Moreover, epidemiologic maps of the origins and peak incidence of BSE in the UK, suggestively match those of England's areas of highest bovine tuberculosis, the Southwest, where Britain's mad cow epidemic began. The neurotoxic potential for cow tuberculosis was shown in pre-1960 England, where one quarter of all tuberculous meningitis victims suffered from Mycobacterium bovis infection. And Harley's study showed pathology identical to "mad cow" from systemic M. bovis in cattle, causing a tuberculous spongiform encephalitis. In addition to M. bovis, Mycobacterium avium subspecies paratuberculosis (fowl tuberculosis) causes Johne's disease, a problem known and neglected in cattle and sheep for almost a century, and rapidly emerging as the disease of the new millennium. Not only has M. paratuberculosis been found in human Crohn's disease, but both Crohn's and Johne's both cross-react with the antigens of cattle paratuberculosis. Furthermore, central neurologic manifestations of Crohn's disease are not unknown. There is no known disease which better fits into what is occurring in Mad Cow and the spongiform enchephalopathies than bovine tuberculosis and its blood-brain barrier penetrating, virus-like, cell-wall-deficient forms. It is for these reasons that future research needs to be aimed in this direction. Copyright 2004 Elsevier Ltd.

TU-AB-202-12: A Novel Method to Map Endoscopic Video to CT for Treatment Planning and Toxicity Analysis in Radiation Therapy

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

Ingram, W; Yang, J; Beadle, B

Purpose: Endoscopic examinations are routine procedures for head-and-neck cancer patients. Our goal is to develop a method to map the recorded video to CT, providing valuable information for radiotherapy treatment planning and toxicity analysis. Methods: We map video frames to CT via virtual endoscopic images rendered at the real endoscope’s CT-space coordinates. We developed two complementary methods to find these coordinates by maximizing real-to-virtual image similarity:(1)Endoscope Tracking: moves the virtual endoscope frame-by-frame until the desired frame is reached. Utilizes prior knowledge of endoscope coordinates, but sensitive to local optima. (2)Location Search: moves the virtual endoscope along possible paths through themore » volume to find the desired frame. More robust, but more computationally expensive. We tested these methods on clay phantoms with embedded markers for point mapping and protruding bolus material for contour mapping, and we assessed them qualitatively on three patient exams. For mapped points we calculated 3D-distance errors, and for mapped contours we calculated mean absolute distances (MAD) from CT contours. Results: In phantoms, Endoscope Tracking had average point error=0.66±0.50cm and average bolus MAD=0.74±0.37cm for the first 80% of each video. After that the virtual endoscope got lost, increasing these values to 4.73±1.69cm and 4.06±0.30cm. Location Search had point error=0.49±0.44cm and MAD=0.53±0.28cm. Point errors were larger where the endoscope viewed the surface at shallow angles<10 degrees (1.38±0.62cm and 1.22±0.69cm for Endoscope Tracking and Location Search, respectively). In patients, Endoscope Tracking did not make it past the nasal cavity. However, Location Search found coordinates near the correct location for 70% of test frames. Its performance was best near the epiglottis and in the nasal cavity. Conclusion: Location Search is a robust and accurate technique to map endoscopic video to CT. Endoscope Tracking is sensitive to erratic camera motion and local optima, but could be used in conjunction with anchor points found using Location Search.« less

The "Mad Hatter's" Adventures in Education: Joseph King (1860-1943) and the Impact of Personality

ERIC Educational Resources Information Center

Palmer, Amy

2017-01-01

Joseph King (1860-1943), known as the "Mad Hatter" because of his appearance and eccentric manner, was a man who cared very much about education in a wide range of arenas. He was a founder of Mansfield House University Settlement in London and of the peasant arts movement, both philanthropic organisations which aimed to improve the lot…

Accuracy evaluation of contour next compared with five blood glucose monitoring systems across a wide range of blood glucose concentrations occurring in a clinical research setting.

PubMed

Klaff, Leslie J; Brazg, Ronald; Hughes, Kristen; Tideman, Ann M; Schachner, Holly C; Stenger, Patricia; Pardo, Scott; Dunne, Nancy; Parkes, Joan Lee

2015-01-01

This study evaluated the accuracy of Contour(®) Next (CN; Bayer HealthCare LLC, Diabetes Care, Whippany, NJ) compared with five blood glucose monitoring systems (BGMSs) across a wide range of clinically occurring blood glucose levels. Subjects (n=146) were ≥ 18 years and had type 1 or type 2 diabetes. Subjects' glucose levels were safely lowered or raised to provide a wide range of glucose values. Capillary blood samples were tested on six BGMSs and a YSI glucose analyzer (YSI Life Sciences, Inc., Yellow Springs, OH) as the reference. Extreme glucose values were achieved by glucose modification of the blood sample. System accuracy was assessed by mean absolute difference (MAD) and mean absolute relative difference (MARD) across several glucose ranges, with <70 mg/dL evaluated by MAD as the primary end point. In the low glucose range (<70 mg/dL), MAD values were as follows: Accu-Chek(®) Aviva Nano (Roche Diagnostics, Indianapolis, IN), 3.34 mg/dL; CN, 2.03 mg/dL; FreeStyle Lite(®) (FSL; Abbott Diabetes Care, Inc., Alameda, CA), 2.77 mg/dL; OneTouch(®) Ultra(®) 2 (LifeScan, Inc., Milpitas, CA), 10.20 mg/dL; OneTouch(®) Verio(®) Pro (LifeScan, Inc.), 4.53 mg/dL; and Truetrack(®) (Nipro Diagnostics, Inc., Fort Lauderdale, FL), 11.08 mg/dL. The lowest MAD in the low glucose range, from CN, was statistically significantly lower than those of the other BGMSs with the exception of the FSL. CN also had a statistically significantly lower MARD than all other BGMSs in the low glucose range. In the overall glucose range (21-496 mg/dL), CN yielded the lowest MAD and MARD values, which were statistically significantly lower in comparison with the other BGMSs. When compared with other BGMSs, CN demonstrated the lowest mean deviation from the reference value (by MAD and MARD) across multiple glucose ranges.

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

Hitomi, Toshiaki; Habu, Toshiyuki; Kobayashi, Hatasu

Highlights: •Overexpression of RNF213 R4810K inhibited cell proliferation. •Overexpression of RNF213 R4810K had the time of mitosis 4-fold and mitotic failure. •R4810K formed a complex with MAD2 more readily than wild-type. •iPSECs from the MMD patients had elevated mitotic failure compared from the control. •RNF213 R4810K induced mitotic abnormality and increased risk of aneuploidy. -- Abstract: Moyamoya disease (MMD) is a cerebrovascular disease characterized by occlusive lesions in the Circle of Willis. The RNF213 R4810K polymorphism increases susceptibility to MMD. In the present study, we characterized phenotypes caused by overexpression of RNF213 wild type and R4810K variant in the cellmore » cycle to investigate the mechanism of proliferation inhibition. Overexpression of RNF213 R4810K in HeLa cells inhibited cell proliferation and extended the time of mitosis 4-fold. Ablation of spindle checkpoint by depletion of mitotic arrest deficiency 2 (MAD2) did not shorten the time of mitosis. Mitotic morphology in HeLa cells revealed that MAD2 colocalized with RNF213 R4810K. Immunoprecipitation revealed an RNF213/MAD2 complex: R4810K formed a complex with MAD2 more readily than RNF213 wild-type. Desynchronized localization of MAD2 was observed more frequently during mitosis in fibroblasts from patients (n = 3, 61.0 ± 8.2%) compared with wild-type subjects (n = 6, 13.1 ± 7.7%; p < 0.01). Aneuploidy was observed more frequently in fibroblasts (p < 0.01) and induced pluripotent stem cells (iPSCs) (p < 0.03) from patients than from wild-type subjects. Vascular endothelial cells differentiated from iPSCs (iPSECs) of patients and an unaffected carrier had a longer time from prometaphase to metaphase than those from controls (p < 0.05). iPSECs from the patients and unaffected carrier had significantly increased mitotic failure rates compared with controls (p < 0.05). Thus, RNF213 R4810K induced mitotic abnormalities and increased risk of genomic instability.« less

Impact of social inequalities at birth on the longevity of children born 1914-1916: A cohort study.

PubMed

Todd, Nicolas; Le Fur, Sophie; Bougnères, Pierre; Valleron, Alain-Jacques

2017-01-01

Testing whether familial socioeconomic status (SES) in childhood is a predictor of mortality has rarely been done on historical cohorts. The birth certificates of 4,805 individuals born 1914-1916 in 16 districts of the Paris region were retrieved. The handwritten information provided the occupation of parents, the legitimacy status, life events (e.g. marriage, divorce), and the precise date of death when after 1945 (i.e. age 31 years (y) in the cohort). We used the median age at death (MAD) as a global measure of mortality, then studied separately survival to and after 31 y. Multivariate Imputation by Chained Equations (MICE), Generalized Additive Models (GAMs) and mixed effect Cox models were used. MAD showed large variations according to paternal occupation. The lowest MAD in both sexes was that of workers' children: it was 56.3 y (95% CI: [48.6-62.7]) in men and 67.4 y (95% CI: [60.8-72.7]) in women, respectively (95% CI: 13.4 y [5.7-21.3]) and 12.3 y (95% CI: [4.0-19.2]) below the highest MAD attained. MAD experienced by illegitimate children was 18.9 y (95% CI: [13.3-32.3]) shorter than of legitimate children. The multivariate analysis revealed that in both sexes survival to age 31 y was predicted independently by legitimacy and paternal occupation. Paternal occupation was found significantly associated with mortality after age 31 y in females only: accordingly difference in life expectancy at age 31 y was 4.4 y (95% CI: [1.2-7.6]) between upper class and workers' daughters. Paternal occupation and legitimacy status were strong predictors of offspring longevity in this one-century historical cohort born during World War One.

A Monochromatic, Aberration-Corrected, Dual-Beam Low Energy Electron Microscope

PubMed Central

Mankos, Marian; Shadman, Khashayar

2013-01-01

The monochromatic, aberration-corrected, dual-beam low energy electron microscope (MAD-LEEM) is a novel instrument aimed at imaging of nanostructures and surfaces at sub-nanometer resolution that includes a monochromator, aberration corrector and dual beam illumination. The monochromator reduces the energy spread of the illuminating electron beam, which significantly improves spectroscopic and spatial resolution. The aberration corrector utilizes an electron mirror with negative aberrations that can be used to compensate the aberrations of the LEEM objective lens for a range of electron energies. Dual flood illumination eliminates charging generated when a conventional LEEM is used to image insulating specimens. MAD-LEEM is designed for the purpose of imaging biological and insulating specimens, which are difficult to image with conventional LEEM, Low-Voltage SEM, and TEM instruments. The MAD-LEEM instrument can also be used as a general purpose LEEM with significantly improved resolution. The low impact energy of the electrons is critical for avoiding beam damage, as high energy electrons with keV kinetic energies used in SEMs and TEMs cause irreversible change to many specimens, in particular biological materials. A potential application for MAD-LEEM is in DNA sequencing, which demands imaging techniques that enable DNA sequencing at high resolution and speed, and at low cost. The key advantages of the MAD-LEEM approach for this application are the low electron impact energies, the long read lengths, and the absence of heavy-atom DNA labeling. Image contrast simulations of the detectability of individual nucleotides in a DNA strand have been developed in order to refine the optics blur and DNA base contrast requirements for this application. PMID:23582636

A monochromatic, aberration-corrected, dual-beam low energy electron microscope.

PubMed

Mankos, Marian; Shadman, Khashayar

2013-07-01

The monochromatic, aberration-corrected, dual-beam low energy electron microscope (MAD-LEEM) is a novel instrument aimed at imaging of nanostructures and surfaces at sub-nanometer resolution that includes a monochromator, aberration corrector and dual beam illumination. The monochromator reduces the energy spread of the illuminating electron beam, which significantly improves spectroscopic and spatial resolution. The aberration corrector utilizes an electron mirror with negative aberrations that can be used to compensate the aberrations of the LEEM objective lens for a range of electron energies. Dual flood illumination eliminates charging generated when a conventional LEEM is used to image insulating specimens. MAD-LEEM is designed for the purpose of imaging biological and insulating specimens, which are difficult to image with conventional LEEM, Low-Voltage SEM, and TEM instruments. The MAD-LEEM instrument can also be used as a general purpose LEEM with significantly improved resolution. The low impact energy of the electrons is critical for avoiding beam damage, as high energy electrons with keV kinetic energies used in SEMs and TEMs cause irreversible change to many specimens, in particular biological materials. A potential application for MAD-LEEM is in DNA sequencing, which demands imaging techniques that enable DNA sequencing at high resolution and speed, and at low cost. The key advantages of the MAD-LEEM approach for this application are the low electron impact energies, the long read lengths, and the absence of heavy-atom DNA labeling. Image contrast simulations of the detectability of individual nucleotides in a DNA strand have been developed in order to refine the optics blur and DNA base contrast requirements for this application. Copyright © 2013 Elsevier B.V. All rights reserved.

Concentration-Response Modeling of ECG Data From Early-Phase Clinical Studies as an Alternative Clinical and Regulatory Approach to Assessing QT Risk - Experience From the Development Program of Lemborexant.

PubMed

Murphy, Patricia J; Yasuda, Sanae; Nakai, Kenya; Yoshinaga, Takashi; Hall, Nancy; Zhou, Meijian; Aluri, Jagadeesh; Rege, Bhaskar; Moline, Margaret; Ferry, Jim; Darpo, Borje

2017-01-01

Lemborexant is a novel dual orexin receptor antagonist being developed to treat insomnia. Its potential to cause QT prolongation was evaluated using plasma concentration-response (CR) modeling applied to data from 2 multiple ascending-dose (MAD) studies. In the primary MAD study, placebo or lemborexant (2.5 to 75 mg) was administered for 14 consecutive nights. In another MAD study designed to "bridge" pharmacokinetic and safety data between Japanese and non-Japanese subjects (J-MAD), placebo or lemborexant (2.5, 10, or 25 mg) was administered for 14 consecutive nights. QT intervals were estimated using a high-precision measurement technique and evaluated using a linear mixed-effects CR model, for each study separately and for the pooled data set. When each study was analyzed separately, the slopes of the CR relationship were shallow and not statistically significant. In the pooled analysis, the slope of the CR relationship was -0.00002 milliseconds per ng/mL (90%CI, -0.01019 to 0.01014 milliseconds). The highest observed C max was 400 ng/mL, representing a margin 8-fold above exposures expected for the highest planned clinical dose. The model-predicted QTc effect at 400 ng/mL was 1.1 milliseconds (90%CI, -3.49 to 5.78 milliseconds). In neither the J-MAD study nor the pooled analysis was an effect of race identified. CR modeling of data from early-phase clinical studies, including plasma levels far exceeding those anticipated clinically, indicated that a QT effect >10 milliseconds could be excluded. Regulatory agreement with this methodology demonstrates the effectiveness of a CR modeling approach as an alternative to thorough QT studies. © 2016, The American College of Clinical Pharmacology.

Investigating the Impact of a Genome-Wide Supported Bipolar Risk Variant of MAD1L1 on the Human Reward System.

PubMed

Trost, Sarah; Diekhof, Esther K; Mohr, Holger; Vieker, Henning; Krämer, Bernd; Wolf, Claudia; Keil, Maria; Dechent, Peter; Binder, Elisabeth B; Gruber, Oliver

2016-10-01

Recent genome-wide association studies have identified MAD1L1 (mitotic arrest deficient-like 1) as a susceptibility gene for bipolar disorder and schizophrenia. The minor allele of the single-nucleotide polymorphism (SNP) rs11764590 in MAD1L1 was associated with bipolar disorder. Both diseases, bipolar disorder and schizophrenia, are linked to functional alterations in the reward system. We aimed at investigating possible effects of the MAD1L1 rs11764590 risk allele on reward systems functioning in healthy adults. A large homogenous sample of 224 young (aged 18-31 years) participants was genotyped and underwent functional magnetic resonance imaging (fMRI). All participants performed the 'Desire-Reason Dilemma' paradigm investigating the neural correlates that underlie reward processing and active reward dismissal in favor of a long-term goal. We found significant hypoactivations of the ventral tegmental area (VTA), the bilateral striatum and bilateral frontal and parietal cortices in response to conditioned reward stimuli in the risk allele carriers compared with major allele carriers. In the dilemma situation, functional connectivity between prefrontal brain regions and the ventral striatum was significantly diminished in the risk allele carriers. Healthy risk allele carriers showed a significant deficit of their bottom-up response to conditioned reward stimuli in the bilateral VTA and striatum. Furthermore, functional connectivity between the ventral striatum and prefrontal areas exerting top-down control on the mesolimbic reward system was reduced in this group. Similar alterations in reward processing and disturbances of prefrontal control mechanisms on mesolimbic brain circuits have also been reported in bipolar disorder and schizophrenia. Together, these findings suggest the existence of an intermediate phenotype associated with MAD1L1.

Monitoring baseline suspended sediment in forested basins: the effects of sampling on suspended sediment rating curves

Treesearch

Robert B. Thomas

1988-01-01

Abstract - Rating curves are widely used for directly assessing changes in the suspended sediment delivery process and indirectly for estimating total yields. Four sampling methods were simulated-over a 31-day record of suspended sediment from the North Fork of the Mad River near Korbel, California. The position and size of the four groups of plotted slope/intercept...

The Effect of Drill and Practice Software on Multiplication Skills: "Multiplication Puzzles" versus "The Mad Minute."

ERIC Educational Resources Information Center

Williams, Lynda Patterson

The purpose of the study was to compare two methods of learning multiplication facts in order to develop speed and accuracy. The researcher conducted the action research project with a seventh grade enrichment class, which met for seven weeks during the school year. As part of the curriculum students were provided with activities to refine their…

A Multi-Index Approach to Delineate Surface Water Bodies in the Pastoral Regions of Mali Using ASTER Imagery

NASA Astrophysics Data System (ADS)

Alemu, H.; Velpuri, N.; Senay, G. B.; Angerer, J.

2011-12-01

Information on the location and availability of water resources is a day-to-day challenge for pastoralists in the Sahelian region of Mali. They move seasonally along their migration corridors in search for water and forage. Satellite data can be used to map the spatial and temporal dynamics of these water resources. In this work, ASTER imagery is selected for its high (15 m) spatial resolution and suitable spectral bands for water body identification. Our research indicates that as most of the waterholes of interest in the study area are very shallow and heavily sediment-laden, using only one of those commonly used water identification indices such as the Simple Band Ratio (SBR), or the Normalized Difference Water Index (NDWI) alone does not help in effectively characterizing all the surface water bodies in the region. As a result, we used four different spectral indices to identify surface water features: (i) Simple Band Ratio (SBR), (ii) Normalized Difference Water Index (NDWI), (iii) Modified Normalized Difference Water Index (MNDWI), and (iv) the Mean Absolute Deviation (MAD) to identify and delineate surface water bodies using 91 ASTER images. Initial results indicate that the SBR method identified 17 waterholes while the NDWI 18, the MNDWI 36, and the MAD method identified 28 waterholes. However, by combining the results from the four aforementioned spectral indices following a multi-index approach, 89 waterholes that were previously unidentified by a single approach alone were identified. Furthermore, our analysis indicates that the SBR and the NDWI methods identify relatively clearer waterholes better (29% of the waterholes), whereas MNDWI and MAD proved to be good indices for identifying sediment-laden waterholes. Identifying the location and spatial distribution of surface water bodies is the first step towards monitoring their seasonal dynamics using a hydrologic modeling system, similar to an existing setup for east Africa (http://watermon.tamu.edu/). Seasonal trends in relative surface water levels are one of the most important inputs in the livestock early warning system (LEWS) along with forage and livestock market prices.

A computationally efficient parallel Levenberg-Marquardt algorithm for highly parameterized inverse model analyses

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

Lin, Youzuo; O'Malley, Daniel; Vesselinov, Velimir V.

Inverse modeling seeks model parameters given a set of observations. However, for practical problems because the number of measurements is often large and the model parameters are also numerous, conventional methods for inverse modeling can be computationally expensive. We have developed a new, computationally-efficient parallel Levenberg-Marquardt method for solving inverse modeling problems with a highly parameterized model space. Levenberg-Marquardt methods require the solution of a linear system of equations which can be prohibitively expensive to compute for moderate to large-scale problems. Our novel method projects the original linear problem down to a Krylov subspace, such that the dimensionality of themore » problem can be significantly reduced. Furthermore, we store the Krylov subspace computed when using the first damping parameter and recycle the subspace for the subsequent damping parameters. The efficiency of our new inverse modeling algorithm is significantly improved using these computational techniques. We apply this new inverse modeling method to invert for random transmissivity fields in 2D and a random hydraulic conductivity field in 3D. Our algorithm is fast enough to solve for the distributed model parameters (transmissivity) in the model domain. The algorithm is coded in Julia and implemented in the MADS computational framework (http://mads.lanl.gov). By comparing with Levenberg-Marquardt methods using standard linear inversion techniques such as QR or SVD methods, our Levenberg-Marquardt method yields a speed-up ratio on the order of ~10 1 to ~10 2 in a multi-core computational environment. Furthermore, our new inverse modeling method is a powerful tool for characterizing subsurface heterogeneity for moderate- to large-scale problems.« less

A computationally efficient parallel Levenberg-Marquardt algorithm for highly parameterized inverse model analyses

DOE PAGES

Lin, Youzuo; O'Malley, Daniel; Vesselinov, Velimir V.

2016-09-01

Inverse modeling seeks model parameters given a set of observations. However, for practical problems because the number of measurements is often large and the model parameters are also numerous, conventional methods for inverse modeling can be computationally expensive. We have developed a new, computationally-efficient parallel Levenberg-Marquardt method for solving inverse modeling problems with a highly parameterized model space. Levenberg-Marquardt methods require the solution of a linear system of equations which can be prohibitively expensive to compute for moderate to large-scale problems. Our novel method projects the original linear problem down to a Krylov subspace, such that the dimensionality of themore » problem can be significantly reduced. Furthermore, we store the Krylov subspace computed when using the first damping parameter and recycle the subspace for the subsequent damping parameters. The efficiency of our new inverse modeling algorithm is significantly improved using these computational techniques. We apply this new inverse modeling method to invert for random transmissivity fields in 2D and a random hydraulic conductivity field in 3D. Our algorithm is fast enough to solve for the distributed model parameters (transmissivity) in the model domain. The algorithm is coded in Julia and implemented in the MADS computational framework (http://mads.lanl.gov). By comparing with Levenberg-Marquardt methods using standard linear inversion techniques such as QR or SVD methods, our Levenberg-Marquardt method yields a speed-up ratio on the order of ~10 1 to ~10 2 in a multi-core computational environment. Furthermore, our new inverse modeling method is a powerful tool for characterizing subsurface heterogeneity for moderate- to large-scale problems.« less

Goodness-of-Fit Tests for Generalized Normal Distribution for Use in Hydrological Frequency Analysis

NASA Astrophysics Data System (ADS)

Das, Samiran

2018-04-01

The use of three-parameter generalized normal (GNO) as a hydrological frequency distribution is well recognized, but its application is limited due to unavailability of popular goodness-of-fit (GOF) test statistics. This study develops popular empirical distribution function (EDF)-based test statistics to investigate the goodness-of-fit of the GNO distribution. The focus is on the case most relevant to the hydrologist, namely, that in which the parameter values are unidentified and estimated from a sample using the method of L-moments. The widely used EDF tests such as Kolmogorov-Smirnov, Cramer von Mises, and Anderson-Darling (AD) are considered in this study. A modified version of AD, namely, the Modified Anderson-Darling (MAD) test, is also considered and its performance is assessed against other EDF tests using a power study that incorporates six specific Wakeby distributions (WA-1, WA-2, WA-3, WA-4, WA-5, and WA-6) as the alternative distributions. The critical values of the proposed test statistics are approximated using Monte Carlo techniques and are summarized in chart and regression equation form to show the dependence of shape parameter and sample size. The performance results obtained from the power study suggest that the AD and a variant of the MAD (MAD-L) are the most powerful tests. Finally, the study performs case studies involving annual maximum flow data of selected gauged sites from Irish and US catchments to show the application of the derived critical values and recommends further assessments to be carried out on flow data sets of rivers with various hydrological regimes.

Philippe Pinel's "Memoir on Madness" of December 11, 1794: a fundamental text of modern psychiatry.

PubMed

Weiner, D B

1992-06-01

Philippe Pinel's "Memoir on Madness" can now be precisely dated. It was read to the Society for Natural History in Paris on Dec. 11, 1794, soon after the fall of the Jacobin dictatorship. It is thus a political document, an appeal to the Revolutionary government to build asylums where the mentally ill could be decently treated. It is translated here for the first time. Philippe Pinel (1745-1826) served as "physician of the infirmaries" at Bicêtre, the public hospice for men near Paris, from 1793 to 1795. In the "Memoir on Madness" he explains his "psychologic treatment," the principles of the humane method that made him the founder of psychiatry in France. Pinel states that mental illness is often curable. To arrive at a diagnosis, the physician must carefully observe a patient's behavior, interview him, listen carefully, and take notes. He must understand the natural history of the disease and the precipitating event and write an accurate case history. Diagnosis and prognosis can then be made. Periodic patterns of mental illness can be helpful for therapy. Usually only one faculty is affected. Patients with delusions may be malicious or murderous. They may have to be restrained; it was Pinel's assistant, Jean Baptiste Pussin, who removed the chains from the insane men at Bicêtre Hospice in 1797 and replaced them with strait-jackets. Pinel followed suit at the Salpêtrière, the public hospice for women, 3 years later. Pinel here states that one must "dominate agitated madmen while respecting human rights."

Crystallization and X-ray data analysis of the 10 kDa C-terminal lid subdomain from Caenorhabditis elegans Hsp70

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

Worrall, Liam; Walkinshaw, Malcolm D., E-mail: m.walkinshaw@ed.ac.uk

Crystals of the C-terminal 10 kDa lid subdomain from the C. elegans chaperone Hsp70 have been obtained that diffract X-rays to ∼3.5 Å and belong to space group I2{sub 1}2{sub 1}2{sub 1}. Analysis of X-ray data and initial heavy-atom phasing reveals 24 monomers in the asymmetric unit related by 432 non-crystallographic symmetry. Hsp70 is an important molecular chaperone involved in the regulation of protein folding. Crystals of the C-terminal 10 kDa helical lid domain (residues 542–640) from a Caenorhabditis elegans Hsp70 homologue have been produced that diffract X-rays to ∼3.4 Å. Crystals belong to space group I2{sub 1}2{sub 1}2{sub 1},more » with unit-cell parameters a = b = 197, c = 200 Å. The Matthews coefficient, self-rotation function and Patterson map indicate 24 monomers in the asymmetric unit, showing non-crystallographic 432 symmetry. Molecular-replacement studies using the corresponding domain from rat, the only eukaryotic homologue with a known structure, failed and a mercury derivative was obtained. Preliminary MAD phasing using SHELXD and SHARP for location and refinement of the heavy-atom substructure and SOLOMON for density modification produced interpretable maps with a clear protein–solvent boundary. Further density-modification, model-building and refinement are currently under way.« less

Emerging diseases. Hunt for mad cow in sheep reassuring.

PubMed

Balter, M

2000-08-11

Experts on brain-riddling spongiform diseases have grown steadily more uneasy over signs that so-called mad cow disease or bovine spongiform encephalopathy (BSE), which is linked to a lethal human illness, may be lurking in sheep. A study in the 10 August issue of Nature now offers evidence that BSE is not rampant in sheep after all, although scientists are far from ready to let their guard down.

Japan-U.S. Relations: Issues for Congress

DTIC Science & Technology

2010-06-11

imposed a ban on imported U.S. beef in response to the discovery of the first U.S. case of bovine spongiform encephalopathy (BSE or “ mad cow disease ...imports.11 9 For more information, see CRS Report RS21709, Mad Cow Disease and U.S. Beef...in Washington state. In the months before the diagnosis in the United States, nearly a dozen Japanese cows infected with BSE had been discovered

Japan-U.S. Relations: Issues for Congress

DTIC Science & Technology

2010-07-30

on beef imports.11 9 For more information, see CRS Report RS21709, Mad Cow Disease and...2003, Japan imposed a ban on imported U.S. beef in response to the discovery of the first U.S. case of bovine spongiform encephalopathy (BSE or “ mad cow ... disease ”) in Washington state. In the months before the diagnosis in the United States, nearly a dozen Japanese cows infected with BSE had been

Mad cows and Englishmen: the aftermath of a BSE scare

PubMed Central

Richmond, C

1997-01-01

The consumption of prime beef cuts is down, animals have been slaughtered by the thousand and 3 farmers have committed suicide as the mad-cow issue continues to cause concern in the United Kingdom. In this report from London, Caroline Richmond also notes that the royal colleges have published a report stating that chronic fatigue syndrome is a real illness and patients need help. PMID:9099178

Modified Atkins diet vs classic ketogenic formula in intractable epilepsy.

PubMed

El-Rashidy, O F; Nassar, M F; Abdel-Hamid, I A; Shatla, R H; Abdel-Hamid, M H; Gabr, S S; Mohamed, S G; El-Sayed, W S; Shaaban, S Y

2013-12-01

The study was designed to evaluate the efficacy, safety, and tolerability of the ketogenic diet (KD) whether classic 4:1 formula or the modified Atkins diet (MAD) in intractable childhood epilepsy. Anthropometric measurements and serum lipid profile were measured upon enrollment and after 3 and 6 months in 40 patients with symptomatic intractable epilepsy. Fifteen were given MAD diet, ten were kept on classic 4:1 ketogenic liquid formula, and the rest were allowed to eat as desired. The liquid ketogenic formula group showed significantly higher body mass index compared with those who did not receive KD after 6 months. The lipid profile of KD patients was within normal limits for age and sex during the study period. The rate of change of frequency and severity of seizures showed best improvement in ketogenic liquid formula patients followed by the MAD group than the patients on anti-epileptic medications alone. The KD whether classic 4:1 or MAD is a tolerable, safe, and effective adjuvant therapy for intractable symptomatic childhood epilepsy with limited adverse effects on the growth parameters and accepted changes in the lipid profile. The liquid ketogenic formula patients showed better growth pattern and significantly more seizure control. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Differences in DNA Binding Specificity of Floral Homeotic Protein Complexes Predict Organ-Specific Target Genes.

PubMed

Smaczniak, Cezary; Muiño, Jose M; Chen, Dijun; Angenent, Gerco C; Kaufmann, Kerstin

2017-08-01

Floral organ identities in plants are specified by the combinatorial action of homeotic master regulatory transcription factors. However, how these factors achieve their regulatory specificities is still largely unclear. Genome-wide in vivo DNA binding data show that homeotic MADS domain proteins recognize partly distinct genomic regions, suggesting that DNA binding specificity contributes to functional differences of homeotic protein complexes. We used in vitro systematic evolution of ligands by exponential enrichment followed by high-throughput DNA sequencing (SELEX-seq) on several floral MADS domain protein homo- and heterodimers to measure their DNA binding specificities. We show that specification of reproductive organs is associated with distinct binding preferences of a complex formed by SEPALLATA3 and AGAMOUS. Binding specificity is further modulated by different binding site spacing preferences. Combination of SELEX-seq and genome-wide DNA binding data allows differentiation between targets in specification of reproductive versus perianth organs in the flower. We validate the importance of DNA binding specificity for organ-specific gene regulation by modulating promoter activity through targeted mutagenesis. Our study shows that intrafamily protein interactions affect DNA binding specificity of floral MADS domain proteins. Differential DNA binding of MADS domain protein complexes plays a role in the specificity of target gene regulation. © 2017 American Society of Plant Biologists. All rights reserved.

The social structure of the medical model of madness and the physician's role.

PubMed

Fernandez, G

1981-08-01

In this paper the origins of the medical model of madness are traced in the sociohistorical context of institutional and professional development. The paper establishes the emergence of the three primary conditions necessary for the medical model to exist: (a) the view that madness is a separate ontological reality which can be differentiated from the insane person; (b) the concept that insane people do not have a completely free will and therefore cannot be held responsible for their actions; and (c) the creation of specific criteria to classify the disease into empirically derived nosologies. These conditions and their acceptance as an explanatory paradigm of insanity result from the political economy of the late Middle Ages and are reflected in the institutional arrangement for insane persons of the 17th and 18th centuries. Finally, the role of the physician-psychiatrist is explained in terms of an ability to (a) serve as a technician for the new political forces, and (b) dislodge the moral entrepreneurs and become the only profession able to offer a proper scientific and secular treatment of madness. The psychiatrist is presented as a by-product of the dominance of the medical model rather than as the agent who created it.

Evidence that β7 Integrin Regulates Hematopoietic Stem Cell Homing and Engraftment Through Interaction with MAdCAM-1.

PubMed

Murakami, Jodi L; Xu, Baohui; Franco, Christopher B; Hu, Xingbin; Galli, Stephen J; Weissman, Irving L; Chen, Ching-Cheng

2016-01-01

α4β7 integrin is a cell adhesion receptor that is crucial for the migration of hematopoietic progenitors and mature effector cells in the periphery, but its role in adult hematopoiesis is controversial. We identified a subset of hematopoietic stem cells (HSCs) in the bone marrow (BM) that expressed β7 integrin. These β7(+) HSCs were capable of multilineage, long-term reconstitution and had an inherent competitive advantage over β7(-) HSCs. On the other hand, HSCs that lacked β7 integrin (β7KO) had reduced engraftment potential. Interestingly, quantitative RT-PCR and flow cytometry revealed that β7KO HSCs expressed lower levels of the chemokine receptor CXCR4. Accordingly, β7KO HSCs exhibited impaired migration abilities in vitro and BM homing capabilities in vivo. Lethal irradiation induced expression of the α4β7 integrin ligand-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) on BM endothelial cells. Moreover, blocking MAdCAM-1 reduced the homing of HSCs and impaired the survival of recipient mice. Altogether, these data indicate that β7 integrin, when expressed by HSCs, interacted with its endothelial ligand MAdCAM-1 in the BM microenvironment, thereby promoting HSC homing and engraftment.

"Now he walks and walks, as if he didn't have a home where he could eat": food, healing, and hunger in Quechua narratives of madness.

PubMed

Orr, David M R

2013-12-01

In the Quechua-speaking peasant communities of southern Peru, mental disorder is understood less as individualized pathology and more as a disturbance in family and social relationships. For many Andeans, food and feeding are ontologically fundamental to such relationships. This paper uses data from interviews and participant observation in a rural province of Cuzco to explore the significance of food and hunger in local discussions of madness. Carers' narratives, explanatory models, and theories of healing all draw heavily from idioms of food sharing and consumption in making sense of affliction, and these concepts structure understandings of madness that differ significantly from those assumed by formal mental health services. Greater awareness of the salience of these themes could strengthen the input of psychiatric and psychological care with this population and enhance knowledge of the alternative treatments that they use. Moreover, this case provides lessons for the global mental health movement on the importance of openness to the ways in which indigenous cultures may construct health, madness, and sociality. Such local meanings should be considered by mental health workers delivering services in order to provide care that can adjust to the alternative ontologies of sufferers and carers.

Transcriptional Regulation of Fruit Ripening by Tomato FRUITFULL Homologs and Associated MADS Box Proteins[W

PubMed Central

Fujisawa, Masaki; Shima, Yoko; Nakagawa, Hiroyuki; Kitagawa, Mamiko; Kimbara, Junji; Nakano, Toshitsugu; Kasumi, Takafumi; Ito, Yasuhiro

2014-01-01

The tomato (Solanum lycopersicum) MADS box FRUITFULL homologs FUL1 and FUL2 act as key ripening regulators and interact with the master regulator MADS box protein RIPENING INHIBITOR (RIN). Here, we report the large-scale identification of direct targets of FUL1 and FUL2 by transcriptome analysis of FUL1/FUL2 suppressed fruits and chromatin immunoprecipitation coupled with microarray analysis (ChIP-chip) targeting tomato gene promoters. The ChIP-chip and transcriptome analysis identified FUL1/FUL2 target genes that contain at least one genomic region bound by FUL1 or FUL2 (regions that occur mainly in their promoters) and exhibit FUL1/FUL2-dependent expression during ripening. These analyses identified 860 direct FUL1 targets and 878 direct FUL2 targets; this set of genes includes both direct targets of RIN and nontargets of RIN. Functional classification of the FUL1/FUL2 targets revealed that these FUL homologs function in many biological processes via the regulation of ripening-related gene expression, both in cooperation with and independent of RIN. Our in vitro assay showed that the FUL homologs, RIN, and tomato AGAMOUS-LIKE1 form DNA binding complexes, suggesting that tetramer complexes of these MADS box proteins are mainly responsible for the regulation of ripening. PMID:24415769

Angular Momentum Transport in Thin Magnetically Arrested Disks

NASA Astrophysics Data System (ADS)

Marshall, Megan D.; Avara, Mark J.; McKinney, Jonathan C.

2018-05-01

In accretion disks with large-scale ordered magnetic fields, the magnetorotational instability (MRI) is marginally suppressed, so other processes may drive angular momentum transport leading to accretion. Accretion could then be driven by large-scale magnetic fields via magnetic braking, and large-scale magnetic flux can build-up onto the black hole and within the disk leading to a magnetically-arrested disk (MAD). Such a MAD state is unstable to the magnetic Rayleigh-Taylor (RT) instability, which itself leads to vigorous turbulence and the emergence of low-density highly-magnetized bubbles. This instability was studied in a thin (ratio of half-height H to radius R, H/R ≈ 0.1) MAD simulation, where it has a more dramatic effect on the dynamics of the disk than for thicker disks. Large amounts of flux are pushed off the black hole into the disk, leading to temporary decreases in stress, then this flux is reprocessed as the stress increases again. Throughout this process, we find that the dominant component of the stress is due to turbulent magnetic fields, despite the suppression of the axisymmetric MRI and the dominant presence of large-scale magnetic fields. This suggests that the magnetic RT instability plays a significant role in driving angular momentum transport in MADs.

A rapid method for direct detection of metabolic conversion and magnetization exchange with application to hyperpolarized substrates

NASA Astrophysics Data System (ADS)

Larson, Peder E. Z.; Kerr, Adam B.; Leon Swisher, Christine; Pauly, John M.; Vigneron, Daniel B.

2012-12-01

In this work, we present a new MR spectroscopy approach for directly observing nuclear spins that undergo exchange, metabolic conversion, or, generally, any frequency shift during a mixing time. Unlike conventional approaches to observe these processes, such as exchange spectroscopy (EXSY), this rapid approach requires only a single encoding step and thus is readily applicable to hyperpolarized MR in which the magnetization is not replenished after T1 decay and RF excitations. This method is based on stimulated-echoes and uses phase-sensitive detection in conjunction with precisely chosen echo times in order to separate spins generated during the mixing time from those present prior to mixing. We are calling the method Metabolic Activity Decomposition Stimulated-echo Acquisition Mode or MAD-STEAM. We have validated this approach as well as applied it in vivo to normal mice and a transgenic prostate cancer mouse model for observing pyruvate-lactate conversion, which has been shown to be elevated in numerous tumor types. In this application, it provides an improved measure of cellular metabolism by separating [1-13C]-lactate produced in tissue by metabolic conversion from [1-13C]-lactate that has flowed into the tissue or is in the blood. Generally, MAD-STEAM can be applied to any system in which spins undergo a frequency shift.

A rapid method for direct detection of metabolic conversion and magnetization exchange with application to hyperpolarized substrates.

PubMed

Larson, Peder E Z; Kerr, Adam B; Swisher, Christine Leon; Pauly, John M; Vigneron, Daniel B

2012-12-01

In this work, we present a new MR spectroscopy approach for directly observing nuclear spins that undergo exchange, metabolic conversion, or, generally, any frequency shift during a mixing time. Unlike conventional approaches to observe these processes, such as exchange spectroscopy (EXSY), this rapid approach requires only a single encoding step and thus is readily applicable to hyperpolarized MR in which the magnetization is not replenished after T(1) decay and RF excitations. This method is based on stimulated-echoes and uses phase-sensitive detection in conjunction with precisely chosen echo times in order to separate spins generated during the mixing time from those present prior to mixing. We are calling the method Metabolic Activity Decomposition Stimulated-echo Acquisition Mode or MAD-STEAM. We have validated this approach as well as applied it in vivo to normal mice and a transgenic prostate cancer mouse model for observing pyruvate-lactate conversion, which has been shown to be elevated in numerous tumor types. In this application, it provides an improved measure of cellular metabolism by separating [1-(13)C]-lactate produced in tissue by metabolic conversion from [1-(13)C]-lactate that has flowed into the tissue or is in the blood. Generally, MAD-STEAM can be applied to any system in which spins undergo a frequency shift. Copyright © 2012 Elsevier Inc. All rights reserved.

MAD COW DISEASE: New Recruits for French Prion Research.

PubMed

Casassus, B

2000-12-01

As panic over "mad cow disease" engulfs France and threatens to spread to other countries in Western Europe, French research minister Roger-Gérard Schwartzenberg last week unveiled detailed plans for spending $27 million the government has earmarked for prion disease research in 2001. Next year's budget for studying prions--infectious, abnormal proteins linked to bovine spongiform encephalopathy and its human form, variant Creutzfeldt-Jakob disease--will triple France's current prion research spending.

Could inhibition of the proteasome cause mad cow disease?

PubMed

Hooper, Nigel M

2003-04-01

The proteasome is the cellular machinery responsible for the degradation of normal and misfolded proteins. Inhibitors of the proteasome are being evaluated as therapeutic agents and recent work suggests that such inhibition might promote the neurotoxic properties of the prion protein (the causative agent of mad cow disease) and its conformational conversion to the infectious form, thus raising the question as to whether proteasome inhibitors might facilitate the development of prion diseases.

Madness and sanity at the time of Indian independence.

PubMed

Jain, Sanjeev; Murthy, Pratima; Sarin, Alok

2016-01-01

The backdrop of the Indian Independence offers glimpses of many 'metaphors of madness'. In this article, we explore this through a few instances, starting from 1857, around the time of the First War of Independence, to 1947, when India became an independent nation. Such metaphors have their parallels both in historical as well as in contemporary times, where instances of one man's imagination becoming another's concept of irrationality and insanity continue.

Some reflections on madness and culture in the post-war world.

PubMed

Scull, Andrew

2014-12-01

This article examines the treatment of madness as a theme in drama, opera and films, concentrating its attention for the most part on the period between World War II and the 1980s. These were the years in which psychoanalysis dominated psychiatry in the USA, and so Freud's influence in the broader culture forms the central though not the sole focus of the analysis. © The Author(s) 2014.

[Food safety and animal diseases. The French Food Safety Agency, from mad cow disease to bird flu].

PubMed

Keck, Frédéric

2008-01-01

Why has the French food safety agency been particularly mobilized on zoonoses like bovine spongiform encephalopathy ("mad cow disease") or highly pathogenic avian influenza ("bird flu") ? Because sanitary crisis make explicit an ambivalent relationship between humans and animals (animals being perceived alternatively as providers of goods and as bearers of threats), and to the circulation of life in general (the contaminated blood crises being due to the rapprochement of blood giving and blood receiving). The sociology of risks needs therefore to reintegrate the idea of an intention of the risk bearer (risk with enemy), and the sociology of alimentation needs to reintegrate the analysis of the conditions of production. Mad cow disease is the paradigmatic food safety crisis because it brings together the poles of production and consumption, of animals and humans. It therefore belongs to anthropology.

[From the Scrapie syndrome of sheep and goat to the mad cow disease - the history of the discovery of prion].

PubMed

Liu, Rui; Weng, Yi

2009-05-01

Since the discovery of Scrapie Syndrome in sheep and goats in 1730, there emerged a series of diseases such as Creutzfeldt-Jakob disease, kuru disease and mad cow disease etc. In the research of kuru disease, the American scientist D. Carlteton Gajdusek found a new virus without the characteristic of DNA and RNA, which was awarded the Nobel Prize in physiology in 1976. Since then another American scientist, Stanley B. Prusiner, found a new virus-prion, taking protein as the genetic medium, which was awarded the Nobel prize in physiology and medicine in 1997. The discovery of prion is a great landmark in the research of life science, which laid a theoretical foundation for people to conquer a series of diseases such as Scrapie syndrome in sheep and goats, Creutzfeldt-Jakob disease, kuru disease and mad cow disease etc.

Transculturation of Madness: The Double Origin of Lu Xun's "Diary of a Madman".

PubMed

Ma, Xiaolu

2015-01-01

Over the years scholars have examined the allegorical features of the depiction of madness in Lu Xun's "Diary of a Madman," yet to date little research has taken into consideration the intercultural angle embedded in the narrative's intersection of three cultures, namely Russian, Japanese and Chinese. This paper traces the European-Japanese-Sino route of modern neologisms of madness to explore the introduction of such neologisms into the modern Chinese language and how it corresponds with changing patterns of knowledge and power. I use my study of transculturation on the macro scale to frame a reexamination of the lexicon in "Diary of a Madman." I focus especially on kuangren and pohaikuang, the two key words employed by Lu Xun, to see how they contribute to the ambiguity in his attitude towards the power struggle between the East and the West, the old and the new.

Between passion and repression: medical views of demon dreams, demonic fetuses, and female sexual madness in late imperial China.

PubMed

Chen, Hsiu-fen

2011-01-01

This article argues that early Chinese physicians had already related female ailments to their sexual frustration. Moreover, many physicians paid more attention to non-reproductive women – nuns, widows, and unmarried women – as if they were more prone to suffer from unfulfilled desires and sexual frustration and, as a result, produce the sexual dreams and monstrous births that were described in the medical literature of medieval China as physical ailments. The earlier body-oriented etiology of these female illnesses gradually shifted to emotion-oriented perspectives in late imperial China. In particular, the sixteenth- and seventeenth-century doctors began to categorize women's sexual frustration as "yu disorders" or "love madness." In this article I will show not only the changing medical views of female sexual madness throughout the ages, but how these views were shaped by the societies in which both the doctors and patients were situated.

Antirationalist critique or fifth column of scientism? Challenges from Doctor Who to the mad scientist trope.

PubMed

Orthia, Lindy A

2011-07-01

Much of the public understanding of science literature dealing with fictional scientists claims that scientist villains by their nature embody an antiscience critique. I characterize this claim and its founding assumptions as the "mad scientist" trope. I show how scientist villain characters from the science fiction television series Doctor Who undermine the trope via the programme's use of rhetorical strategies similar to Gilbert and Mulkay's empiricist and contingent repertoires, which define and patrol the boundaries between "science" and "non-science." I discuss three such strategies, including the literal framing of scientist villains as "mad." All three strategies exclude the characters from science, relieve science of responsibility for their villainy, and overtly or covertly contribute to the delivery of pro-science messages consistent with rationalist scientism. I focus on scientist villains from the most popular era of Doctor Who, the mid 1970s, when the show embraced the gothic horror genre.

Thin Disks Gone MAD: Magnetically Arrested Accretion in the Thin Regime

NASA Astrophysics Data System (ADS)

Avara, Mark J.; McKinney, Jonathan C.; Reynolds, Christopher S.

2015-01-01

The collection and concentration of surrounding large scale magnetic fields by black hole accretion disks may be required for production of powerful, spin driven jets. So far, accretion disks have not been shown to grow sufficient poloidal flux via the turbulent dynamo alone to produce such persistent jets. Also, there have been conflicting answers as to how, or even if, an accretion disk can collect enough magnetic flux from the ambient environment. Extending prior numerical studies of magnetically arrested disks (MAD) in the thick (angular height, H/R~1) and intermediate (H/R~.2-.6) accretion regimes, we present our latest results from fully general relativistic MHD simulations of the thinnest BH (H/R~.1) accretion disks to date exhibiting the MAD mode of accretion. We explore the significant deviations of this accretion mode from the standard picture of thin, MRI-driven accretion, and demonstrate the accumulation of large-scale magnetic flux.

Analysis of macrolinguistic aspects of narratives from individuals with Alzheimer's disease, mild cognitive impairment, and no cognitive impairment.

PubMed

Toledo, Cíntia Matsuda; Aluísio, Sandra Maria; Dos Santos, Leandro Borges; Brucki, Sonia Maria Dozzi; Trés, Eduardo Sturzeneker; de Oliveira, Maira Okada; Mansur, Letícia Lessa

2018-01-01

The depiction of features in discourse production promotes accurate diagnosis and helps to establish the therapeutic intervention in cognitive impairment and dementia. We aimed to identify alterations in the macrolinguistic aspects of discourse using a new computational tool. Sixty individuals, aged 60 years and older, were distributed in three different groups: mild Alzheimer's disease (mAD), amnestic mild cognitive impairment, and healthy controls. A narrative created by individuals was analyzed through the Coh-Metrix-Dementia program, extracting the features of interest automatically. mAD showed worse overall performance compared to the other groups: less informative discourse, greater impairment in global coherence, greater modalization, and inferior narrative structure. It was not possible to discriminate between amnestic mild cognitive impairment and healthy controls. Our results are in line with the literature, verifying a pathological change in the macrostructure of discourse in mAD.

[The discourse of psychosis in contemporary philosophy].

PubMed

Stompe, Thomas; Ritter, Kristina

2009-01-01

The preoccupation of philosophy with madness can be traced back till the Greek antiquity. For many philosophers like Descartes psychotic phenomena were symbols for the fragility of human mental powers, while others like Plato or Nietzsche saw madness as a way to escape the constraints of rationality. After 1960 three direction of contemporary philosophy dealt with the topics madness--schizophrenia--psychosis: Following Nietzsche and Bataille, Foucault as well as Deleuze and Guattari considered schizophrenia as the societal oppressed reverse of modern rationality, a notion which had a strong influence on the anti-psychiatric movement. Philosophical phenomenology primarily focussed on ontological problems of the psychotic existence. Finally Philosophy of Mind, the modern Anglo-American version of analytical philosophy, analyzed the logical coherence of psychotic inferences and experiences. Especially the insights of analytical philosophy may be important for a more sophisticated interpretation of psychopathological research as well as of the new findings of neuroscience.

Mixed anxiety depression should not be included in DSM-5.

PubMed

Batelaan, Neeltje M; Spijker, Jan; de Graaf, Ron; Cuijpers, Pim

2012-06-01

Subthreshold anxiety and subthreshold depressive symptoms often co-occur in the general population and in primary care. Based on their associated significant distress and impairment, a psychiatric classification seems justified. To enable classification, mixed anxiety depression (MAD) has been proposed as a new diagnostic category in DSM-5. In this report, we discuss arguments against the classification of MAD. More research is needed before reifying a new category we know so little about. Moreover, we argue that in patients with MAD symptoms and a history of an anxiety or depressive disorder, symptoms should be labeled as part of the course trajectories of these disorders, rather than calling it a different diagnostic entity. In patients with incident co-occurring subthreshold anxiety and subthreshold depression, subthreshold categories of both anxiety and depression could be classified to maintain a consistent classification system at both threshold and subthreshold levels.

Thinking the unthinkable: Alzheimer's, Creutzfeldt-Jakob and Mad Cow disease: the age-related reemergence of virulent, foodborne, bovine tuberculosis or losing your mind for the sake of a shake or burger.

PubMed

Broxmeyer, Lawrence

2005-01-01

The possibility of the age-related reemergence of foodborne Mycobacterium bovis (bovine tuberculosis) as a vector for Creutzfeldt-Jakob Disease (CJD or human Mad Cow Disease) and Mad Cow disease itself is real. The CDC reported last May of an outbreak of CJD linked to the consumption of meat contaminated "with the agent causing" bovine spongiform encephalopathy (BSE) in a New Jersey racetrack between the time frame 1995-2004. In the opinion of experts, ample justification exists for considering a similar pathogenesis for Alzheimer's, Creutzfeldt-Jakob and the other spongiform encephalopathies such as Mad Cow disease. In fact, Creutzfeldt-Jakob and Alzheimer's often coexist and at this point are thought to differ merely by time-dependent physical changes. A recent study links up to 13% of all "Alzheimer's" victims as really having Creutzfeldt-Jakob disease. Bovine tuberculosis, which includes Mycobacterium bovis and M. avium-intracellulare or paratuberculosis, is and has always been the most prevalent threat to the cattle industry, and the USDA reports that between 20% and 40% of US dairy herds are infected with paratuberculosis alone. The health risk for milk tainted with M. bovis has been known for decades and there was a time not so long ago when "tuberculin-tested" was printed on every milk container. Schliesser stated that meat from tuberculous animals may also constitute a significant risk of infection. At the turn of the 20th century 25% of the many US deaths from TB in adults were caused by M. bovis. Dairy products aside, when past and present meat consumption are factored in, there is three times the risk of developing Alzheimer's in meat eaters as opposed to vegetarians. The investigation into the causal trail for Creutzfeldt-Jakob, indistinguishable from Alzheimer's except for its shorter, lethal course might have grown cold where it not for Roel's and others who linked mad cow in cattle with M. bovis and related paratuberculosis on clinical, pathologic and epidemiological grounds. The southwest of the UK, the very cradle of British BSE and CJD outbreaks, saw an exponential increase in bovine tuberculosis just prior to it's spongiform outbreaks. All of this brings up the unthinkable: that Alzheimer's, Cruetzfeldt-Jackob, and Mad Cow Disease might just be caused by eating the meat or dairy in consumer products or feed. It is only appropriate therefore to explore the role of bovine TB and the atypical mycobacteria in Alzheimer's, JCD and Mad Cow disease and develop better serological surveillance for these pathogens.

Method or Madness: Federal Oversight Structures for Critical Infrastructure Protection

DTIC Science & Technology

2007-12-01

to dramatically reduce their operating costs and completely revamp their business models. In fact, many companies no longer have the capacity or...increasing reliance on private sector companies in many critical infrastructure segments, government agencies have been reluctant to try innovative...as it is applied to infrastructure services, is effectively limited to “economic growth and the free flow of commerce.”15 The collection of essays

Dual ultrasonic-assisted dispersive liquid-liquid microextraction coupled with microwave-assisted derivatization for simultaneous determination of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol by ultra high performance liquid chromatography-tandem mass spectrometry.

PubMed

Zhao, Xian-En; Lv, Tao; Zhu, Shuyun; Qu, Fei; Chen, Guang; He, Yongrui; Wei, Na; Li, Guoliang; Xia, Lian; Sun, Zhiwei; Zhang, Shijuan; You, Jinmao; Liu, Shu; Liu, Zhiqiang; Sun, Jing; Liu, Shuying

2016-03-11

This paper, for the first time, reported a speedy hyphenated technique of low toxic dual ultrasonic-assisted dispersive liquid-liquid microextraction (dual-UADLLME) coupled with microwave-assisted derivatization (MAD) for the simultaneous determination of 20(S)-protopanaxadiol (PPD) and 20(S)-protopanaxatriol (PPT). The developed method was based on ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) detection using multiple-reaction monitoring (MRM) mode. A mass spectrometry sensitizing reagent, 4'-carboxy-substituted rosamine (CSR) with high reaction activity and ionization efficiency was synthesized and firstly used as derivatization reagent. Parameters of dual-UADLLME, MAD and UHPLC-MS/MS conditions were all optimized in detail. Low toxic brominated solvents were used as extractant instead of traditional chlorinated solvents. Satisfactory linearity, recovery, repeatability, accuracy and precision, absence of matrix effect and extremely low limits of detection (LODs, 0.010 and 0.015ng/mL for PPD and PPT, respectively) were achieved. The main advantages were rapid, sensitive and environmentally friendly, and exhibited high selectivity, accuracy and good matrix effect results. The proposed method was successfully applied to pharmacokinetics of PPD and PPT in rat plasma. Copyright © 2016 Elsevier B.V. All rights reserved.

3D prostate MR-TRUS non-rigid registration using dual optimization with volume-preserving constraint

NASA Astrophysics Data System (ADS)

Qiu, Wu; Yuan, Jing; Fenster, Aaron

2016-03-01

We introduce an efficient and novel convex optimization-based approach to the challenging non-rigid registration of 3D prostate magnetic resonance (MR) and transrectal ultrasound (TRUS) images, which incorporates a new volume preserving constraint to essentially improve the accuracy of targeting suspicious regions during the 3D TRUS guided prostate biopsy. Especially, we propose a fast sequential convex optimization scheme to efficiently minimize the employed highly nonlinear image fidelity function using the robust multi-channel modality independent neighborhood descriptor (MIND) across the two modalities of MR and TRUS. The registration accuracy was evaluated using 10 patient images by calculating the target registration error (TRE) using manually identified corresponding intrinsic fiducials in the whole prostate gland. We also compared the MR and TRUS manually segmented prostate surfaces in the registered images in terms of the Dice similarity coefficient (DSC), mean absolute surface distance (MAD), and maximum absolute surface distance (MAXD). Experimental results showed that the proposed method with the introduced volume-preserving prior significantly improves the registration accuracy comparing to the method without the volume-preserving constraint, by yielding an overall mean TRE of 2:0+/-0:7 mm, and an average DSC of 86:5+/-3:5%, MAD of 1:4+/-0:6 mm and MAXD of 6:5+/-3:5 mm.

Performing skin microbiome research: A method to the madness

PubMed Central

Kong, Heidi H.; Andersson, Björn; Clavel, Thomas; Common, John E.; Jackson, Scott A.; Olson, Nathan D.; Segre, Julia A.; Traidl-Hoffmann, Claudia

2017-01-01

Growing interest in microbial contributions to human health and disease has increasingly led investigators to examine the microbiome in both healthy skin and cutaneous disorders, including acne, psoriasis and atopic dermatitis. The need for common language, effective study design, and validated methods are critical for high-quality, standardized research. Features, unique to skin, pose particular challenges when conducting microbiome research. This review discusses microbiome research standards and highlights important factors to consider, including clinical study design, skin sampling, sample processing, DNA sequencing, control inclusion, and data analysis. PMID:28063650

Spatially varying accuracy and reproducibility of prostate segmentation in magnetic resonance images using manual and semiautomated methods.

PubMed

Shahedi, Maysam; Cool, Derek W; Romagnoli, Cesare; Bauman, Glenn S; Bastian-Jordan, Matthew; Gibson, Eli; Rodrigues, George; Ahmad, Belal; Lock, Michael; Fenster, Aaron; Ward, Aaron D

2014-11-01

Three-dimensional (3D) prostate image segmentation is useful for cancer diagnosis and therapy guidance, but can be time-consuming to perform manually and involves varying levels of difficulty and interoperator variability within the prostatic base, midgland (MG), and apex. In this study, the authors measured accuracy and interobserver variability in the segmentation of the prostate on T2-weighted endorectal magnetic resonance (MR) imaging within the whole gland (WG), and separately within the apex, midgland, and base regions. The authors collected MR images from 42 prostate cancer patients. Prostate border delineation was performed manually by one observer on all images and by two other observers on a subset of ten images. The authors used complementary boundary-, region-, and volume-based metrics [mean absolute distance (MAD), Dice similarity coefficient (DSC), recall rate, precision rate, and volume difference (ΔV)] to elucidate the different types of segmentation errors that they observed. Evaluation for expert manual and semiautomatic segmentation approaches was carried out. Compared to manual segmentation, the authors' semiautomatic approach reduces the necessary user interaction by only requiring an indication of the anteroposterior orientation of the prostate and the selection of prostate center points on the apex, base, and midgland slices. Based on these inputs, the algorithm identifies candidate prostate boundary points using learned boundary appearance characteristics and performs regularization based on learned prostate shape information. The semiautomated algorithm required an average of 30 s of user interaction time (measured for nine operators) for each 3D prostate segmentation. The authors compared the segmentations from this method to manual segmentations in a single-operator (mean whole gland MAD = 2.0 mm, DSC = 82%, recall = 77%, precision = 88%, and ΔV = - 4.6 cm(3)) and multioperator study (mean whole gland MAD = 2.2 mm, DSC = 77%, recall = 72%, precision = 86%, and ΔV = - 4.0 cm(3)). These results compared favorably with observed differences between manual segmentations and a simultaneous truth and performance level estimation reference for this data set (whole gland differences as high as MAD = 3.1 mm, DSC = 78%, recall = 66%, precision = 77%, and ΔV = 15.5 cm(3)). The authors found that overall, midgland segmentation was more accurate and repeatable than the segmentation of the apex and base, with the base posing the greatest challenge. The main conclusions of this study were that (1) the semiautomated approach reduced interobserver segmentation variability; (2) the segmentation accuracy of the semiautomated approach, as well as the accuracies of recently published methods from other groups, were within the range of observed expert variability in manual prostate segmentation; and (3) further efforts in the development of computer-assisted segmentation would be most productive if focused on improvement of segmentation accuracy and reduction of variability within the prostatic apex and base.

Bovine spongiform encephalopathy: "mad cow disease".

PubMed

1996-07-01

Bovine spongiform encephalopathy (BSE), also known as "mad cow disease," is a fatal brain disease of cattle first recognized in the United Kingdom. In humans, the most common transmissible spongiform encephalopathy is Creutzfeldt-Jacob Disease (CJD). Although no cases of CJD have been directly linked to beef consumption, an advisory committee has reported that 10 recent cases of a CJD variant may be associated with BSE. This announcement has alarmed consumers well beyond the borders of the United Kingdom.

Japan-U.S. Relations: Issues for Congress

DTIC Science & Technology

2010-02-24

discovery of the first U.S. case of bovine spongiform encephalopathy (BSE or “ mad cow disease ”) in Washington state. In the months before the diagnosis in...information, see CRS Report RS21709, Mad Cow Disease and U.S. Beef Trade, by Charles E. Hanrahan and Geoffrey S. Becker. 12 International Trade Daily. May...the United States, nearly a dozen Japanese cows infected with BSE had been discovered, creating a scandal over the Agricultural Ministry’s handling

Feasibility study of proton-based quality assurance of proton range compensator

NASA Astrophysics Data System (ADS)

Park, S.; Jeong, C.; Min, B. J.; Kwak, J.; Lee, J.; Cho, S.; Shin, D.; Lim, Y. K.; Park, S. Y.; Lee, S. B.

2013-06-01

All patient specific range compensators (RCs) are customized for achieving distal dose conformity of target volume in passively scattered proton therapy. Compensators are milled precisely using a computerized machine. In proton therapy, precision of the compensator is critical and quality assurance (QA) is required to protect normal tissues and organs from radiation damage. This study aims to evaluate the precision of proton-based quality assurance of range compensator. First, the geometry information of two compensators was extracted from the DICOM Radiotherapy (RT) plan. Next, RCs were irradiated on the EBT film individually by proton beam which is modulated to have a photon-like percent depth dose (PDD). Step phantoms were also irradiated on the EBT film to generate calibration curve which indicates relationship between optical density of irradiated film and perpendicular depth of compensator. Comparisons were made using the mean absolute difference (MAD) between coordinate information from DICOM RT and converted depth information from the EBT film. MAD over the whole region was 1.7, and 2.0 mm. However, MAD over the relatively flat regions on each compensator selected for comparison was within 1 mm. These results shows that proton-based quality assurance of range compensator is feasible and it is expected to achieve MAD over the whole region less than 1 mm with further correction about scattering effect of proton imaging.

Evolution of AGL6-like MADS Box Genes in Grasses (Poaceae): Ovule Expression Is Ancient and Palea Expression Is New[W][OA

PubMed Central

Reinheimer, Renata; Kellogg, Elizabeth A.

2009-01-01

AGAMOUS-like6 (AGL6) genes encode MIKC-type MADS box transcription factors and are closely related to SEPALLATA and AP1/FUL-like genes. Here, we focus on the molecular evolution and expression of the AGL6-like genes in grasses. We have found that AGL6-like genes are expressed in ovules, lodicules (second whorl floral organs), paleas (putative first whorl floral organs), and floral meristems. Each of these expression domains was acquired at a different time in evolution, indicating that each represents a distinct function of the gene product and that the AGL6-like genes are pleiotropic. Expression in the inner integument of the ovule appears to be an ancient expression pattern corresponding to the expression of the gene in the megasporangium and integument in gymnosperms. Expression in floral meristems appears to have been acquired in the angiosperms and expression in second whorl organs in monocots. Early in grass evolution, AGL6-like orthologs acquired a new expression domain in the palea. Stamen expression is variable. Most grasses have a single AGL6-like gene (orthologous to the rice [Oryza sativa] gene MADS6). However, rice and other species of Oryza have a second copy (orthologous to rice MADS17) that appears to be the result of an ancient duplication. PMID:19749151

Measurement of urinary metanephrines to screen for pheochromocytoma in an unselected hospital referral population.

PubMed

Brain, Keith L; Kay, Jonathan; Shine, Brian

2006-11-01

Despite the rarity of pheochromocytoma, diagnosis is important because of the dangers of uncontrolled severe hypertension and the availability of very effective surgical treatment. Urinary or plasma catecholamines or catecholamine derivatives are commonly used to screen for pheochromocytomas before imaging, but data from 24-h urinary metanephrine results, patient age, and sex may better predict tumors in populations with a low pretest probability. We retrospectively studied outcomes of an unselected population (1819 patients) referred to a tertiary hospital laboratory for urinary metanephrine testing and investigated the usefulness of some simple derivative measures for detecting pheochromocytoma. We normalized values for urinary 24-h excretion of metanephrine, normetanephrine, and 3-methoxytyramine by dividing by an age- and sex-specific reference range. We then compared pheochromocytoma prediction by the use of products of these normalized measures with the gold standard of biopsy-confirmed tumor. The product of the excretion of normalized metanephrine (nMAD) and normalized normetanephrine (nNMT) (nMAD.nNMT) was a highly sensitive (100%) and specific (99.1%) measure, yielding a positive predictive value of 82%. ROC curves were not improved by including the normalized 3-methoxytyramine concentrations in the product. The test for nMAD.nNMT gave higher sensitivity and specificity than the tests for either substance alone. The test for nMAD.nNMT is a useful measure for identifying pheochromocytoma in a population with a low pretest probability.

Mad2, Bub3, and Mps1 regulate chromosome segregation and mitotic synchrony in Giardia intestinalis, a binucleate protist lacking an anaphase-promoting complex

PubMed Central

Vicente, Juan-Jesus; Cande, W. Zacheus

2014-01-01

The binucleate pathogen Giardia intestinalis is a highly divergent eukaryote with a semiopen mitosis, lacking an anaphase-promoting complex/cyclosome (APC/C) and many of the mitotic checkpoint complex (MCC) proteins. However, Giardia has some MCC components (Bub3, Mad2, and Mps1) and proteins from the cohesin system (Smc1 and Smc3). Mad2 localizes to the cytoplasm, but Bub3 and Mps1 are either located on chromosomes or in the cytoplasm, depending on the cell cycle stage. Depletion of Bub3, Mad2, or Mps1 resulted in a lowered mitotic index, errors in chromosome segregation (including lagging chromosomes), and abnormalities in spindle morphology. During interphase, MCC knockdown cells have an abnormal number of nuclei, either one nucleus usually on the left-hand side of the cell or two nuclei with one mislocalized. These results suggest that the minimal set of MCC proteins in Giardia play a major role in regulating many aspects of mitosis, including chromosome segregation, coordination of mitosis between the two nuclei, and subsequent nuclear positioning. The critical importance of MCC proteins in an organism that lacks their canonical target, the APC/C, suggests a broader role for these proteins and hints at new pathways to be discovered. PMID:25057014

Identification of pathways directly regulated by SHORT VEGETATIVE PHASE during vegetative and reproductive development in Arabidopsis

PubMed Central

2013-01-01

Background MADS-domain transcription factors play important roles during plant development. The Arabidopsis MADS-box gene SHORT VEGETATIVE PHASE (SVP) is a key regulator of two developmental phases. It functions as a repressor of the floral transition during the vegetative phase and later it contributes to the specification of floral meristems. How these distinct activities are conferred by a single transcription factor is unclear, but interactions with other MADS domain proteins which specify binding to different genomic regions is likely one mechanism. Results To compare the genome-wide DNA binding profile of SVP during vegetative and reproductive development we performed ChIP-seq analyses. These ChIP-seq data were combined with tiling array expression analysis, induction experiments and qRT-PCR to identify biologically relevant binding sites. In addition, we compared genome-wide target genes of SVP with those published for the MADS domain transcription factors FLC and AP1, which interact with SVP during the vegetative and reproductive phases, respectively. Conclusions Our analyses resulted in the identification of pathways that are regulated by SVP including those controlling meristem development during vegetative growth and flower development whereas floral transition pathways and hormonal signaling were regulated predominantly during the vegetative phase. Thus, SVP regulates many developmental pathways, some of which are common to both of its developmental roles whereas others are specific to only one of them. PMID:23759218

The petunia AGL6 gene has a SEPALLATA-like function in floral patterning.

PubMed

Rijpkema, Anneke S; Zethof, Jan; Gerats, Tom; Vandenbussche, Michiel

2009-10-01

SEPALLATA (SEP) MADS-box genes are required for the regulation of floral meristem determinacy and the specification of sepals, petals, stamens, carpels and ovules, specifically in angiosperms. The SEP subfamily is closely related to the AGAMOUS LIKE6 (AGL6) and SQUAMOSA (SQUA) subfamilies. So far, of these three groups only AGL6-like genes have been found in extant gymnosperms. AGL6 genes are more similar to SEP than to SQUA genes, both in sequence and in expression pattern. Despite the ancestry and wide distribution of AGL6-like MADS-box genes, not a single loss-of-function mutant exhibiting a clear phenotype has yet been reported; consequently the function of AGL6-like genes has remained elusive. Here, we characterize the Petunia hybrida AGL6 (PhAGL6, formerly called PETUNIA MADS BOX GENE4/pMADS4) gene, and show that it functions redundantly with the SEP genes FLORAL BINDING PROTEIN2 (FBP2) and FBP5 in petal and anther development. Moreover, expression analysis suggests a function for PhAGL6 in ovary and ovule development. The PhAGL6 and FBP2 proteins interact in in vitro experiments overall with the same partners, indicating that the two proteins are biochemically quite similar. It will be interesting to determine the functions of AGL6-like genes of other species, especially those of gymnosperms.

Control of Floral Meristem Determinacy in Petunia by MADS-Box Transcription Factors1[W

PubMed Central

Ferrario, Silvia; Shchennikova, Anna V.; Franken, John; Immink, Richard G.H.; Angenent, Gerco C.

2006-01-01

The shoot apical meristem (SAM), a small group of undifferentiated dividing cells, is responsible for the continuous growth of plants. Several genes have been identified that control the development and maintenance of the SAM. Among these, WUSCHEL (WUS) from Arabidopsis (Arabidopsis thaliana) is thought to be required for maintenance of a stem cell pool in the SAM. The MADS-box gene AGAMOUS, in combination with an unknown factor, has been proposed as a possible negative regulator of WUS, leading to the termination of meristematic activity within the floral meristem. Transgenic petunia (Petunia hybrida) plants were produced in which the E-type and D-type MADS-box genes FLORAL BINDING PROTEIN2 (FBP2) and FBP11, respectively, are simultaneously overexpressed. These plants show an early arrest in development at the cotyledon stage. Molecular analysis of these transgenic plants revealed a possible combined action of FBP2 and FBP11 in repressing the petunia WUS homolog, TERMINATOR. Furthermore, the ectopic up-regulation of the C-type and D-type homeotic genes FBP6 and FBP7, respectively, suggests that they may also participate in a complex, which causes the determinacy in transgenic plants. These data support the model that a transcription factor complex consisting of C-, D-, and E-type MADS-box proteins controls the stem cell population in the floral meristem. PMID:16428599

[The mentally ill artist--a historical retrospect].

PubMed

Bergdolt, K

1995-07-01

The painting of the mentally ill has fascinated artists and their public throughout the 20th century. Yet the psychologically as well as art-historically interesting topic can be traced back over a long period in the history of Western culture. Aristotle emphasizes that all men who create great works, such as artists, philosophers, poets and politicians, are prone to melancholy, that excess of black gall which is characteristic of artists and depressive. Although Plato distinguished between creative and clinical mania, the topos of "genius and madness" prevails up to our century. The cult of melancholy is taken up bei Marsilio Ficino and becomes fashionable among the artists of the 16th and 17th centuries. During the Romantic period of the early 19th century the psychologically unstable or even sick intellectual and artist becomes the focus of attention. Artistic madness is glorified in an almost mystical fashion. However, disillusionment was soon to follow. Schopenhauer, Lombroso and many physicians stress the close relationship between genius and madness. However, they judge madness to be merely morbid and negative. During the 20th century the artists of the avantgarde show much interest in psychoanalysis and in the art of the mentally ill. The rise of National Socialism brought about a drastic break in the appraisal of the art of the mentally ill, which today is an acknowledged factor in contemporary art.

[The suspicion of simulation. A psychiatric case history between appropriation and disciplinary action at the end of the 19th century].

PubMed

Bretthauer, Annett; Hess, Volker

2009-01-01

This case history explores how the question of agency was dealt with historically in two developing, normative orders of deviant behaviour. Examining the institutional career of the supposed adulterer, marriage swindler, and craft baker, we can trace the different observation regimes and systems of knowledge acquisition in the prison and in psychiatry, in both institutions there was talk of simulated madness; the explanations, however, were different. For the prison doctors and civil servants, the baker was a criminal; his deviant behaviour was a matter of consciously planned-out deception. For the examining psychiatrist, on the other hand, he was mentally ill and could not be held responsible for his own behaviour. The case also shows how the suspicion of simulated madness stabilized an intermediate space between the two regimes that can be seen in the incoherence of the historical sources. This conflict was never resolved; the very indecisiveness marked the defiance and agency of the historical actor that could not be clearly decided within the institutional observation regimes and their methods of recording.

The galactoside 2-α-L-fucosyltransferase FUT1 from Arabidopsis thaliana: crystallization and experimental MAD phasing.

PubMed

Rocha, Joana; Cicéron, Félix; Lerouxel, Olivier; Breton, Christelle; de Sanctis, Daniele

2016-07-01

The plant cell wall is a complex network of polysaccharides made up of cellulose, hemicelluloses and pectins. Xyloglucan (XyG), which is the main hemicellulosic component of dicotyledonous plants, has attracted much attention for its role in plant development and for its many industrial applications. The XyG-specific fucosyltransferase (FUT1) adds a fucose residue from GDP-fucose to the 2-O position of the terminal galactosyl residues on XyG side chains. Recombinant FUT1 from Arabidopsis thaliana was crystallized in two different crystal forms, with the best diffracting crystals (up to 1.95 Å resolution) belonging to the monoclinic space group P21, with unit-cell parameters a = 87.6, b = 84.5, c = 150.3 Å, β = 96.3°. Ab initio phases were determined using a two-wavelength anomalous dispersion experiment on a tantalum bromide-derivatized crystal with data collected at the rising and descending inflection points of the Ta white line. An interpretable electron-density map was obtained after elaborate density modification. Model completion and structural analysis are currently under way.

A comparison of methods for converting DCE values onto the full health-dead QALY scale.

PubMed

Rowen, Donna; Brazier, John; Van Hout, Ben

2015-04-01

Preference elicitation techniques such as time trade-off (TTO) and standard gamble (SG) receive criticism for their complexity and difficulties of use. Ordinal techniques such as discrete choice experiment (DCE) are arguably easier to understand but generate values that are not anchored onto the full health-dead 1-0 quality-adjusted life-year (QALY) scale required for use in economic evaluation. This article compares existing methods for converting modeled DCE latent values onto the full health-dead QALY scale: 1) anchoring DCE values using dead as valued in the DCE and 2) anchoring DCE values using TTO value for worst state to 2 new methods: 3) mapping DCE values onto TTO and 4) combining DCE and TTO data in a hybrid model. Models are compared using their ability to predict mean TTO health state values. We use postal DCE data (n = 263) and TTO data (n = 307) collected by interview in a general population valuation study of an asthma condition-specific measure (AQL-5D). New methods 3 and 4 using mapping and hybrid models are better able to predict mean TTO health state values (mean absolute difference [MAD], 0.052-0.084) than the anchor-based methods (MAD, 0.075-0.093) and were better able to predict mean TTO health state values even when using in their estimation a subsample of the available TTO data. These new mapping and hybrid methods have a potentially useful role for producing values on the QALY scale from data elicited using ordinal techniques such as DCE for use in economic evaluation that makes best use of the desirable properties of each elicitation technique and elicited data. Further research is encouraged. © The Author(s) 2014.

NASA Aeronautics Multidisciplinary Analysis and Design Fellowship Program

NASA Technical Reports Server (NTRS)

Grossman, B.; Gurdal, Z.; Kapania, R. K.; Mason, W. H.; Schetz, J. A.

1999-01-01

This program began as a grant from NASA Headquarters, NGT-10025, which was in effect from 10/l/93 until 10/31/96. The remaining funding for this effort was transferred from NASA Headquarters to NASA Langley and a new grant NGT-1-52155 was issued covering the period II/l/96 to 5/15/99. This report serves as the final report of NGT-1-52155. For a number of years, Virginia Tech had been on the forefront of research in the area of multidisciplinary analysis and design. In June of 1994, faculty members from aerospace and ocean engineering, engineering science and mechanics, mechanical engineering, industrial engineering, mathematics and computer sciences, at Virginia Tech joined together to form the Multidisciplinary Analysis and Design (MAD) Center for Advanced Vehicles. The center was established with the single goal: to perform research that is relevant to the needs of the US industry and to foster collaboration between the university, government and industry. In October of 1994, the center was chosen by NASA headquarters as one of the five university centers to establish a fellowship program to develop a graduate program in multidisciplinary analysis and design. The fellowship program provides full stipend and tuition support for seven U. S. students per year during their graduate studies. The grant is currently being administered by the NMO Branch of NASA Langley. To advise us regarding the problems faced by the industry, an industrial advisory board has been formed consisting of representatives from industry as well as government laboratories. The present membership includes major aerospace companies: Aurora Flight Sciences, Boeing: Philadelphia, Boeing: Long Beach, Boeing: Seattle, Boeing: St. Louis, Cessna, Ford, General Electric, Hughes, Lockheed-Martin: Palo Alto, Northrop-Grumman, Sikorsky, smaller, aerospace software companies: Aerosoft, Phoenix Integration and Proteus Engineering, along with representatives from government agencies, including: NASA Ames, Langley and Lewis. The function of the advisory board is to channel information from its member companies to faculty members concerning problems that need research attention in the general area of multidisciplinary design optimization (MDO). The faculty and their graduate students make presentations to the board on their research. The board makes recommendations on the research and suggests new areas and problems which need attention. Many students participating in the program spend 3-6 months in industry working on their research projects. We are completing the fifth year of the fellowship program and have had four advisory board meetings in Blacksburg. Ten students have spent the three month periods in industry. In addition to the research element of the MAD Center efforts we also have an academic component. We have developed a menu of design-related graduate courses and two new courses: one in Aerospace Manufacturing and another in MDO. Some of the MAD Center activities are described on the world-wide web at http://www.aoe.vt.edu/mads.html The MAD Center represents an innovative approach for joint Industry-Government-University cooperation in the development of a comprehensive program in engineering education which addresses the design needs of industry. The following charts list detail of the grant: mission of the MAD center, faculty members, purpose of the advisory board, board members, summary of the graduate and undergraduate program, history of the fellowship program, mission of the fellowship program, requirements of MAD fellows, course requirements, students supported, advisory board participants, and MAD center research papers

Predicting the Impact of Alternative Splicing on Plant MADS Domain Protein Function

PubMed Central

Severing, Edouard I.; van Dijk, Aalt D. J.; Morabito, Giuseppa; Busscher-Lange, Jacqueline; Immink, Richard G. H.; van Ham, Roeland C. H. J.

2012-01-01

Several genome-wide studies demonstrated that alternative splicing (AS) significantly increases the transcriptome complexity in plants. However, the impact of AS on the functional diversity of proteins is difficult to assess using genome-wide approaches. The availability of detailed sequence annotations for specific genes and gene families allows for a more detailed assessment of the potential effect of AS on their function. One example is the plant MADS-domain transcription factor family, members of which interact to form protein complexes that function in transcription regulation. Here, we perform an in silico analysis of the potential impact of AS on the protein-protein interaction capabilities of MIKC-type MADS-domain proteins. We first confirmed the expression of transcript isoforms resulting from predicted AS events. Expressed transcript isoforms were considered functional if they were likely to be translated and if their corresponding AS events either had an effect on predicted dimerisation motifs or occurred in regions known to be involved in multimeric complex formation, or otherwise, if their effect was conserved in different species. Nine out of twelve MIKC MADS-box genes predicted to produce multiple protein isoforms harbored putative functional AS events according to those criteria. AS events with conserved effects were only found at the borders of or within the K-box domain. We illustrate how AS can contribute to the evolution of interaction networks through an example of selective inclusion of a recently evolved interaction motif in the MADS AFFECTING FLOWERING1-3 (MAF1–3) subclade. Furthermore, we demonstrate the potential effect of an AS event in SHORT VEGETATIVE PHASE (SVP), resulting in the deletion of a short sequence stretch including a predicted interaction motif, by overexpression of the fully spliced and the alternatively spliced SVP transcripts. For most of the AS events we were able to formulate hypotheses about the potential impact on the interaction capabilities of the encoded MIKC proteins. PMID:22295091

A De Novo Floral Transcriptome Reveals Clues into Phalaenopsis Orchid Flower Development

PubMed Central

Huang, Jian-Zhi; Lin, Chih-Peng; Cheng, Ting-Chi; Chang, Bill Chia-Han; Cheng, Shu-Yu; Chen, Yi-Wen; Lee, Chen-Yu; Chin, Shih-Wen; Chen, Fure-Chyi

2015-01-01

Phalaenopsis has a zygomorphic floral structure, including three outer tepals, two lateral inner tepals and a highly modified inner median tepal called labellum or lip; however, the regulation of its organ development remains unelucidated. We generated RNA-seq reads with the Illumina platform for floral organs of the Phalaenopsis wild-type and peloric mutant with a lip-like petal. A total of 43,552 contigs were obtained after de novo assembly. We used differentially expressed gene profiling to compare the transcriptional changes in floral organs for both the wild-type and peloric mutant. Pair-wise comparison of sepals, petals and labellum between peloric mutant and its wild-type revealed 1,838, 758 and 1,147 contigs, respectively, with significant differential expression. PhAGL6a (CUFF.17763), PhAGL6b (CUFF.17763.1), PhMADS1 (CUFF.36625.1), PhMADS4 (CUFF.25909) and PhMADS5 (CUFF.39479.1) were significantly upregulated in the lip-like petal of the peloric mutant. We used real-time PCR analysis of lip-like petals, lip-like sepals and the big lip of peloric mutants to confirm the five genes’ expression patterns. PhAGL6a, PhAGL6b and PhMADS4 were strongly expressed in the labellum and significantly upregulated in lip-like petals and lip-like sepals of peloric-mutant flowers. In addition, PhAGL6b was significantly downregulated in the labellum of the big lip mutant, with no change in expression of PhAGL6a. We provide a comprehensive transcript profile and functional analysis of Phalaenopsis floral organs. PhAGL6a PhAGL6b, and PhMADS4 might play crucial roles in the development of the labellum in Phalaenopsis. Our study provides new insights into how the orchid labellum differs and why the petal or sepal converts to a labellum in Phalaenopsis floral mutants. PMID:25970572

Duplication and Whorl-Specific Down-Regulation of the Obligate AP3-PI Heterodimer Genes Explain the Origin of Paeonia lactiflora Plants with Spontaneous Corolla Mutation.

PubMed

Gong, Pichang; Ao, Xiang; Liu, Gaixiu; Cheng, Fangyun; He, Chaoying

2017-03-01

Herbaceous peony (Paeonia lactiflora) is a globally important ornamental plant. Spontaneous floral mutations occur frequently during cultivation, and are selected as a way to release new cultivars, but the underlying evolutionary developmental genetics remain largely elusive. Here, we investigated a collection of spontaneous corolla mutational plants (SCMPs) whose other floral organs were virtually unaffected. Unlike the corolla in normal plants (NPs) that withered soon after fertilization, the transformed corolla (petals) in SCMPs was greenish and persistent similar to the calyx (sepals). Epidermal cellular morphology of the SCMP corolla was also similar to that of calyx cells, further suggesting a sepaloid corolla in SCMPs. Ten floral MADS-box genes from these Paeonia plants were comparatively characterized with respect to sequence and expression. Codogenic sequence variation of these MADS-box genes was not linked to corolla changes in SCMPs. However, we found that both APETALA3 (AP3) and PISTILLATA (PI) lineages of B-class MADS-box genes were duplicated, and subsequent selective expression alterations of these genes were closely associated with the origin of SCMPs. AP3-PI obligate heterodimerization, essential for organ identity of corolla and stamens, was robustly detected. However, selective down-regulation of these duplicated genes might result in a reduction of this obligate heterodimer concentration in a corolla-specific manner, leading to the sepaloid corolla in SCMPs, thus representing a new sepaloid corolla model taking advantage of gene duplication. Our work suggests that modifying floral MADS-box genes could facilitate the breeding of novel cultivars with distinct floral morphology in ornamental plants, and also provides new insights into the functional evolution of the MADS-box genes in plants. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Anti-MAdCAM Antibody Increases ß7+ T Cells and CCR9 Gene Expression in the Peripheral Blood of Patients With Crohn's Disease.

PubMed

Hassan-Zahraee, Mina; Banerjee, Anindita; Cheng, John B; Zhang, Weidong; Ahmad, Alaa; Page, Karen; von Schack, David; Zhang, Baohong; Martin, Steven W; Nayak, Satyaprakash; Reddy, Padma; Xi, Li; Neubert, Hendrik; Fernandez Ocana, Mireia; Gorelick, Ken; Clare, Robert; Vincent, Michael; Cataldi, Fabio; Hung, Kenneth

2018-01-05

To define pharmacodynamic biomarkers in the peripheral blood of patients with Crohn's disease [CD] after treatment with PF-00547659, an anti-human mucosal addressin cell adhesion molecule-1 [MAdCAM-1] monoclonal antibody. In this Phase 2, randomised, double-blind, controlled study [OPERA], blood samples were analysed from patients with moderate to severe active CD who received placebo or 22.5 mg, 75 mg, or 225 mg of PF-00547659 subcutaneously at baseline and at Weeks 4 and 8, with follow-up at Week 12. Soluble MAdCAM [sMAdCAM] was measured by mass spectrometry, β7-expressing T cells by flow cytometry, and gene transcriptome by RNA sequencing. A slight increase in sMAdCAM was measured in the placebo group from baseline to Week 12 [6%], compared with significant decreases in all PF-00547659 groups [-87% to -98%]. A slight increase from baseline to Week 12 was observed in frequency and molecules of equivalent soluble fluorochrome for β7+ central memory T cells in the placebo group [4%], versus statistically significant increases in the active treatment groups [48% to 81%]. Similar trends were seen for β7+ effector memory T cells [placebo, 8%; PF-00547659, 84-138%] and β7+ naïve T cells [8%; 13-50%]. CCR9 gene expression had statistically significant up-regulation [p = 1.09e-06; false discovery rate < 0.1] with PF-00547659 treatment, and was associated with an increase in β7+ T cells. Results of the OPERA study demonstrate positive pharmacology and dose-dependent changes in pharmacodynamic biomarker measurements in blood, including changes in cellular composition of lymphocytes and corresponding CCR9 gene expression changes. Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com

Pharmacokinetics of surotomycin from phase 1 single and multiple ascending dose studies in healthy volunteers.

PubMed

Chandorkar, Gurudatt; Zhan, Qiao; Donovan, Julie; Rege, Shruta; Patino, Hernando

2017-03-28

Surotomycin, a novel, orally administered, cyclic, lipopeptide antibacterial in development for the treatment of Clostridium difficile-associated diarrhea, has demonstrated minimal intestinal absorption in animal models. Safety, tolerability, and plasma pharmacokinetics of single and multiple ascending oral doses (SAD/MAD) of surotomycin in healthy volunteers were characterized in two randomized, double-blind, placebo-controlled, phase 1 studies. Participants were sequentially enrolled into one of four SAD (500, 1000, 2000, 4000 mg surotomycin) or three MAD (250, 500, 1000 mg surotomycin twice/day for 14 days) cohorts. Ten subjects were randomized 4:1 into each cohort to receive surotomycin or placebo. Surotomycin plasma concentrations rose as dose increased (maximum plasma concentration [C max ]: 10.5, 21.5, 66.6, and 86.7 ng/mL). Systemic levels were generally low, with peak median surotomycin plasma concentrations observed 6-12 h after the first dose. In the MAD study, surotomycin plasma concentrations were higher on day 14 (C max : 25.5, 37.6, and 93.5 ng/mL) than on day 1 (C max : 6.8, 11.0, and 21.1 ng/mL for increasing doses), indicating accumulation. In the SAD study, <0.01% of the administered dose was recovered in urine. Mean surotomycin stool concentration from the 1000 mg MAD cohort was 6394 μg/g on day 5. Both cohorts were well tolerated with all adverse events reported as mild to moderate. Both SAD and MAD studies of surotomycin demonstrated minimal systemic exposure, with feces the primary route of elimination following oral administration; consistent with observations with similar compounds, such as fidaxomicin. Results of these phase 1 studies support the continued clinical development of surotomycin for the treatment of Clostridium difficile-associated diarrhea. NCT02835118 and NCT02835105 . Retrospectively registered, July 13 2016.

Madness and Rulers: Events in Coorg and London in 1810, as observed by the Hon. Arthur Cole, the resident at Mysore

PubMed Central

Jain, Sanjeev; Sarin, Alok

2015-01-01

What happens if a King becomes mentally ill? Excerpts from the personal papers of Arthur Henry Cole, Resident to the Kingdom of Mysore in 1809, open up fascinating insights into the madness of rulers, in neighboring Coorg and faraway London, and ways in which different societies responded to this. Musings on legal capacity and restrictions imposed on account of insanity, as well as migration and ennui in imperial colonies inevitably follow. PMID:26124533

'Robert Schumann's mental illnesses. (Genius and madness)', by Mlle Dr Pascal (1908a): Introduction and translation by Felicia Gordon.

PubMed

Gordon, Felicia

2015-09-01

Dr Constance Pascal's study of Robert Schumann's mental illnesses, dating from the early years of the twentieth century, reflects contemporary theories on the relations between gifted individuals and mental illness: the genius vs. madness debate. Pascal's reading of Schumann's musical career, in conjunction with his mental profile, offers a sympathetic and nuanced overview of the composer and a critical perspective on extant theories of his illness. © The Author(s) 2015.

Genetic Instability of Breast Cancer Cells Induced by Aberrant Expression of hMpS1

DTIC Science & Technology

2004-09-01

and function of the mitotic spindle is dependent on the MpS1 protein kinase. The components of mitotic spindle checkpoints were first identified in...yeast and their homologs of higher organisms were then identified and characterized. These include Bubl, Bub2, Bub3, Madl, Mad2, Mad3 and MpS1 . MpS 1...spindle checkpoint and centrosome duplication (1-6). Although several recent reports demonstrated that vertebrate MpS1 proteins regulate the spindle

Incorporation of Prior Knowledge of Signal Behavior Into the Reconstruction to Accelerate the Acquisition of Diffusion MRI Data.

PubMed

Abascal, Juan F P J; Desco, Manuel; Parra-Robles, Juan

2018-02-01

Diffusion MRI data are generally acquired using hyperpolarized gases during patient breath-hold, which yields a compromise between achievable image resolution, lung coverage, and number of -values. In this paper, we propose a novel method that accelerates the acquisition of diffusion MRI data by undersampling in both the spatial and -value dimensions and incorporating knowledge about signal decay into the reconstruction (SIDER). SIDER is compared with total variation (TV) reconstruction by assessing its effect on both the recovery of ventilation images and the estimated mean alveolar dimensions (MADs). Both methods are assessed by retrospectively undersampling diffusion data sets ( =8) of healthy volunteers and patients with Chronic Obstructive Pulmonary Disease (COPD) for acceleration factors between x2 and x10. TV led to large errors and artifacts for acceleration factors equal to or larger than x5. SIDER improved TV, with a lower solution error and MAD histograms closer to those obtained from fully sampled data for acceleration factors up to x10. SIDER preserved image quality at all acceleration factors, although images were slightly smoothed and some details were lost at x10. In conclusion, we developed and validated a novel compressed sensing method for lung MRI imaging and achieved high acceleration factors, which can be used to increase the amount of data acquired during breath-hold. This methodology is expected to improve the accuracy of estimated lung microstructure dimensions and provide more options in the study of lung diseases with MRI.

From Creutzfeldt-Jakob disease to the mad cow epidemic.

PubMed

Sternbach, G; Dibble, C L; Varon, J

1997-01-01

Hans-Gerhard Creutzfeldt and Alfons Jakob independently authored clinical and pathologic descriptions of a new syndrome in the 1920s. This syndrome, which subsequently came to be named after them, was characterized by dementia, motor and coordination abnormalities, a fatal course, and pathologic findings of diffuse spongiform neuronal degeneration. Although it appeared for many years to be little more than a medical curiosity, Creutzfeldt-Jakob disease attained widespread attention by its pathologic similarity to kuru and bovine spongiform encephalopathy, "mad cow disease." Because there are sporadic, familial, and iatrogenic forms of Creutzfeldt-Jakob disease, it is considered to have both genetic and infectious aspects. Although its causation has for some time been ascribed to "slow viruses," the etiology of Creutzfeldt-Jakob disease is currently thought to be due to prions, small proteinaceous infectious particles that have genetic encoding. The debate regarding whether the appearance of atypical Creutzfeldt-Jakob disease can be linked to the epidemic of "mad cow disease" is currently unresolved.

Application of multivariate statistics to vestibular testing: discriminating between Meniere's disease and migraine associated dizziness

NASA Technical Reports Server (NTRS)

Dimitri, P. S.; Wall, C. 3rd; Oas, J. G.; Rauch, S. D.

2001-01-01

Meniere's disease (MD) and migraine associated dizziness (MAD) are two disorders that can have similar symptomatologies, but differ vastly in treatment. Vestibular testing is sometimes used to help differentiate between these disorders, but the inefficiency of a human interpreter analyzing a multitude of variables independently decreases its utility. Our hypothesis was that we could objectively discriminate between patients with MD and those with MAD using select variables from the vestibular test battery. Sinusoidal harmonic acceleration test variables were reduced to three vestibulo-ocular reflex physiologic parameters: gain, time constant, and asymmetry. A combination of these parameters plus a measurement of reduced vestibular response from caloric testing allowed us to achieve a joint classification rate of 91%, independent quadratic classification algorithm. Data from posturography were not useful for this type of differentiation. Overall, our classification function can be used as an unbiased assistant to discriminate between MD and MAD and gave us insight into the pathophysiologic differences between the two disorders.

Release of Mps1 from kinetochores is crucial for timely anaphase onset.

PubMed

Jelluma, Nannette; Dansen, Tobias B; Sliedrecht, Tale; Kwiatkowski, Nicholas P; Kops, Geert J P L

2010-10-18

Mps1 kinase activity is required for proper chromosome segregation during mitosis through its involvements in microtubule-chromosome attachment error correction and the mitotic checkpoint. Mps1 dynamically exchanges on unattached kinetochores but is largely removed from kinetochores in metaphase. Here we show that Mps1 promotes its own turnover at kinetochores and that removal of Mps1 upon chromosome biorientation is a prerequisite for mitotic checkpoint silencing. Inhibition of Mps1 activity increases its half-time of recovery at unattached kinetochores and causes accumulation of Mps1 protein at these sites. Strikingly, preventing dissociation of active Mps1 from kinetochores delays anaphase onset despite normal chromosome attachment and alignment, and high interkinetochore tension. This delay is marked by continued recruitment of Mad1 and Mad2 to bioriented chromosomes and is attenuated by Mad2 depletion, indicating chronic engagement of the mitotic checkpoint in metaphase. We propose that release of Mps1 from kinetochores is essential for mitotic checkpoint silencing and a fast metaphase-to-anaphase transition.

Thin Disk Accretion in the Magnetically-Arrested State

NASA Astrophysics Data System (ADS)

Avara, Mark J.; McKinney, Jonathan; Reynolds, Christopher S.

2016-01-01

Shakura-Sunyaev thin disk theory is fundamental to black hole astrophysics. Though applications of the theory are wide-spread and powerful tools for explaining observations, such as Soltan's argument using quasar power, broadened iron line measurements, continuum fitting, and recently reverberation mapping, a significant large-scale magnetic field causes substantial deviations from standard thin disk behavior. We have used fully 3D general relativistic MHD simulations with cooling to explore the thin (H/R~0.1) magnetically arrested disk (MAD) state and quantify these deviations. This work demonstrates that accumulation of large-scale magnetic flux into the MAD state is possible, and then extends prior numerical studies of thicker disks, allowing us to measure how jet power scales with the disk state, providing a natural explanation of phenomena like jet quenching in the high-soft state of X-ray binaries. We have also simulated thin MAD disks with a misaligned black hole spin axis in order to understand further deviations from thin disk theory that may significantly affect observations.

[Michel Foucault and the persistence of psychiatric power].

PubMed

Caponi, Sandra

2009-01-01

This article aims studying the course held by Michel Foucault at the Collège de France in 1973-1974. The records of this course were published in 2003 under the name ' Psychiatric power' . The objective was to compare the different ways in which Foucault analyzes the question of madness in ' Psychiatric power' and in ' History of Madness in the Classical Age' (1961). It is a comparative study about the different ways of analyzing madness developed by Michel Foucault during the archeological and genealogic periods of his work. The absence of the body; binary diagnosis; the description of the surface of symptoms; the classification of diseases more similar to the botanical classification than to pathology; the process of cure directly linked to restitution of behaviors and moral values; as well as the over-power of the psychiatrist, seem to speak about the persistence of an old model of power, a pre-modern and pre-capitalist model, a residue of the old sovereign power.

Duplication and diversification of the LEAFY HULL STERILE1 and Oryza sativa MADS5 SEPALLATA lineages in graminoid Poales

PubMed Central

2012-01-01

Background Gene duplication and the subsequent divergence in function of the resulting paralogs via subfunctionalization and/or neofunctionalization is hypothesized to have played a major role in the evolution of plant form. The LEAFY HULL STERILE1 (LHS1) SEPALLATA (SEP) genes have been linked with the origin and diversification of the grass spikelet, but it is uncertain 1) when the duplication event that produced the LHS1 clade and its paralogous lineage Oryza sativa MADS5 (OSM5) occurred, and 2) how changes in gene structure and/or expression might have contributed to subfunctionalization and/or neofunctionalization in the two lineages. Methods Phylogenetic relationships among 84 SEP genes were estimated using Bayesian methods. RNA expression patterns were inferred using in situ hybridization. The patterns of protein sequence and RNA expression evolution were reconstructed using maximum parsimony (MP) and maximum likelihood (ML) methods, respectively. Results Phylogenetic analyses mapped the LHS1/OSM5 duplication event to the base of the grass family. MP character reconstructions estimated a change from cytosine to thymine in the first codon position of the first amino acid after the Zea mays MADS3 (ZMM3) domain converted a glutamine to a stop codon in the OSM5 ancestor following the LHS1/OSM5 duplication event. RNA expression analyses of OSM5 co-orthologs in Avena sativa, Chasmanthium latifolium, Hordeum vulgare, Pennisetum glaucum, and Sorghum bicolor followed by ML reconstructions of these data and previously published analyses estimated a complex pattern of gain and loss of LHS1 and OSM5 expression in different floral organs and different flowers within the spikelet or inflorescence. Conclusions Previous authors have reported that rice OSM5 and LHS1 proteins have different interaction partners indicating that the truncation of OSM5 following the LHS1/OSM5 duplication event has resulted in both partitioned and potentially novel gene functions. The complex pattern of OSM5 and LHS1 expression evolution is not consistent with a simple subfunctionalization model following the gene duplication event, but there is evidence of recent partitioning of OSM5 and LHS1 expression within different floral organs of A. sativa, C. latifolium, P. glaucum and S. bicolor, and between the upper and lower florets of the two-flowered maize spikelet. PMID:22340849

The neurovascular complexity index as a potential indicator of traumatic brain injury severity: A case-series study.

PubMed

Howard, Jeffrey T; Janak, Jud C; Bukhman, Vladislav; Robertson, Claudia; Frolov, Iurii; Nawn, Corinne D; Schiller, Alicia M; Convertino, Victor A

2017-07-01

Multimodal monitoring of brain physiology following a traumatic brain injury (TBI) shows promise as a strategy to improve management and outcomes of TBI patients within civilian and military trauma. Valid and reliable measures of different aspects of brain physiology following a TBI could prove critical to accurately capturing these changes. Using a case-series design with a control subject group comparison, we evaluated a new proprietary algorithm called the Neurovascular Complexity Index (NCI) using transcranial Doppler to noninvasively obtain measures of cerebral blood flow variability. Baseline NCI data from 169 control subjects were compared with 12 patients with moderate to severe TBI. Patients with TBI exhibited significantly greater mean and variability in NCI scores compared with control subjects (F = 195.48; p < 0.001). The mean absolute deviation (MAD) of NCI scores increased significantly and in a monotonic fashion with severity of injury, where control subjects exhibited a small MAD of 0.44, patients with moderate TBI had a higher MAD of 4.20, and patients with severe TBI had an MAD of 6.51 (p < 0.001). Advancement in multimodal monitoring of TBI patients is important in reducing the potential risk of secondary injury. This study reports results indicating that a new noninvasive quantifiable assessment of TBI based on a noninvasive measure of cerebral blood flow variability shows potential for continuous monitoring and early identification of brain-injured patients, deployable in far-forward military environments, to better inform individualized management. Case series, level IV.

The DAL10 gene from Norway spruce (Picea abies) belongs to a potentially gymnosperm-specific subclass of MADS-box genes and is specifically active in seed cones and pollen cones.

PubMed

Carlsbecker, Annelie; Sundström, Jens; Tandre, Karolina; Englund, Marie; Kvarnheden, Anders; Johanson, Urban; Engström, Peter

2003-01-01

Transcription factors encoded by different members of the MADS-box gene family have evolved central roles in the regulation of reproductive organ development in the flowering plants, the angiosperms. Development of the stamens and carpels, the pollen- and seed-bearing organs, involves the B- and C-organ-identity MADS-box genes. B- and C-type gene orthologs with activities specifically in developing pollen- and seed-bearing organs are also present in the distantly related gymnosperms: the conifers and the gnetophytes. We now report on the characterization of DAL10, a novel MADS-box gene from the conifer Norway spruce, which unlike the B- and C-type conifer genes shows no distinct orthology relationship to any angiosperm gene or clade in phylogenetic analyses. Like the B- and C-type genes, it is active specifically in developing pollen cones and seed cones. In situ RNA localization experiments show DAL10 to be expressed in the cone axis, which carry the microsporophylls of the young pollen cone. In contrast, in the seed cone it is expressed both in the cone axis and in the bracts, which subtend the ovuliferous scales. Expression data and the phenotype of transgenic Arabidopsis plants expressing DAL10 suggest that the gene may act upstream to or in concert with the B- and C-type genes in the establishment of reproductive identity of developing cones.

Effects of training on collagen fibril populations in the suspensory ligament and deep digital flexor tendon of young thoroughbreds.

PubMed

Patterson-Kane, J C; Firth, E C; Parry, D A; Wilson, A M; Goodship, A E

1998-01-01

To determine the effect of a specific galloping exercise regimen on collagen fibril mass-average diameters (MAD) in the deep digital flexor tendon (DDFT) and suspensory ligament (SL) of young Thoroughbreds. 12 Thoroughbred fillies, 21 +/- 1 (mean +/- SD) months old. 6 horses underwent a specific 18-month treadmill training program involving galloping exercise. The remaining 6 horses served as controls, undertaking low-volume walking exercise over the same period. Sections were excised from the midpoint of the DDFT and SL, and small strips were dissected from central and peripheral locations for each structure. Fibril diameters were measured from micrographs of transverse ultrathin sections, using a computerized image analysis program. An MAD value was calculated for the central and peripheral regions of the DDFT and SL for each horse. Values for both regions were compared between exercised and control horses. The MAD did not change significantly with exercise for either the DDFT or the SL. Loading of the DDFT as a result of this exercise regimen was not sufficient to stimulate collagen fibril hypertrophy, in keeping with current data that indicate this tendon, compared with the SL and superficial digital flexor tendon (SDFT), is subjected to low loads. Microtrauma, in terms of reduction in fibril MAD, may have occurred in the SL at a site different from that sampled. Another possibility is that, between the trot and the gallop, loading of the SL does not increase to the same extent as that of the SDFT.

Flower development of Phalaenopsis orchid involves functionally divergent SEPALLATA-like genes

PubMed Central

Pan, Zhao-Jun; Chen, You-Yi; Du, Jian-Syun; Chen, Yun-Yu; Chung, Mei-Chu; Tsai, Wen-Chieh; Wang, Chun-Neng; Chen, Hong-Hwa

2014-01-01

The Phalaenopsis orchid produces complex flowers that are commercially valuable, which has promoted the study of its flower development. E-class MADS-box genes, SEPALLATA (SEP), combined with B-, C- and D-class MADS-box genes, are involved in various aspects of plant development, such as floral meristem determination, organ identity, fruit maturation, seed formation and plant architecture. Four SEP-like genes were cloned from Phalaenopsis orchid, and the duplicated PeSEPs were grouped into PeSEP1/3 and PeSEP2/4. All PeSEPs were expressed in all floral organs. PeSEP2 expression was detectable in vegetative tissues. The study of protein–protein interactions suggested that PeSEPs may form higher order complexes with the B-, C-, D-class and AGAMOUS LIKE6-related MADS-box proteins to determine floral organ identity. The tepal became a leaf-like organ when PeSEP3 was silenced by virus-induced silencing, with alterations in epidermis identity and contents of anthocyanin and chlorophyll. Silencing of PeSEP2 had minor effects on the floral phenotype. Silencing of the E-class genes PeSEP2 and PeSEP3 resulted in the downregulation of B-class PeMADS2-6 genes, which indicates an association of PeSEP functions and B-class gene expression. These findings reveal the important roles of PeSEP in Phalaenopsis floral organ formation throughout the developmental process by the formation of various multiple protein complexes. PMID:24571782

An Optimal Design for Placements of Tsunami Observing Systems Around the Nankai Trough, Japan

NASA Astrophysics Data System (ADS)

Mulia, I. E.; Gusman, A. R.; Satake, K.

2017-12-01

Presently, there are numerous tsunami observing systems deployed in several major tsunamigenic regions throughout the world. However, documentations on how and where to optimally place such measurement devices are limited. This study presents a methodological approach to select the best and fewest observation points for the purpose of tsunami source characterizations, particularly in the form of fault slip distributions. We apply the method to design a new tsunami observation network around the Nankai Trough, Japan. In brief, our method can be divided into two stages: initialization and optimization. The initialization stage aims to identify favorable locations of observation points, as well as to determine the initial number of observations. These points are generated based on extrema of an empirical orthogonal function (EOF) spatial modes derived from 11 hypothetical tsunami events in the region. In order to further improve the accuracy, we apply an optimization algorithm called a mesh adaptive direct search (MADS) to remove redundant measurements from the initially generated points by the first stage. A combinatorial search by the MADS will improve the accuracy and reduce the number of observations simultaneously. The EOF analysis of the hypothetical tsunamis using first 2 leading modes with 4 extrema on each mode results in 30 observation points spread along the trench. This is obtained after replacing some clustered points within the radius of 30 km with only one representative. Furthermore, the MADS optimization can improve the accuracy of the EOF-generated points by approximately 10-20% with fewer observations (23 points). Finally, we compare our result with the existing observation points (68 stations) in the region. The result shows that the optimized design with fewer number of observations can produce better source characterizations with approximately 20-60% improvement of accuracies at all the 11 hypothetical cases. It should be note, however, that our design is a tsunami-based approach, some of the existing observing systems are equipped with additional devices to measure other parameter of interests, i.e., for monitoring seismic activities.

X Linkage of AP3A, a Homolog of the Y-Linked MADS-Box Gene AP3Y in Silene latifolia and S. dioica

PubMed Central

Penny, Rebecca H.; Montgomery, Benjamin R.; Delph, Lynda F.

2011-01-01

Background The duplication of autosomal genes onto the Y chromosome may be an important element in the evolution of sexual dimorphism.A previous cytological study reported on a putative example of such a duplication event in a dioecious tribe of Silene (Caryophyllaceae): it was inferred that the Y-linked MADS-box gene AP3Y originated from a duplication of the reportedly autosomal orthologAP3A. However, a recent study, also using cytological methods, indicated that AP3A is X-linked in Silenelatifolia. Methodology/Principal Findings In this study, we hybridized S. latifolia and S. dioicato investigate whether the pattern of X linkage is consistent among distinct populations, occurs in both species, and is robust to genetic methods. We found inheritance patterns indicative of X linkage of AP3A in widely distributed populations of both species. Conclusions/Significance X linkage ofAP3A and Y linkage of AP3Yin both species indicates that the genes' ancestral progenitor resided on the autosomes that gave rise to the sex chromosomesand that neither gene has moved between chromosomes since species divergence.Consequently, our results do not support the contention that inter-chromosomal gene transfer occurred in the evolution of SlAP3Y from SlAP3A. PMID:21533056

Spin polarisation of tt¯γγ production at NLO+PS with GoSam interfaced to MadGraph5_aMC@NLO

DOE PAGES

van Deurzen, Hans; Frederix, Rikkert; Hirschi, Valentin; ...

2016-04-22

Here, we present an interface between the multipurpose Monte Carlo tool MadGraph5_aMC@NLO and the automated amplitude generator GoSam. As a first application of this novel framework, we compute the NLO corrections to pp→ tt¯H and pp→ tt¯γγ matched to a parton shower. In the phenomenological analyses of these processes, we focus our attention on observables which are sensitive to the polarisation of the top quarks.

Spin polarisation of tt¯γγ production at NLO+PS with GoSam interfaced to MadGraph5_aMC@NLO

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

van Deurzen, Hans; Frederix, Rikkert; Hirschi, Valentin

Here, we present an interface between the multipurpose Monte Carlo tool MadGraph5_aMC@NLO and the automated amplitude generator GoSam. As a first application of this novel framework, we compute the NLO corrections to pp→ tt¯H and pp→ tt¯γγ matched to a parton shower. In the phenomenological analyses of these processes, we focus our attention on observables which are sensitive to the polarisation of the top quarks.

Elizabethan madness: on London's stage.

PubMed

Dalby, J T

1997-12-01

During the reign of Elizabeth I (1558-1603) a renaissance of both literary and political history occurred. The stage was transformed from primitive echoes of the morality plays to a vibrant and diverse exploration of human endeavor and man's place in the universe. The titanic literary figure of Shakespeare today veils a group of friends and challengers whose pens strove for the same goal. The depiction of madness was ubiquitous during plays of this time and reflection on the views of this group of men gives us a more reliable insight into mental illness then and today.

KENNEDY SPACE CENTER, FLA. - Several exhibit entrances within the KSC Visitor Complex are seen: The Universe Theatre, which shows the film “Quest for Life”; Mad Mission to Mars 2025, a live-action stage show; and, in the background, the Rocket Garden, featuring eight authentic rockets from the past.

NASA Image and Video Library

2003-07-22

KENNEDY SPACE CENTER, FLA. - Several exhibit entrances within the KSC Visitor Complex are seen: The Universe Theatre, which shows the film “Quest for Life”; Mad Mission to Mars 2025, a live-action stage show; and, in the background, the Rocket Garden, featuring eight authentic rockets from the past.

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

Hayashida, Misa; Malac, Marek; Egerton, Ray F.

Electron tomography is a method whereby a three-dimensional reconstruction of a nanoscale object is obtained from a series of projected images measured in a transmission electron microscope. We developed an electron-diffraction method to measure the tilt and azimuth angles, with Kikuchi lines used to align a series of diffraction patterns obtained with each image of the tilt series. Since it is based on electron diffraction, the method is not affected by sample drift and is not sensitive to sample thickness, whereas tilt angle measurement and alignment using fiducial-marker methods are affected by both sample drift and thickness. The accuracy ofmore » the diffraction method benefits reconstructions with a large number of voxels, where both high spatial resolution and a large field of view are desired. The diffraction method allows both the tilt and azimuth angle to be measured, while fiducial marker methods typically treat the tilt and azimuth angle as an unknown parameter. The diffraction method can be also used to estimate the accuracy of the fiducial marker method, and the sample-stage accuracy. A nano-dot fiducial marker measurement differs from a diffraction measurement by no more than ±1°.« less

X-ray and neutron diffraction studies of crystallinity in hydroxyapatite coatings.

PubMed

Girardin, E; Millet, P; Lodini, A

2000-02-01

To standardize industrial implant production and make comparisons between different experimental results, we have to be able to quantify the crystallinity of hydroxyapatite. Methods of measuring crystallinity ratio were developed for various HA samples before and after plasma spraying. The first series of methods uses X-ray diffraction. The advantage of these methods is that X-ray diffraction equipment is used widely in science and industry. In the second series, a neutron diffraction method is developed and the results recorded are similar to those obtained by the modified X-ray diffraction methods. The advantage of neutron diffraction is the ability to obtain measurements deep inside a component. It is a nondestructive method, owing to the very low absorption of neutrons in most materials. Copyright 2000 John Wiley & Sons, Inc.

A Computationally Efficient Parallel Levenberg-Marquardt Algorithm for Large-Scale Big-Data Inversion

NASA Astrophysics Data System (ADS)

Lin, Y.; O'Malley, D.; Vesselinov, V. V.

2015-12-01

Inverse modeling seeks model parameters given a set of observed state variables. However, for many practical problems due to the facts that the observed data sets are often large and model parameters are often numerous, conventional methods for solving the inverse modeling can be computationally expensive. We have developed a new, computationally-efficient Levenberg-Marquardt method for solving large-scale inverse modeling. Levenberg-Marquardt methods require the solution of a dense linear system of equations which can be prohibitively expensive to compute for large-scale inverse problems. Our novel method projects the original large-scale linear problem down to a Krylov subspace, such that the dimensionality of the measurements can be significantly reduced. Furthermore, instead of solving the linear system for every Levenberg-Marquardt damping parameter, we store the Krylov subspace computed when solving the first damping parameter and recycle it for all the following damping parameters. The efficiency of our new inverse modeling algorithm is significantly improved by using these computational techniques. We apply this new inverse modeling method to invert for a random transitivity field. Our algorithm is fast enough to solve for the distributed model parameters (transitivity) at each computational node in the model domain. The inversion is also aided by the use regularization techniques. The algorithm is coded in Julia and implemented in the MADS computational framework (http://mads.lanl.gov). Julia is an advanced high-level scientific programing language that allows for efficient memory management and utilization of high-performance computational resources. By comparing with a Levenberg-Marquardt method using standard linear inversion techniques, our Levenberg-Marquardt method yields speed-up ratio of 15 in a multi-core computational environment and a speed-up ratio of 45 in a single-core computational environment. Therefore, our new inverse modeling method is a powerful tool for large-scale applications.

Predicting free-living energy expenditure using a miniaturized ear-worn sensor: an evaluation against doubly labeled water.

PubMed

Bouarfa, Loubna; Atallah, Louis; Kwasnicki, Richard Mark; Pettitt, Claire; Frost, Gary; Yang, Guang-Zhong

2014-02-01

Accurate estimation of daily total energy expenditure (EE)is a prerequisite for assisted weight management and assessing certain health conditions. The use of wearable sensors for predicting free-living EE is challenged by consistent sensor placement, user compliance, and estimation methods used. This paper examines whether a single ear-worn accelerometer can be used for EE estimation under free-living conditions.An EE prediction model as first derived and validated in a controlled setting using healthy subjects involving different physical activities. Ten different activities were assessed showing a tenfold cross validation error of 0.24. Furthermore, the EE prediction model shows a mean absolute deviation(MAD) below 1.2 metabolic equivalent of tasks. The same model was applied to a free-living setting with a different population for further validation. The results were compared against those derived from doubly labeled water. In free-living settings, the predicted daily EE has a correlation of 0.74, p 0.008, and a MAD of 272 kcal day. These results demonstrate that laboratory-derived prediction models can be used to predict EE under free-living conditions [corrected].

Tensor integrand reduction via Laurent expansion

DOE PAGES

Hirschi, Valentin; Peraro, Tiziano

2016-06-09

We introduce a new method for the application of one-loop integrand reduction via the Laurent expansion algorithm, as implemented in the public C++ library Ninja. We show how the coefficients of the Laurent expansion can be computed by suitable contractions of the loop numerator tensor with cut-dependent projectors, making it possible to interface Ninja to any one-loop matrix element generator that can provide the components of this tensor. We implemented this technique in the Ninja library and interfaced it to MadLoop, which is part of the public MadGraph5_aMC@NLO framework. We performed a detailed performance study, comparing against other public reductionmore » tools, namely CutTools, Samurai, IREGI, PJFry++ and Golem95. We find that Ninja out-performs traditional integrand reduction in both speed and numerical stability, the latter being on par with that of the tensor integral reduction tool Golem95 which is however more limited and slower than Ninja. Lastly, we considered many benchmark multi-scale processes of increasing complexity, involving QCD and electro-weak corrections as well as effective non-renormalizable couplings, showing that Ninja’s performance scales well with both the rank and multiplicity of the considered process.« less

Transgenic Suppression of AGAMOUS Genes in Apple Reduces Fertility and Increases Floral Attractiveness

PubMed Central

Klocko, Amy L.; Borejsza-Wysocka, Ewa; Brunner, Amy M.; Shevchenko, Olga; Aldwinckle, Herb; Strauss, Steven H.

2016-01-01

We investigated the ability of RNA interference (RNAi) directed against two co-orthologs of AGAMOUS (AG) from Malus domestica (domestic apple, MdAG) to reduce the risks of invasiveness and provide genetic containment of transgenes, while also promoting the attractiveness of flowers for ornamental usage. Suppression of two MdAG-like genes, MdMADS15 and MdMADS22, led to the production of trees with highly showy, polypetalous flowers. These “double-flowers” had strongly reduced expression of both MdAG-like genes. Members of the two other clades within in the MdAG subfamily showed mild to moderate differences in gene expression, or were unchanged, with the level of suppression approximately proportional to the level of sequence identity between the gene analyzed and the RNAi fragment. The double-flowers also exhibited reduced male and female fertility, had few viable pollen grains, a decreased number of stigmas, and produced few viable seeds after cross-pollination. Despite these floral alterations, RNAi-AG trees with double-flowers set full-sized fruit. Suppression or mutation of apple AG-like genes appears to be a promising method for combining genetic containment with improved floral attractiveness. PMID:27500731

Effects of surgical vs. nonsurgical therapy on erectile dysfunction and quality of life in obstructive sleep apnea syndrome: a pilot study.

PubMed

Shin, Hyun-Woo; Park, Ju-Hyun; Park, Jong-Wan; Rhee, Chae-Seo; Lee, Chul Hee; Min, Yang-Gi; Kim, Dong-Young

2013-08-01

Obstructive sleep apnea syndrome (OSAS) is associated with erectile dysfunction (ED). The improvement of ED after medical therapy including continuous positive airway pressure (CPAP) or mandibular advancement devices (MADs) is still controversial. Furthermore, the efficacy of surgical treatment has been little investigated. The aim of this nonrandomized prospective study was to evaluate the effects of surgical (uvulopalatopharyngoplasty [UPPP]) and nonsurgical approaches (CPAP and MAD) on ED and quality of life (QOL) in OSAS. OSAS patients underwent UPPP (N = 30), CPAP (N = 16), or MAD (N = 10) and completed the Korean versions of the International Index of Erectile Function questionnaire (KIIEF-5) and the Calgary Sleep Apnea Quality of Life Index (SAQLI) before and after a median of 7 months of treatment (interquartile range, 4-15 months). All patients underwent a full-night in-laboratory polysomnography at baseline and follow-up. The main outcome measures are the KIIEF-5 and SAQLI scores. CPAP group showed older age, higher body mass index, and more severe OSAS than other groups. Apnea-hypopnea index and lowest oxygen saturation level improved significantly in all groups, but Epworth Sleepiness Scale score decreased significantly in UPPP and MAD groups. Significant increase of KIIEF-5 was observed in patients who underwent UPPP (P = 0.039, paired t-test), but not in nonsurgical treatment group. All groups had the tendency of better QOL after treatment, but statistical significance was found only in MAD group. Neck circumference (r = 0.360, P = 0.006) and KIIEF-5 score (r = -0.484, P < 0.001) at baseline were significantly related to the improvement of KIIEF-5. This study demonstrated that ED in OSAS may improve following UPPP. Better disease-specific QOL was observed after both surgical and nonsurgical therapies in OSAS. These findings suggest that interventions for OSAS can provide the alleviation of ED and increase QOL in OSAS patients with ED, especially if they had pronounced complaints of ED and wide neck circumferences. © 2013 International Society for Sexual Medicine.

Characterization of TM8, a MADS-box gene expressed in tomato flowers.

PubMed

Daminato, Margherita; Masiero, Simona; Resentini, Francesca; Lovisetto, Alessandro; Casadoro, Giorgio

2014-11-30

The identity of flower organs is specified by various MIKC MADS-box transcription factors which act in a combinatorial manner. TM8 is a MADS-box gene that was isolated from the floral meristem of a tomato mutant more than twenty years ago, but is still poorly known from a functional point of view in spite of being present in both Angiosperms and Gymnosperms, with some species harbouring more than one copy of the gene. This study reports a characterization of TM8 that was carried out in transgenic tomato plants with altered expression of the gene. Tomato plants over-expressing either TM8 or a chimeric repressor form of the gene (TM8:SRDX) were prepared. In the TM8 up-regulated plants it was possible to observe anomalous stamens with poorly viable pollen and altered expression of several floral identity genes, among them B-, C- and E-function ones, while no apparent morphological modifications were visible in the other whorls. Oblong ovaries and fruits, that were also parthenocarpic, were obtained in the plants expressing the TM8:SRDX repressor gene. Such ovaries showed modified expression of various carpel-related genes. No apparent modifications could be seen in the other flower whorls. The latter plants had also epinastic leaves and malformed flower abscission zones. By using yeast two hybrid assays it was possible to show that TM8 was able to interact in yeast with MACROCALIX. The impact of the ectopically altered TM8 expression on the reproductive structures suggests that this gene plays some role in the development of the tomato flower. MACROCALYX, a putative A-function MADS-box gene, was expressed in all the four whorls of fully developed flowers, and showed quantitative variations that were opposite to those of TM8 in the anomalous stamens and ovaries. Since the TM8 protein interacted in vitro only with the A-function MADS-box protein MACROCALYX, it seems that for the correct differentiation of the tomato reproductive structures possible interactions between TM8 and MACROCALYX proteins might be important.

Spectral methods in edge-diffraction theories

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

Arnold, J.M.

Spectral methods for the construction of uniform asymptotic representations of the field diffracted by an aperture in a plane screen are reviewed. These are separated into contrasting approaches, roughly described as physical and geometrical. It is concluded that the geometrical methods provide a direct route to the construction of uniform representations that are formally identical to the equivalent-edge-current concept. Some interpretive and analytical difficulties that complicate the physical methods of obtaining uniform representations are analyzed. Spectral synthesis proceeds directly from the ray geometry and diffraction coefficients, without any intervening current representation, and the representation is uniform at shadow boundaries andmore » caustics of the diffracted field. The physical theory of diffraction postulates currents on the diffracting screen that give rise to the diffracted field. The difficulties encountered in evaluating the current integrals are throughly examined, and it is concluded that the additional data provided by the physical theory of diffraction (diffraction coefficients off the Keller diffraction cone) are not actually required for obtaining uniform asymptotics at the leading order. A new diffraction representation that generalizes to arbitrary plane-convex apertures a formula given by Knott and Senior [Proc. IEEE 62, 1468 (1974)] for circular apertures is deduced. 34 refs., 1 fig.« less

Integration of BpMADS4 on various linkage groups improves the utilization of the rapid cycle breeding system in apple.

PubMed

Weigl, Kathleen; Wenzel, Stephanie; Flachowsky, Henryk; Peil, Andreas; Hanke, Magda-Viola

2015-02-01

Rapid cycle breeding in apple is a new approach for the rapid introgression of agronomically relevant traits (e.g. disease resistances) from wild apple species into domestic apple cultivars (Malus × domestica Borkh.). This technique drastically shortens the long-lasting juvenile phase of apple. The utilization of early-flowering apple lines overexpressing the BpMADS4 gene of the European silver birch (Betula pendula Roth.) in hybridization resulted in one breeding cycle per year. Aiming for the selection of non-transgenic null segregants at the end of the breeding process, the flower-inducing transgene and the gene of interest (e.g. resistance gene) that will be introgressed by hybridization need to be located on different chromosomes. To improve the flexibility of the existing approach in apple, this study was focused on the development and characterization of eleven additional BpMADS4 overexpressing lines of four different apple cultivars. In nine lines, the flowering gene was mapped to different linkage groups. The differences in introgressed T-DNA sequences and plant genome deletions post-transformation highlighted the unique molecular character of each line. However, transgenic lines demonstrated no significant differences in flower organ development and pollen functionality compared with non-transgenic plants. Hybridization studies using pollen from the fire blight-resistant wild species accession Malus fusca MAL0045 and the apple scab-resistant cultivar 'Regia' indicated that BpMADS4 introgression had no significant effect on the breeding value of each transgenic line. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Terminator field-aligned current system: A new finding from model-assimilated data set (MADS)

NASA Astrophysics Data System (ADS)

Zhu, L.; Schunk, R. W.; Scherliess, L.; Sojka, J. J.; Gardner, L. C.; Eccles, J. V.; Rice, D.

2013-12-01

Physics-based data assimilation models have been recognized by the space science community as the most accurate approach to specify and forecast the space weather of the solar-terrestrial environment. The model-assimilated data sets (MADS) produced by these models constitute an internally consistent time series of global three-dimensional fields whose accuracy can be estimated. Because of its internal consistency of physics and completeness of descriptions on the status of global systems, the MADS has also been a powerful tool to identify the systematic errors in measurements, reveal the missing physics in physical models, and discover the important dynamical physical processes that are inadequately observed or missed by measurements due to observational limitations. In the past years, we developed a data assimilation model for the high-latitude ionospheric plasma dynamics and electrodynamics. With a set of physical models, an ensemble Kalman filter, and the ingestion of data from multiple observations, the data assimilation model can produce a self-consistent time-series of the complete descriptions of the global high-latitude ionosphere, which includes the convection electric field, horizontal and field-aligned currents, conductivity, as well as 3-D plasma densities and temperatures, In this presentation, we will show a new field-aligned current system discovered from the analysis of the MADS produced by our data assimilation model. This new current system appears and develops near the ionospheric terminator. The dynamical features of this current system will be described and its connection to the active role of the ionosphere in the M-I coupling will be discussed.

Early Cone Setting in Picea abies acrocona Is Associated with Increased Transcriptional Activity of a MADS Box Transcription Factor1[W][OA

PubMed Central

Uddenberg, Daniel; Reimegård, Johan; Clapham, David; Almqvist, Curt; von Arnold, Sara; Emanuelsson, Olof; Sundström, Jens F.

2013-01-01

Conifers normally go through a long juvenile period, for Norway spruce (Picea abies) around 20 to 25 years, before developing male and female cones. We have grown plants from inbred crosses of a naturally occurring spruce mutant (acrocona). One-fourth of the segregating acrocona plants initiate cones already in their second growth cycle, suggesting control by a single locus. The early cone-setting properties of the acrocona mutant were utilized to identify candidate genes involved in vegetative-to-reproductive phase change in Norway spruce. Poly(A+) RNA samples from apical and basal shoots of cone-setting and non-cone-setting plants were subjected to high-throughput sequencing (RNA-seq). We assembled and investigated 33,383 expressed putative protein-coding acrocona transcripts. Eight transcripts were differentially expressed between selected sample pairs. One of these (Acr42124_1) was significantly up-regulated in apical shoot samples from cone-setting acrocona plants, and the encoded protein belongs to the MADS box gene family of transcription factors. Using quantitative real-time polymerase chain reaction with independently derived plant material, we confirmed that the MADS box gene is up-regulated in both needles and buds of cone-inducing shoots when reproductive identity is determined. Our results constitute important steps for the development of a rapid cycling model system that can be used to study gene function in conifers. In addition, our data suggest the involvement of a MADS box transcription factor in the vegetative-to-reproductive phase change in Norway spruce. PMID:23221834

Elder women's decision-making in breast cancer care: An Israeli study.

PubMed

Kadmon, Ilana; Pierce, Penny; Antonakos, Cathy L

2012-07-01

Much research has examined women's decision-making behaviour in breast cancer care. Patient age has shaped preferences, values, decision style and participation in treatment decisions. The aim of this study was to test the validity of the Michigan Assessment of Decision Style (MADS) (Pierce, 1995) in an older cohort and provide information on decision styles to identify areas of tailored decision support necessary for Israeli women. This study examined the decision-making styles of older Israeli women receiving routine mammography screening. Fifty two women over 65 years of age, attending a routine mammography screening, were administered a questionnaire containing demographic information and the MADS to determine hypothetical treatment decision-making. The MADS is a 16-item questionnaire assessing decision-making behaviour by characterizing four factors: avoiding, deferring, information-seeking and deliberation. Age, family history of breast cancer, and having a current mammography were not significantly associated with any of the four MADS factors. Deliberation and Deferring had the highest mean scores, followed closely by Information-Seeking and Avoidance. Correlations among the factors indicate a significant, positive correlation between Deliberation and Information-Seeking and a significant negative correlation between Deliberation and Deferring, consistent with previous studies. These findings indicate that older Israeli women's decision style is characterized by information seeking and deliberation reflecting a disposition towards engagement. The findings contribute to clinicians' understanding of women's preferences by countering the traditionally accepted stereotype that older women will employ a passive role when faced with an important health care decision. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effect of exercise on age-related changes in collagen fibril diameter distributions in the common digital extensor tendons of young horses.

PubMed

Edwards, Lindsey J; Goodship, Allen E; Birch, Helen L; Patterson-Kane, Janet C

2005-04-01

To determine whether specific treadmill exercise regimens would accelerate age-related changes in collagen fibril diameter distributions in the common digital extensor tendon (CDET) of the forelimbs of young Thoroughbreds. 24 female Thoroughbreds. Horses were trained for 18 weeks (6 horses; short term) or 18 months (5 horses; long term) on a high-speed treadmill; 2 age-matched control groups (6 horses/group) performed walking exercise only. Horses were (mean +/- SD) 24 +/- 1 months and 39 +/- 1 months old at termination of the short-term and long-term regimens, respectively. Midmetacarpal CDET specimens were obtained and processed for transmission electron microscopy. Diameter and area of at least 1,000 collagen fibrils/specimen were measured by use of computerized image analysis. Mass-average diameter (MAD) of collagen fibrils and collagen fibril index were calculated for each horse. Collagen fibril MAD for the older horses was significantly less than that for the younger horses. Exercise did not significantly affect fibril diameter or distributions in either age group, and collagen fibril index did not differ significantly between groups. Age-related reduction in collagen fibril MAD agreed with findings for other tendons and species. Training did not accelerate age-related change in the CDET in contrast to a reported decrease in collagen fibril MAD in the superficial digital flexor tendon of horses trained long term. Our results support the concept that the functionally distinct nature of the CDET and superficial digital flexor tendon in horses results in fundamentally different responses to high-speed exercise regimens.

Dispersion corrected hartree-fock and density functional theory for organic crystal structure prediction.

PubMed

Brandenburg, Jan Gerit; Grimme, Stefan

2014-01-01

We present and evaluate dispersion corrected Hartree-Fock (HF) and Density Functional Theory (DFT) based quantum chemical methods for organic crystal structure prediction. The necessity of correcting for missing long-range electron correlation, also known as van der Waals (vdW) interaction, is pointed out and some methodological issues such as inclusion of three-body dispersion terms are discussed. One of the most efficient and widely used methods is the semi-classical dispersion correction D3. Its applicability for the calculation of sublimation energies is investigated for the benchmark set X23 consisting of 23 small organic crystals. For PBE-D3 the mean absolute deviation (MAD) is below the estimated experimental uncertainty of 1.3 kcal/mol. For two larger π-systems, the equilibrium crystal geometry is investigated and very good agreement with experimental data is found. Since these calculations are carried out with huge plane-wave basis sets they are rather time consuming and routinely applicable only to systems with less than about 200 atoms in the unit cell. Aiming at crystal structure prediction, which involves screening of many structures, a pre-sorting with faster methods is mandatory. Small, atom-centered basis sets can speed up the computation significantly but they suffer greatly from basis set errors. We present the recently developed geometrical counterpoise correction gCP. It is a fast semi-empirical method which corrects for most of the inter- and intramolecular basis set superposition error. For HF calculations with nearly minimal basis sets, we additionally correct for short-range basis incompleteness. We combine all three terms in the HF-3c denoted scheme which performs very well for the X23 sublimation energies with an MAD of only 1.5 kcal/mol, which is close to the huge basis set DFT-D3 result.

Motion compensation for cone-beam CT using Fourier consistency conditions

NASA Astrophysics Data System (ADS)

Berger, M.; Xia, Y.; Aichinger, W.; Mentl, K.; Unberath, M.; Aichert, A.; Riess, C.; Hornegger, J.; Fahrig, R.; Maier, A.

2017-09-01

In cone-beam CT, involuntary patient motion and inaccurate or irreproducible scanner motion substantially degrades image quality. To avoid artifacts this motion needs to be estimated and compensated during image reconstruction. In previous work we showed that Fourier consistency conditions (FCC) can be used in fan-beam CT to estimate motion in the sinogram domain. This work extends the FCC to 3\\text{D} cone-beam CT. We derive an efficient cost function to compensate for 3\\text{D} motion using 2\\text{D} detector translations. The extended FCC method have been tested with five translational motion patterns, using a challenging numerical phantom. We evaluated the root-mean-square-error and the structural-similarity-index between motion corrected and motion-free reconstructions. Additionally, we computed the mean-absolute-difference (MAD) between the estimated and the ground-truth motion. The practical applicability of the method is demonstrated by application to respiratory motion estimation in rotational angiography, but also to motion correction for weight-bearing imaging of knees. Where the latter makes use of a specifically modified FCC version which is robust to axial truncation. The results show a great reduction of motion artifacts. Accurate estimation results were achieved with a maximum MAD value of 708 μm and 1184 μm for motion along the vertical and horizontal detector direction, respectively. The image quality of reconstructions obtained with the proposed method is close to that of motion corrected reconstructions based on the ground-truth motion. Simulations using noise-free and noisy data demonstrate that FCC are robust to noise. Even high-frequency motion was accurately estimated leading to a considerable reduction of streaking artifacts. The method is purely image-based and therefore independent of any auxiliary data.

Core shifts, magnetic fields and magnetization of extragalactic jets

NASA Astrophysics Data System (ADS)

Zdziarski, Andrzej A.; Sikora, Marek; Pjanka, Patryk; Tchekhovskoy, Alexander

2015-07-01

We study the effect of radio-jet core shift, which is a dependence of the position of the jet radio core on the observational frequency. We derive a new method of measuring the jet magnetic field based on both the value of the shift and the observed radio flux, which complements the standard method that assumes equipartition. Using both methods, we re-analyse the blazar sample of Zamaninasab et al. We find that equipartition is satisfied only if the jet opening angle in the radio core region is close to the values found observationally, ≃0.1-0.2 divided by the bulk Lorentz factor, Γj. Larger values, e.g. 1/Γj, would imply magnetic fields much above equipartition. A small jet opening angle implies in turn the magnetization parameter of ≪1. We determine the jet magnetic flux taking into account this effect. We find that the transverse-averaged jet magnetic flux is fully compatible with the model of jet formation due to black hole (BH) spin-energy extraction and the accretion being a magnetically arrested disc (MAD). We calculate the jet average mass-flow rate corresponding to this model and find it consists of a substantial fraction of the mass accretion rate. This suggests the jet composition with a large fraction of baryons. We also calculate the average jet power, and find it moderately exceeds the accretion power, dot{M} c^2, reflecting BH spin energy extraction. We find our results for radio galaxies at low Eddington ratios are compatible with MADs but require a low radiative efficiency, as predicted by standard accretion models.

Quantification of esophageal wall thickness in CT using atlas-based segmentation technique

NASA Astrophysics Data System (ADS)

Wang, Jiahui; Kang, Min Kyu; Kligerman, Seth; Lu, Wei

2015-03-01

Esophageal wall thickness is an important predictor of esophageal cancer response to therapy. In this study, we developed a computerized pipeline for quantification of esophageal wall thickness using computerized tomography (CT). We first segmented the esophagus using a multi-atlas-based segmentation scheme. The esophagus in each atlas CT was manually segmented to create a label map. Using image registration, all of the atlases were aligned to the imaging space of the target CT. The deformation field from the registration was applied to the label maps to warp them to the target space. A weighted majority-voting label fusion was employed to create the segmentation of esophagus. Finally, we excluded the lumen from the esophagus using a threshold of -600 HU and measured the esophageal wall thickness. The developed method was tested on a dataset of 30 CT scans, including 15 esophageal cancer patients and 15 normal controls. The mean Dice similarity coefficient (DSC) and mean absolute distance (MAD) between the segmented esophagus and the reference standard were employed to evaluate the segmentation results. Our method achieved a mean Dice coefficient of 65.55 ± 10.48% and mean MAD of 1.40 ± 1.31 mm for all the cases. The mean esophageal wall thickness of cancer patients and normal controls was 6.35 ± 1.19 mm and 6.03 ± 0.51 mm, respectively. We conclude that the proposed method can perform quantitative analysis of esophageal wall thickness and would be useful for tumor detection and tumor response evaluation of esophageal cancer.

AN EXPERIMENTAL STUDY OF "MAD ITCH" WITH ESPECIAL REFERENCE TO ITS RELATIONSHIP TO PSEUDORABIES

PubMed Central

Shope, Richard E.

1931-01-01

The clinical picture and gross pathology of spontaneous and experimental "mad itch" have been described and the inciting agent has been shown to be a filtrable virus. It has been possible to prepare virucidal serum capable of neutralizing the virus. Fatal infections are regularly produced in rabbits when the virus is administered subcutaneously, intracerebrally, intravenously, intratesticularly, intraperitoneally, intranasally, or when it is dropped on a scarified area of skin. Its infectivity for other species by various routes is reported upon. The rabbit, guinea pig, white rat, white mouse, gray field mouse, cow, cat, duck, chicken, and hog are susceptible to experimental infection. The disease is not contagious under laboratory conditions and the virus is restricted in the animal body largely to the region of inoculation and the lung. The virus can be stored for relatively long periods in 50 per cent glycerol or in the dried state. A comparison of "mad itch" with pseudorabies leads to the tentative conclusion that the inciting agents of both are the same, although the strains of the two viruses that are under study possess readily demonstrable differences PMID:19869913

A MAD Model for Gamma-Ray Burst Variability

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

Lloyd-Ronning, Nicole Marie; Dolence, Joshua C.; Fryer, Christopher Lee

Here we present a model for the temporal variability of long gamma-ray bursts during the prompt phase (the highly variable first 100 seconds or so), in the context of a magnet- ically arrested disk (MAD) around a black hole. In this state, sufficient magnetic flux is held on to the black hole such that it stalls the accretion near the inner region of the disk. The system transitions in and out of the MAD state, which we relate to the vari- able luminosity of the GRB during the prompt phase, with a characteristic timescale defined by the free fall timemore » in the region over which the accretion is arrested. We present simple analytic estimates of the relevant energetics and timescales, and com- pare them to gamma-ray burst observations. In particular, we show how this model can reproduce the characteristic one second time scale that emerges from various analyses of the prompt emission light curve. Finally, we also discuss how our model can accommodate the potentially physically important correlation between a burst quiescent time and the duration of its subsequent pulse (Ramirez-Ruiz & Merloni 2001).« less

Opera and neuroscience.

PubMed

Lorusso, Lorenzo; Franchini, Antonia Francesca; Porro, Alessandro

2015-01-01

Opera is the most complete form of theatrical representation, characterized by musical accompaniment, both instrumental and vocal. It has played an important role in sociocultural spheres, affecting the various social strata and reflecting customs and ideas in different centuries. Composers have created pieces that have also shown the development of medicine. Since the birth of opera in seventeenth century in Italy, neuroscience has played an important role in influencing the representation of madness and neurological aspects. From the Folly of the Renaissance, a path toward a representation of madness was developed, initially linked to the myths of classical antiquity. In the seventeenth and eighteenth centuries, madness was represented as comical or funny, of a loving nature and influenced by the spread of the Commedia dell'Arte (Comedy of Art). In the nineteenth century, with the rise of the first scientific theories of the mind, insanity took more precise connotations and was separated from other psychiatric and neurological diseases. The operas of the twentieth century depicted psychiatric and neurological diseases, taking into account newer medical and scientific discoveries. © 2015 Elsevier B.V. All rights reserved.

"May all Be Shattered into God": Mary Barnes and Her Journey through Madness in Kingsley Hall.

PubMed

Chapman, Adrian

2018-06-02

Contributing to renewed scholarly interest in R. D. Laing and his circle, and in the radical therapeutic community of Kingsley Hall, London (1965-1970), this article offers the first article-length reading of Mary Barnes' and Joseph Berke's Mary Barnes: Two Accounts of a Journey through Madness. This text offers views of anti-psychiatry 'on the ground' that critique the 1960s utopianism of Laing's championing of madness as a metanoic, quasi-psychedelic voyage. Barnes' story, too, reveals tensions within the anti-psychiatric movement. Moving beyond existing criticism of the text, Barnes, it is argued here, emerges as far more than an exemplary patient, victim or anti-psychiatric puppet. Particular attention is paid in this reading of Two Accounts to the following: the ways in which the spiritually inclined Barnes and the psychoanalytic Berke differ in this dual narrative text; the ways in which each differs from Laing; the metaphor of the journey; and the setting of Barnes' story in the often conflicted, experimental household of Kingsley Hall.

Changes in growth conditions alter the male strobilus gene expression pattern in Cryptomeria japonica.

PubMed

Fukui, Mitsue

2003-11-01

Two-year old saplings grown from cuttings of Cryptomeria japonica D. Don initiate strobilus development following treatment with gibberellic acid under long-day photoperiods. At 25 degrees C with a 14-h photoperiod in a phytotron, male strobili initiated normally; however, they remained green and fell from the saplings prematurely. To examine the change in male strobilus development at the molecular level, three genes expressed specifically in male strobili were analyzed. Two were MADS box genes homologous to the B-function genes in angiosperms, CjMADS1 and CjMADS2, and the third was Cry j I, which encodes an allergen protein, and this gene is expressed mainly in microspores. Under phytotron growing conditions, the homeotic genes were expressed constantly, which reflected the extended early developmental stage of male strobili. On the other hand, Cry j I expression was detected after a long delay just before strobilus development ceased. These results indicate that the expression of the genes related to male reproductive development in C. japonica is regulated by a factor(s) that is sensitive to environmental signals.

Cesare Lombroso: an anthropologist between evolution and degeneration.

PubMed

Mazzarello, Paolo

2011-01-01

Cesare Lombroso (1835-1909) was a prominent Italian medical doctor and intellectual in the second half of the nineteenth century. He became world famous for his theory that criminality, madness and genius were all sides of the same psychobiological condition: an expression of degeneration, a sort of regression along the phylogenetic scale, and an arrest at an early stage of evolution. Degeneration affected criminals especially, in particular the "born delinquent" whose development had stopped at an early stage, making them the most "atavistic" types of human being. Lombroso also advocated the theory that genius was closely linked with madness. A man of genius was a degenerate, an example of retrograde evolution in whom madness was a form of "biological compensation" for excessive intellectual development. To confirm this theory, in August 1897, Lombroso, while attending the Twelfth International Medical Congress in Moscow, decided to meet the great Russian writer Lev Tolstoy in order to directly verify, in him, his theory of degeneration in the genius. Lombroso's anthropological ideas fuelled a heated debate on the biological determinism of human behaviour.

A role for the Rab6A′ GTPase in the inactivation of the Mad2-spindle checkpoint

PubMed Central

Miserey-Lenkei, Stéphanie; Couëdel-Courteille, Anne; Del Nery, Elaine; Bardin, Sabine; Piel, Matthieu; Racine, Victor; Sibarita, Jean-Baptiste; Perez, Franck; Bornens, Michel; Goud, Bruno

2006-01-01

The two isoforms of the Rab6 GTPase, Rab6A and Rab6A′, regulate a retrograde transport route connecting early endosomes and the endoplasmic reticulum via the Golgi complex in interphasic cells. Here we report that when Rab6A′ function is altered cells are unable to progress normally through mitosis. Such cells are blocked in metaphase, despite displaying a normal Golgi fragmentation and with the Mad2-spindle checkpoint activated. Furthermore, the Rab6 effector p150Glued, a subunit of the dynein/dynactin complex, remains associated with some kinetochores. A similar phenotype was observed when GAPCenA, a GTPase-activating protein of Rab6, was depleted from cells. Our results suggest that Rab6A′ likely regulates the dynamics of the dynein/dynactin complex at the kinetochores and consequently the inactivation of the Mad2-spindle checkpoint. Rab6A′, through its interaction with p150Glued and GAPCenA, may thus participate in a pathway involved in the metaphase/anaphase transition. PMID:16395330

Regulation of kinetochore recruitment of two essential mitotic spindle checkpoint proteins by Mps1 phosphorylation.

PubMed

Xu, Quanbin; Zhu, Songcheng; Wang, Wei; Zhang, Xiaojuan; Old, William; Ahn, Natalie; Liu, Xuedong

2009-01-01

Mps1 is a protein kinase that plays essential roles in spindle checkpoint signaling. Unattached kinetochores or lack of tension triggers recruitment of several key spindle checkpoint proteins to the kinetochore, which delays anaphase onset until proper attachment or tension is reestablished. Mps1 acts upstream in the spindle checkpoint signaling cascade, and kinetochore targeting of Mps1 is required for subsequent recruitment of Mad1 and Mad2 to the kinetochore. The mechanisms that govern recruitment of Mps1 or other checkpoint proteins to the kinetochore upon spindle checkpoint activation are incompletely understood. Here, we demonstrate that phosphorylation of Mps1 at T12 and S15 is required for Mps1 recruitment to the kinetochore. Mps1 kinetochore recruitment requires its kinase activity and autophosphorylation at T12 and S15. Mutation of T12 and S15 severely impairs its kinetochore association and markedly reduces recruitment of Mad2 to the kinetochore. Our studies underscore the importance of Mps1 autophosphorylation in kinetochore targeting and spindle checkpoint signaling.

A MAD model for gamma-ray burst variability

NASA Astrophysics Data System (ADS)

Lloyd-Ronning, Nicole M.; Dolence, Joshua C.; Fryer, Christopher L.

2016-09-01

We present a model for the temporal variability of long gamma-ray bursts (GRBs) during the prompt phase (the highly variable first 100 s or so), in the context of a magnetically arrested disc (MAD) around a black hole. In this state, sufficient magnetic flux is held on to the black hole such that it stalls the accretion near the inner region of the disc. The system transitions in and out of the MAD state, which we relate to the variable luminosity of the GRB during the prompt phase, with a characteristic time-scale defined by the free-fall time in the region over which the accretion is arrested. We present simple analytic estimates of the relevant energetics and time-scales, and compare them to GRB observations. In particular, we show how this model can reproduce the characteristic one second time-scale that emerges from various analyses of the prompt emission light curve. We also discuss how our model can accommodate the potentially physically important correlation between a burst quiescent time and the duration of its subsequent pulse.

A MAD Model for Gamma-Ray Burst Variability

DOE PAGES

Lloyd-Ronning, Nicole Marie; Dolence, Joshua C.; Fryer, Christopher Lee

2016-06-09

Here we present a model for the temporal variability of long gamma-ray bursts during the prompt phase (the highly variable first 100 seconds or so), in the context of a magnet- ically arrested disk (MAD) around a black hole. In this state, sufficient magnetic flux is held on to the black hole such that it stalls the accretion near the inner region of the disk. The system transitions in and out of the MAD state, which we relate to the vari- able luminosity of the GRB during the prompt phase, with a characteristic timescale defined by the free fall timemore » in the region over which the accretion is arrested. We present simple analytic estimates of the relevant energetics and timescales, and com- pare them to gamma-ray burst observations. In particular, we show how this model can reproduce the characteristic one second time scale that emerges from various analyses of the prompt emission light curve. Finally, we also discuss how our model can accommodate the potentially physically important correlation between a burst quiescent time and the duration of its subsequent pulse (Ramirez-Ruiz & Merloni 2001).« less

BTA Magnet Field Map Archive and MAD Model

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

Glenn,J.W.

2008-04-01

This note publishes some and information that has resided in private files. The attached tables were provided by Joseph Skelly from his archives. They show magnetic field measurements versus excitation current for the Booster to AGS transfer line quadrupoles and dipoles based on field measurements [we believe] were done by the Magnet Division. Also given are Ed Blesser's fifth order fits of field versus current. The results are given in 'Tesla' or T-M/M. These tables are attached to provide an archive of this data. The MAD model of the BTA line does have the same values as shown in themore » attached fits so the transfer was correct. MAD uses as its 'gradient' for quads Tesla per meter normalized to rigidity [B-rho]. The model of the BTA line in use uses the T-M/M given in the tables divided by the length to give T M which is then normalized by Brho. Thus, the input to the model appears to be correct. The original model is also attached as part of a memo by Skelly describing it.« less

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

DOE PAGES

Ye, Qiaozhen; Rosenberg, Scott C.; Moeller, Arne; ...

2015-04-28

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from amore » signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.« less

Comparative evaluation of Bacopa monniera and Panax quniquefolium in experimental anxiety and depressive models in mice.

PubMed

Chatterjee, Manavi; Verma, Pinki; Palit, Gautam

2010-03-01

The present study was undertaken to compare medicinal plants against mixed anxiety-depressive disorder (MAD) to evaluate their potency in combating MAD disorders. Previous studies from our lab have shown that Bacopa monniera (BM), and Panax quniquefolium (PQ) have significant adaptogenic properties. Hence, we have further confirmed their activity in stress related disorders like anxiety and depression in animal model, rodents and assessed their efficacy. In our experimental protocol, gross behaviour was observed through Digiscan animal activity monitor. Anxiety was studied through light dark test, elevated plus maze test and holeboard test. Depression experiments were conducted following tail suspension test and forced swim test. Further, rotarod test was also used to study any defects in motor in-coordination in mice. It was observed that BM at the dose of 80 mg/kg (po) and PQ at 100 mg/kg (po) were effective as an anti-anxiety as well anti-depressant activity and had no motor in-coordination in mice. Hence, these extracts can be used as a potent therapeutic agent in treating mixed anxiety-depressive disorder (MAD).

Near-field diffraction from amplitude diffraction gratings: theory, simulation and results

NASA Astrophysics Data System (ADS)

Abedin, Kazi Monowar; Rahman, S. M. Mujibur

2017-08-01

We describe a computer simulation method by which the complete near-field diffract pattern of an amplitude diffraction grating can be generated. The technique uses the method of iterative Fresnel integrals to calculate and generate the diffraction images. Theoretical background as well as the techniques to perform the simulation is described. The program is written in MATLAB, and can be implemented in any ordinary PC. Examples of simulated diffraction images are presented and discussed. The generated images in the far-field where they reduce to Fraunhofer diffraction pattern are also presented for a realistic grating, and compared with the results predicted by the grating equation, which is applicable in the far-field. The method can be used as a tool to teach the complex phenomenon of diffraction in classrooms.

The Killer Will Remain Free: On Pat Parker and the Poetics of Madness.

PubMed

Ali, Kazim

2015-01-01

Poet and scholar Kazim Ali reads Pat Parker's Movement in Black intimately, one poet to another, uncovering the shadow-fact of the lives of most people of color: not only the anger that is somehow sublimated into every part of our lives but also the issue that carrying this feeling around has on our mental health itself-that "anger" and "madness" might have sources in one another. Ali concludes that Parker offers a brutal and clear-eyed and ultimately hopeful assessment of the conditions that were faced at the time, and even now, by communities of color.

The influence of media communication on risk perception and behavior related to mad cow disease in South Korea.

PubMed

Park, Jee-Eun; Sohn, Aeree

2013-08-01

The purpose of this study was to ascertain the influence of media communication on risk behavior related to mad cow disease (MCD). Mothers of elementary school students in Seoul were recruited as the survey participants of this study. Media reports affected risk behavior related to MCD. Also, knowledge and attitude toward MCD affects risk behavior. Risk-related information provided by the media should maintain consistency and objectivity. For effective risk communication, there should be an open communication between the government and public, experts, and related industries, who should all collaborate.

Coupled optics reconstruction from TBT data using MAD-X

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

Alexahin, Y.; Gianfelice-Wendt, E.; /Fermilab

2007-06-01

Turn-by-turn BPM data provide immediate information on the coupled optics functions at BPM locations. In the case of small deviations from the known (design) uncoupled optics some cognizance of the sources of perturbation, BPM calibration errors and tilts can also be inferred without detailed lattice modeling. In practical situations, however, fitting the lattice model with the help of some optics code would lead to more reliable results. We present an algorithm for coupled optics reconstruction from TBT data on the basis of MAD-X and give examples of its application for the Fermilab Tevatron accelerator.

Does UV CETI Suffer from the Mad Syndrome?

NASA Technical Reports Server (NTRS)

Drake, Jeremy

1999-01-01

Photometric data have been analyzed and searched for events of flaring and other variability. Some flaring has been detected, though probably not at a level that will hinder our continuing spectral analysis. X-ray diagnostics for the very hot coronal emission measure are under investigation in order to determine whether or not the very hot coronal plasma contributes significantly to the observed X-ray flux in the (EUV) Extreme Ultraviolet Radiation. The key test of the MAD syndrome lies in whether or not the coronal lines indicate a depletion in metals in the corona relative to the underlying photosphere.

Confrontation of the Magnetically Arrested Disc scenario with observations of FR II sources

NASA Astrophysics Data System (ADS)

Rusinek, Katarzyna; Sikora, Marek

2017-10-01

The main aim of our work was to check whether powers of jets in FR II radio galaxies (RGs) and quasars (QSOs) can be reproduced by the Magnetically Arrested Disc (MAD) scenario. Assuming that established in the recent numerical simulations of the MAD scenario the (H/R)^2 dependence of the jet production efficiency is correct, we demonstrate that in order to reproduce the observed jet powers in FR II sources: (i) accretion discs must be geometrically much thicker than the standard ones; (ii) and/or that the jet production is strongly modulated.

Detection and characterization of murine colitis and carcinogenesis by molecularly targeted contrast-enhanced ultrasound

PubMed Central

Brückner, Markus; Heidemann, Jan; Nowacki, Tobias M; Cordes, Friederike; Stypmann, Jörg; Lenz, Philipp; Gohar, Faekah; Lügering, Andreas; Bettenworth, Dominik

2017-01-01

AIM To study mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) and vascular endothelial growth factor (VEGF)-targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis. METHODS C57BL/6 mice were challenged with 3% dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAdCAM-1-targeted contrast agent was used to detect and quantify MAdCAM-1 expression. Inflammatory driven colorectal azoxymethane (AOM)/DSS-induced carcinogenesis was examined on day 42 and 84 using VEGF-targeted contrast agent. Highly specific tissue echogenicity was quantified using specialized software. Sonographic findings were correlated to tissue staining, western blot analysis and immunohistochemistry to quantify the degree of inflammation and stage of carcinogenesis. RESULTS Native ultrasound detected increased general bowel wall thickening that correlated with more progressed and more severe DSS-colitis (healthy mice: 0.3 mm ± 0.03 vs six days DSS: 0.5 mm ± 0.2 vs nine days DSS: 0.6 mm ± 0.2, P < 0.05). Moreover, these sonographic findings correlated well with clinical parameters such as weight loss (r2 = 0.74) and histological damage (r2 = 0.86) (P < 0.01). In acute DSS-induced murine colitis, CEUS targeted against MAdCAM-1 detected and differentiated stages of mild, moderate and severe colitis via calculation of mean pixel contrast intensity in decibel (9.6 dB ± 1.6 vs 12.9 dB ± 1.4 vs 18 dB ± 3.33, P < 0.05). Employing the AOM/DSS-induced carcinogenesis model, tumor development was monitored by CEUS targeted against VEGF and detected a significantly increased echogenicity in tumors as compared to adjacent healthy mucosa (healthy mucosa, 1.6 dB ± 1.4 vs 42 d, 18.2 dB ± 3.3 vs 84 d, 18.6 dB ± 4.9, P < 0.01). Tissue echogenicity strongly correlated with histological analysis and immunohistochemistry findings (VEGF-positive cells in 10 high power fields of healthy mucosa: 1 ± 1.2 vs 42 d after DSS start: 2.4 ± 1.6 vs 84 d after DSS start: 3.5 ± 1.3, P < 0.01). CONCLUSION Molecularly targeted CEUS is a highly specific and non-invasive imaging modality, which characterizes murine intestinal inflammation and carcinogenesis in vivo. PMID:28522908

Application of focused-beam flat-sample method to synchrotron powder X-ray diffraction with anomalous scattering effect

NASA Astrophysics Data System (ADS)

Tanaka, M.; Katsuya, Y.; Matsushita, Y.

2013-03-01

The focused-beam flat-sample method (FFM), which is a method for high-resolution and rapid synchrotron X-ray powder diffraction measurements by combination of beam focusing optics, a flat shape sample and an area detector, was applied for diffraction experiments with anomalous scattering effect. The advantages of FFM for anomalous diffraction were absorption correction without approximation, rapid data collection by an area detector and good signal-to-noise ratio data by focusing optics. In the X-ray diffraction experiments of CoFe2O4 and Fe3O4 (By FFM) using X-rays near the Fe K absorption edge, the anomalous scattering effect between Fe/Co or Fe2+/Fe3+ can be clearly detected, due to the change of diffraction intensity. The change of observed diffraction intensity as the incident X-ray energy was consistent with the calculation. The FFM is expected to be a method for anomalous powder diffraction.

Rietveld analysis using powder diffraction data with anomalous scattering effect obtained by focused beam flat sample method

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

Tanaka, Masahiko, E-mail: masahiko@spring8.or.jp; Katsuya, Yoshio, E-mail: katsuya@spring8.or.jp; Sakata, Osami, E-mail: SAKATA.Osami@nims.go.jp

2016-07-27

Focused-beam flat-sample method (FFM) is a new trial for synchrotron powder diffraction method, which is a combination of beam focusing optics, flat shape powder sample and area detectors. The method has advantages for X-ray diffraction experiments applying anomalous scattering effect (anomalous diffraction), because of 1. Absorption correction without approximation, 2. High intensity X-rays of focused incident beams and high signal noise ratio of diffracted X-rays 3. Rapid data collection with area detectors. We applied the FFM to anomalous diffraction experiments and collected synchrotron X-ray powder diffraction data of CoFe{sub 2}O{sub 4} (inverse spinel structure) using X-rays near Fe K absorptionmore » edge, which can distinguish Co and Fe by anomalous scattering effect. We conducted Rietveld analyses with the obtained powder diffraction data and successfully determined the distribution of Co and Fe ions in CoFe{sub 2}O{sub 4} crystal structure.« less

SESAME, A 3rd Generation Synchrotron Light Source for the Middle East

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

Einfeld, D.; Hasnain, S.S.; Sayers, Z.

2004-05-12

Developed under the auspices of UNESCO, SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East) will be a major international research centre in the Middle East and Mediterranean region. On 6th of January 2003, the official foundation of SESAME took place. The facility is located in Allan, Jordan, 30 km North-West of Amman. As of August 2003 the Founding Members are Bahrain, Egypt, Iran, Israel, Jordan, Pakistan, Palestine, Turkey and United Arabic Emirates, representing a population of over 300 million. SESAME will be a 2.5 GeV 3rd Generation light source (emittance 24.6 nm.rad, circumference {approx}125m). About 40% ofmore » the circumference is available for insertion devices (average length 2.75m) in 13 straight sections. Beam lines are up to 36m. The site and a building are provided by Jordan. Construction started in August 2003. The scientific program will start with up to 6 beam lines: MAD Protein Crystallography, SAXS and WAXS for polymers and proteins, Powder Diffraction for material science, UV/VUV/SXR Photoelectron Spectroscopy and Photoabsorption Spectroscopy, IR Spectroscopy, and EXAFS.« less

Focusing, collimation and flux throughput at the IMCA-CAT bending-magnet beamline at the Advanced Photon Source

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

Koshelev, Irina; Huang, Rong; Graber, Timothy

2009-09-02

The IMCA-CAT bending-magnet beamline was upgraded with a collimating mirror in order to achieve the energy resolution required to conduct high-quality multi- and single-wavelength anomalous diffraction (MAD/SAD) experiments without sacrificing beamline flux throughput. Following the upgrade, the bending-magnet beamline achieves a flux of 8 x 10{sup 11} photons s{sup -1} at 1 {angstrom} wavelength, at a beamline aperture of 1.5 mrad (horizontal) x 86 {mu}rad (vertical), with energy resolution (limited mostly by the intrinsic resolution of the monochromator optics) {delta}E/E = 1.5 x 10{sup -4} (at 10 kV). The beamline operates in a dynamic range of 7.5-17.5 keV and deliversmore » to the sample focused beam of size (FWHM) 240 {micro}m (horizontally) x 160 {micro}m (vertically). The performance of the 17-BM beamline optics and its deviation from ideally shaped optics is evaluated in the context of the requirements imposed by the needs of protein crystallography experiments. An assessment of flux losses is given in relation to the (geometric) properties of major beamline components.« less

Expression, purification and preliminary crystallographic analysis of oligopeptidase B from Trypanosoma brucei

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

Rea, Dean; Hazell, Carole; Andrews, Norma W.

2006-08-01

Recombinant oligopeptidase B from T. brucei has been prepared and crystallized. Data were collected to 2.7 Å. Heavy-atom soaks and preparation of selenomethionine-substituted protein are in progress for structure determination by MAD or MIR. African sleeping sickness, also called trypanosomiasis, is a significant cause of morbidity and mortality in sub-Saharan Africa. Peptidases from Trypanosoma brucei, the causative agent, include the serine peptidase oligopeptidase B, a documented virulence factor and therapeutic target. Determination of the three-dimensional structure of oligopeptidase B is desirable to facilitate the development of novel inhibitors. Oligopeptidase B was overexpressed in Escherichia coli as an N-terminally hexahistidine-tagged fusionmore » protein, purified using metal-affinity chromatography and crystallized using the hanging-drop vapour-diffusion technique in 7%(w/v) polyethylene glycol 6000, 1 M LiCl, 0.1 M bis-tris propane pH 7.5. Diffraction data to 2.7 Å resolution were collected using synchrotron radiation. The crystals belong to space group P3{sub 1}21 or P3{sub 2}21, with unit-cell parameters a = b = 124.5, c = 249.9 Å. A complete data set to 2.7 Å was collected using synchrotron radiation.« less

Estimating Additive and Non-Additive Genetic Variances and Predicting Genetic Merits Using Genome-Wide Dense Single Nucleotide Polymorphism Markers

PubMed Central

Su, Guosheng; Christensen, Ole F.; Ostersen, Tage; Henryon, Mark; Lund, Mogens S.

2012-01-01

Non-additive genetic variation is usually ignored when genome-wide markers are used to study the genetic architecture and genomic prediction of complex traits in human, wild life, model organisms or farm animals. However, non-additive genetic effects may have an important contribution to total genetic variation of complex traits. This study presented a genomic BLUP model including additive and non-additive genetic effects, in which additive and non-additive genetic relation matrices were constructed from information of genome-wide dense single nucleotide polymorphism (SNP) markers. In addition, this study for the first time proposed a method to construct dominance relationship matrix using SNP markers and demonstrated it in detail. The proposed model was implemented to investigate the amounts of additive genetic, dominance and epistatic variations, and assessed the accuracy and unbiasedness of genomic predictions for daily gain in pigs. In the analysis of daily gain, four linear models were used: 1) a simple additive genetic model (MA), 2) a model including both additive and additive by additive epistatic genetic effects (MAE), 3) a model including both additive and dominance genetic effects (MAD), and 4) a full model including all three genetic components (MAED). Estimates of narrow-sense heritability were 0.397, 0.373, 0.379 and 0.357 for models MA, MAE, MAD and MAED, respectively. Estimated dominance variance and additive by additive epistatic variance accounted for 5.6% and 9.5% of the total phenotypic variance, respectively. Based on model MAED, the estimate of broad-sense heritability was 0.506. Reliabilities of genomic predicted breeding values for the animals without performance records were 28.5%, 28.8%, 29.2% and 29.5% for models MA, MAE, MAD and MAED, respectively. In addition, models including non-additive genetic effects improved unbiasedness of genomic predictions. PMID:23028912

SU-G-JeP3-05: Geometry Based Transperineal Ultrasound Probe Positioning for Image Guided Radiotherapy

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

Camps, S; With, P de; Verhaegen, F

2016-06-15

Purpose: The use of ultrasound (US) imaging in radiotherapy is not widespread, primarily due to the need for skilled operators performing the scans. Automation of probe positioning has the potential to remove this need and minimize operator dependence. We introduce an algorithm for obtaining a US probe position that allows good anatomical structure visualization based on clinical requirements. The first application is on 4D transperineal US images of prostate cancer patients. Methods: The algorithm calculates the probe position and orientation using anatomical information provided by a reference CT scan, always available in radiotherapy workflows. As initial test, we apply themore » algorithm on a CIRS pelvic US phantom to obtain a set of possible probe positions. Subsequently, five of these positions are randomly chosen and used to acquire actual US volumes of the phantom. Visual inspection of these volumes reveal if the whole prostate, and adjacent edges of bladder and rectum are fully visualized, as clinically required. In addition, structure positions on the acquired US volumes are compared to predictions of the algorithm. Results: All acquired volumes fulfill the clinical requirements as specified in the previous section. Preliminary quantitative evaluation was performed on thirty consecutive slices of two volumes, on which the structures are easily recognizable. The mean absolute distances (MAD) between actual anatomical structure positions and positions predicted by the algorithm were calculated. This resulted in MAD of 2.4±0.4 mm for prostate, 3.2±0.9 mm for bladder and 3.3±1.3 mm for rectum. Conclusion: Visual inspection and quantitative evaluation show that the algorithm is able to propose probe positions that fulfill all clinical requirements. The obtained MAD is on average 2.9 mm. However, during evaluation we assumed no errors in structure segmentation and probe positioning. In future steps, accurate estimation of these errors will allow for better evaluation of the achieved accuracy.« less

Sampling factors influencing accuracy of sperm kinematic analysis.

PubMed

Owen, D H; Katz, D F

1993-01-01

Sampling conditions that influence the accuracy of experimental measurement of sperm head kinematics were studied by computer simulation methods. Several archetypal sperm trajectories were studied. First, mathematical models of typical flagellar beats were input to hydrodynamic equations of sperm motion. The instantaneous swimming velocities of such sperm were computed over sequences of flagellar beat cycles, from which the resulting trajectories were determined. In a second, idealized approach, direct mathematical models of trajectories were utilized, based upon similarities to the previous hydrodynamic constructs. In general, it was found that analyses of sampling factors produced similar results for the hydrodynamic and idealized trajectories. A number of experimental sampling factors were studied, including the number of sperm head positions measured per flagellar beat, and the time interval over which these measurements are taken. It was found that when one flagellar beat is sampled, values of amplitude of lateral head displacement (ALH) and linearity (LIN) approached their actual values when five or more sample points per beat were taken. Mean angular displacement (MAD) values, however, remained sensitive to sampling rate even when large sampling rates were used. Values of MAD were also much more sensitive to the initial starting point of the sampling procedure than were ALH or LIN. On the basis of these analyses of measurement accuracy for individual sperm, simulations were then performed of cumulative effects when studying entire populations of motile cells. It was found that substantial (double digit) errors occurred in the mean values of curvilinear velocity (VCL), LIN, and MAD under the conditions of 30 video frames per second and 0.5 seconds of analysis time. Increasing the analysis interval to 1 second did not appreciably improve the results. However, increasing the analysis rate to 60 frames per second significantly reduced the errors. These findings thus suggest that computer-aided sperm analysis (CASA) application at 60 frames per second will significantly improve the accuracy of kinematic analysis in most applications to human and other mammalian sperm.

SU-E-J-158: Audiovisual Biofeedback Reduces Image Artefacts in 4DCT: A Digital Phantom Study

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

Pollock, S; Kipritidis, J; Lee, D

2015-06-15

Purpose: Irregular breathing motion has a deleterious impact on 4DCT image quality. The breathing guidance system: audiovisual biofeedback (AVB) is designed to improve breathing regularity, however, its impact on 4DCT image quality has yet to be quantified. The purpose of this study was to quantify the impact of AVB on thoracic 4DCT image quality by utilizing the digital eXtended Cardiac Torso (XCAT) phantom driven by lung tumor motion patterns. Methods: 2D tumor motion obtained from 4 lung cancer patients under two breathing conditions (i) without breathing guidance (free breathing), and (ii) with guidance (AVB). There were two breathing sessions, yieldingmore » 8 tumor motion traces. This tumor motion was synchronized with the XCAT phantom to simulate 4DCT acquisitions under two acquisition modes: (1) cine mode, and (2) prospective respiratory-gated mode. Motion regularity was quantified by the root mean square error (RMSE) of displacement. The number of artefacts was visually assessed for each 4DCT and summed up for each breathing condition. Inter-session anatomic reproducibility was quantified by the mean absolute difference (MAD) between the Session 1 4DCT and Session 2 4DCT. Results: AVB improved tumor motion regularity by 30%. In cine mode, the number of artefacts was reduced from 61 in free breathing to 40 with AVB, in addition to AVB reducing the MAD by 34%. In gated mode, the number of artefacts was reduced from 63 in free breathing to 51 with AVB, in addition to AVB reducing the MAD by 23%. Conclusion: This was the first study to compare the impact of breathing guidance on 4DCT image quality compared to free breathing, with AVB reducing the amount of artefacts present in 4DCT images in addition to improving inter-session anatomic reproducibility. Results thus far suggest that breathing guidance interventions could have implications for improving radiotherapy treatment planning and interfraction reproducibility.« less

A strategy for improved computational efficiency of the method of anchored distributions

NASA Astrophysics Data System (ADS)

Over, Matthew William; Yang, Yarong; Chen, Xingyuan; Rubin, Yoram

2013-06-01

This paper proposes a strategy for improving the computational efficiency of model inversion using the method of anchored distributions (MAD) by "bundling" similar model parametrizations in the likelihood function. Inferring the likelihood function typically requires a large number of forward model (FM) simulations for each possible model parametrization; as a result, the process is quite expensive. To ease this prohibitive cost, we present an approximation for the likelihood function called bundling that relaxes the requirement for high quantities of FM simulations. This approximation redefines the conditional statement of the likelihood function as the probability of a set of similar model parametrizations "bundle" replicating field measurements, which we show is neither a model reduction nor a sampling approach to improving the computational efficiency of model inversion. To evaluate the effectiveness of these modifications, we compare the quality of predictions and computational cost of bundling relative to a baseline MAD inversion of 3-D flow and transport model parameters. Additionally, to aid understanding of the implementation we provide a tutorial for bundling in the form of a sample data set and script for the R statistical computing language. For our synthetic experiment, bundling achieved a 35% reduction in overall computational cost and had a limited negative impact on predicted probability distributions of the model parameters. Strategies for minimizing error in the bundling approximation, for enforcing similarity among the sets of model parametrizations, and for identifying convergence of the likelihood function are also presented.

Bayesian approach for three-dimensional aquifer characterization at the Hanford 300 Area

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

Murakami, Haruko; Chen, X.; Hahn, Melanie S.

2010-10-21

This study presents a stochastic, three-dimensional characterization of a heterogeneous hydraulic conductivity field within DOE's Hanford 300 Area site, Washington, by assimilating large-scale, constant-rate injection test data with small-scale, three-dimensional electromagnetic borehole flowmeter (EBF) measurement data. We first inverted the injection test data to estimate the transmissivity field, using zeroth-order temporal moments of pressure buildup curves. We applied a newly developed Bayesian geostatistical inversion framework, the method of anchored distributions (MAD), to obtain a joint posterior distribution of geostatistical parameters and local log-transmissivities at multiple locations. The unique aspects of MAD that make it suitable for this purpose are itsmore » ability to integrate multi-scale, multi-type data within a Bayesian framework and to compute a nonparametric posterior distribution. After we combined the distribution of transmissivities with depth-discrete relative-conductivity profile from EBF data, we inferred the three-dimensional geostatistical parameters of the log-conductivity field, using the Bayesian model-based geostatistics. Such consistent use of the Bayesian approach throughout the procedure enabled us to systematically incorporate data uncertainty into the final posterior distribution. The method was tested in a synthetic study and validated using the actual data that was not part of the estimation. Results showed broader and skewed posterior distributions of geostatistical parameters except for the mean, which suggests the importance of inferring the entire distribution to quantify the parameter uncertainty.« less

Beam propagation modeling of modified volume Fresnel zone plates fabricated by femtosecond laser direct writing.

PubMed

Srisungsitthisunti, Pornsak; Ersoy, Okan K; Xu, Xianfan

2009-01-01

Light diffraction by volume Fresnel zone plates (VFZPs) is simulated by the Hankel transform beam propagation method (Hankel BPM). The method utilizes circularly symmetric geometry and small step propagation to calculate the diffracted wave fields by VFZP layers. It is shown that fast and accurate diffraction results can be obtained with the Hankel BPM. The results show an excellent agreement with the scalar diffraction theory and the experimental results. The numerical method allows more comprehensive studies of the VFZP parameters to achieve higher diffraction efficiency.

An action spectrum for UV-B radiation and the rat lens.

PubMed

Merriam, J C; Löfgren, S; Michael, R; Söderberg, P; Dillon, J; Zheng, L; Ayala, M

2000-08-01

To determine an action spectrum for UV-B radiation and the rat lens and to show the effect of the atmosphere and the cornea on the action spectrum. One eye of young female rats was exposed to 5-nm bandwidths of UV-B radiation (290, 295, 300, 305, 310, and 315 nm). Light scattering of exposed and nonexposed lenses was measured 1 week after irradiation. A quadratic polynomial was fit to the dose-response curve for each wave band. The dose at each wave band that produced a level of light scattering greater than 95% of the nonexposed lenses was defined as the maximum acceptable dose (MAD). Transmittance of the rat cornea was measured with a fiberoptic spectrophotometer. The times to be exposed to the MAD in Stockholm (59.3 degrees N) and La Palma (28 degrees N) were compared. Significant light scattering was detected after UV-B at 295, 300, 305, 310, and 315 nm. The lens was most sensitive to UV-B at 300 nm. Correcting for corneal transmittance showed that the rat lens is at least as sensitive to UV radiation at 295 nm as at 300 nm. The times to be exposed to the MAD at each wave band were greater in Stockholm than in La Palma, and in both locations the theoretical time to be exposed to the MAD was least at 305 nm. After correcting for corneal transmittance, the biological sensitivity of the rat lens to UV-B is at least as great at 295 nm as at 300 nm. After correcting for transmittance by the atmosphere, UV-B at 305 nm is the most likely wave band to injure the rat lens in both Stockholm and La Palma.

Neutrophil-to-lymphocyte ratio decreases in obstructive sleep apnea treated with mandibular advancement devices.

PubMed

Al-Halawani, Moh'd; Naik, Sreelatha; Chan, Michael; Kreinin, Iouri; Meiers, Jonathan; Kryger, Meir

2018-02-07

Obstructive sleep apnea has been associated with chronic inflammation triggered by nocturnal hypoxemia. The neutrophil-to-lymphocyte ratio (NLR) is a measure of subclinical systemic inflammation. We hypothesize that NLR levels would improve as chronic inflammation diminishes in obstructive sleep apnea (OSA) patients treated with mandibular advancement devices (MADs). We studied patients with OSA who were treated with MAD as a first-line treatment or because they could not tolerate CPAP. We obtained pre-treatment and post-treatment complete blood counts. NLR was calculated by dividing the number of neutrophils by the number of lymphocytes obtained from the CBCs. Patients with other conditions known to affect NLR were excluded from the study. We compared the values of NLR and oxygen desaturation index (ODI) before and after treatment with MAD in 22 patients who met inclusion criteria and completed the study protocol. There was a significant difference in NLR before and after treatment (p = 0.01). There was also a significant difference in the 3% ODI and 4% ODI before and after treatment with MAD (p = 0.014, 0.007), respectively. A subgroup analysis compared NLR in two groups of patients, the optimally treated and suboptimally treated. There was a significant decrease in the NLR in the optimally treated group (n = 10) (p < 0.01), whereas it did not change in the suboptimally treated group (n = 12) (p = 0.349). The neutrophil-to-lymphocyte ratio may be useful in documenting improvement in inflammation for OSA patients treated with mandibular advancement devices. Our results specifically suggest that the NLR values are associated with the decrease in the ODI.

Increased lymphocyte trafficking to colonic microvessels is dependent on MAdCAM-1 and C-C chemokine mLARC/CCL20 in DSS-induced mice colitis.

PubMed

Teramoto, K; Miura, S; Tsuzuki, Y; Hokari, R; Watanabe, C; Inamura, T; Ogawa, T; Hosoe, N; Nagata, H; Ishii, H; Hibi, T

2005-03-01

Although enhanced lymphocyte trafficking is associated with colitis formation, little information about its regulation is available. The aim of this study was to examine how the murine liver and activation-regulated chemokine (mLARC/CCL20) contributes to lymphocyte recruitment in concert with vascular adhesion molecules in murine chronic experimental colitis. T and B lymphocytes isolated from the spleen were fluorescence-labelled and administered to recipient mice. Lymphocyte adhesion to microvessels of the colonic mucosa and submucosa was observed with an intravital microscope. To induce colitis, the mice received two cycles of treatment with 2% dextran sodium sulphate (DSS). In some of the experiments antibodies against the adhesion molecules or anti-mLARC/CCL20 were administered, or CC chemokine receptor 6 (CCR6) of the lymphocytes was desensitized with excess amounts of mLARC/CCL20. Significant increases in T and B cell adhesion to the microvessels of the DSS-treated mucosa and submucosa were observed. In chronic colitis, the accumulation of lymphocytes was significantly inhibited by anti-mucosal addressin cell adhesion molecule (MAdCAM)-1 mAb, but not by anti-vascular cell adhesion molecule-1. In DSS-treated colonic tissue, the expression of mLARC/CCL20 was significantly increased, the blocking of mLARC/CCL20 by monoclonal antibody or the desensitization of CCR6 with mLARC/CCL20 significantly attenuated the DSS-induced T and B cell accumulation. However, the combination of blocking CCR6 with MAdCAM-1 did not further inhibit these accumulations. These results suggest that in chronic DSS-induced colitis, both MAdCAM-1 and mLARC/CCL20 may play important roles in T and B lymphocyte adhesion in the inflamed colon under flow conditions.

Isolation and Functional Characterization of a Floral Repressor, BcMAF1, From Pak-choi (Brassica rapa ssp. Chinensis).

PubMed

Huang, Feiyi; Liu, Tongkun; Hou, Xilin

2018-01-01

MADS-box genes form a large gene family in plants and are involved in multiple biological processes, such as flowering. However, the regulation mechanism of MADS-box genes in flowering remains unresolved, especially under short-term cold conditions. In the present study, we isolated BcMAF1 , a Pak-choi ( Brassica rapa ssp. Chinensis ) MADS AFFECTING FLOWERING ( MAF ), as a floral repressor and functionally characterized BcMAF1 in Arabidopsis and Pak-choi. Subcellular localization and sequence analysis indicated that BcMAF1 was a nuclear protein and contained a conserved MADS-box domain. Expression analysis revealed that BcMAF1 had higher expression levels in leaves, stems, and petals, and could be induced by short-term cold conditions in Pak-choi. Overexpressing BcMAF1 in Arabidopsis showed that BcMAF1 had a negative function in regulating flowering, which was further confirmed by silencing endogenous BcMAF1 in Pak-choi. In addition, qPCR results showed that AtAP3 expression was reduced and AtMAF2 expression was induced in BcMAF1 -overexpressing Arabidopsis . Meanwhile, BcAP3 transcript was up-regulated and BcMAF2 transcript was down-regulated in BcMAF1 -silencing Pak-choi. Yeast one-hybrid and dual luciferase transient assays showed that BcMAF1 could bind to the promoters of BcAP3 and BcMAF2 . These results indicated that BcAP3 and BcMAF2 might be the targets of BcMAF1. Taken together, our results suggested that BcMAF1 could negatively regulate flowering by directly activating BcMAF2 and repressing BcAP3 .

Chronic exposure to pollutants in Madín Reservoir (Mexico) alters oxidative stress status and flesh quality in the common carp Cyprinus carpio.

PubMed

Morachis-Valdez, Gabriela; Dublán-García, Octavio; López-Martínez, Leticia Xochitl; Galar-Martínez, Marcela; Saucedo-Vence, Karinne; Gómez-Oliván, Leobardo Manuel

2015-06-01

Madín Reservoir (MR) is located on the Río Tlalnepantla in Mexico. Previous studies seeking to identify pollutants at this site evidence that MR water contains a considerable metal load as well as nonsteroidal anti-inflammatory drugs (NSAIDs) at concentrations above those determined suitable for aquatic life. This study aimed to evaluate whether chronic exposure to pollutants in MR alters oxidative stress status and flesh quality in muscle of the common carp Cyprinus carpio. The following biomarkers were evaluated in muscle of carp caught in the general area of discharge from the town of Viejo Madín: hydroperoxide content (HPC), lipid peroxidation (LPX), protein carbonyl content (PCC), and activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Physicochemical and textural properties of muscle were also evaluated. Results show that the metals Al and Fe were accumulated in muscle of C. carpio at levels of 21.3 and 29.6 μg L(-1), respectively, and the NSAIDs diclofenac, ibuprofen, and naproxen at levels from 0.08 to 0.21 ng L(-1). Fish exposed to discharge from the town of Viejo Madín showed significant increases in HPC (9.77 %), LPX (69.33 %), and PCC (220 %) with respect to control specimens (p < 0.05). Similarly, enzyme activity increased significantly: SOD (80.82 %), CAT (98.03 %), and GPx (49.76 %). In muscle, physicochemical properties evidenced mainly significant reductions compared to control values while textural properties showed significant increases. Thus, water in this reservoir is contaminated with xenobiotics that alter some biological functions in C. carpio, a fish species consumed by the local human population.

Identification and Characterization of Three Orchid MADS-Box Genes of the AP1/AGL9 Subfamily during Floral Transition1

PubMed Central

Yu, Hao; Goh, Chong Jin

2000-01-01

Gene expressions associated with in vitro floral transition in an orchid hybrid (Dendrobium grex Madame Thong-In) were investigated by differential display. One clone, orchid transitional growth related gene 7 (otg7), encoding a new MADS-box gene, was identified to be specifically expressed in the transitional shoot apical meristem (TSAM). Using this clone as a probe, three orchid MADS-box genes, DOMADS1, DOMADS2, and DOMADS3, were subsequently isolated from the TSAM cDNA library. Phylogenetic analyses show that DOMADS1 and DOMADS2 are new members of the AGL2 subfamily and SQUA subfamily, respectively. DOMADS3 contains the signature amino acids as with the members in the independent OSMADS1 subfamily separated from the AGL2 subfamily. All three of the DOMADS genes were expressed in the TSAM during floral transition and later in mature flowers. DOMADS1 RNA was uniformly expressed in both of the inflorescence meristem and the floral primordium and later localized in all of the floral organs. DOMADS2 showed a novel expression pattern that has not been previously characterized for any other MADS-box genes. DOMADS2 transcript was expressed early in the 6-week-old vegetative shoot apical meristem in which the obvious morphological change to floral development had yet to occur. It was expressed throughout the process of floral transition and later in the columns of mature flowers. The onset of DOMADS3 transcription was in the early TSAM at the stage before the differentiation of the first flower primordium. Later, DOMADS3 transcript was only detectable in the pedicel tissues. Our results suggest that the DOMADS genes play important roles in the process of floral transition. PMID:10938351

Activin receptor inhibition by Smad2 regulates Drosophila wing disc patterning through BMP-response elements

PubMed Central

Peterson, Aidan J.; O'Connor, Michael B.

2013-01-01

Imaginal disc development in Drosophila requires coordinated cellular proliferation and tissue patterning. In our studies of TGFβ superfamily signaling components, we found that a protein null mutation of Smad2, the only Activin subfamily R-Smad in the fruit fly, produces overgrown wing discs that resemble gain of function for BMP subfamily signaling. The wing discs are expanded specifically along the anterior-posterior axis, with increased proliferation in lateral regions. The morphological defect is not observed in mutants for the TGFβ receptor baboon, and epistasis tests showed that baboon is epistatic to Smad2 for disc overgrowth. Rescue experiments indicate that Baboon binding, but not canonical transcription factor activity, of Smad2 is required for normal disc growth. Smad2 mutant discs generate a P-Mad stripe that is narrower and sharper than the normal gradient, and activation targets are correspondingly expressed in narrowed domains. Repression targets of P-Mad are profoundly mis-regulated, with brinker and pentagone reporter expression eliminated in Smad2 mutants. Loss of expression requires a silencer element previously shown to be controlled by BMP signaling. Epistasis experiments show that Baboon, Mad and Schnurri are required to mediate the ectopic silencer output in the absence of Smad2. Taken together, our results show that loss of Smad2 permits promiscuous Baboon activity, which represses genes subject to control by Mad-dependent silencer elements. The absence of Brinker and Pentagone in Smad2 mutants explains the compound wing disc phenotype. Our results highlight the physiological relevance of substrate inhibition of a kinase, and reveal a novel interplay between the Activin and BMP pathways. PMID:23293296

SEPALLATA1/2-suppressed mature apples have low ethylene, high auxin and reduced transcription of ripening-related genes

PubMed Central

Schaffer, Robert J.; Ireland, Hilary S.; Ross, John J.; Ling, Toby J.; David, Karine M.

2012-01-01

Background and aims Fruit ripening is an important developmental trait in fleshy fruits, making the fruit palatable for seed dispersers. In some fruit species, there is a strong association between auxin concentrations and fruit ripening. We investigated the relationship between auxin concentrations and the onset of ethylene-related ripening in Malus × domestica (apples) at both the hormone and transcriptome levels. Methodology Transgenic apples suppressed for the SEPALLATA1/2 (SEP1/2) class of gene (MADS8/9) that showed severely reduced ripening were compared with untransformed control apples. In each apple type, free indole-3-acetic acid (IAA) concentrations were measured during early ripening. The changes observed in auxin were assessed in light of global changes in gene expression. Principal results It was found that mature MADS8/9-suppressed apples had a higher concentration of free IAA. This was associated with increased expression of the auxin biosynthetic genes in the indole-3-acetamide pathway. Additionally, in the MADS8/9-suppressed apples, there was less expression of the GH3 auxin-conjugating enzymes. A number of genes involved in the auxin-regulated transcription (AUX/IAA and ARF classes of genes) were also observed to change in expression, suggesting a mechanism for signal transduction at the start of ripening. Conclusions The delay in ripening observed in MADS8/9-suppressed apples may be partly due to high auxin concentrations. We propose that, to achieve low auxin associated with fruit maturation, the auxin homeostasis is controlled in a two-pronged manner: (i) by the reduction in biosynthesis and (ii) by an increase in auxin conjugation. This is associated with the change in expression of auxin-signalling genes and the up-regulation of ripening-related genes. PMID:23346344

Effect on oxidative stress, hepatic chemical metabolizing parameters, and genotoxic damage of mad honey intake in rats.

PubMed

Eraslan, G; Kanbur, M; Karabacak, M; Arslan, K; Siliğ, Y; Soyer Sarica, Z; Tekeli, M Y; Taş, A

2017-01-01

A total of 66 male Wistar rats were used and six groups (control: 10 animals and experimental: 12 animals) were formed. While a separate control group was established for each study period, mad honey application to the animals in the experimental group was carried out with a single dose (12.5 g kg -1 body weight (b.w.); acute stage), at a dose of 7.5 g kg -1 b.w. for 21 days (subacute stage), and at a dose of 5 g kg -1 b.w. for 60 days (chronic stage). Tissue and blood oxidative stress markers (malondialdehyde (MDA), nitric oxide (NO), 4-hydroxynonenal (HNE), superoxide dismutase, catalase, glutathione (GSH) peroxidase, and glucose-6-phosphate dehydrogenase), hepatic chemical metabolizing parameters in the liver (cytochrome P450 2E1, nicotinamide adenine dinucleotide (NADH)-cytochrome b5 reductase, nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase (CYTC), GSH S-transferase (GST), and GSH), and micronucleus and comet test in some samples were examined. Findings from the study showed that single and repeated doses given over the period increased MDA, NO, and HNE levels while decreasing/increasing tissue and blood antioxidant enzyme activities. From hepatic chemical metabolizing parameters, GST activity increased in the subacute and chronic stages and CYTC activity increased in the acute period, whereas GSH level decreased in the subacute stage. Changes in tail and head intensities were found in most of the comet results. Mad honey caused oxidative stresses for each exposure period and made some significant changes on the comet test in certain periods for some samples obtained. In other words, according to the available research results obtained, careless consumption of mad honey for different medical purposes is not appropriate.

Controlled dehydration improves the diffraction quality of two RNA crystals.

PubMed

Park, HaJeung; Tran, Tuan; Lee, Jun Hyuck; Park, Hyun; Disney, Matthew D

2016-11-03

Post-crystallization dehydration methods, applying either vapor diffusion or humidity control devices, have been widely used to improve the diffraction quality of protein crystals. Despite the fact that RNA crystals tend to diffract poorly, there is a dearth of reports on the application of dehydration methods to improve the diffraction quality of RNA crystals. We use dehydration techniques with a Free Mounting System (FMS, a humidity control device) to recover the poor diffraction quality of RNA crystals. These approaches were applied to RNA constructs that model various RNA-mediated repeat expansion disorders. The method we describe herein could serve as a general tool to improve diffraction quality of RNA crystals to facilitate structure determinations.

Web life: The Evil Mad Scientist Project

NASA Astrophysics Data System (ADS)

2009-04-01

What is it? Have you ever tried to electrocute a hot dog? Wondered how to make a robot out of a toothbrush, watch battery and phone-pager motor? Seen a cantaloupe melon and thought, "Hmm, I could make this look like the Death Star from the original Star Wars films"? If you have not, but you would like to - preferably as soon as you can find a pager motor - then this is the site for you. The Evil Mad Scientist Project (EMSP) blog is packed full of ideas for unusual, silly and frequently physics-related creations that bring science out of the laboratory and into kitchens, backyards and tool sheds.

Ectopic expression of the HAM59 gene causes homeotic transformations of reproductive organs in sunflower (Helianthus annuus L.).

PubMed

Shulga, O A; Neskorodov, Ya B; Shchennikova, A V; Gaponenko, A K; Skryabin, K G

2015-01-01

The function of the HAM59 MADS-box gene in sunflower (Helianthus annuus L.) was studied to clarify homeotic C activity in the Asteraceae plant family. For the first time, transgenic sunflower plants with a modified pattern of HAM59 expression were obtained. It was shown that the HAM59 MADS-box transcription factor did mediate C activity in sunflower. In particular, it participated in termination of the floral meristem, repression of the cadastral function of A-activity, and together with other C-type sunflower protein HAM45-in the specification of the identity of stamens and pistils.

Space madness: the dreaded disease that never was.

PubMed

Hersch, Matthew H

2012-03-01

Psychiatrists working with the National Aeronautics and Space Administration in the late-1950s feared the worst of the men they examined to be America's first astronauts: that they would be impulsive, suicidal, sexually aberrant thrill-seekers. The examiners, though, were surprised - and a little disappointed - when tests revealed the would-be astronauts to be sane, poised professionals able to absorb extraordinary stresses. A Space Age malady with no incidence among human populations, 'space madness' is the stuff of Hollywood: a cultural manifestation of popular fears of a lonely, dehumanizing, and claustrophobic future among the stars. Copyright © 2011 Elsevier Ltd. All rights reserved.

Solenoid Fringe Field Effects for the Neutrino Factory Linac - MAD-X Investigation

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

M. Aslaninejad,C. Bontoiu,J. Pasternak,J. Pozimski,Alex Bogacz

2010-05-01

International Design Study for the Neutrino Factory (IDS-NF) assumes the first stage of muon acceleration (up to 900 MeV) to be implemented with a solenoid based Linac. The Linac consists of three styles of cryo-modules, containing focusing solenoids and varying number of SRF cavities for acceleration. Fringe fields of the solenoids and the focusing effects in the SRF cavities have significant impact on the transverse beam dynamics. Using an analytical formula, the effects of fringe fields are studied in MAD-X. The resulting betatron functions are compared with the results of beam dynamics simulations using OptiM code.

The impact of social amplification and attenuation of risk and the public reaction to mad cow disease in Canada.

PubMed

Lewis, Roxanne E; Tyshenko, Michael G

2009-05-01

Following the detection of bovine spongiform encephalopathy (BSE) in Canada, and subsequently in the United States, confidence in the safety of beef products remained high. Consumers actually increased their consumption of beef slightly after the news of an increased risk from mad cow disease, which has been interpreted as public support for beef farmers and confidence in government regulators. The Canadian public showed a markedly different reaction to the news of domestic BSE than the furious and panicked responses observed in the United Kingdom, Germany, and Japan. Using the social amplification of risk framework, we show that, while other countries displayed social amplification of risk, Canada experienced a social attenuation of risk. The attenuated reaction in Canada toward mad cow disease and increased human health risks from variant Creutzfeldt-Jakob disease (vCJD) was due to the social context at the time when BSE was discovered domestically. Mortality, morbidity, and psychosocial impacts resulting from other major events such as severe acute respiratory syndrome (SARS), West Nile virus (WNV), and the U.S.-Iraq war made the theoretical risks of BSE and vCJD a lower priority, reducing its concern as a risk issue.

Hyperprolinemia in Type 2 Glutaric Aciduria and MADD-Like Profiles.

PubMed

Pontoizeau, Clément; Habarou, Florence; Brassier, Anaïs; Veauville-Merllié, Alice; Grisel, Coraline; Arnoux, Jean-Baptiste; Vianey-Saban, Christine; Barouki, Robert; Chadefaux-Vekemans, Bernadette; Acquaviva, Cécile; de Lonlay, Pascale; Ottolenghi, Chris

2016-01-01

Classical neonatal-onset glutaric aciduria type 2 (MAD deficiency) is a severe disorder of mitochondrial fatty acid oxidation associated with poor survival. Secondary dysfunction of acyl-CoA dehydrogenases may result from deficiency for riboflavin transporters, leading to severe disorders that, nevertheless, are treatable by riboflavin supplementation. In the last 10 years, we identified nine newborns with biochemical features consistent with MAD deficiency, only four of whom survived past the neonatal period. A likely iatrogenic cause of riboflavin deficiency was found in two premature newborns having parenteral nutrition, one of whom recovered upon multivitamin supplementation, whereas the other died before diagnosis. Four other patients had demonstrated mutations involving ETF or ETF-DH flavoproteins, whereas the remaining three patients presumably had secondary deficiencies of unknown mechanism. Interestingly, six newborns among the seven tested for plasma amino acids had pronounced hyperprolinemia. In one case, because the initial diagnostic workup did not include organic acids and acylcarnitine profiling, clinical presentation and hyperprolinemia suggested the diagnosis. Analysis of our full cohort of >50,000 samples from >30,000 patients suggests that the proline/alanine ratio may be a good marker of MAD deficiency and could contribute to a more effective management of the treatable forms.